Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Urachal Cancer; Parathyroid Carcinoma; Fibrolamellar Carcinoma; Angiosarcoma; Secretory Carcinoma of Breast; Anal Neoplasms; Metaplastic Breast Carcinoma; Translocation Renal Cell Carcinoma; Carcinosarcoma; Small Intestine Neoplasms; Cholangiocarcinoma; Sertoli-Leydig Cell Tumor; Adenoid Cystic Carcinoma; Mesothelioma; Neuroblastoma; Adrenal Gland Neoplasms; Penile Neoplasms; Apocrine Carcinoma; Fibrosarcoma; Cancer of Unknown Primary; Hemangioblastoma; Thyroid Neoplasms; Hepatoblastoma; Fallopian Tube Neoplasms; Leiomyosarcoma; Vaginal Neoplasms; Neurofibrosarcoma; Gallbladder Neoplasms; Osteosarcoma; Biliary Tract Neoplasms; Clear Cell Endometrial Cancer; Yolk Sac Tumor; Vulvar Neoplasms; Kaposi Sarcoma; Ovarian Epithelial Cancer; Soft Tissue Sarcoma; Urethral Neoplasms; Granulosa Cell Tumor; Primitive Neuroectodermal Tumor; Neuroendocrine Tumors; Trophoblastic Tumor
Interventions: Drug: Nivolumab
Sponsors: Instituto do Cancer do Estado de SÃ£o Paulo; Financiadora de Estudos e Projetos
Recruiting
Outcomes and Prognostic Factors in Hepatopancreatoduodenectomy

Posted: October 8th, 2024, 11:00pm UTC

Conditions: Hepatopancreaticobiliary (HPB) Malignancy; Gall Bladder Cancer; Bile Duct Cancer; Pancreatoduodenectomy; Hepatectomy
Interventions: Other: Hepatopancreatoduodenectomy
Sponsors: Seoul National University Hospital
Completed
Liver Cancer Investigation for Prognosis Study

Posted: October 2nd, 2024, 11:00pm UTC

Conditions: Liver Neoplasms
Sponsors: Sun Yat-sen University
Not yet recruiting
D07001 Softgel-Capsules and Capecitabine Combination Therapy in Patients With Advanced Biliary Tract Cancer

Posted: October 1st, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer (BTC)
Interventions: Drug: D07001-Softgel Capsules; Drug: Placebo; Combination Product: Capecitabine
Sponsors: InnoPharmax Inc.
Not yet recruiting
Adebrelimab Combined With Capecitabine for Adjuvant Therapy in Cholangiocarcinoma With High-risk Recurrence Post-surgery

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Cancer; Adebrelimab (SHR-1316)
Interventions: Drug: Adebrelimab and capecitabine; Drug: capecitabine
Sponsors: The First Affiliated Hospital with Nanjing Medical University
Not yet recruiting
Ivosidenib in Locally Advanced or Metastatic Cholangiocarcinoma with IDH1 R132 Mutation After At Least One Prior Systemic Treatment - an Observational Study

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Sponsors: iOMEDICO AG; Servier Deutschland GmbH
Not yet recruiting
A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Non-small Cell Lung Cancer; Colorectal Cancer; Advanced Solid Tumor; Metastatic Solid Tumor
Interventions: Drug: LY4066434.; Drug: Cetuximab; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: 5Fluorouracil; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab
Sponsors: Eli Lilly and Company
Not yet recruiting
A Clinical Trial Evaluating the Safety and Efficacy of Intravenous HNF4Î± srRNA in Treating Advanced ICC Patients

Posted: September 4th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HNF4Î± srRNA
Sponsors: Shanghai Changzheng Hospital
Not yet recruiting
The Safety and Efficacy of CD-801 in Patients With Advanced Intrahepatic Cholangiocarcinoma

Posted: August 27th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Genetic: Injection of CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4Î± (HNF4Î±)
Sponsors: Shanghai Changzheng Hospital
Not yet recruiting
Oral Protein Supplements for Nutritional and Quality of Life Improvement After Pancreatic Resection in Elderly Patients

Posted: August 26th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer; Cholangiocarcinoma; Intraductal Papillary Mucinous Neoplasm; Neuroendocrine Tumor; Solid Pseudopapillary Tumor
Interventions: Dietary Supplement: oral protein supplements; Genetic: placebo
Sponsors: Yonsei University
Completed
Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in Resectable iCCA

Posted: August 26th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Resectable
Interventions: Drug: Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig
Sponsors: University Health Network, Toronto; Sunnybrook Health Sciences Centre; Hamilton Health Sciences Corporation
Not yet recruiting
Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma

Posted: August 22nd, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma; Chemotherapy Effect; Immunotherapy
Interventions: Drug: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody
Sponsors: Third Affiliated Hospital, Sun Yat-Sen University; Second Affiliated Hospital of Guangzhou Medical University
Not yet recruiting
A French Multicenter Observational Retrospective Study of Rare Primary Liver Cancers

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Hepatocholangiocarcinoma; Fibrolamellar Carcinoma; Hepatic Epithelioid Hemangioendothelioma; Hepatoblastoma; Hepatic Neuroendocrine Carcinoma; Hepatic Carcinosarcomas; Hepatic Cystadenoma; Hepatic Leiomyosarcomas; Hepatic Angiosarcomas; Cholangiocarcinoma
Sponsors: Federation Francophone de Cancerologie Digestive; SociÃ©tÃ© Nationale FranÃ§aise de GastroentÃ©rologie
Recruiting
Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma

Posted: August 6th, 2024, 11:00pm UTC

Conditions: Living Donor Liver Transplantation; Liver Transplantation; Neoadjuvant Therapy
Interventions: Procedure: Living donor liver transplantation
Sponsors: Jena University Hospital
Not yet recruiting
Impact of Preoperative Endoscopic Ultrasound-guided Fine-needle Aspiration in Cholangiocarcinoma Patients

Posted: August 2nd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Patients
Interventions: Diagnostic Test: Endoscopic ultrasound-guided fine-needle aspiration
Sponsors: Asian Institute of Gastroenterology, India
Not yet recruiting
Pemigatinib Combined With Durvalumab for Previously Treated Biliary Tract Carcinoma

Posted: July 31st, 2024, 11:00pm UTC

Conditions: Biliary Tract Carcinoma; Cholangiocarcinoma
Interventions: Drug: Pemigatinib and Durvalumab
Sponsors: Eastern Hepatobiliary Surgery Hospital
Not yet recruiting
Testing Ivonescimab Versus FOLFOX in Advanced Biliary Tract Cancer Patients

Posted: July 31st, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer
Interventions: Drug: Ivonescimab; Drug: FOLFOX regimen
Sponsors: UNICANCER; Cancer Research UK & UCL Cancer Trials Centre; Belgian Group of Digestive Oncology; Summit Therapeutics
Not yet recruiting
Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumor
Interventions: Drug: Neratinib tablets
Sponsors: Convalife (Shanghai) Co., Ltd.
Not yet recruiting
Futibatinib in Patients Previously Enrolled in an Antecedent Futibatinib as Monotherapy or Combination Therapy.

Posted: July 18th, 2024, 11:00pm UTC

Conditions: Advanced/Metastatic Cancer
Interventions: Drug: futibatinib; Drug: futibatinib, fulvestrant
Sponsors: Taiho Oncology, Inc.
Enrolling by invitation
GEMOX-HAIC Plus GEM-SYS in Combination With Lenvatinib and PD-1 Inhibitor for Large Unresectable ICC

Posted: July 17th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Gemcitabine-Oxaliplatin Regimen
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Posted: July 16th, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Cholangiocarcinoma; Gastric Cancer; Bladder Cancer; Hepatocellular Carcinoma; Pheochromocytoma; Ovarian Cancer
Interventions: Drug: [18F]FAPI-74; Drug: [18F]FDG
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Interventions: Drug: Ivosidenib; Drug: Durvalumab (for the first 8, 21-day, cycles); Drug: Gemcitabine (for the first 8, 21-day, cycles); Drug: Cisplatin (for the first 8, 21-day, cycles); Drug: Durvalumab (starting from cycle 9); Drug: Ivosidenib Recommended Combination Dose (RCD)
Sponsors: Institut de Recherches Internationales Servier
Not yet recruiting
Consolidative Radiotherapy (CSRT) in Patients With Oligometastatic/Locally Advanced Unresectable Bilary Tract Cancer (BTC)

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer
Interventions: Radiation: Consolidative radiotherapy; Drug: Standard-of-care systemic therapy: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab
Sponsors: Shanghai Zhongshan Hospital
Not yet recruiting
Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma

Posted: July 10th, 2024, 11:00pm UTC

Conditions: Klatskin Tumor
Interventions: Radiation: Stereotactic body radiation therapy
Sponsors: Erasmus Medical Center; Dutch Cancer Society
Recruiting
Phase 2 Study: OBI-833/OBI-821 Maintenance for Globo H+ Advanced Biliary Tract Cancer After Gemcitabine/Cisplatin

Posted: July 8th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Chemotherapy Effect; Immunotherapy
Interventions: Drug: OBI-833/OBI-821
Sponsors: Chang Gung Memorial Hospital
Not yet recruiting
TACE Combined With Immune Checkpoint Inhibitors for Liver Malignant Tumors

Posted: July 4th, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma Non-resectable; Cholangiocarcinoma Non-resectable; Liver Metastases; Liver Malignant Tumors
Interventions: Procedure: TACE with ICI
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Recruiting
Liquid Biopsy MonitORing Of CholangioCarcinOma for Treatment Response and Prognostic Outcomes (MOROCCO)

Posted: June 25th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Other: Non-Interventional Study
Sponsors: Mayo Clinic
Enrolling by invitation
A Study to Evaluate LB1410 in Combination With LB4330 in Patients With Advanced or Metastatic Solid Tumors

Posted: June 21st, 2024, 11:00pm UTC

Conditions: Solid Tumor
Interventions: Drug: LB1410; Drug: LB4330
Sponsors: L & L biopharma Co., Ltd., Shanghai China; Shanghai East Hospital
Recruiting
Microwave Ablation Versus Liver Resection for Intrahepatic Cholangiocarcinoma

Posted: June 17th, 2024, 11:00pm UTC

Conditions: Overall Survival; Disease-free Survival
Interventions: Procedure: Microwave ablation (MWA) versus Liver Resection (LR)
Sponsors: Chinese PLA General Hospital
Recruiting
Treatment of Distal Malignant Biliary Obstruction by Uncovered, Partially Covered, or Fully Covered Metal Stents

Posted: June 11th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer Non-resectable; Bile Duct Cancer; Papillary Carcinoma; Duodenal Cancer
Interventions: Procedure: Randomization to uncovered SEMS treating jaundice due to distal malignant biliary obstruction.; Procedure: Randomization to partially covered SEMS treating jaundice due to distal malignant biliary obstruction.; Procedure: Randomization to fully covered SEMS treating jaundice due to distal malignant biliary obstruction.
Sponsors: Region Stockholm
Recruiting
Combining Chemoradiotherapy With Sintilimab in First-Line ICC

Posted: June 7th, 2024, 11:00pm UTC

Conditions: ICC
Interventions: Radiation: radiotherapy; Drug: gemcitabine + cisplatin; Drug: slulimumab
Sponsors: Shanghai Zhongshan Hospital
Not yet recruiting
Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma

Posted: June 4th, 2024, 11:00pm UTC

Conditions: Extrahepatic Cholangiocarcinoma; Unresectable Perihilar or Ductal CCA
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Procedure: ID-RFA
Sponsors: Institut fÃ¼r Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; UniversitÃ¤tsklinikum DÃ¼sseldorf, Germany; UniversitÃ¤tsklinikum KÃ¶ln, Germany; AstraZeneca
Recruiting
Phase II Study of the Combination of Durvalumab (MEDI4736) (PDL1 Inhibitor) and Olaparib (PARP Inhibitor) in Advanced Cholangiocarcinoma After Initial Chemotherapy and Durvalumab (BIL-PPP)

Posted: June 4th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: Durvalumab; Drug: Olaparib
Sponsors: Australasian Gastro-Intestinal Trials Group; Wayne Elphinstone Research Fund; AstraZeneca
Not yet recruiting
Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Combination Product: Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil
Sponsors: West China Hospital
Not yet recruiting
INSPIRE: A Multi-Cancer Early Detection Study

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Lung Cancer; Gastric Cancer; Liver Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Breast Cancer; Cervical Cancer; Ovarian Cancer; Endometrial Cancer; Bladder Cancer; Prostate Cancer; Cholangiocarcinoma
Sponsors: Singlera Genomics Inc.; Fudan University; Hubei Cancer Hospital, Huazhong University of Science and Technology; China-Japan Friendship Hospital; Shanxi Provincial Cancer Hospital; Xuhui Central Hospital, Fudan University; Shanghai Electric Power Hospital; East Hospital, Tongji University; The First Affiliated Hospital of Xi' an Jiaotong University; GaoZhou People's Hosipital; Anhui Provincial Hospital; Beijing Friendship Hospital
Not yet recruiting
Phase II Trial of Pemigatinib in Combination With Atezolizumab and Bevacizumab for Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Advanced Cholangiocarcinoma; FGFR2 Fusion
Interventions: Drug: Pemigatinib; Drug: Atezolizumab; Drug: Bevacizumab
Sponsors: M.D. Anderson Cancer Center; Incyte Corporation; Genentech, Inc.
Not yet recruiting
Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma

Posted: May 30th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Radiation: Proton Beam Therapy; Drug: Concurrent oral capecitabine chemotherapy; Drug: Cisplatin & Gemcitabine intravenous chemotherapy; Procedure: Orthotropic Liver Transplant
Sponsors: The Christie NHS Foundation Trust; University College London Hospitals; University College, London; Royal Free Hospital NHS Foundation Trust
Not yet recruiting
hepatomiR cACLD Study

Posted: May 29th, 2024, 11:00pm UTC

Conditions: Chronic Liver Disease and Cirrhosis; Chronic Liver Disease; Portal Hypertension
Interventions: Diagnostic Test: hepatomiR
Sponsors: Karl Landsteiner University of Health Sciences; University Hospital St. PÃ¶lten
Recruiting
NXP800 for the Treatment of Patients With Advanced or Metastatic Cholangiocarcinoma

Posted: May 20th, 2024, 11:00pm UTC

Conditions: Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma; Refractory Cholangiocarcinoma; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Heat Shock Factor 1 Pathway Inhibitor NXP800; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Ultrasound-Guided Biopsy
Sponsors: Mayo Clinic
Recruiting
Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

Posted: May 16th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Lenvatinib
Sponsors: Zhiyong Huang
Not yet recruiting
Diagnostic Approach for Cholangiocarcinoma Using Liquid Bile Biopsy

Posted: May 16th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Diagnostic Test: Proteomic profile
Sponsors: University Hospital, Bordeaux
Not yet recruiting
Neoantigen Vaccine Plus Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma After Radical Resection

Posted: May 9th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Combination Product: Neoantigen Vaccine plus Capecitabine
Sponsors: Yongyi Zeng
Not yet recruiting
A Prospective, Single-arm, Multicenter Phase II Clinical Study of HAIC in Combination With Adebrelimab and Bevacizumab for Potentially Resectable Hepatocellular Carcinoma

Posted: May 8th, 2024, 11:00pm UTC

Conditions: Adebrelimab; Hepatocellular Carcinoma
Interventions: Drug: Adebrelimab
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Recruiting
A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

Posted: May 6th, 2024, 11:00pm UTC

Conditions: Colorectal Cancer; Cholangiocarcinoma; Appendiceal Adenocarcinoma; Pancreatic Adenocarcinoma; Gastric Adenocarcinoma; Endometrial Adenocarcinoma; Triple Negative Breast Cancer; Ovarian Cancer; Prostate Cancer
Interventions: Drug: APL-5125
Sponsors: Apollo Therapeutics Ltd
Recruiting
Disitamab Vedotin Plus Cadonilimab in Patients With HER2 Mutant Advanced or Metastatic Bile Duct Adenocarcinoma

Posted: April 25th, 2024, 11:00pm UTC

Conditions: Bile Duct Adenocarcinoma Non-Resectable; HER2 Gene Mutation
Interventions: Drug: Disitamab Vedotin Plus Cadonilimab
Sponsors: Zhejiang Cancer Hospital
Recruiting
Detecting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma

Posted: April 24th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma Resectable; Cholangiocarcinoma; Liver
Interventions: Diagnostic Test: LyMIC (Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma)
Sponsors: City of Hope Medical Center
Recruiting
Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Radiation: radioembolization with Y-90; Drug: Durvalumab; Drug: Cisplatin; Drug: Gemcitabine
Sponsors: Francesco De Cobelli; Cardarelli Hospital; A.O. Ospedale Papa Giovanni XXIII; AOU Pisana, Pisa, Italy
Recruiting
A Single Arm, Single Centered Phase II Trial on the Combination of Adebrelimab, Surufatinib and Irinotecan Liposome-based HAIC in Advanced iCC

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Adebrelimab
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Not yet recruiting
First-line Treatment for Unresectable Locally Advanced Distal Cholangiocarcinoma Combining Radiotherapy and HAIC

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Radiation: Radiotherapy; Drug: HAIC (GEMOX); Drug: Chemotherapy
Sponsors: Shandong Cancer Hospital and Institute
Recruiting
Prognostic Factors for Survival in Patients With Cholangiocarcinoma

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Procedure: Resection/Ablation of tumor; Procedure: Palliative chemotherapy; Procedure: Neoadjuvant chemotherapy; Procedure: Stereotatic radiotherapy; Procedure: Best supportive care
Sponsors: Rigshospitalet, Denmark
Recruiting
Rollover Study to Provide Continued Access to TT-00420 (Tinengotinib) for Subjects With Advanced Solid Tumors

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumors; Cholangiocarcinoma
Interventions: Drug: Tinengotinib
Sponsors: TransThera Sciences (Nanjing), Inc.
Available
Digital Single-operator Cholangioscopy and Intraductal Ultrasound for Nonicteric Biliary Strictures

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Biliary Stricture
Sponsors: Soonchunhyang University Hospital
Not yet recruiting
Plasma Metabolic Biomarkers for Multi-Cancer Diagnosis

Posted: April 12th, 2024, 11:00pm UTC

Conditions: Lung Cancer; Breast Cancer; Colorectal Cancer; Thyroid Cancer; Gastric Cancer; Cervical Cancer; Liver Cancer; Pancreatic Cancer; Cholangiocarcinoma; Prostate Cancer; Esophageal Cancer; Ovarian Cancer; Renal Cell Carcinoma
Sponsors: Beijing Friendship Hospital
Recruiting
EchoTip AcuCore Post-Market Clinical Study

Posted: April 10th, 2024, 11:00pm UTC

Conditions: Adenocarcinoma; Neuroendocrine Tumors; Hepatocellular Carcinoma; Cholangiocarcinoma; Malignant Lymphoma; Metastasis; Chronic Pancreatitis; Autoimmune Pancreatitis
Interventions: Device: EchoTip AcuCore
Sponsors: Cook Research Incorporated
Recruiting
Extent of Intrahepatic Infiltration of PHCC

Posted: April 10th, 2024, 11:00pm UTC

Conditions: Perihilar Cholangiocarcinoma
Sponsors: Beijing Tsinghua Chang Gung Hospital
Completed
The Effect of [18F] F-FAPI PET-CT on Management in Patients With Proximal Cholangiocarcinoma

Posted: April 9th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: [18F]F-FAPI PET-CT
Sponsors: Mara Veenstra, MD; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); UMC Utrecht
Not yet recruiting
Neo-adjuvant Chemo and Immunotherapy in The Pre-operAtive Treatment of Locally Advanced cholangIOcarciNoma

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: Durvalumab 1120 mg; Drug: Durvalumab 1500 mg; Drug: Tremelimumab i.v. at 300 mg; Combination Product: Cisplatin (CDDP) 25 mg/mq i.v; Combination Product: Gemcitabine (GEM) 1000 mg/mq i.v.
Sponsors: National Cancer Institute, Naples
Recruiting
An Exosome-Based Liquid Biopsy for the Differential Diagnosis of Primary Liver Cancer

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma; Primary Liver Cancer; Primary Liver Carcinoma; Hepatic Cancer; Hepatic Carcinoma
Interventions: Diagnostic Test: ELUCIDATE
Sponsors: City of Hope Medical Center
Recruiting
Washington University Participant Engagement and Cancer Genomic Sequencing Center (WU-PE-CGS)

Posted: April 1st, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Multiple Myeloma; Colon Cancer; Rectal Cancer
Interventions: Other: Return of Genetic Results: Biomarker information from cancer cells; Other: Return of Genetic Results: Inherited mutations related to cancer; Other: Return of Genetic Results: Inherited mutations related to other medical issues
Sponsors: Washington University School of Medicine; National Cancer Institute (NCI); The Foundation for Barnes-Jewish Hospital
Recruiting
EUS Examination Using EndoSound Vision System vs. Standard Echoendoscope

Posted: April 1st, 2024, 11:00pm UTC

Conditions: Pancreatic Disease; Pancreatic Cancer; Pancreatic Cyst; Gastrointestinal Tumor; Bile Duct Diseases; Bile Duct Cancer; Lymph Node Disease; Submucosal Tumor of Gastrointestinal Tract; Gastrointestinal Cancer
Interventions: Device: Endoscopic ultrasound examination
Sponsors: Orlando Health, Inc.
Recruiting
HAIC Combined With Cadonilimab and Regorafenib as 2nd-line Treatment for ICC

Posted: March 28th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HAIC-GEMOX+Cadonilimab+Regorafenib
Sponsors: Fudan University
Recruiting
A Phase 1a/1b Study of ACTM-838 in Patients With Advanced Solid Tumors

Posted: March 28th, 2024, 11:00pm UTC

Conditions: Solid Tumor
Interventions: Drug: ACTM-838
Sponsors: Actym Therapeutics, Inc.
Recruiting
A Single Center, Retrospective Clinical Study on the Clinical Characteristics of Primary Liver Cancer

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Primary Liver Cancer
Sponsors: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Recruiting
HAI-Floxuridine, or SIRT, Combined With Gemox For Patients With Intra-Hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)

Posted: March 15th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma; Chemotherapy Effect
Interventions: Drug: Floxuridine; Procedure: Selective Internal Radiation Therapy (SIRT)
Sponsors: Oslo University Hospital
Recruiting
Surufatinib Combined With Toripalimab and HAIC in the Treatment of Inoperable or Metastatic Intrahepatic Cholangiocarcinoma

Posted: March 15th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Surufatinibã€Toripalimabã€Gemcitabineã€Oxaliplatin
Sponsors: Fudan University
Not yet recruiting
Open Versus Laparoscopic Ablation of Liver Malignancies

Posted: March 12th, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Liver Metastases
Interventions: Procedure: Laparoscopic ablation; Procedure: Open ablation
Sponsors: Rigshospitalet, Denmark
Recruiting
$Permalink for 'Pemigatinib + Afatinib in Advanced Refractory Solid Tumors'$
Pemigatinib + Afatinib in Advanced Refractory Solid Tumors

Posted: March 12th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumor; Unresectable Solid Tumor; Metastatic Solid Tumor; Cholangiocarcinoma
Interventions: Drug: Afatinib; Drug: Pemigatinib
Sponsors: Massachusetts General Hospital; Boehringer Ingelheim; Incyte Corporation
Recruiting
Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Posted: March 7th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: combined therapy using gemcitabine and cisplatin chemotherapy, Lenvatinib and Adebrelimab
Sponsors: Nanfang Hospital, Southern Medical University
Recruiting
Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC

Posted: March 6th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: HAIC; Drug: Adebrelimab; Drug: Apatinib
Sponsors: Lei ZHAO
Recruiting
A Machine-learning Model to Predict Lymph Node Metastasis of Intrahepatic Cholangiocarcinoma

Posted: March 4th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma; Machine Learning
Interventions: Procedure: lymph nodes dissection
Sponsors: West China Hospital
Recruiting
Clinical Utility of Selected Circulating Tumor DNA Assays in Patients With Advanced Malignancy

Posted: March 4th, 2024, 1:00am UTC

Conditions: Metastatic Colorectal Cancer; Pancreas Adenocarcinoma; Cholangiocarcinoma
Interventions: Diagnostic Test: Multiplex PCR-test for circulating tumor DNA
Sponsors: Oslo University Hospital
Recruiting
Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies

Fetched: February 29th, 2024, 3:01am UTC

Conditions: Metastatic Cancer; Solid Tumor
Interventions: Drug: Sym021; Drug: Sym022; Drug: Sym023; Drug: Irinotecan Hydrochloride
Sponsors: Symphogen A/S
Completed
FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis

Posted: February 29th, 2024, 1:00am UTC

Conditions: Primary Sclerosing Cholangitis; Inflammatory Bowel Diseases
Interventions: Biological: Faecal Microbiota Transplant; Other: FMT Placebo
Sponsors: University of Birmingham; PSC Support; Life Arc
Recruiting
Chemotherapy Combined With Adebrelimab and Apatinib as the Perioperative Treatment in Patients With Biliary Tract Cancer

Posted: February 28th, 2024, 1:00am UTC

Conditions: Resectable Intrahepatic Cholangiocarcinoma With High Risk of Recurrence
Interventions: Drug: Adebrelimab, Apatinib, Gemcitabine, cisplatin
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
An Exploratory Clinical Study to Evaluate the Safety and Efficacy of NK Cells (Combined With Standard Therapy) in the Treatment of Solid Tumor Patients

Posted: February 28th, 2024, 1:00am UTC

Conditions: Solid Tumors (Pancreatic Cancer, Esophageal Cancer, Gastric Cancer, Cholangiocarcinoma, Lung Cancer and Ovarian Cancer)
Interventions: Drug: Allogeneic NKï¼ˆCCT-ANK-11)
Sponsors: Beijing Kejing Biotechnology Co., Ltd.
Withdrawn
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

Posted: February 28th, 2024, 1:00am UTC

Conditions: Biliary Tract Cancer; HER2 Gene Mutation
Interventions: Drug: Zanidatamab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Durvalumab
Sponsors: Jazz Pharmaceuticals
Recruiting
Evaluation of diagnostiC Capacity of eccDNAs as Biomarkers in Indetermined biLiary Stricture(ECCBILE)

Posted: February 26th, 2024, 1:00am UTC

Conditions: Biliary Stricture; Bile Duct Cancer; Pancreas Cancer
Sponsors: Peking University Third Hospital; Beijing Tsinghua Changgeng Hospital
Recruiting
Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer

Posted: February 23rd, 2024, 1:00am UTC

Conditions: Bile Duct Cancer
Interventions: Drug: Gemcitabin, Cisplatin and Durvalumab; Procedure: Biliary Radiofrequency Ablation; Procedure: Endoscopic Retrograde Cholangio-Pancreatography with stenting
Sponsors: Insel Gruppe AG, University Hospital Bern; Swiss Cancer League
Not yet recruiting
Targeted Navigation in Hepatocellular Carcinoma (HCC)

Posted: February 15th, 2024, 1:00am UTC

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Hepatobiliary Cancer
Interventions: Behavioral: Target Navigation Pilot Program
Sponsors: University of Miami; The V Foundation
Recruiting
MicroRNAs as Bile-based Biomarkers in Pancreaticobiliary Cancers

Posted: February 14th, 2024, 1:00am UTC

Conditions: Pancreatic Cancer; Cholangiocarcinoma; Ampullary Cancer; Biliary Stricture; Gallstone Disease
Interventions: Diagnostic Test: Small RNA Sequencing and Validation of candidate miRNAs
Sponsors: Imperial College London; Royal Surrey County Hospital NHS Foundation Trust; Royal Free Hospital NHS Foundation Trust
Completed
Phase 1 Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors

Posted: February 13th, 2024, 1:00am UTC

Conditions: Malignant Mesothelioma; Colorectal Cancer; Bile Duct Cancer; Rectal Cancer; Ovary Cancer; Pancreatic Cancer; Breast Cancer Female
Interventions: Biological: UCMYM802 Injection
Sponsors: UTC Therapeutics Inc.; Peking University Cancer Hospital & Institute
Recruiting
HAIC Sequential TAE Combined With Tislelizumab and Surufatinib in Unresectable Intrahepatic Cholangiocarcinoma

Posted: February 2nd, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HAIC+TAE; Drug: Tislelizumab; Drug: Surufatinib
Sponsors: Qilu Hospital of Shandong University; BeiGene
Recruiting
A Study of ZG005 Combined With Donafenib in Patients With Advanced Solid Tumor

Posted: February 2nd, 2024, 1:00am UTC

Conditions: Solid Tumor
Interventions: Drug: ZG005 Powder for Injection; Drug: Donafenib Tosilate Tablets
Sponsors: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Recruiting
Effect of PVE on Surgical Outcomes and Long-term Survival in Perihilar Cholangiocarcinoma

Posted: January 25th, 2024, 1:00am UTC

Conditions: Biliary Tract Cancer; Portal Vein Embolization
Interventions: Procedure: Potal vein embilization
Sponsors: Seoul National University Hospital
Completed
Neoadjuvant Therapy of HAICï¼ˆGEMOXï¼‰ Combined With Adebrelimab and Lenvatinib for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factorsï¼šNEO-ERA-01 Study

Posted: January 17th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Adebrelimab; Drug: Lenvatinib; Drug: Gemcitabine; Drug: Oxaliplatin
Sponsors: The First Affiliated Hospital with Nanjing Medical University; Jiangsu Hengrui Pharmaceutical Co., Ltd.
Recruiting
Clinical Efficacy and Safety of Paclitaxel Polymeric Micelles for Injection in the Treatment of Patients With Taxans-resistant Pancreatic Adenocarcinoma, Cholangiocarcinoma, Lung Cancer, Gastric Cancer, Esophageal Carcinoma, or Breast Cancer

Posted: January 10th, 2024, 1:00am UTC

Conditions: Pancreatic Adenocarcinoma; Cholangiocarcinoma; Lung Cancer; Stomach Cancer; Esophageal Carcinoma; Breast Cancer
Interventions: Drug: Paclitaxel Polymeric Micelles for Injection
Sponsors: Liu Huang
Recruiting
A RCT of Low MBO Drainage Strategies

Posted: January 9th, 2024, 1:00am UTC

Conditions: Jaundice, Obstructive; Cholangiopancreatography, Endoscopic Retrograde; Endoscopic Ultrasound-Guided Drainage
Interventions: Procedure: EUS-BD; Procedure: ERCP-BD
Sponsors: Peking Union Medical College Hospital
Recruiting
Early Phase I Study of Autologous T Cells (EX02 CAR-T) for Unresectable Pancreatic/Bile Duct Cancer

Posted: January 9th, 2024, 1:00am UTC

Conditions: Pancreatic Cancer; Advanced Biliary Cancer
Interventions: Drug: anti-EX02 CAR T cells
Sponsors: Zhang Xiaofeng,MD; Zeno Therapeutics Pte. Ltd
Not yet recruiting
DEB-TACE, Lenvatinib and Anti-PD(L)1 Antibody as Conversion Therapy for Intrahepatic Cholangiocarcinoma

Posted: January 8th, 2024, 1:00am UTC

Conditions: Cholangiocarcinoma Non-resectable
Interventions: Procedure: drug eluting beads-transcatheter arterial chemoembolization; Drug: envatinib plus anti-PD(L)1
Sponsors: Ze-yang Ding, MD; Geneplus-Beijing Co. Ltd.; Chinese Cooperative Group of Liver Cancer (CCGLC)
Recruiting
Combined HAIC, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

Posted: January 5th, 2024, 1:00am UTC

Conditions: Cholangiocarcinoma Non-resectable
Interventions: Procedure: HAIC; Drug: Lenvatinib plus pucotenlimab
Sponsors: Ze-yang Ding, MD; Geneplus-Beijing Co. Ltd.; Chinese Cooperative Group of Liver Cancer
Recruiting
Combined DEB-TACE, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

Posted: January 5th, 2024, 1:00am UTC

Conditions: Cholangiocarcinoma Non-resectable
Interventions: Procedure: DEB-TACE; Drug: Lenvatinib plus pucotenlimab
Sponsors: Tongji Hospital; Geneplus-Beijing Co. Ltd.; Chinese Cooperative Group of Liver Cancer (CCGLC)
Recruiting
Efficacy and Safety of GemCis Plus Trastuzumab Plus Pembrolizumab in Previously Untreated HER2-positive Biliary Tract Cancer

Posted: December 21st, 2023, 1:00am UTC

Conditions: Biliary Tract Cancer; HER2 Gene Mutation
Interventions: Drug: SOC plus trastuzumab and pembrolizumab
Sponsors: Institut fÃ¼r Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Medizinische Hochschule Hannover, Germany, Prof. Dr. Arndt Vogel; MSD Sharp & Dohme GmbH, Germany
Recruiting
Sacituzumab Govitecan for the Treatment for Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma

Posted: December 21st, 2023, 1:00am UTC

Conditions: Locally Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma; Recurrent Cholangiocarcinoma; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Sacituzumab Govitecan
Sponsors: University of Kansas Medical Center; National Cancer Institute (NCI)
Recruiting
Endoscopic Radiofrequency Ablation for Unresectable Cholangiocarcinoma

Posted: December 19th, 2023, 1:00am UTC

Conditions: Cholangiocarcinoma; Klatskin Tumor; Bile Duct Cancer; Liver Cancer
Interventions: Procedure: Intraductal biliary radiofrequency ablation
Sponsors: UniversitÃ¤tsklinikum Hamburg-Eppendorf
Not yet recruiting
Intraductal Radiofrequency Thermoablation and Radiotherapy Combined Treatment for Extrahepatic Cholangiocarcinoma

Posted: December 13th, 2023, 1:00am UTC

Conditions: Biliary Tract Carcinoma; Radiotherapy; Radio-frequency Ablation
Interventions: Procedure: ID-RFA and Radiotherapy
Sponsors: National Cancer Center, Korea; Boston Scientific Corporation
Not yet recruiting
Congenital Biliary Dilatation Diagnosis Based on 3D Morphological Characteristics

Posted: December 8th, 2023, 1:00am UTC

Conditions: Congenital Biliary Dilatation
Interventions: Other: Contrast-enhanced computed tomography (CECT) and 3D morphological analysis
Sponsors: Tsinghua University; Beijing Tsinghua Chang Gung Hospital
Completed
Safety and Anti-Tumor Activity of TYRA-200 in Advanced Cholangiocarcinoma With Activating FGFR2 Gene Alterations

Posted: December 7th, 2023, 1:00am UTC

Conditions: Locally Advanced Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Solid Tumor; Metastatic Cholangiocarcinoma
Interventions: Drug: Phase 1 Part A - dose escalation TYRA-200 taken once daily by mouth in 28-day cycles; Drug: Phase 1 Part B - dose expansion TYRA-200 taken once daily by mouth in 28-day cycles
Sponsors: Tyra Biosciences, Inc
Recruiting
Precision Medicine for Combined Hepatocellular-Cholangiocarcinoma

Posted: November 24th, 2023, 1:00am UTC

Conditions: Liver Cancer
Interventions: Other: phenotyping
Sponsors: Inserm U955
Recruiting
Liver Transplantation in Intrahepatic Cholangiocarcinoma

Posted: November 20th, 2023, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma, Intrahepatic
Interventions: Procedure: Liver Transplant
Sponsors: Rutgers, The State University of New Jersey
Recruiting
Combination Therapy of HAIC, Surufatinib and Tislelizumab for Unresectable or Metastatic Biliary Tract Cancer

Posted: November 16th, 2023, 1:00am UTC

Conditions: Carcinoma; Intrahepatic Cholangiocarcinoma; Gallbladder Cancer; Surufatinib; Angiogenesis Inhibitors; Tislelizumab; Antineoplastic Agents, Immunological; Immunotherapy
Interventions: Drug: HAIC; Drug: Surufatinib; Drug: Tislelizumab
Sponsors: Wuhan Union Hospital, China
Not yet recruiting

Trial - Bile Duct Cancer

Agnostic Therapy in Rare Solid Tumors

Posted: October 14th, 2024, 11:00pm UTC

Conditions: Urachal Cancer; Parathyroid Carcinoma; Fibrolamellar Carcinoma; Angiosarcoma; Secretory Carcinoma of Breast; Anal Neoplasms; Metaplastic Breast Carcinoma; Translocation Renal Cell Carcinoma; Carcinosarcoma; Small Intestine Neoplasms; Cholangiocarcinoma; Sertoli-Leydig Cell Tumor; Adenoid Cystic Carcinoma; Mesothelioma; Neuroblastoma; Adrenal Gland Neoplasms; Penile Neoplasms; Apocrine Carcinoma; Fibrosarcoma; Cancer of Unknown Primary; Hemangioblastoma; Thyroid Neoplasms; Hepatoblastoma; Fallopian Tube Neoplasms; Leiomyosarcoma; Vaginal Neoplasms; Neurofibrosarcoma; Gallbladder Neoplasms; Osteosarcoma; Biliary Tract Neoplasms; Clear Cell Endometrial Cancer; Yolk Sac Tumor; Vulvar Neoplasms; Kaposi Sarcoma; Ovarian Epithelial Cancer; Soft Tissue Sarcoma; Urethral Neoplasms; Granulosa Cell Tumor; Primitive Neuroectodermal Tumor; Neuroendocrine Tumors; Trophoblastic Tumor
Interventions: Drug: Nivolumab
Sponsors: Instituto do Cancer do Estado de SÃ£o Paulo; Financiadora de Estudos e Projetos
Recruiting
SCINTIX [BgRT} Using RMRS in Solid and Soft Tissue Tumors

Posted: October 10th, 2024, 11:00pm UTC

Conditions: Thoracic Cancer; Head and Neck Cancer; Pelvic Cancer; Hepatobiliary Carcinoma in Situ; Retroperitoneal Cancer; Distributed and Orphan Tumors
Interventions: Device: RefleXion X1 Radiotherapy System [Imaging Only]
Sponsors: RefleXion Medical
Not yet recruiting
Outcomes and Prognostic Factors in Hepatopancreatoduodenectomy

Posted: October 8th, 2024, 11:00pm UTC

Conditions: Hepatopancreaticobiliary (HPB) Malignancy; Gall Bladder Cancer; Bile Duct Cancer; Pancreatoduodenectomy; Hepatectomy
Interventions: Other: Hepatopancreatoduodenectomy
Sponsors: Seoul National University Hospital
Completed
Liver Cancer Investigation for Prognosis Study

Posted: October 2nd, 2024, 11:00pm UTC

Conditions: Liver Neoplasms
Sponsors: Sun Yat-sen University
Not yet recruiting
D07001 Softgel-Capsules and Capecitabine Combination Therapy in Patients With Advanced Biliary Tract Cancer

Posted: October 1st, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer (BTC)
Interventions: Drug: D07001-Softgel Capsules; Drug: Placebo; Combination Product: Capecitabine
Sponsors: InnoPharmax Inc.
Not yet recruiting
Endoscopic Ultrasound-guided Fine-needle Biopsy for Tissue Sampling of Biliary Strictures: a Multicenter Prospective Study

Posted: September 26th, 2024, 11:00pm UTC

Conditions: Biliary Strictures
Interventions: Device: EUS-FNB
Sponsors: Ospedali Riuniti di Foggia
Recruiting
ERCP With and Without EUS Guided HGS for Bilateral Biliary Decompression in Malignant Hilar Biliary Obstruction

Posted: September 26th, 2024, 11:00pm UTC

Conditions: Malignant Hilar Stricture
Interventions: Procedure: ERCP biliary drainage; Procedure: Combined ERCP and EUS-HGS biliary drainage
Sponsors: Mansoura University
Recruiting
Adebrelimab Combined With Capecitabine for Adjuvant Therapy in Cholangiocarcinoma With High-risk Recurrence Post-surgery

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Cancer; Adebrelimab (SHR-1316)
Interventions: Drug: Adebrelimab and capecitabine; Drug: capecitabine
Sponsors: The First Affiliated Hospital with Nanjing Medical University
Not yet recruiting
Ivosidenib in Locally Advanced or Metastatic Cholangiocarcinoma with IDH1 R132 Mutation After At Least One Prior Systemic Treatment - an Observational Study

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Sponsors: iOMEDICO AG; Servier Deutschland GmbH
Not yet recruiting
A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

Posted: September 23rd, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Non-small Cell Lung Cancer; Colorectal Cancer; Advanced Solid Tumor; Metastatic Solid Tumor
Interventions: Drug: LY4066434.; Drug: Cetuximab; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: 5Fluorouracil; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab
Sponsors: Eli Lilly and Company
Not yet recruiting
Real-world Study of Triple Therapy for Intermediate-advanced HCC With BDTT (TALENP002)

Posted: September 19th, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma
Interventions: Combination Product: TACE, Lenvatinib, combined with Tislelizumab group
Sponsors: Fujian Provincial Hospital
Recruiting
A Clinical Trial Evaluating the Safety and Efficacy of Intravenous HNF4Î± srRNA in Treating Advanced ICC Patients

Posted: September 4th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HNF4Î± srRNA
Sponsors: Shanghai Changzheng Hospital
Not yet recruiting
Medication Adherence to Phone-supervised Pancreatic Enzyme Replacement Therapy

Posted: September 2nd, 2024, 11:00pm UTC

Conditions: Chronic Pancreatitis; Pancreatic Exocrine Insufficiency
Interventions: Behavioral: Phone-based PERT education intervention
Sponsors: Changhai Hospital
Recruiting
The Safety and Efficacy of CD-801 in Patients With Advanced Intrahepatic Cholangiocarcinoma

Posted: August 27th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Genetic: Injection of CD-801, a lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4Î± (HNF4Î±)
Sponsors: Shanghai Changzheng Hospital
Not yet recruiting
Oral Protein Supplements for Nutritional and Quality of Life Improvement After Pancreatic Resection in Elderly Patients

Posted: August 26th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer; Cholangiocarcinoma; Intraductal Papillary Mucinous Neoplasm; Neuroendocrine Tumor; Solid Pseudopapillary Tumor
Interventions: Dietary Supplement: oral protein supplements; Genetic: placebo
Sponsors: Yonsei University
Completed
Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in Resectable iCCA

Posted: August 26th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Resectable
Interventions: Drug: Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig
Sponsors: University Health Network, Toronto; Sunnybrook Health Sciences Centre; Hamilton Health Sciences Corporation
Not yet recruiting
Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma

Posted: August 22nd, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma; Chemotherapy Effect; Immunotherapy
Interventions: Drug: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody
Sponsors: Third Affiliated Hospital, Sun Yat-Sen University; Second Affiliated Hospital of Guangzhou Medical University
Not yet recruiting
A French Multicenter Observational Retrospective Study of Rare Primary Liver Cancers

Posted: August 7th, 2024, 11:00pm UTC

Conditions: Hepatocholangiocarcinoma; Fibrolamellar Carcinoma; Hepatic Epithelioid Hemangioendothelioma; Hepatoblastoma; Hepatic Neuroendocrine Carcinoma; Hepatic Carcinosarcomas; Hepatic Cystadenoma; Hepatic Leiomyosarcomas; Hepatic Angiosarcomas; Cholangiocarcinoma
Sponsors: Federation Francophone de Cancerologie Digestive; SociÃ©tÃ© Nationale FranÃ§aise de GastroentÃ©rologie
Recruiting
Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma

Posted: August 6th, 2024, 11:00pm UTC

Conditions: Living Donor Liver Transplantation; Liver Transplantation; Neoadjuvant Therapy
Interventions: Procedure: Living donor liver transplantation
Sponsors: Jena University Hospital
Not yet recruiting
Impact of Preoperative Endoscopic Ultrasound-guided Fine-needle Aspiration in Cholangiocarcinoma Patients

Posted: August 2nd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma Patients
Interventions: Diagnostic Test: Endoscopic ultrasound-guided fine-needle aspiration
Sponsors: Asian Institute of Gastroenterology, India
Not yet recruiting
Pemigatinib Combined With Durvalumab for Previously Treated Biliary Tract Carcinoma

Posted: July 31st, 2024, 11:00pm UTC

Conditions: Biliary Tract Carcinoma; Cholangiocarcinoma
Interventions: Drug: Pemigatinib and Durvalumab
Sponsors: Eastern Hepatobiliary Surgery Hospital
Not yet recruiting
Testing Ivonescimab Versus FOLFOX in Advanced Biliary Tract Cancer Patients

Posted: July 31st, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer
Interventions: Drug: Ivonescimab; Drug: FOLFOX regimen
Sponsors: UNICANCER; Cancer Research UK & UCL Cancer Trials Centre; Belgian Group of Digestive Oncology; Summit Therapeutics
Not yet recruiting
Neoadjuvant SBRT Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma

Posted: July 29th, 2024, 11:00pm UTC

Conditions: Resectable Hepatocellular Carcinoma; Macrovascular Invasion; CNLC IIIA Stage
Interventions: Drug: Neoadjuvant SBRT combined with Lenvatinib and Pucotenlimab
Sponsors: Sun Yat-sen University
Active, not recruiting
Neratinib Tablets Monotherapy for Advanced Solid Tumors With HER2 Mutations

Posted: July 25th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumor
Interventions: Drug: Neratinib tablets
Sponsors: Convalife (Shanghai) Co., Ltd.
Not yet recruiting
Futibatinib in Patients Previously Enrolled in an Antecedent Futibatinib as Monotherapy or Combination Therapy.

Posted: July 18th, 2024, 11:00pm UTC

Conditions: Advanced/Metastatic Cancer
Interventions: Drug: futibatinib; Drug: futibatinib, fulvestrant
Sponsors: Taiho Oncology, Inc.
Enrolling by invitation
GEMOX-HAIC Plus GEM-SYS in Combination With Lenvatinib and PD-1 Inhibitor for Large Unresectable ICC

Posted: July 17th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Gemcitabine-Oxaliplatin Regimen
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Posted: July 16th, 2024, 11:00pm UTC

Conditions: Pancreatic Ductal Adenocarcinoma; Cholangiocarcinoma; Gastric Cancer; Bladder Cancer; Hepatocellular Carcinoma; Pheochromocytoma; Ovarian Cancer
Interventions: Drug: [18F]FAPI-74; Drug: [18F]FDG
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Interventions: Drug: Ivosidenib; Drug: Durvalumab (for the first 8, 21-day, cycles); Drug: Gemcitabine (for the first 8, 21-day, cycles); Drug: Cisplatin (for the first 8, 21-day, cycles); Drug: Durvalumab (starting from cycle 9); Drug: Ivosidenib Recommended Combination Dose (RCD)
Sponsors: Institut de Recherches Internationales Servier
Not yet recruiting
Consolidative Radiotherapy (CSRT) in Patients With Oligometastatic/Locally Advanced Unresectable Bilary Tract Cancer (BTC)

Posted: July 15th, 2024, 11:00pm UTC

Conditions: Biliary Tract Cancer
Interventions: Radiation: Consolidative radiotherapy; Drug: Standard-of-care systemic therapy: Gemcitabine + cisplatin/oxaliplatin + Durvalumab/Pembrolizumab/Sintilimab/Toripalimab
Sponsors: Shanghai Zhongshan Hospital
Not yet recruiting
Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma

Posted: July 10th, 2024, 11:00pm UTC

Conditions: Klatskin Tumor
Interventions: Radiation: Stereotactic body radiation therapy
Sponsors: Erasmus Medical Center; Dutch Cancer Society
Recruiting
Phase 2 Study: OBI-833/OBI-821 Maintenance for Globo H+ Advanced Biliary Tract Cancer After Gemcitabine/Cisplatin

Posted: July 8th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Chemotherapy Effect; Immunotherapy
Interventions: Drug: OBI-833/OBI-821
Sponsors: Chang Gung Memorial Hospital
Not yet recruiting
TACE Combined With Immune Checkpoint Inhibitors for Liver Malignant Tumors

Posted: July 4th, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma Non-resectable; Cholangiocarcinoma Non-resectable; Liver Metastases; Liver Malignant Tumors
Interventions: Procedure: TACE with ICI
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Recruiting
ALgerian Cholecystectomy Outcomes and Determinants Study (AL-CODS)

Posted: July 1st, 2024, 11:00pm UTC

Conditions: Cholecystectomy; Adults; Gall Stone; Polyps; Pancreatitis Biliary; Gallbladder Dyskinesia; Cholecystitis
Sponsors: University of Oran 1
Not yet recruiting
Impact of Peri-Operative Hyponatremia on Postoperative Outcomes in Major HPB Surgeries for Cancers

Posted: June 26th, 2024, 11:00pm UTC

Conditions: Carcinoma
Sponsors: Institute of Liver and Biliary Sciences, India
Recruiting
Liquid Biopsy MonitORing Of CholangioCarcinOma for Treatment Response and Prognostic Outcomes (MOROCCO)

Posted: June 25th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Other: Non-Interventional Study
Sponsors: Mayo Clinic
Enrolling by invitation
A Study to Evaluate LB1410 in Combination With LB4330 in Patients With Advanced or Metastatic Solid Tumors

Posted: June 21st, 2024, 11:00pm UTC

Conditions: Solid Tumor
Interventions: Drug: LB1410; Drug: LB4330
Sponsors: L & L biopharma Co., Ltd., Shanghai China; Shanghai East Hospital
Recruiting
Microwave Ablation Versus Liver Resection for Intrahepatic Cholangiocarcinoma

Posted: June 17th, 2024, 11:00pm UTC

Conditions: Overall Survival; Disease-free Survival
Interventions: Procedure: Microwave ablation (MWA) versus Liver Resection (LR)
Sponsors: Chinese PLA General Hospital
Recruiting
Treatment of Distal Malignant Biliary Obstruction by Uncovered, Partially Covered, or Fully Covered Metal Stents

Posted: June 11th, 2024, 11:00pm UTC

Conditions: Pancreatic Cancer Non-resectable; Bile Duct Cancer; Papillary Carcinoma; Duodenal Cancer
Interventions: Procedure: Randomization to uncovered SEMS treating jaundice due to distal malignant biliary obstruction.; Procedure: Randomization to partially covered SEMS treating jaundice due to distal malignant biliary obstruction.; Procedure: Randomization to fully covered SEMS treating jaundice due to distal malignant biliary obstruction.
Sponsors: Region Stockholm
Recruiting
Combining Chemoradiotherapy With Sintilimab in First-Line ICC

Posted: June 7th, 2024, 11:00pm UTC

Conditions: ICC
Interventions: Radiation: radiotherapy; Drug: gemcitabine + cisplatin; Drug: slulimumab
Sponsors: Shanghai Zhongshan Hospital
Not yet recruiting
A Study Observing Everyday Effectiveness and Safety of the Drug Elafibranor in Participants With Primary Biliary Cholangitis Who Are Receiving Ongoing Treatment

Posted: June 6th, 2024, 11:00pm UTC

Conditions: Primary Biliary Cholangitis
Sponsors: Ipsen
Recruiting
Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma

Posted: June 4th, 2024, 11:00pm UTC

Conditions: Extrahepatic Cholangiocarcinoma; Unresectable Perihilar or Ductal CCA
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Procedure: ID-RFA
Sponsors: Institut fÃ¼r Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; UniversitÃ¤tsklinikum DÃ¼sseldorf, Germany; UniversitÃ¤tsklinikum KÃ¶ln, Germany; AstraZeneca
Recruiting
Phase II Study of the Combination of Durvalumab (MEDI4736) (PDL1 Inhibitor) and Olaparib (PARP Inhibitor) in Advanced Cholangiocarcinoma After Initial Chemotherapy and Durvalumab (BIL-PPP)

Posted: June 4th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: Durvalumab; Drug: Olaparib
Sponsors: Australasian Gastro-Intestinal Trials Group; Wayne Elphinstone Research Fund; AstraZeneca
Not yet recruiting
Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Combination Product: Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil
Sponsors: West China Hospital
Not yet recruiting
INSPIRE: A Multi-Cancer Early Detection Study

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Lung Cancer; Gastric Cancer; Liver Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Breast Cancer; Cervical Cancer; Ovarian Cancer; Endometrial Cancer; Bladder Cancer; Prostate Cancer; Cholangiocarcinoma
Sponsors: Singlera Genomics Inc.; Fudan University; Hubei Cancer Hospital, Huazhong University of Science and Technology; China-Japan Friendship Hospital; Shanxi Provincial Cancer Hospital; Xuhui Central Hospital, Fudan University; Shanghai Electric Power Hospital; East Hospital, Tongji University; The First Affiliated Hospital of Xi' an Jiaotong University; GaoZhou People's Hosipital; Anhui Provincial Hospital; Beijing Friendship Hospital
Not yet recruiting
Phase II Trial of Pemigatinib in Combination With Atezolizumab and Bevacizumab for Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion

Posted: June 3rd, 2024, 11:00pm UTC

Conditions: Advanced Cholangiocarcinoma; FGFR2 Fusion
Interventions: Drug: Pemigatinib; Drug: Atezolizumab; Drug: Bevacizumab
Sponsors: M.D. Anderson Cancer Center; Incyte Corporation; Genentech, Inc.
Not yet recruiting
Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma

Posted: May 30th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Radiation: Proton Beam Therapy; Drug: Concurrent oral capecitabine chemotherapy; Drug: Cisplatin & Gemcitabine intravenous chemotherapy; Procedure: Orthotropic Liver Transplant
Sponsors: The Christie NHS Foundation Trust; University College London Hospitals; University College, London; Royal Free Hospital NHS Foundation Trust
Not yet recruiting
hepatomiR cACLD Study

Posted: May 29th, 2024, 11:00pm UTC

Conditions: Chronic Liver Disease and Cirrhosis; Chronic Liver Disease; Portal Hypertension
Interventions: Diagnostic Test: hepatomiR
Sponsors: Karl Landsteiner University of Health Sciences; University Hospital St. PÃ¶lten
Recruiting
Tocilizumab for Painful Chronic Pancreatitis

Posted: May 23rd, 2024, 11:00pm UTC

Conditions: Pancreatitis, Chronic
Interventions: Drug: Tocilizumab 20 MG/ML [Actemra]; Drug: Sodium Chloride 0.9% Inj
Sponsors: Soren Schou Olesen; Aarhus University Hospital; University of Aarhus; Viborg Regional Hospital; Stanford University; Haukeland University Hospital
Recruiting
NXP800 for the Treatment of Patients With Advanced or Metastatic Cholangiocarcinoma

Posted: May 20th, 2024, 11:00pm UTC

Conditions: Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma; Refractory Cholangiocarcinoma; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Heat Shock Factor 1 Pathway Inhibitor NXP800; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Ultrasound-Guided Biopsy
Sponsors: Mayo Clinic
Recruiting
The Application of Digital Intelligent Diagnostic and Therapeutic Technology in Biliary Dilation Diagnosis

Posted: May 17th, 2024, 11:00pm UTC

Conditions: Congenital Biliary Dilatation; Choledochal Cyst
Interventions: Device: Three-dimensional visualization technology
Sponsors: Zhujiang Hospital
Recruiting
Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

Posted: May 16th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Lenvatinib
Sponsors: Zhiyong Huang
Not yet recruiting
Diagnostic Approach for Cholangiocarcinoma Using Liquid Bile Biopsy

Posted: May 16th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Diagnostic Test: Proteomic profile
Sponsors: University Hospital, Bordeaux
Not yet recruiting
Nasogastric Decompression Following Pancreaticoduodenectomy

Posted: May 14th, 2024, 11:00pm UTC

Conditions: Pancreatic Head Neoplasm; Delayed Gastric Emptying; Post Operative Ileus; Whipple Procedure
Interventions: Procedure: pancreaticoduodenectomy
Sponsors: Baylor College of Medicine
Completed
Neoantigen Vaccine Plus Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma After Radical Resection

Posted: May 9th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Combination Product: Neoantigen Vaccine plus Capecitabine
Sponsors: Yongyi Zeng
Not yet recruiting
A Prospective, Single-arm, Multicenter Phase II Clinical Study of HAIC in Combination With Adebrelimab and Bevacizumab for Potentially Resectable Hepatocellular Carcinoma

Posted: May 8th, 2024, 11:00pm UTC

Conditions: Adebrelimab; Hepatocellular Carcinoma
Interventions: Drug: Adebrelimab
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Recruiting
A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

Posted: May 6th, 2024, 11:00pm UTC

Conditions: Colorectal Cancer; Cholangiocarcinoma; Appendiceal Adenocarcinoma; Pancreatic Adenocarcinoma; Gastric Adenocarcinoma; Endometrial Adenocarcinoma; Triple Negative Breast Cancer; Ovarian Cancer; Prostate Cancer
Interventions: Drug: APL-5125
Sponsors: Apollo Therapeutics Ltd
Recruiting
Disitamab Vedotin Plus Cadonilimab in Patients With HER2 Mutant Advanced or Metastatic Bile Duct Adenocarcinoma

Posted: April 25th, 2024, 11:00pm UTC

Conditions: Bile Duct Adenocarcinoma Non-Resectable; HER2 Gene Mutation
Interventions: Drug: Disitamab Vedotin Plus Cadonilimab
Sponsors: Zhejiang Cancer Hospital
Recruiting
Detecting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma

Posted: April 24th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma Resectable; Cholangiocarcinoma; Liver
Interventions: Diagnostic Test: LyMIC (Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma)
Sponsors: City of Hope Medical Center
Recruiting
The Role of the Human Microbiome in Patients After Pancreatic Resection.

Posted: April 24th, 2024, 11:00pm UTC

Conditions: Pancreas Cancer; Pancreas Neoplasm; Pancreas Adenocarcinoma; Periampullary Cancer; Periampullary Carcinoma; Microbial Colonization
Interventions: Procedure: Pancreatic resection
Sponsors: St. Antonius Hospital
Not yet recruiting
EUS-Gallbladder vs CDS as First Line in MBDO- Palliative (CARPEGIEM Trial)

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Malignant Biliary Obstruction; Biliary Tract Neoplasms; Pancreatic Cancer Non-resectable
Interventions: Procedure: Endoscopic biliary drainage; Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS); Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS)
Sponsors: Hospital Universitari de Bellvitge; Hospital ClÃnico Universitario de Valencia; Hospital General Universitario de Alicante; Hospital Mutua de Terrassa; Hospital Universitario Ramon y Cajal; Hospital General Universitario de CastellÃ³n; Complejo Hospitalario de Navarra; University Hospital Virgen de las Nieves; Hospital de Sant Pau; University of Salamanca; Complejo Hospitalario Universitario de Santiago; Complejo Hospitalario Universitario de Vigo
Not yet recruiting
Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Radiation: radioembolization with Y-90; Drug: Durvalumab; Drug: Cisplatin; Drug: Gemcitabine
Sponsors: Francesco De Cobelli; Cardarelli Hospital; A.O. Ospedale Papa Giovanni XXIII; AOU Pisana, Pisa, Italy
Recruiting
A Single Arm, Single Centered Phase II Trial on the Combination of Adebrelimab, Surufatinib and Irinotecan Liposome-based HAIC in Advanced iCC

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Adebrelimab
Sponsors: Tianjin Medical University Cancer Institute and Hospital
Not yet recruiting
EUS-guided CDS vs ERCP as First Line in Malignant Distal Obstruction in Borderline Disease (CARPEDIEM-2 Trial)

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Malignant Biliary Obstruction; Pancreatic Cancer; Biliary Tract Neoplasms
Interventions: Procedure: Endoscopic biliary drainage; Device: Self-expandable metallic stent (SEMS); Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS)
Sponsors: Hospital Universitari de Bellvitge; Hospital Mutua de Terrassa; Hospital ClÃnico Universitario de Valencia; Hospital General Universitario de Alicante; Hospital Universitario Ramon y Cajal; Hospital General Universitario de CastellÃ³n; Hospital Ãlvaro Cunqueiro; Complejo Hospitalario Universitario de Santiago; University Hospital Virgen de las Nieves; Complejo Hospitalario de Navarra; Hospital de Sant Pau; University of Salamanca
Not yet recruiting
EUS-guided Choledochoduodenostomy vs ERCP as First Line in Malignant Distal Obstruction in Resectable Disease (CARPEDIEM-1 Trial)

Posted: April 19th, 2024, 11:00pm UTC

Conditions: Malignant Biliary Obstruction; Pancreatic Cancer Resectable; Biliary Tract Neoplasms
Interventions: Procedure: Endoscopic biliary drainage; Device: Self-expandable metallic stent (SEMS); Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS)
Sponsors: Hospital Universitari de Bellvitge; Hospital Mutua de Terrassa; Hospital ClÃnico Universitario de Valencia; Hospital General Universitario de Alicante; Hospital Universitario Ramon y Cajal; Hospital General Universitario de CastellÃ³n; Hospital Ãlvaro Cunqueiro; Complejo Hospitalario Universitario de Santiago; University Hospital Virgen de las Nieves; Complejo Hospitalario de Navarra; Hospital de Sant Pau; University of Salamanca
Not yet recruiting
First-line Treatment for Unresectable Locally Advanced Distal Cholangiocarcinoma Combining Radiotherapy and HAIC

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Radiation: Radiotherapy; Drug: HAIC (GEMOX); Drug: Chemotherapy
Sponsors: Shandong Cancer Hospital and Institute
Recruiting
Prognostic Factors for Survival in Patients With Cholangiocarcinoma

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Procedure: Resection/Ablation of tumor; Procedure: Palliative chemotherapy; Procedure: Neoadjuvant chemotherapy; Procedure: Stereotatic radiotherapy; Procedure: Best supportive care
Sponsors: Rigshospitalet, Denmark
Recruiting
Rollover Study to Provide Continued Access to TT-00420 (Tinengotinib) for Subjects With Advanced Solid Tumors

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumors; Cholangiocarcinoma
Interventions: Drug: Tinengotinib
Sponsors: TransThera Sciences (Nanjing), Inc.
Available
Digital Single-operator Cholangioscopy and Intraductal Ultrasound for Nonicteric Biliary Strictures

Posted: April 17th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Biliary Stricture
Sponsors: Soonchunhyang University Hospital
Not yet recruiting
Interventional Reference Levels (IRL) in Digestive Endoscopy

Posted: April 12th, 2024, 11:00pm UTC

Conditions: Each Endoscopic Intervention Using X-rays
Interventions: Procedure: ERCP; Procedure: endoscopic ultrasound; Procedure: gastroscopy; Procedure: Colonoscopy; Procedure: placement of a nasojejunal tube
Sponsors: Central Hospital, Nancy, France
Not yet recruiting
Plasma Metabolic Biomarkers for Multi-Cancer Diagnosis

Posted: April 12th, 2024, 11:00pm UTC

Conditions: Lung Cancer; Breast Cancer; Colorectal Cancer; Thyroid Cancer; Gastric Cancer; Cervical Cancer; Liver Cancer; Pancreatic Cancer; Cholangiocarcinoma; Prostate Cancer; Esophageal Cancer; Ovarian Cancer; Renal Cell Carcinoma
Sponsors: Beijing Friendship Hospital
Recruiting
EchoTip AcuCore Post-Market Clinical Study

Posted: April 10th, 2024, 11:00pm UTC

Conditions: Adenocarcinoma; Neuroendocrine Tumors; Hepatocellular Carcinoma; Cholangiocarcinoma; Malignant Lymphoma; Metastasis; Chronic Pancreatitis; Autoimmune Pancreatitis
Interventions: Device: EchoTip AcuCore
Sponsors: Cook Research Incorporated
Recruiting
Extent of Intrahepatic Infiltration of PHCC

Posted: April 10th, 2024, 11:00pm UTC

Conditions: Perihilar Cholangiocarcinoma
Sponsors: Beijing Tsinghua Chang Gung Hospital
Completed
The Effect of [18F] F-FAPI PET-CT on Management in Patients With Proximal Cholangiocarcinoma

Posted: April 9th, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: [18F]F-FAPI PET-CT
Sponsors: Mara Veenstra, MD; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); UMC Utrecht
Not yet recruiting
The Effects of Bromelain Supplement in Patients With Ulcerative Colitis

Posted: April 8th, 2024, 11:00pm UTC

Conditions: Ulcerative Colitis; Primary Sclerosing Cholangitis
Interventions: Dietary Supplement: Bromlein; Other: Placebo
Sponsors: National Nutrition and Food Technology Institute
Recruiting
Neo-adjuvant Chemo and Immunotherapy in The Pre-operAtive Treatment of Locally Advanced cholangIOcarciNoma

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma
Interventions: Drug: Durvalumab 1120 mg; Drug: Durvalumab 1500 mg; Drug: Tremelimumab i.v. at 300 mg; Combination Product: Cisplatin (CDDP) 25 mg/mq i.v; Combination Product: Gemcitabine (GEM) 1000 mg/mq i.v.
Sponsors: National Cancer Institute, Naples
Recruiting
An Exosome-Based Liquid Biopsy for the Differential Diagnosis of Primary Liver Cancer

Posted: April 2nd, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma; Primary Liver Cancer; Primary Liver Carcinoma; Hepatic Cancer; Hepatic Carcinoma
Interventions: Diagnostic Test: ELUCIDATE
Sponsors: City of Hope Medical Center
Recruiting
Washington University Participant Engagement and Cancer Genomic Sequencing Center (WU-PE-CGS)

Posted: April 1st, 2024, 11:00pm UTC

Conditions: Cholangiocarcinoma; Multiple Myeloma; Colon Cancer; Rectal Cancer
Interventions: Other: Return of Genetic Results: Biomarker information from cancer cells; Other: Return of Genetic Results: Inherited mutations related to cancer; Other: Return of Genetic Results: Inherited mutations related to other medical issues
Sponsors: Washington University School of Medicine; National Cancer Institute (NCI); The Foundation for Barnes-Jewish Hospital
Recruiting
EUS Examination Using EndoSound Vision System vs. Standard Echoendoscope

Posted: April 1st, 2024, 11:00pm UTC

Conditions: Pancreatic Disease; Pancreatic Cancer; Pancreatic Cyst; Gastrointestinal Tumor; Bile Duct Diseases; Bile Duct Cancer; Lymph Node Disease; Submucosal Tumor of Gastrointestinal Tract; Gastrointestinal Cancer
Interventions: Device: Endoscopic ultrasound examination
Sponsors: Orlando Health, Inc.
Recruiting
HAIC Combined With Cadonilimab and Regorafenib as 2nd-line Treatment for ICC

Posted: March 28th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HAIC-GEMOX+Cadonilimab+Regorafenib
Sponsors: Fudan University
Recruiting
A Phase 1a/1b Study of ACTM-838 in Patients With Advanced Solid Tumors

Posted: March 28th, 2024, 11:00pm UTC

Conditions: Solid Tumor
Interventions: Drug: ACTM-838
Sponsors: Actym Therapeutics, Inc.
Recruiting
A Single Center, Retrospective Clinical Study on the Clinical Characteristics of Primary Liver Cancer

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Primary Liver Cancer
Sponsors: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Recruiting
Exploratory Pharmacokinetic Study of Virgin Coconut Oil (VCO)

Posted: March 22nd, 2024, 11:00pm UTC

Conditions: Pharmacological Action
Interventions: Dietary Supplement: Virgin Coconut Oil
Sponsors: Food and Nutrition Research Institute, Philippines; Ateneo de Manila University; De La Salle Medical and Health Sciences Institute
Active, not recruiting
Impact of External Drainage of the Main Pancreatic Duct and Common Bile Duct on Pancreatic Fistula Following Pancreaticoduodenectomy

Posted: March 21st, 2024, 11:00pm UTC

Conditions: Pancreaticoduodenectomy
Interventions: Procedure: Main pancreatic duct and biliary duct external drainage; Procedure: Main pancreatic duct and biliary duct internal drainage
Sponsors: Shanghai Zhongshan Hospital; Huadong Hospital; RenJi Hospital; The First People's Hospital of Yunnan; First Affiliated Hospital Xi'an Jiaotong University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Recruiting
HAI-Floxuridine, or SIRT, Combined With Gemox For Patients With Intra-Hepatic Cholangiocarcinoma Not Amenable to Resection (TOMCAT)

Posted: March 15th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma; Chemotherapy Effect
Interventions: Drug: Floxuridine; Procedure: Selective Internal Radiation Therapy (SIRT)
Sponsors: Oslo University Hospital
Recruiting
Surufatinib Combined With Toripalimab and HAIC in the Treatment of Inoperable or Metastatic Intrahepatic Cholangiocarcinoma

Posted: March 15th, 2024, 11:00pm UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Surufatinibã€Toripalimabã€Gemcitabineã€Oxaliplatin
Sponsors: Fudan University
Not yet recruiting
Open Versus Laparoscopic Ablation of Liver Malignancies

Posted: March 12th, 2024, 11:00pm UTC

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Liver Metastases
Interventions: Procedure: Laparoscopic ablation; Procedure: Open ablation
Sponsors: Rigshospitalet, Denmark
Recruiting
$Permalink for 'Pemigatinib + Afatinib in Advanced Refractory Solid Tumors'$
Pemigatinib + Afatinib in Advanced Refractory Solid Tumors

Posted: March 12th, 2024, 11:00pm UTC

Conditions: Advanced Solid Tumor; Unresectable Solid Tumor; Metastatic Solid Tumor; Cholangiocarcinoma
Interventions: Drug: Afatinib; Drug: Pemigatinib
Sponsors: Massachusetts General Hospital; Boehringer Ingelheim; Incyte Corporation
Recruiting
Effectiveness of Endoscopic Papillectomy With Stent for Treating Duodenal Papillary Adenoma

Posted: March 8th, 2024, 1:00am UTC

Conditions: Duodenal Adenoma; Complication of Treatment
Interventions: Procedure: Stent Placement in Pancreatic and Bile Ducts
Sponsors: Beijing Friendship Hospital
Completed
Combined Therapy Using Gemcitabine and Cisplatin Chemotherapy, Lenvatinib and Adebrelimab for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Posted: March 7th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: combined therapy using gemcitabine and cisplatin chemotherapy, Lenvatinib and Adebrelimab
Sponsors: Nanfang Hospital, Southern Medical University
Recruiting
Perioperative Treatment of Resectable Intrahepatic Cholangiocarcinoma With the Combination of Adebrelimab and Apatinib and HAIC

Posted: March 6th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: HAIC; Drug: Adebrelimab; Drug: Apatinib
Sponsors: Lei ZHAO
Recruiting
A Machine-learning Model to Predict Lymph Node Metastasis of Intrahepatic Cholangiocarcinoma

Posted: March 4th, 2024, 1:00am UTC

Conditions: Intrahepatic Cholangiocarcinoma; Machine Learning
Interventions: Procedure: lymph nodes dissection
Sponsors: West China Hospital
Recruiting
Clinical Utility of Selected Circulating Tumor DNA Assays in Patients With Advanced Malignancy

Posted: March 4th, 2024, 1:00am UTC

Conditions: Metastatic Colorectal Cancer; Pancreas Adenocarcinoma; Cholangiocarcinoma
Interventions: Diagnostic Test: Multiplex PCR-test for circulating tumor DNA
Sponsors: Oslo University Hospital
Recruiting
FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis

Posted: February 29th, 2024, 1:00am UTC

Conditions: Primary Sclerosing Cholangitis; Inflammatory Bowel Diseases
Interventions: Biological: Faecal Microbiota Transplant; Other: FMT Placebo
Sponsors: University of Birmingham; PSC Support; Life Arc
Recruiting
Chemotherapy Combined With Adebrelimab and Apatinib as the Perioperative Treatment in Patients With Biliary Tract Cancer

Posted: February 28th, 2024, 1:00am UTC

Conditions: Resectable Intrahepatic Cholangiocarcinoma With High Risk of Recurrence
Interventions: Drug: Adebrelimab, Apatinib, Gemcitabine, cisplatin
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
An Exploratory Clinical Study to Evaluate the Safety and Efficacy of NK Cells (Combined With Standard Therapy) in the Treatment of Solid Tumor Patients

Posted: February 28th, 2024, 1:00am UTC

Conditions: Solid Tumors (Pancreatic Cancer, Esophageal Cancer, Gastric Cancer, Cholangiocarcinoma, Lung Cancer and Ovarian Cancer)
Interventions: Drug: Allogeneic NKï¼ˆCCT-ANK-11)
Sponsors: Beijing Kejing Biotechnology Co., Ltd.
Withdrawn
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

Posted: February 28th, 2024, 1:00am UTC

Conditions: Biliary Tract Cancer; HER2 Gene Mutation
Interventions: Drug: Zanidatamab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Durvalumab
Sponsors: Jazz Pharmaceuticals
Recruiting
Evaluation of diagnostiC Capacity of eccDNAs as Biomarkers in Indetermined biLiary Stricture(ECCBILE)

Posted: February 26th, 2024, 1:00am UTC

Conditions: Biliary Stricture; Bile Duct Cancer; Pancreas Cancer
Sponsors: Peking University Third Hospital; Beijing Tsinghua Changgeng Hospital
Recruiting
Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer

Posted: February 23rd, 2024, 1:00am UTC

Conditions: Bile Duct Cancer
Interventions: Drug: Gemcitabin, Cisplatin and Durvalumab; Procedure: Biliary Radiofrequency Ablation; Procedure: Endoscopic Retrograde Cholangio-Pancreatography with stenting
Sponsors: Insel Gruppe AG, University Hospital Bern; Swiss Cancer League
Not yet recruiting
Feasibility Study of Multi-Platform Profiling of Resected Biliary Tract Cancer

Fetched: February 21st, 2024, 3:01am UTC

Conditions: Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer; Intrahepatic Cholangiocarcinoma; Perihilar Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Hilar Cholangiocarcinoma; Distal Bile Duct Cancer
Interventions: Diagnostic Test: Multi-Platform Profiling with Organoid Drug Sensitivity Screening and ctDNA Monitoring
Sponsors: University of Washington; Natera, Inc.; SEngine Precision Medicine, Inc.
Active, not recruiting
Targeted Navigation in Hepatocellular Carcinoma (HCC)

Posted: February 15th, 2024, 1:00am UTC

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Hepatobiliary Cancer
Interventions: Behavioral: Target Navigation Pilot Program
Sponsors: University of Miami; The V Foundation
Recruiting

Google - Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma Market Report 2034 | - openPR

Posted: October 15th, 2024, 10:58am UTC

Intrahepatic Cholangiocarcinoma Market Report 2034 | openPR
Efficacy analysis of HAIC combined with lenvatinib plus PD1 inhibitor vs. first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma - Nature.com

Posted: October 13th, 2024, 8:48pm UTC

Efficacy analysis of HAIC combined with lenvatinib plus PD1 inhibitor vs. first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma Nature.com
Cholangiocarcinoma Clinical Trials 2024: EMA, PDMA, FDA - openPR

Posted: October 8th, 2024, 7:04am UTC

Cholangiocarcinoma Clinical Trials 2024: EMA, PDMA, FDA openPR
Research Trends and Hotspots Evolution of Artificial Intelligence for Cholangiocarcinoma Over the Past 10 Years: A Bibliometric Analysis - Frontiers

Posted: October 3rd, 2024, 2:33pm UTC

Research Trends and Hotspots Evolution of Artificial Intelligence for Cholangiocarcinoma Over the Past 10 Years: A Bibliometric Analysis Frontiers
Research Trends and Hotspots Evolution of Artificial Intelligence for Cholangiocarcinoma Over the Past 10 Years: A Bibliometric Analysis - Frontiers

Posted: October 3rd, 2024, 2:33pm UTC

Research Trends and Hotspots Evolution of Artificial Intelligence for Cholangiocarcinoma Over the Past 10 Years: A Bibliometric Analysis Frontiers
N-acetyltransferase 10 affects the proliferation of intrahepatic cholangiocarcinoma and M2-type polarization of macrophages by regulating C-C motif chemokine ligand 2 - Journal of Translational Medicine

Posted: September 30th, 2024, 5:16am UTC

N-acetyltransferase 10 affects the proliferation of intrahepatic cholangiocarcinoma and M2-type polarization of macrophages by regulating C-C motif chemokine ligand 2 Journal of Translational Medicine
A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma - Nature.com

Posted: September 30th, 2024, 3:33am UTC

A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma Nature.com
A case report: deep and durable response to low-dose lenvatinib and tislelizumab in an elderly patient with advanced intrahepatic cholangiocarcinoma - Frontiers

Posted: September 25th, 2024, 2:00am UTC

A case report: deep and durable response to low-dose lenvatinib and tislelizumab in an elderly patient with advanced intrahepatic cholangiocarcinoma Frontiers
Lisata Therapeutics Announces First Patient Treated in the Second-line Cholangiocarcinoma Cohort of the BOLSTER Trial - Yahoo Finance

Posted: September 17th, 2024, 7:00am UTC

Lisata Therapeutics Announces First Patient Treated in the Second-line Cholangiocarcinoma Cohort of the BOLSTER Trial Yahoo Finance
Elucidating the molecular markers and biological pathways associated with extrahepatic cholangiocarcinoma: a transcriptome sequencing study - Frontiers

Posted: September 17th, 2024, 10:56pm UTC

Elucidating the molecular markers and biological pathways associated with extrahepatic cholangiocarcinoma: a transcriptome sequencing study Frontiers
The pathological significance and potential mechanism of ACLY in cholangiocarcinoma - Frontiers

Posted: September 10th, 2024, 4:54pm UTC

The pathological significance and potential mechanism of ACLY in cholangiocarcinoma Frontiers
Researchers compare tumor characteristics, survival outcome of different bile duct cancers - Medical Xpress

Posted: September 10th, 2024, 1:44pm UTC

Researchers compare tumor characteristics, survival outcome of different bile duct cancers Medical Xpress
Efficacy and safety of endoscopic nasobiliary drainage versus percutaneous transhepatic cholangial drainage in the treatment of advanced hilar cholangiocarcinoma: a systematic review and meta-analysis - BMC Gastroenterology

Posted: September 6th, 2024, 6:36am UTC

Efficacy and safety of endoscopic nasobiliary drainage versus percutaneous transhepatic cholangial drainage in the treatment of advanced hilar cholangiocarcinoma: a systematic review and meta-analysis BMC Gastroenterology
Artificial intelligence for ultrasonographic detection and diagnosis of hepatocellular carcinoma and cholangiocarcinoma - Nature.com

Posted: September 4th, 2024, 10:39am UTC

Artificial intelligence for ultrasonographic detection and diagnosis of hepatocellular carcinoma and cholangiocarcinoma Nature.com
Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression - Frontiers

Posted: September 3rd, 2024, 11:55pm UTC

Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression Frontiers
Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative option for advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study - Frontiers

Posted: September 2nd, 2024, 2:00am UTC

Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative option for advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study Frontiers
ZNF460-mediated upregulation of APCDD1L-DT promotes cholangiocarcinoma development by inhibiting the ubiquitin-mediated degradation of DVL2 - Nature.com

Posted: August 29th, 2024, 9:13pm UTC

ZNF460-mediated upregulation of APCDD1L-DT promotes cholangiocarcinoma development by inhibiting the ubiquitin-mediated degradation of DVL2 | Cancer Gene Therapy Nature.com
Identification of autoantibodies as potential non-invasive biomarkers for intrahepatic cholangiocarcinoma - Nature.com

Posted: August 28th, 2024, 2:26pm UTC

Identification of autoantibodies as potential non-invasive biomarkers for intrahepatic cholangiocarcinoma Nature.com
Elucidating the Molecular Markers and Biological Pathways Associated with Extrahepatic Cholangiocarcinoma: A Transcriptome Sequencing Study - Frontiers

Posted: August 26th, 2024, 7:55am UTC

Elucidating the Molecular Markers and Biological Pathways Associated with Extrahepatic Cholangiocarcinoma: A Transcriptome Sequencing Study Frontiers
UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis - Nature.com

Posted: August 23rd, 2024, 1:43pm UTC

UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis Nature.com
Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration - Frontiers

Posted: August 21st, 2024, 9:27pm UTC

Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration Frontiers
Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative optionfor advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study - Frontiers

Posted: August 19th, 2024, 9:40am UTC

Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative optionfor advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study Frontiers
Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration - Frontiers

Posted: August 19th, 2024, 8:11am UTC

Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration Frontiers
Prognostic factors in patients with intrahepatic cholangiocarcinoma - Nature.com

Posted: August 17th, 2024, 7:43am UTC

Prognostic factors in patients with intrahepatic cholangiocarcinoma Nature.com
AMDHD1 acts as a tumor suppressor and contributes to activation of TGF-Î² signaling pathway in cholangiocarcinoma - Nature.com

Posted: August 14th, 2024, 2:59pm UTC

AMDHD1 acts as a tumor suppressor and contributes to activation of TGF-Î² signaling pathway in cholangiocarcinoma Nature.com
Obituary, Visitation & Funeral Information | Tina House - Webb Funeral Home

Posted: August 14th, 2024, 2:00am UTC

Obituary, Visitation & Funeral Information | Tina House Webb Funeral Home
Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma - Frontiers

Posted: August 7th, 2024, 12:41am UTC

Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma Frontiers
Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial - ASCO Journals

Posted: August 5th, 2024, 3:23pm UTC

Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial ASCO Journals
MSH6 germline mutations leading to Lynch syndrome-associated cholangiocarcinoma: a case report - Frontiers

Posted: August 5th, 2024, 12:35am UTC

MSH6 germline mutations leading to Lynch syndrome-associated cholangiocarcinoma: a case report Frontiers
Neoadjuvant therapy reduces node positivity but does not confer survival benefit versus up-front resection for resectable intrahepatic cholangiocarcinoma: A propensity-matched analysis - Wiley Online Library

Posted: July 31st, 2024, 2:00am UTC

Neoadjuvant therapy reduces node positivity but does not confer survival benefit versus up-front resection for resectable intrahepatic cholangiocarcinoma: A propensity-matched analysis Wiley Online Library
The Prognostic Value of Preoperative Peripheral Blood Inflammatory Biomarkers in Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis - Frontiers

Posted: July 30th, 2024, 4:44pm UTC

The Prognostic Value of Preoperative Peripheral Blood Inflammatory Biomarkers in Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis Frontiers
Finding a rare bile duct cancerâ€™s weaknesses - Fred Hutchinson Cancer Center

Posted: July 30th, 2024, 10:03am UTC

Finding a rare bile duct cancerâ€™s weaknesses Fred Hutchinson Cancer Center
Research Progress and Prospect of Postoperative Adjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma - Frontiers

Posted: July 29th, 2024, 4:53pm UTC

Research Progress and Prospect of Postoperative Adjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma Frontiers
Editorial: Clinical management of cholangiocarcinoma: surgical approaches and therapies - Frontiers

Posted: July 29th, 2024, 12:49am UTC

Editorial: Clinical management of cholangiocarcinoma: surgical approaches and therapies Frontiers
Editorial: Clinical management of cholangiocarcinoma: surgical approaches and therapies - Frontiers

Posted: July 29th, 2024, 12:48am UTC

Editorial: Clinical management of cholangiocarcinoma: surgical approaches and therapies Frontiers
Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study - Frontiers

Posted: July 26th, 2024, 2:00am UTC

Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study Frontiers
Hot Peeps Beat is back - taylorpress.net

Posted: July 23rd, 2024, 8:09pm UTC

Hot Peeps Beat is back taylorpress.net
MSH6 germline mutations leading to Lynch syndromeassociated cholangiocarcinoma: A case report - Frontiers

Posted: July 22nd, 2024, 9:27am UTC

MSH6 germline mutations leading to Lynch syndromeassociated cholangiocarcinoma: A case report Frontiers
MSH6 germline mutations leading to Lynch syndromeassociated cholangiocarcinoma: A case report - Frontiers

Posted: July 22nd, 2024, 9:27am UTC

MSH6 germline mutations leading to Lynch syndromeassociated cholangiocarcinoma: A case report Frontiers
FIGHT-202: Analyzing the Effects of Pemigatinib in Patients With Cholangiocarcinoma - DocWire News

Posted: July 22nd, 2024, 7:01am UTC

FIGHT-202: Analyzing the Effects of Pemigatinib in Patients With Cholangiocarcinoma DocWire News
FIGHT-202: Analyzing the Effects of Pemigatinib in Patients With Cholangiocarcinoma - DocWire News

Posted: July 22nd, 2024, 6:48am UTC

FIGHT-202: Analyzing the Effects of Pemigatinib in Patients With Cholangiocarcinoma DocWire News
MRI features of combined hepatocellular-cholangiocarcinoma - springermedicine.com

Posted: July 20th, 2024, 2:00am UTC

MRI features of combined hepatocellular-cholangiocarcinoma springermedicine.com
Retraction Note: csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis - Parasites & Vectors

Posted: July 18th, 2024, 12:06pm UTC

Retraction Note: csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis Parasites & Vectors
Retraction Note: csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis - Parasites & Vectors

Posted: July 18th, 2024, 12:06pm UTC

Retraction Note: csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis Parasites & Vectors
The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials - Frontiers

Posted: July 17th, 2024, 2:00am UTC

The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials Frontiers
Lisata Therapeutics Announces Completion of Enrollment in its Phase 2a BOLSTER Trial of Certepetide in First-Line Cholangiocarcinoma - StockTitan

Posted: July 16th, 2024, 7:00am UTC

Lisata Therapeutics Announces Completion of Enrollment in its Phase 2a BOLSTER Trial of Certepetide in First-Line Cholangiocarcinoma StockTitan
Lisata Therapeutics Announces Completion of Enrollment in its Phase 2a BOLSTER Trial of Certepetide in First-Line Cholangiocarcinoma - Yahoo Finance

Posted: July 16th, 2024, 7:00am UTC

Lisata Therapeutics Announces Completion of Enrollment in its Phase 2a BOLSTER Trial of Certepetide in First-Line Cholangiocarcinoma Yahoo Finance
Best of SAGES 2024: Robotic Cholangiocarcinoma Resection With Hepaticojejunostomy - General Surgery News

Posted: July 15th, 2024, 11:01pm UTC

SAGES Robotic Cholangiocarcinoma Resection With Hepaticojejunostomy General Surgery News
Case report: Translational treatment of unresectable intrahepatic cholangiocarcinoma: Tislelizumab, Lenvatinib, and GEMOX in one case - Frontiers

Posted: July 14th, 2024, 2:00am UTC

Case report: Translational treatment of unresectable intrahepatic cholangiocarcinoma: Tislelizumab, Lenvatinib, and GEMOX in one case Frontiers
Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study - Frontiers

Posted: July 13th, 2024, 9:36pm UTC

Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study Frontiers
Lisataâ€™s certepetide showing promising early results as cholangiocarcinoma treatment â€“ ICYMI - Proactive Investors UK

Posted: July 13th, 2024, 12:28pm UTC

Lisataâ€™s certepetide showing promising early results as cholangiocarcinoma treatment â€“ ICYMI Proactive Investors UK
Systematic Profiling of Mitochondria-Related Transcriptome in Tumorigenesis, Prognosis, and Tumor Immune Microenvironment of Intrahepatic Cholangiocarcinoma: A Multi-Center Cohort Study - Frontiers

Posted: July 12th, 2024, 11:50am UTC

Systematic Profiling of Mitochondria-Related Transcriptome in Tumorigenesis, Prognosis, and Tumor Immune Microenvironment of Intrahepatic Cholangiocarcinoma: A Multi-Center Cohort Study Frontiers
Bile Duct Cancer (Cholangiocarcinoma) Drugs, FDA Approvals, - openPR

Posted: July 12th, 2024, 10:16pm UTC

Bile Duct Cancer (Cholangiocarcinoma) Drugs, FDA Approvals, openPR
Lisata announces promising preclinical results in cholangiocarcinoma study - Proactive Investors USA

Posted: July 11th, 2024, 5:41pm UTC

Lisata announces promising preclinical results in cholangiocarcinoma study Proactive Investors USA
Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway - Nature.com

Posted: July 11th, 2024, 11:11am UTC

Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway Nature.com
Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway - Nature.com

Posted: July 11th, 2024, 11:11am UTC

Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway Nature.com
Lisataâ€™s Certepetide: promising preclinical results in cholangiocarcinoma - Proactive Investors USA

Posted: July 11th, 2024, 10:44am UTC

Lisataâ€™s Certepetide: promising preclinical results in cholangiocarcinoma Proactive Investors USA
Lisata announces promising preclinical results in cholangiocarcinoma study - Proactive Investors Australia

Posted: July 11th, 2024, 10:39am UTC

Lisata announces promising preclinical results in cholangiocarcinoma study Proactive Investors Australia
Lisataâ€™s Certepetide: promising preclinical results in cholangiocarcinoma - Proactive Investors Australia

Posted: July 11th, 2024, 10:39am UTC

Lisataâ€™s Certepetide: promising preclinical results in cholangiocarcinoma Proactive Investors Australia
Bile Duct Cancer (Cholangiocarcinoma) Treatment Market Size | Global Demand and Business Trends 2032 - WICZ

Posted: July 11th, 2024, 2:00am UTC

Bile Duct Cancer (Cholangiocarcinoma) Treatment Market Size | Global Demand and Business Trends 2032 WICZ
Lisata Therapeuticsâ€™ Certepetide Shows Promise in Improving Standard Treatment for Intrahepatic Cholangiocarcinoma in a Preclinical Model - StockTitan

Posted: July 10th, 2024, 7:00am UTC

Lisata Therapeuticsâ€™ Certepetide Shows Promise in Improving Standard Treatment for Intrahepatic Cholangiocarcinoma in a Preclinical Model StockTitan
Lisata Therapeuticsâ€™ Certepetide Shows Promise in Improving Standard Treatment for Intrahepatic Cholangiocarcinoma in a Preclinical Model - Yahoo Finance

Posted: July 10th, 2024, 2:00am UTC

Lisata Therapeuticsâ€™ Certepetide Shows Promise in Improving Standard Treatment for Intrahepatic Cholangiocarcinoma in a Preclinical Model Yahoo Finance
Imugene doses first patient for VAXINIA bile tract cancer trial in Melbourne - Proactive Investors UK

Posted: July 9th, 2024, 7:35pm UTC

Imugene doses first patient for VAXINIA bile tract cancer trial in Melbourne Proactive Investors UK
Liver fibrosis as a predictor of liver failure and outcome following ALPPS among patients with primary liver cancer - Nature

Posted: July 9th, 2024, 10:04am UTC

Liver fibrosis as a predictor of liver failure and outcome following ALPPS among patients with primary liver cancer Nature
Intrahepatic Cholangiocarcinoma Pipeline Analysis 2024: FDA - openPR

Posted: July 9th, 2024, 7:08am UTC

Intrahepatic Cholangiocarcinoma Pipeline Analysis 2024: FDA openPR
Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma - ScienceDirect.com

Posted: July 8th, 2024, 4:08pm UTC

Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma ScienceDirect.com
Mining the interpretable prognostic features from pathological image of intrahepatic cholangiocarcinoma using multi-modal deep learning - BMC Medicine

Posted: July 8th, 2024, 2:00am UTC

Mining the interpretable prognostic features from pathological image of intrahepatic cholangiocarcinoma using multi-modal deep learning BMC Medicine
Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review - springermedicine.com

Posted: July 7th, 2024, 2:00am UTC

Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review springermedicine.com
Use of the Advanced Lung Cancer Inflammation Index as a Prognostic Indicator for Patients With Cholangiocarcinoma - Frontiers

Posted: July 5th, 2024, 3:03pm UTC

Use of the Advanced Lung Cancer Inflammation Index as a Prognostic Indicator for Patients With Cholangiocarcinoma Frontiers
Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach - Frontiers

Posted: July 4th, 2024, 8:32am UTC

Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach Frontiers
Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach - Frontiers

Posted: July 4th, 2024, 8:32am UTC

Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach Frontiers
Transplant Oncology Offers New Hope for Intra Hepatic Cholangiocarcinoma - Lelezard

Posted: July 3rd, 2024, 11:10pm UTC

Transplant Oncology Offers New Hope for Intra Hepatic Cholangiocarcinoma Lelezard
Bile Duct Cancer (Cholangiocarcinoma) Treatment Market Size Report 2024-2032 | 128 Pages Report - WICZ

Posted: June 30th, 2024, 4:14am UTC

Bile Duct Cancer (Cholangiocarcinoma) Treatment Market Size Report 2024-2032 | 128 Pages Report WICZ
A novel nomogram for adult primary perihilar cholangiocarcinoma and considerations concerning lymph node dissection - Frontiers

Posted: June 30th, 2024, 1:18am UTC

A novel nomogram for adult primary perihilar cholangiocarcinoma and considerations concerning lymph node dissection Frontiers
Gemcitabine-Induced Thrombotic Microangiopathy in a Patient With Cholangiocarcinoma: An Atypical Case - Cureus

Posted: June 28th, 2024, 10:45am UTC

Gemcitabine-Induced Thrombotic Microangiopathy in a Patient With Cholangiocarcinoma: An Atypical Case Cureus
A metabolomics approach reveals metabolic disturbance of human cholangiocarcinoma cells after parthenolide treatment - ScienceDirect.com

Posted: June 28th, 2024, 2:00am UTC

A metabolomics approach reveals metabolic disturbance of human cholangiocarcinoma cells after parthenolide treatment ScienceDirect.com
Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a ... - Nature.com

Posted: June 27th, 2024, 6:49am UTC

Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a single-center propensity score matching analysis Nature.com
Establishment and validation of a nomogram containing cytokeratin fragment antigen 21-1 for the differential diagnosis ... - Frontiers

Posted: June 27th, 2024, 2:00am UTC

Establishment and validation of a nomogram containing cytokeratin fragment antigen 21-1 for the differential diagnosis of intrahepatic cholangiocarcinoma and hepatocellular carcinoma Frontiers
Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a single-center propensity score matching analysis - Nature.com

Posted: June 27th, 2024, 2:00am UTC

Evaluation of the outcomes of biliary-enteric reconstruction in robotic radical resection of hilar cholangiocarcinoma: a single-center propensity score matching analysis Nature.com
CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray ... - Frontiers

Posted: June 26th, 2024, 8:23pm UTC

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray ... Frontiers
Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy ... - Frontiers

Posted: June 26th, 2024, 11:16am UTC

Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients Frontiers
Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients - Frontiers

Posted: June 26th, 2024, 11:16am UTC

Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients Frontiers
Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic ... - Nature.com

Posted: June 26th, 2024, 10:23am UTC

Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma | Cell Death Discovery Nature.com
Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma | Cell Death Discovery - Nature.com

Posted: June 26th, 2024, 10:23am UTC

Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma | Cell Death Discovery Nature.com
Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the ... - Frontiers

Posted: June 26th, 2024, 2:19am UTC

Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics Frontiers
Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics - Frontiers

Posted: June 26th, 2024, 2:19am UTC

Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics Frontiers
Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study - Frontiers

Posted: June 26th, 2024, 11:25pm UTC

Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study Frontiers
Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand - Frontiers

Posted: June 25th, 2024, 4:13pm UTC

Modification of the eighth AJCC/UICC staging system for perihilar cholangiocarcinoma: An alternative pathological staging system from cholangiocarcinoma-prevalent Northeast Thailand Frontiers
Intrahepatic Cholangiocarcinoma Pipeline and Clinical Trials Assessment 2024: FDA Approvals, Therapies and Key ... - openPR

Posted: June 25th, 2024, 3:38pm UTC

Intrahepatic Cholangiocarcinoma Pipeline and Clinical Trials Assessment 2024: FDA Approvals, Therapies and Key ... openPR
Case report: Toceranib as adjuvant chemotherapy in a dog with incompletely resected combined hepatocellular ... - Frontiers

Posted: June 25th, 2024, 1:07pm UTC

Case report: Toceranib as adjuvant chemotherapy in a dog with incompletely resected combined hepatocellular-cholangiocarcinoma Frontiers
Editorial: Novel therapeutic approaches for biliary tract cancer and hepatocellular carcinoma - Frontiers

Posted: June 25th, 2024, 11:11am UTC

Editorial: Novel therapeutic approaches for biliary tract cancer and hepatocellular carcinoma Frontiers
Preoperative prognostic nutritional index predicts short-term complications after radical resection of distal ... - Frontiers

Posted: June 25th, 2024, 5:22am UTC

Preoperative prognostic nutritional index predicts short-term complications after radical resection of distal ... Frontiers
Development of machine learning models for patients in the high intrahepatic cholangiocarcinoma incidence age group - BMC Geriatrics

Posted: June 25th, 2024, 2:00am UTC

Development of machine learning models for patients in the high intrahepatic cholangiocarcinoma incidence age group BMC Geriatrics
Cholangiocarcinoma Market Expected to Expand at a Steady 2024-2031 - openPR

Posted: June 24th, 2024, 6:18am UTC

Cholangiocarcinoma Market Expected to Expand at a Steady 2024-2031 openPR
Mucin in Primary Liver Carcinomas: Combined Hepatocellular-Cholangiocarcinoma or Variant Hepatocellular Carcinoma - Wiley Online Library

Posted: June 23rd, 2024, 1:52pm UTC

Mucin in Primary Liver Carcinomas: Combined Hepatocellular-Cholangiocarcinoma or Variant Hepatocellular Carcinoma Wiley Online Library
Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma - Nature.com

Posted: June 22nd, 2024, 2:00am UTC

Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma Nature.com
Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma - Nature.com

Posted: June 22nd, 2024, 2:00am UTC

Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma Nature.com
Study highlights importance of early detection in bile duct cancer for patients with rare liver disease - Medical Xpress

Posted: June 20th, 2024, 2:38pm UTC

Study highlights importance of early detection in bile duct cancer for patients with rare liver disease Medical Xpress
Challenges in treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis - News-Medical.Net

Posted: June 20th, 2024, 12:49pm UTC

Challenges in treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis News-Medical.Net
Early detection crucial in bile duct cancer for patients with rare liver disease - EurekAlert

Posted: June 20th, 2024, 10:43am UTC

Early detection crucial in bile duct cancer for patients with rare liver disease EurekAlert

PubMed - Bile Duct Cancer

Nomograms predicting benefit after immunotherapy in oral bifidobacteria supplementation ICC patients: a retrospective study

Fetched: October 16th, 2024, 2:01am UTC by Sihui Zhu

BMC Cancer. 2024 Oct 14;24(1):1274. doi: 10.1186/s12885-024-12982-4.

ABSTRACT

PURPOSE: The objective of this study was to develop nomograms for predicting outcomes following immunotherapy in patients diagnosed with intrahepatic cholangiocarcinoma (ICC).

PATIENTS AND METHODS: A retrospective analysis was conducted on data from 75 ICC patients who received immunotherapy at Jinling Hospital and Drum Hospital. The discriminative power, accuracy, and clinical applicability of the nomograms were assessed using the concordance index (C-index), calibration curve, and decision curve analysis (DCA). The predictive performance of the nomograms for overall survival (OS) and progression-free survival (PFS) was evaluated using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier curves were also generated for validation purposes.

RESULTS: Multivariable analysis identified independent prognostic factors for OS, including CA19-9 levels, portal vein tumor thrombus (PVTT) grade, bifidobacteria administration, and surgery. The C-index of the nomogram for OS prediction was 0.722 (95% confidence interval [CI]: 0.661-0.783). Independent prognostic factors for PFS included CA19-9 levels, albumin, and bilirubin, with a C-index of 0.678 (95% CI: 0.612-0.743) for the nomogram predicting PFS. Calibration curves demonstrated strong concordance between predicted and observed outcomes, while DCA and Kaplan-Meier curves further supported the clinical utility of the nomogram.

CONCLUSION: The nomogram developed in this study demonstrated favorable performance in predicting the prognosis of ICC patients undergoing immunotherapy. Additionally, our findings, for the first time, identified probiotics as a potential prognostic marker for immunotherapy. This prognostic model has the potential to enhance patient selection for immunotherapy and improve clinical decision-making.

PMID:39402531 | DOI:10.1186/s12885-024-12982-4
miR-182-5p promotes the proliferation and invasion of hilar cholangiocarcinoma cells by inhibiting FBXW7

Fetched: October 16th, 2024, 2:01am UTC by Hang Zhou

J Cancer Res Clin Oncol. 2024 Oct 15;150(10):461. doi: 10.1007/s00432-024-05961-6.

ABSTRACT

BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment.

METHODS: HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3'UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes.

RESULTS: miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 'UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo.

CONCLUSION: miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.

PMID:39402299 | DOI:10.1007/s00432-024-05961-6
Prognostic Role of Hemoglobin Combined With Geriatric Nutritional Risk Index in Patients With Vater Ampulla Carcinoma Undergoing Pancreaticoduodenectomy

Fetched: October 16th, 2024, 2:01am UTC by Jieping Ying

Cancer Med. 2024 Oct;13(19):e70334. doi: 10.1002/cam4.70334.

ABSTRACT

OBJECTIVES: The purpose of this investigation was to assess the prognostic importance of the combination of preoperative hemoglobin (Hb) levels and Geriatric Nutritional Risk Index (GNRI) in forecasting postoperative survival outcomes for patients undergoing pancreaticoduodenectomy (PD) due to Vater ampulla carcinoma (VPC).

METHODS: The GNRI nutritional screening was conducted for all patients, and patient outcomes, including overall survival (OS), were subsequently monitored. An H- GNRI scoring system was established using the optimal critical values of 125.5 g/L for Hb and 91.72 for GNRI, as determined by X-tile software. According to the H-GNRI score, the patients were categorized into three groups, namely low H-GNRI group (H-GNRI score = 0, n = 47) with Hb < 125.5 g/L and GNRI < 91.72; medium H-GNRI group (H-GNRI score = 1, n = 77) with Hb < 125.5 g/L and GNRI â‰¥ 91.72, or Hb â‰¥ 125.5 g/L and GNR < 91.72; and high H-GNRI group (H-GNRI score = 2, n = 51) with Hb â‰¥ 125.5 g/L and GNRI â‰¥ 91.72. The Kaplan-Meier analysis and log-rank tests were employed to evaluate the OS rate and compare survival disparities among various groups. Additionally, both univariate and multivariate analyses were conducted utilizing the Cox regression model, with p < 0.05 considered statistically significant. Finally, to evaluate the predictive effectiveness of Hb, GNRI, and H-GNRI, a receiver operating characteristic (ROC) curve was constructed to compare the area under curve (AUC) values.

RESULTS: The OS rate was higher in patients with high Hb levels (â‰¥ 125.5 g/L) compared to those with low Hb levels (< 125.5 g/L). Likewise, patients in the high GNRI group (â‰¥ 91.72) exhibited significantly superior OS compared to those in the low GNRI group (< 91.72). Compared with both the medium and low H-GNRI groups, the high H-GNRI group demonstrated a notably higher OS rate. The T stage (HR = 2.523, 95% CI: 1.694-3.757, p < 0.001), N stage (HR = 2.018, 95% CI: 1.255-3.246, p = 0.004), and the H-GNRI score (H-GNRI score of 2 used as the baseline; H-GNRI score of 0: HR = 2.569, 95% CI: 1.499-4.402, p < 0.001; H-GNRI score of 1: HR = 1.835, 95% CI: 1.118-3.014, p = 0.016), after adjusting for gender, were determined to be independent significant predictors affecting the OS of patients with VPC. The AUC of H-GNRI was 0.677, exceeding that of Hb levels (0.631) and GNRI (0.615).

CONCLUSIONS: The combination of preoperative Hb levels and GNRI demonstrates superior predictive efficacy for VPC patients undergoing PD, compared with either Hb levels or GNRI score alone. Therefore, the H-GNRI score can be utilized to promptly identify high-risk patients, establish comprehensive nutritional pre-rehabilitation plans through interdisciplinary collaboration, and inform decisions regarding additional adjunctive therapies.

PMID:39400987 | PMC:PMC11472652 | DOI:10.1002/cam4.70334
The pathological significance and potential mechanism of ACLY in cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Xiaoyan Sun

Front Immunol. 2024 Sep 27;15:1477267. doi: 10.3389/fimmu.2024.1477267. eCollection 2024.

ABSTRACT

BACKGROUND AND AIM: Cholangiocarcinoma (CCA) is a rare cancer, yet its incidence and mortality rates have been steadily increasing globally over the past few decades. Currently, there are no effective targeted treatment strategies available for patients. ACLY (ATP Citrate Lyase), a key enzyme in de novo lipogenesis, is aberrantly expressed in several tumors and is associated with malignant progression. However, its role and mechanisms in CCA have not yet been elucidated.

METHODS: The expression of ACLY in CCA was assessed using transcriptomic profiles and tissue microarrays. Kaplan-Meier curves were employed to evaluate the prognostic significance of ACLY in CCA. Functional enrichment analysis was used to explore the potential mechanisms of ACLY in CCA. A series of assays were conducted to examine the effects of ACLY on the proliferation and migration of CCA cells. Ferroptosis inducers and inhibitors, along with lipid peroxide probes and MDA assay kits, were utilized to explore the role of ACLY in ferroptosis within CCA. Additionally, lipid-depleted fetal bovine serum and several fatty acids were used to evaluate the impact of fatty acids on ferroptosis induced by ACLY inhibition. Correlation analyses were performed to elucidate the relationship between ACLY and tumor stemness as well as tumor microenvironment.

RESULTS: The expression of ACLY was found to be higher in CCA tissues compared to adjacent normal tissues. Patients with elevated ACLY expression demonstrated poorer overall survival outcomes. ACLY were closed associated with fatty acid metabolism and tumor-initiating cells. Knockdown of ACLY did not significantly impact the proliferation and migration of CCA cells. However, ACLY inhibition led to increased accumulation of lipid peroxides and enhanced sensitivity of CCA cells to ferroptosis inducers. Polyunsaturated fatty acids were observed to inhibit the proliferation of ACLY-knockdown cells; nonetheless, this inhibitory effect was diminished when the cells were cultured in medium supplemented with lipid-depleted fetal bovine serum. Additionally, ACLY expression was negatively correlated with immune cell infiltration and immune scores in CCA.

CONCLUSION: ACLY promotes ferroptosis by disrupting the balance of saturated and unsaturated fatty acids. ACLY may therefore serve as a potential diagnostic and therapeutic target for CCA.

PMID:39399493 | PMC:PMC11466796 | DOI:10.3389/fimmu.2024.1477267
Efficacy analysis of HAIC combined with lenvatinib plus PD1 inhibitor vs. first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Zhipeng Lin

Sci Rep. 2024 Oct 14;14(1):23961. doi: 10.1038/s41598-024-75102-z.

ABSTRACT

This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People's Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients.

PMID:39397104 | PMC:PMC11471826 | DOI:10.1038/s41598-024-75102-z
Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers

Fetched: October 16th, 2024, 2:01am UTC by Hyein Jeon

Front Oncol. 2024 Sep 26;14:1454882. doi: 10.3389/fonc.2024.1454882. eCollection 2024.

ABSTRACT

Claudins, a family of tetraspan transmembrane proteins, are critical to the integrity of tight junctions in epithelia and endothelia, influencing cellular processes such as development, differentiation, and apoptosis. Abnormal claudin expression is associated with various malignancies, particularly affecting tissue architecture and potentially facilitating tumor invasion and metastasis. In this comprehensive review, we explore the multifaceted functions of claudins: their expression, specific roles in cancer with a focus on hepato-pancreato-biliary malignancies and highlight their potential as therapeutic targets. We discuss current claudin-targeted therapies, including monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engager and chimeric antigen receptor T-cell therapies. These approaches show promise in pre-clinical and clinical studies, particularly in hepato-pancreato-biliary cancers with large unmet needs. Despite these early signs of efficacy, challenges remain in effectively targeting these proteins due to their structural resemblance and overlapping functions.

PMID:39391254 | PMC:PMC11464258 | DOI:10.3389/fonc.2024.1454882
Biliary drainage in palliative and curative intent European patients with hilar cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis

Fetched: October 16th, 2024, 2:01am UTC by Jan Drews

BMC Gastroenterol. 2024 Oct 10;24(1):359. doi: 10.1186/s12876-024-03429-y.

ABSTRACT

BACKGROUND AND AIMS: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented.

PATIENTS AND METHODS: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients.

RESULTS: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia.

CONCLUSIONS: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

PMID:39390363 | PMC:PMC11468282 | DOI:10.1186/s12876-024-03429-y
Different Etiologies of Dilated Pancreatic Duct Based on Endoscopic Ultrasonography Findings

Fetched: October 16th, 2024, 2:01am UTC by Elham Sobhrakhshankhah

Middle East J Dig Dis. 2024 Jul;16(3):155-159. doi: 10.34172/mejdd.2024.382. Epub 2024 Jul 31.

ABSTRACT

BACKGROUND: Pancreatic duct (PD) dilation could be presented in both benign and malignant diseases. Endoscopic ultrasonography (EUS) is a sensitive modality that provides both structural assessment and tissue sampling. This study aims to explore the importance of PD dilation as a potential indicator related to various pancreatobiliary pathologies identified via EUS.

METHODS: Among 3109 subjects who underwent EUS, 599 had evidence of dilated PD and met the inclusion criteria of this retrospective study. Also, the patients underwent EUS fine needle aspiration (EUS-FNA) to evaluate the etiology when required. All data were extracted from patients' medical records to perform statistical analysis.

RESULTS: The study sample revealed 64% being male with a median age was 65-years. Pancreatic adenocarcinoma was the most common etiology diagnosed in 236 patients (39.4%), followed by sphincter of Oddi dysfunction (SOD) in 13% of subjects. Ampullary carcinoma, common bile duct stone, and cholangiocarcinoma were found at 9.5%, 8.8%, and 6.8%, respectively. Abdominal pain was the most common symptom seen in 440 (73.4%) patients. Opium consumption was reported in 170 (28.4%) subjects. Opium consumption was significantly more prevalent in patients with SOD (P<0.05).

CONCLUSION: We suggest that PD dilation could be associated with a wide range of pancreaticobiliary pathologies, especially pancreatic neoplasms. In this regard, PD dilation should be considered as a crucial indicator of pancreatic neoplasm despite it may be associated with no clear etiologies.

PMID:39386335 | PMC:PMC11459282 | DOI:10.34172/mejdd.2024.382
Amputation neuroma with a difficult differential diagnosis from perihilar cholangiocarcinoma:a case report

Fetched: October 16th, 2024, 2:01am UTC by Shinya Yamaga

Nihon Shokakibyo Gakkai Zasshi. 2024;121(10):842-850. doi: 10.11405/nisshoshi.121.842.

ABSTRACT

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

PMID:39384397 | DOI:10.11405/nisshoshi.121.842
Intraductal papillary mucinous neoplasm of the bile duct with choledochoduodenal fistula: a case report and literature review

Fetched: October 16th, 2024, 2:01am UTC by Cong Ding

AME Case Rep. 2024 Jul 18;8:86. doi: 10.21037/acr-24-54. eCollection 2024.

ABSTRACT

BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a neoplastic disease of the bile duct with papillary hyperplasia and mucus secretion, which originates from the duct epithelium and rarely complicates with fistula formation.

CASE DESCRIPTION: The patient was admitted to the hospital due to abdominal pain and yellow skin. Laboratory results showed alanine aminotransferase 299 U/L, total bilirubin 350 Âµmol/L, computerized tomography showed severe dilatation of common bile duct and extrahepatic bile duct. Magnetic resonance cholangiopancreatography showed the intra- and extrahepatic bile ducts were markedly dilated, and the signal of the bile ducts was uneven. Endoscope identified a large amount of mucus above the papilla that flowing out from the fistula. Further cholangiography through the fistula showed significant dilatation of the extrahepatic bile duct. SpyGlass examination showed a large amount of gelatinous mucus in the bile duct lumen and "fish-scaly or coral" changes in the mucosa of the right anterior branch bile duct, hepatic hilum as well as lower common bile duct. IPMN-B with choledochoduodenal fistula was diagnosed. The patient was then discharged with nasal biliary drainage and biliary stenting, oral antipyretic and hepatoprotective drugs. The patient's biliary obstruction and symptoms of infection improved with medical treatment but recured. Unfortunately, the patient died 10 months after his first visit.

CONCLUSIONS: SpyGlass has advantages in identifying the nature and extent of lesions, providing important references for diagnosis and treatment. Endoscopic intervention relieves biliary obstruction to some extent in patients with high operative risk or reluctance to undergo surgery.

PMID:39380853 | PMC:PMC11459443 | DOI:10.21037/acr-24-54
Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors

Fetched: October 16th, 2024, 2:01am UTC by Hasan Ahmad Al-Saffar

Scand J Surg. 2024 Oct 8:14574969241282480. doi: 10.1177/14574969241282480. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement.

METHODS: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method.

RESULTS: One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively).

CONCLUSION: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

PMID:39380179 | DOI:10.1177/14574969241282480
A case report: mucinous carcinoma of extrahepatic bile ducts with periportal calcification suggestive of lymphatic calcification

Fetched: October 16th, 2024, 2:01am UTC by Yuichi Yoshie

Abdom Radiol (NY). 2024 Oct 9. doi: 10.1007/s00261-024-04621-0. Online ahead of print.

ABSTRACT

Mucinous carcinoma is a rare subtype of extrahepatic bile duct (EHBD) cancer in which abundant mucin surrounds cancer cell nests. Calcification is often observed in mucus-producing tumors, and we herein report a case of mucinous carcinoma of EHBD with diffuse periportal calcifications. A 92-year-old woman was seen for jaundice. Non-contrast CT showed diffuse semi-linear branching calcifications extending from the hepatoduodenal ligament along the long axis of the intra- and extrahepatic portal veins. A bile duct mass and multiple lymph nodes were hyperintense on T2-weighted MRI images, and periportal abnormal intensity was visible along the intrahepatic portal tract. On contrast-enhanced CT, the mass and enlarged lymph nodes showed a weak enhancing effect. In addition, a lesion with a similar enhancing effect was observed in parallel with periportal calcification, raising suspicion of tumor extension. An endoscopic bile duct biopsy was performed, which resulted in the tumor being diagnosed as a mucinous carcinoma. Considering the imaging findings, it was determined to be a mucinous carcinoma of EHBD origin, with lymphatic vessel infiltration and multiple lymph node metastases. The lymphatic tracts presented lymphangitic carcinomatosis extending from the hepatoduodenal ligament to intrahepatic portal tracts, and the diffuse periportal calcification was presumed to be calcification associated with the mucin component of tumor infiltration.

PMID:39379517 | DOI:10.1007/s00261-024-04621-0
Novel self-expandable metallic stent with dumbbell-shape and spiral outer cover for malignant distal biliary obstruction

Fetched: October 16th, 2024, 2:01am UTC by Haruo Miwa

Endoscopy. 2024 Dec;56(S 01):E849-E850. doi: 10.1055/a-2420-7965. Epub 2024 Oct 8.

NO ABSTRACT

PMID:39379055 | PMC:PMC11461090 | DOI:10.1055/a-2420-7965
The clinical significance of the lymph node ratio as a recurrence indicator in ampullary cancer after curative pancreaticoduodenectomy

Fetched: October 16th, 2024, 2:01am UTC by Shinichiro Hasegawa

Langenbecks Arch Surg. 2024 Oct 8;409(1):302. doi: 10.1007/s00423-024-03481-y.

ABSTRACT

BACKGROUND: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer.

METHODS: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined.

RESULTS: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 Â± 0.11 vs. 0.089 Â± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions.

CONCLUSION: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer.

PMID:39377937 | DOI:10.1007/s00423-024-03481-y
Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

Fetched: October 16th, 2024, 2:01am UTC by Shin Ito

Cancer Sci. 2024 Oct 8. doi: 10.1111/cas.16365. Online ahead of print.

ABSTRACT

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

PMID:39377143 | DOI:10.1111/cas.16365
Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Yue Li

BMC Cancer. 2024 Oct 7;24(1):1232. doi: 10.1186/s12885-024-12970-8.

ABSTRACT

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3⁺ T cells and CD8⁺ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be â‰¥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3⁺ T cells and CD8⁺ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

PMID:39375615 | PMC:PMC11457400 | DOI:10.1186/s12885-024-12970-8
A case of giant hilar cholangiocarcinoma accompanied by hyperbilirubinemia achieved disease stabilization via hepatic artery infusion chemotherapy combined with targeted therapy

Fetched: October 16th, 2024, 2:01am UTC by B Y Wu

Zhonghua Gan Zang Bing Za Zhi. 2024 Sep 20;32(9):845-849. doi: 10.3760/cma.j.cn501113-20231014-00143.

ABSTRACT

1ä¾‹51å²å¥³æ€§æ‚£è€…ï¼Œæ‚£è‚é—¨éƒ¨å·¨å¤§èƒ†ç®¡ç™Œï¼Œä»¥é»„ç–¸ä¸ºä¸»è¦èµ·ç—…è¡¨çŽ°ï¼Œåœ¨å¤–é™¢ç»é¶å‘/å…ç–«/åŒ–ç–—æ²»ç–—åŽç–¾ç—…è¿›å±•ï¼Œå…¥é™¢åŽç»å¤šå¦ç§‘è¯Šç–—è®¨è®ºï¼Œæ ¹æ®åŸºå› æ£€æµ‹ç»“æžœï¼Œç»™äºˆäº†ç»çš®ç»è‚èƒ†ç®¡å¼•æµæœ¯ï¼ˆPTBDï¼‰+mFOLFOX-è‚åŠ¨è„‰ç½®ç®¡åŒ–ç–—æœ¯ï¼ˆHAICï¼‰+é¶å‘ï¼ˆè‰¾ä¼å°¼å¸ƒï¼‰æ²»ç–—çš„æ–¹æ¡ˆã€‚æ²»ç–—æœŸé—´æ‚£è€…è‚¿ç˜¤å¤§å°ç¨³å®šã€èƒ†çº¢ç´ æ°´å¹³ç¨³å®šï¼Œæ€»ç”Ÿå˜æœŸè¾¾åˆ°äº†25ä¸ªæœˆã€‚è¿™æç¤ºåŸºå› æ£€æµ‹å¯¹èƒ†ç®¡ç™Œç²¾å‡†åŒ–ã€ä¸ªä½“åŒ–è¯Šç–—æœ‰é‡è¦æ„ä¹‰ï¼Œä»¥åŠmFOLFOX-HAICè”åˆåº”ç”¨é¶å‘è¯ç‰©æ²»ç–—æ–¹æ¡ˆåœ¨ä¼´é«˜èƒ†çº¢ç´ è¡€ç—‡çš„è‚èƒ†è‚¿ç˜¤æ‚£è€…ä¸å…·æœ‰æœ‰æ•ˆæ€§å’Œå®‰å…¨æ€§ã€‚.

PMID:39375106 | DOI:10.3760/cma.j.cn501113-20231014-00143
Bie Jia Jian pill ameliorates BDL-induced cholestatic hepatic fibrosis in rats by regulating intestinal microbial composition and TMAO-mediated PI3K/AKT signaling pathway

Fetched: October 16th, 2024, 2:01am UTC by Xiaoyan Cui

J Ethnopharmacol. 2024 Oct 5;337(Pt 2):118910. doi: 10.1016/j.jep.2024.118910. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: As a compound of traditional Chinese medicine (TCM), Bie Jia Jian pill (BJJP) is extensively used to treat the clinical chronic liver disease. Nevertheless, the specific mechanism through which BJJP affects hepatic fibrosis (HF) remains unknown.

AIM OF THE STUDY: To explore the role and potential mechanism of BJJP involved in treating HF.

MATERIALS AND METHODS: HF model of Sprague-Dawley (SD) rats was induced by a bile duct ligation (BDL). The function of BJJP involved in the intestinal microbiota (IM) and its metabolites in BDL-induced HF rats were explored through the 16S rRNA sequencing and untargeted metabolomics technologies. Network pharmacology was used to forecast mechanism underlying BJJP's anti-HF effects, which were validated in BDL-induced rats and trimethylamine N-oxide (TMAO)-induced LX-2 and HSC-T6 cells.

RESULTS: BJJP effectively ameliorated pathological liver damage, inflammation, and fibrosis of the BDL-induced HF rats. BJJP regulated IM diversity and composition and interfered with trimethylamine (TMA)-flavin monooxygenase 3 (FMO3)-TMAO process. In vitro, BJJP significantly inhibited the TMAO-induced activation of hepatic stellate cells (HSCs) (rat HSC cell line, HSC-T6; human HSC cell line, LX-2). Network pharmacology results demonstrated that PI3K/AKT signal pathway is crucially involved in BJJP treatment of HF. Further research revealed that BJJP inhibited the PI3K/AKT signal pathway in BDL-induced HF rats. Moreover, TMAO activated the PI3K/AKT pathway, whereas BJJP suppressed TMAO-induced activation. Subsequent intervention with 740Y-P (the PI3K agonist) successfully neutralized the repression effect on PI3K/AKT signal pathway by BJJP.

CONCLUSION: These results clearly show that BJJP attenuates HF by regulating the IM, as well as inhibiting PI3K/AKT pathway mediated by TMAO.

PMID:39369915 | DOI:10.1016/j.jep.2024.118910
Preoperative prognostic stratification and prediction of long-term outcomes after pancreatoduodenectomy for distal cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Tomotaka Kato

Eur J Surg Oncol. 2024 Sep 18;50(12):108691. doi: 10.1016/j.ejso.2024.108691. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging.

METHODS: This single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS).

RESULTS: Among 170 patients examined, the median tumor depth was 10 mm, and 37 % of the patients were diagnosed with pT3. Overall, 46 % of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50 %, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) â‰¥15 mm and main pancreatic duct (MPD) dilatation (â‰¥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39 %) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64 % (5-year OS: 8 %). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72 %) to those with pStage I DCC.

CONCLUSION: A simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.

PMID:39366161 | DOI:10.1016/j.ejso.2024.108691
A flexible deep learning framework for liver tumor diagnosis using variable multi-phase contrast-enhanced CT scans

Fetched: October 16th, 2024, 2:01am UTC by Shixin Huang

J Cancer Res Clin Oncol. 2024 Oct 3;150(10):443. doi: 10.1007/s00432-024-05977-y.

ABSTRACT

BACKGROUND: Liver cancer is a significant cause of cancer-related mortality worldwide and requires tailored treatment strategies for different types. However, preoperative accurate diagnosis of the type presents a challenge. This study aims to develop an automatic diagnostic model based on multi-phase contrast-enhanced CT (CECT) images to distinguish between hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and normal individuals.

METHODS: We designed a Hierarchical Long Short-Term Memory (H-LSTM) model, whose core components consist of a shared image feature extractor across phases, an internal LSTM for each phase, and an external LSTM across phases. The internal LSTM aggregates features from different layers of 2D CECT images, while the external LSTM aggregates features across different phases. H-LSTM can handle incomplete phases and varying numbers of CECT image layers, making it suitable for real-world decision support scenarios. Additionally, we applied phase augmentation techniques to process multi-phase CECT images, improving the model's robustness.

RESULTS: The H-LSTM model achieved an overall average AUROC of 0.93 (0.90, 1.00) on the test dataset, with AUROC for HCC classification reaching 0.97 (0.93, 1.00) and for ICC classification reaching 0.90 (0.78, 1.00). Comprehensive validation in scenarios with incomplete phases was performed, with the H-LSTM model consistently achieving AUROC values over 0.9.

CONCLUSION: The proposed H-LSTM model can be employed for classification tasks involving incomplete phases of CECT images in real-world scenarios, demonstrating high performance. This highlights the potential of AI-assisted systems in achieving accurate diagnosis and treatment of liver cancer. H-LSTM offers an effective solution for processing multi-phase data and provides practical value for clinical diagnostics.

PMID:39361193 | PMC:PMC11450020 | DOI:10.1007/s00432-024-05977-y
Clinical prognosticators and targets in the immune microenvironment of intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Isis Lozzi

Oncoimmunology. 2024 Oct 1;13(1):2406052. doi: 10.1080/2162402X.2024.2406052. eCollection 2024.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation.

METHODS: Liver tissue samples were collected during 2008-2019 from patients (n = 139) diagnosed with ICC who underwent curative intent surgery without neoadjuvant chemotherapy. Samples from the discovery cohort (n = 86) were immunohistochemically analyzed on tissue microarrays (TMAs) for the expression of CD68, CD3, CD4, CD8, Foxp3, PD-L1, STAT1, and p-STAT1 in tumor core and stroma areas. Results were digitally analyzed using QuPath software and correlated with clinicopathological characteristics. For validation of TIME-related biomarkers, we performed multiplex imaging mass cytometry (IMC) in a validation cohort (n = 53).

RESULTS: CD68+ cells were the predominant immune cell type in the TIME of ICC. CD4+^high T cell density correlated with better overall survival (OS). Prediction modeling together with validation cohort confirmed relevance of CD4+ cells, PD-L1 expression by immune cells in the stroma and N-stage on overall disease outcome. In turn, IMC analyses revealed that silent CD3+CD4+ clusters inversely impacted survival. Among annotated immune cell clusters, PD-L1 was most relevantly expressed by CD4+FoxP3+ cells. A subset of tumors with high density of immune cells ("hot" cluster) correlated with PD-L1 expression and could identify a group of candidates for immune checkpoint inhibition (ICI). Ultimately, higher levels of STAT1 expression were associated with higher lymphocyte infiltration and PD-L1 expression.

CONCLUSIONS: These results highlight the importance of CD4+ T cells in immune response against ICC. Secondly, a subset of tumors with "hot" TIME represents potential candidates for ICI, while stimulation of STAT1 pathway could be a potential target to turn "cold" into "hot" TIME in ICC.

PMID:39359389 | PMC:PMC11445892 | DOI:10.1080/2162402X.2024.2406052
Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study

Fetched: October 16th, 2024, 2:01am UTC by Shanshan Wang

Cancer Immunol Immunother. 2024 Oct 3;73(12):249. doi: 10.1007/s00262-024-03841-z.

ABSTRACT

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.

METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.

RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).

CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

PMID:39358645 | PMC:PMC11447168 | DOI:10.1007/s00262-024-03841-z
Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects

Fetched: October 16th, 2024, 2:01am UTC by Jan MaÅ¡ek

EMBO Mol Med. 2024 Oct 2. doi: 10.1038/s44321-024-00145-8. Online ahead of print.

ABSTRACT

Fibrosis contributes to tissue repair, but excessive fibrosis disrupts organ function. Alagille syndrome (ALGS, caused by mutations in JAGGED1) results in liver disease and characteristic fibrosis. Here, we show that Jag1^Ndr/Ndr mice, a model for ALGS, recapitulate ALGS-like fibrosis. Single-cell RNA-seq and multi-color flow cytometry of the liver revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration despite cholestasis in Jag1^Ndr/Ndr mice. Thymic and splenic regulatory T cells (Tregs) were enriched and Jag1^Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive transfer into Rag1^-/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1^Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1^+/+ lymphocytes in response to DSS. Cholestasis induced by BDL in Rag1^-/- mice with Jag1^Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1^-/- mice with Jag1^+/+ lymphocytes. Finally, the Jag1^Ndr/Ndr hepatocyte expression profile and Treg overrepresentation were corroborated in patients' liver samples. Jag1-dependent hepatic and immune defects thus interact to determine the fibrotic process in ALGS.

PMID:39358604 | DOI:10.1038/s44321-024-00145-8
Glycerophospholipid-driven lipid metabolic reprogramming as a common key mechanism in the progression of human primary hepatocellular carcinoma and cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Yanran Bi

Lipids Health Dis. 2024 Oct 1;23(1):326. doi: 10.1186/s12944-024-02298-4.

ABSTRACT

Metabolic reprogramming, a key mechanism regulating the growth and recurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), still lacks effective clinical strategies for its integration into the precise screening of primary liver cancer. This study utilized ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry to conduct a comprehensive, non-targeted metabolomics analysis, revealing significant upregulation of lipid metabolites such as phosphatidylcholine and lysophosphatidylcholine in patients with HCC and CCA, particularly within the glycerophospholipid metabolic pathway. Hematoxylin and eosin and immunohistochemical staining demonstrated marked upregulation of phospholipase A2 in tumor tissues, further emphasizing the potential of lipid metabolism as a therapeutic target and its important part in the course of cancer. This work provides a new viewpoint for addressing the clinical challenges associated with HCC and CCA, laying the groundwork for the broad application of early diagnosis and personalized treatment strategies, and ultimately aiming to provide tailored and precise therapeutic options for patients.

PMID:39354487 | PMC:PMC11443871 | DOI:10.1186/s12944-024-02298-4
Glucagon-like peptide 1 receptor agonist: A potential game changer for cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Ronnakrit Trakoonsenathong

World J Gastroenterol. 2024 Sep 14;30(34):3862-3867. doi: 10.3748/wjg.v30.i34.3862.

ABSTRACT

Glucagon-like peptide-1 receptor (GLP-1R) agonist, a subgroup of incretin-based anti-diabetic therapies, is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection. Contrarily, concerns have been raised about GLP-1R agonists increasing the risk of particular cancers. Recently, several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma (CCA). The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA. Later studies, however, showed a null effect of incretin-based therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist. Mechanistically, glucagon-like peptide 1 receptor is multifunctional, including promoting cell growth. High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro. Unexpectedly, the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms. Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo, leading to the inhibition of CCA tumor growth. This editorial reviews recent evidence, discusses the potential effects of GLP-1R agonists in CCA patients, and proposes underlying mechanisms that would benefit from further basic and clinical investigation.

PMID:39350782 | PMC:PMC11438652 | DOI:10.3748/wjg.v30.i34.3862
MBD2 regulates the progression and chemoresistance of cholangiocarcinoma through interaction with WDR5

Fetched: October 16th, 2024, 2:01am UTC by Da Wang

J Exp Clin Cancer Res. 2024 Sep 30;43(1):272. doi: 10.1186/s13046-024-03188-4.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant, rapidly progressing tumor of the bile duct. Owing to its chemoresistance, it always has an extremely poor prognosis. Therefore, detailed elucidation of the mechanisms of chemoresistance and identification of therapeutic targets are still needed.

METHODS: We analyzed the expression of MBD2 (Methyl-CpG-binding domain 2) in CCA and normal bile duct tissues using the public database and immunohistochemistry (IHC). The roles of MBD2 in CCA cell proliferation, migration, and chemoresistance ability were validated through CCK-8, plate cloning assay, wound healing assays and xenograft mouse model. In addition, we constructed a primary CCA mouse model to further confirm the effect of MBD2. RNA-seq and co-IP-MS were used to identify the mechanisms by how MBD2 leads to chemoresistance.

RESULTS: MBD2 was upregulated in CCA. It promoted the proliferation, migration and chemoresistance of CCA cells. Mechanistically, MBD2 directly interacted with WDR5, bound to the promoter of ABCB1, promoted the trimethylation of H3K4 in this region through KMT2A, and activated the expression of ABCB1. Knocking down WDR5 or KMT2A blocked the transcriptional activation of ABCB1 by MBD2. The molecular inhibitor MM-102 targeted the interaction of WDR5 with KMT2A. MM-102 inhibited the expression of ABCB1 in CCA cells and decreased the chemoresistance of CCA to cisplatin.

CONCLUSION: MBD2 promotes the progression and chemoresistance of CCA through interactions with WDR5. MM-102 can effectively block this process and increase the sensitivity of CCA to cisplatin.

PMID:39350229 | PMC:PMC11440836 | DOI:10.1186/s13046-024-03188-4
N-acetyltransferase 10 affects the proliferation of intrahepatic cholangiocarcinoma and M2-type polarization of macrophages by regulating C-C motif chemokine ligand 2

Fetched: October 16th, 2024, 2:01am UTC by Teng Cai

J Transl Med. 2024 Sep 30;22(1):875. doi: 10.1186/s12967-024-05664-z.

ABSTRACT

BACKGROUND: N-acetyltransferase 10 (NAT10) plays a crucial role in the occurrence and development of various tumors. However, the current regulatory mechanism of NAT10 in tumors is limited to its presence in tumor cells. Here, we aimed to reveal the role of NAT10 in intrahepatic cholangiocarcinoma (ICC) and investigate its effect on macrophage polarization in the tumor microenvironment (TME).

METHODS: The correlation between NAT10 and ICC clinicopathology was analyzed using tissue microarray (TMA), while the effect of NAT10 on ICC proliferation was verified in vitro and in vivo. Additionally, the downstream target of NAT10, C-C motif chemokine ligand 2 (CCL2), was identified by Oxford Nanopore Technologies full-length transcriptome sequencing, RNA immunoprecipitation-quantitative polymerase chain reaction, and coimmunoprecipitation experiments. It was confirmed by co-culture that ICC cells could polarize macrophages towards M2 type through the influence of NAT10 on CCL2 protein expression level. Through RNA-sequencing, molecular docking, and surface plasmon resonance (SPR) assays, it was confirmed that berberine (BBR) can specifically bind CCL2 to inhibit ICC development.

RESULTS: High expression level of NAT10 was associated with poor clinicopathological manifestations of ICC. In vitro, the knockdown of NAT10 inhibited the proliferative activity of ICC cells and tumor growth in vivo, while its overexpression promoted ICC proliferation. Mechanically, by binding to CCL2 messenger RNA, NAT10 increased CCL2 protein expression level in ICC and their extracellular matrix, thereby promoting the proliferation of ICC cells and M2-type polarization of macrophages. BBR can target CCL2, inhibit ICC proliferation, and reduce M2-type polarization of macrophages.

CONCLUSIONS: NAT10 promotes ICC proliferation and M2-type polarization of macrophages by up-regulating CCL2, whereas BBR inhibits ICC proliferation and M2-type polarization of macrophages by inhibiting CCL2.

PMID:39350174 | PMC:PMC11440763 | DOI:10.1186/s12967-024-05664-z
A live single-cell reporter system reveals drug-induced plasticity of a cancer stem cell-like population in cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Krittiyabhorn Kongtanawanich

Sci Rep. 2024 Sep 30;14(1):22619. doi: 10.1038/s41598-024-73581-8.

ABSTRACT

Cancer stem cells (CSC) play an important role in carcinogenesis and are acknowledged to be responsible for chemoresistance in cholangiocarcinoma (CCA). Studying CCA CSC has been challenging, due to lack of consensus CSC markers, and to their plastic nature. Since dual expression of the core pluripotent factors SOX2/OCT4 has been shown to correlate with poor outcome in CCA patients, we selected the SOX2/OCT4 activating short half-life GFP-based live reporter (SORE6-dsCopGFP) to study CSC dynamics at the single-cell level. Transduction of five human CCA cell lines resulted in the expression of 1.8-13.1% GFP-positive (SORE6^POS) cells. By live imaging, we found that SORE6^POS CCA cells possess self-renewal capacity and that they can be induced to differentiate. Significantly, the SORE6^POS cells were highly tumorigenic, both in vitro and in vivo, thus implicating the characteristics of primary CSCs. When we then analyzed for selected CSC-related markers, we found that the majority of both CD133⁺/CD44⁺, and CD133⁺/LGR5⁺ CCA cells were SORE6^POS cells. Exposing transduced cells to standard CCA chemotherapy revealed higher growth rate inhibition at 50% (GR50s) for SORE6^POS cells compared to GFP-negative (SORE6^NEG) ones indicating that these CSC-like cells were more resistant to the treatment. Moreover, the chemotherapy induced SORE6^POS from SORE6^NEG cells, while retaining the existing SORE6^POS population. Finally, treatment of transduced cells with CDK4/6 inhibitors in vitro for 3 days resulted in a lowered CSC number in the culture. Thus, applying a live reporter system allowed us to elucidate the stem cell diversity and drug-induced plasticity of CCA CSCs. These findings have clear implications for future management of such patients.

PMID:39349745 | PMC:PMC11442615 | DOI:10.1038/s41598-024-73581-8
The Dominant Component and Clinicopathological Characteristics of Combined Hepatocellular-cholangiocarcinoma After Radical Resection

Fetched: October 16th, 2024, 2:01am UTC by Keiso Matsubara

Anticancer Res. 2024 Oct;44(10):4551-4559. doi: 10.21873/anticanres.17284.

ABSTRACT

BACKGROUND/AIM: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver carcinoma, characterized by the unequivocal presence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, its clinicopathological characteristics have not yet been thoroughly elucidated. In particular, cholangiolocellular carcinoma (CLC) was classified as a subtype of cHCC-CCA according to the 2010 World Health Organization (WHO) classification. However, according to the 2019 WHO classification, tumors displaying histological features consistent with CLC but lacking evidence of hepatocellular differentiation should be regarded as a distinct subtype of iCCA. Nevertheless, there may be notable differences in prognosis between CLC and iCCA, indicating the necessity for refining the classification when devising clinical treatment strategies. This study aimed to determine the clinicopathological features and prognostic factors of cHCC-CCAs following radical resection.

PATIENTS AND METHODS: Between January 2010 and September 2020, based on the 2010 WHO classification, we retrospectively studied the clinicopathological features and prognoses of patients with cHCC-CCAs in relation to the pathological dominant classification. The patients were classified according to the pathological dominant components of cHCC-CCA as HCC-dominant (HCC-D), iCCA-dominant (iCCA-D), or CLC-dominant (CLC-D).

RESULTS: Data of 55 patients who underwent primary radical hepatectomy for cHCC-CCA were analyzed. The prevalences of each dominant classification were HCC-D, 21 (38.2%); iCCA-D, 11 (20.0%); and CLC-D, 23 (41.8%). Multivariate analysis showed that dominant classification was an independent risk factor for recurrence and cancer-specific survival (CSS).

CONCLUSION: The dominant classification of cHCC-CCA has the potential to predict recurrence and CSS.

PMID:39348996 | DOI:10.21873/anticanres.17284
SRPK Inhibitors Reduce the Phosphorylation and Translocation of SR Protein Splicing Factors, thereby Correcting BIN1, MCL-1 and BCL2 Splicing Errors and Enabling Apoptosis of Cholangiocarcinoma Cells

Fetched: October 16th, 2024, 2:01am UTC by Preenapan Changphasuk

Front Biosci (Schol Ed). 2024 Sep 29;16(3):17. doi: 10.31083/j.fbs1603017.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy of the bile duct epithelium that is commonly found in the Thai population. CCA has poor prognosis and a low survival rate due to the lack of early diagnosis methods and the limited effectiveness of current treatments. A number of oncogenic spliced-transcripts resulting from mRNA splicing errors have been reported in CCA, and aberrant mRNA splicing is suspected to be a key driver of this cancer type. The hyperphosphorylation of serine/arginine rich-splicing factors (SRSFs) by serine/arginine protein kinases (SRPKs) causes them to translocate to the nucleus where they facilitate gene splicing errors that generate cancer-related mRNA/protein isoforms.

METHODS: The correlation between SRPK expression and the survival of CCA patients was analyzed using data from The Cancer Genome Atlas (TCGA) dataset. The effect of SRPK inhibitors (SRPIN340 and SPHINX31) on two CCA cell lines (KKU-213A and TFK-1) was also investigated. The induction of cell death was studied by Calcein-AM/PI staining, AnnexinV/7AAD staining, immunofluorescence (IF), and Western blotting (WB). The phosphorylation and nuclear translocation of SRSFs was tracked by WB and IF, and the repair of splicing errors was examined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR).

RESULTS: High levels of SRPK1 and SRPK2 transcripts, and in particular SRPK1, correlated with shorter survival in CCA patients. SRPIN340 and SPHINX31 increased the number of dead and apoptotic cells in a dose-dependent manner. CCA also showed diffuse expression of cytoplasmic cytochrome C and upregulation of cleaved caspase-3. Moreover, SRSFs showed low levels of phosphorylation, resulting in the accumulation of cytoplasmic SRSF1. To link these phenotypes with aberrant gene splicing, the apoptosis-associated genes Bridging Integrator 1 (BIN1), Myeloid cell leukemia factor 1 (MCL-1) and B-cell lymphoma 2 (BCL2) were selected for further investigation. Treatment with SRPIN340 and SPHINX31 decreased anti-apoptotic BIN1+12A and increased pro-apoptotic MCL-1S and BCL-xS.

CONCLUSIONS: The SRPK inhibitors SRPIN340 and SPHINX31 can suppress the phosphorylation of SRSFs and their nuclear translocation, thereby producing BIN1, MCL-1 and BCL2 isoforms that favor apoptosis and facilitate CCA cell death.

PMID:39344395 | DOI:10.31083/j.fbs1603017
Contrast-enhanced ultrasound-guided percutaneous transhepatic cholangiodrainage is a safe and effective procedure for patients with malignant biliary obstruction and stage 3 chronic kidney disease

Fetched: October 16th, 2024, 2:01am UTC by Qiuqing Zheng

Eur J Radiol. 2024 Sep 25;181:111761. doi: 10.1016/j.ejrad.2024.111761. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to validate the efficacy and safety of contrast-enhanced ultrasound-guided percutaneous transhepatic cholangiodrainage (CEUS-PTCD) as a biliary drainage procedure in patients with malignant biliary obstruction and stage 3 chronic kidney disease (CKD3).

MATERIALS AND METHODS: Between January 2019 and December 2023, 634 patients who underwent CEUS-PTCD were retrospectively enrolled in this study. During the procedure, imaging parameters such as the maximum diameter of the dilated bile duct, presence of ascites, detailed findings from CEUS, and clinical outcomes were meticulously recorded. Laboratory results, including serum bilirubin levels, liver function tests, and estimated glomerular filtration rate (eGFR), were evaluated in one day before and three days after procedure. The aforementioned parameters were compared using the paired-sample t test and the Wilcoxon test.

RESULTS: A total of 66 (10.41 %) patients with malignant biliary obstruction and CKD3 were included in the final analysis (median age: 66, range: 30-89 years, 46 males and 20 females). Procedure records indicated that 23 patients (34.8 %) had a maximum biliary duct dilation diameter of â‰¤ 4 mm, while 5 patients (7.6 %) exhibited mild ascites. Additionally, 24 patients (36.4 %) had ultrasound contrast agent entry into both the biliary duct and bloodstream. All patients successfully achieved external bile drainage following CEUS-PTCD, with no significant complications observed during or after the intervention. Post-procedure, there was a statistically significant reduction in all previously elevated serum bilirubin and liver enzyme levels (P-values were less than 0.05). Furthermore, no statistically significant alterations in eGFR were observed prior to or following CEUS-PTCD across all patients (P = 0.295), including comparisons between groups with and without the ultrasound contrast agent into the bloodstream (P = 0.254).

CONCLUSION: CEUS-PTCD is a safe and effective biliary drainage procedure for patients with malignant biliary obstruction and CKD3.

PMID:39342886 | DOI:10.1016/j.ejrad.2024.111761
Feasibility of Endoscopic Ultrasound-Guided Hepaticogastrostomy for Malignant Hilar Biliary Obstruction

Fetched: October 16th, 2024, 2:01am UTC by Akihisa Ohno

Dig Dis Sci. 2024 Sep 29. doi: 10.1007/s10620-024-08652-x. Online ahead of print.

ABSTRACT

BACKGROUND: Almost all previous reports on endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) involve malignant distal bile duct strictures. However, the feasibility of EUS-HGS for malignant hilar biliary obstruction (MHBO) remains unclear.

AIMS: This study aimed to evaluate the efficacy and safety of EUS-HGS for MHBO and identify the risk factors associated with technical failure.

METHODS: In this multicenter retrospective study, we reviewed consecutive patients who underwent EUS-HGS between April 2017 and March 2023 at five institutions. We assessed the overall feasibility and efficacy of EUS-HGS for MHBO, including the factors associated with technical failure, using multivariable logistic regression analysis.

RESULTS: A total of 85 patients were enrolled (mean age, 72 years; 36.4% female). Thirty-six patients (42.3%) had surgically altered anatomy, and 43 (50.6%) underwent biliary stenting by transpapillary or percutaneous biliary drainage before EUS-HGS. The rates of technical success, clinical success, and adverse events were 87.0% (74/85), 76.4% (65/85), and 11.8% (10/85), respectively. Multivariable analysis demonstrated that a bile duct diameter â‰¤ 4 mm was the only independent risk factor for technical failure (odds ratio, 6.12; 95% confidence interval, 1.02-36.6; P = 0.047). The most common reason for technical failure was cholangiography failure (45.4%), followed by inappropriate guidewire position (36.4%).

CONCLUSIONS: EUS-HGS is a challenging but promising treatment option for MHBO. Patients with a bile duct diameter â‰¤ 4 mm or inappropriate guidewire position should be careful as these factors can lead to the technical failure of EUS-HGS for MHBO.

PMID:39342525 | DOI:10.1007/s10620-024-08652-x
Diagnostic Yield of Endoscopic Ultrasound in Common Bile Duct Dilation: A Real Breakthrough

Fetched: October 16th, 2024, 2:01am UTC by A I Ferreira

Dig Dis Sci. 2024 Sep 28. doi: 10.1007/s10620-024-08628-x. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic ultrasound (EUS) is important for the evaluation of patients with common bile duct (CBD) dilation.

AIMS: The purpose of this study was to evaluate the diagnostic performance of EUS for CBD dilation in patients with negative initial studies.

METHODS: This was a retrospective cohort study that included patients who underwent EUS for CBD dilation (â‰¥ 7 mm if intact anatomy or â‰¥ 10 mm if prior cholecystectomy) in the absence of pathology on previous ultrasonography (US), computed tomography (CT), and/or magnetic resonance cholangiopancreatography (MRCP).

RESULTS: A total of 109 patients were included, among whom 41 had a positive EUS: 33 choledocholithiasis (30.3%), 6 chronic pancreatitis (5.5%), and 2 ampullary cancer (1.8%). If the EUS was negative, no pathology was found during 1-year follow-up. Older age was associated with positive EUS (79 versus 71 years, p = 0.030). Patients with jaundice, cholelithiasis, and altered liver biochemistry were 16.2 (p = 0.002), 3.1 (p = 0.024), and 2.9 (p = 0.009) times more likely to have positive EUS, respectively. A total of 53 patients had a negative MRCP (48.6%); those with biliary abdominal pain and jaundice were 15.5 (p < 0.001) and 20.0 (p = 0.007) times more likely to have positive EUS, respectively. Considering asymptomatic patients with normal liver tests, CBD diameter â‰¥ 10 mm in US and â‰¥ 11 mm in CT can predict a positive EUS (AUC 0.754, p = 0.047 and AUC 0.734, p = 0.048).

CONCLUSIONS: EUS is a useful diagnostic method for patients with unexplained CBD dilation, even if negative MRCP, and especially in patients with older age, abdominal pain, jaundice, cholelithiasis, and/or altered liver biochemistry. CBD diameter in US and CT had a moderate discriminative ability in predicting positive EUS in asymptomatic patients without altered liver biochemistry.

PMID:39342067 | DOI:10.1007/s10620-024-08628-x
Facilitating cholangiocarcinoma inhibition by targeting CD47

Fetched: October 16th, 2024, 2:01am UTC by Kulthida Vaeteewoottacharn

Exp Mol Pathol. 2024 Sep 27;140:104935. doi: 10.1016/j.yexmp.2024.104935. Online ahead of print.

ABSTRACT

Immune evasion is one of the mechanisms by which cancer cells acquire immunity during cancer development and progression. One of these is the increased expression of cluster of differentiation 47 (CD47), a transmembrane glycoprotein that protects cells from phagocytic elimination. The interaction between CD47 and signal regulatory protein alpha (SIRPÎ±) on macrophages alleviates the phagocytic signal. The present group previously reported high CD47 expression in cholangiocarcinoma (CCA), a major health problem in Thailand and East Asia, and that blocking CD47 using anti-CD47 antibodies promoted the removal of CCA. However, the mechanism through which CD47 inhibition attenuates CCA growth remains unclear. This study explored the clinical significance of targeting CD47 in CCA. Expression levels of CD47 and the macrophage marker CD68 were determined in CCA tissues by immunohistochemistry and correlated with clinical parameters. The role of CD47 in CCA cells was established using CD47-deficient KKU-213A CCA clones in vitro and in vivo. The results showed that CD47 was highly expressed in CCA tissues and significantly correlated with lymph node metastasis (P = 0.038). Moderate-to-dense CD68-positive infiltrating cells in CCA tissues were significantly associated with shorter survival of patients (P = 0.019) and were an independent prognostic factor of CCA patients as determined by the Cox proportional hazard model (hazard ratio, 2.040; 95 % confidence interval, 1.109-3.752; P = 0.022). Three CD47-deficient KKU-213A clones (#19, #23, and #28) were generated. The elimination of CD47 did not affect cell proliferation but increased monocyte-derived macrophage-mediated phagocytosis in vitro. Decreased tumor weights and volumes were observed in mice injected with CD47-deficient CCA clones. This revealed a significant role for CD47 in CCA, with a focus on protecting cancer cells from macrophage phagocytosis.

PMID:39341065 | DOI:10.1016/j.yexmp.2024.104935
Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells

Fetched: October 16th, 2024, 2:01am UTC by Saowaluk Saisomboon

Int J Mol Sci. 2024 Sep 22;25(18):10170. doi: 10.3390/ijms251810170.

ABSTRACT

We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3Î²/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.

PMID:39337655 | PMC:PMC11432552 | DOI:10.3390/ijms251810170
Diagnostic Challenges in Follicular Cholangitis Mimicking Hilar Cholangiocarcinoma: A Case Report and Review of the Literature

Fetched: October 16th, 2024, 2:01am UTC by Jungnam Lee

Medicina (Kaunas). 2024 Sep 17;60(9):1513. doi: 10.3390/medicina60091513.

ABSTRACT

Introduction: Distinguishing benign from malignant biliary strictures remains challenging despite diagnostic advancements. Follicular cholangitis, a rare benign condition, presents with symptoms and imaging similar to malignancies like cholangiocarcinoma, often complicating diagnosis, particularly when tumor markers are elevated and imaging suggests metastasis. Case presentation: A 57-year-old woman with hypertension and diabetes was admitted with jaundice. Elevated bilirubin and liver enzymes alongside high carbohydrate antigen 19-9 (CA19-9) levels but normal carcinoembryonic antigen (CEA) were noted. Imaging showed thickening from the hilar duct to the proximal common bile duct, accompanied by suspected lymph node metastases. Comprehensive ERCP-guided biopsies found no malignancy. Surgical resection led to a diagnosis of follicular cholangitis. Conclusions: Follicular cholangitis' long-term prognosis is elusive due to its rarity, and preoperative diagnosis is challenging. Increased awareness may improve diagnostic and treatment approaches, as this case adds to the disease's understanding.

PMID:39336554 | PMC:PMC11433704 | DOI:10.3390/medicina60091513
Preoperative monocyte-to-lymphocyte ratio as a prognosis predictor after curative hepatectomy for intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Bin-Feng Tao

BMC Cancer. 2024 Sep 27;24(1):1179. doi: 10.1186/s12885-024-12929-9.

ABSTRACT

BACKGROUND: Several inflammatory indicators have been reported to have predictive value in many types of malignant cancer. This research was aimed to explore the ability of the monocyte-to-lymphocyte ratio (MLR) to predict prognosis in patients with intrahepatic cholangiocarcinoma (ICC) who subjected to curative hepatectomy.

METHODS: This retrospective analysis included 196 patients with ICC who underwent curative hepatectomy between May 2018 and April 2023. The predictive abilities of the preoperative MLR in assessing overall survival (OS) and disease-free survival (DFS) in those patients were compared with other inflammation-based scores, including monocyte-to-white ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-white ratio, platelet-to-lymphocyte ratio, platelet-to-white ratio, and systemic immune-inflammation index, as well as tumor markers, like carcinoembryonic antigen (CEA) and carbohydrate antigen 19 - 9 (CA19-9).

RESULTS: The area under the time-dependent receiver operating characteristic curve indicated that the preoperative MLR had higher predictive efficiency in contrast with other inflammation-based scores and tumor markers in assessing OS and DFS. Stratifying patients according to the optimal cut-off value for the preoperative MLR, the data showed that both OS and DFS in the high MLR group were significantly worse than those in the low MLR group (p < 0.05 for all). Univariable and multivariable Cox analyses revealed that the preoperative MLR was an independent risk factor for OS and DFS in patients with ICC. In addition to predicting OS in patients with high CEA levels and predicting DFS in patients with high CA19-9 levels, patients with different CEA and CA19-9 levels were divided into completely different OS and DFS subgroups based on the risk stratification of the preoperative MLR.

CONCLUSIONS: Our results demonstrated that the preoperative MLR was a good prognosis indicator to predict DFS and OS following curative hepatectomy in patients with ICC.

PMID:39333901 | PMC:PMC11437980 | DOI:10.1186/s12885-024-12929-9
The role of forkhead box M1-methionine adenosyltransferase 2â€‰A/2B axis in liver inflammation and fibrosis

Fetched: October 16th, 2024, 2:01am UTC by Bing Yang

Nat Commun. 2024 Sep 27;15(1):8388. doi: 10.1038/s41467-024-52527-8.

ABSTRACT

Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl4) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl4-induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1^Hep-/-, hepatocytes from Foxm1^HSC-/-, and HSCs and hepatocytes from Foxm1^KC-/- have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.

PMID:39333125 | PMC:PMC11436801 | DOI:10.1038/s41467-024-52527-8
Large-cell neuroendocrine carcinoma of the bile duct: Case report of surgical treatment and adjuvant chemotherapy of 2 cases

Fetched: October 16th, 2024, 2:01am UTC by Chang Ho Seo

Medicine (Baltimore). 2024 Sep 27;103(39):e39848. doi: 10.1097/MD.0000000000039848.

ABSTRACT

RATIONALE: Neuroendocrine carcinoma originating from extrahepatic bile duct is very rare, and only a few cases have been reported. Because of its scarcity of incidence, not much is known about the disease but for its aggressiveness and poor prognosis.

PATIENT CONCERNS: In this report, we present 2 cases of large cell neuroendocrine carcinoma (LCNEC) originating from extrahepatic bile duct. Case 1: a 60-year-old woman presented with jaundice but no abdominal pain. Case 2: a 67-year-old man also presented with jaundice, along with abdominal discomfort and appetite loss.

DIAGNOSES: Case 1: LCNEC with a focal adenocarcinoma component (pT2aN1M0, pStage IIIB). Case 2: LCNEC with a focal adenocarcinoma component (pT1N1M0, pStage IIB).

INTERVENTIONS: Case 1: the patient underwent left hepatectomy and caudatectomy with hepaticojejunostomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). Case 2: the patient underwent laparoscopic pylorus-preserving pancreatoduodenectomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin).

OUTCOMES: Case 1: liver metastasis was detected 6 months postoperatively, and despite multiple chemotherapy regimens, the patient died 24 months post-surgery. Case 2: liver metastasis was detected 23 months postoperatively. The patient is still alive 36 months post-surgery after receiving multiple chemotherapy regimens and radiotherapy.

LESSONS: Given the rarity of LCNEC, it is essential to continue collecting and reporting additional case studies to build a more comprehensive understanding of the disease. Although the prognosis for LCNEC is generally poor, the use of a multidisciplinary approach and further research will be critical in developing more effective treatment strategies in the future.

PMID:39331932 | PMC:PMC11441850 | DOI:10.1097/MD.0000000000039848
Case Report of Concomitant Diagnosis of Locally Advanced Intrahepatic Cholangiocarcinoma and Solitary Plasmacytoma of T11 Vertebra: Impact on Diagnostic and Clinical Management

Fetched: October 16th, 2024, 2:01am UTC by Yann Touchefeu

Curr Oncol. 2024 Sep 2;31(9):5164-5170. doi: 10.3390/curroncol31090382.

ABSTRACT

A solitary bone plasmacytoma is a rare tumor. Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma. We present the case of a 48-year-old female patient who consulted for recent back pain, with a final diagnosis of T10 solitary plasmacytoma and synchronous intrahepatic cholangiocarcinoma. Imaging suggested cholangiocarcinoma with bone metastasis. The patient underwent neurosurgical management with laminectomy, arthrodesis, and arthrectomy, with biopsies revealing monotypic kappa plasmacytic proliferation. Liver biopsies revealed an adenocarcinoma with expression of cytokeratin 19, cytokeratin 7, N-cadherin, and high expression of carbonic anydrase IX. The plasmacytoma was treated with external radiotherapy. The cholangiocarcinoma was treated with selective internal radiation therapy and concomitant systemic treatment with combinations of cisplatin and durvalumab, with capecitabine during radiotherapy, switched for gemcitabine after completion of irradiation. One year after initial management, imaging revealed a partial metabolic response of the intrahepatic cholangiocarcinoma, and a complete metabolic response of the plasmacytoma. This case illustrates the importance of not ignoring two primary tumors and the management of two concomitant treatments exploiting potential therapeutic synergies and limiting expected toxicities.

PMID:39330010 | PMC:PMC11431636 | DOI:10.3390/curroncol31090382
Current Gallstone Treatment Methods, State of the Art

Fetched: October 16th, 2024, 2:01am UTC by Xiangtian Li

Diseases. 2024 Aug 26;12(9):197. doi: 10.3390/diseases12090197.

ABSTRACT

This study aims to provide valuable references for clinicians in selecting appropriate surgical methods for biliary tract stones based on patient conditions. In this paper, the advantages and disadvantages of various minimally invasive cholelithiasis surgical techniques are systematically summarized and innovative surgical approaches and intelligent stone removal technologies are introduced. The goal is to evaluate and predict future research priorities and development trends in the field of gallstone surgery. In recent years, the incidence of gallstone-related diseases, including cholecystolithiasis and choledocholithiasis, has significantly increased. This surge in cases has prompted the development of several innovative methods for gallstone extraction, with minimally invasive procedures gaining the most popularity. Among these techniques, PTCS, ERCP, and LCBDE have garnered considerable attention, leading to new surgical techniques; however, it must be acknowledged that each surgical method has its unique indications and potential complications. The primary challenge for clinicians is selecting a surgical approach that minimizes patient trauma while reducing the incidence of complications such as pancreatitis and gallbladder cancer and preventing the recurrence of gallstones. The integration of artificial intelligence with stone extraction surgeries offers new opportunities to address this issue. Regarding the need for preoperative preparation for PTCS surgery, we recommend a combined approach of PTBD and PTOBF. For ERCP-based stone extraction, we recommend a small incision of the Oddi sphincter followed by 30 s of balloon dilation as the optimal procedure. If conditions permit, a biliary stent can be placed post-extraction. For the surgical approach of LCBDE, we recommend the transduodenal (TD) approach. Artificial intelligence is involved throughout the entire process of gallstone detection, treatment, and prognosis, and more AI-integrated medical technologies are expected to be applied in the future.

PMID:39329866 | PMC:PMC11431374 | DOI:10.3390/diseases12090197
3D Modeling: Insights into the Metabolic Reprogramming of Cholangiocarcinoma Cells

Fetched: October 16th, 2024, 2:01am UTC by Giorgia Ciufolini

Cells. 2024 Sep 13;13(18):1536. doi: 10.3390/cells13181536.

ABSTRACT

Developing accurate in vitro models that replicate the in vivo tumor environment is essential for advancing cancer research and therapeutic development. Traditional 2D cell cultures often fail to capture the complex structural and functional heterogeneity of tumors, limiting the translational relevance of findings. In contrast, 3D culture systems, such as spheroids, provide a more physiologically relevant context by replicating key aspects of the tumor microenvironment. This study aimed to compare the metabolism of three intrahepatic cholangiocarcinoma cell lines in 2D and 3D cultures to identify metabolic shifts associated with spheroid formation. Cells were cultured in 2D on adhesion plates and in 3D using ultra-low attachment plates. Metabolic exchange rates were measured using NMR, and intracellular metabolites were analyzed using LC-MS. Significant metabolic differences were observed between 2D and 3D cultures, with notable changes in central carbon and glutathione metabolism in 3D spheroids. The results suggest that 3D cultures, which more closely mimic the in vivo environment, may offer a more accurate platform for cancer research and drug testing.

PMID:39329720 | PMC:PMC11430555 | DOI:10.3390/cells13181536
Prospective assessment of probe-based confocal laser endomicroscopy under direct cholangioscopic visualization for biliary strictures that could not be definitively diagnosed using endoscopic retrograde cholangiopancreatography (with video)

Fetched: October 16th, 2024, 2:01am UTC by Yuki Tanisaka

DEN Open. 2024 Sep 25;5(1):e70007. doi: 10.1002/deo2.70007. eCollection 2025 Apr.

ABSTRACT

The definitive diagnosis of patients with indeterminate biliary strictures remains challenging. Probe-based confocal laser endomicroscopy (pCLE) provides real-time histological assessment of bile duct tissues. Since no previous studies have evaluated the efficacy of pCLE under direct cholangioscopic visualization for biliary strictures that cannot be definitively diagnosed through endoscopic retrograde cholangiopancreatography using fluoroscopy, we prospectively assessed the feasibility and safety of this procedure in three cases. pCLE findings were obtained in three cases, providing accurate diagnoses. Additionally, no adverse event was reported. pCLE under direct cholangioscopic visualization for indeterminate biliary strictures might be feasible and safe, even though these strictures were not previously diagnosed using endoscopic retrograde cholangiopancreatography. Further studies with more cases are warranted to clarify the effectiveness of pCLE under direct cholangioscopic visualization.

PMID:39328351 | PMC:PMC11424493 | DOI:10.1002/deo2.70007
Beyond body mass index: Body composition profiling for perioperative risk stratification in intrahepatic cholangiocarcinoma patients

Fetched: October 16th, 2024, 2:01am UTC by Johannes Kolck

Cancer Rep (Hoboken). 2024 Sep;7(9):e2070. doi: 10.1002/cnr2.2070.

ABSTRACT

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCC) is an aggressive tumor, usually detected at an advanced stage. Our aim was to investigate the potential of body composition analysis (BCA) derived from presurgical staging computed tomography (CT) in predicting perisurgical complications.

METHODS: In this retrospective cohort study, we enrolled 86 patients who underwent CT imaging prior to liver surgery. Cox and logistic regression were performed to assess risk factors for prolonged hospital and intensive care unit (ICU) stays, as well as the occurrence of various complications. BCA parameters served as covariates besides conventional risk factors.

RESULTS: Postoperative complications after resection of iCC significantly prolonged the overall length of hospitalization (p < .001). Presence of sarcopenia was associated with longer ICU stays. Complications were common, with 62.5% classified as Clavien-Dindo grade IIIa or lower and 37.5% as more severe. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were identified as risk factors for complications, including bile leakage (in 24 cases, p = .025), pleural effusions (in 26 cases, p = .025), and intra-abdominal abscess formation (in 24 cases, p = .043). SAT was associated with severe complications requiring interventional therapy, whereas VAT was correlated with abscess formation. Despite normal prevalence of obesity (22%), body mass index (BMI) did not have an impact on the development of perioperative complications.

CONCLUSION: BCA is a useful tool for preoperative risk stratification in patients with iCC and is superior to BMI assessment. Increased SAT and VAT were associated with the risk of perisurgical complications, prolonging hospitalization. Therefore, BCA derived from routine staging CT should be considered in the preoperative assessment of patients with iCC.

PMID:39324689 | PMC:PMC11425665 | DOI:10.1002/cnr2.2070
Endoscopic biliary drainage for distal bile duct obstruction due to pancreatic cancer

Fetched: October 16th, 2024, 2:01am UTC by Masahiro Itonaga

Clin Endosc. 2024 Sep 26. doi: 10.5946/ce.2023.294. Online ahead of print.

ABSTRACT

Approximately 60% of pancreatic cancers occur in the pancreatic head and may present as obstructive jaundice due to bile duct invasion. Obstructive jaundice often leads to poor general conditions and acute cholangitis, interfering with surgery and chemotherapy and requiring biliary drainage. The first choice of treatment for biliary drainage is the endoscopic transpapillary approach. In unresectable tumors, self-expandable metal stents (SEMSs) are most commonly used and are classified into uncovered and covered SEMSs. Recently, antireflux metal stents and large- or small-diameter SEMSs have become commercially available, and their usefulness has been reported. Plastic stents are infrequently used in patients with resectable biliary obstruction; however, owing to the recent trend in preoperative chemotherapy, SEMSs are frequently used because of the long time to recurrent biliary obstruction. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is often performed in patients who are not eligible for the transpapillary approach, and favorable outcomes have been reported. Different EUS-BD techniques and specialized stents have been developed and can be safely used in high-volume centers. The indications for EUS-BD are expected to further expand in the future.

PMID:39322288 | DOI:10.5946/ce.2023.294
Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose

Fetched: October 16th, 2024, 2:01am UTC by Hung-Chun Tung

Sci Transl Med. 2024 Sep 25;16(766):eadk8446. doi: 10.1126/scitranslmed.adk8446. Epub 2024 Sep 25.

ABSTRACT

Activation of extracellular matrix-producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)-, carbon tetrachloride (CCl4)-, or bile duct ligation (BDL)-induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARÎ±. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis.

PMID:39321267 | DOI:10.1126/scitranslmed.adk8446
Laparoscopic Duodenum and Spleen-Preserving Subtotal or Total Pancreatectomy: A Parenchyma-Sparing Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms (with Video)

Fetched: October 16th, 2024, 2:01am UTC by Zheng Li

Ann Surg Oncol. 2024 Sep 23. doi: 10.1245/s10434-024-16244-2. Online ahead of print.

ABSTRACT

BACKGROUND: For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy.

PATIENTS AND METHODS: On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure.

RESULTS: We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3-5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien-Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control.

CONCLUSIONS: LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations.

PMID:39312053 | DOI:10.1245/s10434-024-16244-2
Intraductal Papillary Neoplasms of the Bile Duct: Clinical Case Insights and Literature Review

Fetched: October 16th, 2024, 2:01am UTC by Luca Toti

Clin Pract. 2024 Aug 27;14(5):1669-1681. doi: 10.3390/clinpract14050133.

ABSTRACT

BACKGROUND: Intraductal papillary neoplasms of the bile duct (IPNB) are rare precancerous lesions with implications for the development of cholangiocarcinoma (CCA). Recognizing IPNB and managing its recurrence pose challenges in clinical practice. We present two cases. Case 1: a 60-year-old man presented with an 8 Ã— 8 Ã— 9 cm hepatic cyst initially suspected to be a hydatid cyst. Histology post-resection revealed an IPNB with foci of adenocarcinoma. Despite negative oncologic margins, recurrence occurred eight years later as an rT2N0 lesion. Surgical resection was performed without adjuvant chemotherapy, resulting in the patient's survival at 48 months post-surgery. Case 2: a 28-year-old female with cognitive impairment was admitted with pulmonary embolism and a liver lesion diagnosed as a simple cyst. Subsequent evaluation revealed adenocarcinoma with local metastases, extensive vascular involvement, and thrombosis. Despite aggressive management, including thrombectomy and chemotherapy, the patient's condition deteriorated, leading to hepatic failure and eventual demise.

CONCLUSION: IPNB represents a rare premalignant subtype with a propensity for progression to CCA. R0 surgical resection typically offers favorable oncological outcomes with a minimal recurrence risk. Surgical intervention for localized resectable recurrence is both safe and feasible. International registries tracking IPNB recurrence are essential for advancing understanding and optimizing diagnosis, management, and treatment strategies.

PMID:39311283 | PMC:PMC11417733 | DOI:10.3390/clinpract14050133
CT Texture Analysis of Perihilar Cholangiocarcinoma-Associations With Tumor Grading, Tumor Markers and Clinical Outcome

Fetched: October 16th, 2024, 2:01am UTC by Jakob Leonhardi

Cancer Rep (Hoboken). 2024 Sep;7(9):e2132. doi: 10.1002/cnr2.2132.

ABSTRACT

BACKGROUND: Texture analysis derived from computed tomography (CT) may provide clinically relevant imaging biomarkers associated with tumor histopathology. Perihilar cholangiocarcinoma is a malignant disease with an overall poor prognosis.

AIMS: The present study sought to elucidate possible associations between texture features derived from CT images with grading, tumor markers, and survival in extrahepatic, perihilar cholangiocarcinomas tumors.

METHODS: This retrospective study included 22 patients (10 females, 45%) with a mean age of 71.8 Â± 8.7 years. Texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. Survival and clinical parameters were used as primary study outcomes.

RESULTS: In discrimination analysis, "S(1,1)SumVarnc" was statistically significantly different between patients with long-term survival and nonlong-term survival (mean 275.8 Â± 32.6 vs. 239.7 Â± 26.0, p = 0.01). The first-order parameter "skewness" was associated with the tumor marker "carcinoembryonic antigen" (CEA) (r = -0.7, p = 0.01). A statistically significant correlation of the texture parameter "S(5,0)SumVarnc" with tumor grading was identified (r = -0.6, p < 0.01). Several other texture features correlated with tumor markers CA-19-9 and AFP, as well as with T and N stage of tumors.

CONCLUSION: Several texture features derived from CT images were associated with tumor characteristics and survival in patients with perihilar cholangiocarcinomas. CT texture features could be used as valuable novel imaging markers in clinical routine.

PMID:39307946 | PMC:PMC11417006 | DOI:10.1002/cnr2.2132
Pancreaticoduodenectomy (Whipple Procedure)

Fetched: October 16th, 2024, 2:01am UTC by Jason R. D'Cruz

2024 Oct 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Janâ€“.

ABSTRACT

Pancreaticoduodenectomy, commonly known as the Whipple procedure, is a complex and technically challenging surgery primarily used to treat malignancies in the pancreatic head, periampullary region, and distal bile duct. The procedure involves the resection of the pancreatic head and uncinate process, duodenum, proximal jejunum, distal bile duct, gallbladder, and usually part of the stomach, followed by restoring bilioenteric continuity (see Image. Pancreaticoduodenectomy [Whipple Procedure]). While predominantly performed for malignant conditions, it is also indicated for benign conditions like chronic pancreatitis, large symptomatic cysts, or premalignant lesions such as intrapancreatic mucinous neoplasms.

The procedure was first performed by Walter Kausch in Germany and later refined by Allen Whipple in the United States and has become a cornerstone in managing pancreatic and periampullary cancers. Advances in surgical techniques, including minimally invasive approaches like laparoscopy with or without robotic assistance, have improved outcomes, yet the Whipple procedure remains associated with significant morbidity and mortality. Successful outcomes hinge on meticulous patient selection, comprehensive preoperative preparation, skilled surgical and anesthetic techniques, and coordinated postoperative care.

PMID:32809582 | Bookshelf:NBK560747
Telotristat ethyl, a tryptophan hydroxylase inhibitor, enhances antitumor efficacy of standard chemotherapy in preclinical cholangiocarcinoma models

Fetched: September 4th, 2024, 2:01am UTC by Niranjan Awasthi

J Cell Mol Med. 2024 Sep;28(17):e18585. doi: 10.1111/jcmm.18585.

ABSTRACT

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer, carries a grim prognosis with a 5-year survival rate of 5%-15%. Standard chemotherapy regimens for CCA, gemcitabine plus cisplatin (GemCis) or its recently approved combination with durvalumab demonstrate dismal clinical activity, yielding a median survival of 12-14 months. Increased serotonin accumulation and secretion have been implicated in the oncogenic activity of CCA. This study investigated the therapeutic efficacy of telotristat ethyl (TE), a tryptophan hydroxylase inhibitor blocking serotonin biosynthesis, in combination with standard chemotherapies in preclinical CCA models. Nab-paclitaxel (NPT) significantly enhanced animal survival (60%), surpassing the marginal effects of TE (11%) or GemCis (9%) in peritoneal dissemination xenografts. Combining TE with GemCis (26%) or NPT (68%) further increased survival rates. In intrahepatic (iCCA), distal (dCCA) and perihilar (pCCA) subcutaneous xenografts, TE exhibited substantial tumour growth inhibition (41%-53%) compared to NPT (56%-69%) or GemCis (37%-58%). The combination of TE with chemotherapy demonstrated enhanced tumour growth inhibition in all three cell-derived xenografts (67%-90%). PDX studies revealed TE's marked inhibition of tumour growth (40%-73%) compared to GemCis (80%-86%) or NPT (57%-76%). Again, combining TE with chemotherapy exhibited an additive effect. Tumour cell proliferation reduction aligned with tumour growth inhibition in all CDX and PDX tumours. Furthermore, TE treatment consistently decreased serotonin levels in all tumours under all therapeutic conditions. This investigation decisively demonstrated the antitumor efficacy of TE across a spectrum of CCA preclinical models, suggesting that combination therapies involving TE, particularly for patients exhibiting serotonin overexpression, hold the promise of improving clinical CCA therapy.

PMID:39223878 | DOI:10.1111/jcmm.18585
Predictors and risk factors of bile duct injury after transcatheter arterial chemoembolization for hepatocellular carcinoma

Fetched: September 3rd, 2024, 2:01am UTC by Haohao Lu

BMC Cancer. 2024 Sep 2;24(1):1085. doi: 10.1186/s12885-024-12864-9.

ABSTRACT

PURPOSE: Bile duct injury is a serious complication after transcatheter arterial chemoembolization (TACE). If it is not detected early and treated actively, it will not only affect the subsequent tumor-related treatment of hepatocellular carcinoma (HCC) patients, but also may lead to serious consequences such as infection, liver failure and even death. To analyze the risk factors of bile duct injury after TACE in patients with HCC and explore the predictive indicators of bile duct injury after TACE, which is helpful for doctors to detect and intervene early and avoid the occurrence of serious complications.

METHOD: We retrospectively analyzed the clinical data of 847 patients with primary hepatocellular carcinoma who underwent TACE for the first time in our interventional department. Patients were divided into two groups according to whether bile duct injury occurred after TACE: (1) bile duct injury group, N = 55; (2) no bile duct injury group, N = 792. The basic data, intraoperative conditions and the outcome of bile duct injury were analyzed. The chi-square test was used for comparison of enumeration data. The Mann-Whitney U test was used for comparison of measurement data. Risk factor analysis was performed using binary logistic regression analysis.

RESULTS: Basic data and intraoperative conditions were compared between the bile duct injury group and the group without bile duct injury: preoperative alkaline phosphatase (ALP) (103.24 Â± 32.77U/L vs. 89.17 Â± 37.35U/L, P = 0.003); history of hepatobiliary surgery (36.4% vs. 20.8%, P = 0.011); intraoperative lipiodol volume (P = 0.007); combined use of gelatin sponge particles (65.5% vs. 35.0%, P < 0.001); hypovascularity (58.2% vs. 24.5%, P < 0.001); and embolization site (P < 0.001). Comparison of postoperative liver function between bile duct injury group and non-bile duct injury group: postoperative total bilirubin (43.34 Â± 25.18umol/L vs. 21.94 Â± 9.82umol/L, P < 0.001); postoperative Î³-glutamyltransferase(GGT) (188.09 Â± 55.62U/L vs. 84.04 Â± 36.47U/L, P < 0.001); postoperative ALP(251.51 Â± 61.51U/L vs. 99.92 Â± 45.98U/L, P < 0.001).

CONCLUSION: The dosage of lipiodol in TACE, supplementation of gelatin sponge particles, embolization site, and hypovascularity of the tumor are risk factors for biliary duct injury after TACE. After TACE, GGT and ALP increased â‰¥ 2 times compared with preoperative indicators as predictors of bile duct injury. Bile duct injury occurring after TACE can achieve good outcomes with aggressive management.

PMID:39223485 | DOI:10.1186/s12885-024-12864-9
A Retrospective Study on the Clinical Characteristics and Computed Tomography, Biochemical, and Blood Parameters of Duodenal Papillary Diseases

Fetched: September 3rd, 2024, 2:01am UTC by Ning Wang

Cancer Control. 2024 Jan-Dec;31:10732748241278921. doi: 10.1177/10732748241278921.

ABSTRACT

OBJECTIVE: This study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignancies, aiming to contribute to the early diagnosis of these diseases.

METHODS: The clinical characteristics, laboratory data, and computed tomography (CT) findings of 17 patients with adenoma of the major duodenal papilla (the adenoma group) and 58 patients with cancer of the major duodenal papilla (the cancer group) were retrospectively analyzed. The measurement data were analyzed using t test and expressed as mean Â± standard deviation. The counting data were analyzed using the Ï‡² test and expressed in n (%). Pearson correlation analysis was also conducted, and a scatter plot was drawn.

RESULTS: There were significant differences in the diameter, shape, margin, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, enhancement uniformity, fever, direct bilirubin, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9, and jaundice between the adenoma group and the cancer group (P < .01). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the duodenal papilla diameter (P < .05). Additionally, 12 patients in the cancer group suffered from malignant transformation of adenomas.

CONCLUSION: Firstly, CT is of high value in the diagnosis of duodenal papilla diseases. Secondly, the enhancement magnitude of the duodenal papilla is correlated with the lesion size. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, thereby requiring close follow-up.

PMID:39222361 | DOI:10.1177/10732748241278921
Impact of Serum Triglyceride Levels on Severity and Outcomes in Acute Biliary Pancreatitis: A Retrospective Cohort Study

Fetched: September 3rd, 2024, 2:01am UTC by Ihtisham Ul Haq

Cureus. 2024 Aug 1;16(8):e65928. doi: 10.7759/cureus.65928. eCollection 2024 Aug.

ABSTRACT

Background Acute biliary pancreatitis (ABP), a major inflammatory illness, is primarily caused by gallstone blockage of the common bile duct. The pathophysiology of ABP has been linked to serum triglyceride (TG) levels, suggesting a potential role for TG in predicting disease severity. Objective The research objective was to investigate the association between serum TG levels and the severity of ABP. Methodology This retrospective cohort study sought to determine the relationship between blood TG levels and the severity of ABP. It was conducted at Lady Reading Hospital in Peshawar, Pakistan, from September 2023 to March 2024. A total of 530 ABP patients were divided into two groups based on their TG levels: normal (<150 mg/dl) and elevated (â‰¥150 mg/dl). Clinical data were gathered, including demographics, comorbidities, laboratory results, severity ratings (APACHE II and Ranson's criteria), and clinical outcomes. Descriptive statistics, Chi-square tests, and multivariate logistic regression were used in the statistical analysis. Results Patients with elevated TG levels (n=130) demonstrated higher median Ranson's criteria (3.24 vs. 2.53, p<0.001) and APACHE II scores (10.53 vs. 8.73, p<0.001) compared to those with normal TG levels (n=400). Elevated TG levels were associated with increased severity of ABP, with ORs of 2.41 (95% CI: 1.23-4.74) for mild vs. severe ABP. Clinical outcomes such as ICU admission (21.54% vs. 3.25%, p<0.001), mortality (6.15% vs. 0.50%, p<0.001), and pancreatic necrosis (10.77% vs. 1.25%, p<0.001) were significantly worse in the elevated TG group. Conclusion Elevated serum TG levels (â‰¥150 mg/dl) are independently associated with increased severity of ABP, as indicated by higher severity scores and poorer clinical outcomes.

PMID:39221319 | PMC:PMC11365021 | DOI:10.7759/cureus.65928
Combined bacterial translocation and cholestasis aggravates liver injury by activation pyroptosis in obstructive jaundice

Fetched: September 3rd, 2024, 2:01am UTC by Xin Shen

Heliyon. 2024 Aug 3;10(16):e35793. doi: 10.1016/j.heliyon.2024.e35793. eCollection 2024 Aug 30.

ABSTRACT

This study explores the mechanism by which obstructive jaundice (OJ) induces liver damage through pyroptosis. We induced OJ in rats via bile duct ligation and assessed liver damage using serum biochemical markers and histological analysis of liver tissue. Pyroptosis was investigated through immunofluorescence, ELISA, Western blot, and quantitative RT-PCR techniques. Additionally, we examined intestinal function and fecal microbiota alterations in the rats using 16S rDNA sequencing. In vitro experiments involved co-culturing Kupffer cells and hepatocytes, which were then exposed to bile and lipopolysaccharide (LPS). Our findings indicated that OJ modified the gut microbiota, increasing LPS levels, which, in conjunction with bile, initiated a cycle of inflammation, fibrosis, and cell death in the liver. Mechanistically, OJ elevated necrotic markers such as ATP, which in turn activated pyroptotic pathways. Increased levels of pyroptosis-related molecules, including NLRP3, caspase-1, gasdermin D, and IL-18, were confirmed. In our co-cultured cell model, bile exposure resulted in cell death and ATP release, leading to the activation of the NLRP3 inflammasome and its downstream effectors, caspase-1 and IL-18. The combination of bile and LPS significantly intensified pyroptotic responses. This study is the first to demonstrate that LPS and bile synergistically exacerbate liver injury by promoting necrosis and pyroptosis, unveiling a novel mechanism of OJ-associated hepatic damage and suggesting avenues for potential preventive or therapeutic interventions.

PMID:39220957 | PMC:PMC11363856 | DOI:10.1016/j.heliyon.2024.e35793
Role of endoscopic ultrasound-guided biliary drainage for palliation of malignant biliary obstruction

Fetched: September 3rd, 2024, 2:01am UTC by Sahib Singh

World J Gastrointest Surg. 2024 Aug 27;16(8):2369-2373. doi: 10.4240/wjgs.v16.i8.2369.

ABSTRACT

Endoscopic ultrasound-guided biliary drainage (EUS-BD) directs bile flow into the digestive tract and has been mostly used in patients with malignant biliary obstruction (MBO) where endoscopic retrograde cholangiopancreatography-guided biliary drainage was unsuccessful or was not feasible. Lumen apposing metal stents (LAMS) are deployed during EUS-BD, with the newer electrocautery-enhanced LAMS reducing procedure time and complication rates due to the inbuilt cautery at the catheter tip. EUS-BD with electrocautery-enhanced LAMS has high technical and clinical success rates for palliation of MBO, with bleeding, cholangitis, and stent occlusion being the most common adverse events. Recent studies have even suggested comparable efficacy between EUS-BD and endoscopic retrograde cholangiopancreatography as the primary approach for distal MBO. In this editorial, we commented on the article by Peng et al published in the recent issue of the World Journal of Gastrointestinal Surgery in 2024.

PMID:39220057 | PMC:PMC11362943 | DOI:10.4240/wjgs.v16.i8.2369
Outcome of Minimally Invasive and Open Pancreatoduodenectomy in Patients with Intestinal- and Pancreatobiliary Subtype Ampullary Cancer: An International Multicenter Cohort Study

Fetched: September 3rd, 2024, 2:01am UTC by Bas A Uijterwijk

Ann Surg. 2024 Sep 2. doi: 10.1097/SLA.0000000000006515. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare minimally invasive and open pancreatoduodenectomy in different subtypes of ampullary adenocarcinoma.

SUMMARY BACKGROUND DATA: Ampullary adenocarcinoma (AAC) is widely seen as the best indication for minimally invasive pancreatoduodenectomy (MIPD) due to the lack of vascular involvement and dilated bile and pancreatic duct. However, it is unknown whether outcomes of MIPD for AAC differ between the pancreatobiliary (AAC-PB) and intestinal (AAC-IT) subtypes as large studies are lacking.

METHODS: This is an international cohort study, encompassing 27 centers from 12 countries. Outcome of MIPD and open pancreatoduodenectomy (OPD) were compared in patients with AAC-IT and AAC-PB. Primary end points were R1 rate, lymph node yield, and 5-year overall survival (5yOS).

RESULTS: Overall, 1187 patients after MIPD for AAC were included, of whom 572 with AAC-IT (62 MIPD, 510 OPD) and 615 with AAC-PB (41 MIPD and 574 OPD). The rate of R1 resection was not significantly different between MIPD and OPD for both AAC-IT (3.4% vs 6.9%, P=0,425) and AAC-PB (9.8% vs 14.9%, P=0,625). AAC-IT, more lymph nodes were resected with MIPD group (19 vs 16, P=0.007), compared to OPD. The 5y-OS did not differ after MIPD and OPD for both AAC-IT (56.8% vs 59.5%, P=0.827 and AAC-PB (52.5% vs 44.4%, P=0.357). The rates of surgical complication between MIPD and OPD did not differ between AmpIT and AmpPB.

DISCUSSION: This international multicenter study found no differences in outcomes between MIPD and OPD for AAC-IT and AAC-PB. MIPD and OPD demonstrated comparable outcomes in oncological resection, survival and surgical outcomes for both subtypes of AAC.

PMID:39219532 | DOI:10.1097/SLA.0000000000006515
microRNA profiling of exosomes derived from plasma and their potential as biomarkers for Opisthorchis viverrini-associated cholangiocarcinoma

Fetched: September 2nd, 2024, 2:01am UTC by Kittiya Supradit

Acta Trop. 2024 Oct;258:107362. doi: 10.1016/j.actatropica.2024.107362. Epub 2024 Aug 14.

ABSTRACT

Cholangiocarcinoma (CCA) is a life-threatening disease that impacts patients worldwide. In Southeast Asian countries, the liver fluke Opisthorchis viverrini plays a major role in inducing carcinogenesis of the bile ducts. Due to its asymptomatic nature, O. viverrini infections are rarely treated, consequently leading to the development of advanced stages of CCA before diagnosis. Despite the current use of exosomal microRNAs (miRNA) as diagnostic biomarkers for the early detection of many types of cancer, the applications for miRNA remain limited with CCA. Circulating exosomes, membranous vesicles essential for intercellular communication, were found to contain unique miRNA. In this study, we conducted next-generation sequencing (Ion Torrent PGM) and bioinformatics to characterize and compare the contents of exosomal miRNA derived from the plasma of CCA patients, O. viverrini-infected patients, and healthy individuals, as well as to identify and validate key molecules as markers for screening the diagnosis of CCA and O. viverrini infection. The obtained results showed the success of using NGS technology in discovering exosomal miRNAs, specifically miR-194-5p and miR-192-5p, both of which were upregulated in the O. viverrini-infected group. Interestingly, miR-192-5p was upregulated while miR-194-5p was downregulated in CCA, suggesting their potential use as biomarkers for screening CCA and O. viverrini infection, especially in O. viverrini-endemic areas.

PMID:39151716 | DOI:10.1016/j.actatropica.2024.107362
HSPB8-BAG3 chaperone complex modulates cell invasion in intrahepatic cholangiocarcinoma by regulating CASA-mediated Filamin A degradation

Fetched: September 1st, 2024, 2:01am UTC by Bo Shu

Cancer Biol Ther. 2024 Dec 31;25(1):2396694. doi: 10.1080/15384047.2024.2396694. Epub 2024 Aug 31.

ABSTRACT

The incidence of intrahepatic cholangiocarcinoma (ICC) is steadily rising, and it is associated with a high mortality rate. Clinical samples were collected to detect the expression of HSPB8 and BAG3 in ICC tissues. ICC cells were cultured and transfected with plasmids that overexpressed or silenced specific genes to investigate the impact of gene expression alterations on cell function. qPCR and Western blot techniques were utilized to measure gene and protein expression levels. A wound healing assay was conducted to assess cell migration ability. The Transwell assay was used to assess cell invasion ability. Co-IP was used to verify the binding relationship between HSPB8 and BAG3. The effects of HSPB8 and BAG3 on lung metastasis of tumors in vivo were verified by constructing a metastatic tumor model. Through the above experiments, we discovered that the expressions of HSPB8 and BAG3 were up-regulated in ICC tissues and cells, and their expressions were positively correlated. The metastatic ability of ICC cells could be promoted or inhibited by upregulating or downregulating the expression of BAG3. Furthermore, the HSPB8-BAG3 chaperone complex resulted in the abnormal degradation of Filamin A by activating autophagy. Increased expression of Filamin A inhibits the migration and invasion of ICC cells. Overexpression of HSPB8 and BAG3 in vivo promoted the lung metastasis ability of ICC cells. The HSPB8-BAG3 chaperone complex promotes ICC cell migration and invasion by regulating CASA-mediated degradation of Filamin A, offering insights for enhancing ICC therapeutic strategies.

PMID:39215616 | DOI:10.1080/15384047.2024.2396694
Cannabidiol exhibits potent anti-cancer activity against gemcitabine-resistant cholangiocarcinoma via ER-stress induction in vitro and in vivo

Fetched: September 1st, 2024, 2:01am UTC by Thatsanapong Pongking

BMC Complement Med Ther. 2024 Aug 30;24(1):325. doi: 10.1186/s12906-024-04610-2.

ABSTRACT

BACKGROUND: Failure of treatment with gemcitabine in most cholangiocarcinoma (CCA) patients is due to drug resistance. The therapeutic potential of natural plant secondary compounds with minimal toxicity, such as cannabidiol (CBD), is a promising line of investigation in gemcitabine-resistant CCA. We aim to investigate the effects of CBD on gemcitabine-resistant CCA (KKU-213B^GemR) cells in vitro and in vivo.

MATERIALS: In vitro, cell proliferation, colony formation, apoptosis and cell cycle arrest were assessed using MTT assay, clonogenicity assay and flow cytometry. The effect of CBD on ROS production was evaluated using the DCFH-DA fluorescent probe. The mechanism exerted by CBD on ER stress-associated apoptosis was investigated by western blot analysis. A gemcitabine-resistant CCA xenograft model was also used and the expression of PCNA and CHOP were evaluated by immunohistochemical analysis.

RESULTS: The IC50 values of CBD for KKU-213B^GemR cells ranged from 19.66 to 21.05 ÂµM. For a non-cancerous immortalized fibroblast cell line, relevant values were 18.29 to 19.21 ÂµM. CBD suppressed colony formation by KKU-213B^GemR cells in a dose-dependent manner in the range of 10 to 30 ÂµM. CBD at 30 ÂµM significantly increased apoptosis at early (16.37%) (P = 0.0024) and late (1.8%) stages (P < 0.0001), for a total of 18.17% apoptosis (P = 0.0017), in part by increasing ROS production (P < 0.0001). Multiphase cell cycle arrest significantly increased at G0/G1 with CBD 10 and 20 ÂµM (P = 0.004 and P = 0.017), and at G2/M with CBD 30 ÂµM (P = 0.005). CBD treatment resulted in increased expression of ER stress-associated apoptosis proteins, including p-PERK, BiP, ATF4, CHOP, BAX, and cytochrome c. In xenografted mouse, CBD significantly suppressed tumors at 10 and 40 mg/kgÂ·Bw (P = 0.0007 and P = 0.0278, respectively), which was supported by an increase in CHOP, but a decrease in PCNA expression in tumor tissues (P < 0.0001).

CONCLUSION: The results suggest that CBD exhibits potent anti-cancer activity against gemcitabine-resistant CCA in vitro and in vivo, in part via ER stress-mediated mechanisms. These results indicate that clinical explorative use of CBD on gemcitabine-resistant CCA patients is warranted.

PMID:39215312 | PMC:PMC11365133 | DOI:10.1186/s12906-024-04610-2
Cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Matthew E Dixon

Cancer Treat Res. 2024;192:165-184. doi: 10.1007/978-3-031-61238-1_9.

ABSTRACT

Cholangiocarcinoma (CC) is a heterogeneous group of malignancies that originates at any point along the biliary tree. CC is an uncommon malignancy as it represents approximately 3% of all gastrointestinal malignancies, though its global incidence is rising. CC can often be asymptomatic in its early stages and as a result, it is frequently diagnosed in later stages, leading to challenges in clinical management.

PMID:39212921 | DOI:10.1007/978-3-031-61238-1_9
Haemobilia as a primary presentation of cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Peter Stapleton

BMJ Case Rep. 2024 Aug 29;17(8):e260524. doi: 10.1136/bcr-2024-260524.

ABSTRACT

We present a case of haemobilia as a primary presentation for underlying cholangiocarcinoma. A man in his 50s initially presented to emergency with Quincke's triad, RUQ pain, jaundice and UGI bleeding. The initial diagnosis of haemobilia was made on endoscopic retrograde cholangiopancreatography (ERCP) on primary presentation, but the presence of blood and the recurrent clot obstruction of the biliary tract made the underlying diagnosis extremely difficult, resulting in the patient having 4 ERCP, 1 spyglass and multiple CTs and magnetic resonance cholangiopancreatography. Eventually, the patient underwent a Whipple's procedure without tissue diagnosis, confirming cholangiocarcinoma on histopathology. This case emphasises the difficulty of diagnosis of underlying malignancy in the setting of haemobilia, the benefit of multidisciplinary meeting discussions to support significant interventions and the need to be cautious and curious when managing atypical presentations.

PMID:39209753 | DOI:10.1136/bcr-2024-260524
Utilization of an artificial intelligence-enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study

Fetched: September 1st, 2024, 2:01am UTC by Neil B Marya

Cancer Cytopathol. 2024 Aug 29. doi: 10.1002/cncy.22898. Online ahead of print.

ABSTRACT

BACKGROUND: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool.

METHODS: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being "positive," "negative," or "indeterminate." The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared.

RESULTS: Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622-0.859), CADe (0.807; 95% CI, 0.750-0.856), and OCI (0.807; 95% CI, 0.671-0.900) were similar.

CONCLUSIONS: This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

PMID:39207803 | DOI:10.1002/cncy.22898
Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Baoluhe Zhang

Cancer Med. 2024 Aug;13(16):e70135. doi: 10.1002/cam4.70135.

ABSTRACT

BACKGROUND: This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA).

METHODS AND RESULTS: The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients.

CONCLUSIONS: In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.

PMID:39206584 | PMC:PMC11358702 | DOI:10.1002/cam4.70135
Investigation of Social Innovations for Handling Opisthorchis viverrini and Cholangiocarcinoma in Thailand's Highest-Risk Areas for Further Development of Successful Solution

Fetched: September 1st, 2024, 2:01am UTC by Nopparat Songserm

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2911-2917. doi: 10.31557/APJCP.2024.25.8.2911.

ABSTRACT

BACKGROUND: Despite the national campaigns in 1997 to control Opisthorchis viverrini (OV), a significant risk factor for cholangiocarcinoma (CCA) was accounted for in the northeast of Thailand, which is also considered the highest-risk area for CCA as per the latest national-wide survey in 2019. Social innovations were employed to address OV and CCA issues in this area, but they have yet to be thoroughly investigated. Investigating social innovations in areas where issues can already be solved is a particular approach for expanding on a broad basis.

OBJECTIVE: This study aimed to search for social innovations used to handle OV and CCA in northeast of Thailand.

METHODS: Researchers coordinated with the Office of Disease Prevention and Control Region-10 (1 of 12 regional offices under the Department of Disease Control, Ministry of Public Health) to specify the model areas for taking OV and CCA. In addition, researchers cooperated with local coordination units for data collection. The data were coded and classified for content analysis, and triangulation was performed for comparative analysis. Finally, a meeting was conducted to summarize the social innovations discovered in each study site area.

RESULTS: Our findings have been presented according to the epidemiologic triad: agent (risk factors), host (individuals/communities), and environment. The researchers and experts addressed and proposed social innovations for dealing with OV and CCA, such as the "3 Health" (Health Behaviours, Health Hygiene, and Environmental Health), in order to achieve a CCA-free society.

CONCLUSIONS: This is the first study to highlight the significance of social innovations in managing OV and CCA. The findings will be utilized to further create strategies for addressing these public health issues in this and other regions in a sustainable and successful manner.

PMID:39205590 | DOI:10.31557/APJCP.2024.25.8.2911
Re- Infection Rate of Opisthorchis Viverrini Five Years After Treatment with Praziquantel in High-Risk Area: A Community-Based Study

Fetched: September 1st, 2024, 2:01am UTC by Phubet Saengsawang

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2679-2684. doi: 10.31557/APJCP.2024.25.8.2679.

ABSTRACT

BACKGROUND: Opisthorchis viverrini (OV) is a significant public health problem in Thailand, and OV reinfection poses a serious risk of cholangiocarcinoma with little evidence of a decrease. While numerous studies have explored OV reinfection and prevalence, most have been limited to short study period. Therefore, there is a need for long-term investigations to gather sufficient evidence.

OBJECTIVES: This study aimed to access the current status of re-infection rates in high- risk areas and to determine associations between factors of and re-infection of OV at 5 years after treatment with praziquantel.

MATERIALS AND METHODS: In total, this study included 457 participants from a cohort study. Each participant was required to answer a questionnaire and undergo stool examination using the formalin ethyl acetate concentration technique. Data were analyzed using descriptive statistics and multiple logistic regression.

RESULT: Out of the total 457 participants, 418 (91.5%) successfully completed the questionnaires and underwent stool examinations. Among the participants, 10.8% showed re-infection with OV. Using multivariate analysis, factors significantly associated with reinfection OV included yearly income (OR adj = 2.14, 95%CI = 1.11- 4.12, p-value = 0.022) and past stool examination five years (OR adj = 2.47, 95%CI = 1.13-5.43, p-value = 0.023), respectively.

CONCLUSIONS: Subjects who frequently experience OV reinfection should undergo CCA screening by experts while closely monitoring their raw fish consumption behavior. Moreover, it is essential to implement comprehensive programs aimed at promoting behavioral changes and provide preventive education, with a specific focus on high epidemic areas, to discourage the consumption of raw fish.

PMID:39205565 | DOI:10.31557/APJCP.2024.25.8.2679
Plasma Cell-Free DNA and MiRNA in Cholangiocarcinoma and Opisthorchiasis Viverrini Patients: Comment

Fetched: September 1st, 2024, 2:01am UTC by Rujittika Mungmunpuntipantip

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2579. doi: 10.31557/APJCP.2024.25.8.2579.

NO ABSTRACT

PMID:39205552 | DOI:10.31557/APJCP.2024.25.8.2579
Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Kankamol Kerdkumthong

Biomolecules. 2024 Aug 8;14(8):969. doi: 10.3390/biom14080969.

ABSTRACT

Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein-protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial-mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets.

PMID:39199357 | PMC:PMC11352417 | DOI:10.3390/biom14080969
Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations

Fetched: September 1st, 2024, 2:01am UTC by Hisashi Tamada

Diagn Pathol. 2024 Aug 28;19(1):116. doi: 10.1186/s13000-024-01537-7.

ABSTRACT

BACKGROUND: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC).

METHODS: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed.

RESULTS: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397).

CONCLUSIONS: These findings suggest that LGR5 is a promising, novel prognostic marker.

PMID:39198902 | PMC:PMC11350935 | DOI:10.1186/s13000-024-01537-7
Identification of autoantibodies as potential non-invasive biomarkers for intrahepatic cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Wachira Kajornsrichon

Sci Rep. 2024 Aug 28;14(1):20012. doi: 10.1038/s41598-024-70595-0.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) presents a challenging diagnosis due to its nonspecific early clinical manifestations, often resulting in late-stage detection and high mortality. Diagnosing iCCA is further complicated by its limited accuracy, often necessitating multiple invasive procedures for precise identification. Despite carbohydrate antigen 19-9 (CA19-9) having been investigated and employed for iCCA diagnosis, it demonstrates modest diagnostic performance. Consequently, the identification of novel biomarkers with improved sensitivity and specificity remains an imperative yet formidable task. Autoantibodies, as early indicators of the immune response against cancer, offer a promising avenue for enhancing diagnostic accuracy. Our study aimed to identify non-invasive blood-based autoantibody biomarkers capable of distinguishing iCCA patients from healthy individuals (CTRs). We profiled autoantibodies in 26 serum samples (16 iCCAs and 10 CTRs) using protein microarrays containing 1622 functional proteins. Leveraging machine learning techniques, we identified a signature composed of three autoantibody biomarkers (NDE1, PYCR1, and VIM) in conjunction with CA19-9 for iCCA detection. This combined signature demonstrated superior diagnostic performance with an AUC of 96.9%, outperforming CA19-9 alone (AUC: 83.8%). These results suggest the potential of autoantibody biomarkers to develop a complementary non-invasive diagnostic utility for routine iCCA screening.

PMID:39198554 | PMC:PMC11358490 | DOI:10.1038/s41598-024-70595-0
HER2 amplification subtype intrahepatic cholangiocarcinoma exhibits high mutation burden and T cell exhaustion microenvironment

Fetched: September 1st, 2024, 2:01am UTC by Xiaohong Pu

J Cancer Res Clin Oncol. 2024 Aug 28;150(8):403. doi: 10.1007/s00432-024-05894-0.

ABSTRACT

OBJECTIVE: This study aimed to establish a uniform standard for the interpretation of HER2 gene and protein statuses in intrahepatic cholangiocarcinoma (ICC). We also intended to explore the clinical pathological characteristics, molecular features, RNA expression and immune microenvironment of HER2-positive ICC.

METHODS: We analyzed a cohort of 304 ICCs using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to identify HER2 status. Comprehensive analyses of the clinicopathological, molecular genetic, and RNA expression characterizations of ICCs with varying HER2 statuses were performed using next-generation sequencing. We further investigated the tumor microenvironment of ICCs with different HER2 statuses using IHC and multiplex immunofluorescence staining.

RESULTS: HER2/CEP17 ratio of â‰¥ 2.0 and HER2 copy number â‰¥ 4.0; or HER2 copy number â‰¥ 6.0 were setup as FISH positive criteria. Based on this criterion, 13 (4.27%, 13/304) samples were classified as having HER2 amplification. The agreement between FISH and IHC results in ICC was poor. HER2-amplified cases demonstrated a higher tumor mutational burden compared to non-amplified cases. No significant differences were observed in immune markers between the two groups. However, an increased density of CD8 + CTLA4 + and CD8 + FOXP3 + cells was identified in HER2 gene-amplified cases.

CONCLUSION: FISH proves to be more appropriate as the gold standard for HER2 evaluation in ICC. HER2 gene-amplified ICCs exhibit poorer prognosis, higher mutational burden, and T cell exhaustion and immune suppressed microenvironment.

PMID:39198311 | PMC:PMC11358322 | DOI:10.1007/s00432-024-05894-0
Unveiling the unexplored secret: Aggressive behavior and poor survival in intrahepatic mucinous adenocarcinoma compared to conventional adenocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Wenhui Wang

Biosci Trends. 2024 Aug 29. doi: 10.5582/bst.2024.01227. Online ahead of print.

ABSTRACT

Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.

PMID:39198179 | DOI:10.5582/bst.2024.01227
Enhancement of gemcitabine sensitivity in intrahepatic cholangiocarcinoma through Saikosaponin-a mediated modulation of the p-AKT/BCL-6/ABCA1 axis

Fetched: September 1st, 2024, 2:01am UTC by Fei Song

Phytomedicine. 2024 Oct;133:155944. doi: 10.1016/j.phymed.2024.155944. Epub 2024 Aug 8.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains a significant challenge in cancer therapy, especially due to its resistance to established treatments like Gemcitabine, necessitating novel therapeutic approaches.

METHODS: This study utilized Gemcitabine-resistant cell lines, patient-derived organotypic tumor spheroids (PDOTs), and patient-derived xenografts (PDX) to evaluate the effects of Saikosaponin-a (SSA) on ICC cellular proliferation, migration, apoptosis, and its potential synergistic interaction with Gemcitabine. Techniques such as transcriptome sequencing, Luciferase reporter assays, and molecular docking were employed to unravel the molecular mechanisms.

RESULTS: SSA exhibited antitumor effects in both in vitro and PDX models, indicating its considerable potential for ICC treatment. SSA markedly inhibited ICC progression by reducing cellular proliferation, enhancing apoptosis, and decreasing migration and invasion. Crucially, it augmented Gemcitabine's efficacy by targeting the p-AKT/BCL6/ABCA1 signaling pathway. This modulation led to the downregulation of p-AKT and suppression of BCL6 transcriptional activity, ultimately reducing ABCA1 expression and enhancing chemosensitivity to Gemcitabine. Additionally, ABCA1 was validated as a predictive biomarker for drug resistance, with a direct correlation between ABCA1 expression levels and the IC50 values of various small molecule drugs in ICC gene profiles.

CONCLUSION: This study highlights the synergistic potential of SSA combined with Gemcitabine in enhancing therapeutic efficacy against ICC and identifies ABCA1 as a key biomarker for drug responsiveness. Furthermore, the introduction of the novel PDOTs microfluidic model provides enhanced insights into ICC research. This combination strategy may provide a novel approach to overcoming treatment challenges in ICC.

PMID:39146879 | DOI:10.1016/j.phymed.2024.155944
Hepatic arterial infusion of GEMOX plus systemic gemcitabine chemotherapy combined with lenvatinib and PD-1 inhibitor in large unresectable intrahepatic cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Jia-Yan Ni

Int Immunopharmacol. 2024 Oct 25;140:112872. doi: 10.1016/j.intimp.2024.112872. Epub 2024 Aug 8.

ABSTRACT

PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC).

METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0.

RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs.

CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.

PMID:39121605 | DOI:10.1016/j.intimp.2024.112872
An Unusual Radiologic Image of Extensive Tumor Mass Infiltrating Hepatic Hilum without Signs of Cholestasis-A Case Report and a Literature Review of Non-Cancerous Lesions Mimicking Intrahepatic Cholangiocarcinoma

Fetched: August 29th, 2024, 2:01am UTC by Jakub Ciesielka

Curr Oncol. 2024 Aug 4;31(8):4507-4518. doi: 10.3390/curroncol31080336.

ABSTRACT

BACKGROUND: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted.

METHODS: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis.

RESULTS: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients.

CONCLUSIONS: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination.

PMID:39195319 | PMC:PMC11352376 | DOI:10.3390/curroncol31080336
Analysis of the Effector Functions of VÎ´2 Î³Î´ T Cells and NK Cells against Cholangiocarcinoma Cells

Fetched: August 29th, 2024, 2:01am UTC by Inthuon Kulma

Cells. 2024 Aug 8;13(16):1322. doi: 10.3390/cells13161322.

ABSTRACT

Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by VÎ´2 Î³Î´ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-Î³. VÎ´2 Î³Î´ T cells demonstrated cytotoxicity and IFN-Î³ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both VÎ´2 Î³Î´ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA.

PMID:39195212 | PMC:PMC11352430 | DOI:10.3390/cells13161322
Transcriptome Analyses of Liver Sinusoidal Endothelial Cells Reveal a Consistent List of Candidate Genes Associated with Endothelial Dysfunction and the Fibrosis Progression

Fetched: August 29th, 2024, 2:01am UTC by Penghui Li

Curr Issues Mol Biol. 2024 Jul 25;46(8):7997-8014. doi: 10.3390/cimb46080473.

ABSTRACT

Liver fibrosis is an important step in the transformation of chronic liver disease into cirrhosis and liver cancer, and structural changes and functional disorders of liver sinusoidal endothelial cells (LSECs) are early events in the occurrence of liver fibrosis. Therefore, it is necessary to identify the key regulatory genes of endothelial dysfunction in the process of liver fibrosis to provide a reference for the diagnosis and treatment of liver fibrosis. In this study, we identified 230 common differentially expressed genes (Co-DEGs) by analyzing transcriptomic data of primary LSECs from three different liver fibrosis mouse models (carbon tetrachloride; choline-deficient, l-amino acid-defined diet; and nonalcoholic steatohepatitis). Enrichment analysis revealed that the Co-DEGs were mainly involved in regulating the inflammatory response, immune response, angiogenesis, formation and degradation of the extracellular matrix, and mediating chemokine-related pathways. A Venn diagram analysis was used to identify 17 key genes related to the progression of liver cirrhosis. Regression analysis using the Lasso-Cox method identified genes related to prognosis among these key genes: SOX4, LGALS3, SERPINE2, CD52, and LPXN. In mouse models of liver fibrosis (bile duct ligation and carbon tetrachloride), all five key genes were upregulated in fibrotic livers. This study identified key regulatory genes for endothelial dysfunction in liver fibrosis, namely SOX4, LGALS3, SERPINE2, CD52, and LPXN, which will provide new targets for the development of therapeutic strategies targeting endothelial dysfunction in LSECs and liver fibrosis.

PMID:39194690 | PMC:PMC11352563 | DOI:10.3390/cimb46080473
Malignant Melanoma With Neural Marker-Positive Distant Organ Cancers

Fetched: August 29th, 2024, 2:01am UTC by Natsumi Hara

Cureus. 2024 Jul 28;16(7):e65594. doi: 10.7759/cureus.65594. eCollection 2024 Jul.

ABSTRACT

Malignant melanoma is a melanocyte-derived tumor known for its aggressive clinical behavior. Melanocytes originate from the neural crest, which also gives rise to neural tissues. Malignant melanoma can occasionally exhibit neural differentiation. We report a case of a 70-year-old male with malignant melanoma exhibiting neural marker positivity in the absence of typical melanoma markers. The patient initially presented with a dark nodule on his left heel, which was confirmed as malignant melanoma through cytology. Surgical resection and lymph node dissection were performed, revealing atypical melanocytes. Despite postoperative nivolumab treatment, metastases in the brain and lungs were observed. Histological examination of the brain tumor showed neural differentiation markers (thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK7), AE1/AE3, and epidermal growth factor receptor (EGFR)) with negative melanoma markers. The patient eventually succumbed to the disease despite multiple treatments. An autopsy revealed multiple organ tumors (brain, duodenum, stomach, liver, and bile duct) negative for melanoma markers but positive for neuroendocrine markers (CD56, synaptophysin, and chromogranin A). This case suggests two possibilities: the coexistence of malignant melanoma with neuroendocrine tumors or a transformation of melanoma into a neuroendocrine phenotype. This case highlights the need for clinicians to consider the potential for melanoma to lose typical markers and transform into neuroendocrine cancer.

PMID:39192931 | PMC:PMC11349388 | DOI:10.7759/cureus.65594
Unaccounted Gallbladder

Fetched: August 28th, 2024, 2:01am UTC by Sunil Vishwakarma

Cureus. 2024 Jul 27;16(7):e65490. doi: 10.7759/cureus.65490. eCollection 2024 Jul.

ABSTRACT

Gallbladder agenesis is a rare anatomical variant, and most cases are asymptomatic and diagnosed on autopsy. Few of them may present with features suggestive of biliary tract pathology. A 32-year-old male presented with complaints of intermittent epigastric pain for three months. Abdominal ultrasonography was suggestive of chronic calculous cholecystitis, and he was planned for laparoscopic cholecystectomy. However, no gallbladder was found during the surgery. Postoperative evaluation was suggestive of an absent gallbladder with a normal ductal system. A provisional diagnosis of sphincter of Oddi dysfunction was made based on his symptoms. Congenital absence of gallbladder is a rare anomaly and only a few of the affected individuals are symptomatic. Lack of specific features, coupled with the inability of standard abdominal ultrasonography to detect the absence of gallbladder, can put the treating surgeon in a dilemma intraoperatively. Agenesis of the gallbladder is often missed and this entity should be kept in mind while having difficulty in visualizing the gallbladder. An astute surgeon should be wary of this diagnosis during difficult dissection to avoid bile duct injuries.

PMID:39188464 | PMC:PMC11345654 | DOI:10.7759/cureus.65490
Anatomical biliary reconstruction as an ultimum refugium for selective cases-History and current state of knowledge

Fetched: August 28th, 2024, 2:01am UTC by Jan Sevcik

J Hepatobiliary Pancreat Sci. 2024 Aug 26. doi: 10.1002/jhbp.12067. Online ahead of print.

ABSTRACT

Reconstruction of extrahepatic bile ducts is a staple procedure of HPB surgery. The current standard for most cases is a nonanatomical bilioenteric reconstruction, a satisfactory option for the majority of patients. However, it cannot be used for a small number of selective cases (short bowel syndrome, severe abdominal adhesions), where an anatomical reconstruction with or without an interponate can be used. This review summarizes current knowledge about tissue and material usage for experimental and clinical anatomical bile duct reconstruction in the last 100 years. A Pubmed database was searched for published articles about anatomical extrahepatic bile duct reconstruction in experimental and clinical settings ranging from 1920 to 2022. To date, the truly optimal interponate material has not yet been found. However, evidence reveals important properties of such material, most importantly its biodegradability and neovascularization in the recipient's body. The role of internal bile duct stenting for anatomical reconstruction seems important for the outcome. Anatomical reconstruction of extrahepatic bile ducts is an uncommon but usable technique in unique cases when a nonanatomical reconstruction cannot be done. The optimal properties of interponate material for anatomical bile duct reconstruction have been more clarified, although further research is required.

PMID:39187445 | DOI:10.1002/jhbp.12067
Anti-Tumor and Chemosensitizing Effects of the CDK Inhibitor Dinaciclib on Cholangiocarcinoma In Vitro and In Vivo

Fetched: August 28th, 2024, 2:01am UTC by Prin Sungwan

In Vivo. 2024 Sep-Oct;38(5):2284-2293. doi: 10.21873/invivo.13693.

ABSTRACT

BACKGROUND/AIM: Cholangiocarcinoma (CCA) is a highly aggressive disease. Most of CCA patients are diagnosed in an advanced stage of the disease, when it is unresectable and there is chemoresistance, resulting in poor prognosis. However, effective therapeutic regimens and molecular targets for CCA remain poor. Cyclin-dependent kinases (CDKs) are key regulatory enzymes in cell cycle progression. Aberrant CDK activation is a hallmark of cancer. Dinaciclib is a small molecule inhibitor of multiple CDKs, currently under clinical evaluation for treating advanced malignancies. The efficacy of anti-tumor activity of dinaciclib against chemotherapy resistant CCA cells was examined in vitro and in vivo.

MATERIALS AND METHODS: In this study, the effect of dinaciclib on growth and cell cycle in CCA cell lines were determined using the MTT assay and cell cycle analysis. The anti-tumor activity of dinaciclib was investigated in CCA-inoculated mice. In addition, the chemosensitizing effect of dinaciclib was investigated in gemcitabine-treated CCA cell lines.

RESULTS: Dinaciclib significantly suppressed cell proliferation, induced G1/S phase cell cycle arrest and apoptosis of CCA cell lines. It significantly suppressed the growth of CCA cells in xenograft mouse models. We also found that dinaciclib significantly inhibited the growth of gemcitabine-resistant CCA cell lines (KKU-213A-GemR and KKU-100-GemR). Furthermore, dinaciclib significantly enhanced the anti-tumor activity of gemcitabine in CCA cell lines.

CONCLUSION: Dinaciclib has the potential to be an effective therapeutic agent to control tumor cell growth of both parental and gemcitabine-resistant CCA cells.

PMID:39187317 | PMC:PMC11363801 | DOI:10.21873/invivo.13693
Percutaneous Metallic Stents in Malignant Biliary Obstruction: Comparison of Nitinol and Wall Stents

Fetched: August 27th, 2024, 2:01am UTC by Ä°lker Ã–zgÃ¼r Koska

J Gastrointest Cancer. 2024 Sep;55(3):1425-1432. doi: 10.1007/s12029-024-01101-y. Epub 2024 Aug 13.

ABSTRACT

INTRODUCTION: Palliation of malign biliary obstruction is important which is commonly carried out by percutaneous biliary stenting. Our primary aim with this study was assessment of performance of wall stents, and nitinol stents for the palliation of malign biliary obstruction.

METHODS: The medical records of 157 patients who underwent biliary stenting in our department between January 1, 1995, and December 31, 2005, were retrospectively analyzed. Technical success, treatment success, mortality in the first 30 days, minor, and major complications were evaluated and compared among the wall stent, and the nitinol stent groups in all patients which constituted the primary study endpoints. Additionally, stent patency, and mean patient survival times after stent implantation were evaluated in patients for whom follow-up information could be obtained.

RESULTS: A total of 213 metallic stents were placed in 157 patients. Wall stent was placed in 83 of the patients with mean age, and SD of 60.4 and 13.5. Nitinol stent was placed in 74 of the patients with mean age of 57.8, and SD of 15.5. Gender ratio was equal in both groups. Biliary stent dysfunction was observed in 13 patients in each of nitinol, and wall stent groups throughout the study period. There was no statistical difference among re-occlusion rates (p = 0.91). For the nitinol stent group median primary patency time was 119 days (90-185 days CI 95%), and for the wall stent group median primary patency time was 81 days (60-150 days CI 95%).

CONCLUSION: Nitinol stents, and wall stents are safe options that can be safely used in the percutaneous treatment of malignant biliary obstruction with similar treatment and therapeutic success, low complication rates, and patency times that can extend beyond expected survival times.

PMID:39136894 | DOI:10.1007/s12029-024-01101-y
Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center

Fetched: August 27th, 2024, 2:01am UTC by Yusheng Du

BMC Surg. 2024 Aug 24;24(1):241. doi: 10.1186/s12893-024-02533-w.

ABSTRACT

BACKGROUND: The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy.

METHODS: A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb.

RESULTS: Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190-450), and the median estimated blood loss was 360 mL (range, 260-1200). The postoperative hospital stay duration was 14.3 Â± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3-43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.

CONCLUSION: Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

PMID:39182023 | PMC:PMC11344452 | DOI:10.1186/s12893-024-02533-w
Design of the distribution of iron oxide (Fe3O4) nano-particle drug in realistic cholangiocarcinoma model and the simulation of temperature increase during magnetic induction hyperthermia

Fetched: August 25th, 2024, 2:00am UTC by Yawen Lu

Pharmacol Res. 2024 Sep;207:107333. doi: 10.1016/j.phrs.2024.107333. Epub 2024 Jul 30.

ABSTRACT

The prognosis for Cholangiocarcinoma (CCA) is unfavorable, necessitating the development of new therapeutic approach such as magnetic hyperthermia therapy (MHT) which is induced by magnetic nano-particle (MNPs) drug to bridge the treatment gap. Given the deep location of CCA within the abdominal cavity and proximity to vital organs, accurately predict the individualized treatment effects and safety brought by the distribution of MNPs in tumor will be crucial for the advancement of MHT in CCA. The Mimics software was used in this study to conduct three-dimensional reconstruction of abdominal computed tomography (CT) and magnetic reso-nance imaging images from clinical patients, resulting in the generation of a realistic digital geometric model representing the human biliary tract and its adjacent structures. Subsequently, The COMSOL Multiphysics software was utilized for modeling CCA and calculating the heat transfer law resulting from the multi-regional distribution of MNPs in CCA. The temperature within the central region of irregular CCA measured approximately 46Â°C, and most areas within the tumor displayed temperatures surpassing 41Â°C. The temperature of the inner edge of CCA is only 39 âˆ¼ 41â„ƒ, however, it can be ameliorated by adjusting the local drug concentration through simulation system. For CCA with diverse morphologies and anatomical locations, the multi-regional distribution patterns of intratumoral MNPs and a slight overlap of drug distribution areas synergistically enhance intratumoral temperature while ensuring treatment safety. The present study highlights the practicality and imperative of incorporating personalized intratumoral MNPs distribution strategy into clinical practice for MHT, which can be achieved through the development of an integrated simulation system which incorporates medical image data and numerical calculations.

PMID:39089399 | DOI:10.1016/j.phrs.2024.107333
FTO-mediated m 6A demethylation of ULK1 mRNA promotes autophagy and activation of hepatic stellate cells in liver fibrosis

Fetched: August 24th, 2024, 2:01am UTC by Tingjuan Huang

Acta Biochim Biophys Sin (Shanghai). 2024 Aug 23. doi: 10.3724/abbs.2024098. Online ahead of print.

ABSTRACT

The activation of hepatic stellate cells (HSCs) is central to the occurrence and development of liver fibrosis. Our previous studies showed that autophagy promotes HSC activation and ultimately accelerates liver fibrosis. Unc-51-like autophagy activating kinase 1 (ULK1) is an autophagic initiator in mammals, and N ⁶-methyladenosine (m ⁶A) modification is closely related to autophagy. In this study, we find that the m ⁶A demethylase fat mass and obesity-associated protein (FTO), which is the m ⁶A methylase with the most significant difference in expression, is upregulated during HSC activation and bile duct ligation (BDL)-induced hepatic fibrosis. Importantly, we identify that FTO overexpression aggravates HSC activation and hepatic fibrosis via autophagy. Mechanistically, compared with other autophagy-related genes, ULK1 is a target of FTO because FTO mainly mediates the m ⁶A demethylation of ULK1 and upregulates its expression, thereby enhancing autophagy and the activation of HSCs. Notably, the m ⁶A reader YTH domain-containing protein 2 (YTHDC2) decreases ULK1 mRNA level by recognizing the m ⁶A binding site and ultimately inhibiting autophagy and HSC activation. Taken together, our findings highlight m6A-dependent ULK1 as an essential regulator of HSC autophagy and reveal that ULK1 is a novel potential therapeutic target for hepatic fibrosis treatment.

PMID:39175431 | DOI:10.3724/abbs.2024098
Nanofiber-based delivery of evodiamine impedes malignant properties of intrahepatic cholangiocarcinoma cells by targeting HDAC4 and restoring TPM1 transcription

Fetched: August 23rd, 2024, 2:01am UTC by Rui Zou

Hum Cell. 2024 Sep;37(5):1505-1521. doi: 10.1007/s13577-024-01105-7. Epub 2024 Jul 29.

ABSTRACT

The electrospun nanofiber system is correlated with high efficacy of drug delivery. This study aims to investigate the effect of nanofiber-based delivery of evodiamine, an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth, on intrahepatic cholangiocarcinoma (ICC), as well as to explore the molecular mechanisms. An electrospun nanofiber system carrying evodiamine was generated. Compared to evodiamine treatment alone, the nano-evodiamine exhibited more pronounced effects on suppressing proliferation, colony formation, invasiveness, migration, apoptosis resistance, cell cycle progression, and in vivo tumorigenesis of two ICC cell lines (HUCC-T1 and RBE). ICC cells exhibited increased expression of histone deacetylase 4 (HDAC4) while decreased tropomyosin 1 (TPM1). HDAC4 suppressed TPM1 expression by removing H3K9ac modifications from its promoter. Nano-evodiamine reduced HDAC4 protein levels in ICC cells, thus promoting transcription and expression of TPM1. Either overexpression of HDAC4 or downregulation of TPM1 negated the tumor-suppressive effects of nano-evodiamine. Collectively, this study demonstrates that the electrospun nanofiber system enhances the efficiency of evodiamine. Additionally, evodiamine suppresses the malignant properties of ICC cells. The findings may provide fresh insights into the application of electrospun nanofiber system for drug delivery and the effects of evodiamine on tumor suppression.

PMID:39073525 | DOI:10.1007/s13577-024-01105-7
CHOLECYSTECTOMY WITH INTRAOPERATIVE ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: DOES THE ORDER MATTER?

Fetched: August 22nd, 2024, 2:00am UTC by JoÃ£o de Bona Castelan Filho

Arq Bras Cir Dig. 2024 Aug 19;37:e1816. doi: 10.1590/0102-6720202400023e1816. eCollection 2024.

ABSTRACT

BACKGROUND: The recommended treatment for cholecystocholedocholithiasis is cholecystectomy (CCT) associated with endoscopic retrograde cholangiopancreatography (ERCP). CCT with intraoperative ERCP is associated with higher success rates and lower hospital stays and hospital costs. However, some case series do not describe the exact methodology used: whether ERCP or CCT was performed first.

AIMS: Verify if there is a difference, in terms of outcomes and complications, when intraoperative ERCP is performed immediately before or after CCT.

METHODS: This is a retrospective case-control study analyzing all patients who underwent CCT with intraoperative ERCP between January 2021 and June 2022, in a tertiary hospital in southern Brazil, for the treatment of cholecystocholedocholithiasis.

RESULTS: Out of 37 patients analyzed, 16 (43.2%) underwent ERCP first, immediately followed by CCT. The overall success rate for the cannulation of the bile duct was 91.9%, and bile duct clearance was achieved in 75.7% of cases. The post-ERCP pancreatitis rate was 10.8%. When comparing the "ERCP First" and "CCT First" groups, there was no difference in technical difficulty for performing CCT. The "CCT First" group had a higher rate of success in bile duct cannulation (p=0.020, p<0.05). Younger ages, presence of stones in the distal common bile duct and shorter duration of the procedure were factors statistically associated with the success of the bile duct clearance. Lymphopenia and cholecystitis as an initial presentation, in turn, were associated with failure to clear the bile duct.

CONCLUSIONS: There was no significant difference in terms of complications and success in clearing the bile ducts among patients undergoing CCT and ERCP in the same surgical/anesthetic procedure, regardless of which procedure was performed first. Lymphopenia and cholecystitis have been associated with failure to clear the bile duct.

PMID:39166653 | PMC:PMC11338519 | DOI:10.1590/0102-6720202400023e1816
Knockdown of long noncoding RNA AL161431.1 inhibits malignant progression of cholangiocarcinoma

Fetched: August 21st, 2024, 2:01am UTC by Zhoulan Bai

Aging (Albany NY). 2024 Aug 1;16(15):11501-11512. doi: 10.18632/aging.205898. Epub 2024 Aug 1.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is one of the most deadly cancers in the world. It usually has a bad prognosis and is challenging to identify in its early stages. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be important in the control of signaling pathways, cell behaviors, and epigenetic modification that contribute to the growth of tumors. The purpose of this work was to examine the relationship between CCA and lncRNA AL161431.1.

METHODS: Using TCGA clinical survival data, we evaluated the association between AL161431.1 expression and patient prognosis. Using the program cluster Profiler R, enrichment analysis was performed. Additionally, the association between immune cell infiltration and AL161431.1 expression was evaluated by a review of the TCGA database. Next, to ascertain if AL161431.1 influences tumor growth, migration, and invasion in CCA, functional in vitro assays were conducted. Quantitative real-time polymerase chain reaction (qPCR) was employed to gauge AL161431.1 expression levels in CCA cells. Western blot was used to measure protein levels.

RESULTS: In CCA, AL161431.1 was extremely expressed. The patients in the high-risk group had a significantly poorer overall survival (OS) than the patients in the low-risk group. A more thorough look at the TCGA data showed a relationship between high expression levels of AL161431.1 and increased infiltration of T cells, T helper cells, and NK CD56dim cells. Furthermore, AL161431.1 knockdown in CCA cells impeded invasion, migration, and proliferation and also lowered the expression of phosphorylated Smad2/Smad3 to restrain the TGFÎ²/SMAD signaling pathway.

CONCLUSIONS: Our results indicate that the lncRNA AL161431.1 activates the TGFÎ²/SMAD signaling pathway to enhance CCA development and metastasis. AL161431.1 could be a novel target for cholangiocarcinoma treatment or a diagnostic marker.

PMID:39103208 | PMC:PMC11346779 | DOI:10.18632/aging.205898
Optimizing adjuvant treatment strategies for non-pancreatic periampullary cancers

Fetched: August 20th, 2024, 2:01am UTC by Nouredin Messaoudi

Br J Cancer. 2024 Sep;131(4):617-618. doi: 10.1038/s41416-024-02808-2. Epub 2024 Jul 31.

ABSTRACT

Non-pancreatic periampullary tumors have long been neglected, leading to blurred adjuvant treatment strategies. Recent research, like the ISGACA group's study, is uncovering nuances in chemotherapy efficacy for these diverse cancers. Tailored approaches show promise, with artificial intelligence (AI) aiding in personalized treatment plans.

PMID:39085361 | PMC:PMC11333485 | DOI:10.1038/s41416-024-02808-2
Percutaneous endobiliary radiofrequency ablation and stent placement for unresectable malignant biliary obstruction: a propensity score matching retrospective study

Fetched: August 20th, 2024, 2:01am UTC by Wei Cui

BMC Gastroenterol. 2024 Aug 19;24(1):270. doi: 10.1186/s12876-024-03357-x.

ABSTRACT

BACKGROUND: Whether endobiliary radiofrequency ablation (EB-RFA) changes the standard role of stent placement in treating unresectable malignant biliary obstruction (MBO) remains unclear. The aim of this study is to compare percutaneous EB-RFA and metal stent placement (RFA-Stent) with metal stent placement alone (Stent) in treating unresectable MBO using a propensity score matching (PSM) analysis.

METHODS: From June 2013 to June 2018, clinical data from 163 patients with malignant biliary obstruction who underwent percutaneous RFA-Stent or stenting alone were retrospectively analyzed using a nearest-neighbor algorithm to one-to-one PSM analysis to compare primary and secondary stent patency (PSP, SSP), overall survival (OS) and complications between the two groups.

RESULTS: Before matching, for whole patients, RFA-Stent resulted in longer median PSP (8.0 vs. 5.1 months, P = 0.003), SSP (9.8 vs. 5.1 months, P < 0.001) and OS (7.0 vs. 4.5 months, P = 0.034) than the Stent group. After matching (54 pairs), RFA-Stent also resulted in better median PSP (8.5 vs. 5.1 months, P < 0.001), SSP (11.0 vs. 6.0 months, P < 0.001), and OS (8.0 vs. 4.0 months, P = 0.007) than Stent. RFA-Stent was comparable with Stent for complication rates. In Cox analysis, RFA-Stent modality and serum total bilirubin level were independent prognostic factors for PSP. RFA-Stent modality, performance status score and combination therapy after stent were independent prognostic factors for OS.

CONCLUSION: Percutaneous RFA-Stent was superior to Stent in terms of PSP, SSP, and OS in selected patients with unresectable MBO.

PMID:39160477 | PMC:PMC11331891 | DOI:10.1186/s12876-024-03357-x
Single-Cell Transcriptomic Profiling of Cholangiocyte Organoids Derived from Bile Ducts of Primary Sclerosing Cholangitis Patients

Fetched: August 20th, 2024, 2:01am UTC by Anna Katharina Frank

Dig Dis Sci. 2024 Aug 19. doi: 10.1007/s10620-024-08570-y. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disorder without effective medical treatment which is characterized by inflammation and fibrotic structures around the bile ducts. Biliary epithelial cells (cholangiocytes) are the target and potential disease drivers in PSC, yet little is known if cholangiocytes from PSC patients differ from non-PSC controls. To characterize cholangiocytes at early rather than end-stage disease, cholangiocyte organoids (COs) were derived from diseased bile ducts of PSC patients and compared to organoids generated from disease controls.

METHODS: Cholangiocytes were obtained during endoscopic retrograde cholangiopancreatography (ERCP) brushing of diseased bile duct areas and expanded as organoids using previously established culture methods. Stable CO lines were analyzed for cell type identity, basic cholangiocyte function, and transcriptomic signature.

RESULTS: We demonstrate that cholangiocytes, derived from the damaged area within the bile ducts of PSC patients, can be expanded in culture without displaying functional or genetic disease-related features. We further show that COs from patients who later were diagnosed with dysplasia exhibit higher expression of the cancer-associated genes PGC, FXYD2, MIR4435-2HG, and HES1.

CONCLUSIONS: Our results demonstrate that PSC organoids are largely similar to control organoids after culture and highlight the significance of COs as a tool for regenerative medicine approaches as well as their potential for discovering new potential biomarkers for diagnosing cholangiocarcinoma.

PMID:39160386 | DOI:10.1007/s10620-024-08570-y
Combining single-cell spatial transcriptomics and molecular simulation to develop in vivo probes targeting the perineural invasion region of adenoid cystic carcinoma

Fetched: August 20th, 2024, 2:01am UTC by Xiaotian Yuan

Heliyon. 2024 Jul 19;10(15):e34628. doi: 10.1016/j.heliyon.2024.e34628. eCollection 2024 Aug 15.

ABSTRACT

BACKGROUND AND OBJECTIVES: Perineural invasion (PNI) refers to the invasion, encasement, or penetration of tumor cells around or through nerves. Various malignant tumors, including pancreatic cancer, head and neck tumors, and bile duct cancer, exhibit the characteristic of PNI. Particularly, in head and neck-skull base tumors such as adenoid cystic carcinoma (ACC), PNI is a significant factor leading to incomplete surgical resection and postoperative recurrence.

METHODS: Spatial transcriptomic and single-cell transcriptomic sequencing were conducted on a case of ACC tissue with PNI to identify potential probes targeting PNI. The efficacy of the probes was validated through in vivo and in vitro experiments.

RESULTS: Spatial transcriptomic and single-cell RNA sequencing revealed phenotypic changes in Schwann cells within the PNI region of ACC. Peptide probes were designed based on the antigen-presenting characteristics of Schwann cells in the PNI region, which are dependent on Major Histocompatibility Complex II (MHC-II) molecules. Successful validation in vitro and in vivo experiments confirmed that these probes can label viable Schwann cells in the PNI region, serving as a tool for dynamic in vivo marking of tumor invasion into nerves.

CONCLUSIONS: Peptide probes targeting Schwann cells' MHC-II molecules have the potential to demonstrate the occurrence of PNI in patients with ACC.

PMID:39157355 | PMC:PMC11327542 | DOI:10.1016/j.heliyon.2024.e34628
Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management

Fetched: August 20th, 2024, 2:01am UTC by Zohaib Jamal

Cureus. 2024 Jul 17;16(7):e64762. doi: 10.7759/cureus.64762. eCollection 2024 Jul.

ABSTRACT

Introduction Cholecystectomy, the surgical removal of the gallbladder, is a common procedure worldwide. Despite no visible anomalies, routine histopathological examination (HPE) of gallbladder specimens post-surgery is standard practice to exclude pathologies, notably gallbladder cancer (GBC). Incidence rates of GBC vary geographically and ethnically. Surgical intervention is recommended for advanced GBC stages, while early stages may require cholecystectomy alone. Although rare, GBC and bile duct cancers pose increased risks in certain demographics, such as women and individuals over 65. Routine HPE practices vary globally based on resource availability and GBC incidence. This study assesses the necessity of routine HPE by evaluating the selective processing of gallbladder specimens suspected of GBC, prioritizing patient safety. Materials and methods This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine HPE for excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC) outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to HPE post-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited GBC; however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo HPE, seems prudent, especially in regions with low GBC incidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.

PMID:39156251 | PMC:PMC11329314 | DOI:10.7759/cureus.64762
Prognostic factors in patients with intrahepatic cholangiocarcinoma

Fetched: August 19th, 2024, 2:01am UTC by Yun-Jau Chang

Sci Rep. 2024 Aug 17;14(1):19084. doi: 10.1038/s41598-024-70124-z.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan-Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 Â± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25-201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (â‰¤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I-III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (â‰¤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.

PMID:39154139 | PMC:PMC11330494 | DOI:10.1038/s41598-024-70124-z
Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses

Fetched: August 17th, 2024, 2:00am UTC by Constanza Gonzalez

Int J Cancer. 2024 Aug 16. doi: 10.1002/ijc.35138. Online ahead of print.

ABSTRACT

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

PMID:39150415 | DOI:10.1002/ijc.35138
A Complex Case of Obstructive Jaundice in a Septuagenarian: Diagnostic Challenges and Therapeutic Strategies

Fetched: August 17th, 2024, 2:00am UTC by Sana Anwar

Cureus. 2024 Jul 15;16(7):e64598. doi: 10.7759/cureus.64598. eCollection 2024 Jul.

ABSTRACT

Obstructive jaundice occurs when an obstruction in the bile duct system prevents bile from flowing from the liver into the intestine, accumulating bilirubin in the blood. This condition can result from various causes, including gallstones, tumors, or inflammation of the bile ducts. The management of obstructive jaundice depends on the underlying cause (malignant obstructions such as cholangiocarcinoma or pancreatic cancer), indicating the need for surgical intervention. The Whipple procedure (pancreaticoduodenectomy) is the standard curative approach for resectable distal common bile duct (CBD) adenocarcinoma. Doctors usually recommend adjuvant chemotherapy to reduce the risk of recurrence. We report the case of a 70-year-old male with a history of untreated hypertension, type 2 diabetes, and long-term smoking, who presented with classic signs of obstructive jaundice, including yellowing of the eyes, itching, right upper quadrant pain, and intermittent fevers. Laboratory findings revealed elevated inflammatory markers, bilirubin, liver enzymes, and leukocyte count, indicative of an inflammatory and obstructive biliary condition. Imaging studies confirmed a distal CBD stricture, including abdominal ultrasound, computed tomography scans, and endoscopic retrograde cholangiopancreatography (ERCP). Brush cytology obtained during ERCP revealed a well-differentiated adenocarcinoma of the distal CBD. The patient's treatment plan included preoperative optimization, surgical resection via the Whipple procedure, and postoperative adjuvant therapy. This case emphasizes the importance of a thorough diagnostic workup and a multidisciplinary treatment strategy in managing complex cases of obstructive jaundice in the elderly, highlighting the need for personalized care to achieve optimal outcomes.

PMID:39149640 | PMC:PMC11325256 | DOI:10.7759/cureus.64598
Association of county-level provider density with hepatobiliary cancer incidence and mortality

Fetched: August 16th, 2024, 2:00am UTC by Muhammad Muntazir Mehdi Khan

World J Surg. 2024 Aug 15. doi: 10.1002/wjs.12316. Online ahead of print.

ABSTRACT

BACKGROUND: Access to healthcare providers is a key factor in reducing cancer incidence and mortality, underscoring the significance of provider density as a crucial metric of health quality. We sought to characterize the association of provider density on hepatobiliary cancer population-level incidence and mortality.

STUDY DESIGN: County-level hepatobiliary cancer incidence and mortality data from 2016 to 2020 and provider data from 2016 to 2018 were obtained from the CDC and Area Health Resource File. Multivariable logistic regression was utilized to evaluate the relationship between provider density and hepatobiliary cancer incidence and mortality.

RESULTS: Among 1359 counties, 851 (62.6%) and 508 (37.4%) counties were categorized as urban and rural, respectively. The median number of providers in any given county was 104 (IQR: 44-306), while provider density was 120.1 (IQR: 86.7-172.2) per 100,000 population; median household income was $51,928 (IQR: $45,050-$61,655). Low provider-density counties were more likely to have a greater proportion of residents over 65 years of age (52.7% vs. 49.6%) who were uninsured (17.4% vs. 13.2%) versus higher provider-density counties (p < 0.05). Moreover, all-stage incidence, late-stage incidence, and mortality rates were higher in counties with low provider density. On multivariable analysis, moderate, and high provider density were associated with lower odds of all-stage incidence, late-stage incidence, and mortality.

CONCLUSION: Higher county-level provider density was associated with lower hepatobiliary cancer-related incidence and mortality. Efforts to increase access to healthcare providers may improve healthcare equity as well as long-term cancer outcomes.

PMID:39148145 | DOI:10.1002/wjs.12316
Comparison of the clinicoradiological features and outcomes of lymphoepithelioma-like cholangiocarcinoma and conventional intrahepatic cholangiocarcinoma: A propensity score matching analysis

Fetched: August 16th, 2024, 2:00am UTC by Yan-Chih Peng

J Formos Med Assoc. 2024 Aug 14:S0929-6646(24)00379-6. doi: 10.1016/j.jfma.2024.08.011. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma (ICC). We aim to analyze the differences in the clinical and radiological features of LELCC and ICC.

METHODS: Between January 2003 and December 2019, a total of 21 patients diagnosed with LELCC were retrospectively enrolled, and 84 patients with ICC were selected through propensity score matching by sex, age, and initial cancer stage. The clinical characteristics, pathological findings, and radiological features were analyzed. The differences in overall survival (OS) between LELCC and ICC were evaluated using the Kaplan-Meier method.

RESULTS: The serum carbohydrate antigen 19-9 (CA 19-9) level was higher in the ICC group than in the LELCC group (77.9 vs 30.0 U/mL, p = 0.004). Non-rim arterial phase hyperenhancement (47.1% vs 13.7%, p = 0.005) and portovenous washout (35.3% vs 4.1%, p = 0.001) were more frequently observed in the LELCC group than in the ICC group. Intrahepatic duct dilatation was a distinct feature of the ICC group. The 5-year OS rates in the LELCC and ICC groups were 69.3% and 58.2%, respectively (p = 0.047). The 5-year OS of patients with stages I and II LELCC between ICC were not significantly different (90.0% vs 83.4%, p = 0.464). However, the 5-year OS of patients with stages III and IV LELCC was more favorable than that of patients with ICC (29.2% vs 23.0%, p = 0.017).

CONCLUSIONS: LELCC had a favorable outcome and several different clinicoradiological features compared with ICC.

PMID:39147686 | DOI:10.1016/j.jfma.2024.08.011
Experiences of informal caregivers supporting individuals with upper gastrointestinal cancers: a systematic review

Fetched: August 15th, 2024, 2:01am UTC by Melinda Furtado

BMC Health Serv Res. 2024 Aug 14;24(1):932. doi: 10.1186/s12913-024-11306-3.

ABSTRACT

BACKGROUND: Upper gastrointestinal cancers (UGICs) are increasingly prevalent. With a poor prognosis and significant longer-term effects, UGICs present significant adjustment challenges for individuals with cancer and their informal caregivers. However, the supportive care needs of these informal caregivers are largely unknown. This systematic review of qualitative studies synthesises and critically evaluates the current evidence base on the experience of informal caregivers of individuals with UGIC.

METHODS: A Joanna Briggs Institute systematic review was conducted. Searches were performed in four databases (MEDLINE, PsycINFO, Embase, CINAHL) from database inception to February 2021. Included studies explored experiences of informal caregivers of individuals diagnosed with primary cancer of the oesophagus, stomach, pancreas, bile duct, gallbladder, or liver. Studies were independently screened for eligibility and included studies were appraised for quality by two reviewers. Data were extracted and synthesised using meta-aggregation.

RESULTS: 19 papers were included in this review, and 328 findings were extracted. These were aggregated into 16 categories across three findings: (1) UGIC caregiver burden; UGIC caregivers undertake extensive responsibilities, especially around patient diet as digestion is severely impacted by UGICs. (2) Mediators of caregiver burden; The nature of UGICs, characterised by disruptive life changes for caregivers, was identified as a mediator for caregiver burden. (3) Consequences of caregiver burden: UGIC caregivers' experiences were shaped by unmet needs, a lack of information and a general decline in social interaction.

CONCLUSIONS: The findings of this review suggest the need for a cultural shift within health services. Caregiving for UGIC patients is suggested to adversely affect caregivers' quality of life, similarly to other cancer caregiving populations and therefore they should be better incorporated as co-clients in care-planning and execution by including them in discussions about the patient's diagnosis, treatment options, and potential side effects.

PMID:39143501 | PMC:PMC11325824 | DOI:10.1186/s12913-024-11306-3
Strategies for treating the cold tumors of cholangiocarcinoma: core concepts and future directions

Fetched: August 15th, 2024, 2:01am UTC by GuanBo Zhang

Clin Exp Med. 2024 Aug 14;24(1):193. doi: 10.1007/s10238-024-01460-7.

ABSTRACT

Cholangiocarcinoma (CCA) is a rare type of digestive tract cancer originating from the epithelial cells of the liver and biliary tract. Current treatment modalities for CCA, such as chemotherapy and radiation therapy, have demonstrated limited efficacy in enhancing survival rates. Despite the revolutionary potential of immunotherapy in cancer management, its application in CCA remains restricted due to the minimal infiltration of immune cells in these tumors, rendering them cold and unresponsive to immune checkpoint inhibitors (ICIs). Cancer cells within cold tumors deploy various mechanisms for evading immune attack, thus impeding clinical management. Recently, combination immunotherapy has become increasingly essential to comprehend the mechanisms underlying cold tumors to enhance a deficient antitumor immune response. Therefore, a thorough understanding of the knowledge on the combination immunotherapy of cold CCA is imperative to leverage the benefits of immunotherapy in treating patients. Moreover, gut microbiota plays an essential role in the immunotherapeutic responses in CCA. In this review, we summarize the current concepts of immunotherapy in CCA and clarify the intricate dynamics within the tumor immune microenvironment (TIME) of CCA. We also delve into the evasion mechanisms employed by CCA tumors against the anti-tumor immune responses. The context of combination immunotherapies in igniting cold tumors of CCA and the critical function of gut microbiota in prompting immune responses have also been annotated. Furthermore, we have proposed future directions in the realm of CCA immunotherapy, aiming to improve the clinical prognosis of CCA patients.

PMID:39141161 | PMC:PMC11324771 | DOI:10.1007/s10238-024-01460-7

PubMed - Cholangiocarcinoma

The risk of cholangiocarcinoma in patients with MASLD is not increased compared to the general population

Fetched: October 16th, 2024, 2:01am UTC by Christina Villard

Scand J Gastroenterol. 2024 Oct 9:1-3. doi: 10.1080/00365521.2024.2412735. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in prevalence globally. MASLD is associated with an increased rate of comorbidities, including cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (HCC). While the link between MASLD and HCC is well known, the potential association with biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), is less certain. To evaluate whether individuals with MASLD are at increased risk of developing CCA compared to the general population, we performed a nationwide cohort study investigating the longitudinal association between MASLD and CCA.

METHODS: A retrospective cohort study was performed including all patients â‰¥18 years of age, diagnosed with MASLD, from 1^st of January 1987 to 31^st of December 2020, through the Swedish National Patient Register. For each patient with MASLD, ten individuals, matched to the MASLD patient on year of diagnosis, age, sex, and municipality were selected as reference individuals. The international Classification of Diseases (ICD) codes were used to define MASLD and incident CCA. Incidence rates were calculated, and regression analyses were performed.

RESULTS: Out of the 11,940 exposed patients with MASLD, 11 developed CCA (0.1%) out of whom three were diagnosed with iCCA (0.03%), during a median follow-up time of five years. Out of 112,537 reference individuals, 62 were diagnosed with CCA (0.3%), out of whom 15 were diagnosed with iCCA (0.01%). The rate of GBC was not higher compared to the reference population.

CONCLUSION: This large cohort study found a low incidence of CCA in patients with MASLD, comparable to the general population which can reassure clinicians and patients that no specific vigilance for CCA should be considered in MASLD patients at present.

PMID:39381919 | DOI:10.1080/00365521.2024.2412735
Improvement of survival outcomes of cholangiocarcinoma by ultrasonography surveillance: Multicenter retrospective cohorts

Fetched: October 16th, 2024, 2:01am UTC by Nittaya Chamadol

Heliyon. 2024 Sep 20;10(18):e38191. doi: 10.1016/j.heliyon.2024.e38191. eCollection 2024 Sep 30.

ABSTRACT

BACKGROUND: Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients.

METHODS: The retrospective clinical data and medical records for this study were accessed in June 30, 2021. 5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using the Kaplan-Meier method. Multivariate analyses were performed for significant factors from univariate analyses.

RESULTS: A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9 %, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9 % and MST was 15.6 months (p < 0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014).

CONCLUSION: US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.

PMID:39381227 | PMC:PMC11458967 | DOI:10.1016/j.heliyon.2024.e38191
Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors

Fetched: October 16th, 2024, 2:01am UTC by Hasan Ahmad Al-Saffar

Scand J Surg. 2024 Oct 8:14574969241282480. doi: 10.1177/14574969241282480. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement.

METHODS: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method.

RESULTS: One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively).

CONCLUSION: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

PMID:39380179 | DOI:10.1177/14574969241282480
Current management of hepatobiliary malignancies between centers with or without a liver transplant program: A multi-society national survey

Fetched: October 16th, 2024, 2:01am UTC by Matteo Serenari

Dig Liver Dis. 2024 Oct 7:S1590-8658(24)01007-7. doi: 10.1016/j.dld.2024.09.007. Online ahead of print.

ABSTRACT

BACKGROUND: Availability of liver transplantation (LT) as a treatment for hepatocellular carcinoma (HCC) and other liver malignancies may determine heterogeneity of therapeutic strategies across different centers.

AIMS: To investigate the practice between hepato-biliary centers without (HB centers) and with a LT program (LT centers), we launched a 38-item web-based national survey, with directors of centers as a target.

METHODS: The survey, including 4 clinical vignettes, collected data on their approach to HCC and transplant oncology.

RESULTS: After duplicates removal, 75 respondents were considered. Respondents from LT centers (n = 22, 29.3 %) were more in favor of LT in the case of HCC outside Milan criteria (90.9 % vs. 67.9 %, p = 0.037), recurrent HCC (95.5 % vs. 50.9 %, p = 0.002) and other malignancies such as cholangiocarcinoma or neuroendocrine tumors. No significant difference was observed concerning the proportion of centers favorable to LT for unresectable colorectal liver metastases (100 % vs. 88.7 %, p = 0.100).

CONCLUSION: This national survey showed how management of HCC and awareness of transplant oncology may differ between HB and LT centers. Effective networking between HB and LT centers is crucial to provide optimal treatment and access to LT.

PMID:39379228 | DOI:10.1016/j.dld.2024.09.007
Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

Fetched: October 16th, 2024, 2:01am UTC by Shin Ito

Cancer Sci. 2024 Oct 8. doi: 10.1111/cas.16365. Online ahead of print.

ABSTRACT

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

PMID:39377143 | DOI:10.1111/cas.16365
Correction: STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A

Fetched: October 16th, 2024, 2:01am UTC by Junsheng Chen

J Exp Clin Cancer Res. 2024 Oct 8;43(1):279. doi: 10.1186/s13046-024-03198-2.

NO ABSTRACT

PMID:39375788 | PMC:PMC11460208 | DOI:10.1186/s13046-024-03198-2
Clinicopathological characteristics and prognosis of combined hepatocellular cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Yue Li

BMC Cancer. 2024 Oct 7;24(1):1232. doi: 10.1186/s12885-024-12970-8.

ABSTRACT

There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3⁺ T cells and CD8⁺ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be â‰¥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3⁺ T cells and CD8⁺ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

PMID:39375615 | PMC:PMC11457400 | DOI:10.1186/s12885-024-12970-8
Artificial intelligence in predicting recurrence after first-line treatment of liver cancer: a systematic review and meta-analysis

Fetched: October 16th, 2024, 2:01am UTC by Linyong Wu

BMC Med Imaging. 2024 Oct 7;24(1):263. doi: 10.1186/s12880-024-01440-z.

ABSTRACT

BACKGROUND: The aim of this study was to conduct a systematic review and meta-analysis to comprehensively evaluate the performance and methodological quality of artificial intelligence (AI) in predicting recurrence after single first-line treatment for liver cancer.

METHODS: A rigorous and systematic evaluation was conducted on the AI studies related to recurrence after single first-line treatment for liver cancer, retrieved from the PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. The area under the curve (AUC), sensitivity (SENC), and specificity (SPEC) of each study were extracted for meta-analysis.

RESULTS: Six percutaneous ablation (PA) studies, 16 surgical resection (SR) studies, and 5 transarterial chemoembolization (TACE) studies were included in the meta-analysis for predicting recurrence after hepatocellular carcinoma (HCC) treatment, respectively. Four SR studies and 2 PA studies were included in the meta-analysis for recurrence after intrahepatic cholangiocarcinoma (ICC) and colorectal cancer liver metastasis (CRLM) treatment. The pooled SENC, SEPC, and AUC of AI in predicting recurrence after primary HCC treatment via PA, SR, and TACE were 0.78, 0.90, and 0.92; 0.81, 0.77, and 0.86; and 0.73, 0.79, and 0.79, respectively. The values for ICC treated with SR and CRLM treated with PA were 0.85, 0.71, 0.86 and 0.69, 0.63,0.74, respectively.

CONCLUSION: This systematic review and meta-analysis demonstrates the comprehensive application value of AI in predicting recurrence after a single first-line treatment of liver cancer, with satisfactory results, indicating the clinical translation potential of AI in predicting recurrence after liver cancer treatment.

PMID:39375586 | PMC:PMC11457388 | DOI:10.1186/s12880-024-01440-z
Hepatic adenosquamous carcinoma with sarcomatous transformation: a case report and review of the literature

Fetched: October 16th, 2024, 2:01am UTC by Quynh Thi Nguyen

Med Mol Morphol. 2024 Oct 7. doi: 10.1007/s00795-024-00406-y. Online ahead of print.

ABSTRACT

Adenosquamous carcinoma (ASC) with the presence of a sarcomatous component is exceptionally uncommon in intrahepatic cholangiocarcinoma (iCCA). We report a case of hepatic ASC with rhabdoid transformation, one variation of sarcomatous change. A 72-year-old man was admitted to our hospital after being diagnosed with a 45 mm-diameter neoplastic lesion in the right hepatic duct on abdominal computed tomography. Laboratory findings showed increases in AST, ALT, ALP, gamma-GT, CA19-9 and DUPAN-II. The patient then underwent an extended right hepatectomy. Histopathologically, the tumor was composed of an ASC component within an abundant fibrous stroma and a sarcomatoid carcinoma component. By immunohistochemistry, keratin 7 and keratin 19 were expressed by all tumor cells. Expression of keratin 5/6, p40 and p63 was restricted to the squamous component. The sarcomatoid component was immunoreactive for vimentin with no loss of INI1 expression. This component also showed a loss of membranous E-cadherin expression and a reduction of membranous Î²-catenin expression. Staining for desmin, myoglobin and HepPar1 was negative in any tumor cells. The patient died of liver failure 3 months after surgery. This report aims to provide a better understanding of the clinicopathological characteristics and disease progression of the rare variants of iCCA to aid diagnosis and treatment.

PMID:39375230 | DOI:10.1007/s00795-024-00406-y
A case of giant hilar cholangiocarcinoma accompanied by hyperbilirubinemia achieved disease stabilization via hepatic artery infusion chemotherapy combined with targeted therapy

Fetched: October 16th, 2024, 2:01am UTC by B Y Wu

Zhonghua Gan Zang Bing Za Zhi. 2024 Sep 20;32(9):845-849. doi: 10.3760/cma.j.cn501113-20231014-00143.

ABSTRACT

1ä¾‹51å²å¥³æ€§æ‚£è€…ï¼Œæ‚£è‚é—¨éƒ¨å·¨å¤§èƒ†ç®¡ç™Œï¼Œä»¥é»„ç–¸ä¸ºä¸»è¦èµ·ç—…è¡¨çŽ°ï¼Œåœ¨å¤–é™¢ç»é¶å‘/å…ç–«/åŒ–ç–—æ²»ç–—åŽç–¾ç—…è¿›å±•ï¼Œå…¥é™¢åŽç»å¤šå¦ç§‘è¯Šç–—è®¨è®ºï¼Œæ ¹æ®åŸºå› æ£€æµ‹ç»“æžœï¼Œç»™äºˆäº†ç»çš®ç»è‚èƒ†ç®¡å¼•æµæœ¯ï¼ˆPTBDï¼‰+mFOLFOX-è‚åŠ¨è„‰ç½®ç®¡åŒ–ç–—æœ¯ï¼ˆHAICï¼‰+é¶å‘ï¼ˆè‰¾ä¼å°¼å¸ƒï¼‰æ²»ç–—çš„æ–¹æ¡ˆã€‚æ²»ç–—æœŸé—´æ‚£è€…è‚¿ç˜¤å¤§å°ç¨³å®šã€èƒ†çº¢ç´ æ°´å¹³ç¨³å®šï¼Œæ€»ç”Ÿå˜æœŸè¾¾åˆ°äº†25ä¸ªæœˆã€‚è¿™æç¤ºåŸºå› æ£€æµ‹å¯¹èƒ†ç®¡ç™Œç²¾å‡†åŒ–ã€ä¸ªä½“åŒ–è¯Šç–—æœ‰é‡è¦æ„ä¹‰ï¼Œä»¥åŠmFOLFOX-HAICè”åˆåº”ç”¨é¶å‘è¯ç‰©æ²»ç–—æ–¹æ¡ˆåœ¨ä¼´é«˜èƒ†çº¢ç´ è¡€ç—‡çš„è‚èƒ†è‚¿ç˜¤æ‚£è€…ä¸å…·æœ‰æœ‰æ•ˆæ€§å’Œå®‰å…¨æ€§ã€‚.

PMID:39375106 | DOI:10.3760/cma.j.cn501113-20231014-00143
Intravascular large B-cell lymphoma of the liver: report of a case

Fetched: October 16th, 2024, 2:01am UTC by J Z Yang

Zhonghua Bing Li Xue Za Zhi. 2024 Oct 8;53(10):1042-1044. doi: 10.3760/cma.j.cn112151-20240203-00080.

ABSTRACT

æ‚£è€…ç”·ï¼Œ69å²ã€‚ä¸»è¦ç—‡çŠ¶ä¸ºè…¹ç—›å’Œå‘çƒã€‚è…¹éƒ¨ç£å…±æŒ¯æˆåƒæ£€æŸ¥æ˜¾ç¤ºè‚å·¦å¶å¼‚å¸¸ä¿¡å·ï¼Œåˆæ¥è€ƒè™‘è‚è„“è‚¿æˆ–è‚å†…èƒ†ç®¡ç™Œã€‚ç©¿åˆºè‚ç»„ç»‡é•œä¸‹9ä¸ªæ±‡ç®¡åŒºå‡è§ç‚Žæ€§ç»†èƒžæµ¸æ¶¦ï¼Œæ±‡ç®¡åŒºè¡€ç®¡å†…è§å¼‚åž‹æ·‹å·´ç»†èƒžå¢žç”Ÿï¼Œç»†èƒžä½“ç§¯å¤§ï¼Œç©ºæ³¡çŠ¶æ ¸ï¼Œæ ¸ä»æ˜Žæ˜¾ï¼Œæ ¸åˆ†è£‚è±¡æ˜“è§ï¼Œå‘ˆéžè‚è¡€çª¦å†…ç”Ÿé•¿æ¨¡å¼ã€‚å…ç–«ç»„ç»‡åŒ–å¦ç»“æžœç¤ºè‚¿ç˜¤ç»†èƒžä½äºŽè¡€ç®¡è…”å†…ï¼Œå¹¶è¡¨è¾¾CD20ç‰Bæ·‹å·´ç»†èƒžæ ‡å¿—ç‰©ã€‚Bæ·‹å·´ç»†èƒžåŸºå› å…‹éš†æ€§é‡æŽ’é˜³æ€§ã€‚è‚è„è¡€ç®¡å†…å¤§Bç»†èƒžæ·‹å·´ç˜¤å‘ˆéžè‚çª¦å†…ç”Ÿé•¿æ¨¡å¼ç—…ä¾‹ç½•è§ï¼Œæ˜“è¢«æ¼è¯Šæˆ–è¯¯è¯Šï¼Œè¯Šæ–æ—¶éœ€ä¸Žååº”æ€§ç‚Žç—‡ã€è½¬ç§»æ€§ä½Žåˆ†åŒ–ç™Œæˆ–ä¸Šçš®æ ·è¡€ç®¡å†…çš®ç˜¤ç‰é‰´åˆ«ã€‚ç¡®è¯Šéœ€è¦ä¾èµ–äºŽç»„ç»‡å½¢æ€å¦ã€å…ç–«ç»„ç»‡åŒ–å¦å’ŒåŸºå› é‡æŽ’ç‰å¤šæ–¹é¢çš„ç»¼åˆåˆ†æžã€‚.

PMID:39375088 | DOI:10.3760/cma.j.cn112151-20240203-00080
Standardized reporting of intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Andrea Siobhan Kierans

Abdom Radiol (NY). 2024 Oct 7. doi: 10.1007/s00261-024-04582-4. Online ahead of print.

NO ABSTRACT

PMID:39373770 | DOI:10.1007/s00261-024-04582-4
[Retracted] SRC-like adaptor protein negatively regulates Wnt signaling in intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Yong Wang

Oncol Lett. 2024 Sep 23;28(6):559. doi: 10.3892/ol.2024.14692. eCollection 2024 Dec.

ABSTRACT

[This retracts the article DOI: 10.3892/ol.2019.9901.].

PMID:39372663 | PMC:PMC11450687 | DOI:10.3892/ol.2024.14692
Aberrant Expression of Pneumocytic Markers (TTF-1 and Napsin-A) in Biliary Duct and Gallbladder Adenocarcinomas; A Potential Diagnostic Pitfall

Fetched: October 16th, 2024, 2:01am UTC by Rutvij Khedkar

Int J Surg Pathol. 2024 Oct 7:10668969241286082. doi: 10.1177/10668969241286082. Online ahead of print.

ABSTRACT

Cholangiocarcinomas and gallbladder carcinomas are epithelial tumours with biliary differentiation. On histology and immunohistochemistry, they resemble adenocarcinomas and possess overlapping immunohistochemical profiles. Diagnosing these tumours is best done using appropriate imaging and clinical features with compatible immunohistochemistry. Immuno-staining for thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin A (Napsin-A) is believed to be specific for primary pulmonary adenocarcinomas. We herein report uncommon instances of strong and diffuse expression of these markers in two examples of adenocarcinomas arising from the bile duct and gallbladder. A review of the literature and a summary of similar studies relating to aberrant TTF-1 and Napsin-A expression in biliary tract adenocarcinomas are presented.

PMID:39370909 | DOI:10.1177/10668969241286082
Notch-Driven Cholangiocarcinogenesis Involves the Hippo Pathway Effector TAZ via METTL3-m6A-YTHDF1

Fetched: October 16th, 2024, 2:01am UTC by Wenbo Ma

Cell Mol Gastroenterol Hepatol. 2024 Oct 4:101417. doi: 10.1016/j.jcmgh.2024.101417. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Notch and TAZ are implicated in cholangiocarcinogenesis, but whether and how these oncogenic molecules interact remain unknown.

METHODS: The development of CCA was induced by hydrodynamic tail vein (HDTV) injection of oncogenes (NICD/AKT) to the FVB/NJ mice. CCA xenograft was developed by inoculation of human CCA cells into the livers of SCID mice. Tissues and cells were analyzed using qRT-PCR, Western blotting analyses, Immunohistochemistry, ChIP-qPCR and WST-1 cell proliferation Assay.

RESULTS: Our experimental findings show that TAZ is indispensable in NICD-driven cholangiocarcinogenesis. Notch activation induces the expression of METTL3 (Methyltransferase like-3) which catalyzes N6-methyladenosine (m6A) modification of TAZ mRNA and that this mechanism plays a central role in the crosstalk between Notch and TAZ in CCA cells. Mechanistically, Notch regulates the expression of METTL3 through the binding of NICD to its downstream transcription factor CSL in the promoter region of METTL3. METTL3 in turn mediates m6A modification of TAZ mRNA which is recognized by the m6A reader YTHDF1 to enhance TAZ protein translation. We observed that inhibition of Notch signaling decreased the protein levels of both MELLT3 and TAZ. Depletion of METTL3 by shRNAs or by the next generation GapmeR antisense oligonucleotides (ASOs) decreased the level of TAZ protein and inhibited the growth of human CCA cells in vitro and in mice.

CONCLUSION: This study describes a novel Notch-METTL3-TAZ signaling cascade which is important in CCA development and progression. Our experimental results provide new insight into how the Notch pathway cooperates with TAZ signaling in CCA, and the findings may have important therapeutic implications.

PMID:39369960 | DOI:10.1016/j.jcmgh.2024.101417
Kinase library screening identifies IGF-1R as an oncogenic vulnerability in intrahepatic cholangiocarcinoma stem-like cells

Fetched: October 16th, 2024, 2:01am UTC by Chotirat Rattanasinchai

Biochim Biophys Acta Mol Basis Dis. 2024 Oct 5;1871(1):167521. doi: 10.1016/j.bbadis.2024.167521. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer of the peripheral bile ducts and is recognized by the abundance of cancer stem-like cells (CSCs) within the tumor mass. While CSC markers in iCCA are well-defined, the molecular vulnerabilities of this subpopulation remain elusive.

METHODS: The 96-well, three dimensional (3D) tumorsphere culture was adapted from a well-established CSC model, validated for CSC markers through gene expression analysis. Kinase library screening was then conducted to reveal potential oncogenic vulnerable pathways. RNA interference was utilized to stably silence the candidate gene in three iCCA cell lines and its impact on iCCA cell proliferation and tumorsphere formation efficiency (TFE) was evaluated.

RESULTS: Kinase inhibitor library screening identified the top 50 kinase inhibitors crucial for tumorsphere viability, with 11 inhibitors targeting the IGF-1R/PI3K/AKT axis. Further dose-dependent analysis of the top 'hit' inhibitors confirmed IGF-1R as the candidate molecule. Upon stably silencing of IGF-1R, all three iCCA cell lines exhibited decreased AKT activation, impeded proliferation and reduced TFE, indicating a decline in CSC subpopulations.

CONCLUSIONS: IGF-1R plays a critical role in maintaining iCCA-stem like cell populations.

GENERAL SIGNIFICANCE: Our data highlight the potential utility of IGF-1R as a prognostic marker of iCCA and a therapeutic target for eliminating its CSC subpopulation.

PMID:39369614 | DOI:10.1016/j.bbadis.2024.167521
Mitotic spindle positioning protein serves as prognostic biomarker in patients with colorectal cancer

Fetched: October 16th, 2024, 2:01am UTC by Jin Li

Scand J Gastroenterol. 2024 Oct 5:1-9. doi: 10.1080/00365521.2024.2411405. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear.

METHODS: This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry.

RESULTS: MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan-Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC.

CONCLUSION: Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC.

PMID:39369263 | DOI:10.1080/00365521.2024.2411405
Machine Learning Model to Predict Early Recurrence in Patients with Perihilar Cholangiocarcinoma Planned Treatment with Curative Resection: A Multicenter Study

Fetched: October 16th, 2024, 2:01am UTC by Xiang Wang

J Gastrointest Surg. 2024 Oct 3:S1091-255X(24)00642-5. doi: 10.1016/j.gassur.2024.09.027. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Early recurrence is the leading cause of death for patients with perihilar cholangiocarcinoma (pCCA) after surgery. Identifying high-risk patients preoperatively is important. This study aimed to construct a preoperative prediction model for the early recurrence of pCCA patients planned treatment with curative resection.

METHODS: This study ultimately enrolled 400 pCCA patients after curative resection in five hospitals between 2013 and 2019. They were randomly divided into training (n=300) and testing groups (n=100) at a ratio of 3:1. Associated variables were identified via LASSO regression. Four machine learning models were constructed: support vector machine (SVM), random forest (RF), logistic regression, and K-nearest neighbors (KNN). The predictive ability of the models was evaluated via receiver operating characteristic (ROC) curves, precision-recall curve (PRC) curves, and decision curve analysis (DCA). KaplanMeier survival curves were drawn for the high/low-risk population.

RESULTS: Five factors, CA19-9, tumor size, total bilirubin, hepatic artery invasion, and portal vein invasion, were selected by LASSO regression. In both the training and testing groups, the ROC curve (AUC: 0.983 vs 0.952) and the PRC (0.981 vs 0.939) showed that RF was the best. The cutoff value for distinguishing high- and low-risk patients was 0.51. KM survival curves revealed that in both groups, there was a significant difference in RFS between high- and low-risk patients (P<0.001).

CONCLUSION: This study used preoperative variables from a large, multicenter database to construct a machine learning model that could effectively predict the early recurrence of pCCA patients planned treatment with curative resection and help clinicians make better treatment decisions.

PMID:39368645 | DOI:10.1016/j.gassur.2024.09.027
Real-time indocyanine green fluorescence imaging and navigation for cone unit laparoscopic hepatic resection of intrahepatic duct stone: a case series study

Fetched: October 16th, 2024, 2:01am UTC by Jianjie Hao

Minim Invasive Ther Allied Technol. 2024 Oct 5:1-7. doi: 10.1080/13645706.2024.2410369. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic bile duct stones, although common and benign, require varying therapeutic strategies due to their recurrent nature. Inadequate management can escalate to liver cirrhosis or cholangiocarcinoma. A surgical method merging indocyanine green fluorescence imaging (ICG-FI) with liver cone unit resection is optimal, ensuring complete lesion removal and healthy liver tissue conservation.

METHOD: A retrospective descriptive study was conducted on 15 patients with intrahepatic bile duct stones who were admitted to Sichuan Provincial People's Hospital from January 2021 to December 2023. All patients underwent laparoscopic anatomical liver resection guided by ICG-FI.

RESULTS: Among the 15 patients included in the study, ten were male and five were female, with an average age of 52 years. All patients were free from underlying medical conditions. Intraoperatively, ICG-FI was good, with clear boundaries, and all patients successfully underwent surgery without any conversions to open surgery. The mean operative time was 236 Â± 56 min, and the estimated blood loss was 320 Â± 75 ml. Patients had a postoperative hospital stay of 5.5 Â± 1.5 days. No severe complications occurred.

CONCLUSIONS: Real-time ICG-FI with anatomical liver resection is a safe and effective approach for managing intrahepatic bile duct stones.

PMID:39367997 | DOI:10.1080/13645706.2024.2410369
$Permalink for 'Cholangiocarcinoma patients with FGFR2 fusions/rearrangements but primary refractory to pemigatinib: the real challenge?'$
Cholangiocarcinoma patients with FGFR2 fusions/rearrangements but primary refractory to pemigatinib: the real challenge?

Fetched: October 16th, 2024, 2:01am UTC by A Rizzo

ESMO Open. 2024 Oct 3;9(10):103936. doi: 10.1016/j.esmoop.2024.103936. Online ahead of print.

NO ABSTRACT

PMID:39366293 | DOI:10.1016/j.esmoop.2024.103936
Preoperative prognostic stratification and prediction of long-term outcomes after pancreatoduodenectomy for distal cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Tomotaka Kato

Eur J Surg Oncol. 2024 Sep 18;50(12):108691. doi: 10.1016/j.ejso.2024.108691. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging.

METHODS: This single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS).

RESULTS: Among 170 patients examined, the median tumor depth was 10 mm, and 37 % of the patients were diagnosed with pT3. Overall, 46 % of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50 %, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) â‰¥15 mm and main pancreatic duct (MPD) dilatation (â‰¥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39 %) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64 % (5-year OS: 8 %). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72 %) to those with pStage I DCC.

CONCLUSION: A simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.

PMID:39366161 | DOI:10.1016/j.ejso.2024.108691
Detecting Cholangiocarcinoma in the Setting of Primary Sclerosing Cholangitis: Is Biliary Tract Fluorescence In Situ Hybridization Helpful?

Fetched: October 16th, 2024, 2:01am UTC by Lauren J Miller

Cytopathology. 2024 Oct 4. doi: 10.1111/cyt.13452. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVE: Biliary brushing cytology (BB) to detect cholangiocarcinoma (CCA) is integral in the surveillance of patients with primary sclerosing cholangitis (PSC). Since reactive changes can mimic carcinoma, indeterminant results are frequent. Fluorescence in situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of CCA. This study evaluates the performance of FISH for detecting CCA in patients with and without PSC.

MATERIALS AND METHODS: A query of our pathology database for atypical and suspicious BB with concurrent FISH results was performed from 2014 to 2021. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed to identify patients with PSC and CCA. CCA was confirmed by pathology or clinical impression.

RESULTS: Of the 65 patients (103 BB) in the PSC cohort, 59 patients (94 BB) without CCA and 6 patients (9 BB) with CCA were identified. 33 non-PSC patients (41 BB) with CCA were included for comparison. Positive FISH was highest in non-PSC patients with CCA (10/41 BB, 24%). Positive FISH was seen in both PSC with (1/9 BB, 11%) and without (2/94 BB, 2%) CCA.

CONCLUSIONS: FISH positivity was lower than expected and was positive in PSC patients without CCA. These results question the clinical utility of FISH for CCA surveillance in PSC patients.

PMID:39366926 | DOI:10.1111/cyt.13452
Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas After Liver Transplantation

Fetched: October 16th, 2024, 2:01am UTC by Bradley T Busebee

Clin Transplant. 2024 Oct;38(10):e15431. doi: 10.1111/ctr.15431.

ABSTRACT

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear.

METHODS: In this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13-year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics.

RESULTS: Of 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN-associated cancer and 5 cases of worrisome features) over an average follow-up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression.

CONCLUSION: IPMN progression is rare after liver transplantation even over an extended follow-up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

PMID:39365117 | DOI:10.1111/ctr.15431
Care Patterns and Outcomes for Intrahepatic Cholangiocarcinoma by Rurality of Patient Residence in a Midwestern State

Fetched: October 16th, 2024, 2:01am UTC by Mohammed O Suraju

J Surg Oncol. 2024 Oct 4. doi: 10.1002/jso.27939. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of the liver and has the worst prognosis of any tumor arising from the liver, with a 5-year survival as low as 10%. However, whether the rurality of a patient's residence impacts care received and survival has not been well studied. We aimed to assess differences in care patterns associated with the rurality of patient's residences and their impact on survival outcomes, hypothesizing that patients in rural areas would experience lower survival.

METHODS: Adult patients diagnosed with ICC between 2010 and 2020 were identified in the Iowa Cancer Registry. Chi-square tests were used to compare values categorical variables by rural/urban status. Cox proportional hazards regression was used to determine associations with cancer-specific mortality.

RESULTS: Of 672 patients diagnosed with ICC during the study period, 53%, 27%, and 21% resided in metropolitan, micropolitan, and rural areas, respectively. There were no significant differences in age, sex, stage at diagnosis, the proportion receiving chemotherapy within 12 weeks of diagnosis, and undergoing surgery across all groups. Additionally, the proportion receiving definitive care at a National Cancer Institute (NCI) designated center was comparable across the three groups (37% metro vs. 43% micro vs. 35% rural). However, rural residents had the highest proportion of traveling â‰¥ 50 miles for definitive care (22% metro vs. 41% micro vs. 56% rural). In multivariable analysis of patients with Stage 1-3 disease, younger age, receipt of chemotherapy, surgery, and definitive care at an NCI center were independently associated with decreased mortality risk. However, rural residence was not significantly associated with survival (HR: 0.64 [95% CI: 0.38-1.06]).

CONCLUSION: Similar to other complex cancer diagnoses, we found that definitive care at an NCI center was associated with decreased mortality risk for patients with ICC. Although rural residence was not independently associated with survival in this cohort, rural residents traveled significantly longer distances to access definitive care. This highlights a crucial need to improve access to specialized centers for complex cancer care.

PMID:39364893 | DOI:10.1002/jso.27939
A flexible deep learning framework for liver tumor diagnosis using variable multi-phase contrast-enhanced CT scans

Fetched: October 16th, 2024, 2:01am UTC by Shixin Huang

J Cancer Res Clin Oncol. 2024 Oct 3;150(10):443. doi: 10.1007/s00432-024-05977-y.

ABSTRACT

BACKGROUND: Liver cancer is a significant cause of cancer-related mortality worldwide and requires tailored treatment strategies for different types. However, preoperative accurate diagnosis of the type presents a challenge. This study aims to develop an automatic diagnostic model based on multi-phase contrast-enhanced CT (CECT) images to distinguish between hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and normal individuals.

METHODS: We designed a Hierarchical Long Short-Term Memory (H-LSTM) model, whose core components consist of a shared image feature extractor across phases, an internal LSTM for each phase, and an external LSTM across phases. The internal LSTM aggregates features from different layers of 2D CECT images, while the external LSTM aggregates features across different phases. H-LSTM can handle incomplete phases and varying numbers of CECT image layers, making it suitable for real-world decision support scenarios. Additionally, we applied phase augmentation techniques to process multi-phase CECT images, improving the model's robustness.

RESULTS: The H-LSTM model achieved an overall average AUROC of 0.93 (0.90, 1.00) on the test dataset, with AUROC for HCC classification reaching 0.97 (0.93, 1.00) and for ICC classification reaching 0.90 (0.78, 1.00). Comprehensive validation in scenarios with incomplete phases was performed, with the H-LSTM model consistently achieving AUROC values over 0.9.

CONCLUSION: The proposed H-LSTM model can be employed for classification tasks involving incomplete phases of CECT images in real-world scenarios, demonstrating high performance. This highlights the potential of AI-assisted systems in achieving accurate diagnosis and treatment of liver cancer. H-LSTM offers an effective solution for processing multi-phase data and provides practical value for clinical diagnostics.

PMID:39361193 | PMC:PMC11450020 | DOI:10.1007/s00432-024-05977-y
Clinical prognosticators and targets in the immune microenvironment of intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Isis Lozzi

Oncoimmunology. 2024 Oct 1;13(1):2406052. doi: 10.1080/2162402X.2024.2406052. eCollection 2024.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation.

METHODS: Liver tissue samples were collected during 2008-2019 from patients (n = 139) diagnosed with ICC who underwent curative intent surgery without neoadjuvant chemotherapy. Samples from the discovery cohort (n = 86) were immunohistochemically analyzed on tissue microarrays (TMAs) for the expression of CD68, CD3, CD4, CD8, Foxp3, PD-L1, STAT1, and p-STAT1 in tumor core and stroma areas. Results were digitally analyzed using QuPath software and correlated with clinicopathological characteristics. For validation of TIME-related biomarkers, we performed multiplex imaging mass cytometry (IMC) in a validation cohort (n = 53).

RESULTS: CD68+ cells were the predominant immune cell type in the TIME of ICC. CD4+^high T cell density correlated with better overall survival (OS). Prediction modeling together with validation cohort confirmed relevance of CD4+ cells, PD-L1 expression by immune cells in the stroma and N-stage on overall disease outcome. In turn, IMC analyses revealed that silent CD3+CD4+ clusters inversely impacted survival. Among annotated immune cell clusters, PD-L1 was most relevantly expressed by CD4+FoxP3+ cells. A subset of tumors with high density of immune cells ("hot" cluster) correlated with PD-L1 expression and could identify a group of candidates for immune checkpoint inhibition (ICI). Ultimately, higher levels of STAT1 expression were associated with higher lymphocyte infiltration and PD-L1 expression.

CONCLUSIONS: These results highlight the importance of CD4+ T cells in immune response against ICC. Secondly, a subset of tumors with "hot" TIME represents potential candidates for ICI, while stimulation of STAT1 pathway could be a potential target to turn "cold" into "hot" TIME in ICC.

PMID:39359389 | PMC:PMC11445892 | DOI:10.1080/2162402X.2024.2406052
Expression of the large amino acid transporter SLC7A5/LAT1 on immune cells is enhanced in primary sclerosing cholangitis-associated cholangiocarcinoma and correlates with poor prognosis in cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Vittorio Branchi

Hum Pathol. 2024 Oct 13:105670. doi: 10.1016/j.humpath.2024.105670. Online ahead of print.

ABSTRACT

Biliary tract cancers (BTC) are rare lethal malignancies arising along the biliary tree. Unfortunately, effective therapeutics are lacking and the prognosis remains dismal even for patients eligible for surgical resection. Therefore, novel therapeutic approaches along with early detection strategies and prognostic markers are urgently needed. Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts leading to fibrosis and ultimately cirrhosis. Patients with PSC have a 5-20% lifetime risk of developing BTC; yet the molecular mechanisms that underpin the development of PSC- associated biliary tract cancer (PSC-BTC) have not been fully elucidated. SLC7A5/LAT1, a large amino acid transporter, has been shown to modulate cell growth and proliferation as well as other intracellular processes in solid tumors. In this study, we evaluated SLC7A5 expression in PSC-BTC and in sporadic BTC (sBTC) and its role as a prognostic factor. Analysis of the TGCA cohort showed a significantly higher expression of SLC7A5 in tumor tissue compared with adjacent normal tissue (p= 0.0002) in BTC. In our cohort (comprised of 69 BTC patients including 16 PSC-BTC), SLC7A5/LAT1 expression was observed in both tumor and intratumoral immune cells. A significantly higher percentage of SLC7A5/LAT1 positive intratumoral immune cells was observed in PSC-BTC compared with sBTC (p = 0.004). Multiplex immunofluorescence co-detection by indexing (CODEX) analysis identified CD4+ regulatory T Lymphocytes and CD68+ macrophages as the largest immune cell populations expressing LAT1. SLC7A5/LAT1 expression as well as a higher intratumoral infiltration of SLC7A5/LAT1-positive immune cells (â‰¥2%) were associated with a shorter overall survival in our cohort (LogRank test, p=0.04 and p= 0.008; respectively). SLC7A5/LAT1 expressing tumors are higher staged tumors (pT3/4 versus pT1/2, p = 0.048). These results underline the potential use of SLC7A5/LAT1 as a prognostic marker in BTC. Furthermore, the higher frequency of SLC7A5/LAT1 positive immune cells in PSC-BTC compared to sBTC may hint at the potential role of SLC7A5/LAT1 in inflammation-driven carcinogenesis.

PMID:39406289 | DOI:10.1016/j.humpath.2024.105670
Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3

Fetched: October 16th, 2024, 2:01am UTC by Maitane Asensio

Biomed Pharmacother. 2024 Oct 13;180:117533. doi: 10.1016/j.biopha.2024.117533. Online ahead of print.

ABSTRACT

AIMS: Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance.

METHODS: Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors. The effect of manipulating MRP3 function/expression was evaluated in vitro and in vivo.

RESULTS: High MRP3 expression at the plasma membrane of human CCA cells was found. MRP3 overexpression in HEK293T cells selectively impaired the cytotoxic effect of etoposide, cisplatin, SN-38, and mitoxantrone. Reduced MRP3 activity with shRNAs or pan-MRP blockers enhanced the sensitivity to these drugs. MRP3 interaction with natural and semisynthetic compounds (â‰ˆ40,000) was evaluated by virtual drug screening and molecular docking. Two identified potential MRP3 inhibitors (EM-114, EM-188), and sorafenib impaired MRP3 transport activity and enhanced sensitivity of CCA cells to etoposide and cisplatin. The antitumor effect of cisplatin in the mouse xenograft model was enhanced by co-treatment with sorafenib, which was accompanied by a higher intratumor accumulation of cisplatin.

CONCLUSIONS: Genetic and pharmacological MRP3 inhibition enhances the anti-CCA effect of several drugs, which constitutes a promising strategy to improve the response to chemotherapy in CCA patients.

PMID:39405909 | DOI:10.1016/j.biopha.2024.117533
Failure to Rescue After Resection of Perhilar Cholangiocarcinoma in an International Multicenter Cohort

Fetched: October 16th, 2024, 2:01am UTC by Pim B Olthof

Ann Surg Oncol. 2024 Oct 15. doi: 10.1245/s10434-024-16293-7. Online ahead of print.

ABSTRACT

BACKGROUND: Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR.

PATIENTS AND METHOD: Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals.

RESULTS: In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02-1.05) years], ASA 3 or 4 [1.40 (1.01-1.95)], jaundice at presentation [1.79 (1.16-2.76)], right-sided resection [1.45 (1.06-1.98)], and annual hospital volume < 6 [1.44 (1.07-1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76-13.68).

CONCLUSION: FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR.

PMID:39404989 | DOI:10.1245/s10434-024-16293-7
Nomograms predicting benefit after immunotherapy in oral bifidobacteria supplementation ICC patients: a retrospective study

Fetched: October 16th, 2024, 2:01am UTC by Sihui Zhu

BMC Cancer. 2024 Oct 14;24(1):1274. doi: 10.1186/s12885-024-12982-4.

ABSTRACT

PURPOSE: The objective of this study was to develop nomograms for predicting outcomes following immunotherapy in patients diagnosed with intrahepatic cholangiocarcinoma (ICC).

PATIENTS AND METHODS: A retrospective analysis was conducted on data from 75 ICC patients who received immunotherapy at Jinling Hospital and Drum Hospital. The discriminative power, accuracy, and clinical applicability of the nomograms were assessed using the concordance index (C-index), calibration curve, and decision curve analysis (DCA). The predictive performance of the nomograms for overall survival (OS) and progression-free survival (PFS) was evaluated using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier curves were also generated for validation purposes.

RESULTS: Multivariable analysis identified independent prognostic factors for OS, including CA19-9 levels, portal vein tumor thrombus (PVTT) grade, bifidobacteria administration, and surgery. The C-index of the nomogram for OS prediction was 0.722 (95% confidence interval [CI]: 0.661-0.783). Independent prognostic factors for PFS included CA19-9 levels, albumin, and bilirubin, with a C-index of 0.678 (95% CI: 0.612-0.743) for the nomogram predicting PFS. Calibration curves demonstrated strong concordance between predicted and observed outcomes, while DCA and Kaplan-Meier curves further supported the clinical utility of the nomogram.

CONCLUSION: The nomogram developed in this study demonstrated favorable performance in predicting the prognosis of ICC patients undergoing immunotherapy. Additionally, our findings, for the first time, identified probiotics as a potential prognostic marker for immunotherapy. This prognostic model has the potential to enhance patient selection for immunotherapy and improve clinical decision-making.

PMID:39402531 | DOI:10.1186/s12885-024-12982-4
miR-182-5p promotes the proliferation and invasion of hilar cholangiocarcinoma cells by inhibiting FBXW7

Fetched: October 16th, 2024, 2:01am UTC by Hang Zhou

J Cancer Res Clin Oncol. 2024 Oct 15;150(10):461. doi: 10.1007/s00432-024-05961-6.

ABSTRACT

BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment.

METHODS: HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3'UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes.

RESULTS: miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 'UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo.

CONCLUSION: miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.

PMID:39402299 | DOI:10.1007/s00432-024-05961-6
The pathological significance and potential mechanism of ACLY in cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Xiaoyan Sun

Front Immunol. 2024 Sep 27;15:1477267. doi: 10.3389/fimmu.2024.1477267. eCollection 2024.

ABSTRACT

BACKGROUND AND AIM: Cholangiocarcinoma (CCA) is a rare cancer, yet its incidence and mortality rates have been steadily increasing globally over the past few decades. Currently, there are no effective targeted treatment strategies available for patients. ACLY (ATP Citrate Lyase), a key enzyme in de novo lipogenesis, is aberrantly expressed in several tumors and is associated with malignant progression. However, its role and mechanisms in CCA have not yet been elucidated.

METHODS: The expression of ACLY in CCA was assessed using transcriptomic profiles and tissue microarrays. Kaplan-Meier curves were employed to evaluate the prognostic significance of ACLY in CCA. Functional enrichment analysis was used to explore the potential mechanisms of ACLY in CCA. A series of assays were conducted to examine the effects of ACLY on the proliferation and migration of CCA cells. Ferroptosis inducers and inhibitors, along with lipid peroxide probes and MDA assay kits, were utilized to explore the role of ACLY in ferroptosis within CCA. Additionally, lipid-depleted fetal bovine serum and several fatty acids were used to evaluate the impact of fatty acids on ferroptosis induced by ACLY inhibition. Correlation analyses were performed to elucidate the relationship between ACLY and tumor stemness as well as tumor microenvironment.

RESULTS: The expression of ACLY was found to be higher in CCA tissues compared to adjacent normal tissues. Patients with elevated ACLY expression demonstrated poorer overall survival outcomes. ACLY were closed associated with fatty acid metabolism and tumor-initiating cells. Knockdown of ACLY did not significantly impact the proliferation and migration of CCA cells. However, ACLY inhibition led to increased accumulation of lipid peroxides and enhanced sensitivity of CCA cells to ferroptosis inducers. Polyunsaturated fatty acids were observed to inhibit the proliferation of ACLY-knockdown cells; nonetheless, this inhibitory effect was diminished when the cells were cultured in medium supplemented with lipid-depleted fetal bovine serum. Additionally, ACLY expression was negatively correlated with immune cell infiltration and immune scores in CCA.

CONCLUSION: ACLY promotes ferroptosis by disrupting the balance of saturated and unsaturated fatty acids. ACLY may therefore serve as a potential diagnostic and therapeutic target for CCA.

PMID:39399493 | PMC:PMC11466796 | DOI:10.3389/fimmu.2024.1477267
Cholangioscopy-based convoluted neuronal network vs. confocal laser endomicroscopy in identification of neoplastic biliary strictures

Fetched: October 16th, 2024, 2:01am UTC by Carlos Robles-Medranda

Endosc Int Open. 2024 Oct 10;12(10):E1118-E1126. doi: 10.1055/a-2404-5699. eCollection 2024 Oct.

ABSTRACT

Background and study aims Artificial intelligence (AI) models have demonstrated high diagnostic performance identifying neoplasia during digital single-operator cholangioscopy (DSOC). To date, there are no studies directly comparing AI vs. DSOC-guided probe-base confocal laser endomicroscopy (DSOC-pCLE). Thus, we aimed to compare the diagnostic accuracy of a DSOC-based AI model with DSOC-pCLE for identifying neoplasia in patients with indeterminate biliary strictures. Patients and methods This retrospective cohort-based diagnostic accuracy study included patients â‰¥ 18 years old who underwent DSOC and DSOC-pCLE (June 2014 to May 2022). Four methods were used to diagnose each patient's biliary structure, including DSOC direct visualization, DSOC-pCLE, an offline DSOC-based AI model analysis performed in DSOC recordings, and DSOC/pCLE-guided biopsies. The reference standard for neoplasia was a diagnosis based on further clinical evolution, imaging, or surgical specimen findings during a 12-month follow-up period. Results A total of 90 patients were included in the study. Eighty-six of 90 (95.5%) had neoplastic lesions including cholangiocarcinoma (98.8%) and tubulopapillary adenoma (1.2%). Four cases were inflammatory including two cases with chronic inflammation and two cases of primary sclerosing cholangitis. Compared with DSOC-AI, which obtained an area under the receiver operator curve (AUC) of 0.79, DSOC direct visualization had an AUC of 0.74 ( P = 0.763), DSOC-pCLE had an AUC of 0.72 ( P = 0.634), and DSOC- and pCLE-guided biopsy had an AUC of 0.83 ( P = 0.809). Conclusions The DSOC-AI model demonstrated an offline diagnostic performance similar to that of DSOC-pCLE, DSOC alone, and DSOC/pCLE-guided biopsies. Larger multicenter, prospective, head-to-head trials with a proportional sample among neoplastic and nonneoplastic cases are advisable to confirm the obtained results.

PMID:39398445 | PMC:PMC11466527 | DOI:10.1055/a-2404-5699
Efficacy analysis of HAIC combined with lenvatinib plus PD1 inhibitor vs. first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Zhipeng Lin

Sci Rep. 2024 Oct 14;14(1):23961. doi: 10.1038/s41598-024-75102-z.

ABSTRACT

This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People's Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients.

PMID:39397104 | PMC:PMC11471826 | DOI:10.1038/s41598-024-75102-z
Letter to the editor-Comment on: "Intrahepatic cholangiocarcinoma with arterial phase hyperenhancement and specialized tumor microenvironment associated with good prognosis after radical resection: A single-center retrospective study"

Fetched: October 16th, 2024, 2:01am UTC by Yin-Fang Wu

Surgery. 2024 Oct 11:S0039-6060(24)00776-1. doi: 10.1016/j.surg.2024.09.015. Online ahead of print.

NO ABSTRACT

PMID:39395858 | DOI:10.1016/j.surg.2024.09.015
A case report: deep and durable response to low-dose lenvatinib and tislelizumab in an elderly patient with advanced intrahepatic cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Pei Zhang

Front Pharmacol. 2024 Sep 26;15:1447582. doi: 10.3389/fphar.2024.1447582. eCollection 2024.

ABSTRACT

BACKGROUND: Older patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment.

CASE PRESENTATION: We report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm Ã— 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months.

CONCLUSION: The case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

PMID:39391699 | PMC:PMC11464426 | DOI:10.3389/fphar.2024.1447582
Advancements in cholangiocarcinoma: evolving strategies for diagnosis, treatment, and palliation over three decades

Fetched: October 16th, 2024, 2:01am UTC by Charbel Elias

Chin Clin Oncol. 2024 Sep 23:cco-23-144. doi: 10.21037/cco-23-144. Online ahead of print.

ABSTRACT

In recent years, significant progress has been made in the diagnosis, treatment, and palliation of cholangiocarcinoma (CC). CC accounts for 15% of all primary liver neoplasms and 3% of all gastrointestinal malignancies. Despite the significant advances in the diagnosis and treatment of CC, this tumor remains a formidable challenge, accounting for 2% of all cancer-related deaths. Chronic inflammation, genetic predisposition, and congenital biliary abnormalities are the primary risk factors for CC. CC is anatomically categorized into intrahepatic CC (ICC), perihilar, and distal types, with the latter two collectively termed extrahepatic CC (ECC). Although the incidence of ICC surpasses that of ECC, both have exhibited an upward trend over the last two decades. The advancements in diagnostic techniques, including highresolution imaging modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, have improved the early detection and staging of CC. Molecular profiling and biomarker discovery have further enabled personalized treatment approaches. Endoscopic techniques have also evolved, providing minimally invasive options for biopsy and stent placement, which improve both diagnosis and palliative care. Treatment strategies have seen significant evolution, with surgical resection and liver transplantation being the only curative options. The refinement of surgical techniques and perioperative care has increased the success rates of these procedures. Additionally, neoadjuvant and adjuvant therapies, including chemoradiation, have shown promise in improving surgical outcomes and overall survival rates. Multidisciplinary teams (MDTs) play a crucial role in managing CC, ensuring that patients receive comprehensive care that includes surgical, medical, and supportive treatments. This team approach has led to the development of more effective treatment protocols and improved patient outcomes. Palliative care has also advanced, with new chemotherapeutic agents and targeted therapies providing better management of symptoms and prolongation of life. Innovations in interventional radiology, such as radiofrequency ablation and transcatheter arterial chemoembolization (TACE), offer additional palliative options that can significantly enhance quality of life. This review article outlines the progress made in diagnosing and treating individuals with CC over the last 30 years, highlighting the critical role of technological advancements and multidisciplinary care in improving patient outcomes.

PMID:39390920 | DOI:10.21037/cco-23-144
American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis and management of solid pancreatic masses: summary and recommendations

Fetched: October 16th, 2024, 2:01am UTC by ASGE Standards of Practice Committee

Gastrointest Endosc. 2024 Oct 8:S0016-5107(24)03255-3. doi: 10.1016/j.gie.2024.06.002. Online ahead of print.

ABSTRACT

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the diagnosis and management of pancreatic masses. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses needle selection (fine-needle biopsy [FNB] needle vs FNA needle), needle caliber (22-gauge vs 25-gauge needles), FNB needle type (novel or contemporary [fork-tip and Franseen] vs alternative FNB needle designs), and sample processing (rapid on-site evaluation [ROSE] vs no ROSE). In addition, this guideline addresses stent selection (self-expandable metal stent [SEMS] vs plastic stent), SEMS type (covered [cSEMS] vs uncovered [uSEMS]), and pain management (celiac plexus neurolysis [CPN] vs medical analgesic therapy). In patients with solid pancreatic masses undergoing EUS-guided tissue acquisition (EUS-TA), the ASGE recommends FNB needles over FNA needles. With regard to needle caliber, the ASGE suggests 22-gauge over 25-gauge needles. When an FNB needle is used, the ASGE recommends using either a fork-tip or a Franseen needle over alternative FNB needle designs. After a sample has been obtained, the ASGE suggests against the routine use of ROSE in patients undergoing an initial EUS-TA of a solid pancreatic mass. In patients with distal malignant biliary obstruction undergoing drainage with ERCP, the ASGE suggests using SEMSs over plastic stents. In patients with proven malignancy undergoing SEMS placement, the ASGE suggests using cSEMSs over uSEMSs. If malignancy has not been histopathologically confirmed, the ASGE recommends against the use of uSEMSs. Finally, in patients with unresectable pancreatic cancer and abdominal pain, the ASGE suggests the use of CPN as an adjunct for the treatment of abdominal pain. This document outlines the process, analyses, and decision approaches used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

PMID:39387777 | DOI:10.1016/j.gie.2024.06.002
Optimal results through enhanced recovery: Achieving textbook outcomes with high compliance in elective liver surgery

Fetched: October 16th, 2024, 2:01am UTC by Juliette Gosse

World J Surg. 2024 Oct 10. doi: 10.1002/wjs.12345. Online ahead of print.

ABSTRACT

BACKGROUND: Existing studies suggest a positive correlation between high compliance with enhanced recovery programs (ERP) and improved outcomes. While individual outcome measures have advantages, composite benchmarks, such as textbook outcome (TO), offer a more comprehensive assessment of healthcare performance. Given the link between ERP and postoperative outcomes, this study aims to investigate the impact of ERP on TO attainment after liver surgery (LS).

METHODS: A prospective multicenter cohort of patients undergoing LS and exposed to ERP from 2016 to 2022 in France was analyzed. The primary outcome was to compare the rates of TO achieved between patients with high ERP compliance (>70%) and those with low ERP compliance (<70%) after LS.

RESULTS: A total of 706 patients were included in the study, and 217 (30.7%) achieved TO: 170 patients with high ERP compliance (24%) versus 47 patients (6.6%) with low ERP compliance attained TO (p < 0.001). High ERP compliance was associated to an increased likelihood of achieving TO [odds ratio (OR) = 1.49 (95% CI: 1.01, 2.24); p = 0.049], while cholangiocarcinoma [OR = 0.11 (95% CI: 0.02, 0.39); p = 0.003], high complexity LS [OR = 0.22 (95% CI: 0.13, 0.36); p < 0.001], intraoperative hypotension requiring vasopressors [OR = 0.29 (95% CI: 0.10, 0.68); p = 0.010], and post-operative ileus [OR = 0.08 (95% CI: 0.00, 0.37); p = 0.013] were negatively associated to the likelihood of achieving TO.

CONCLUSIONS: Patients with high ERP compliance after LS experience elevated rates of TO, compared to those with low ERP compliance.

PMID:39390605 | DOI:10.1002/wjs.12345
Biliary drainage in palliative and curative intent European patients with hilar cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis

Fetched: October 16th, 2024, 2:01am UTC by Jan Drews

BMC Gastroenterol. 2024 Oct 10;24(1):359. doi: 10.1186/s12876-024-03429-y.

ABSTRACT

BACKGROUND AND AIMS: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented.

PATIENTS AND METHODS: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients.

RESULTS: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia.

CONCLUSIONS: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

PMID:39390363 | PMC:PMC11468282 | DOI:10.1186/s12876-024-03429-y
Portal Vein Arterialization as a Lifesaving Strategy for Hepatic Artery Injury in Robotic Hepatectomy

Fetched: October 16th, 2024, 2:01am UTC by Yan Li

Ann Surg Oncol. 2024 Oct 10. doi: 10.1245/s10434-024-16342-1. Online ahead of print.

ABSTRACT

BACKGROUND: Robotic vascular resection and reconstruction is a challenging procedure. Portal vein arterialization (PVA) can offer an efficient solution in those cases in which the hepatic artery cannot be reconstructed.1.Can J Surg 64:e173-e182;2.The Paul Brousse Hospital Experience. HPB (Oxford) 16:723-738;3.J Am Coll Surg 207:e1-6; PVA increases oxygen supply to the remaining part of the liver, promotes liver regeneration, and prevents liver failure.Majlesara A, Golriz M, Ramouz A, et al. Portal vein arterialization as a salvage method in advanced hepatopancreatobiliary surgery. Br J Surg. 2024;111. In this multimedia article, we describe a patient who was treated with PVA for a robotic hepatic artery injury during robotic left-liver-first anterior radical modular orthotopic right hemihepatectomy (Rob-Larmorth).5.Ann Surg Oncol 31:5636-5637 METHODS: A 52-year-old male patient was admitted with epigastric pain. Further imaging showed intrahepatic cholangiocarcinoma involving the root of the right anterior branch of the portal vein. Following multidisciplinary consultation, surgical resection was recommended as the primary approach. The robotic technique was chosen in this operation, with preoperative anticipation of needing Rob-Larmorth. Unfortunately, the left hepatic artery sustained unintended damage during skeletonization of the duodenal ligaments. Anastomosis could not be performed due to severe damage to the distal end intima. We utilized PVA technology to anastomose the hepatic artery to the portal vein. Finally, Rob-Larmorth and PVA were successfully performed.

RESULTS: The surgery took 490 min and the estimated blood loss was approximately 300 mL. No blood transfusion was performed. Postoperatively, the patient recovered smoothly without liver failure, although percutaneous drainage was required due to bile leakage. Pathological examination revealed moderately to poorly differentiated bile duct cell carcinoma (T2N0M0, stage II). No recurrence was observed during the 12-month follow-up.

DISCUSSION: PVA can be an effective solution when no other revascularization options are available. Implementing PVA as a bridging procedure increases oxygen delivery to the remnant liver, facilitating regeneration and reducing the risk of liver failure. The development of arterial collaterals is a significant concern for individuals undergoing PVA. Complications reported after PVA include early shunt thrombosis, portal hypertension, and a notable 90-day mortality rate.1.Can J Surg 64:e173-e182 However, Majlesara and colleagues found no evidence of postoperative liver damage associated with PVA. They also reported low morbidity rates and no associated mortality for both one- and two-stage embolization of the arterioportal shunt.Majlesara A, Golriz M, Ramouz A, et al. Portal vein arterialization as a salvage method in advanced hepatopancreatobiliary surgery. Br J Surg. 2024;111.

CONCLUSIONS: PVA can offer an effective solution when hepatic artery reconstruction is not feasible.

PMID:39388018 | DOI:10.1245/s10434-024-16342-1
Survival and cardiovascular disease mortality among primary liver cancer patients: A population-based study

Fetched: October 16th, 2024, 2:01am UTC by Lidong Wang

Heliyon. 2024 Sep 11;10(19):e37869. doi: 10.1016/j.heliyon.2024.e37869. eCollection 2024 Oct 15.

ABSTRACT

BACKGROUND: The prognosis of primary liver cancer (PLC) was influenced by death due to non-cancer causes, particularly death related to cardiovascular disease (CVD). This study aimed to analyze mortality of non-cancer causes and identify the independent risk factors associated with CVD-related deaths in PLC patients.

METHODS: In total, 112140 patients were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Independent risk factors for death from CVD in patients with PLC were identified by Cox proportional hazards model.

RESULTS: The median follow-up time of all PLC patients was 76 months (interquartile range (IQR): 36-129). The median overall survival (OS) was 12 months (IQR: 3-40). Patients with intrahepatic cholangiocarcinoma (ICC) had shorter OS than patients with hepatocellular carcinoma (HCC) (8 vs. 14 months; P < 0.001). A total of 87299 deaths were observed, among which 61477 (70.42 % of all deaths) were from PLC, and 12727 (14.58 % of all deaths) were from other cancers. Of all non-cancer deaths (9276, 10.63 %), 2860(30.86 %) were results of CVD. PLC patients had higher risks on CVD-related deaths, compared with general population (standard mortality ratio, SMR, 2.20; 95 % confidence interval, CI, 2.12-2.28). Typically, the highest SMRs appeared in the first year following cancer diagnosis. The multivariable analysis revealed the characteristics listed as followed to be independently risk factors of CVD: age, male (hazard ratio, HR: 1.248, 95%CI: 1.147-1.359), black race (HR: 1.334, 95%CI: 1.195-1.490), year 2016-2019 of diagnosis (HR 0.758, 95%CI: 0.671-0.856), ICC (HR: 1.202, 95%CI: 1.086-1.330), without surgery (HR: 2.479, 95%CI: 2.266-2.711) and without chemotherapy (HR: 2.211, 95%CI: 2.033-2.403).

CONCLUSION: It is essential to take cardiovascular health into consideration at the time of diagnosis for PLC patients as the risk of CVD mortality is significantly higher than that of general population.

PMID:39386844 | PMC:PMC11462467 | DOI:10.1016/j.heliyon.2024.e37869
Clinicopathological features and surgical treatments of intraductal papillary neoplasm of the bile duct: a case report and literature review

Fetched: October 16th, 2024, 2:01am UTC by Chang Fu

Front Med (Lausanne). 2024 Sep 25;11:1443599. doi: 10.3389/fmed.2024.1443599. eCollection 2024.

ABSTRACT

Intraductal papillary neoplasm of bile duct (IPNB), as a precancerous lesion of cholangiocarcinoma, is a rare biliary tract tumor. A 66-year-old female patient was found to have a bile duct mass by routine examination. The liver function tests and tumor markers were normal. Imaging findings revealed a 2.6 cm mass in the common hepatic duct, accompanied by dilatation of both intrahepatic and extrahepatic bile ducts. The patient underwent open extrahepatic bile duct resection, cholecystectomy and Roux-en-Y hepaticojejunostomy. We also conducted a literature review to summarize the clinicopathological features and surgical treatments of IPNB.

PMID:39386752 | PMC:PMC11461345 | DOI:10.3389/fmed.2024.1443599
Different Etiologies of Dilated Pancreatic Duct Based on Endoscopic Ultrasonography Findings

Fetched: October 16th, 2024, 2:01am UTC by Elham Sobhrakhshankhah

Middle East J Dig Dis. 2024 Jul;16(3):155-159. doi: 10.34172/mejdd.2024.382. Epub 2024 Jul 31.

ABSTRACT

BACKGROUND: Pancreatic duct (PD) dilation could be presented in both benign and malignant diseases. Endoscopic ultrasonography (EUS) is a sensitive modality that provides both structural assessment and tissue sampling. This study aims to explore the importance of PD dilation as a potential indicator related to various pancreatobiliary pathologies identified via EUS.

METHODS: Among 3109 subjects who underwent EUS, 599 had evidence of dilated PD and met the inclusion criteria of this retrospective study. Also, the patients underwent EUS fine needle aspiration (EUS-FNA) to evaluate the etiology when required. All data were extracted from patients' medical records to perform statistical analysis.

RESULTS: The study sample revealed 64% being male with a median age was 65-years. Pancreatic adenocarcinoma was the most common etiology diagnosed in 236 patients (39.4%), followed by sphincter of Oddi dysfunction (SOD) in 13% of subjects. Ampullary carcinoma, common bile duct stone, and cholangiocarcinoma were found at 9.5%, 8.8%, and 6.8%, respectively. Abdominal pain was the most common symptom seen in 440 (73.4%) patients. Opium consumption was reported in 170 (28.4%) subjects. Opium consumption was significantly more prevalent in patients with SOD (P<0.05).

CONCLUSION: We suggest that PD dilation could be associated with a wide range of pancreaticobiliary pathologies, especially pancreatic neoplasms. In this regard, PD dilation should be considered as a crucial indicator of pancreatic neoplasm despite it may be associated with no clear etiologies.

PMID:39386335 | PMC:PMC11459282 | DOI:10.34172/mejdd.2024.382
Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study

Fetched: October 16th, 2024, 2:01am UTC by Arunkumar Krishnan

J Clin Transl Endocrinol. 2024 Sep 18;38:100370. doi: 10.1016/j.jcte.2024.100370. eCollection 2024 Dec.

ABSTRACT

AIM: To examine the association between the use of incretin-based drugs [glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is)] and the risk of cholangiocarcinoma (CCA) in the United States.

METHODS: This large population-based, retrospective cohort study using the TriNetX datasets included adult patients with type 2 diabetes mellitus (T2DM) who were new users of GLP-1RAs, DPP-4Is, or other second- or third-line antidiabetic drugs between 2010 and 2021. The primary outcome was the incidence of CCA.

RESULTS: A total of 3,816,071 patients were included (mean age, 61.4 years, female, 49.3 %). A 51 % and 23 % risk reduction in CCA after 1 year of exposure to GLP-1RAs (hazard ratio 0.49; 95 % CI 0.40-0.60) and DPP4Is (0.77, 95 % CI 0.67-0.90), respectively compared to new second-or third-line users. Results were consistent at 3, 5, and 7 years of follow-up (0.66, 0.71, and 0.72 for GLP-1RAs and 0.84, 0.87, and 0.85 for DPP-4Is, respectively). Compared to new metformin users, GLP-1RA users were associated with a 42 % lower risk of developing CCA, whereas DPP-4I group was not associated with an increased risk.

CONCLUSIONS: GLP-1RAs and DPP-4Is were not associated with a significantly increased risk of CCA. GLP-1RAs even showed a reduced risk of CCA development. They can be considered as safe and effective treatment options for patients with T2DM at risk of CCA.

PMID:39386155 | PMC:PMC11460491 | DOI:10.1016/j.jcte.2024.100370
Dunking Pancreaticojejunostomy With Braun's Jejunojejunostomy: Perioperative Outcomes of a Hundred Pancreaticoduodenectomies

Fetched: October 16th, 2024, 2:01am UTC by Sampanna Pandey

Cureus. 2024 Sep 9;16(9):e68988. doi: 10.7759/cureus.68988. eCollection 2024 Sep.

ABSTRACT

Background The optimal surgical technique for pancreaticojejunostomy (PJ) following pancreaticoduodenectomy (PD) is still debated. Dunking and duct-to-mucosa PJ are the most commonly adopted techniques. Incorporating Braun's jejunojejunostomy (JJ) could reduce the incidence and severity of delayed gastric emptying (DGE). This retrospective descriptive study seeks to clarify the outcomes of dunking PJ with Braun's JJ in 100 PD patients. Methodology We retrospectively reviewed 100 patients who underwent PDs in a single unit of the Department of Surgical Gastroenterology of Tribhuvan University Teaching Hospital from October 2012 to February 2023. Demographic and historical data, indications, procedure-related data, complications, and mortality data were collected and analyzed. Results The mean age was 50.96 Â± 14.97 years, and 64 (64%) were males. The most common indication was ampullary carcinoma (53, 53%) followed by distal cholangiocarcinoma (18, 18%) and pancreatic ductal adenocarcinoma (7, 7%). Operative time was 5.83 Â± 1.09 hours, intraoperative blood loss was 515 Â± 194 mL, and the average time for PJ and Braun's JJ was 22 Â± 6 and 15 Â± 3 minutes, respectively. Soft pancreas was encountered in 52 (52%) patients and clinically significant postoperative pancreatic fistula (Grade B, C) was seen in 23 (23%). Postpancreatectomy hemorrhage was seen in 21 (21%) patients (Grades A: 3, B: 12, C: 6). DGE (Grade B) occurred in two (2%) patients, and bile leak was observed in 4% of patients (Grades A: 1, B: 2, C: 1). Major complications (Clavien-Dindo â‰¥IIIA) occurred in 24%, and 11 patients died. Conclusions The dunking technique is easily adaptable, less time-consuming, and can be performed in the pancreas of any texture or duct size but is associated with an increased incidence of post-pancreatectomy hemorrhage. Incorporation of Braun's anastomosis lowers DGE, allows early initiation of feeding, and reduces complication rates.

PMID:39385867 | PMC:PMC11463102 | DOI:10.7759/cureus.68988
Tumor budding in pre-neoadjuvant biopsy and post-neoadjuvant resection specimens is associated with poor prognosis in intrahepatic cholangiocarcinoma-a cohort study of 147 cases by modified ITBCC criteria

Fetched: October 16th, 2024, 2:01am UTC by Gaohua Wu

Virchows Arch. 2024 Oct 10. doi: 10.1007/s00428-024-03937-y. Online ahead of print.

ABSTRACT

Tumor budding (TB) has been associated with poor survival in a variety of cancers including intrahepatic cholangiocarcinoma (iCCA). As tumor histomorphological features are significantly altered after neoadjuvant therapy (NAT), our study aims to assess the prognostic significance of TB in iCCA patients before and after NAT, by the modified International Tumor Budding Consensus Conference (ITBCC) criteria. 147 NAT-treated iCCA cases were included in this study. In biopsy specimens obtained before NAT, the TB-positive subgroup had lower overall survival (OS) in univariate analysis (P = 0.010). In resection specimens obtained after NAT, the TB-positive subgroup had reduced OS (P = 0.002) and recurrence-free survival (RFS) (P = 0.013) in univariate analysis. In multivariate analysis including TNM stage, lymphovascular invasion and perineural invasion, TB-positive in post-NAT resection was also found as an independent prognostic factor for both OS and RFS (OS, HR, 3.005; 95% CI, 1.333-6.775, P = 0.008; RFS, HR, 1.748; 95% CI, 1.085-2.816, P = 0.022). In conclusion, assessing the presence of TB by modified ITBCC criteria provides robust prognostic information in the NAT setting of iCCA patients and can be considered to be included in routine pathological reporting.

PMID:39384623 | DOI:10.1007/s00428-024-03937-y
Amputation neuroma with a difficult differential diagnosis from perihilar cholangiocarcinoma:a case report

Fetched: October 16th, 2024, 2:01am UTC by Shinya Yamaga

Nihon Shokakibyo Gakkai Zasshi. 2024;121(10):842-850. doi: 10.11405/nisshoshi.121.842.

ABSTRACT

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

PMID:39384397 | DOI:10.11405/nisshoshi.121.842
Pharmacological characteristics and clinical effectiveness of Futibatinib (LytgobiÂ® Tablets), a covalently-binding, irreversible FGFR1-4 inhibitor

Fetched: October 16th, 2024, 2:01am UTC by Katsuya Takagaki

Nihon Yakurigaku Zasshi. 2024 Oct 10. doi: 10.1254/fpj.24045. Online ahead of print.

ABSTRACT

Futibatinib (LytgobiÂ® Tablets 4 â€mg), a novel fibroblast growth factor receptor (FGFR) inhibitor developed by Taiho Pharmaceutical using the Cysteinomix Drug Discovery Platform, was approved in Japan in June 2023 for the treatment of patients with unresectable biliary tract cancer with FGFR2 fusion or rearrangement that had progressed after at least one prior chemotherapy. Futibatinib covalently binds to the cysteine residue in the FGFR kinase domain P-loop structure and is believed to exert antitumor activity by selectively and irreversibly inhibiting FGFR1-4. Many FGFR inhibitors under development are ATP-competitive; however, futibatinib is the first approved covalently-binding irreversible FGFR inhibitor. It inhibits cell proliferation by inhibiting FGFR phosphorylation and its downstream signaling pathways in cancer cell lines. Futibatinib showed inhibitory activity against a wider range of FGFR mutants than ATP-competitive, reversible FGFR inhibitors and inhibited cell proliferation without significantly deviating from the inhibitory effect on wild-type FGFR. Futibatinib showed antitumor efficacy in mice subcutaneously transplanted with human tumor cell lines driven by FGFR. The international phase 2 study (TAS-120-101) was conducted in patients with refractory intrahepatic cholangiocarcinoma with FGFR2 fusion or rearrangement. The overall response rate was 41.7%, showing consistent efficacy regardless of co-occurring genomic alterations. Although some typical FGFR inhibitor-related side effects were observed, they were manageable and futibatinib had a good safety profile. Futibatinib is an important drug for biliary tract cancer, which has limited treatment options; its development is underway for other types of cancer, and it is expected to benefit more patients.

PMID:39384389 | DOI:10.1254/fpj.24045
The preoperative recurrence score: Predicting early recurrence in peri-hilar cholangiocarcinoma

Fetched: October 16th, 2024, 2:01am UTC by Simone Conci

Eur J Surg Oncol. 2024 Oct 5;50(12):108745. doi: 10.1016/j.ejso.2024.108745. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite advances in surgical techniques, the rate of early recurrence in perihilar cholangiocarcinoma (PCC) remains high. We sought to develop the Preoperative Recurrence Score (PRS), a model to estimate the risk of early recurrence after resection based on preoperative radiological characteristics.

MATERIALS AND METHODS: Data of patients who underwent surgery for PCC were retrospectively collected, and preoperative imaging was reviewed to assess tumor characteristics. A model to assess the risk of early recurrence based on preoperative radiologic characteristics was internally developed and externally validated on two cohorts of patients from two European major hepatobiliary surgery referral centers.

RESULTS: A total of 215 patients among three different patient cohorts were included in the study. Tumor size â‰¥18 mm (HR 2.70, 95 % CI 1.48-4.92, p = 0.001), macroscopic portal vein involvement (HR 2.28, 95%CI 1.19-4.34, p = 0.013), hepatic arteries involvement (HR 2.44, 95%CI 1.26-4.71, p = 0.008), and presence of suspicious lymph nodes (HR 1.98, 95%CI 1.02-3.83, p = 0.043) were significantly associated with recurrence-free survival (RFS). The model showed excellent discrimination both on the internal (AUC 0.83) and external validation cohorts (external 1: AUC 0.84; external 2: AUC 0.70). High PRS was associated with worse RFS among all three cohorts, with a 1-year recurrence probability of 80.1 %, 100.0 %, and 54.2 % in the internal and external validation cohorts 1 and 2, respectively.

CONCLUSIONS: The PRS is a simple tool that can accurately assess the risk of early recurrence in patients with PCC. Up-front surgery should be carefully evaluated in patients with high PRS, as it could result in a futile resection.

PMID:39383775 | DOI:10.1016/j.ejso.2024.108745
Gallbladder tuberculosis mimicking carcinoma: A case report of a rare entity

Fetched: September 4th, 2024, 2:02am UTC by Arkadeep Dhali

Int J Surg Case Rep. 2024 Aug 31;123:110228. doi: 10.1016/j.ijscr.2024.110228. Online ahead of print.

ABSTRACT

INTRODUCTION: Gallbladder TB (GBTB) is a rare disease with a non-specific presentation, simulating cholecystitis and gallbladder malignancies. We describe a rare case of infiltrative GBTB with biliary strictures in a young female who was initially diagnosed with metastatic gallbladder carcinoma.

CASE PRESENTATION: A 33-year-old female presented with recurrent episodes of obstructive jaundice, significant weight loss, fatigue, and oligomenorrhoea. Imaging studies revealed features of locally advanced gallbladder carcinoma with proximal and distal common bile duct strictures. However, biopsy of the liver tissue surrounding the gallbladder mass confirmed necrotizing granulomatous inflammation with similar findings from fine needle aspiration of the cervical lymph node. Along with the histopathological findings, radiological evidence of pulmonary tuberculosis confirmed the diagnosis of infiltrative GBTB. The patient was successfully managed with anti-tubercular drugs along with biliary decompression.

DISCUSSION: The rarity of GBTB is attributed to the high alkalinity of bile and bile acids, which afford protection against tubercle bacilli. Patients commonly present with abdominal pain, fever, abdominal lump, anorexia, and weight loss. Biliary strictures, though rare, have been described in GBTB and simulate cholangiocarcinoma. Due to the non-specific findings of pre-operative laboratory and radiological investigations, most patients are taken up for surgery and diagnosed with TB on post-operative histological analysis.

CONCLUSION: Gallbladder TB is a rare disease which poses a diagnostic challenge because it lacks any pathognomonic features. A tissue diagnosis must be carried out before confirming gallbladder and biliary tract malignancies. Physicians in TB-endemic regions should possess a high index of suspicion for diagnosing GBTB.

PMID:39226636 | DOI:10.1016/j.ijscr.2024.110228
Understanding and Overcoming Resistance to Selective FGFR inhibitors Across FGFR2-Driven Malignancies

Fetched: September 4th, 2024, 2:02am UTC by Francesco Facchinetti

Clin Cancer Res. 2024 Sep 3. doi: 10.1158/1078-0432.CCR-24-1834. Online ahead of print.

ABSTRACT

PURPOSE: Understanding resistance to selective FGFR inhibitors is crucial to improve the clinical outcomes of patients with FGFR2-driven malignancies.

EXPERIMENTAL DESIGN: We analyzed sequential ctDNA, +/- WES or targeted NGS on tissue biopsies from patients with tumors harboring activating FGFR2 alterations progressing on pan-FGFR-selective inhibitors, collected in the prospective UNLOCK program. FGFR2::BICC1 Ba/F3 and patient-derived xenografts (PDX) models were used for functional studies.

RESULTS: Thirty-six patients were included. In cholangiocarcinoma, at resistance to both reversible inhibitors (e.g. pemigatinib, erdafitinib) and the irreversible inhibitor futibatinib, polyclonal FGFR2 kinase domain mutations were frequent (14/27 patients). Tumors other than cholangiocarcinoma shared the same mutated FGFR2 residues, but polyclonality was rare (1/9 patients). At resistance to reversible inhibitors, 14 residues in the FGFR2 kinase domain were mutated; after futibatinib, only the molecular brake N550 and the gatekeeper V565. Off-target alterations in PI3K/mTOR and MAPK pathways were found in 11 patients, often together with on-target mutations. At progression to a first FGFR inhibitor, 12 patients received futibatinib or lirafugratinib (irreversible inhibitors), with variable clinical outcomes depending on previous resistance mechanisms. Two patients with TSC1 or PIK3CA mutations benefitted from everolimus. In cell viability assays on Ba/F3 and in pharmacologic studies on PDX, irreversible inhibitors retained better activity against FGFR2 kinase domain mutations, with lirafugratinib active against the recalcitrant V565L/F/Y.

CONCLUSIONS: At progression to FGFR inhibitors, FGFR2-driven malignancies are characterized by high intra- and inter-patient molecular heterogeneity, particularly in cholangiocarcinoma. Resistance to FGFR inhibitors can be overcome by sequential, molecularly-oriented treatment strategies across FGFR2-driven tumors.

PMID:39226398 | DOI:10.1158/1078-0432.CCR-24-1834
Telotristat ethyl, a tryptophan hydroxylase inhibitor, enhances antitumor efficacy of standard chemotherapy in preclinical cholangiocarcinoma models

Fetched: September 4th, 2024, 2:02am UTC by Niranjan Awasthi

J Cell Mol Med. 2024 Sep;28(17):e18585. doi: 10.1111/jcmm.18585.

ABSTRACT

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer, carries a grim prognosis with a 5-year survival rate of 5%-15%. Standard chemotherapy regimens for CCA, gemcitabine plus cisplatin (GemCis) or its recently approved combination with durvalumab demonstrate dismal clinical activity, yielding a median survival of 12-14 months. Increased serotonin accumulation and secretion have been implicated in the oncogenic activity of CCA. This study investigated the therapeutic efficacy of telotristat ethyl (TE), a tryptophan hydroxylase inhibitor blocking serotonin biosynthesis, in combination with standard chemotherapies in preclinical CCA models. Nab-paclitaxel (NPT) significantly enhanced animal survival (60%), surpassing the marginal effects of TE (11%) or GemCis (9%) in peritoneal dissemination xenografts. Combining TE with GemCis (26%) or NPT (68%) further increased survival rates. In intrahepatic (iCCA), distal (dCCA) and perihilar (pCCA) subcutaneous xenografts, TE exhibited substantial tumour growth inhibition (41%-53%) compared to NPT (56%-69%) or GemCis (37%-58%). The combination of TE with chemotherapy demonstrated enhanced tumour growth inhibition in all three cell-derived xenografts (67%-90%). PDX studies revealed TE's marked inhibition of tumour growth (40%-73%) compared to GemCis (80%-86%) or NPT (57%-76%). Again, combining TE with chemotherapy exhibited an additive effect. Tumour cell proliferation reduction aligned with tumour growth inhibition in all CDX and PDX tumours. Furthermore, TE treatment consistently decreased serotonin levels in all tumours under all therapeutic conditions. This investigation decisively demonstrated the antitumor efficacy of TE across a spectrum of CCA preclinical models, suggesting that combination therapies involving TE, particularly for patients exhibiting serotonin overexpression, hold the promise of improving clinical CCA therapy.

PMID:39223878 | DOI:10.1111/jcmm.18585
Teaching Strategies to Enhance Knowledge and Understanding of Opisthorchis viverrini and Cholangiocarcinoma in Thailand: Lessons for Asian Countries

Fetched: September 3rd, 2024, 2:01am UTC by Sirapatsorn Moonsan

J Cancer Educ. 2024 Sep 2. doi: 10.1007/s13187-024-02498-7. Online ahead of print.

ABSTRACT

Although Opisthorchis viverrini (OV) is a neglected tropical disease, the International Agency for Research on Cancer (IARC) listed it as a human carcinogen 30 years ago. Cholangiocarcinoma (CCA) is the ultimate pathology outcome. However, it remains a significant public health problem in the Greater Mekong Subregion and Asia. Its widespread impact on human health requires urgent action using various strategies. This study aimed to investigate and prioritize the need for developing teaching and learning management of OV and CCA among primary school students in Thailand endemic areas. The samples consisted of 36 Grade 6 students. This study was conducted by using a needs questionnaire. Data were analyzed using Mean and Standard Deviation. The needs were prioritized using the Modified Priority Needs Index (PNI modified). The findings revealed a moderate overall need for teaching and learning management development. The area with the highest need was learning activity organization (PNI = 0.410), followed by audiovisual equipment (PNI = 0.276) and buildings (PNI = 0.265). The teaching content the students needed most included CCA prevention, risk factors, and disease symptoms (58.33%). Based on the findings, it is suggested that teachers design various learning activities and emphasize hands-on activities for students. Additionally, administrators should allocate budgets to improve buildings and audiovisual equipment, and relevant organizations should establish policies to promote learning on these issues in educational institutions. Essential lessons from this study can provide a starting point for executives and public health personnel worldwide to apply to develop educational strategies for cancer education and cancer prevention and control.

PMID:39223426 | DOI:10.1007/s13187-024-02498-7
Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer

Fetched: September 3rd, 2024, 2:01am UTC by Yoshiyuki Shibata

World J Gastrointest Surg. 2024 Aug 27;16(8):2555-2564. doi: 10.4240/wjgs.v16.i8.2555.

ABSTRACT

BACKGROUND: Recent advancements in biliary tract cancer (BTC) treatment have expanded beyond surgery to include adjuvant therapy, yet the prognosis remains poor. Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.

AIM: To determine transmembrane serine protease 4 (TMPRSS4) utility as a prognostic biomarker of radical resection for BTC.

METHODS: Medical records of patients who underwent radical resection for BTC, excluding intrahepatic cholangiocarcinoma, were retrospectively reviewed. The associations between TMPRSS4 expression and clinicopathological factors, overall survival, and recurrence-free survival were analyzed.

RESULTS: Among the 85 patients undergoing radical resection for BTC, 46 (54%) were TMPRSS4-positive. The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9 (CA19-9) values and greater lymphatic invasion than the TMPRSS4-negative group (P = 0.019 and 0.039, respectively). Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group (median survival time: 25.3 months vs not reached, P < 0.001; median survival time: 28.7 months vs not reached, P = 0.043, respectively). Multivariate overall survival analysis indicated TMPRSS4 positivity, pT3/T4, and resection status R1 were independently associated with poor prognosis (P = 0.032, 0.035 and 0.030, respectively). TMPRSS4 positivity correlated with preoperative CA19-9 values â‰¥ 37 U/mL and pathological tumor size â‰¥ 30 mm (P = 0.016 and 0.038, respectively).

CONCLUSION: TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

PMID:39220090 | PMC:PMC11362932 | DOI:10.4240/wjgs.v16.i8.2555
Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

Fetched: September 3rd, 2024, 2:01am UTC by Lewis A Hall

World J Gastrointest Surg. 2024 Aug 27;16(8):2689-2701. doi: 10.4240/wjgs.v16.i8.2689.

ABSTRACT

BACKGROUND: The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse.

AIM: To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement.

METHODS: A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected.

RESULTS: Twelve studies were included. The definition of "unresectable" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively.

CONCLUSION: Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network^Â® criteria for pancreatic ductal adenocarcinoma.

PMID:39220089 | PMC:PMC11362928 | DOI:10.4240/wjgs.v16.i8.2689
New oncological indications for liver transplantation

Fetched: September 3rd, 2024, 2:01am UTC by Massimo Leo

Rev Med Suisse. 2024 Aug 28;20(884):1478-1482. doi: 10.53738/REVMED.2024.20.884.1478.

ABSTRACT

Transplantation oncology represents a specificity of liver transplantation. Hepatocellular carcinoma is now an accepted indication with very good long-term results. Cholangiocarcinoma, hepatic -metastases from colorectal cancer and neuroendocrine tumors are emerging indications with outcome superior to those that can be achieved with systemic treatments in very selected patients.

PMID:39219389 | DOI:10.53738/REVMED.2024.20.884.1478
Comment On: "Preoperative Platelet Count as an Independent Predictor of Long-Term Outcomes Among Patients Undergoing Resection for Intrahepatic Cholangiocarcinoma"

Fetched: September 3rd, 2024, 2:01am UTC by Qingqing Zhao

J Surg Oncol. 2024 Sep 1. doi: 10.1002/jso.27864. Online ahead of print.

NO ABSTRACT

PMID:39219051 | DOI:10.1002/jso.27864
HSPB8-BAG3 chaperone complex modulates cell invasion in intrahepatic cholangiocarcinoma by regulating CASA-mediated Filamin A degradation

Fetched: September 1st, 2024, 2:01am UTC by Bo Shu

Cancer Biol Ther. 2024 Dec 31;25(1):2396694. doi: 10.1080/15384047.2024.2396694. Epub 2024 Aug 31.

ABSTRACT

The incidence of intrahepatic cholangiocarcinoma (ICC) is steadily rising, and it is associated with a high mortality rate. Clinical samples were collected to detect the expression of HSPB8 and BAG3 in ICC tissues. ICC cells were cultured and transfected with plasmids that overexpressed or silenced specific genes to investigate the impact of gene expression alterations on cell function. qPCR and Western blot techniques were utilized to measure gene and protein expression levels. A wound healing assay was conducted to assess cell migration ability. The Transwell assay was used to assess cell invasion ability. Co-IP was used to verify the binding relationship between HSPB8 and BAG3. The effects of HSPB8 and BAG3 on lung metastasis of tumors in vivo were verified by constructing a metastatic tumor model. Through the above experiments, we discovered that the expressions of HSPB8 and BAG3 were up-regulated in ICC tissues and cells, and their expressions were positively correlated. The metastatic ability of ICC cells could be promoted or inhibited by upregulating or downregulating the expression of BAG3. Furthermore, the HSPB8-BAG3 chaperone complex resulted in the abnormal degradation of Filamin A by activating autophagy. Increased expression of Filamin A inhibits the migration and invasion of ICC cells. Overexpression of HSPB8 and BAG3 in vivo promoted the lung metastasis ability of ICC cells. The HSPB8-BAG3 chaperone complex promotes ICC cell migration and invasion by regulating CASA-mediated degradation of Filamin A, offering insights for enhancing ICC therapeutic strategies.

PMID:39215616 | DOI:10.1080/15384047.2024.2396694
Cannabidiol exhibits potent anti-cancer activity against gemcitabine-resistant cholangiocarcinoma via ER-stress induction in vitro and in vivo

Fetched: September 1st, 2024, 2:01am UTC by Thatsanapong Pongking

BMC Complement Med Ther. 2024 Aug 30;24(1):325. doi: 10.1186/s12906-024-04610-2.

ABSTRACT

BACKGROUND: Failure of treatment with gemcitabine in most cholangiocarcinoma (CCA) patients is due to drug resistance. The therapeutic potential of natural plant secondary compounds with minimal toxicity, such as cannabidiol (CBD), is a promising line of investigation in gemcitabine-resistant CCA. We aim to investigate the effects of CBD on gemcitabine-resistant CCA (KKU-213B^GemR) cells in vitro and in vivo.

MATERIALS: In vitro, cell proliferation, colony formation, apoptosis and cell cycle arrest were assessed using MTT assay, clonogenicity assay and flow cytometry. The effect of CBD on ROS production was evaluated using the DCFH-DA fluorescent probe. The mechanism exerted by CBD on ER stress-associated apoptosis was investigated by western blot analysis. A gemcitabine-resistant CCA xenograft model was also used and the expression of PCNA and CHOP were evaluated by immunohistochemical analysis.

RESULTS: The IC50 values of CBD for KKU-213B^GemR cells ranged from 19.66 to 21.05 ÂµM. For a non-cancerous immortalized fibroblast cell line, relevant values were 18.29 to 19.21 ÂµM. CBD suppressed colony formation by KKU-213B^GemR cells in a dose-dependent manner in the range of 10 to 30 ÂµM. CBD at 30 ÂµM significantly increased apoptosis at early (16.37%) (P = 0.0024) and late (1.8%) stages (P < 0.0001), for a total of 18.17% apoptosis (P = 0.0017), in part by increasing ROS production (P < 0.0001). Multiphase cell cycle arrest significantly increased at G0/G1 with CBD 10 and 20 ÂµM (P = 0.004 and P = 0.017), and at G2/M with CBD 30 ÂµM (P = 0.005). CBD treatment resulted in increased expression of ER stress-associated apoptosis proteins, including p-PERK, BiP, ATF4, CHOP, BAX, and cytochrome c. In xenografted mouse, CBD significantly suppressed tumors at 10 and 40 mg/kgÂ·Bw (P = 0.0007 and P = 0.0278, respectively), which was supported by an increase in CHOP, but a decrease in PCNA expression in tumor tissues (P < 0.0001).

CONCLUSION: The results suggest that CBD exhibits potent anti-cancer activity against gemcitabine-resistant CCA in vitro and in vivo, in part via ER stress-mediated mechanisms. These results indicate that clinical explorative use of CBD on gemcitabine-resistant CCA patients is warranted.

PMID:39215312 | PMC:PMC11365133 | DOI:10.1186/s12906-024-04610-2
Gradual Telomere Shortening in the Tumorigenesis of Pancreatic and Hepatic Mucinous Cystic Neoplasms

Fetched: September 1st, 2024, 2:01am UTC by You-Na Sung

Hum Pathol. 2024 Aug 28;152:105653. doi: 10.1016/j.humpath.2024.105653. Online ahead of print.

ABSTRACT

Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 Â± 0.78), ovarian-type stroma (2.90 Â± 0.93), non-mucinous lining epithelium (2.84 Â± 0.79), mucinous lining epithelium (2.49 Â± 0.93), and adenocarcinoma (1.19 Â± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.

PMID:39214240 | DOI:10.1016/j.humpath.2024.105653
Tumor burden score is superior to primary liver cancer stages in predicting prognosis for patients with combined hepatocellular-cholangiocarcinoma after surgery: A multi-center study

Fetched: September 1st, 2024, 2:01am UTC by Chuang Jiang

Eur J Surg Oncol. 2024 Aug 22;50(11):108610. doi: 10.1016/j.ejso.2024.108610. Online ahead of print.

ABSTRACT

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial.

METHODS: Patients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation.

RESULTS: A total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results.

CONCLUSIONS: TBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions.

PMID:39213695 | DOI:10.1016/j.ejso.2024.108610
Cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Matthew E Dixon

Cancer Treat Res. 2024;192:165-184. doi: 10.1007/978-3-031-61238-1_9.

ABSTRACT

Cholangiocarcinoma (CC) is a heterogeneous group of malignancies that originates at any point along the biliary tree. CC is an uncommon malignancy as it represents approximately 3% of all gastrointestinal malignancies, though its global incidence is rising. CC can often be asymptomatic in its early stages and as a result, it is frequently diagnosed in later stages, leading to challenges in clinical management.

PMID:39212921 | DOI:10.1007/978-3-031-61238-1_9
A Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma With Massive Multinucleated Giant Cell Reaction

Fetched: September 1st, 2024, 2:01am UTC by Fang Luyao

Int J Surg Pathol. 2024 Aug 30:10668969241268392. doi: 10.1177/10668969241268392. Online ahead of print.

ABSTRACT

Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare liver tumor that appears as a hepatic nodule on imaging with a specific pathological pattern, and the definitive diagnosis relies on its pathological histomorphology, immunophenotype, and Epstein-Barr encoding region test. Radical surgical resection is the primary treatment modality, and immunotherapy is expected to be a new adjuvant treatment option. LEL-ICC with massive multinucleated giant cell infiltration has not been reported so far. In this article, we report a patient with LEL-ICC showing massive multinucleated giant cell infiltration, review the relevant literature, and analyze its clinicopathological features and prognosis to accumulate experience for the accurate diagnosis of LEL-ICC.

PMID:39211988 | DOI:10.1177/10668969241268392
Type I choledochal cyst. Total laparoscopic resection and Roux-en-Y reconstruction to two separated ducts

Fetched: September 1st, 2024, 2:01am UTC by Natalia Reyes

J Surg Case Rep. 2024 Aug 28;2024(8):rjae543. doi: 10.1093/jscr/rjae543. eCollection 2024 Aug.

ABSTRACT

A choledochal cyst is a rare condition that requires surgical treatment to prevent complications, such as obstructive jaundice, cyst rupture, cholangitis, and the risk of malignancy. Complete cyst excision is considered the best option, as it reduces the risk of inflammation and the development of cholangiocarcinoma. Therefore, cholecystectomy and complete cyst resection followed by reconstruction with a Roux-en-Y hepaticojejunostomy is the treatment of choice. We present a case (with video) that shows the complete resection of a type I choledochal cyst with Roux-en-Y reconstruction of two separate ducts since the right posterior duct reached the cyst independently. The laparoscopic approach offers all the advantages of mini-invasive surgery and better visualization of the structures; however, biliary reconstruction to fine ducts implies a surgical challenge that requires high training in mini-invasive surgery.

PMID:39211375 | PMC:PMC11358056 | DOI:10.1093/jscr/rjae543
The Italian experience on liver transplantation for unresectable peri-hilar cholangiocarcinoma: a national survey and future perspectives

Fetched: September 1st, 2024, 2:01am UTC by Enrico Gringeri

Updates Surg. 2024 Aug 29. doi: 10.1007/s13304-024-01889-1. Online ahead of print.

ABSTRACT

Liver transplantation (LT) was considered an ineffective treatment for perihilar cholangiocarcinoma (pCCA) until the successful experience of the Mayo Clinic, proposing a protocol with strict inclusion criteria and neoadjuvant radio-chemotherapy. Since 2015, pCCA is considered an indication for LT in Italy only in the context of controlled prospective studies. We performed a survey among the 22 Italian Liver Transplant Centers to assess the results of LT for pCCA. Eight centers reported 53 cases from 1986 to 2021 (Bologna 12, Padova 10, Niguarda 10, Milano Tumori 8, Torino 5, Pisa 4, Ancona 2, Modena 2). Patients were divided according to whether they recieved neoadjuvant radio-chemotherapy (Group 1, 25 cases) or not (Group 2, 28 cases). Eleven patients were transplanted without neoadjuvant treatment after 2015. Overall survival at 1, 3 and 5 years was 83.8%, 56.6% and 50.6% in Group 1 and 72.4%, 41.4% and 35.5% in Gropu 2 (p = 0.13). Recurrence-free survival at 1, 3, and 5 years was 91.2%, 61.1% and 47.2% in Group 1 and 58.2%, 42.2%, and 36.1% in Group 2 (p = 0.16). A competing risk regression analysis showed a 5-year risk of cancer-related death of 19% for patients in Group 1 against 62.3% in Group 2, with a hazard ratio of 0.31 (95%CI [0.10-0.98], p 0.047). This survey promoted a discussion about the limitations of the Mayo protocol and set the basis for the adoption of a new nationwide protocol (LITHALICA-NCT06125769), having the same inclusion criteria but proposing standard of care chemotherapy as neoadjuvant regimen.

PMID:39210194 | DOI:10.1007/s13304-024-01889-1
ZNF460-mediated upregulation of APCDD1L-DT promotes cholangiocarcinoma development by inhibiting the ubiquitin-mediated degradation of DVL2

Fetched: September 1st, 2024, 2:01am UTC by Xin Gao

Cancer Gene Ther. 2024 Aug 30. doi: 10.1038/s41417-024-00826-z. Online ahead of print.

ABSTRACT

Cholangiocarcinoma (CCA), known for its aggressive nature, poses a formidable challenge in the current medical landscape, particularly in targeted therapies. Against this backdrop, long non-coding RNAs (lncRNAs) have captured the attention of researchers. These unique RNAs are believed to play pivotal roles in various cancers, offering promising avenues for the development of more effective treatment strategies. Previous studies have substantiated the aberrant expression of the APCDD1L-DT in numerous human tumors, demonstrating its positive regulatory roles in disease progression. Nevertheless, the biological functions of APCDD1L-DT in CCA are still not fully understood. This study marks the inaugural documentation of APCDD1L-DT exhibiting aberrant expression in CCA specimen, establishing a close correlation with the TNM staging of tumor patients. Furthermore, suppressing APCDD1L-DT expression hinders both the viability and motility of tumor cells. Mechanistically, the abnormal activation of the transcription factor ZNF460 positively regulated APCDD1L-DT expression in CCA. This activation, in turn, propels the abnormal activation of the Wnt pathway, fostering tumor development by impeding the ubiquitin-mediated degradation of DVL2. Broadly speaking, this study provides auspicious perspectives for comprehending CCA and furnishes support for addressing this daunting malignancy.

PMID:39210030 | DOI:10.1038/s41417-024-00826-z
Track Seeding from Percutaneous Biliary Drainage in a Case of Cholangiocarcinoma: Impact on Transplant Eligibility

Fetched: September 1st, 2024, 2:01am UTC by Ahmad Arar

Cardiovasc Intervent Radiol. 2024 Aug 29. doi: 10.1007/s00270-024-03848-0. Online ahead of print.

NO ABSTRACT

PMID:39210003 | DOI:10.1007/s00270-024-03848-0
Haemobilia as a primary presentation of cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Peter Stapleton

BMJ Case Rep. 2024 Aug 29;17(8):e260524. doi: 10.1136/bcr-2024-260524.

ABSTRACT

We present a case of haemobilia as a primary presentation for underlying cholangiocarcinoma. A man in his 50s initially presented to emergency with Quincke's triad, RUQ pain, jaundice and UGI bleeding. The initial diagnosis of haemobilia was made on endoscopic retrograde cholangiopancreatography (ERCP) on primary presentation, but the presence of blood and the recurrent clot obstruction of the biliary tract made the underlying diagnosis extremely difficult, resulting in the patient having 4 ERCP, 1 spyglass and multiple CTs and magnetic resonance cholangiopancreatography. Eventually, the patient underwent a Whipple's procedure without tissue diagnosis, confirming cholangiocarcinoma on histopathology. This case emphasises the difficulty of diagnosis of underlying malignancy in the setting of haemobilia, the benefit of multidisciplinary meeting discussions to support significant interventions and the need to be cautious and curious when managing atypical presentations.

PMID:39209753 | DOI:10.1136/bcr-2024-260524
Utilization of an artificial intelligence-enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study

Fetched: September 1st, 2024, 2:01am UTC by Neil B Marya

Cancer Cytopathol. 2024 Aug 29. doi: 10.1002/cncy.22898. Online ahead of print.

ABSTRACT

BACKGROUND: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool.

METHODS: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being "positive," "negative," or "indeterminate." The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared.

RESULTS: Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622-0.859), CADe (0.807; 95% CI, 0.750-0.856), and OCI (0.807; 95% CI, 0.671-0.900) were similar.

CONCLUSIONS: This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

PMID:39207803 | DOI:10.1002/cncy.22898
Computed tomography-guided radioactive iodine-125 seed implantation for liver malignancies in challenging locations

Fetched: September 1st, 2024, 2:01am UTC by Lin Li

J Cancer Res Ther. 2024 Aug 1;20(4):1165-1172. doi: 10.4103/jcrt.jcrt_2638_22. Epub 2024 Aug 29.

ABSTRACT

AIMS: This study aimed to retrospectively assess the safety and efficacy of radioactive iodine-125 (I-125) seed implantation for liver malignancies in challenging locations.

MATERIALS AND METHODS: Between December 2015 and December 2021, 49 patients with 60 liver malignancies in challenging locations who underwent computed tomography (CT)-guided I-125 seed implantation were retrospectively analyzed. The primary endpoints included technical success rate and overall survival (OS), whereas the secondary endpoints included progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and liver recurrence. Potential factors associated with liver recurrence were also evaluated.

RESULTS: The technical success rate was 100%. The median follow-up duration was 12 months (range, 2-68 months). The mean OS and PFS were 17.58 months (95% CI: 13.64-21.52 months) and 13.14 months (95% CI: 10.36-15.92 months), respectively. The 2-month, 6-month, and 1-year DCR and ORR were 97.96% and 93.88%, 93.75% and 77.08%, and 93.48% and 60.87%, respectively. The 6- and 12-month tumor recurrence rates were 20.41% and 28.26%, respectively. The Kaplan-Meier method was used to estimate the time of liver recurrence, with our results showing that patients with primary intrahepatic cholangiocarcinoma had an increased likelihood of having earlier liver recurrence. No major complications developed during follow-up.

CONCLUSION: CT-guided radioactive I-125 implantation could be a safe and effective alternative with promising survival benefits and high local control rates for liver malignancies in challenging locations.

PMID:39206978 | DOI:10.4103/jcrt.jcrt_2638_22
Investigation of transcriptional and immunological disparities among patient groups with varied prognostic risk factors in cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Baoluhe Zhang

Cancer Med. 2024 Aug;13(16):e70135. doi: 10.1002/cam4.70135.

ABSTRACT

BACKGROUND: This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA).

METHODS AND RESULTS: The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients.

CONCLUSIONS: In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.

PMID:39206584 | PMC:PMC11358702 | DOI:10.1002/cam4.70135
A Complex Interplay of Tumor Microenvironment Could Enhance Cholangiocarcinoma Progression Even After Surgery: A Prospective Study

Fetched: September 1st, 2024, 2:01am UTC by Asmaa M Zahran

J Clin Med Res. 2024 Aug;16(7-8):363-374. doi: 10.14740/jocmr5201. Epub 2024 Jul 23.

ABSTRACT

BACKGROUND: The current study was conducted to explore the impact of macrophages and programmed cell death protein 1 (PD-1) expression on tumor-infiltrating lymphocytes (TILs) on treatment outcomes and to define the interaction between these factors and the clinicopathologic features of advanced cholangiocarcinoma (CCA) patients.

METHODS: Twenty-five patients with metastatic CCA were recruited for the current study from El-Rajhi Hospital and the Clinical Oncology Department of Assiut University. Additionally, 19 healthy controls were included. Before the flow cytometric detection of immune cells, the diagnosis and staging of CCA were performed based on surgical intervention, imaging, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) determinations. This was followed by flow cytometric detection of CD4⁺, CD8⁺, CD4⁺PD-1⁺, CD8⁺PD-1⁺, and CD11b⁺CD68⁺ macrophages in the peripheral blood of both patients and controls.

RESULTS: The current results revealed higher levels of CD4⁺, CD8⁺, and CD11b⁺CD68⁺ macrophages in controls compared to patients. At the same time, PD-1 expression was significantly higher in patients compared to controls. CD4⁺ was correlated with improved progression-free survival (PFS), while CD8⁺PD-1 was associated with shorter PFS. In general, CD4⁺ and CD8⁺ levels progressively increased with improved response to treatments, differentiation, single organ site metastasis, and surgical interventions. On the contrary, PD-1 expression and macrophages progressively increased with worsening response, dedifferentiation, multiple organ sites, and surgical interventions. The median PFS was 12 months, and the mean Â± standard error (SE) was 13.1 Â± 1.3.

CONCLUSIONS: CCA has a desmoplastic microenvironment with complex immunologic topography and tumor-reactive stroma. The immune landscape of the peripheral blood mononuclear cells (PBMCs) in CCA patients before treatment could reflect the state of systemic immune function and response to treatments. Our results revealed that T-lymphocytes correlated with better prognosis while macrophages and PD-1⁺ expression were associated with poor outcomes.

PMID:39206103 | PMC:PMC11349130 | DOI:10.14740/jocmr5201
Investigation of Social Innovations for Handling Opisthorchis viverrini and Cholangiocarcinoma in Thailand's Highest-Risk Areas for Further Development of Successful Solution

Fetched: September 1st, 2024, 2:01am UTC by Nopparat Songserm

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2911-2917. doi: 10.31557/APJCP.2024.25.8.2911.

ABSTRACT

BACKGROUND: Despite the national campaigns in 1997 to control Opisthorchis viverrini (OV), a significant risk factor for cholangiocarcinoma (CCA) was accounted for in the northeast of Thailand, which is also considered the highest-risk area for CCA as per the latest national-wide survey in 2019. Social innovations were employed to address OV and CCA issues in this area, but they have yet to be thoroughly investigated. Investigating social innovations in areas where issues can already be solved is a particular approach for expanding on a broad basis.

OBJECTIVE: This study aimed to search for social innovations used to handle OV and CCA in northeast of Thailand.

METHODS: Researchers coordinated with the Office of Disease Prevention and Control Region-10 (1 of 12 regional offices under the Department of Disease Control, Ministry of Public Health) to specify the model areas for taking OV and CCA. In addition, researchers cooperated with local coordination units for data collection. The data were coded and classified for content analysis, and triangulation was performed for comparative analysis. Finally, a meeting was conducted to summarize the social innovations discovered in each study site area.

RESULTS: Our findings have been presented according to the epidemiologic triad: agent (risk factors), host (individuals/communities), and environment. The researchers and experts addressed and proposed social innovations for dealing with OV and CCA, such as the "3 Health" (Health Behaviours, Health Hygiene, and Environmental Health), in order to achieve a CCA-free society.

CONCLUSIONS: This is the first study to highlight the significance of social innovations in managing OV and CCA. The findings will be utilized to further create strategies for addressing these public health issues in this and other regions in a sustainable and successful manner.

PMID:39205590 | DOI:10.31557/APJCP.2024.25.8.2911
Re- Infection Rate of Opisthorchis Viverrini Five Years After Treatment with Praziquantel in High-Risk Area: A Community-Based Study

Fetched: September 1st, 2024, 2:01am UTC by Phubet Saengsawang

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2679-2684. doi: 10.31557/APJCP.2024.25.8.2679.

ABSTRACT

BACKGROUND: Opisthorchis viverrini (OV) is a significant public health problem in Thailand, and OV reinfection poses a serious risk of cholangiocarcinoma with little evidence of a decrease. While numerous studies have explored OV reinfection and prevalence, most have been limited to short study period. Therefore, there is a need for long-term investigations to gather sufficient evidence.

OBJECTIVES: This study aimed to access the current status of re-infection rates in high- risk areas and to determine associations between factors of and re-infection of OV at 5 years after treatment with praziquantel.

MATERIALS AND METHODS: In total, this study included 457 participants from a cohort study. Each participant was required to answer a questionnaire and undergo stool examination using the formalin ethyl acetate concentration technique. Data were analyzed using descriptive statistics and multiple logistic regression.

RESULT: Out of the total 457 participants, 418 (91.5%) successfully completed the questionnaires and underwent stool examinations. Among the participants, 10.8% showed re-infection with OV. Using multivariate analysis, factors significantly associated with reinfection OV included yearly income (OR adj = 2.14, 95%CI = 1.11- 4.12, p-value = 0.022) and past stool examination five years (OR adj = 2.47, 95%CI = 1.13-5.43, p-value = 0.023), respectively.

CONCLUSIONS: Subjects who frequently experience OV reinfection should undergo CCA screening by experts while closely monitoring their raw fish consumption behavior. Moreover, it is essential to implement comprehensive programs aimed at promoting behavioral changes and provide preventive education, with a specific focus on high epidemic areas, to discourage the consumption of raw fish.

PMID:39205565 | DOI:10.31557/APJCP.2024.25.8.2679
Plasma Cell-Free DNA and MiRNA in Cholangiocarcinoma and Opisthorchiasis Viverrini Patients: Comment

Fetched: September 1st, 2024, 2:01am UTC by Rujittika Mungmunpuntipantip

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2579. doi: 10.31557/APJCP.2024.25.8.2579.

NO ABSTRACT

PMID:39205552 | DOI:10.31557/APJCP.2024.25.8.2579
MyACR: A Point-of-Care Medical Device for Determination of Albumin-Creatinine Ratio (uACR) in Random Urine Samples as a Marker of Nephropathy

Fetched: September 1st, 2024, 2:01am UTC by Nadda Muhamad

Diagnostics (Basel). 2024 Aug 6;14(16):1702. doi: 10.3390/diagnostics14161702.

ABSTRACT

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world's population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device, MyACR, for uACR measurement, intended for use in community healthcare to screen for the risk and monitor the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25 Â°C) for 30 min before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (0-60 mg/L and 0-2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (R²) of >0.997. Good accuracy (% deviation of mean value (DMV) â‰¤ 5.42%) and precision (% coefficients of variation (CV) â‰¤ 12.69%) were observed from both the intra- and inter-day assays for the determination of albumin and creatinine using MyACR. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined using MyACR and a laboratory spectrophotometer were 5 mg/L and 0.25 mg/dL, respectively, using 37.5 Î¼L urine spiked samples (n = 5). The device was well-applied with clinical samples from 20 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.48 (-17.05 to 21.64)%, with a high correlation coefficient (R² > 0.98). In conclusion, MyACR showed satisfactory test performance in terms of accuracy, reproducibility, and sensitivity. Cost-effectiveness and improvement in clinical decision making need to be proven in future multisite community and home studies.

PMID:39202190 | PMC:PMC11354193 | DOI:10.3390/diagnostics14161702
Unveil Intrahepatic Cholangiocarcinoma Heterogeneity through the Lens of Omics and Multi-Omics Approaches

Fetched: September 1st, 2024, 2:01am UTC by Veronica Porreca

Cancers (Basel). 2024 Aug 20;16(16):2889. doi: 10.3390/cancers16162889.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) is recognized worldwide as the second leading cause of morbidity and mortality among primary liver cancers, showing a continuously increasing incidence rate in recent years. iCCA aggressiveness is revealed through its rapid and silent intrahepatic expansion and spread through the lymphatic system leading to late diagnosis and poor prognoses. Multi-omics studies have aggregated information derived from single-omics data, providing a more comprehensive understanding of the phenomena being studied. These approaches are gradually becoming powerful tools for investigating the intricate pathobiology of iCCA, facilitating the correlation between molecular signature and phenotypic manifestation. Consequently, preliminary stratifications of iCCA patients have been proposed according to their "omics" features opening the possibility of identifying potential biomarkers for early diagnosis and developing new therapies based on personalized medicine (PM). The focus of this review is to provide new and advanced insight into the molecular pathobiology of the iCCA, starting from single- to the latest multi-omics approaches, paving the way for translating new basic research into therapeutic practices.

PMID:39199659 | PMC:PMC11352949 | DOI:10.3390/cancers16162889
Utility of Transpapillary Biopsy and Endoscopic Ultrasound-Guided Tissue Acquisition for Comprehensive Genome Profiling of Unresectable Biliary Tract Cancer

Fetched: September 1st, 2024, 2:01am UTC by Soma Fukuda

Cancers (Basel). 2024 Aug 10;16(16):2819. doi: 10.3390/cancers16162819.

ABSTRACT

Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive genome profiling (CGP) analysis in patients with unresectable BTC (UR-BTC). Pathology precheck criteria for CGP analysis comprised the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Seventy-eight patients with UR-BTC (35 TPB and 43 EUS-TA) were included. The NCCOP analysis suitability achievement rate was higher in EUS-TA specimens than in TPB specimens (34.9% vs. 8.6%, p = 0.007), whereas that of F1CDx was 0% in both groups. EUS-TA was identified as an independent factor that contributed to the suitability of the NCCOP analysis. The suitability of the NCCOP analysis of EUS-TA specimens showed a tendency to be higher for mass lesions (43.8% vs. 9.1%, p = 0.065), especially for target size â‰¥ 18.5 mm, and lower for perihilar cholangiocarcinoma (0% vs. 41.7%, p = 0.077). In TPB, papillary-type lesions (66.7% vs. 3.2%, p = 0.016) and peroral cholangioscopy-assisted biopsies (50.0% vs. 3.3%, p = 0.029) showed better potential for successful NCCOP analysis. EUS-TA is suitable for NCCOP analysis in UR-BTC and may be partially complemented by TPB.

PMID:39199592 | PMC:PMC11353131 | DOI:10.3390/cancers16162819
The Impact of Biliary Injury on the Recurrence of Biliary Cancer and Benign Disease after Liver Transplantation: Risk Factors and Mechanisms

Fetched: September 1st, 2024, 2:01am UTC by Chase J Wehrle

Cancers (Basel). 2024 Aug 7;16(16):2789. doi: 10.3390/cancers16162789.

ABSTRACT

Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.

PMID:39199562 | PMC:PMC11352383 | DOI:10.3390/cancers16162789
Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Kankamol Kerdkumthong

Biomolecules. 2024 Aug 8;14(8):969. doi: 10.3390/biom14080969.

ABSTRACT

Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein-protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial-mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets.

PMID:39199357 | PMC:PMC11352417 | DOI:10.3390/biom14080969
Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations

Fetched: September 1st, 2024, 2:01am UTC by Hisashi Tamada

Diagn Pathol. 2024 Aug 28;19(1):116. doi: 10.1186/s13000-024-01537-7.

ABSTRACT

BACKGROUND: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC).

METHODS: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed.

RESULTS: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397).

CONCLUSIONS: These findings suggest that LGR5 is a promising, novel prognostic marker.

PMID:39198902 | PMC:PMC11350935 | DOI:10.1186/s13000-024-01537-7
Identification of autoantibodies as potential non-invasive biomarkers for intrahepatic cholangiocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Wachira Kajornsrichon

Sci Rep. 2024 Aug 28;14(1):20012. doi: 10.1038/s41598-024-70595-0.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) presents a challenging diagnosis due to its nonspecific early clinical manifestations, often resulting in late-stage detection and high mortality. Diagnosing iCCA is further complicated by its limited accuracy, often necessitating multiple invasive procedures for precise identification. Despite carbohydrate antigen 19-9 (CA19-9) having been investigated and employed for iCCA diagnosis, it demonstrates modest diagnostic performance. Consequently, the identification of novel biomarkers with improved sensitivity and specificity remains an imperative yet formidable task. Autoantibodies, as early indicators of the immune response against cancer, offer a promising avenue for enhancing diagnostic accuracy. Our study aimed to identify non-invasive blood-based autoantibody biomarkers capable of distinguishing iCCA patients from healthy individuals (CTRs). We profiled autoantibodies in 26 serum samples (16 iCCAs and 10 CTRs) using protein microarrays containing 1622 functional proteins. Leveraging machine learning techniques, we identified a signature composed of three autoantibody biomarkers (NDE1, PYCR1, and VIM) in conjunction with CA19-9 for iCCA detection. This combined signature demonstrated superior diagnostic performance with an AUC of 96.9%, outperforming CA19-9 alone (AUC: 83.8%). These results suggest the potential of autoantibody biomarkers to develop a complementary non-invasive diagnostic utility for routine iCCA screening.

PMID:39198554 | PMC:PMC11358490 | DOI:10.1038/s41598-024-70595-0
HER2 amplification subtype intrahepatic cholangiocarcinoma exhibits high mutation burden and T cell exhaustion microenvironment

Fetched: September 1st, 2024, 2:01am UTC by Xiaohong Pu

J Cancer Res Clin Oncol. 2024 Aug 28;150(8):403. doi: 10.1007/s00432-024-05894-0.

ABSTRACT

OBJECTIVE: This study aimed to establish a uniform standard for the interpretation of HER2 gene and protein statuses in intrahepatic cholangiocarcinoma (ICC). We also intended to explore the clinical pathological characteristics, molecular features, RNA expression and immune microenvironment of HER2-positive ICC.

METHODS: We analyzed a cohort of 304 ICCs using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to identify HER2 status. Comprehensive analyses of the clinicopathological, molecular genetic, and RNA expression characterizations of ICCs with varying HER2 statuses were performed using next-generation sequencing. We further investigated the tumor microenvironment of ICCs with different HER2 statuses using IHC and multiplex immunofluorescence staining.

RESULTS: HER2/CEP17 ratio of â‰¥ 2.0 and HER2 copy number â‰¥ 4.0; or HER2 copy number â‰¥ 6.0 were setup as FISH positive criteria. Based on this criterion, 13 (4.27%, 13/304) samples were classified as having HER2 amplification. The agreement between FISH and IHC results in ICC was poor. HER2-amplified cases demonstrated a higher tumor mutational burden compared to non-amplified cases. No significant differences were observed in immune markers between the two groups. However, an increased density of CD8 + CTLA4 + and CD8 + FOXP3 + cells was identified in HER2 gene-amplified cases.

CONCLUSION: FISH proves to be more appropriate as the gold standard for HER2 evaluation in ICC. HER2 gene-amplified ICCs exhibit poorer prognosis, higher mutational burden, and T cell exhaustion and immune suppressed microenvironment.

PMID:39198311 | PMC:PMC11358322 | DOI:10.1007/s00432-024-05894-0
Unveiling the unexplored secret: Aggressive behavior and poor survival in intrahepatic mucinous adenocarcinoma compared to conventional adenocarcinoma

Fetched: September 1st, 2024, 2:01am UTC by Wenhui Wang

Biosci Trends. 2024 Aug 29. doi: 10.5582/bst.2024.01227. Online ahead of print.

ABSTRACT

Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.

PMID:39198179 | DOI:10.5582/bst.2024.01227
Liquid Biopsy-Based Accurate Diagnosis and Genomic Profiling of Hard-to-Biopsy Tumors via Parallel Single-Cell Genomic Sequencing of Exfoliated Tumor Cells

Fetched: August 30th, 2024, 2:01am UTC by Ziyuan Zhang

Anal Chem. 2024 Aug 28. doi: 10.1021/acs.analchem.4c03462. Online ahead of print.

ABSTRACT

Liquid biopsy provides a convenient and safer procedure for the diagnosis and genomic profiling of tumors that are inaccessible to biopsy by analyzing exfoliated tumor cells (ETCs) or tumor-derived cell-free DNA (cfDNA). However, its primary challenge lies in its limited accuracy in comparison to tissue-based approaches. We report a parallel single-ETC genomic sequencing (Past-Seq) method for the accurate diagnosis and genomic profiling of hard-to-biopsy tumors such as cholangiocarcinoma (CCA) and upper tract urothelial carcinoma (UTUC). For CCA, a prospective cohort of patients with suspicious biliary strictures (n = 36) was studied. Parallel single-cell whole genome sequencing and whole exome sequencing were performed on bile ETCs for CCA diagnosis and resolving mutational profiles, respectively, along with bile cfDNA sequenced for comparison. Concordant single-cell copy number alteration (CNA) profiles in multiple ETCs provided compelling evidence for generating a malignant diagnosis. Past-Seq yielded bile-based accurate CCA diagnosis (96% sensitivity, 100% specificity, and positive predictive value), surpassing pathological evaluation (56% sensitivity) and bile cfDNA CNA analysis (13% sensitivity), and generated the best performance in the retrieval tissue mutations. To further explore the applicability of Past-Seq, 10 suspicious UTUC patients were investigated with urine specimens, and Past-Seq exhibited 90% sensitivity in diagnosing UTUC, demonstrating its broad applicability across various liquid biopsies and cancer types.

PMID:39197101 | DOI:10.1021/acs.analchem.4c03462
An Unusual Radiologic Image of Extensive Tumor Mass Infiltrating Hepatic Hilum without Signs of Cholestasis-A Case Report and a Literature Review of Non-Cancerous Lesions Mimicking Intrahepatic Cholangiocarcinoma

Fetched: August 29th, 2024, 2:01am UTC by Jakub Ciesielka

Curr Oncol. 2024 Aug 4;31(8):4507-4518. doi: 10.3390/curroncol31080336.

ABSTRACT

BACKGROUND: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted.

METHODS: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis.

RESULTS: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients.

CONCLUSIONS: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination.

PMID:39195319 | PMC:PMC11352376 | DOI:10.3390/curroncol31080336
In Vivo Tracking and 3D Mapping of Cell Death in Regeneration and Cancer Using Trypan Blue

Fetched: August 29th, 2024, 2:01am UTC by Nicole Procel

Cells. 2024 Aug 20;13(16):1379. doi: 10.3390/cells13161379.

ABSTRACT

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl4 intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo "pulse and chase" tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease.

PMID:39195268 | PMC:PMC11352400 | DOI:10.3390/cells13161379
Analysis of the Effector Functions of Vdelta2 gammadelta T Cells and NK Cells against Cholangiocarcinoma Cells

Fetched: August 29th, 2024, 2:01am UTC by Inthuon Kulma

Cells. 2024 Aug 8;13(16):1322. doi: 10.3390/cells13161322.

ABSTRACT

Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by VÎ´2 Î³Î´ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-Î³. VÎ´2 Î³Î´ T cells demonstrated cytotoxicity and IFN-Î³ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both VÎ´2 Î³Î´ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA.

PMID:39195212 | PMC:PMC11352430 | DOI:10.3390/cells13161322
Electrical Conductivity Measurement in Human Liver Tissue: Assessment on Normal vs. Tumor Tissue and under In Vivo vs. Ex Vivo Conditions

Fetched: August 29th, 2024, 2:01am UTC by Amirhossein Sarreshtehdari

Biosensors (Basel). 2024 Aug 8;14(8):382. doi: 10.3390/bios14080382.

ABSTRACT

BACKGROUND: This study evaluated electrical conductivity in human liver tissue in the 3-1000 kHz frequency range to compare normal versus tumor tissues under in vivo versus ex vivo conditions.

METHODS: Previous informed consent was obtained from twenty patients undergoing liver resection in whom liver electrical conductivity was measured during surgery and after resection.

RESULT: We found higher electrical conductivity values in tumor tissues than in normal tissue in both in vivo (0.41 Â± 0.10 vs. 0.13 Â± 0.06 S/m) and ex vivo (0.27 Â± 0.09 vs. 0.12 Â± 0.07 S/m) conditions (at 3 kHz). The electric properties also showed a promising potential for distinguishing between different tissue types including metastasis, cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), hepatic cirrhosis, and normal liver (both in vivo and ex vivo). At 3 kHz, in vivo electrical conductivity for cholangiocarcinoma, HCC, and metastasis were 0.35, 0.42 Â± 0.13, and 0.41 Â± 0.08 S/m, respectively, which differed significantly from each other (p < 0.05).

CONCLUSIONS: These findings could potentially improve liver disease diagnostics through electrical conductivity measurements and treatment techniques involving electric fields. Future research should focus on expanding the sample size to refine the categorization and comparison processes across diverse human liver tissue types.

PMID:39194611 | PMC:PMC11353108 | DOI:10.3390/bios14080382
OTUD6B promotes cholangiocarcinoma growth by regulating STAT3 phosphorylation through deubiquitination of PTK2

Fetched: August 29th, 2024, 2:01am UTC by Guoqiang Xing

Cell Biol Int. 2024 Aug 27. doi: 10.1002/cbin.12234. Online ahead of print.

ABSTRACT

Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma with uncontrolled cell proliferation, poor prognosis, and high mortality. The ovarian tumor structural domain (OTU) containing protein 6B (OTUD6B) belongs to the OTU deubiquitin family and is vital in tumor development. However, its expression and biological function in CCA remain unknown. The expression of OTUD6B in CCA was analyzed using TIMER2.0, UALCAN, and GEO databases. MTT, clonal formation assay, immunofluorescence staining, immunohistochemistry staining, and flow cytometry examined the regulation of OTUD6B on cell proliferation, cycle, and apoptosis. The effects of OTUD6B on tumor volume and weight were assessed using the xenograft tumor model. The activities of PTK2 and STAT3 were detected by western blot and CO-IP. The biological database identified that OTUD6B was upregulated in CCA. In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis. Cell cycle analysis indicated that the cycle stopped at the G0/G1 phase after OTU6B downregulation. Furthermore, OTUD6B knockdown resulted in a decrease in tumor volume and weight in xenograft tumor models. Mechanistically, OTUD6B is involved in the deubiquitination of PTK2. PTK2 further affected the phosphorylation of STAT3 thereby regulating the CCA process. Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA. These results suggest that OTUD6B may be a potential new strategy for CCA treatment.

PMID:39192576 | DOI:10.1002/cbin.12234
'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer

Fetched: August 28th, 2024, 2:01am UTC by IHPBA-APHPBA International Study Group of Gallbladder Cancer

HPB (Oxford). 2024 Jul 25:S1365-182X(24)02223-8. doi: 10.1016/j.hpb.2024.07.411. Online ahead of print.

ABSTRACT

BACKGROUND: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally.

METHOD: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts.

RESULTS: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC.

CONCLUSIONS: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.

PMID:39191539 | DOI:10.1016/j.hpb.2024.07.411
TTYH3 Promotes Cervical Cancer Progression by Activating the Wnt/Î²-Catenin Signaling Pathway

Fetched: August 28th, 2024, 2:01am UTC by Xiuyan Huang

Cancer Invest. 2024 Aug 27:1-14. doi: 10.1080/07357907.2024.2395014. Online ahead of print.

ABSTRACT

The role of tweety homolog 3 (TTYH3) has been studied in several cancers, including hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. The results showed that TTYH3 is highly expression in cervical cancer tissues and cells and high TTYH3 expression correlates with poor prognosis in patients with cervical cancer. TTYH3 markedly reduced the apoptosis rate and promoted proliferation, migration, and invasion. Silencing of TTYH3 has been shown to have an inhibitory effect on cervical cancer progression. Moreover, TTYH3 enhanced EMT and activated Wnt/Î²-catenin signaling. Furthermore, TTYH3 knockdown inhibited the tumor growth in vivo. In conclusion, TTYH3 promoted cervical cancer progression by activating the Wnt/Î²-catenin signaling.

PMID:39189652 | DOI:10.1080/07357907.2024.2395014
Nocardia masquerading as pulmonary malignancy in a patient with adult-onset immunodeficiency on 18F-FDG PET/CT

Fetched: August 28th, 2024, 2:01am UTC by Harshil Dharamdasani Detaram

Radiol Case Rep. 2024 Aug 3;19(10):4517-4521. doi: 10.1016/j.radcr.2024.07.058. eCollection 2024 Oct.

ABSTRACT

A 77-year-old man with a history of left nephrectomy for renal cell carcinoma and partial hepatectomy for cholangiocarcinoma underwent ¹⁸F-FDG PET/CT for assessment of an irregular lung lesion. FDG-PET demonstrated development of an intensely avid spiculated left lower lobe pulmonary lesion and intensely avid left pulmonary hilar nodes, raising suspicion for a malignancy. Eleven days following the PET study, the patient was admitted to hospital with an altered mental state. CT brain revealed diffuse round hyperdensities within the brain parenchyma. Microbiology of the lung lesion was positive for Nocardia Beijingensis and he was subsequently diagnosed with disseminated nocardiosis.

PMID:39188623 | PMC:PMC11345279 | DOI:10.1016/j.radcr.2024.07.058
Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression

Fetched: August 28th, 2024, 2:01am UTC by Maria Adriana Cocozza

Cardiovasc Intervent Radiol. 2024 Aug 26. doi: 10.1007/s00270-024-03825-7. Online ahead of print.

ABSTRACT

PURPOSE: Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA.

METHODS: We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity.

RESULTS: We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naÃ¯ve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naÃ¯ve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naÃ¯ve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe.

CONCLUSIONS: Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naÃ¯ve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.

PMID:39187651 | DOI:10.1007/s00270-024-03825-7
Anti-Tumor and Chemosensitizing Effects of the CDK Inhibitor Dinaciclib on Cholangiocarcinoma In Vitro and In Vivo

Fetched: August 28th, 2024, 2:01am UTC by Prin Sungwan

In Vivo. 2024 Sep-Oct;38(5):2284-2293. doi: 10.21873/invivo.13693.

ABSTRACT

BACKGROUND/AIM: Cholangiocarcinoma (CCA) is a highly aggressive disease. Most of CCA patients are diagnosed in an advanced stage of the disease, when it is unresectable and there is chemoresistance, resulting in poor prognosis. However, effective therapeutic regimens and molecular targets for CCA remain poor. Cyclin-dependent kinases (CDKs) are key regulatory enzymes in cell cycle progression. Aberrant CDK activation is a hallmark of cancer. Dinaciclib is a small molecule inhibitor of multiple CDKs, currently under clinical evaluation for treating advanced malignancies. The efficacy of anti-tumor activity of dinaciclib against chemotherapy resistant CCA cells was examined in vitro and in vivo.

MATERIALS AND METHODS: In this study, the effect of dinaciclib on growth and cell cycle in CCA cell lines were determined using the MTT assay and cell cycle analysis. The anti-tumor activity of dinaciclib was investigated in CCA-inoculated mice. In addition, the chemosensitizing effect of dinaciclib was investigated in gemcitabine-treated CCA cell lines.

RESULTS: Dinaciclib significantly suppressed cell proliferation, induced G1/S phase cell cycle arrest and apoptosis of CCA cell lines. It significantly suppressed the growth of CCA cells in xenograft mouse models. We also found that dinaciclib significantly inhibited the growth of gemcitabine-resistant CCA cell lines (KKU-213A-GemR and KKU-100-GemR). Furthermore, dinaciclib significantly enhanced the anti-tumor activity of gemcitabine in CCA cell lines.

CONCLUSION: Dinaciclib has the potential to be an effective therapeutic agent to control tumor cell growth of both parental and gemcitabine-resistant CCA cells.

PMID:39187317 | PMC:PMC11363801 | DOI:10.21873/invivo.13693
Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling

Fetched: August 27th, 2024, 2:01am UTC by Kishor Pant

Hepatology. 2024 Aug 23. doi: 10.1097/HEP.0000000000001055. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: The primary cilium, an organelle that protrudes from cell surfaces, is essential for sensing extracellular signals. With disturbed cellular communication and chronic liver pathologies, this organelle's dysfunctions have been linked to disorders, including polycystic liver disease (PLD) and Cholangiocarcinoma (CCA). The goal of this study was to elucidate the relationship between primary cilia and the crucial regulator of cellular proliferation, the epidermal growth factor receptor (EGFR) signaling pathway, which has been associated with various clinical conditions.

APPROACH RESULTS: The study identified aberrant EGFR signaling pathways in cholangiocytes lacking functional primary cilia. Using liver-specific IFT88 knockout mice, a Pkhd1 mutant rat model, and human cell lines that didn't have functional cilia. Cilia-deficient cholangiocytes showed persistent EGFR activation because of impaired receptor degradation, in contrast to their normal counterparts, where EGFR localization to the cilia promotes appropriate signaling. Using HDAC6 inhibitors to restore primary cilia accelerates EGFR degradation, thereby reducing maladaptive signaling. Importantly, experimental intervention with the HDAC6 inhibitor tubastatin A in an orthotopic rat model moved EGFR to cilia and reduced ERK phosphorylation. Concurrent administration of EGFR and HDAC6 inhibitors in cholangiocarcinoma and polycystic liver disease cells demonstrated synergistic anti-proliferative effects, which were associated with the restoration of functioning primary cilia.

CONCLUSION: This study's findings shed light on ciliary function and robust EGFR signaling with slower receptor turnover. We could use therapies that restore the function of primary cilia to treat EGFR-driven diseases in PLD and CCA.

PMID:39186465 | DOI:10.1097/HEP.0000000000001055
Endoscopic ultrasound with tissue acquisition of lymph nodes in patients with potentially resectable intrahepatic cholangiocarcinoma

Fetched: August 27th, 2024, 2:01am UTC by David M de Jong

Endosc Int Open. 2024 Aug 23;12(8):E998-E1005. doi: 10.1055/a-2366-2592. eCollection 2024 Aug.

ABSTRACT

Background and study aims Lymph node (LN) involvement is a poor prognostic factor for patients with intrahepatic cholangiocarcinoma (iCCA). The aim of this study was to evaluate the yield and impact on clinical decision making of endoscopic ultrasound with tissue acquisition (EUS-TA) of LNs in patients with potentially resectable iCCA. Patients and methods In this multicenter cohort study, patients with potentially resectable iCCA and preoperative EUS between 2010 and 2020 were retrospectively included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to pathologically confirmed positive LNs found with EUS-TA. Results A total of 56 patients underwent EUS, with 91% of patients to target suspicious LNs on imaging. EUS-TA of LNs confirmed malignancy in 21 LNs among 19 patients (34%). In 17 patients (30%), surgical exploration was withheld due to nodal involvement. Finally, 24 patients (43%) underwent surgical exploration among whom positive regional LNs were identified in six patients (25%). Conclusions In patients with potentially resectable iCCA and suspicious LNs on cross-sectional imaging, EUS-TA confirmed LN involvement in 30% of patients. Surgical exploration was withheld mostly because of extraregional LN involvement and regional LN involvement in patients with high surgical risk.

PMID:39184062 | PMC:PMC11343620 | DOI:10.1055/a-2366-2592
Tackling challenges in rare diseases: The ISGACA approach on non-pancreatic cancers in the periampullary region

Fetched: August 27th, 2024, 2:01am UTC by Bas A Uijterwijk

Eur J Surg Oncol. 2024 Aug 13;50(11):108601. doi: 10.1016/j.ejso.2024.108601. Online ahead of print.

ABSTRACT

OBJECTIVE: Rare but aggressive cancer types like non-pancreatic periampullary cancers pose unique challenges for cancer research due to their low incidence rates and lack of consensus on optimal treatment strategies, therefore necessitating a collaborative approach. The International Study Group on non-pancreatic peri-Ampullary CAncer (ISGACA) aimed to build a collaborative initiative to pool expertise, funding opportunities, and data from over 60 medical centers, in order to improve outcomes for underrepresented patients with rare cancers.

METHODS: The ISGACA approach predefined a stepwise approach including a research scope, establishing a dedicated steering committee, creating a recognizable brand, identifying research gaps, following a well-defined timeline, ensuring robust data collection, addressing legal and ethical considerations, securing financial resources, investing in research ethics training and statistical expertise, raising awareness, creating uniformity, and initiating prospective studies.

RESULTS: Overall, 60 medical centers joined the ISGACA consortium (41 in Europe, 15 in North-America, three in Asia, one in Australia). The database includes 4309 patients. Nine publications and several ongoing studies which in turn allowed for a successful application of research grants. Subsequently, an international consensus meeting established uniform definitions and classifications, and one prospective multicenter international clinical trial has been initiated.

CONCLUSION: By sharing knowledge, expertise, and clinical data, the ISGACA approach has not only gathered sufficient evidence to secure grants and ethical approvals for prospective studies, but also demonstrates options for standardizing patient care and improving outcomes for patients with rare cancers. The ISGACA approach offers a detailed methodology for initiating research on rare cancers and could serve as a replicable model for future research initiatives.

PMID:39182309 | DOI:10.1016/j.ejso.2024.108601
Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center

Fetched: August 27th, 2024, 2:01am UTC by Yusheng Du

BMC Surg. 2024 Aug 24;24(1):241. doi: 10.1186/s12893-024-02533-w.

ABSTRACT

BACKGROUND: The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy.

METHODS: A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb.

RESULTS: Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190-450), and the median estimated blood loss was 360 mL (range, 260-1200). The postoperative hospital stay duration was 14.3 Â± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3-43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.

CONCLUSION: Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

PMID:39182023 | PMC:PMC11344452 | DOI:10.1186/s12893-024-02533-w

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