Precision Medicine for Combined Hepatocellular-Cholangiocarcinoma

Posted: November 24th, 2023, 3:00am GMT

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

Posted: November 20th, 2023, 3:00am GMT

Conditions: Locally Advanced Non-metastatic Intrahepatic Cholangiocarcinoma; Determine Efficacy of Liver Transplantation After Neoadjuvant Systemic Therapy in Patients With Locally Advanced Non-metastatic Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Liver Transplant
Sponsors: Rutgers, The State University of New Jersey
Not yet recruiting
Combination Therapy of HAIC, Surufatinib and Tislelizumab for Unresectable or Metastatic Biliary Tract Cancer

Posted: November 16th, 2023, 3:00am GMT

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
Clinical Study of CEA Targeting Chimeric Antigen Receptor T Lymphocytes（CAR-T） for CEA Positive Advanced Malignant Solid Tumors

Posted: November 10th, 2023, 3:00am GMT

Conditions: Gastric Cancer; Colon Cancer; Rectal Cancer; Breast Cancer; Lung Cancer; Esophagus Cancer; Cholangiocarcinoma; Pancreas Cancer
Interventions: Biological: CEA-targeted CAR-T cells; Biological: CEA-targeted CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; First Affiliated Hospital of Wannan Medical College
Recruiting
LIver TrAnspLantation for Non-resectable Peri-HIlar cholangioCArcinoma (LITALHICA)

Posted: November 9th, 2023, 3:00am GMT

Conditions: Perihilar Cholangiocarcinoma
Interventions: Procedure: Liver transplantation
Sponsors: Azienda Sanitaria Ospedaliera; Istituto Oncologico Veneto IRCCS
Not yet recruiting
A Single-center, Prospective Cohort Study on the Differentiation of Benign and Malignant Bile Duct Stenosis Based on Bile and Peripheral Blood cfDNA Methylation Profiles

Posted: November 3rd, 2023, 2:00am GMT

Conditions: Bile Duct Neoplasms; Jaundice, Obstructive; Bile Duct Diseases
Interventions: Diagnostic Test: cfDNA methylation detection
Sponsors: Air Force Military Medical University, China
Recruiting
A Study of Rilvegostomig Plus Chemotherapy as Adjuvant Therapy for Biliary Tract Cancer After Resection

Posted: October 31st, 2023, 2:00am GMT

Conditions: Biliary Tract Cancer
Interventions: Drug: Rilvegostomig; Drug: Placebo; Drug: Capecitabine; Drug: Gemcitabine/Cisplatin; Drug: S-1 [Tegafur/Oteracil/gimeracil]
Sponsors: AstraZeneca
Not yet recruiting
Endoscopic Scissors Cutting Nasobiliary Duct VS Bilateral Plastic Stent

Posted: October 30th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma, Hilar; Biliary Stricture; Hilar Cholangiocarcinoma; Klatskin Tumor; Biliary Disease; Bile Duct Diseases; Bile Duct Stenosis
Interventions: Device: Endoscopic nasobiliary duct cutting; Device: Bilateral plastic stent
Sponsors: First People's Hospital of Hangzhou
Recruiting
Locally ablatIVe thErapy for oLigo-progressive gastrOintestiNal maliGnancies (LIVELONG)

Posted: October 26th, 2023, 2:00am GMT

Conditions: Esophageal Cancer; Small Bowel Cancer; Gastroesophageal-junction Cancer; Gastric Cancer; Colorectal Cancer; Appendiceal Cancer; Biliary Cancer; Gall Bladder Cancer; Intrahepatic Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Oligoprogressive
Interventions: Device: Ablative local therapy
Sponsors: University of California, Davis; National Cancer Institute (NCI)
Recruiting
LIver Transplantation for Non-Resectable Intrahepatic CholAngiocarcinoma

Posted: October 24th, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Liver transplantation
Sponsors: Azienda Sanitaria Ospedaliera; Istituto Oncologico Veneto IRCCS
Not yet recruiting
Surufatinib Plus Cadonilimab in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma

Posted: October 20th, 2023, 2:00am GMT

Conditions: Bile Duct Adenocarcinoma
Interventions: Drug: surufatinib plus cadonilimab
Sponsors: Zhejiang Cancer Hospital
Recruiting
A Study to Evaluate the Safety and Efficacy of PRRT With 177Lu-EB-FAPI in Patients With Advanced Cholopancreatic Tumors

Posted: October 13th, 2023, 2:00am GMT

Conditions: Advanced Pancreatic Cancer and Cholangiocarcinoma
Interventions: Drug: PRRT with 177Lu-EB-FAPI
Sponsors: Zhejiang University
Recruiting
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Posted: October 13th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic
Interventions: Drug: Ivosidenib
Sponsors: Servier
Not yet recruiting
Modified vs Conventional Blumgart Anastomosis of LPD for the Effects of Pancreatic Fistula of Periampullary Carcinoma

Posted: October 10th, 2023, 2:00am GMT

Conditions: Ampullary Cancer; Bile Duct Cancer; Pancreas Cancer; Duodenum Cancer
Interventions: Procedure: Modified Blumgart Anastomosis in LPD; Procedure: conventional Blumgart anastomosis in LPD
Sponsors: Affiliated Hospital of Guangdong Medical University
Enrolling by invitation
Radioembolization With Tremelimumab and Durvalumab for Locally Advanced, Unresectable Intrahepatic Cholangiocarcinoma

Posted: September 28th, 2023, 2:00am GMT

Conditions: Locally Advanced Intrahepatic Cholangiocarcinoma; Oligometastatic Intrahepatic Cholangiocarcinoma; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Angiography; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Tremelimumab; Procedure: Yttrium-90 Microsphere Radioembolization
Sponsors: Mayo Clinic
Not yet recruiting
Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor

Posted: September 27th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma Metastatic
Interventions: Drug: TT-00420 (tinengotinib)
Sponsors: TransThera Sciences (Nanjing), Inc.
Not yet recruiting
Durvalumab With Gemcitabine and Cisplatin for the Treatment of High Risk Resectable Liver Cancer Before Surgery

Posted: September 22nd, 2023, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging; Procedure: Resection
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
Prospective Observational Study to Predict the Response of Biliary Tract Tumors to Immunotherapy

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Biliary Tract Tumor; Cholangiocarcinoma
Interventions: Other: Blood samples, tumor biopsy specimens will be collected
Sponsors: Zhejiang Cancer Hospital
Recruiting
Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Biliary Tract Carcinoma; Cholangiocarcinoma; Bile Duct Cancer
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Zimberelimab; Drug: Quemliclustat
Sponsors: Nataliya Uboha; Arcus Biosciences, Inc.; Gilead Sciences; University of Wisconsin, Madison
Not yet recruiting
A Clinical Trial Targeting CEA Chimeric Antigen Receptor T (CAR-T) for CEA Positive Advanced Malignant Solid Tumors

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Colorectal Cancer; Esophagus Cancer; Gastric Cancer; Pancreas Cancer; Non-small Cell Lung Cancer; Breast Cancer; Bile Duct Cancer
Interventions: Biological: CEA-targeted CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; Zhejiang University
Recruiting
CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence

Posted: September 14th, 2023, 2:00pm GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma
Interventions: Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Cisplatin; Procedure: Curative Surgery; Drug: Capecitabine
Sponsors: Gruppo Oncologico del Nord-Ovest
Recruiting
Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

Posted: September 12th, 2023, 2:00pm GMT

Conditions: Combined Hepatocellular Cholangiocarcinoma
Interventions: Drug: gemcitabine ,oxaliplatin,anlotinib,Sintilimab
Sponsors: Sichuan University
Not yet recruiting
A Prospective, Observational Study on the Prevalence of Clinically Useful Mutations in Solid Tumor Characterized by Next Generation Sequencing Methods on Liquid Biopsy Analysis (POPCORN)

Posted: September 8th, 2023, 2:00pm GMT

Conditions: Solid Tumor; Advanced Solid Tumor; Locally Advanced Solid Tumor; Colon Rectal Cancer; Gastric Cancer; Pancreatic Cancer; Bile Duct Cancer; Hepatocarcinoma; Breast Cancer; Ovarian Cancer; Endometrial Cancer; Cervical Cancer; Vulva Cancer; Melanoma
Sponsors: Centro di Riferimento Oncologico - Aviano
Recruiting
Neoadjuvant Tremelimumab and Durvalumab With Gem/Cis in Intrahepatic Cholangiocarcinoma

Posted: August 30th, 2023, 2:00pm GMT

Conditions: Borderline Resectable Carcinoma; Biliary Tract Cancer
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Gemcitabine; Drug: Cisplatin; Procedure: Surgical Resection
Sponsors: Georgetown University; AstraZeneca
Not yet recruiting
Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors

Posted: August 25th, 2023, 2:00pm GMT

Conditions: Gastric Cancer; Colon Cancer; Pancreas Cancer; Esophagus Cancer; Cholangiocarcinoma; Lung Cancer; Breast Cancer
Interventions: Biological: CEA CAR-T cells; Biological: CEA CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; The First Affiliated Hospital of Nanchang University
Recruiting
Diagnostic Efficacy of EUS-FNA/B Versus ERCP With or Without POCS-TB in Patients With Suspected Hilar Cholangiocarcinoma

Posted: August 15th, 2023, 2:00pm GMT

Conditions: Klatskin Tumor; Cholangiocarcinoma; Biopsy, Fine-Needle; Endoscopic Retrograde Cholangiopancreatography
Interventions: Diagnostic Test: The sampling method selected in patients with suspected hilar cholangiocarcinoma
Sponsors: Qilu Hospital of Shandong University; First Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital of Guangxi Medical University; LanZhou University; Sir Run Run Shaw Hospital; Wuhan Union Hospital, China
Recruiting
IAH0968 in Combination With GC for the Treatment of HER2-Positive Unresectable Advanced/Metastatic Malignant Tumors

Posted: August 14th, 2023, 2:00pm GMT

Condition: HER2 Gene Mutation
Interventions: Combination Product: Injection of IAH0968+Gemcitabine+Cisplatin; Combination Product: Gemcitabine+Cisplatin
Sponsor: SUNHO（China）BioPharmaceutical CO., Ltd.
Recruiting
Cadonilimab With Chemotherapy in Treating Advanced Biliary Cancer

Posted: August 7th, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma Non-resectable
Interventions: Drug: Candonilimab; Drug: Cisplatin; Drug: Gemcitabine
Sponsor: West China Hospital
Recruiting
IMM2510, a PD-L1 and VEGF Bispecific Fusion Protein, in Patients With Advanced Solid Tumors

Posted: August 2nd, 2023, 2:00pm GMT

Condition: Advanced Solid Tumors
Intervention: Drug: IMM2510
Sponsors: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.; Zhejiang Cancer Hospital; Fudan University
Recruiting
A Single-Arm Study of Pembrolizumab With Gemcitabine and Cisplatin as Perioperative Therapy for Potentially Resectable Intrahepatic Cholangiocarcinoma

Posted: August 1st, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma
Interventions: Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin
Sponsor: M.D. Anderson Cancer Center
Not yet recruiting
[68Ga]Ga-FAPI-46 Positron Emission Tomography (PET) Scan to Improve the Imaging of Pancreatic and Bile Duct Cancer

Posted: July 24th, 2023, 2:00pm GMT

Conditions: Pancreatic Cancer; Cholangiocarcinoma
Intervention: Diagnostic Test: [68Ga]Ga-FAPI-46 PET/CT
Sponsors: Amsterdam UMC, location VUmc; Dutch Cancer Society; Leiden University Medical Center
Recruiting
Treatment With NPX267 for Subjects With Solid Tumors Known to Express HHLA-2

Posted: July 24th, 2023, 2:00pm GMT

Conditions: Metastatic Malignant Neoplasm
Interventions: Drug: NPX267
Sponsors: NextPoint Therapeutics, Inc.
Recruiting
Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma

Posted: July 17th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma
Interventions: Drug: Tinengotinib 8 mg; Drug: Tinengotinib 10 mg; Drug: Physician's Choice
Sponsors: TransThera Sciences (Nanjing), Inc.
Not yet recruiting
HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study

Posted: July 5th, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HMPL-453; Drug: Rabeprazole
Sponsors: Hutchmed
Completed
Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma

Posted: June 27th, 2023, 2:00pm GMT

Conditions: IDH1-mutant Cholangiocarcinoma
Interventions: Drug: Ivosidenib; Drug: Recommended Combination Dose (RCD) of ivosidenib; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Servier Bio-Innovation LLC; Institut de Recherches Internationales Servier
Recruiting
Senior Adult Hepatobiliary Prehab Study

Posted: June 27th, 2023, 2:00pm GMT

Conditions: Hepatobiliary Cancer; Cholangiocarcinoma; Liver Metastases
Interventions: Behavioral: Resistance Training; Behavioral: Aerobic Training
Sponsors: H. Lee Moffitt Cancer Center and Research Institute
Recruiting
Pemigatinib Combined With PD-1 Inhibitor in Unresectable or Metastatic Intrahepatic Cholangiocarcinoma

Posted: June 22nd, 2023, 2:00pm GMT

Conditions: Carcinoma; Intrahepatic Cholangiocarcinoma; Digestive System Neoplasms; PD-1 Inhibitor; First-line Treatment
Interventions: Drug: Pemigatinib; Drug: PD-1 Inhibitors
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; First Affiliated Hospital of Jinan University; Shenzhen University General Hospital
Recruiting
Combined Treatment of Treated Bile Duct Cancer

Posted: June 22nd, 2023, 2:00pm GMT

Condition: Bile Duct Cancer
Intervention: Drug: envolizumab , sovalteinib
Sponsor: Zhejiang Cancer Hospital
Not yet recruiting
The Construction of Clinical Database and Multiomics Biobank Based on a Multicentral Prospective Cohort of Benign and Malignant Biliary Tract Diseases

Posted: June 9th, 2023, 2:00pm GMT

Conditions: Biliary Tract Diseases; Gallbladder Cancer; Extrahepatic Bile Duct Cancer; Intrahepatic Cholangiocarcinoma; Biliary Tract Neoplasms; Gall Stone
Intervention: Other: no interventions
Sponsor: RenJi Hospital
Not yet recruiting
Phase 3b Study of Ivosidenib for Patients With Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

Posted: May 25th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma
Interventions: Drug: Ivosidenib Oral Tablet
Sponsors: Servier Affaires Médicales
Recruiting
Endoscopic Drainage of Presumed Resectable pCCA Using an Intrahepatic Plastic Stent With Retrieval String

Posted: May 25th, 2023, 2:00pm GMT

Condition: Perihilar Cholangiocarcinoma
Intervention: Device: Intrahepatic biliary stent with retrieval string
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Recruiting
Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutation Cholangiocarcinoma

Posted: May 24th, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma
Intervention: Drug: GNS561 + Trametinib
Sponsor: Genfit
Not yet recruiting
Study of WM-A1-3389 in Participants With Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer

Posted: May 24th, 2023, 2:00pm GMT

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Cholangiocarcinoma; Head and Neck Cancer; Non Small Cell Lung Cancer
Interventions: Biological: WM-A1-3389; Biological: Pembrolizumab
Sponsors: Wellmarker Bio; Merck Sharp & Dohme LLC
Not yet recruiting
Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors

Posted: May 15th, 2023, 2:00pm GMT

Conditions: Melanoma; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; High Grade Serous Adenocarcinoma of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Endometrial Cancer; Cervical Cancer; Renal Cell Carcinoma; Bladder Cancer; Esophageal Cancer; Gastric Cancer; Gastroesophageal-junction Cancer; Colorectal Cancer; Anal Cancer; Hepatocellular Carcinoma; Bile Duct Cancer
Interventions: Drug: AI-061
Sponsors: OncoC4, Inc.; OncoC4 AU Pty Ltd; Avance Clinical
Recruiting
A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)

Posted: May 9th, 2023, 2:00pm GMT

Conditions: Biliary Cancer; Bile Duct Cancer; Cancer of the Bile Duct
Interventions: Drug: oxaliplatin; Drug: capecitabine; Biological: Keytruda; Biological: CDX-1140
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors

Posted: May 8th, 2023, 2:00pm GMT

Conditions: Breast Cancer Metastatic; Pancreatic Cancer; NSCLC, Metastatic; Synovial Sarcoma; Colon Cancer; Metastatic Colon Cancer; Melanoma Recurrent; Metastatic Skin Cancer; Melanoma Stage IV; Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer; Cholangiocarcinoma; Ovarian Cancer; Metastatic Melanoma; Hepatocellular Carcinoma
Interventions: Drug: ST316
Sponsors: Sapience Therapeutics
Recruiting
Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)

Posted: April 28th, 2023, 2:00pm GMT

Condition: Advanced Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Cryoablation; Drug: Sintilimab; Drug: Lenvatinib
Sponsor: Fudan University
Recruiting
Lenvatinib, Tislelizumab Combined With Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma

Posted: April 21st, 2023, 2:00pm GMT

Conditions: Advanced Cholangiocarcinoma
Interventions: Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin; Drug: Gemcitabine and cisplatin
Sponsors: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhengzhou University; The Affiliated Tumor Hospital of Xinjiang Medical University
Recruiting
IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor

Posted: April 17th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma With IDH1 Mutation; Solid Tumors With IDH1 Mutation
Intervention: Drug: AB-218 capsule
Sponsor: AnHeart Therapeutics Inc.
Not yet recruiting
IMM2902 in Patients With Advanced Solid Tumors Expressing HER2

Posted: April 10th, 2023, 2:00pm GMT

Conditions: Advanced Solid Tumor; Advanced Lung Cancer; Advanced Gastric Carcinoma; Advanced Cholangiocarcinoma
Intervention: Drug: IMM2902
Sponsor: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Recruiting
AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease

Posted: March 30th, 2023, 2:00pm GMT

Conditions: Advanced Cholangiocarcinoma; Advanced Hepatocellular Carcinoma; Advanced Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Liver; Refractory Malignant Solid Neoplasm; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: RNA Transcription Modulator AU-409
Sponsors: University of Southern California; National Cancer Institute (NCI); Auransa, Inc.
Recruiting
A Phase 1 Dose-escalation and Expansion Study of the PD-1 x ILT4 Bispecific Antibody CDX-585 in Patients With Advanced Malignancies

Posted: March 29th, 2023, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Gastric Cancer; Head and Neck Cancer; Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Bladder Urothelial Carcinoma; Colorectal Cancer; Esophageal Cancer; Hepatic Cancer; Renal Cell Carcinoma; Cholangiocarcinoma; Pancreatic Cancer; Other Solid Tumors
Interventions: Drug: CDX-585
Sponsors: Celldex Therapeutics
Recruiting
Cadonilimab Combined With Gem/Cis as First Line Therapy in Patients With Advanced ICC

Posted: March 23rd, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Cadonilimab+Gem/Cis
Sponsors: Shen Feng
Active, not recruiting
Durvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)

Posted: March 16th, 2023, 2:00pm GMT

Conditions: Biliary Tract Cancer
Interventions: Biological: Durvalumab; Drug: Gemcitabine monotherapy; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + oxaliplatin; Drug: Gemcitabine + carboplatin; Drug: Gemcitabine + cisplatin + S-1; Drug: Gemcitabine + S-1; Drug: Gemcitabine + cisplatin + albumin-bound paclitaxel
Sponsors: AstraZeneca
Recruiting
Application of 18F-PSMA PET / CT Imaging in Prostate Specific Membrane Antigen Positive Tumor

Posted: March 9th, 2023, 3:00pm GMT

Condition: Malignancy
Intervention: Drug: Al18F-PSMA-BCH PET/CT
Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Recruiting
First-line Trastuzumab, Gemcitabine, Cisplatin and Nivolumab in Advanced HER2- Positive Biliary Tract Cancer: a Multicenter, Open-label, Single-arm Phase Ib/II Trial (HERBOT)

Posted: March 1st, 2023, 3:00pm GMT

Condition: HER2 Positive Advanced/Metastatic/Nonresectable Biliary Tract Cancer
Intervention: Drug: Trastuzumab+Nivolumab+Gemcitabine+Cisplatin
Sponsor: Yonsei University
Not yet recruiting
A-LiNK: Improving Outcomes in Autoimmune Liver Disease

Posted: March 1st, 2023, 3:00pm GMT

Conditions: Autoimmune Hepatitis; Primary Sclerosing Cholangitis
Intervention: Other: No interventions
Sponsor: Children's Hospital Medical Center, Cincinnati
Recruiting
ctDNA Detection of MRD in Predicting Postoperative Recurrence in Biliary Tract Cancers：A Multicenter Prospective Trial.

Posted: February 24th, 2023, 3:00pm GMT

Condition: Biliary Tract Cancer
Intervention: Procedure: No intervention
Sponsor: The First Affiliated Hospital with Nanjing Medical University
Recruiting
Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Posted: February 21st, 2023, 3:00pm GMT

Conditions: Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Drug: Camrelizumab; Drug: Gemcitabine Injection; Drug: Cisplatin injection; Drug: Cisplatin-Eluting Beads; Procedure: D-TACE
Sponsors: Hua Li
Recruiting
Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

Posted: February 17th, 2023, 3:00pm GMT

Conditions: Locally Advanced Solid Tumor
Interventions: Drug: TNG462
Sponsors: Tango Therapeutics, Inc.
Recruiting
Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement

Posted: February 14th, 2023, 3:00pm GMT

Conditions: Advanced Cholangiocarcinoma; FGFR2 Fusions; Gene Rearrangement
Interventions: Drug: TAS-120
Sponsors: Taiho Oncology, Inc.
Recruiting
Domvanalimab and Zimberelimab in Advanced Liver Cancers

Posted: February 13th, 2023, 3:00pm GMT

Conditions: Hepatobiliary Cancer; Liver Cancer; Cholangiocarcinoma; Hepatocellular Carcinoma
Interventions: Drug: Zimberelimab; Drug: Domvanalimab
Sponsors: University of Texas Southwestern Medical Center; Arcus Biosciences, Inc.; Cancer Prevention Research Institute of Texas
Recruiting
Study on the Accuracy of Proteomics in Evaluating Lymph Node Metastasis Status in Cholangiocarcinoma Patients

Posted: February 10th, 2023, 3:00pm GMT

Condition: Cholangiocarcinoma
Intervention: Diagnostic Test: No interventions.
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
FGF19 in Obstructive Cholestasis: "Unveil the Signal"

Posted: February 8th, 2023, 3:00pm GMT

Conditions: Cholestasis; Icterus; Cholangiocarcinoma; Pancreatic Neoplasms; Liver Metastasis Colon Cancer
Intervention: Other: Biospecimen sampling
Sponsors: Nicole Hildebrand; RWTH Aachen University
Recruiting
Liver Embolization Approaches for Tumor Management

Posted: February 6th, 2023, 3:00pm GMT

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Metastatic Colon Cancer; Metastatic Cancer; Metastatic Gastric Cancer; Primary Liver Cancer; Metastatic Pancreatic Cancer
Intervention: Procedure: Embolization
Sponsor: IRCCS San Raffaele
Recruiting
Looking At Bile Duct Cancer Patient Experience Patterns in Medical Trials

Posted: January 31st, 2023, 3:00pm GMT

Condition: Bile Duct Cancer
Intervention:
Sponsor: Power Life Sciences Inc.
Not yet recruiting
Therapeutic Assistance and Decision-making Algorithms in Hepatobiliary Tumor Boards

Posted: January 12th, 2023, 3:00pm GMT

Conditions: Hepatocellular Carcinoma; Fibrolamellar Hepatocellular Carcinoma; Cholangiocarcinoma, Perihilar; Intrahepatic Cholangiocarcinoma; Metastasis to Liver; Gallbladder Carcinoma
Intervention: Other: ADBoard
Sponsors: Charite University, Berlin, Germany; German Research Center for Artificial Intelligence
Not yet recruiting
Preoperative Evaluation of Lymph Nodes of Cholangiocarcinoma

Posted: January 10th, 2023, 3:00pm GMT

Conditions: Hilar Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Common Bile Duct Neoplasms; Cholangiocarcinoma; Adenocarcinoma
Interventions: Procedure: Endoscopic Ultrasound registration
Sponsors: Erasmus Medical Center
Recruiting
Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio

Posted: December 19th, 2022, 3:00pm GMT

Conditions: Bile Duct Cancer; Cholangiocarcinoma; Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic; Metastatic Intrahepatic Cholangiocarcinoma
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Radiation: Yttrium-90
Sponsors: Beth Israel Deaconess Medical Center; AstraZeneca; Sirtex Medical; Dana-Farber Cancer Institute
Recruiting
Study of [18F]FAPI-74 PET in Patients With Gastrointestinal Cancers

Posted: December 8th, 2022, 3:00pm GMT

Conditions: Gastrointestinal Cancers; Cholangiocarcinoma; Gastric Cancer; Colorectal Cancer; Pancreatic Ductal Adenocarcinoma; Hepatocellular Carcinoma
Interventions: Drug: [18F]FAPI-74 PET/CT
Sponsors: SOFIE
Recruiting
Personalized Medicine for Advanced Biliary Cancer Patients

Posted: November 14th, 2022, 3:00pm GMT

Conditions: Biliary Tract Neoplasms
Interventions: Drug: Futibatinib; Drug: Ivosidenib; Drug: Zanidatamab; Drug: Trastuzumab; Drug: Neratinib; Drug: Encorafenib; Drug: Binimetinib; Drug: Niraparib; Drug: Cisplatin; Drug: Gemcitabine
Sponsors: UNICANCER; Cancer Research UK & UCL Cancer Trials Centre; Belgian Group of Digestive Oncology; National Cancer Institute, France; Cancer Research UK; Taiho Oncology, Inc.; Servier; Zymeworks Inc.; Accord Healthcare, Inc.; Pierre Fabre Medicament; GlaxoSmithKline Research & Development Limited
Not yet recruiting
Screening Single-operator Cholangioscopy for Neoplastic Bile Duct Lesions

Posted: November 1st, 2022, 2:00am GMT

Conditions: Cholangiocarcinoma; Bile Duct Neoplasms
Interventions: Procedure: Single-operator cholangioscopy
Sponsors: Soonchunhyang University Hospital
Recruiting
EUS-guided Choledochoduodenostomy for Primary Drainage of Malignant Distal Biliary Obstruction

Posted: October 26th, 2022, 2:00pm GMT

Conditions: Biliary Obstruction; Pancreas Neoplasm; Distal Cholangiocarcinoma
Intervention: Device: EUS-CDS
Sponsors: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); VU University of Amsterdam
Recruiting
SynKIR-110 for Mesothelin Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma

Posted: October 6th, 2022, 2:00pm GMT

Conditions: Ovarian Cancer; Cholangiocarcinoma Recurrent; Mesothelioma, Malignant
Interventions: Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR
Sponsors: Verismo Therapeutics
Recruiting
Pemigatinib After Curative Local Therapy in Advanced iCCA With FGFR2 Fusion/Rearrangements

Posted: October 4th, 2022, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma; FGFR2 Gene Mutation; FGFR2 Gene Rearrangement; FGFR2 Gene Translocation
Intervention: Drug: Pemigatinib
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Incyte Biosciences International Sàrl
Recruiting
89Zr-girentuximab for PET Imaging of CAIX Positive Solid Tumors

Posted: October 3rd, 2022, 2:00pm GMT

Conditions: Cervical Cancer; Colorectal Cancer; Esophageal Cancer; Gastric Cancer; Glioblastoma Multiforme; Cholangiocarcinoma; Hepatocellular Carcinoma; Head and Neck Squamous Cell Carcinoma; Nasopharyngeal Carcinoma; Non Small Cell Lung Cancer; Small Cell Lung Cancer; Epithelial Ovarian Cancer; Pancreatic Ductal Adenocarcinoma; Soft Tissue Sarcoma
Intervention: Drug: 89Zr-DFO-girentuximab
Sponsor: Telix International Pty Ltd
Recruiting
Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)

Posted: October 3rd, 2022, 2:00pm GMT

Conditions: Recurrent Biliary Tract Carcinoma; Recurrent Distal Bile Duct Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Stage III Distal Bile Duct Cancer AJCC v8; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Distal Bile Duct Cancer AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Biliary Tract Carcinoma; Unresectable Distal Bile Duct Adenocarcinoma; Unresectable Gallbladder Carcinoma; Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Drug: Binimetinib; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Oxaliplatin
Sponsors: National Cancer Institute (NCI)
Recruiting
Endoscopy and Radiology-guided Ablation for Inoperable Cholangiocarcinoma

Posted: October 3rd, 2022, 2:00am GMT

Conditions: Perihilar Cholangiocarcinoma
Interventions: Procedure: Endoluminal radiofrequency ablation; Procedure: Endoscopic biliary stenting
Sponsors: Clinical Hospital Colentina; Carol Davila University of Medicine and Pharmacy; Universitatea din Bucuresti
Recruiting
GOT Applied as Neoadjuvant Regimen for Patients of Resectable ICC With High-risk Factors of Recurrence

Posted: September 28th, 2022, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Tislelizumab combined with GEMOX (GOT) regimen
Sponsors: Zhejiang Cancer Hospital
Recruiting
Treatment of Non-resectable Bile Duct Cancer With Radiofrequency Ablation or Photodynamic Therapy

Posted: September 22nd, 2022, 2:00pm GMT

Condition: Hilar Cholangiocarcinoma
Interventions: Drug: Photosensitizer; Procedure: Radiofrequency ablation (RFA)
Sponsors: University of Leipzig; Zentrum für Klinische Studien Leipzig
Recruiting
Preoperative Nab-paclitaxel, Cisplatin, and Gemcitabine Chemotherapy With or Without Infigratinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, The OPTIC Trial

Posted: August 25th, 2022, 2:00pm GMT

Conditions: Resectable Intrahepatic Cholangiocarcinoma; Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8; Stage I Intrahepatic Cholangiocarcinoma AJCC v8; Stage II Intrahepatic Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Infigratinib Phosphate; Drug: Nab-paclitaxel
Sponsors: Emory University; National Cancer Institute (NCI)
Not yet recruiting
Phase Ib Trial of Infigratinib In Combination With Atezolizumab And Bevacizumab for The Second-Line Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion/Amplification

Posted: August 22nd, 2022, 2:00pm GMT

Conditions: Cholangiocarcinoma; Liver Cancer
Interventions: Drug: Infigratinib; Drug: Atezolizumab; Drug: Bevacizumab
Sponsors: M.D. Anderson Cancer Center; Helsinn Healthcare
Not yet recruiting
A Study of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors

Posted: August 16th, 2022, 2:00pm GMT

Conditions: Advanced Solid Tumor; BRAF V600 Mutation
Intervention: Drug: ABM-1310
Sponsor: ABM Therapeutics Shanghai Company Limited
Recruiting
Ablation of Hepatocellular Carcinoma: a Nationwide Study

Posted: August 12th, 2022, 2:00am GMT

Conditions: Hepatocellular Carcinoma; Ablation; Hepatitis C
Interventions: Procedure: Ablation therapy
Sponsors: Rigshospitalet, Denmark
Completed
Pilot Comparing ctDNA IDV vs. SPV Sample in Pts Undergoing Biopsies for Hepatobiliary and Pancreatic Cancers

Posted: August 11th, 2022, 2:00pm GMT

Conditions: Hepatobiliary Cancer; Pancreatic Cancer; Hepatocellular Carcinoma; Cholangiocarcinoma; Ampullary Cancer; Pancreatic Carcinoma
Intervention: Diagnostic Test: ctDNA Blood Collection
Sponsor: University of California, Irvine
Recruiting
Mass Response of Tumor Cells as a Biomarker for Rapid Therapy Guidance (TraveraRTGx)

Posted: July 18th, 2022, 2:00pm GMT

Conditions: Pleural Effusion, Malignant; Ascites, Malignant; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Carcinoma, Renal; Carcinoma, Small Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Neuroendocrine; Carcinoma, Thymic; Carcinoma, Pancreatic; Carcinoma Breast; Carcinoma, Ovarian; Carcinoma Bladder; Carcinoma of Unknown Primary; Carcinoma of the Head and Neck; Carcinoma of the Oropharynx; Carcinoma of the Larynx; Carcinoma of the Bladder; Carcinoma of Esophagus; Carcinoma of the Nasopharynx; Carcinoma of the Penis; Carcinoma of the Cervix; Carcinoma of the Anus; Carcinoma of the Vulva; Carcinoma of the Appendix; Carcinoma of the Oral Cavity; Cholangiocarcinoma; Melanoma; Mesothelioma; Pancreatic Cancer
Intervention:
Sponsors: Travera Inc; xCures
Recruiting
A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer

Posted: July 11th, 2022, 2:00pm GMT

Conditions: Mesothelioma; Mesotheliomas Pleural; Mesothelioma, Malignant; Mesothelioma Peritoneum; Ovarian Cancer; Ovarian Serous Adenocarcinoma; Pancreatic Cancer; Pancreatic Adenocarcinoma; Colorectal Cancer; Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer; Ovarian Adenocarcinoma; Pancreatic Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Cholangiocarcinoma; Non Small Cell Lung Cancer
Interventions: Biological: TC-510; Drug: Fludarabine; Drug: Cyclophosphamide
Sponsor: TCR2 Therapeutics
Recruiting
Effect of Sarcopenia on Hepatocellular Carcinoma(HCC) After Systemic Therapies

Posted: July 7th, 2022, 2:00am GMT

Conditions: Hepatocellular Carcinoma; Sarcopenia
Interventions: Diagnostic Test: Diagnostic Test: gait speed; ct scan; grip strength and chair stand test
Sponsors: First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Eastern Hepatobiliary Surgery Hospital; Qilu Hospital of Shandong University
Enrolling by invitation
Effect of Sarcopenia on HCC After Lenvatinib and Anti-PD-1 Treatment

Posted: July 5th, 2022, 2:00am GMT

Conditions: Liver Cancer; Sarcopenia
Interventions: Diagnostic Test: gait speed; ct scan; grip strength and chair stand test
Sponsors: First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Eastern Hepatobiliary Surgery Hospital; Qilu Hospital of Shandong University
Enrolling by invitation
FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)

Posted: June 27th, 2022, 2:00pm GMT

Conditions: Pancreatic Ductal Adenocarcinoma; Colorectal Cancer; Esophageal Cancer; Melanoma (Skin); Soft Tissue Sarcoma; Head and Neck Squamous Cell Carcinoma; Cholangiocarcinoma
Interventions: Drug: [Ga-68]-PNT6555; Drug: [Lu-177]-PNT6555
Sponsors: POINT Biopharma
Active, not recruiting
PD-1 Antibody Plus GEMOX as Postoperative Adjuvant Therapy in Perihilar Cholangiocarcinoma

Posted: June 24th, 2022, 2:00pm GMT

Condition: Perihilar Cholangiocarcinoma
Intervention: Drug: PD-1antibody plus GEMOX
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
The Purpose of This Research Study is to See if Combining Gemcitabine, Cisplatin and Nab-paclitaxel Chemotherapy Treatments With a Direct Tumor Therapy Yittrium-90 (Y-90) Will Work Better Together to Shrink Tumors and Control Cancer

Posted: June 16th, 2022, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Induction Chemotherapy Triplet Therapy; Radiation: Concurrent Y-90 treatment; Drug: Consolidation Doublet Therapy:
Sponsors: Inova Health Care Services
Not yet recruiting
Treatment of ARB202 Advanced Gastrointestinal Cancer Patients

Posted: June 9th, 2022, 2:00am GMT

Conditions: Gastrointestinal Cancer; Cholangiocarcinoma; Liver Cancer; Colorectal Adenocarcinoma; Pancreatic Cancer; Gastric Cancer
Interventions: Drug: ARB202
Sponsors: Arbele Pty Ltd
Recruiting
HAIC Combined With Sintilimab and Bevacizumab for Unresectable Intrahepatic Cholangiocarcinoma

Posted: June 2nd, 2022, 2:00pm GMT

Condition: Intrahepatic Cholangiocarcinoma
Intervention: Drug: HAIC Combined with Tislelizumab and Apatinib
Sponsor: Binkui Li
Recruiting
Contrast-Enhanced Ultrasound for the Prediction of Bile Duct Cancer Response to Radioembolization Treatment

Posted: April 14th, 2022, 2:00pm GMT

Condition: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Perflutren Protein-Type A Microspheres; Procedure: Contrast-Enhanced Ultrasound
Sponsor: Thomas Jefferson University
Recruiting
A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression

Posted: April 13th, 2022, 2:00pm GMT

Conditions: Solid Tumors
Interventions: Drug: Bemarituzumab
Sponsors: Amgen
Recruiting
Prospective Evaluation of Pencil Beam Scanning Proton Therapy for Previously Irradiated Tumors

Posted: April 6th, 2022, 2:00am GMT

Conditions: CNS Cancer; Head and Neck Cancer; GI Cancer; Gynecologic Cancer; Prostate Cancer; Thoracic Cancer; Breast Cancer
Interventions: Radiation: Pencil Beam Scanning Proton Therapy
Sponsors: The New York Proton Center
Recruiting
Long-Term Follow-up Study of Subjects Treated With Autologous T Cells Using the Sleeping Beauty System to Express TCRs

Posted: March 23rd, 2022, 2:00pm GMT

Conditions: Gynecologic Cancer; Colorectal Cancer; Pancreatic Cancer; Non-small Cell Lung Cancer; Cholangiocarcinoma; Ovarian Cancer; Ovary Neoplasm; Squamous Cell Lung Cancer; Adenocarcinoma of Lung; Adenosquamous Cell Lung Cancer
Intervention: Biological: Neoantigen specific TCR-T cell drug product
Sponsor: Alaunos Therapeutics
Recruiting
Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated Primary Liver Cancer

Posted: March 23rd, 2022, 2:00pm GMT

Conditions: Primary Liver Cancer; Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Combined Hepatocellular-cholangiocarcinoma
Interventions: Other: Observation
Sponsors: Geneplus-Beijing Co. Ltd.; Eastern Hepatobiliary Surgery Hospital
Recruiting
M9241 in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

Posted: March 18th, 2022, 2:00pm GMT

Conditions: Metastatic Colorectal Cancer (Mcrc); Intrahepatic Cholangiocarcinoma (Icc); Colorectal Cancer; Colorectal Neoplasms; Cholangiocarcinoma; Intrahepatic Bile Duct Cancer; Bile Duct Cancer; Bile Duct Neoplasms
Interventions: Drug: Floxuridine; Drug: 5-Fluorouracil; Drug: Irinotecan; Device: Intera 3000 Hepatic Artery Infusion Pump (HAIP); Drug: Oxaliplatin; Drug: Leucovorin; Drug: M9241; Drug: Gemcitabine; Drug: Dexamethasone
Sponsors: National Cancer Institute (NCI)
Recruiting

Trial - Bile Duct Cancer

Precision Medicine for Combined Hepatocellular-Cholangiocarcinoma

Posted: November 24th, 2023, 3:00am GMT

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

Posted: November 20th, 2023, 3:00am GMT

Conditions: Locally Advanced Non-metastatic Intrahepatic Cholangiocarcinoma; Determine Efficacy of Liver Transplantation After Neoadjuvant Systemic Therapy in Patients With Locally Advanced Non-metastatic Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Liver Transplant
Sponsors: Rutgers, The State University of New Jersey
Not yet recruiting
Combination Therapy of HAIC, Surufatinib and Tislelizumab for Unresectable or Metastatic Biliary Tract Cancer

Posted: November 16th, 2023, 3:00am GMT

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
Tripegfilgrastim Trial to Reduce the Risk of Severe Neutropenia in Patients With Unresectable Pancreaticobiliary Cancers

Posted: November 16th, 2023, 3:00am GMT

Conditions: Unresectable Pancreatic Cancer; Unresectable Bile Duct Carcinoma; Unresectable Biliary Tract Carcinoma
Interventions: Drug: Tripegfilgrastim
Sponsors: National Cancer Center, Korea; Seoul National University Hospital
Not yet recruiting
Clinical Study of CEA Targeting Chimeric Antigen Receptor T Lymphocytes（CAR-T） for CEA Positive Advanced Malignant Solid Tumors

Posted: November 10th, 2023, 3:00am GMT

Conditions: Gastric Cancer; Colon Cancer; Rectal Cancer; Breast Cancer; Lung Cancer; Esophagus Cancer; Cholangiocarcinoma; Pancreas Cancer
Interventions: Biological: CEA-targeted CAR-T cells; Biological: CEA-targeted CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; First Affiliated Hospital of Wannan Medical College
Recruiting
LIver TrAnspLantation for Non-resectable Peri-HIlar cholangioCArcinoma (LITALHICA)

Posted: November 9th, 2023, 3:00am GMT

Conditions: Perihilar Cholangiocarcinoma
Interventions: Procedure: Liver transplantation
Sponsors: Azienda Sanitaria Ospedaliera; Istituto Oncologico Veneto IRCCS
Not yet recruiting
A Single-center, Prospective Cohort Study on the Differentiation of Benign and Malignant Bile Duct Stenosis Based on Bile and Peripheral Blood cfDNA Methylation Profiles

Posted: November 3rd, 2023, 2:00am GMT

Conditions: Bile Duct Neoplasms; Jaundice, Obstructive; Bile Duct Diseases
Interventions: Diagnostic Test: cfDNA methylation detection
Sponsors: Air Force Military Medical University, China
Recruiting
Ketamine-midazolam as a Sedative Agent in Endoscopic Retrograde Cholangiopancreatography.

Posted: November 1st, 2023, 2:00am GMT

Conditions: Cholangitis; Pancreatic Cancer; Choledocholithiasis; Choledochal Cyst
Interventions: Drug: Ketamine; Drug: Midazolam; Drug: Pethidin
Sponsors: National University of Malaysia
Recruiting
A Study of Rilvegostomig Plus Chemotherapy as Adjuvant Therapy for Biliary Tract Cancer After Resection

Posted: October 31st, 2023, 2:00am GMT

Conditions: Biliary Tract Cancer
Interventions: Drug: Rilvegostomig; Drug: Placebo; Drug: Capecitabine; Drug: Gemcitabine/Cisplatin; Drug: S-1 [Tegafur/Oteracil/gimeracil]
Sponsors: AstraZeneca
Not yet recruiting
Endoscopic Scissors Cutting Nasobiliary Duct VS Bilateral Plastic Stent

Posted: October 30th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma, Hilar; Biliary Stricture; Hilar Cholangiocarcinoma; Klatskin Tumor; Biliary Disease; Bile Duct Diseases; Bile Duct Stenosis
Interventions: Device: Endoscopic nasobiliary duct cutting; Device: Bilateral plastic stent
Sponsors: First People's Hospital of Hangzhou
Recruiting
Locally ablatIVe thErapy for oLigo-progressive gastrOintestiNal maliGnancies (LIVELONG)

Posted: October 26th, 2023, 2:00am GMT

Conditions: Esophageal Cancer; Small Bowel Cancer; Gastroesophageal-junction Cancer; Gastric Cancer; Colorectal Cancer; Appendiceal Cancer; Biliary Cancer; Gall Bladder Cancer; Intrahepatic Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Oligoprogressive
Interventions: Device: Ablative local therapy
Sponsors: University of California, Davis; National Cancer Institute (NCI)
Recruiting
LIver Transplantation for Non-Resectable Intrahepatic CholAngiocarcinoma

Posted: October 24th, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Liver transplantation
Sponsors: Azienda Sanitaria Ospedaliera; Istituto Oncologico Veneto IRCCS
Not yet recruiting
Endoscopic Retrograde Cholangiopancreatography In Patients Older Than 65Years Old With Obstructive Jaundice: Efficacy And Outcome

Posted: October 20th, 2023, 2:00am GMT

Conditions: Obstructive Jaundice
Interventions: Procedure: Endoscopic retrograde cholangiopancreatography
Sponsors: Sohag University
Not yet recruiting
Surufatinib Plus Cadonilimab in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma

Posted: October 20th, 2023, 2:00am GMT

Conditions: Bile Duct Adenocarcinoma
Interventions: Drug: surufatinib plus cadonilimab
Sponsors: Zhejiang Cancer Hospital
Recruiting
A Study to Evaluate the Safety and Efficacy of PRRT With 177Lu-EB-FAPI in Patients With Advanced Cholopancreatic Tumors

Posted: October 13th, 2023, 2:00am GMT

Conditions: Advanced Pancreatic Cancer and Cholangiocarcinoma
Interventions: Drug: PRRT with 177Lu-EB-FAPI
Sponsors: Zhejiang University
Recruiting
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Posted: October 13th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic
Interventions: Drug: Ivosidenib
Sponsors: Servier
Not yet recruiting
Modified vs Conventional Blumgart Anastomosis of LPD for the Effects of Pancreatic Fistula of Periampullary Carcinoma

Posted: October 10th, 2023, 2:00am GMT

Conditions: Ampullary Cancer; Bile Duct Cancer; Pancreas Cancer; Duodenum Cancer
Interventions: Procedure: Modified Blumgart Anastomosis in LPD; Procedure: conventional Blumgart anastomosis in LPD
Sponsors: Affiliated Hospital of Guangdong Medical University
Enrolling by invitation
Use of Stratafix Symmetric™ to Prevent Incisional Hernia in Gastrointestinal and Abdominal Surgery

Posted: October 2nd, 2023, 2:00am GMT

Conditions: C.Surgical Procedure; Disruption of Wound, Suture
Interventions: Device: Stratafix suture; Device: Standard of care suture
Sponsors: West Michigan Cancer Center; Ethicon, Inc.
Recruiting
Robot-assisted vs Laparoscopic vs Open Radical Cholecystectomy for Gallbladder Cancer

Posted: September 29th, 2023, 2:00am GMT

Conditions: Gallbladder Cancer
Interventions: Other: Minimally invasive surgery
Sponsors: Hospital del Mar
Enrolling by invitation
Radioembolization With Tremelimumab and Durvalumab for Locally Advanced, Unresectable Intrahepatic Cholangiocarcinoma

Posted: September 28th, 2023, 2:00am GMT

Conditions: Locally Advanced Intrahepatic Cholangiocarcinoma; Oligometastatic Intrahepatic Cholangiocarcinoma; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Angiography; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Tremelimumab; Procedure: Yttrium-90 Microsphere Radioembolization
Sponsors: Mayo Clinic
Not yet recruiting
Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor

Posted: September 27th, 2023, 2:00am GMT

Conditions: Cholangiocarcinoma Metastatic
Interventions: Drug: TT-00420 (tinengotinib)
Sponsors: TransThera Sciences (Nanjing), Inc.
Not yet recruiting
Durvalumab With Gemcitabine and Cisplatin for the Treatment of High Risk Resectable Liver Cancer Before Surgery

Posted: September 22nd, 2023, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging; Procedure: Resection
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Biliary Tract Carcinoma; Cholangiocarcinoma; Bile Duct Cancer
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Zimberelimab; Drug: Quemliclustat
Sponsors: Nataliya Uboha; Arcus Biosciences, Inc.; Gilead Sciences; University of Wisconsin, Madison
Not yet recruiting
Prospective Observational Study to Predict the Response of Biliary Tract Tumors to Immunotherapy

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Biliary Tract Tumor; Cholangiocarcinoma
Interventions: Other: Blood samples, tumor biopsy specimens will be collected
Sponsors: Zhejiang Cancer Hospital
Recruiting
A Clinical Trial Targeting CEA Chimeric Antigen Receptor T (CAR-T) for CEA Positive Advanced Malignant Solid Tumors

Posted: September 21st, 2023, 2:00pm GMT

Conditions: Colorectal Cancer; Esophagus Cancer; Gastric Cancer; Pancreas Cancer; Non-small Cell Lung Cancer; Breast Cancer; Bile Duct Cancer
Interventions: Biological: CEA-targeted CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; Zhejiang University
Recruiting
CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence

Posted: September 14th, 2023, 2:00pm GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma
Interventions: Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Cisplatin; Procedure: Curative Surgery; Drug: Capecitabine
Sponsors: Gruppo Oncologico del Nord-Ovest
Recruiting
Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

Posted: September 12th, 2023, 2:00pm GMT

Conditions: Combined Hepatocellular Cholangiocarcinoma
Interventions: Drug: gemcitabine ,oxaliplatin,anlotinib,Sintilimab
Sponsors: Sichuan University
Not yet recruiting
A Prospective, Observational Study on the Prevalence of Clinically Useful Mutations in Solid Tumor Characterized by Next Generation Sequencing Methods on Liquid Biopsy Analysis (POPCORN)

Posted: September 8th, 2023, 2:00pm GMT

Conditions: Solid Tumor; Advanced Solid Tumor; Locally Advanced Solid Tumor; Colon Rectal Cancer; Gastric Cancer; Pancreatic Cancer; Bile Duct Cancer; Hepatocarcinoma; Breast Cancer; Ovarian Cancer; Endometrial Cancer; Cervical Cancer; Vulva Cancer; Melanoma
Sponsors: Centro di Riferimento Oncologico - Aviano
Recruiting
Neoadjuvant Tremelimumab and Durvalumab With Gem/Cis in Intrahepatic Cholangiocarcinoma

Posted: August 30th, 2023, 2:00pm GMT

Conditions: Borderline Resectable Carcinoma; Biliary Tract Cancer
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Gemcitabine; Drug: Cisplatin; Procedure: Surgical Resection
Sponsors: Georgetown University; AstraZeneca
Not yet recruiting
Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors

Posted: August 25th, 2023, 2:00pm GMT

Conditions: Gastric Cancer; Colon Cancer; Pancreas Cancer; Esophagus Cancer; Cholangiocarcinoma; Lung Cancer; Breast Cancer
Interventions: Biological: CEA CAR-T cells; Biological: CEA CAR-T cells
Sponsors: Chongqing Precision Biotech Co., Ltd; The First Affiliated Hospital of Nanchang University
Recruiting
Diagnostic Efficacy of EUS-FNA/B Versus ERCP With or Without POCS-TB in Patients With Suspected Hilar Cholangiocarcinoma

Posted: August 15th, 2023, 2:00pm GMT

Conditions: Klatskin Tumor; Cholangiocarcinoma; Biopsy, Fine-Needle; Endoscopic Retrograde Cholangiopancreatography
Interventions: Diagnostic Test: The sampling method selected in patients with suspected hilar cholangiocarcinoma
Sponsors: Qilu Hospital of Shandong University; First Affiliated Hospital, Sun Yat-Sen University; First Affiliated Hospital of Guangxi Medical University; LanZhou University; Sir Run Run Shaw Hospital; Wuhan Union Hospital, China
Recruiting
IAH0968 in Combination With GC for the Treatment of HER2-Positive Unresectable Advanced/Metastatic Malignant Tumors

Posted: August 14th, 2023, 2:00pm GMT

Condition: HER2 Gene Mutation
Interventions: Combination Product: Injection of IAH0968+Gemcitabine+Cisplatin; Combination Product: Gemcitabine+Cisplatin
Sponsor: SUNHO（China）BioPharmaceutical CO., Ltd.
Recruiting
KN026 Plus Chemotherapy With or Without KN-046 in HER2 Positive Colorectal Cancer and Biliary Carcinoma Study: a Phase Ⅱ Study

Posted: August 10th, 2023, 2:00pm GMT

Conditions: HER2-positive Colorectal Cancer; HER2-positive Biliary Tract Cancer
Interventions: Drug: KN026; Drug: KN046; Drug: XELOX
Sponsor: Peking University Cancer Hospital & Institute
Not yet recruiting
Cadonilimab With Chemotherapy in Treating Advanced Biliary Cancer

Posted: August 7th, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma Non-resectable
Interventions: Drug: Candonilimab; Drug: Cisplatin; Drug: Gemcitabine
Sponsor: West China Hospital
Recruiting
IMM2510, a PD-L1 and VEGF Bispecific Fusion Protein, in Patients With Advanced Solid Tumors

Posted: August 2nd, 2023, 2:00pm GMT

Condition: Advanced Solid Tumors
Intervention: Drug: IMM2510
Sponsors: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.; Zhejiang Cancer Hospital; Fudan University
Recruiting
A Single-Arm Study of Pembrolizumab With Gemcitabine and Cisplatin as Perioperative Therapy for Potentially Resectable Intrahepatic Cholangiocarcinoma

Posted: August 1st, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma
Interventions: Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin
Sponsor: M.D. Anderson Cancer Center
Not yet recruiting
The Incidence of Gallstones After Gastrectomy

Posted: July 28th, 2023, 2:00pm GMT

Conditions: Gallstone; Gastric Cancer
Interventions: Procedure: Distal gastrectomy and radical resection; Procedure: Total gastrectomy and radical resection
Sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
Recruiting
[68Ga]Ga-FAPI-46 Positron Emission Tomography (PET) Scan to Improve the Imaging of Pancreatic and Bile Duct Cancer

Posted: July 24th, 2023, 2:00pm GMT

Conditions: Pancreatic Cancer; Cholangiocarcinoma
Intervention: Diagnostic Test: [68Ga]Ga-FAPI-46 PET/CT
Sponsors: Amsterdam UMC, location VUmc; Dutch Cancer Society; Leiden University Medical Center
Recruiting
Treatment With NPX267 for Subjects With Solid Tumors Known to Express HHLA-2

Posted: July 24th, 2023, 2:00pm GMT

Conditions: Metastatic Malignant Neoplasm
Interventions: Drug: NPX267
Sponsors: NextPoint Therapeutics, Inc.
Recruiting
Liver Transplantation After ex Vivo Liver Perfusion

Posted: July 18th, 2023, 2:00am GMT

Conditions: Liver Transplant; Complications; Transplant; Failure, Liver; Transplant Dysfunction; Transplant; Complication, Rejection; Transplant; Liver Metastases; Liver Cancer
Interventions: Procedure: Liver transplantation
Sponsors: Oslo University Hospital; South-Eastern Norway Regional Health Authority
Not yet recruiting
Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma

Posted: July 17th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma
Interventions: Drug: Tinengotinib 8 mg; Drug: Tinengotinib 10 mg; Drug: Physician's Choice
Sponsors: TransThera Sciences (Nanjing), Inc.
Not yet recruiting
Effects of Dexamethasone on Common Bile Duct Cannulation Time

Posted: July 14th, 2023, 2:00pm GMT

Conditions: Common Bile Duct Diseases; Common Bile Duct Calculi; Common Bile Duct Stricture; Common Bile Duct Neoplasms; Common Bile Duct Dilatation
Interventions: Drug: Dexamethasone 4mg
Sponsors: Gujranwala medical college District Headquarters Hospital, Gujranwala
Recruiting
HMPL-453 Food Effect and PPI Study in Healthy Volunteer Study

Posted: July 5th, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: HMPL-453; Drug: Rabeprazole
Sponsors: Hutchmed
Completed
Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma

Posted: June 27th, 2023, 2:00pm GMT

Conditions: IDH1-mutant Cholangiocarcinoma
Interventions: Drug: Ivosidenib; Drug: Recommended Combination Dose (RCD) of ivosidenib; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Servier Bio-Innovation LLC; Institut de Recherches Internationales Servier
Recruiting
Senior Adult Hepatobiliary Prehab Study

Posted: June 27th, 2023, 2:00pm GMT

Conditions: Hepatobiliary Cancer; Cholangiocarcinoma; Liver Metastases
Interventions: Behavioral: Resistance Training; Behavioral: Aerobic Training
Sponsors: H. Lee Moffitt Cancer Center and Research Institute
Recruiting
Combined Treatment of Treated Bile Duct Cancer

Posted: June 22nd, 2023, 2:00pm GMT

Condition: Bile Duct Cancer
Intervention: Drug: envolizumab , sovalteinib
Sponsor: Zhejiang Cancer Hospital
Not yet recruiting
Pemigatinib Combined With PD-1 Inhibitor in Unresectable or Metastatic Intrahepatic Cholangiocarcinoma

Posted: June 22nd, 2023, 2:00pm GMT

Conditions: Carcinoma; Intrahepatic Cholangiocarcinoma; Digestive System Neoplasms; PD-1 Inhibitor; First-line Treatment
Interventions: Drug: Pemigatinib; Drug: PD-1 Inhibitors
Sponsors: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; First Affiliated Hospital of Jinan University; Shenzhen University General Hospital
Recruiting
The Construction of Clinical Database and Multiomics Biobank Based on a Multicentral Prospective Cohort of Benign and Malignant Biliary Tract Diseases

Posted: June 9th, 2023, 2:00pm GMT

Conditions: Biliary Tract Diseases; Gallbladder Cancer; Extrahepatic Bile Duct Cancer; Intrahepatic Cholangiocarcinoma; Biliary Tract Neoplasms; Gall Stone
Intervention: Other: no interventions
Sponsor: RenJi Hospital
Not yet recruiting
Phase 3b Study of Ivosidenib for Patients With Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

Posted: May 25th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma
Interventions: Drug: Ivosidenib Oral Tablet
Sponsors: Servier Affaires Médicales
Recruiting
Endoscopic Drainage of Presumed Resectable pCCA Using an Intrahepatic Plastic Stent With Retrieval String

Posted: May 25th, 2023, 2:00pm GMT

Condition: Perihilar Cholangiocarcinoma
Intervention: Device: Intrahepatic biliary stent with retrieval string
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Recruiting
Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutation Cholangiocarcinoma

Posted: May 24th, 2023, 2:00pm GMT

Condition: Cholangiocarcinoma
Intervention: Drug: GNS561 + Trametinib
Sponsor: Genfit
Not yet recruiting
Study of WM-A1-3389 in Participants With Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer

Posted: May 24th, 2023, 2:00pm GMT

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Cholangiocarcinoma; Head and Neck Cancer; Non Small Cell Lung Cancer
Interventions: Biological: WM-A1-3389; Biological: Pembrolizumab
Sponsors: Wellmarker Bio; Merck Sharp & Dohme LLC
Not yet recruiting
Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors

Posted: May 15th, 2023, 2:00pm GMT

Conditions: Melanoma; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; High Grade Serous Adenocarcinoma of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Endometrial Cancer; Cervical Cancer; Renal Cell Carcinoma; Bladder Cancer; Esophageal Cancer; Gastric Cancer; Gastroesophageal-junction Cancer; Colorectal Cancer; Anal Cancer; Hepatocellular Carcinoma; Bile Duct Cancer
Interventions: Drug: AI-061
Sponsors: OncoC4, Inc.; OncoC4 AU Pty Ltd; Avance Clinical
Recruiting
A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)

Posted: May 9th, 2023, 2:00pm GMT

Conditions: Biliary Cancer; Bile Duct Cancer; Cancer of the Bile Duct
Interventions: Drug: oxaliplatin; Drug: capecitabine; Biological: Keytruda; Biological: CDX-1140
Sponsors: National Cancer Institute (NCI)
Not yet recruiting
A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors

Posted: May 8th, 2023, 2:00pm GMT

Conditions: Breast Cancer Metastatic; Pancreatic Cancer; NSCLC, Metastatic; Synovial Sarcoma; Colon Cancer; Metastatic Colon Cancer; Melanoma Recurrent; Metastatic Skin Cancer; Melanoma Stage IV; Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer; Cholangiocarcinoma; Ovarian Cancer; Metastatic Melanoma; Hepatocellular Carcinoma
Interventions: Drug: ST316
Sponsors: Sapience Therapeutics
Recruiting
Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)

Posted: April 28th, 2023, 2:00pm GMT

Condition: Advanced Intrahepatic Cholangiocarcinoma
Interventions: Procedure: Cryoablation; Drug: Sintilimab; Drug: Lenvatinib
Sponsor: Fudan University
Recruiting
Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States

Posted: April 27th, 2023, 2:00am GMT

Conditions: Cirrhosis; Cirrhosis, Liver; Cirrhosis Early; Cirrhosis Due to Hepatitis B; Cirrhosis Advanced; Cirrhosis Infectious; Cirrhosis Alcoholic; Cirrhosis, Biliary; Cirrhosis Cryptogenic; Cirrhosis Due to Hepatitis C; Cirrhosis Due to Primary Sclerosing Cholangitis
Interventions: Drug: Rosuvastatin
Sponsors: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); The Cleveland Clinic; Columbia University; Weill Medical College of Cornell University; Duke University; Mayo Clinic; University of Miami; University of Michigan; University of California, San Diego; University of California, San Francisco; LAC+USC Medical Center; Virginia Commonwealth University; National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Cancer Institute (NCI); University of Southern California
Recruiting
Lenvatinib, Tislelizumab Combined With Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma

Posted: April 21st, 2023, 2:00pm GMT

Conditions: Advanced Cholangiocarcinoma
Interventions: Drug: Lenvatinib, tislelizumab, gemcitabine and cisplatin; Drug: Gemcitabine and cisplatin
Sponsors: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhengzhou University; The Affiliated Tumor Hospital of Xinjiang Medical University
Recruiting
IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor

Posted: April 17th, 2023, 2:00pm GMT

Conditions: Cholangiocarcinoma With IDH1 Mutation; Solid Tumors With IDH1 Mutation
Intervention: Drug: AB-218 capsule
Sponsor: AnHeart Therapeutics Inc.
Not yet recruiting
IMM2902 in Patients With Advanced Solid Tumors Expressing HER2

Posted: April 10th, 2023, 2:00pm GMT

Conditions: Advanced Solid Tumor; Advanced Lung Cancer; Advanced Gastric Carcinoma; Advanced Cholangiocarcinoma
Intervention: Drug: IMM2902
Sponsor: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Recruiting
AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease

Posted: March 30th, 2023, 2:00pm GMT

Conditions: Advanced Cholangiocarcinoma; Advanced Hepatocellular Carcinoma; Advanced Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Liver; Refractory Malignant Solid Neoplasm; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8
Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: RNA Transcription Modulator AU-409
Sponsors: University of Southern California; National Cancer Institute (NCI); Auransa, Inc.
Recruiting
A Phase 1 Dose-escalation and Expansion Study of the PD-1 x ILT4 Bispecific Antibody CDX-585 in Patients With Advanced Malignancies

Posted: March 29th, 2023, 2:00pm GMT

Conditions: Non-small Cell Lung Cancer; Gastric Cancer; Head and Neck Cancer; Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Bladder Urothelial Carcinoma; Colorectal Cancer; Esophageal Cancer; Hepatic Cancer; Renal Cell Carcinoma; Cholangiocarcinoma; Pancreatic Cancer; Other Solid Tumors
Interventions: Drug: CDX-585
Sponsors: Celldex Therapeutics
Recruiting
Evidence Based Mental Wellness Programming Online for Adults Across Chronic Physical Conditions

Posted: March 27th, 2023, 2:00am GMT

Conditions: Primary Biliary Cholangitis; Heart Failure; Digestive Diseases; Women Who Have Experienced a Cardiac Event; Cirrhosis, Liver; Post-Transplant; Cancer; Chronic Kidney Diseases; Other Chronic Physical Condition
Interventions: Behavioral: Online mind-body wellness program; Behavioral: Online mind-body wellness program + Weekly Check-ins
Sponsors: University of Alberta; Canadian Institutes of Health Research (CIHR)
Recruiting
Cadonilimab Combined With Gem/Cis as First Line Therapy in Patients With Advanced ICC

Posted: March 23rd, 2023, 2:00am GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Cadonilimab+Gem/Cis
Sponsors: Shen Feng
Active, not recruiting
Durvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)

Posted: March 16th, 2023, 2:00pm GMT

Conditions: Biliary Tract Cancer
Interventions: Biological: Durvalumab; Drug: Gemcitabine monotherapy; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + oxaliplatin; Drug: Gemcitabine + carboplatin; Drug: Gemcitabine + cisplatin + S-1; Drug: Gemcitabine + S-1; Drug: Gemcitabine + cisplatin + albumin-bound paclitaxel
Sponsors: AstraZeneca
Recruiting
Application of 18F-PSMA PET / CT Imaging in Prostate Specific Membrane Antigen Positive Tumor

Posted: March 9th, 2023, 3:00pm GMT

Condition: Malignancy
Intervention: Drug: Al18F-PSMA-BCH PET/CT
Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Recruiting
A Multicenter Prospective Randomized Controlled Study of RPD Versus LPD

Posted: March 6th, 2023, 3:00pm GMT

Conditions: Pancreatic Cancer; Common Bile Duct Diseases; Periampullary Carcinoma
Interventions: Procedure: laparoscopic pancreaticoduodenectomy; Procedure: Robot Pancreaticoduodenectomy
Sponsor: The First Affiliated Hospital of University of South China
Not yet recruiting
A Prospective Study on the Safety and Efficacy of Robot-assisted Pancreaticoduodenectomy

Posted: March 6th, 2023, 3:00pm GMT

Conditions: Pancreatic Cancer; Common Bile Duct Diseases; Periampullary Carcinoma
Intervention: Procedure: Robot-assisted Pancreaticoduodenectomy
Sponsor: The First Affiliated Hospital of University of South China
Not yet recruiting
First-line Trastuzumab, Gemcitabine, Cisplatin and Nivolumab in Advanced HER2- Positive Biliary Tract Cancer: a Multicenter, Open-label, Single-arm Phase Ib/II Trial (HERBOT)

Posted: March 1st, 2023, 3:00pm GMT

Condition: HER2 Positive Advanced/Metastatic/Nonresectable Biliary Tract Cancer
Intervention: Drug: Trastuzumab+Nivolumab+Gemcitabine+Cisplatin
Sponsor: Yonsei University
Not yet recruiting
A-LiNK: Improving Outcomes in Autoimmune Liver Disease

Posted: March 1st, 2023, 3:00pm GMT

Conditions: Autoimmune Hepatitis; Primary Sclerosing Cholangitis
Intervention: Other: No interventions
Sponsor: Children's Hospital Medical Center, Cincinnati
Recruiting
ctDNA Detection of MRD in Predicting Postoperative Recurrence in Biliary Tract Cancers：A Multicenter Prospective Trial.

Posted: February 24th, 2023, 3:00pm GMT

Condition: Biliary Tract Cancer
Intervention: Procedure: No intervention
Sponsor: The First Affiliated Hospital with Nanjing Medical University
Recruiting
Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Posted: February 21st, 2023, 3:00pm GMT

Conditions: Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Drug: Camrelizumab; Drug: Gemcitabine Injection; Drug: Cisplatin injection; Drug: Cisplatin-Eluting Beads; Procedure: D-TACE
Sponsors: Hua Li
Recruiting
Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

Posted: February 17th, 2023, 3:00pm GMT

Conditions: Locally Advanced Solid Tumor
Interventions: Drug: TNG462
Sponsors: Tango Therapeutics, Inc.
Recruiting
Exogenous and Endogenous Risk Factors for Early-onset Colorectal Cancer

Posted: February 17th, 2023, 3:00pm GMT

Conditions: Colorectal Cancer; Early Onset Colorectal Cancer; Diet Habit; Risk Reduction
Intervention: Behavioral: Semi Quantitative Food Frequency Questionnaire (SQFFQ)
Sponsors: San Raffaele University; Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Ospedale Civile Guglielmo da Saliceto, Piacenza, Italy; Centro di Riferimento Oncologico di Aviano, Aviano, Italy; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy; Gastroenterology Unit, University Hospital of Padova, Padova, Italy; Clinical Gastroenterology Unit, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy; IRCCS Arcispedale S. Maria Nuova - Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy; Azienda Ospedaliera San Gerardo di Monza, Monza, Italy; Azienda ULSS5 Polesana, Rovigo, Italy; Istituto Tumori Regina Elena - IRCCS IFO, Roma, Italy; University Hospital of Padova, Padova, Italy; IRCCS De Bellis, Castellana Grotte, Italy; University Hospital HELIOS Klinikum Wuppertal, Center for Hereditary Tumors, University of Witten-Herdecke, Wuppertal, Germany; Hospital of the University of Munich (LMU), Campus Großhadern, Munich, Germany; Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Helsinki University Hospital, Helsinki, Finland; Oslo University Hospital (OUS), Institute for Cancer Genetics and Informatics Norwegian Radium Hospital, Oslo, Norway; Department of Medicine University of Chicago Medicine, Illinois, USA; University of Colorado Hospital, CO, USA; University of Michigan Ann Arbor, Michigan, USA; Columbia University Irving Medical Center, New York, NY; The James Comprehensive Cancer Center, Columbus, OH, USA; Ohio State University; Cleveland Clinic Main Campus, Cleveland, OH, USA; Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
Recruiting
Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement

Posted: February 14th, 2023, 3:00pm GMT

Conditions: Advanced Cholangiocarcinoma; FGFR2 Fusions; Gene Rearrangement
Interventions: Drug: TAS-120
Sponsors: Taiho Oncology, Inc.
Recruiting
Domvanalimab and Zimberelimab in Advanced Liver Cancers

Posted: February 13th, 2023, 3:00pm GMT

Conditions: Hepatobiliary Cancer; Liver Cancer; Cholangiocarcinoma; Hepatocellular Carcinoma
Interventions: Drug: Zimberelimab; Drug: Domvanalimab
Sponsors: University of Texas Southwestern Medical Center; Arcus Biosciences, Inc.; Cancer Prevention Research Institute of Texas
Recruiting
Study on the Accuracy of Proteomics in Evaluating Lymph Node Metastasis Status in Cholangiocarcinoma Patients

Posted: February 10th, 2023, 3:00pm GMT

Condition: Cholangiocarcinoma
Intervention: Diagnostic Test: No interventions.
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Recruiting
FGF19 in Obstructive Cholestasis: "Unveil the Signal"

Posted: February 8th, 2023, 3:00pm GMT

Conditions: Cholestasis; Icterus; Cholangiocarcinoma; Pancreatic Neoplasms; Liver Metastasis Colon Cancer
Intervention: Other: Biospecimen sampling
Sponsors: Nicole Hildebrand; RWTH Aachen University
Recruiting
Liver Embolization Approaches for Tumor Management

Posted: February 6th, 2023, 3:00pm GMT

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Metastatic Colon Cancer; Metastatic Cancer; Metastatic Gastric Cancer; Primary Liver Cancer; Metastatic Pancreatic Cancer
Intervention: Procedure: Embolization
Sponsor: IRCCS San Raffaele
Recruiting
Looking At Bile Duct Cancer Patient Experience Patterns in Medical Trials

Posted: January 31st, 2023, 3:00pm GMT

Condition: Bile Duct Cancer
Intervention:
Sponsor: Power Life Sciences Inc.
Not yet recruiting
Baby Detect : Genomic Newborn Screening

Posted: January 18th, 2023, 3:00am GMT

Conditions: Congenital Adrenal Hyperplasia; Familial Hyperinsulinemic Hypoglycemia 1; Phosphoglucomutase 1 Deficiency; Maturity Onset Diabetes of the Young; Cystic Fibrosis; Hypophosphatasia, Infantile; Congenital Hypothyroidism; Deficit in Anterior Pituitary Function and Variable Immunodeficiency; Pituitary Hormone Deficiency, Combined; Diamond Blackfan Anemia; Wiskott-Aldrich Syndrome; Fanconi Anemia; Hemophilia A; Hemophilia B; Glucose 6 Phosphate Dehydrogenase Deficiency; Alpha-Thalassemia; Sickle Cell Disease; Shwachman-Diamond Syndrome; Alpha 1-Antitrypsin Deficiency; Inflammatory Bowel Disease 25, Autosomal Recessive; Wilson Disease; Progressive Familial Intrahepatic Cholestasis; Crigler-Najjar Syndrome; Familial Chylomicronemia; Lysosomal Acid Lipase Deficiency; Familial Hemophagocytic Lymphocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Severe Congenital Neutropenia; Severe Combined Immune Deficiency; Chronic Granulomatous Disease; Menkes Disease; Adrenoleukodystrophy; Smith-Lemli-Opitz Syndrome; Ataxia With Vitamin E Deficiency; Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type); Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type); Thiamine-Responsive Megaloblastic Anemia; Thiamine Metabolism Dysfunction Syndrome 2; Deficiency of GOT2; Cerebral Folate Transport Deficiency; Segawa Syndrome, Autosomal Recessive; Congenital Myasthenic Syndrome; Metachromatic Leukodystrophy; Sepiapterin Reductase Deficiency; Dopamine Beta Hydroxylase Deficiency; Glut1 Deficiency Syndrome; Late-Infantile Neuronal Ceroid Lipofuscinosis; Aromatic L-amino Acid Decarboxylase Deficiency; Charcot-Marie-Tooth Disease, Type 6C; Hereditary Hyperekplexia; Brain Dopamine-Serotonin Vesicular Transport Disease; Very Long Chain Hydroxy Acyl Dehydrogenase Deficiency; Tyrosinemia, Type I; Disaccharide Intolerance I; Beta Ketothiolase Deficiency; Phosphoglycerate Dehydrogenase Deficiency; Succinyl-Coa:3-Ketoacid Coa-Transferase Deficiency; Pyridoxine-5'-Phosphate Oxidase Deficiency; Pyridoxine-Dependent Epilepsy; Propionic Acidemia; Pompe Disease; Phenylalanine Hydroxylase Deficiency; Ornithine Transcarbamylase Deficiency; N Acetyl Glutamate Synthetase Deficiency; Riboflavin Deficiency; Maple Syrup Urine Disease; Medium Chain Acyl CoA Dehydrogenase Deficiency; Malonic Acidemia; Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency; Isovaleric Acidemia; Phosphoserine Aminotransferase Deficiency; Phosphoserine Phosphatase Deficiency; Hyperornithinemia-Hyperammonemia-Homocitrullinuria; S-Adenosylhomocysteine Hydrolase Deficiency; Mucopolysaccharidosis VII; Mucopolysaccharidosis VI; Mucopolysaccharidosis IV A; Mucopolysaccharidosis II; Mucopolysaccharidosis I; Transcobalamin Deficiency; Isolated Methylmalonic Acidemia; Cobalamin Deficiency; Homocystinuria; Holocarboxylase Synthetase Deficiency; Fanconi Bickel Syndrome; Glycogen Storage Disease; Glycine Encephalopathy; Glutaric Acidemia I; Glucose Galactose Malabsorption; Gaucher Disease, Type 1; Galactosemias; Fructosemia; Fructose-1,6-Diphosphatase Deficiency; Carbamoyl Phosphate Synthase 1 Deficiency; Citrullinemia Type II; Citrullinemia 1; Creatine Deficiency Syndrome; Systemic Primary Carnitine Deficiency; Carnitine Palmitoyltransferase Deficiency 2; Carnitine Palmitoyltransferase Deficiency 1; Carnitine Acylcarnitine Translocase Deficiency; Riboflavin Transporter Deficiency; Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency; Andersen Tawil Syndrome; Timothy Syndrome; Jervell-Lange Nielsen Syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Familial Hypertrophic Cardiomyopathy Type 4; Pseudohypoaldosteronism, Type II; Pseudohypoaldosteronism Type 1; Primary Hyperoxaluria; X Linked Hypophosphatemia; Hereditary Nephrogenic Diabetes Insipidus; Cystinosis; Congenital Nephrotic Syndrome, Finnish Type; Alport Syndrome; Hereditary Retinoblastoma; Biotinidase Deficiency; Aciduria, Argininosuccinic; Argininemia; Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of; 3-Hydroxy 3-Methyl Glutaric Aciduria; 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency
Sponsors: Centre Hospitalier Régional de la Citadelle; Centre Hospitalier Universitaire de Liege; University of Liege; Sanofi; Orchard Therapeutics; Takeda; Zentech-Lacar Company; Leon Fredericq Foundation
Recruiting
Therapeutic Assistance and Decision-making Algorithms in Hepatobiliary Tumor Boards

Posted: January 12th, 2023, 3:00pm GMT

Conditions: Hepatocellular Carcinoma; Fibrolamellar Hepatocellular Carcinoma; Cholangiocarcinoma, Perihilar; Intrahepatic Cholangiocarcinoma; Metastasis to Liver; Gallbladder Carcinoma
Intervention: Other: ADBoard
Sponsors: Charite University, Berlin, Germany; German Research Center for Artificial Intelligence
Not yet recruiting
Preoperative Evaluation of Lymph Nodes of Cholangiocarcinoma

Posted: January 10th, 2023, 3:00pm GMT

Conditions: Hilar Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Common Bile Duct Neoplasms; Cholangiocarcinoma; Adenocarcinoma
Interventions: Procedure: Endoscopic Ultrasound registration
Sponsors: Erasmus Medical Center
Recruiting
Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio

Posted: December 19th, 2022, 3:00pm GMT

Conditions: Bile Duct Cancer; Cholangiocarcinoma; Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic; Metastatic Intrahepatic Cholangiocarcinoma
Interventions: Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Radiation: Yttrium-90
Sponsors: Beth Israel Deaconess Medical Center; AstraZeneca; Sirtex Medical; Dana-Farber Cancer Institute
Recruiting
Study of [18F]FAPI-74 PET in Patients With Gastrointestinal Cancers

Posted: December 8th, 2022, 3:00pm GMT

Conditions: Gastrointestinal Cancers; Cholangiocarcinoma; Gastric Cancer; Colorectal Cancer; Pancreatic Ductal Adenocarcinoma; Hepatocellular Carcinoma
Interventions: Drug: [18F]FAPI-74 PET/CT
Sponsors: SOFIE
Recruiting
A Study of NovoTTF-200T(P) in Combination With Gemcitabine and Nab-Paclitaxel for Resectable Pancreatic Adenocarcinoma

Posted: November 22nd, 2022, 3:00am GMT

Conditions: Pancreatic Adenocarcinoma; Resectable Pancreatic Cancer
Interventions: Drug: Nab paclitaxel; Drug: Gemcitabine; Device: NovoTTF-200T(P)
Sponsors: Ashish Manne; NovoCure GmbH; Ohio State University
Recruiting
Personalized Medicine for Advanced Biliary Cancer Patients

Posted: November 14th, 2022, 3:00pm GMT

Conditions: Biliary Tract Neoplasms
Interventions: Drug: Futibatinib; Drug: Ivosidenib; Drug: Zanidatamab; Drug: Trastuzumab; Drug: Neratinib; Drug: Encorafenib; Drug: Binimetinib; Drug: Niraparib; Drug: Cisplatin; Drug: Gemcitabine
Sponsors: UNICANCER; Cancer Research UK & UCL Cancer Trials Centre; Belgian Group of Digestive Oncology; National Cancer Institute, France; Cancer Research UK; Taiho Oncology, Inc.; Servier; Zymeworks Inc.; Accord Healthcare, Inc.; Pierre Fabre Medicament; GlaxoSmithKline Research & Development Limited
Not yet recruiting
Screening Single-operator Cholangioscopy for Neoplastic Bile Duct Lesions

Posted: November 1st, 2022, 2:00am GMT

Conditions: Cholangiocarcinoma; Bile Duct Neoplasms
Interventions: Procedure: Single-operator cholangioscopy
Sponsors: Soonchunhyang University Hospital
Recruiting
EUS-guided Choledochoduodenostomy for Primary Drainage of Malignant Distal Biliary Obstruction

Posted: October 26th, 2022, 2:00pm GMT

Conditions: Biliary Obstruction; Pancreas Neoplasm; Distal Cholangiocarcinoma
Intervention: Device: EUS-CDS
Sponsors: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); VU University of Amsterdam
Recruiting
SynKIR-110 for Mesothelin Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma

Posted: October 6th, 2022, 2:00pm GMT

Conditions: Ovarian Cancer; Cholangiocarcinoma Recurrent; Mesothelioma, Malignant
Interventions: Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR
Sponsors: Verismo Therapeutics
Recruiting
Pemigatinib After Curative Local Therapy in Advanced iCCA With FGFR2 Fusion/Rearrangements

Posted: October 4th, 2022, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma; FGFR2 Gene Mutation; FGFR2 Gene Rearrangement; FGFR2 Gene Translocation
Intervention: Drug: Pemigatinib
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Incyte Biosciences International Sàrl
Recruiting
89Zr-girentuximab for PET Imaging of CAIX Positive Solid Tumors

Posted: October 3rd, 2022, 2:00pm GMT

Conditions: Cervical Cancer; Colorectal Cancer; Esophageal Cancer; Gastric Cancer; Glioblastoma Multiforme; Cholangiocarcinoma; Hepatocellular Carcinoma; Head and Neck Squamous Cell Carcinoma; Nasopharyngeal Carcinoma; Non Small Cell Lung Cancer; Small Cell Lung Cancer; Epithelial Ovarian Cancer; Pancreatic Ductal Adenocarcinoma; Soft Tissue Sarcoma
Intervention: Drug: 89Zr-DFO-girentuximab
Sponsor: Telix International Pty Ltd
Recruiting
Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)

Posted: October 3rd, 2022, 2:00pm GMT

Conditions: Recurrent Biliary Tract Carcinoma; Recurrent Distal Bile Duct Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Stage III Distal Bile Duct Cancer AJCC v8; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Distal Bile Duct Cancer AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Biliary Tract Carcinoma; Unresectable Distal Bile Duct Adenocarcinoma; Unresectable Gallbladder Carcinoma; Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Drug: Binimetinib; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Oxaliplatin
Sponsors: National Cancer Institute (NCI)
Recruiting
Endoscopy and Radiology-guided Ablation for Inoperable Cholangiocarcinoma

Posted: October 3rd, 2022, 2:00am GMT

Conditions: Perihilar Cholangiocarcinoma
Interventions: Procedure: Endoluminal radiofrequency ablation; Procedure: Endoscopic biliary stenting
Sponsors: Clinical Hospital Colentina; Carol Davila University of Medicine and Pharmacy; Universitatea din Bucuresti
Recruiting
GOT Applied as Neoadjuvant Regimen for Patients of Resectable ICC With High-risk Factors of Recurrence

Posted: September 28th, 2022, 2:00pm GMT

Conditions: Intrahepatic Cholangiocarcinoma
Interventions: Drug: Tislelizumab combined with GEMOX (GOT) regimen
Sponsors: Zhejiang Cancer Hospital
Recruiting
Treatment of Non-resectable Bile Duct Cancer With Radiofrequency Ablation or Photodynamic Therapy

Posted: September 22nd, 2022, 2:00pm GMT

Condition: Hilar Cholangiocarcinoma
Interventions: Drug: Photosensitizer; Procedure: Radiofrequency ablation (RFA)
Sponsors: University of Leipzig; Zentrum für Klinische Studien Leipzig
Recruiting
Nanopore Sequencing for Detecting Bacteria in Bile and Preventing Surgical Site Infections in Patients Undergoing Surgery for Benign or Malignant Pancreatic Tumors

Posted: August 31st, 2022, 2:00pm GMT

Conditions: Benign Pancreatic Neoplasm; Malignant Pancreatic Neoplasm
Interventions: Procedure: Biospecimen Collection; Other: Laboratory Procedure; Device: Nanopore Sequencing
Sponsors: Mayo Clinic
Active, not recruiting
Preoperative Nab-paclitaxel, Cisplatin, and Gemcitabine Chemotherapy With or Without Infigratinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, The OPTIC Trial

Posted: August 25th, 2022, 2:00pm GMT

Conditions: Resectable Intrahepatic Cholangiocarcinoma; Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8; Stage I Intrahepatic Cholangiocarcinoma AJCC v8; Stage II Intrahepatic Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Infigratinib Phosphate; Drug: Nab-paclitaxel
Sponsors: Emory University; National Cancer Institute (NCI)
Not yet recruiting
Phase Ib Trial of Infigratinib In Combination With Atezolizumab And Bevacizumab for The Second-Line Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion/Amplification

Posted: August 22nd, 2022, 2:00pm GMT

Conditions: Cholangiocarcinoma; Liver Cancer
Interventions: Drug: Infigratinib; Drug: Atezolizumab; Drug: Bevacizumab
Sponsors: M.D. Anderson Cancer Center; Helsinn Healthcare
Not yet recruiting
A Study of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors

Posted: August 16th, 2022, 2:00pm GMT

Conditions: Advanced Solid Tumor; BRAF V600 Mutation
Intervention: Drug: ABM-1310
Sponsor: ABM Therapeutics Shanghai Company Limited
Recruiting

Google - Cholangiocarcinoma

CBP-1008 by Coherent Biopharma for Triple-Negative Breast ... - Pharmaceutical Technology

Posted: December 5th, 2023, 4:07am GMT

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Posted: December 5th, 2023, 3:57am GMT

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Olutasidenib by Rigel Pharmaceuticals for Chondrosarcoma ... - Pharmaceutical Technology

Posted: December 5th, 2023, 3:41am GMT

Olutasidenib by Rigel Pharmaceuticals for Chondrosarcoma ... Pharmaceutical Technology
(Pembrolizumab + vibostolimab) by Merck for Melanoma: Likelihood ... - Pharmaceutical Technology

Posted: December 5th, 2023, 3:30am GMT

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Niraparib by GSK for Esophageal Cancer: Likelihood of Approval - Pharmaceutical Technology

Posted: December 5th, 2023, 2:31am GMT

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PXS-5505A by Pharmaxis for Scar: Likelihood of Approval - Pharmaceutical Technology

Posted: December 5th, 2023, 2:01am GMT

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Sym-024 by Les Laboratoires Servier for Metastatic Colorectal ... - Pharmaceutical Technology

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Posted: December 5th, 2023, 1:41am GMT

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Posted: December 5th, 2023, 12:55am GMT

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Posted: December 5th, 2023, 12:41am GMT

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Bemarituzumab by Amgen for Lymphoma: Likelihood of Approval - Pharmaceutical Technology

Posted: December 5th, 2023, 12:25am GMT

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Posted: December 4th, 2023, 3:19pm GMT

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Quebec is the First Province to Recommend that Pemazyre ... Yahoo Finance
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New Treatments Offer More Personalized Approach in Hepatobiliary ... Physician's Weekly
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Posted: December 3rd, 2023, 4:01am GMT

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DEATH NOTICE: Lisa Pritchett - Houston Herald

Posted: December 1st, 2023, 10:41am GMT

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Posted: November 30th, 2023, 11:30am GMT

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Guideline Spotlights Early-Line Agents for GEP-NETs - Targeted Oncology

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Posted: November 29th, 2023, 12:02pm GMT

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Marsha Miller Obituary - Alexander-Levitt Funerals & Cremations ... - Legacy.com

Posted: November 29th, 2023, 4:27am GMT

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Emerging TROP-2 Directed ADCs Show Promise in Advanced NSCLC - OncLive

Posted: November 28th, 2023, 5:06pm GMT

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Identification and validation of candidate clinical signatures of ... - Nature.com

Posted: November 28th, 2023, 12:43pm GMT

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Seth Alford | News, Sports, Jobs - Lawrence Journal-World

Posted: November 28th, 2023, 10:49am GMT

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Association between high expression of intratumoral fibroblast ... - BMC Gastroenterology

Posted: November 28th, 2023, 9:58am GMT

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The use of fully covered self-expandable metal stents in the ... - BMC Gastroenterology

Posted: November 28th, 2023, 7:58am GMT

The use of fully covered self-expandable metal stents in the ... BMC Gastroenterology
Marsha Miller Obituary - Levitt-Weinstein Blasberg, Rubin-Zilbert ... - Legacy.com

Posted: November 28th, 2023, 6:00am GMT

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Imugene granted fast-track status for development of Vaxinia to treat ... - Small Caps

Posted: November 28th, 2023, 11:22pm GMT

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Obituary: Seth Austin Alford – The Lawrence Times - The Lawrence Times

Posted: November 27th, 2023, 5:30pm GMT

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$Permalink for 'FDA Approval Sought for Obe-Cel in Relapsed/Refractory B-ALL - OncLive'$
FDA Approval Sought for Obe-Cel in Relapsed/Refractory B-ALL - OncLive

Posted: November 27th, 2023, 3:57pm GMT

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Study finds complex link between lipids and cholelithiasis - ANI News

Posted: November 27th, 2023, 3:34pm GMT

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Study sheds light on the complex relationship between serum lipids ... - News-Medical.Net

Posted: November 27th, 2023, 2:59pm GMT

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Dr Hurwitz on the Feasibility of Utilizing CAR T-Cell Therapy in Solid ... - OncLive

Posted: November 27th, 2023, 1:22pm GMT

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STT-003 by Stcube for Anal Cancer: Likelihood of Approval - Pharmaceutical Technology

Posted: November 27th, 2023, 6:00am GMT

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STT-003 by Stcube for Bile Duct Cancer (Cholangiocarcinoma ... - Pharmaceutical Technology

Posted: November 27th, 2023, 6:00am GMT

STT-003 by Stcube for Bile Duct Cancer (Cholangiocarcinoma ... Pharmaceutical Technology
Plogosertib by Cyclacel Pharmaceuticals for Esophageal Cancer ... - Pharmaceutical Technology

Posted: November 27th, 2023, 6:00am GMT

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Ten-year-old girl cuts hair for grandfather with cancer - Dorset Echo

Posted: November 26th, 2023, 10:00pm GMT

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NICE recommends AstraZeneca’s combination therapy for NHS use - Pf Media

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Dual Lumen Microcatheter in Percutaneous Biliary Drainage for ... - Cureus

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Handok's Vyxeos, Gilead's Trodelvy pass cancer drug review for insurance coverage - KBR

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Dr Leslie on Outpatient CAR T-Cell Therapy Programs for ... - OncLive

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Intrahepatic Cholangiocarcinoma Pipeline Research Report 2023 ... - Yahoo Finance

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AMG 193 Reveals Promising Safety Profile Across Tumor Types - Targeted Oncology

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Dr Phillips on the Management of Toxicities Associated With CAR T ... - OncLive

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Dr In on the Increased Incidence of Gastric Cancer in Minority ... - OncLive

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Accuracy of a new rapid diagnostic test for urinary antigen detection ... - Infectious Diseases of Poverty - BioMed Central

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Posted: November 21st, 2023, 1:37am GMT

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Single-cell and spatial architecture of primary liver cancer ... - Nature.com

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FDA Approval Sought for Amivantamab Plus Chemo in EGFR+ ... - OncLive

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Cholangiocarcinoma Resource Center | Journal of Clinical Pathways - Journal of Clinical Pathways

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Richard Lowe Diver Obituary - The News Journal - The News Journal

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FDA's ODAC to Review Data for Ide-Cel in Triple-Class Exposed R ... - OncLive

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Risks and benefits of TIPS in HCC and other liver malignancies: a ... - BMC Gastroenterology

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Miller-Fisher Syndrome Unveiled in the Presence of ... - Cureus

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Pembrolizumab by Merck for Bile Duct Cancer (Cholangiocarcinoma ... - Pharmaceutical Technology

Posted: November 18th, 2023, 6:00am GMT

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Posted: November 18th, 2023, 6:00am GMT

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Obituary | Todd I Johnson - Johnson Funeral Home Waconia, MN

Posted: November 18th, 2023, 6:00am GMT

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Dr Ecker on the Investigation of the Microbiome in Pancreatic Cancer - OncLive

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HB-002.1T by Huabo Biopharm (Shanghai) for Extrahepatic Bile ... - Pharmaceutical Technology

Posted: November 18th, 2023, 1:16am GMT

HB-002.1T by Huabo Biopharm (Shanghai) for Extrahepatic Bile ... Pharmaceutical Technology
HMPL-306 by Hutchison MediPharma for Myelodysplastic ... - Pharmaceutical Technology

Posted: November 18th, 2023, 1:11am GMT

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Penpulimab by Akeso for Nasopharyngeal Cancer: Likelihood of ... - Pharmaceutical Technology

Posted: November 18th, 2023, 1:11am GMT

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Posted: November 18th, 2023, 11:35pm GMT

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Imifoplatin by Promontory Therapeutics for Squamous Non-Small ... - Pharmaceutical Technology

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Imifoplatin by Promontory Therapeutics for Squamous Non-Small ... Pharmaceutical Technology
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Maxim Downgrades RenovoRx to Hold From Buy -November 15 ... - Marketscreener.com

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Factors associated with patency of self-expandable metal stents in ... - BMC Gastroenterology

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Posted: November 13th, 2023, 8:11pm GMT

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Posted: November 13th, 2023, 7:22pm GMT

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Ryan T. Fischer, MD: Long-Term Odevixibat Benefit for Alagille ... - MD Magazine

Posted: November 13th, 2023, 4:33pm GMT

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PubMed - Bile Duct Cancer

Locoregional therapy combined with systemic therapy (LRT + ST) for unresectable and metastatic intrahepatic cholangiocarcinoma: a systematic review and meta-analysis

Fetched: December 5th, 2023, 5:01am GMT by Mengqi Zhang

Radiol Oncol. 2023 Nov 30;57(4):419-429. doi: 10.2478/raon-2023-0059. eCollection 2023 Dec 1.

ABSTRACT

BACKGROUND: The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and safety of locoregional therapy combined with systemic therapy (LRT + ST) compared with only ST in unresectable and metastatic iCCA by performing a systematic literature review and meta-analysis.

METHODS: A comprehensive search was performed in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 3, 2022. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).

RESULTS: Ten retrospective cohort studies with 3,791 unresectable or metastatic iCCA patients were enrolled in this study, including 1,120 who received ablation, arterially directed therapy (ADT), or external beam radiation therapy (EBRT) combined with ST. The meta-analysis showed that the LRT + ST group had a better OS (HR = 0.51; 95% CI =0.41-0.64; p value < 0.001), PFS (HR = 0.40, 95% CI = 0.22-0.71, p value = 0.002) and ORR (RR = 1.68; 95% CI = 1.17-2.42; p value = 0.005). Subgroup analysis showed that both ST combined with ADT (HR = 0.42, 95% CI = 0.31-0.56, p value < 0.001) and EBRT (HR = 0.67, 95% CI = 0.63-0.72, p value < 0.001) could improve OS. Neutropenia, thrombocytopenia, anemia, anorexia, and vomiting did not show significant differences between the groups (p value > 0.05).

CONCLUSIONS: Compared with only ST, LRT + ST improved survival outcomes for unresectable and metastatic iCCA patients without increasing severe AEs, which can further provide a basis for guidelines.

PMID:38038416 | PMC:PMC10690746 | DOI:10.2478/raon-2023-0059
Should lymphadenectomy performed routinely in patients with primary intrahepatic cholangiocarcinoma undergoing curative hepatectomy? A retrospective cohort study with propensity-score matching analysis

Fetched: December 5th, 2023, 5:01am GMT by Shan Huang

BMC Surg. 2023 Nov 30;23(1):364. doi: 10.1186/s12893-023-02255-5.

ABSTRACT

BACKGROUND: The benefit of routine lymphadenectomy (LD) in improving outcomes for patients with primary intrahepatic cholangiocarcinoma (ICC) undergoing curative hepatectomy remains unclear.

MATERIALS AND METHODS: This study enrolled 269 consecutive patients who underwent liver resection for primary ICC from January 2009 to July 2020 in West China Hospital. The association of the nodal status with disease-free survival (DFS) and overall survival (OS) was analyzed using the Cox proportional hazards model and 1:1 propensity score matching (PSM) analysis.

RESULTS: Seventy-five (27.9%) patients underwent curative liver resection combined with LD (LD+ group), while 194 (72.1%) patients received curative liver resection without LD (LD- group and Nx group). Among the LD+ group, metastatic disease was present in 36 patients (48%, N1 group) and absent in 39 patients (N0 group). During the follow-up period, 116 patients (43.1%) experienced tumor recurrence and 101 patients (37.5%) died due to recurrence. Multivariate analysis revealed that lymph node metastasis (N1, HR 3.682, 95% CI 1.949-6.957, p < 0.001) was associated with worse OS, while LD+ status (HR 0.504, 95% CI 0.298-0.853, p = 0.011) was associated with improved OS. Adjuvant therapy was a protective factor for both DFS (HR 0.602, 95% CI, 0.447-0.810, p = 0.001) and OS (HR 0.683, 95% CI 0.484-0.963, p = 0.030). After 1:1 PSM, the LD+ patients (n = 74) displayed similar 1-, 3- and 5-year DFS rates (40.0, 7.9 and 7.9% vs. 29.0, 13.7 and 13.7%, p = 0.741) and OS rates (56.0, 26.6 and 22.2% vs. 58.9, 25.6, and 16.4%, p = 0.644) to the LD- patients (n = 74). Additionally, among the 75 LD+ patients, 48 patients underwent hepatic hilar lymphadenectomy (HHL), and 27 patients underwent extended hepatic hilar lymphadenectomy (EHL). Both DFS (p = 0.504) and OS (p = 0.215) were similar between the HHL and EHL groups.

CONCLUSION: Routine LD and adjuvant therapy may contribute to improved OS according to the crude analysis. LD could provide accurate staging without excessive risk and guide adjuvant therapy based on the tumor stage, potentially resulting in better survival. These results suggest that a routine LD should be considered during curative hepatectomy for ICC.

PMID:38036995 | PMC:PMC10688469 | DOI:10.1186/s12893-023-02255-5
Prognostic model for oversurvival and tumor-specific survival prediction in patients with advanced extrahepatic cholangiocarcinoma: a population-based analysis

Fetched: December 5th, 2023, 5:01am GMT by Yu Zhang

BMC Gastroenterol. 2023 Nov 30;23(1):422. doi: 10.1186/s12876-023-03017-6.

ABSTRACT

BACKGROUND: The prognosis of patients with extrahepatic cholangiocarcinoma (ECCA) must be determined with precision. However, the usual TNM staging system has the drawback of ignoring age, adjuvant therapy, and gender and lacks the ability to more correctly predict patient prognosis. Therefore, we determine the risk factors of survival for patients with advanced ECCA patients and developed brand-new nomograms to forecast patients with advanced ECCA's overall survival (OS) and cancer-specific survival (CSS).

METHOD: From the Epidemiology and End Results (SEER) database, patients with advanced ECCA were chosen and randomly assigned in a ratio of 6:4 to the training and validation subgroups. The cumulative incidence function (CIF) difference between groups was confirmed by applying Gray's and Fine test and competing risk analyses. Next, the cancer-specific survival (CSS) and overall survival (OS) nomograms for advanced ECCA were developed and validated.

RESULTS: In accordance with the selection criteria, 403 patients with advanced ECCA were acquired from the SEER database and then split at random into two groups: a training group (n = 241) and a validation group (n = 162). The 1-, 2-, and 3-year cancer-specific mortality rates were 58.7, 74.2, and 78.0%, respectively, while the matching mortality rates for the competition were 10.0, 13.8, and 15.0%. Nomograms were generated for estimating OS and CSS, and they were assessed using the ROC curve and the C-index. The calibration curves showed that there was a fair amount of agreement between the expected and actual probabilities of OS and CSS. Additionally, greater areas under the ROC curve were seen in the newly developed nomograms for OS and CSS when compared to the 7th AJCC staging system. The advanced ECCA patients were divided into groupings with an elevated risk and those with a low risk and the Kaplan-Meier method was used for the survival analysis, which showed that survival time was shorter in the high-risk group than in the low-risk group.

CONCLUSION: The proposed nomograms have good predictive ability. The nomograms may can help doctors determine the prognosis of patients with advanced ECCA as well as provide more precise treatment plans for them.

PMID:38036949 | PMC:PMC10691049 | DOI:10.1186/s12876-023-03017-6
Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing

Fetched: December 5th, 2023, 5:01am GMT by Amanda J Craig

Cell Rep. 2023 Nov 28;42(11):113446. doi: 10.1016/j.celrep.2023.113446. Epub 2023 Nov 18.

ABSTRACT

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.

PMID:37980571 | DOI:10.1016/j.celrep.2023.113446
Elevated 2-oxoglutarate antagonizes DNA damage responses in cholangiocarcinoma chemotherapy through regulating aspartate beta-hydroxylase

Fetched: December 5th, 2023, 5:01am GMT by Katsuya Nagaoka

Cancer Lett. 2024 Jan 1;580:216493. doi: 10.1016/j.canlet.2023.216493. Epub 2023 Nov 15.

ABSTRACT

Cholangiocarcinoma (CCA) is resistant to systemic chemotherapies that kill malignant cells mainly through DNA damage responses (DDRs). Recent studies suggest that the involvement of 2-oxoglutarate (2-OG) dependent dioxygenases in DDRs may be associated with chemoresistance in malignancy, but how 2-OG impacts DDRs in CCA chemotherapy remains elusive. We examined serum 2-OG levels in CCA patients before receiving chemotherapy. CCA patients are classified as progressive disease (PD), partial response (PR), and stable disease (SD) after receiving chemotherapy. CCA patients classified as PD showed significantly higher serum 2-OG levels than those defined as SD and PR. Treating CCA cells with 2-OG reduced DDRs. Overexpression of full-length aspartate beta-hydroxylase (ASPH) could mimic the effects of 2-OG on DDRs, suggesting the important role of ASPH in chemoresistance. Indeed, the knockdown of ASPH improved chemotherapy in CCA cells. Targeting ASPH with a specific small molecule inhibitor also enhanced the effects of chemotherapy. Mechanistically, ASPH modulates DDRs by affecting ATM and ATR, two of the major regulators finely controlling DDRs. More importantly, targeting ASPH improved the therapeutic potential of chemotherapy in two preclinical CCA models. Our data suggested the impacts of elevated 2-OG and ASPH on chemoresistance through antagonizing DDRs. Targeting ASPH may enhance DDRs, improving chemotherapy in CCA patients.

PMID:37977350 | DOI:10.1016/j.canlet.2023.216493
8-Chloroadenosine Induces ER Stress and Apoptotic Cell Death in Cholangiocarcinoma Cells

Fetched: December 2nd, 2023, 5:01am GMT by Jomnarong Lertsuwan

Anticancer Res. 2023 Dec;43(12):5425-5436. doi: 10.21873/anticanres.16746.

ABSTRACT

BACKGROUND/AIM: Cholangiocarcinoma is a lethal cancer, and current chemotherapeutic drugs are not very effective. Recent studies reported that cholangiocarcinoma cells were sensitive to adenosine. One adenosine analog, 8-chloroadenosine (8-CA), was shown to be more potent than adenosine and induced apoptosis in leukemia cells. This study examined effects of 8-CA in cholangiocarcinoma cells and immortalized cholangiocytes.

MATERIALS AND METHODS: Cell growth was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell invasion was examined by transwell assay. Cell cycle and cell death were evaluated by flow cytometry. Colorimetric absorbance assay was used to assessed RNA and protein synthesis as well as mitochondrial membrane potential. Protein levels were examined by western blot analysis. Animal experiment was performed in Balb/cAJcl-Nu mice.

RESULTS: 8-CA reduced cholangiocarcinoma cell growth, prevented colony formation and caused endoplasmic reticulum stress and cell-cycle arrest. Eventually, apoptosis was induced. However, treatment with 8-CA did not interfere with RNA synthesis or protein synthesis and did not alter mitochondrial membrane potential. Combination of 8-CA with several chemotherapeutic drugs in vitro was less effective than 8-CA alone and the drugs alone, except for the combination of 8-CA with hydroxychloroquine, which had an additive effect on RMCCA-1 cells. However, further in vivo study showed that treatment with 8-CA alone inhibited tumor growth more than treatment with a combination of 8-CA with hydroxychloroquine.

CONCLUSION: 8-Chloroadenosine inhibited CCA cells by inducing endoplasmic reticulum stress and apoptosis. In vivo study showed that 8-CA inhibited cholangiocarcinoma tumor growth better when administered alone as compared to a combination with hydroxychloroquine.

PMID:38030206 | DOI:10.21873/anticanres.16746
Metabolomic analyses uncover an inhibitory effect of niclosamide on mitochondrial membrane potential in cholangiocarcinoma cells

Fetched: December 2nd, 2023, 5:01am GMT by Thanaporn Kulthawatsiri

PeerJ. 2023 Nov 22;11:e16512. doi: 10.7717/peerj.16512. eCollection 2023.

ABSTRACT

BACKGROUND: Niclosamide is an oral anthelminthic drug that has been used for treating tapeworm infections. Its mechanism involves the disturbance of mitochondrial membrane potential that in turn inhibits oxidative phosphorylation leading to ATP depletion. To date, niclosamide has been validated as the potent anti-cancer agent against several cancers. However, the molecular mechanisms underlying the effects of niclosamide on the liver fluke Opisthorchis viverrini (Ov)-associated cholangiocarcinoma (CCA) cell functions remain to be elucidated. The aims of this study were to investigate the effects of niclosamide on CCA cell proliferation and on metabolic phenoconversion through the alteration of metabolites associated with mitochondrial function in CCA cell lines.

MATERIALS AND METHODS: The inhibitory effect of niclosamide on CCA cells was determined using SRB assay. A mitochondrial membrane potential using tetramethylrhodamine, ethyl ester-mitochondrial membrane potential (TMRE-MMP) assay was conducted. Liquid chromatography-mass spectrometry-based metabolomics was employed to investigate the global metabolic changes upon niclosamide treatment. ATP levels were measured using CellTiter-Glo^® luminescent cell viability assay. NAD metabolism was examined by the NAD⁺/NADH ratio.

RESULTS: Niclosamide strongly inhibited CCA cell growth and reduced the MMP of CCA cells. An orthogonal partial-least square regression analysis revealed that the effects of niclosamide on suppressing cell viability and MMP of CCA cells were significantly associated with an increase in niacinamide, a precursor in NAD synthesis that may disrupt the electron transport system leading to suppression of NAD⁺/NADH ratio and ATP depletion.

CONCLUSION: Our findings unravel the mode of action of niclosamide in the energy depletion that could potentially serve as the promising therapeutic strategy for CCA treatment.

PMID:38025687 | PMC:PMC10676079 | DOI:10.7717/peerj.16512
Association between high expression of intratumoral fibroblast activation protein and survival in patients with intrahepatic cholangiocarcinoma

Fetched: December 1st, 2023, 5:01am GMT by Yuhei Waki

BMC Gastroenterol. 2023 Nov 28;23(1):415. doi: 10.1186/s12876-023-03012-x.

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to exhibit protumorigenic effects. Among the well-known CAF markers such as smooth muscle actin (SMA) and fibroblast activation protein (FAP), high expression of SMA in the peritumoral stroma has been reported to be a prognostic factor in various cancers. However, the effect of high FAP expression in intrahepatic cholangiocarcinoma (IHCC) has not been fully clarified. We evaluated the expression of CAF markers, focusing on FAP expression in the peripheral and intratumoral regions, to clarify the association with survival in patients with IHCC.

METHODS: The study cohort comprised 37 patients who underwent curative resection for IHCC. The FAP expressions were evaluated in the peripheral and intratumoral regions of the resected tissues. Clinicopathological factors and survival outcomes were investigated between patients with high versus low FAP expression. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival and relapse-free survival.

RESULTS: The median area percentages of FAP expression in the peripheral and intratumoral regions were 15.5% and 17.8%, respectively. High FAP expression in the intratumoral region was significantly associated with worse overall survival and disease-free survival than low FAP expression in the intratumoral region. Multivariate analysis identified high intratumoral FAP expression as a risk factor for worse overall survival (hazard ratio, 2.450; p = 0.049) and relapse-free survival (hazard ratio, 2.743; p = 0.034).

CONCLUSIONS: High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.

PMID:38017374 | PMC:PMC10683315 | DOI:10.1186/s12876-023-03012-x
Intrahepatic cholangiocarcinoma initially diagnosed as adenocarcinoma of unknown primary with hepatoduodenal ligament lymph node metastases: A case report

Fetched: November 30th, 2023, 5:01am GMT by Sangik Noh

Oncol Lett. 2023 Nov 8;27(1):7. doi: 10.3892/ol.2023.14140. eCollection 2024 Jan.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) with regional lymph node metastases, which lacks a well-delineated liver mass, may be misdiagnosed as a carcinoma of unknown primary (CUP) origin. The present study reports the case of a 69-year-old man initially diagnosed with CUP, who was incidentally found to have abdominal lymphadenopathy during ultrasonography (US). The clinical course from the time of lymphadenectomy and CUP diagnosis to iCCA detection after long-term follow-up is reported. A patient with a history of hypertensive renal disease presented with an incidental finding of enlarged abdominal lymph nodes in the perihepatic region on US. Abdominal contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed two enlarged lymph nodes in the hepatoduodenal ligament. Exploratory laparotomy and lymphadenectomy were performed for diagnostic and therapeutic purposes, respectively. Poorly differentiated metastatic adenocarcinoma positive for cytokeratin 7 and negative for cytokeratin 20 was identified in two of the 22 lymph nodes. Postoperatively, a positron emission tomography/CT (PET/CT) scan was performed, which failed to locate the primary site. The diagnosis of CUP was confirmed based on clinical, radiological and histopathological characteristics. A sequential abdominal CT scan 48 months after lymphadenectomy revealed a faintly enhancing, intraductal polypoid mass with localized ductal dilatation in liver segment 3. MRI and PET/CT confirmed a mass in the left lobe of the liver. US-guided percutaneous needle biopsy confirmed the presence of moderately differentiated adenocarcinoma. The patient refused surgical treatment because of general weakness caused by Coronavirus disease 2019 infection. The patient received radical radiotherapy and underwent left hepatectomy after recovery of their performance status. Histopathological examination of the surgical specimen demonstrated prevailing fibrosis and mucin accumulation, with scattered cancer cells observed focally in the resected liver specimen owing to the effect of the radiotherapy. Consequently, a definitive diagnosis of primary adenocarcinoma of the intrahepatic bile duct was confirmed. The present report may improve understanding of the pathophysiology and clinical progression of iCCA, with a specific focus on the intraductal growth subtype.

PMID:38028185 | PMC:PMC10664074 | DOI:10.3892/ol.2023.14140
Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map

Fetched: November 30th, 2023, 5:01am GMT by Carolina Requeijo

Clin Epidemiol. 2023 Nov 10;15:1069-1085. doi: 10.2147/CLEP.S431498. eCollection 2023.

ABSTRACT

INTRODUCTION: Despite being commonly recommended, the impact of anticancer drugs (ACDs) on patient-important outcomes beyond survival for advanced hepatobiliary cancers (HBCs) may not have been sufficiently assessed. We aim to identify and map the evidence regarding ACDs versus best supportive care (BSC) for advanced HBCs, considering patient-centered outcomes.

METHODS: In this mapping review, we included systematic reviews, randomized controlled trials, quasi-experimental, and observational studies comparing ACDs (chemotherapy, immunotherapy, biological/targeted therapy) versus BSC for advanced HBCs. We searched MEDLINE (PubMed), EMBASE (Ovid), Cochrane Library, Epistemonikos, PROSPERO and clinicaltrials.gov for eligible studies. Two reviewers performed the screening and data extraction processes. We developed evidence maps for each type of cancer.

RESULTS: We included 87 studies (60 for advanced liver cancer and 27 for gallbladder or bile duct cancers). Most of the evidence favored ACDs for survival outcomes, and BSC for toxicity. We identified several evidence gaps for non-survival outcomes, including quality of life or quality of end-of-life care.

DISCUSSION: Patient-important outcomes beyond survival in advanced HBCs are insufficiently assessed by the available evidence. Future studies need to address these gaps to better inform decision-making processes.

PMID:38025841 | PMC:PMC10644842 | DOI:10.2147/CLEP.S431498
Genetically Predicted Causal Effects of Gut Microbiota and Gut Metabolites on Digestive Tract Cancer: A Two-Sample Mendelian Randomization Analysis

Fetched: November 30th, 2023, 5:01am GMT by Xu Jia Li

World J Oncol. 2023 Dec;14(6):558-569. doi: 10.14740/wjon1737. Epub 2023 Nov 3.

ABSTRACT

BACKGROUND: Evidence from numerous observational studies and clinical trials has linked gut microbiota and metabolites to digestive tract cancer. However, the causal effect between these factors remains uncertain.

METHODS: Data for this study were obtained from the MiBioGen, TwinsUK Registry, and FinnGen (version R8). Two-sample Mendelian randomization analysis with inverse variance weighting method was primarily used, and the results were validated by heterogeneity analysis, pleiotropy test, and sensitivity analysis.

RESULTS: At P < 5 × 10^-8, our analysis identified four gut microbiotas as risk factors for digestive tract cancer and six as risk factors for colorectal cancer. Conversely, one gut microbiota exhibited protection against bile duct cancer, and two showed protective effects against stomach cancer. At P < 1 × 10^-5, our investigation revealed five, six, three, eight, eight, and eight gut microbiotas as risk factors for esophageal, stomach, bile duct, liver, pancreatic, and colorectal cancers, respectively. In contrast, four, two, eight, two, two, and five gut microbiotas exhibited protective effects against these cancers. Additionally, GABA, a metabolite of gut microbiota, displayed a significant protective effect against colorectal cancer.

CONCLUSION: In conclusion, specific gut microbiota and metabolites play roles as risk factors or protective factors for digestive tract cancer, and a causal relationship between them has been established, offering novel insights into gut microbiota-mediated cancer development.

PMID:38022400 | PMC:PMC10681779 | DOI:10.14740/wjon1737
ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells

Fetched: November 30th, 2023, 5:01am GMT by Anghui Peng

Cell Death Dis. 2023 Nov 27;14(11):777. doi: 10.1038/s41419-023-06309-7.

ABSTRACT

p63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples. We further established genetically modified iCCA cell lines in which p63 was overexpressed or knocked down to study the protein function/function of p63 in iCCA. We found that cells overexpressing p63, but not p63 knockdown counterparts, displayed increased proliferation, migration, and invasion. Transcriptome analysis showed that p63 altered the iCCA transcriptome, particularly by affecting cell adhesion-related genes. Moreover, chromatin accessibility decreased at p63 target sites when p63 binding was lost and increased when p63 binding was gained. The majority of the p63 bound sites were located in the distal intergenic regions and showed strong enhancer marks; however, active histone modifications around the Transcription Start Site changed as p63 expression changed. We also detected an interaction between p63 and the chromatin structural protein YY1. Taken together, our results suggest an oncogenic role for p63 in iCCA.

PMID:38012140 | PMC:PMC10682000 | DOI:10.1038/s41419-023-06309-7
Population pharmacokinetic and exposure-response analyses of pemigatinib in patients with advanced solid tumors including cholangiocarcinoma

Fetched: November 30th, 2023, 5:01am GMT by Xiaohua Gong

CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1784-1794. doi: 10.1002/psp4.13064. Epub 2023 Nov 15.

ABSTRACT

Pemigatinib is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with efficacy in patients with previously treated, advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 alterations. A previously developed population pharmacokinetic (PK) model of pemigatinib was refined using an updated dataset with 467 participants from seven clinical studies, including patients with CCA. Updated PK model parameters were used to evaluate the association between pemigatinib exposure and efficacy and safety. Pemigatinib PK was adequately described by a two-compartment model with linear elimination and sequential zero- and first-order absorption. The final model successfully minimized, had a successful covariance step, and showed unbiased goodness-of-fit. Estimated first-order absorption rate constant and apparent clearance were 3.7/h and 10.7 L/h, respectively. Sex, baseline body weight, and concomitant use of phosphate binders, proton pump inhibitors, or histamine-2 antagonists significantly impacted PK parameters; however, the impact of covariates on PK exposure was not clinically significant. Steady-state pemigatinib exposure and mean change from baseline in serum phosphate concentration were associated with objective response rate in a bell-shaped relationship and were significantly associated with increased hyperphosphatemia. Pemigatinib exposure was associated with treatment-emergent adverse events, such as decreased appetite, nausea, and stomatitis, although the relationships were shallow. Overall, analyses indicate that 13.5 mg pemigatinib once daily in 21-day cycles (2 weeks on, 1 week off) offers a favorable benefit-risk profile in patients with advanced/metastatic or surgically unresectable CCA and is the optimal dose for clinical development.

PMID:37969064 | PMC:PMC10681497 | DOI:10.1002/psp4.13064
The role of subspecialized radiologist reviews in preoperative conference for hepato-pancreato-biliary disease

Fetched: November 30th, 2023, 5:01am GMT by Yujin Seo

Eur J Radiol. 2023 Dec;169:111183. doi: 10.1016/j.ejrad.2023.111183. Epub 2023 Nov 3.

ABSTRACT

PURPOSE: To identify the role of subspecialized radiologists in preoperative conferences of radiologists and surgeons in the management of hepato-pancreato-biliary (HPB) diseases.

METHODS: We retrospectively evaluated the prospective data of 247 patients (mean age, 63.8 years; 173 men) who were referred for preoperative conferences (n = 258; 11 were discussed twice) for HPB disease between September 2021 and April 2022. Before each preoperative conference, subspecialized radiologists reviewed all available imaging studies and treatment plan information. After each conference, any change to the treatment plan was documented (major, minor, or none). Additional information provided by the radiologists was collected (significant, supplementary, or none). Uni- and multivariable analyses were performed to determine factors that resulted in a major change to the treatment plan.

RESULTS: Of the 258 reviewed cases, a major change was made to the treatment plan in 26 cases (10.1 %) and a minor change in 41 (15.9 %). Significant information was provided in 27 cases (10.5 %) and supplementary information in 72 (27.9 %). In the multivariable analysis, additional information about local tumor extent (odds ratio [OR], 6.3; 95 % confidence interval [CI], 2.1-19.5; p = 0.001) and distant metastasis detection (OR, 33.2; 95 % CI, 5.1-216.6; p < 0.001) was significantly associated with a major change.

CONCLUSION: The involvement of subspecialized radiologists in preoperative conferences resulted in major treatment plan changes in 10.1 % of the cases, primarily associated with the added information about local tumor extent and distant metastasis.

PMID:37944332 | DOI:10.1016/j.ejrad.2023.111183
Predicting very early recurrence in intrahepatic cholangiocarcinoma after curative hepatectomy using machine learning radiomics based on CECT: A multi-institutional study

Fetched: November 28th, 2023, 5:01am GMT by Bo Chen

Comput Biol Med. 2023 Dec;167:107612. doi: 10.1016/j.compbiomed.2023.107612. Epub 2023 Oct 31.

ABSTRACT

BACKGROUND: Even after curative resection, the prognosis for patients with intrahepatic cholangiocarcinoma (iCCA) remains disappointing due to the extremely high incidence of postoperative recurrence.

METHODS: A total of 280 iCCA patients following curative hepatectomy from three independent institutions were recruited to establish the retrospective multicenter cohort study. The very early recurrence (VER) of iCCA was defined as the appearance of recurrence within 6 months. The 3D tumor region of interest (ROI) derived from contrast-enhanced CT (CECT) was used for radiomics analysis. The independent clinical predictors for VER were histological stage, AJCC stage, and CA199 levels. We implemented K-means clustering algorithm to investigate novel radiomics-based subtypes of iCCA. Six types of machine learning (ML) algorithms were performed for VER prediction, including logistic, random forest (RF), neural network, bayes, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). Additionally, six clinical ML (CML) models and six radiomics-clinical ML (RCML) models were developed to predict VER. Predictive performance was internally validated by 10-fold cross-validation in the training cohort, and further evaluated in the external validation cohort.

RESULTS: Approximately 30 % of patients with iCCA experienced VER with extremely discouraging outcome (Hazard ratio (HR) = 5.77, 95 % Confidence Interval (CI) = 3.73-8.93, P < 0.001). Two distinct iCCA subtypes based on radiomics features were identified, and subtype 2 harbored a higher proportion of VER (47.62 % Vs 25.53 %) and significant shorter survival time than subtype 1. The average AUC values of the CML and RCML models were 0.744 ± 0.018, and 0.900 ± 0.014 in the training cohort, and 0.769 ± 0.065 and 0.929 ± 0.027 in the external validation cohort, respectively.

CONCLUSION: Two radiomics-based iCCA subtypes were identified, and six RCML models were developed to predict VER of iCCA, which can be used as valid tools to guide individualized management in clinical practice.

PMID:37939408 | DOI:10.1016/j.compbiomed.2023.107612
Resistance mechanism to fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma

Fetched: November 28th, 2023, 5:01am GMT by Angela Lamarca

Cancer Treat Rev. 2023 Dec;121:102627. doi: 10.1016/j.ctrv.2023.102627. Epub 2023 Sep 16.

ABSTRACT

Precision medicine is a major achievement that has impacted on management of patients diagnosed with advanced cholangiocarcinoma (CCA) over the last decade. Molecular profiling of CCA has identified targetable alterations, such as fibroblast growth factor receptor-2 (FGFR-2) fusions, and has thus led to the development of a wide spectrum of compounds. Despite favourable response rates, especially with the latest generation FGFRi, there are still a proportion of patients who will not achieve a radiological response to treatment, or who will have disease progression as the best response. In addition, for patients who do respond to treatment, secondary resistance frequently develops and mechanisms of such resistance are not fully understood. This review will summarise the current state of development of FGFR inhibitors in CCA, their mechanism of action, activity, and the hypothesised mechanisms of resistance.

PMID:37925878 | DOI:10.1016/j.ctrv.2023.102627
Synthesis and Preclinical Evaluation of Radiolabeled [103Ru]BOLD-100

Fetched: November 26th, 2023, 5:01am GMT by Barbara Happl

Pharmaceutics. 2023 Nov 15;15(11):2626. doi: 10.3390/pharmaceutics15112626.

ABSTRACT

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy. The synthesis of [¹⁰³Ru]BOLD-100, radiolabeled with carrier added (c.a.) ruthenium-103, was established and the product was characterized by HPLC and UV/Vis spectroscopy. In order to compare the radiolabeled and non-radioactive versions of BOLD-100, both complexes were fully evaluated in vitro and in vivo. The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [¹⁰³Ru]BOLD-100.

PMID:38004604 | PMC:PMC10674160 | DOI:10.3390/pharmaceutics15112626
Difficulty of adjuvant chemotherapy administration in patients with biliary tract cancer

Fetched: November 25th, 2023, 5:01am GMT by Tatsuaki Sumiyoshi

Langenbecks Arch Surg. 2023 Nov 24;408(1):445. doi: 10.1007/s00423-023-03169-9.

ABSTRACT

PURPOSE: This study aimed to elucidate the difficulty of adjuvant chemotherapy administration in patients with biliary tract carcinoma (BTC).

METHODS: Clinical data of patients with BTC who underwent curative-intent surgery were retrospectively analyzed. The eligible patients were stratified into two groups according to the presence or absence of adjuvant chemotherapy administration (adjuvant and non-adjuvant groups), and the clinicopathological features were compared between the two groups. The ratios of adjuvant chemotherapy administration were investigated in each surgical procedure. Independent factors associated with no administration of adjuvant chemotherapy were analyzed using multivariate analyses.

RESULTS: Among 168 eligible patients, 141 (83.9%) received adjuvant chemotherapy (adjuvant group), while 27 (16.1%) did not (non-adjuvant group). The most common surgical procedure was pancreaticoduodenectomy in the adjuvant group, and it was hepatectomy with extrahepatic bile duct resection (BDR) in the non-adjuvant group, respectively. The rate of no adjuvant chemotherapy was significantly higher in patients who underwent hepatectomy with BDR than in those who underwent other surgeries (p < 0.001). The most common cause of no adjuvant chemotherapy was bile leak in 12 patients, which occurred after hepatectomy with BDR in ten patients. Multivariate analyses revealed that hepatectomy with BDR and preoperative anemia were independently associated with no adjuvant chemotherapy (p < 0.001 and p < 0.001, respectively).

CONCLUSIONS: Hepatectomy with BDR and subsequent refractory bile leak can be the obstacle to adjuvant chemotherapy administration in patients with BTC.

PMID:37999810 | DOI:10.1007/s00423-023-03169-9
ASPSCR-1 and Sirt-5 alleviate Clonorchis liver fluke rCsNOSIP-induced oxidative stress, proliferation, and migration in cholangiocarcinoma cells

Fetched: November 25th, 2023, 5:01am GMT by Meng Bian

PLoS Negl Trop Dis. 2023 Nov 10;17(11):e0011727. doi: 10.1371/journal.pntd.0011727. eCollection 2023 Nov.

ABSTRACT

BACKGROUND: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma. It has been well known that NO from chronic inflammation responses are thought to be a major component of the damage and ultimate carcinogenesis ESPs such as nitric oxide synthase interacting protein (NOSIP) are thought to enhance the damage. The objective of this study was to identify the protein candidates interact with recombinant CsNOSIP (rCsNOSIP) and explore their role involved in CCA development or progression.

METHODS: We applied HuProt microarray containing 21,000 probe sets for a systematic identification of rCsNOSIP-binding proteins and grouped binding hits by gene function. Pull-down assays were used to confirm the interaction of rCsNOSIP with alveolar soft part sarcoma (ASPSCR-1) and sirtuins 5 (Sirt-5). ASPSCR-1/Sirt-5 over-expression and siRNA knockdown experiments were employed for obtain of ASPSCR-1/Sirt-5 high or low expression (ASP-oe/Sirt5-oe or ASP-si/Sirt5-si) cholangiocarcinoma cell line (CCLP-1) cells. Nitric oxide (NO) and reactive oxygen species assay (ROS) as well as cell proliferation and wound-healing assays were performed to observe the effect of rCsNOSIP on ASP-oe/Sirt5-oe or ASP-si/Sirt5-si CCLP-1 cells.

RESULTS: Seventy candidate proteins protein "hits" were detected as rCsNOSIP-binding proteins by HuProt microarray and bioinformatics analysis. Pull down assay showed that ASPSCR-1 and Sirt-5 could interact with rCsNOSIP. In addition, endotoxin-free-rCsNOSIP could increase the production of NO and ROS and promote the migration of CCLP-1 cells, while its effect on enhancing cell proliferation was not significant. Furthermore, ROS/NO production, proliferation, or migration were increased in ASP-si or Sirt5-si CCLP-1 cells but decreased in Asp-oe or Sirt5-oe CCLP-1 cells when stimulated with rCsNOSIP.

CONCLUSIONS: Our findings suggest that CsNOSIP as a component of CsESPs might promote the development and invasion of CCA and Sirt5/ ASPSCR1 as host molecules might play a novel protective role against adverse stimulus during C. sinensis infection. This work supports the idea that CsESPs induce the occurrence and progression of CCA through ROS/RNS-induced oxidative and nitrative DNA damage.

PMID:37948465 | PMC:PMC10664913 | DOI:10.1371/journal.pntd.0011727
Durvalumab: A Review in Advanced Biliary Tract Cancer

Fetched: November 24th, 2023, 5:01am GMT by Simon Fung

Target Oncol. 2023 Nov;18(6):965-972. doi: 10.1007/s11523-023-01007-y. Epub 2023 Nov 9.

ABSTRACT

Durvalumab (Imfinzi^®), a therapeutic human monoclonal antibody which binds to and blocks the activity of the immunosuppressive programmed death-ligand 1 (PD-L1) protein, is approved in the USA, EU, Japan and other countries in combination with gemcitabine and cisplatin for adults with advanced biliary tract cancer. In the pivotal phase 3 TOPAZ-1 trial, durvalumab plus gemcitabine and cisplatin significantly prolonged overall survival and progression-free survival compared with placebo plus gemcitabine and cisplatin in adults with advanced biliary tract cancer. Benefit from durvalumab was seen irrespective of primary tumour location, disease status at diagnosis (unresectable or recurrent), or initial levels of PD-L1 expression. The tolerability of durvalumab plus gemcitabine and cisplatin was manageable. Overall, the addition of durvalumab to gemcitabine and cisplatin is a valuable new treatment option for adults with advanced biliary tract cancer.

PMID:37943483 | PMC:PMC10667376 | DOI:10.1007/s11523-023-01007-y
Potential missed opportunities for diagnosis of lymphoepithelioma-like intrahepatic cholangiocarcinoma: report of a rare case

Fetched: November 24th, 2023, 5:01am GMT by Wei Tang

J Int Med Res. 2023 Nov;51(11):3000605231210174. doi: 10.1177/03000605231210174.

ABSTRACT

Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare distinctive variant of liver cancer with unique epidemiological and pathological characteristics, including dense lymphocyte infiltration. We herein describe a 67-year-old Chinese man with LEL-ICC. The patient had undergone endoscopic extraction of a bile duct stone 1 month prior. Contrast-enhanced abdominal computed tomography (CT) revealed a 2.5- × 2.5- × 1.5-cm low-density mass located in a covert part of the left lateral segment of the liver. Contrast-enhanced magnetic resonance imaging revealed a hyperintense lesion on T2-weighted and diffusion-weighted images of the left lateral liver, with similar size and signal characteristics in the arterial and portal venous phases. The patient subsequently underwent left lateral laparoscopic hepatectomy. The results of postoperative pathology and immunohistochemistry allowed for the definitive diagnosis. In situ hybridization using an Epstein-Barr virus-encoded RNA probe revealed extensive reactivity in the tumor cell nuclei, supporting a diagnosis of LEL-ICC. The patient was recurrence-free at 12 months postoperatively as shown by CT. A literature review indicated that in middle-aged patients with Epstein-Barr virus infection, a liver mass with a well-defined margin and a combination of hypervascularity and delayed intratumoral enhancement on CT and magnetic resonance imaging may suggest a diagnosis of LEL-ICC.

PMID:37994034 | PMC:PMC10666819 | DOI:10.1177/03000605231210174
Single-cell and spatial architecture of primary liver cancer

Fetched: November 23rd, 2023, 5:01am GMT by Pei-Yun Zhou

Commun Biol. 2023 Nov 20;6(1):1181. doi: 10.1038/s42003-023-05455-0.

ABSTRACT

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE⁺ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

PMID:37985711 | PMC:PMC10661180 | DOI:10.1038/s42003-023-05455-0
Hodgkin lymphoma associated vanishing bile duct syndrome treated successfully with a brentuximab based regimen

Fetched: November 22nd, 2023, 5:01am GMT by Judah D Morgan

BMJ Case Rep. 2023 Nov 21;16(11):e257211. doi: 10.1136/bcr-2023-257211.

ABSTRACT

We report a combination therapy to successfully treat a patient with Hodgkin's lymphoma complicated by vanishing bile duct syndrome. Our patient was in his 20s and presented with jaundice, emesis, B symptoms and diffuse lymphadenopathy along with cholestatic liver injury prompting a liver biopsy, which revealed this diagnosis, after the exclusion of other aetiologies. Our treatment regimen incorporated brentuximab along with other more conventional agents which attempted to maximise therapeutic efficacy while minimising the consequences of hepatotoxicity on the treatment protocol. Although this patient's treatment course was complicated because of neutropenic infections, the patient achieved a complete metabolic response and is now more than 1 year off therapy.

PMID:37989332 | PMC:PMC10668144 | DOI:10.1136/bcr-2023-257211
Endoscopic Management of Malignant Biliary Obstruction

Fetched: November 22nd, 2023, 5:01am GMT by Woo Hyun Paik

Gastrointest Endosc Clin N Am. 2024 Jan;34(1):127-140. doi: 10.1016/j.giec.2023.07.004. Epub 2023 Aug 28.

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used for managing malignant biliary obstruction; however, it is impossible if the endoscope cannot reach the ampulla of Vater, and it carries a risk of procedure-related pancreatitis. Percutaneous approach is a traditional rescue method when ERCP fails and can be useful in advanced malignant hilar biliary obstruction; however, it is invasive and carries risks of tube dislodgement, recurrent infection, and tract seeding. Endoscopic ultrasound approach may be attempted if ERCP fails and is free from the risk of pancreatitis; however, it is only possible in limited centers, and training is still difficult. Malignant biliary obstruction should be managed by leveraging the complementary strengths of these methods.

PMID:37973224 | DOI:10.1016/j.giec.2023.07.004
Risk factors for cefmetazole-non-susceptible bacteremia in acute cholangitis

Fetched: November 20th, 2023, 5:01am GMT by Katsuhiro Onishi

J Infect Chemother. 2023 Nov 18:S1341-321X(23)00287-8. doi: 10.1016/j.jiac.2023.11.015. Online ahead of print.

ABSTRACT

INTRODUCTION: Cefmetazole (CMZ), an antibiotic with limited international distribution, is recommended by the Tokyo Guidelines 2018 (TG18) for non-severe cases of acute cholangitis (AC). However, the risk factors for CMZ-non-susceptible (CMZ-NS) bacteremia in AC remain unclear. Here, we aimed to investigate the risk factors for CMZ-NS bacteremia and evaluate mortality in patients with AC.

METHODS: This single-center, retrospective, observational study included all patients diagnosed with definite bacteremic AC, based on TG18, from April 2019 to March 2023. Risk factors for CMZ-NS bacteremia were analyzed by univariate, and age- and sex-adjusted, logistic regression analyses. Mortality was compared by cause of obstruction, CMZ-susceptible/CMZ-NS bacteremia, and initial treatment.

RESULTS: In total, 165 patients were enrolled. CMZ-NS bacteremia was diagnosed in 46 (27.9 %) patients. Histories of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy were identified as significant factors associated with the risk of CMZ-NS bacteremia. Thirteen patients died within 30 days of hospital admission. The mortality of patients with AC and malignant biliary obstruction was statistically higher than that of patients with bile duct stones. No patients with AC and bile duct stones died in the group with CMZ-NS bacteremia and inappropriate initial antibiotics.

CONCLUSIONS: In AC, a history of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy are associated with an increased risk of CMZ-NS bacteremia. Therefore, the choice of empiric therapy for AC should be based on the etiology and patient background, rather than on the severity.

PMID:37981024 | DOI:10.1016/j.jiac.2023.11.015
Risk stratification for overall survival and recurrence-free survival after R0 resection for solitary intrahepatic mass-forming cholangiocarcinoma based on preoperative MRI and clinical features

Fetched: November 20th, 2023, 5:01am GMT by Shuang Chen

Eur J Radiol. 2023 Dec;169:111190. doi: 10.1016/j.ejrad.2023.111190. Epub 2023 Nov 7.

ABSTRACT

PURPOSE: This study aimed to establish two nomograms for predicting overall survival (OS) and recurrence-free survival (RFS) in patients with solitary intrahepatic mass-forming cholangiocarcinoma (IMCC) based on preoperative magnetic resonance imaging (MRI) features.

METHODS: This retrospective study included 120 consecutive patients who were diagnosed with solitary IMCC. Preoperative MRI and clinical features were collected. Based on the univariate and multivariate Cox regression analyses, two nomograms were constructed to predict OS and RFS, respectively. The effective performance of the nomograms was evaluated using concordance index (C-index). The prognostic stratification systems for OS and RFS were developed and used to classify patients into high- and low-risk groups.

RESULTS: Suspicious lymph nodes, arterial phase (AP) enhancement patterns, and bile duct dilatation were independent predictors of OS, while suspicious lymph nodes, AP enhancement patterns, and necrosis were independent predictors of RFS. The nomograms achieved the C-index values of 0.705/0.710 for OS and 0.721/0.759 for RFS in the development/validation cohorts, which were significantly higher than those of the T and TNM stages (P < 0.05). Patients were stratified into high- and low-risk groups, the 1-year OS and RFS rates of high-risk patients were poorer than those of patients with low-risk in the development cohort (OS: 93.5% vs 76.3%, P < 0.001; RFS: 74.5% vs 22.4%, P < 0.001). Similar results were observed in the validation cohort.

CONCLUSIONS: Two nomograms were constructed based on preoperative MRI features in patients with solitary IMCC for predicting the OS and RFS and facilitate further prognostic stratification.

PMID:37979460 | DOI:10.1016/j.ejrad.2023.111190
Whole-genome Sequencing and RNA Sequencing Analysis Reveals Novel Risk Genes and Differential Expression Patterns in Hepatoblastoma

Fetched: November 19th, 2023, 5:01am GMT by Wuqian Wang

Gene. 2023 Nov 14:147991. doi: 10.1016/j.gene.2023.147991. Online ahead of print.

ABSTRACT

Hepatoblastoma (HB) is an uncommon malignant liver cancer primarily affecting infants and children, characterized by the presence of tissue that resembling fetal hepatocytes, mature liver cells or bile duct cells. The primary symptom in affected children is abdominal lumps. HB constitutes approximately 28% of all liver tumors and two-thirds of liver malignancies in the pediatric and adolescent population. Despite its high prevalence, the underlying mechanism of HB pathogenesis remain largely unknown. To reveal the genetic alternations associated with HB, we conducted a comprehensive genomic study using whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) techniques on five HB patients. We aimed to use WGS to identify somatic variant loci associated with HB, including single nucleotide polymorphisms (SNPs), insertions and deletions (Indels), and copy number variations (CNVs). Notably, we found deleterious mutation in CTNNB1, AXIN2 and PARP1, previously implicated in HB. In addition, we discovered multiple novel genes potentially associated with HB, including BRCA2 and GPC3 which require further functional validation to reveal their contributions to HB development. Furthermore, the American College of Medical Genetics and Genomics (ACMG) analysis identified the ABCC2 gene was the pathogenic gene as a potential risk gene linked with HB. To study the gene expression patterns in HB, we performed RNA-seq analysis and qPCR validation to reveal differential expression of four candidate genes (IGF1R, METTL1, AXIN2, and TP53) in tumors compared to nonneoplastic liver tissue in HB patients (P-Val<0.01). These findings shed lights on the molecular mechanisms underlying HB development and facilitate to advance future personalized diagnosis and therapeutic interventions of HB.

PMID:37972697 | DOI:10.1016/j.gene.2023.147991
Establishment and characterization of a novel hilar cholangiocarcinoma cell line, CBC3T-1

Fetched: November 16th, 2023, 5:01am GMT by Mingzhen Bai

Hum Cell. 2023 Nov 15. doi: 10.1007/s13577-023-01003-4. Online ahead of print.

ABSTRACT

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis, and high recurrence rate. Immortalized cancer cell lines are the best and easiest models for in vitro cancer research. Here, we established a naturally immortalized highly tumorigenic hilar cholangiocarcinoma (hCCA) cell line, CBC3T-1. The CBC3T-1 cell line was cultured for over 60 passages. Thorough analysis showed that CBC3T-1 cells share characteristics similar to original tumor cells from patients with cholangiocarcinoma and display a stable phenotype, including features of epithelial origin, stem cell-like properties, as well as a high invasive and migratory capability and tumorigenicity in mice. Furthermore, this cell line showed the best sensitivity to paclitaxel, followed by gemcitabine. RNA sequencing and whole‑exome sequencing showed that cancer-associated pathways and somatic mutations played a dominant role in the development of CCA. We established and characterized a new hCCA cell line, CBC3T-1, which contributes to a better understanding of bile duct cancer, and can be used to study tumorigenesis and progression and the role of anticancer drugs.

PMID:37966669 | DOI:10.1007/s13577-023-01003-4
Trans-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells

Fetched: November 16th, 2023, 5:01am GMT by Thidarath Rattanaburee

Molecules. 2023 Oct 30;28(21):7342. doi: 10.3390/molecules28217342.

ABSTRACT

This research aimed to determine the target protein and molecular mechanism of trans-(±)-kusunokinin ((±)-KU) derivatives (trans-(±)-ARC and trans-(±)-TTPG-B). Molecular docking was used to predict potential synthesized (±)-KU targets among 22 proteins. The (±)-TTPG-B bound HSP90α better than EC44, native (±)-KU and (-)-KU, and (±)-KU and (-)-ARC. In contrast, (-)-ARC bound PI3K more strongly than any other test compound. CSF1R and AKR1B1 were not supposed to be the target of (±)-TTPG-B and (±)-ARC, unlike native (±)-KU. The (±)-TTPG-B bound Tyr139 and Trp162 of HSP90α. Moreover, (-)-ARC bound PI3K via hydrogen bonds and π-π stacking at distinct amino acids, which was different from the other tested compounds. Using half of the IC50 concentration, (±)-TTPG-B, (±)-KU and (±)-ARC enhanced cell cycle arrest at the G0/G1 phase after 12 h and 24 h on KKU-M213 (CCA) cells. The (±)-TTPG-B showed a stronger inhibitory effect than (±)-ARC and (±)-KU on HSP90α, PI3K, HSP90β, c-Myc, AKT, MEK1, CyclinB1, CyclinD1, and CDK1 for 24 and 48 h after treatment with the same concentration (0.015 µM). Thus, trans-(±)-TTPG-B, a newly synthesized compound, has pharmacological potential for development as a target therapy for CCA treatment.

PMID:37959760 | PMC:PMC10650166 | DOI:10.3390/molecules28217342
The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches

Fetched: November 16th, 2023, 5:01am GMT by Eleni-Myrto Trifylli

Int J Mol Sci. 2023 Oct 25;24(21):15563. doi: 10.3390/ijms242115563.

ABSTRACT

Cholangiocarcinomas (CCAs) constitute a heterogeneous group of highly malignant epithelial tumors arising from the biliary tree. This cluster of malignant tumors includes three distinct entities, the intrahepatic, perihilar, and distal CCAs, which are characterized by different epidemiological and molecular backgrounds, as well as prognosis and therapeutic approaches. The higher incidence of CCA over the last decades, the late diagnostic time that contributes to a high mortality and poor prognosis, as well as its chemoresistance, intensified the efforts of the scientific community for the development of novel diagnostic tools and therapeutic approaches. Extracellular vesicles (EVs) comprise highly heterogenic, multi-sized, membrane-enclosed nanostructures that are secreted by a large variety of cells via different routes of biogenesis. Their role in intercellular communication via their cargo that potentially contributes to disease development and progression, as well as their prospect as diagnostic biomarkers and therapeutic tools, has become the focus of interest of several current studies for several diseases, including CCA. The aim of this review is to give a rundown of the current knowledge regarding the emerging role of EVs in cholangiocarcinogenesis and their future perspectives as diagnostic and therapeutic tools.

PMID:37958547 | PMC:PMC10649642 | DOI:10.3390/ijms242115563
A comparative study of clinicopathological and imaging features of HBV-negative and HBV-positive intrahepatic cholangiocarcinoma patients with different pathologic differentiation degrees

Fetched: November 16th, 2023, 5:01am GMT by Xiaoli Huang

Sci Rep. 2023 Nov 13;13(1):19726. doi: 10.1038/s41598-023-47108-6.

ABSTRACT

Hepatitis B is a risk factor for the development of intrahepatic cholangiocarcinoma. The prognosis of HBV-related ICC remains to be further investigated. To investigate the clinical, pathological and imaging features of intrahepatic cholangiocarcinoma of hepatitis B virus-positive and -negative patients. Data from January 31, 2012 to December 31, 2019 of 138 patients were retrospectively analyzed. The patients were divided into hepatitis B virus-positive group (group A[n = 66]) and virus-negative group (group B[n = 72]), and the patients were divided into groups according to pathological differentiation degree and tumor size. The differences in clinical, imaging characteristics and the progression-free survival between groups were analyzed. There were significant differences in gender, age, HBc antibody, CA125 and AFP, tumor distribution site, maximum diameter, plain scan density, inferior hepatic angle, peritumoral bile duct dilatation, vascular encasement invasion, intrahepatic bile duct dilatation and lymphadenopathy between the two groups (P < 0.05); There were statistical differences in signs of vascular encasement invasion between the two groups with well-to-moderately differentiated tumors (P < 0.05); there were statistical differences in tumor density uniformity, signs of vascular encasement invasion and lymphadenopathy between the two groups with poorly differentiated tumors (P < 0.05). Large groups A and B showed differences in tumor density uniformity, vascular encasement invasion, arterial phase, overall reinforcement pattern, peritumoral bile duct stones and biliary dilatation (P < 0.05). There was no statistical difference in postoperative PFS between the two groups (P > 0.05). The clinical and imaging features of ICC of hepatitis B virus-positive and -negative patients are different, and there is little difference in postoperative disease-free survival time.

PMID:37957323 | PMC:PMC10643568 | DOI:10.1038/s41598-023-47108-6
Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer

Fetched: November 15th, 2023, 5:01am GMT by Hani Jassim Alramadhan

Cancers (Basel). 2023 Oct 26;15(21):5166. doi: 10.3390/cancers15215166.

ABSTRACT

Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR.

PMID:37958339 | PMC:PMC10650487 | DOI:10.3390/cancers15215166
Liver Transplant for Intrahepatic Cholangiocarcinoma

Fetched: November 15th, 2023, 5:01am GMT by Olanrewaju A Eletta

Surg Clin North Am. 2024 Feb;104(1):215-225. doi: 10.1016/j.suc.2023.07.006. Epub 2023 Aug 17.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) tends to be asymptomatic until late stages, leading most of the patients to present at advanced stages of the disease. A combination of medical and surgical therapy is crucial for patient management. Historically, poor outcomes resulted in liver transplantation being formally contraindicated for patients with iCCA; however, recent advances in patient selection and neoadjuvant therapy have resulted in a paradigm shift in liver transplant oncology. As a result, the feasibility of liver transplantation for iCCA is being reevaluated by several centers as a therapeutic alternative for select patients with locally advanced unresectable disease.

PMID:37953037 | DOI:10.1016/j.suc.2023.07.006
How to Determine Unresectability in Hilar Cholangiocarcinoma

Fetched: November 15th, 2023, 5:01am GMT by Catherine G Pratt

Surg Clin North Am. 2024 Feb;104(1):197-214. doi: 10.1016/j.suc.2023.09.001. Epub 2023 Sep 27.

ABSTRACT

Hilar cholangiocarcinoma is considered a biologically aggressive disease for which surgical resection remains the only curative treatment. Preoperative evaluation for resectability is challenging given tumor proximity to the porta hepatis, but minimal benefit and increased morbidity precludes recommendation for margin positive resection. This article reviews the determination of unresectability in hilar cholangiocarcinoma through discussion of the preoperative assessment, the intraoperative assessment, and key steps of surgical resection, as well as treatment options for unresectable tumors. Overall, evaluating patients preoperatively for resectability requires a multidisciplinary, holistic, and individualized approach to accurately determine resectability and optimize clinical outcomes for patients with hilar cholangiocarcinoma.

PMID:37953036 | DOI:10.1016/j.suc.2023.09.001
Liver Transplantation for Hilar Cholangiocarcinoma

Fetched: November 15th, 2023, 5:01am GMT by Christopher J Sonnenday

Surg Clin North Am. 2024 Feb;104(1):183-196. doi: 10.1016/j.suc.2023.09.004. Epub 2023 Oct 20.

ABSTRACT

Hilar cholangiocarcinoma (hCCA) is an infiltrative disease that often presents with locally advanced and/or metastatic disease, with a minority of patients eligible for surgical resection. Select patients with unresectable hCCA, or patients with hCCA in the setting of primary sclerosing cholangitis, with tumors less than 3 cm and no evidence of extrahepatic disease, can be effectively treated with neoadjuvant chemoradiation followed by liver transplantation. Staging laparotomy documenting lack of occult metastatic disease, including a portal lymphadenectomy documenting no nodal metastases, is essential to achieve optimal outcomes. Overall 5 year survival among treated patients is approximately 60%.

PMID:37953035 | DOI:10.1016/j.suc.2023.09.004
Mitochondrial transplantation inhibits cholangiocarcinoma cells growth by balancing oxidative stress tolerance through PTEN/PI3K/AKT signaling pathway

Fetched: November 14th, 2023, 5:01am GMT by Xiaocong Liu

Tissue Cell. 2023 Dec;85:102243. doi: 10.1016/j.tice.2023.102243. Epub 2023 Oct 14.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a serious threat to human health, and tumor development is associated with abnormal mitochondrial function. It is believed that the introduction of healthy mitochondria into tumor cells can induce the oxidative stress in tumor cells to return to normal levels, thus exerting an inhibitory effect on tumor growth.

METHODS: Mitochondria isolated from 143BρW cells were co-cultured with HuCCT1 cells, and the mitochondria were stained with MitoTracker dye as a tracking label. Changes in apoptosis, proliferation, oxidative stress, and PTEN/PI3K/AKT signaling pathway were assessed. In addition, a CCA nude mouse transplantation tumor model was constructed to analyze the effects of mitochondrial transplantation on the above factors in nude mice. Furthermore, the expression of PTEN was interfered to observe the effect and mechanism of mitochondrial transplantation on the proliferation and apoptosis of CCA cells.

RESULTS: Mitochondrial transplantation promoted apoptosis and inhibited cell proliferation in CCA cell line. SOD, GSH, and CAT activities were significantly increased, the expression of PTEN was activated, and the expression of p-PI3K and p-AKT were inhibited after mitochondrial transplantation. After mitochondrial transplantation + si-PTEN treatment, cell apoptosis, SOD, GSH, CAT activity, and the expression of PTEN were decreased, while the expression of p-PI3K and p-AKT were significantly enhanced.

CONCLUSION: This study reveals the anti-tumor potential of mitochondrial transplantation through PTEN/PI3K/AKT signaling pathway to regulate cellular oxidative stress in CCA.

PMID:37865041 | DOI:10.1016/j.tice.2023.102243
A Rare Case of Metastatic Ampullary Adenocarcinoma Following the Whipple Procedure

Fetched: November 14th, 2023, 5:01am GMT by Aboud Kaliounji

Cureus. 2023 Oct 10;15(10):e46796. doi: 10.7759/cureus.46796. eCollection 2023 Oct.

ABSTRACT

Ampullary carcinoma is an extremely rare type of gastrointestinal cancer that originates at the ampulla of Vater, distal to the junction between the pancreatic duct and the common bile duct (CBD). There are three subtypes depending on the histological findings: pancreatobiliary, intestinal, and mixed subtype. Symptoms can mimic other pathologies related to biliary obstruction, such as jaundice, diarrhea, steatorrhea, and weight loss. In this report, we present a case of a 40-year-old male who presented with painless jaundice and dizziness. Magnetic resonance cholangiopancreatography (MRCP) showed choledocholithiasis and CBD dilatation. Endoscopic ultrasound showed a 24 x 14 mm ampulla mass. Subsequently, he underwent the Whipple procedure that revealed an intestinal-type periampullary adenocarcinoma characterized as stage III (T3bN2M0), with lymphovascular and perineural invasion. He was lost to follow-up but was later found to have metastatic pancreatic adenocarcinoma to the lung and liver. In this report, we also discuss the clinical presentation, pathogenesis, and current evidence-based therapeutic options in the management of this tumor, highlighting the importance of treatment choice depending on the tumor type.

PMID:37954694 | PMC:PMC10634612 | DOI:10.7759/cureus.46796
MRI-based automatic identification and segmentation of extrahepatic cholangiocarcinoma using deep learning network

Fetched: November 14th, 2023, 5:01am GMT by Chunmei Yang

BMC Cancer. 2023 Nov 10;23(1):1089. doi: 10.1186/s12885-023-11575-x.

ABSTRACT

BACKGROUND: Accurate identification of extrahepatic cholangiocarcinoma (ECC) from an image is challenging because of the small size and complex background structure. Therefore, considering the limitation of manual delineation, it's necessary to develop automated identification and segmentation methods for ECC. The aim of this study was to develop a deep learning approach for automatic identification and segmentation of ECC using MRI.

METHODS: We recruited 137 ECC patients from our hospital as the main dataset (C1) and an additional 40 patients from other hospitals as the external validation set (C2). All patients underwent axial T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI). Manual delineations were performed and served as the ground truth. Next, we used 3D VB-Net to establish single-mode automatic identification and segmentation models based on T1WI (model 1), T2WI (model 2), and DWI (model 3) in the training cohort (80% of C1), and compared them with the combined model (model 4). Subsequently, the generalization capability of the best models was evaluated using the testing set (20% of C1) and the external validation set (C2). Finally, the performance of the developed models was further evaluated.

RESULTS: Model 3 showed the best identification performance in the training, testing, and external validation cohorts with success rates of 0.980, 0.786, and 0.725, respectively. Furthermore, model 3 yielded an average Dice similarity coefficient (DSC) of 0.922, 0.495, and 0.466 to segment ECC automatically in the training, testing, and external validation cohorts, respectively.

CONCLUSION: The DWI-based model performed better in automatically identifying and segmenting ECC compared to T1WI and T2WI, which may guide clinical decisions and help determine prognosis.

PMID:37950207 | PMC:PMC10636947 | DOI:10.1186/s12885-023-11575-x
Surgical resection criteria and neoadjuvant therapies for intrahepatic cholangiocarcinoma

Fetched: November 14th, 2023, 5:01am GMT by James O'Bryan

Clin Adv Hematol Oncol. 2023 Nov;21(11):584-591.

ABSTRACT

The staging of intrahepatic cholangiocarcinoma (ICC) is complex, and there is no consensus among international cancer groups on how to most appropriately select candidates with nonmetastatic disease for surgical resection. Factors contributing to a higher stage of disease include larger tumor size, multiple tumors, vascular invasion (either portal venous or arterial), biliary invasion, involvement of local hepatic structures, serosal invasion, and regional lymph node metastases. For patients selected to undergo surgery, it is well-documented that R0 resection translates to a survival benefit. Estimating the risk of post-hepatectomy liver failure and post-surgical residual liver function is vital and may preclude some patients with significant tumor burden from undergoing surgery. Numerous serum and biliary biomarkers of the disease can help detect recurrence in patients undergoing surgical resection. Systemic and locoregional neoadjuvant treatments to facilitate better surgical outcomes have yielded mixed results regarding improving resectability and overall survival. Additional research is needed to identify optimal neoadjuvant treatment approaches and to evaluate which patients will benefit most from these strategies. Therapies targeting genetic mutations and protein aberrations found by tumor molecular profiling may offer additional options for future neoadjuvant treatment.

PMID:37948594
Cholangiocarcinoma Surveillance Recommendations in Patients with Primary Sclerosing Cholangitis

Fetched: November 14th, 2023, 5:01am GMT by Daniel Saca

Clin Liver Dis. 2024 Feb;28(1):183-192. doi: 10.1016/j.cld.2023.07.010. Epub 2023 Aug 28.

ABSTRACT

Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC. Advances in understanding of the genetic factors that lead to CCA are awaited.

PMID:37945159 | DOI:10.1016/j.cld.2023.07.010
Application of single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures in total laparoscopic pancreaticoduodenectomy

Fetched: November 12th, 2023, 5:01am GMT by Dongrui Li

Langenbecks Arch Surg. 2023 Nov 11;408(1):434. doi: 10.1007/s00423-023-03155-1.

ABSTRACT

INTRODUCTION: To investigate the application potential of single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures ("1 + 2" PJ) in total laparoscopic pancreaticoduodenectomy (TLPD). Explore the advantages of "1 + 2" PJ over the traditional double-layer interrupted duct-to-mucosa pancreaticojejunostomy (traditional PJ).

METHODS: We retrospectively collected the clinical data of 184 patients who were admitted in our department from Oct 2019 to Oct 2022, including 95 cases who underwent TLPD with "1 + 2" PJ and 89 cases who underwent TLPD with traditional PJ. The pre/intra/postoperation data were analyzed and compared.

RESULTS: The "1 + 2" PJ procedures were successfully performed in all the 95 cases. When compared with the traditional PJ group, there were no statistically significant variations between the pre-operative and pathological data. However, the "1 + 2" PJ group had a shorter operation time (235 (210, 300) minutes vs. 310 (270, 360) minutes in the traditional PJ group, P < 0.001), shorter pancreaticojejunostomy time (15 (10, 20) minutes vs. 50 (45, 55) minutes in the traditional PJ group, P < 0.001), lower pancreatic fistula (both grade B/C) rate (4.21% vs. 12.34% in the traditional group, P = 0.044), and abdominal infection rate (2.11% vs. 8.99% in the traditional group, P = 0.044), as well as reduced hospital stay (11 (9, 15) days vs. 13 (11, 15) days in the traditional PJ group, P = 0.013). In the "1 + 2" PJ group, the median diameter of the pancreatic duct was 3 (3, 4) mm; 82 cases (86.31%) had a normal pancreatic texture, while nine (9.47%) cases had a hard texture, and seven (7.37%) cases had a soft texture; the median intraoperative blood loss was 200 (100, 400) mL and 19 cases (20.00%) needed intraoperative transfusion; eight cases (8.4%) developed postoperative complications, including four cases (4.2%) of pancreatic fistula (including both grade B/C), one case (1.1%) of bile leakage, three cases (3.2%) of delayed gastric emptying, three cases (3.2%) of postoperative hemorrhage, two cases (2.1%) of abdominal infection, and one case (1.1%) of reoperation; the median hospital stay was 13 (8, 17) days; 25 cases were pathologically classified as pancreatic cancer, 35 cases as bile duct cancer, 23 cases as duodenal cancer, and 12 cases as ampullary cancer.

CONCLUSION: Single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures is a feasible and safe procedure that can be applied in TLPD.

PMID:37949977 | DOI:10.1007/s00423-023-03155-1
Validation study for prognostic scoring system for perihilar cholangiocarcinoma surgery using preoperative factors

Fetched: November 10th, 2023, 5:01am GMT by Yuma Aoki

Langenbecks Arch Surg. 2023 Nov 8;408(1):430. doi: 10.1007/s00423-023-03145-3.

ABSTRACT

PURPOSE: Recently, systemic inflammatory responses (SIR) have been shown to play a pivotal role in the development and progression of cancer. We previously reported that four factors, serum carcinoembryonic antigen (> 7 ng/dL), serum albumin (< 3.5 g/dL), C-reactive protein (> 0.5 mg/dL), and platelet-lymphocyte ratio (PLR; > 150), were independent prognostic factors after perihilar cholangiocarcinoma (PHCC) surgery. We also advocated a prognosis predictive preoperative prognostic score (PPS) using these four factors and showed that PPS could predict patients' prognosis on survival. This retrospective study sought to validate preoperatively available prognostic factors for survival after major hepatectomy as reported previously, including PPS for PHCC.

METHODS: We retrospectively validated our PPS score and reported SIR scoring systems using the data of 125 consecutive patients who underwent PHCC surgery from January 2010 to November 2020.

RESULTS: PPS was an independent preoperative prognostic factors for survival. The T and N categories were independent prognostic factors. Other SIR scores were not independent preoperative factors in the univariate analysis. Among SIR scores, only the PPS was found to be associated with OS and disease-free survival. The PPS was also associated with histopathological factors (T and N categories).

CONCLUSION: PPS could be useful in predicting long-term survival after PHCC and may be a more useful scoring system than other SIR systems.

PMID:37938415 | DOI:10.1007/s00423-023-03145-3
KLF4 suppresses the proliferation of perihilar cholangiocarcinoma by negatively regulating GDF15 and phosphorylating AKT

Fetched: November 10th, 2023, 5:01am GMT by Xiaoming Zhang

Oncol Rep. 2023 Dec;50(6):222. doi: 10.3892/or.2023.8659. Epub 2023 Nov 8.

ABSTRACT

Krüppel‑like factor 4 (KLF4) is a transcription factor which functions as a tumor suppressor or an oncogene in numerous types of solid tumors. However, its expression levels and function in perihilar cholangiocarcinoma (pCCA) have yet to be elucidated. In the present study, in order to investigate its roles in pCCA, reverse transcription‑quantitative PCR (RT‑qPCR), western blot analysis and immunohistochemistry were used to detect KLF4 expression in pCCA. The Chi‑squared test was used to analyze the associations between KLF4 and the clinicopathological features of patients with pCCA. Univariate and multivariate analyses were subsequently used to analyze the prognostic significance of KLF4. The tumor suppression of KLF4 was investigated for the purposes of illustrating its biological function both in vitro and in vivo. Furthermore, the association between KLF4 and growth/differentiation factor 15 (GDF15) was determined using pCCA tissue microarray (TMA) analysis and RT‑qPCR. The underlying molecular mechanisms between KLF4 and GDF15 were subsequently investigated in vitro. In pCCA tissues, KLF4 was found to be downregulated, and this was negatively associated with the histological grade and tumor size. The knockdown of KLF4 was also found to be a prognostic indicator of the poorer survival of patients with pCCA. Based on in vitro and in vivo analyses, KLF4 was found to suppress tumor progression and induce cell apoptosis. Furthermore, it was found that KLF4 executed its tumor suppressive effects via the regulation of the GDF15/AKT signaling pathway. Taken together, the findings of the present study demonstrate that KLF4 may be considered as an independent biomarker of a favorable prognosis of patients with pCCA, and the KLF4/GDF15/AKT signaling pathway may potentially be a novel molecular therapeutic target for patients with pCCA.

PMID:37937607 | PMC:PMC10652240 | DOI:10.3892/or.2023.8659
A novel model for predicting the prognosis of postoperative intrahepatic cholangiocarcinoma patients

Fetched: November 10th, 2023, 5:01am GMT by Yinghao Lv

Sci Rep. 2023 Nov 6;13(1):19267. doi: 10.1038/s41598-023-45056-9.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) accounts for 20% of liver malignancies with a 5-year survival rate of 35% at best with limited prognostic predictors. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers. In this study, we developed a modified prognostic model from LIPI called intrahepatic immune prognostic index (IIPI) for ICC. A retrospectively study was conducted at Liver Transplant Center of West China Hospital between January 2015 and January 2023. Hematological factors and clinical features of ICC patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. In this study, derived neurtrophil to lymphocyte ratio (dNLR), arbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) have higher AUC values. LIPI was composed of dNLR and was further modified by combing CA199 and CEA, forming the IIPI. The IIPI consists of four grades which are None, Light, Moderate and Severe. Compared to other prognostic factors, IIPI exhibited better ability to predict overall survival. The multivariate analysis indicated that cirrhosis, differentiation, hilar invasion and IIPI were independent prognostic factors for ICC patients. An IIPI-based nomogram was also established and could predict the overall survival. In addition, the subgroup analyses based on clinical prognostic factors showed that the IIPI exhibited excellent prognostic influence. IIPI model is suitable for predicting the prognosis of postoperative ICC patients. Further research is needed to explore the relationship between postoperative recurrence and metastasis of ICC patients and IIPI.

PMID:37935735 | PMC:PMC10630332 | DOI:10.1038/s41598-023-45056-9
Upregulation of RSPO3 via targeted promoter DNA demethylation inhibits the progression of cholangiocarcinoma

Fetched: November 9th, 2023, 5:01am GMT by Guanhua Wu

Clin Epigenetics. 2023 Nov 7;15(1):177. doi: 10.1186/s13148-023-01592-9.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research.

RESULTS: Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression.

CONCLUSIONS: Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA.

PMID:37932819 | PMC:PMC10629118 | DOI:10.1186/s13148-023-01592-9
Induction of apoptotic cell death of cholangiocarcinoma cells by tiliacorinine from Tiliacora triandra: A mechanistic insight

Fetched: November 7th, 2023, 5:01am GMT by Marutpong Detarya

Biochim Biophys Acta Gen Subj. 2023 Dec;1867(12):130486. doi: 10.1016/j.bbagen.2023.130486. Epub 2023 Oct 7.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) exhibits poor response to the present chemotherapeutic agents and frequently develops drug resistance. Finding novel anticancer drugs might enhance patient outcomes. Tiliacorinine, a bisbenzylisoquinoline alkaloid from the Thai medicinal plant Tiliacora triandra, effectively induced apoptosis of human CCA cell lines and inhibited tumor growth in mice. Here, we elucidate further the molecular mechanisms underlining the cytotoxicity of tiliacorinine and its implication in overcoming gemcitabine-resistance of CCA cells.

METHODS: Cytotoxicity of tiliacorinine against CCA cell lines was assessed using MTT assay. The molecular signaling was determined using Western blot analysis. Molecular docking simulations were applied to predict the binding affinity and orientation of tiliacorinine to the possible binding site(s) of the target proteins.

RESULTS: Tiliacorinine induced apoptotic cell death of CCA cells in a dose- and time-dependent manner. Tiliacorinine significantly suppressed the expression of anti-apoptotic proteins, Bcl-xL and XIAP; activated apoptotic machinery proteins, caspase-3, caspase-9, and PARP; and decreased the levels of pAkt and pSTAT3. EGF/EGFR activation model and molecular docking simulations revealed EGFR, Akt, and STAT3 as potent targets of tiliacorinine. Molecular docking simulations indicated a strong binding affinity of tiliacorinine to the ATP-binding pockets of EGFR, PI3K, Akt, JAK2, and SH2 domain of STAT3. Tiliacorinine could synergize with gemcitabine and restore the cytotoxicity of gemcitabine against gemcitabine-resistant CCA cells.

CONCLUSION: Tiliacorinine effectively induced apoptosis via binding and blocking the actions of EGFR, Akt, and STAT3.

GENERAL SIGNIFICANCE: Tiliacorinine is a novel multi-kinase inhibitor and possibly a potent anti-cancer agent, in cancers with high activation of EGFR.

PMID:37813201 | DOI:10.1016/j.bbagen.2023.130486
Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral Subtype

Fetched: November 7th, 2023, 5:01am GMT by Tao Wei

Ann Surg Oncol. 2023 Nov 6. doi: 10.1245/s10434-023-14502-3. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system.

METHODS: Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed.

RESULTS: Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001).

CONCLUSIONS: ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.

PMID:37930500 | DOI:10.1245/s10434-023-14502-3
Mechanisms underlying the changes in acetaldehyde dehydrogenase 1 in cholangiocarcinoma

Fetched: November 7th, 2023, 5:01am GMT by Bai Ding

J Cancer. 2023 Sep 25;14(17):3203-3213. doi: 10.7150/jca.86967. eCollection 2023.

ABSTRACT

Cholangiocarcinoma (CCA) is the most recurrent malignant tumor found in the biliary system. It originates from the bile duct epithelial cells characterized by easy metastasis, high intermittent rate, and poor prognosis. Acetaldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, the levels of which are particularly elevated in various of malignant tumors. Additionally, the increased ALDH1 levels are closely related to the degree and prognosis of malignant tumors. This study reviewed the mechanisms underlying the changes in ALDH1 levels in CCA.

PMID:37928420 | PMC:PMC10622993 | DOI:10.7150/jca.86967
Bile Duct Tumor as the Presenting Manifestation of Colon Cancer: A Case Report

Fetched: November 7th, 2023, 5:01am GMT by Krystal Mills

Cureus. 2023 Oct 2;15(10):e46378. doi: 10.7759/cureus.46378. eCollection 2023 Oct.

ABSTRACT

Painless obstructive jaundice is a well-recognized clinical sign of hepatocellular pathology or obstruction of the biliary system. Bile duct tumors are a known etiology of painless obstructive jaundice. Here, we present a case of obstructive jaundice, which was initially thought be caused by cholangiocarcinoma based on computerized tomography imaging and endoscopic retrograde cholangiopancreatography but was later found to be hilar metastasis from an undiscovered colon cancer.

PMID:37927693 | PMC:PMC10620619 | DOI:10.7759/cureus.46378
Associations of Liver Fluke Infection and Cholangiocarcinoma: A Scoping Review

Fetched: November 7th, 2023, 5:01am GMT by Ankitha Sivanand

Cureus. 2023 Oct 3;15(10):e46400. doi: 10.7759/cureus.46400. eCollection 2023 Oct.

ABSTRACT

Cholangiocarcinoma (CCa) is a highly lethal malignancy of biliary tract epithelial cells. Liver fluke infection is one of the well-known causes of CCa in endemic areas of Southeast Asian and Western Pacific regions. Multistep processes underlie carcinogenesis induced by chronic infection with the fish-borne liver fluke. Mechanical injury from fluke feeding and migrating in the bile duct causes damage to the bile duct epithelial cells. The excretory or secretory product of a parasite called OvGRN-1 is internalized by human cholangiocytes and induces changes in gene and protein expression associated with wound healing and cancer pathways. Inflammatory cytokines and their gene polymorphisms may also be linked to biliary pathologies. High plasma levels of interleukin 6 (IL-6) increase the risk of developing advanced periductal fibrosis (APF) and CCa by promoting CCa cell line proliferation. Anti-helminthic drugs can help decrease the risk of CCa caused by flukes. Surgical resection of the tumor and liver transplantation might be helpful too. Chemotherapy is considered for patients with advanced CCa when they cannot undergo surgery or when other treatment options fail to show improvement. Improvements in hygiene, health education, screening for fluke infection, and anti-helminthic therapy can help prevent liver fluke infection and thus the occurrence of CCa.

PMID:37927641 | PMC:PMC10620839 | DOI:10.7759/cureus.46400
Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018

Fetched: November 6th, 2023, 5:01am GMT by Van Nghiem

Cancer Control. 2023 Jan-Dec;30:10732748231211764. doi: 10.1177/10732748231211764.

ABSTRACT

INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear.

METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival.

RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death.

CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.

PMID:37926828 | PMC:PMC10668577 | DOI:10.1177/10732748231211764
Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer

Fetched: November 5th, 2023, 5:01am GMT by Toshiyuki Ogata

Med Dosim. 2023 Nov 2:S0958-3947(23)00100-0. doi: 10.1016/j.meddos.2023.10.004. Online ahead of print.

ABSTRACT

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

PMID:37925300 | DOI:10.1016/j.meddos.2023.10.004
Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation

Fetched: November 5th, 2023, 5:01am GMT by Lei-Bo Xu

Nat Commun. 2023 Nov 3;14(1):7033. doi: 10.1038/s41467-023-42930-y.

ABSTRACT

Bile duct tumor thrombosis (BDTT) is a complication mostly observed in patients with advanced hepatocellular carcinoma (HCC), causing jaundice and associated with poor clinical outcome. However, its underlying molecular mechanism is unclear. Here, we develop spontaneous preclinical HCC animal models with BDTT to identify the role of BMI1 expressing tumor initiating cells (BMI1^high TICs) in inducing BDTT. BMI1 overexpression transforms liver progenitor cells into BMI1^high TICs, which possess strong tumorigenicity and increased trans-intrahepatic biliary epithelial migration ability by secreting lysosomal cathepsin B (CTSB). Orthotopic liver implantation of BMI1^high TICs into mice generates tumors and triggers CTSB mediated bile duct invasion to form tumor thrombus, while CTSB inhibitor treatment prohibits BDTT and extends mouse survival. Clinically, the elevated serum CTSB level determines BDTT incidence in HCC patients. Mechanistically, BMI1 epigenetically up-regulates CTSB secretion in TICs by repressing miR-218-1-3p expression. These findings identify a potential diagnostic and therapeutic target for HCC patients with BDTT.

PMID:37923799 | PMC:PMC10624910 | DOI:10.1038/s41467-023-42930-y
Current Updates on Diagnosis and Management of Cholangiocarcinoma: from Surgery to Targeted Therapy

Fetched: November 4th, 2023, 5:01am GMT by Haryanto Surya

Acta Med Indones. 2023 Jul;55(3):361-370.

ABSTRACT

Cholangiocarcinoma is commonly described as any malignancy arising from the lining of the bile duct and is recognized as one of the most common biliary malignancies. We conducted a literature review of current available evidences and guidelines.Based on the anatomical location of the origin of the mass, cholangiocarcinoma can be divided into intrahepatic, perihilar, and distal cholangiocarcinoma. Each of these subtypes has their own risk factors, best treatment options, and prognosis. The most common risk factors for cholangiocarcinoma also differs based on geography and population backgrounds. Histopathological biopsy remained the gold standard for cholangiocarcinoma diagnosis, however various advances has been made in diagnostic procedure, including MRCP, EUS, ERCP, EBUS, and cholangioscopy. Surgical resection is still the best treatment modality for cholangiocarcinoma, but it can only be done in few patients considering most patients were diagnosed in the unresectable state. Other treatment options includes conventional chemotherapy, locoregional therapy, systemic targeted therapy, and palliative best supportive care. Cholangiocarcinoma has an abundance of molecular targets and advances in biomolecular technologies bring further hope for future curative treatment options. Treatment options should be chosen individually based on each patient's condition and setting. Cholangiocarcinoma is still a major health problem in hepatobiliary malignancies. Multiple options are available for cholangiocarcinoma treatments.

PMID:37915146
IL-8 is a novel prometastatic chemokine in intrahepatic cholangiocarcinoma that induces CXCR2-PI3K/AKT signaling upon CD97 activation

Fetched: November 3rd, 2023, 5:01am GMT by Ze-Wu Meng

Sci Rep. 2023 Oct 31;13(1):18711. doi: 10.1038/s41598-023-45496-3.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is a rare but highly aggressive malignant tumor arising within the liver, with a 5-year survival rate of only 20-40% after surgery. The role of interleukin-8 (IL-8) in ICC progression remains elusive. A transcriptomic approach based on IL-8 stimulation first revealed significant upregulation of the prometastatic gene CD97 and key epithelial-mesenchymal transition (EMT) factors E-cadherin and vimentin. Immunohistochemistry of 125 ICC tissues confirmed the positive correlation between IL-8 and CD97. Multivariable Cox regression indicated that they are both independent predictors of ICC prognosis. Mechanistically, IL-8 treatment induced CD97 expression at 50 and 100 ng/ml in QBC-939 and QBE cells, respectively. Moreover, the induction of cell migration and invasion upon IL-8 treatment was attenuated by CD97 RNA interference, and the expression of EMT-associated genes was dramatically inhibited. To determine whether CXCR1 or CXCR2 are downstream effectors of IL-8, siCXCR2 was applied and shown to significantly attenuate the oncogenic effects of IL-8 by inhibiting the phosphorylation of PI3K/AKT. Finally, the induction of CD97 expression by the PI3K pathway was verified by treatment with the inhibitor LY294002. In vivo, the significant tumor growth and lung metastasis effects induced by intraperitoneal injection of IL-8 were greatly inhibited by silencing CD97 in nude mice. Collectively, the study presents a novel mechanism of the IL-8-CXCR2-PI3K/AKT axis in regulating CD97 expression, which leads to ICC metastasis mainly through EMT. The study may provide alternatives for targeting the tumor microenvironment in metastatic ICC.

PMID:37907543 | PMC:PMC10618468 | DOI:10.1038/s41598-023-45496-3
Hypoxia-induced SKA3 promoted cholangiocarcinoma progression and chemoresistance by enhancing fatty acid synthesis via the regulation of PAR-dependent HIF-1a deubiquitylation

Fetched: November 3rd, 2023, 5:01am GMT by Yananlan Chen

J Exp Clin Cancer Res. 2023 Oct 11;42(1):265. doi: 10.1186/s13046-023-02842-7.

ABSTRACT

BACKGROUND: Spindle and kinetochore-associated complex subunit 3 (SKA3) plays an important role in cell proliferation by regulating the separation of chromosomes and their division into daughter cells. Previous studies demonstrated that SKA3 was strongly implicated in tumor development and progression. However, the roles of SKA3 in cholangiocarcinoma (CCA) and the underlying mechanisms remain unclear.

METHODS: Next-generation sequencing (NGS) was performed with paired CCA tissues and normal adjacent tissues (NATs). SKA3 was chose to be the target gene because of its remarkably upregulation and unknown function in cholangiocarcinoma in TCGA datasets, GSE107943 datasets and our sequencing results. RT-PCR and immunohistochemistry staining were used to detect the expression of SKA3 in paired CCA tissues and normal adjacent tissues. The SKA3 knockdown and overexpression cell line were constructed by small interfering RNA and lentivirus vector transfection. The effect of SKA3 on the proliferation of cholangiocarcinoma under hypoxic conditions was detected by experiments in vitro and in vivo. RNA-seq was used to find out the differentially expressed pathways in cholangiocarcinoma proliferation under hypoxia regulated by SKA3. IP/MS analysis and Western blot assays were used to explore the specific mechanism of SKA3 in regulating the expression of HIF-1a under hypoxia.

RESULTS: SKA3 was up-regulated in NGS, TCGA and GSE107943 databases and was associated with poor prognosis. Functional experiments in vitro and in vivo showed that hypoxia-induced SKA3 promoted cholangiocarcinoma cell proliferation. RNA-sequencing was performed and verified that SKA3 enhanced fatty acid synthesis by up-regulating the expression of key fatty acid synthase, thus promoting cholangiocarcinoma cell proliferation under hypoxic conditions. Further studies indicated that under hypoxic conditions, SKA3 recruited PARP1 to bind to HIF-1a, thus enhancing the poly ADP-ribosylation (PARylation) of HIF-1a. This PARylation enhanced the binding between HIF-1a and USP7, which triggered the deubiquitylation of HIF-1a under hypoxic conditions. Additionally, PARP1 and HIF-1a were upregulated in CCA and promoted CCA cell proliferation. SKA3 promoted CCA cell proliferation and fatty acid synthesis via the PARP1/HIF-1a axis under hypoxic conditions. High SKA3 and HIF-1a expression levels were associated with poor prognosis after surgery.

CONCLUSION: Hypoxia-induced SKA3 promoted CCA progression by enhancing fatty acid synthesis via the regulation of PARylation-dependent HIF-1a deubiquitylation. Furthermore, increased SKA3 level enhanced chemotherapy-resistance to gemcitabine-based regimen under hypoxic conditions. SKA3 and HIF-1a could be potential oncogenes and significant biomarkers for the analysis of CCA patient prognosis.

PMID:37821935 | PMC:PMC10565972 | DOI:10.1186/s13046-023-02842-7
The RNA methyltransferase METTL16 enhances cholangiocarcinoma growth through PRDM15-mediated FGFR4 expression

Fetched: November 3rd, 2023, 5:01am GMT by Nianli Liu

J Exp Clin Cancer Res. 2023 Oct 11;42(1):263. doi: 10.1186/s13046-023-02844-5.

ABSTRACT

BACKGROUND: RNA N6-Methyladenosine (m6A) modification is implicated in the progression of human cancers including cholangiocarcinoma (CCA). METTL16 is recently identified as a new RNA methyltransferase responsible for m6A modification, although the role of METTL16 in CCA has not yet been examined. The current study aims to investigate the effect and mechanism of the RNA methyltransferase METTL16 in CCA.

METHODS: The expression of METTL16 in CCA was examined by analyzing publicly available datasets or by IHC staining on tumor samples. siRNA or CRISPR/Cas9-mediated loss of function studies were performed in vitro and in vivo to investigate the oncogenic role of METTL16 in CCA. MeRIP-Seq was carried out to identify the downstream target of METTL16. ChIP-qPCR, immunoprecipitation, and immunoblots were used to explore the regulation mechanisms for METTL16 expression in CCA.

RESULTS: We observed that the expression of METTL16 was noticeably increased in human CCA tissues. Depletion of METTL16 significantly inhibited CCA cell proliferation and decreased tumor progression. PRDM15 was identified as a key target of METTL16 in CCA cells. Mechanistically, our data showed that METTL16 regulated PRDM15 protein expression via YTHDF1-dependent translation. Accordingly, we observed that restoration of PRDM15 expression could rescue the deficiency of CCA cell proliferation/colony formation induced by METTL16 depletion. Our subsequent analyses revealed that METTL16-PRDM15 signaling regulated the expression of FGFR4 in CCA cells. Specifically, we observed that PRDM15 protein was associated with the FGFR4 promoter to regulate its expression. Furthermore, we showed that the histone acetyltransferase p300 cooperated with the transcription factor YY1 to regulate METTL16 gene expression via histone H3 lysine 27 (H3K27) acetylation in CCA cells.

CONCLUSIONS: This study describes a novel METTL16-PRDM15-FGFR4 signaling axis which is crucial for CCA growth and may have important therapeutic implications. We showed that depletion of METTL16 significantly inhibited CCA cell proliferation and decreased tumor progression.

PMID:37817227 | PMC:PMC10566113 | DOI:10.1186/s13046-023-02844-5
What Role Does Radiotherapy Play in the Molecular Era for Intrahepatic Cholangiocarcinoma?

Fetched: November 3rd, 2023, 5:01am GMT by Eugene J Koay

Cancer J. 2023 Sep-Oct 01;29(5):272-278. doi: 10.1097/PPO.0000000000000685.

ABSTRACT

Intrahepatic cholangiocarcinoma is a rare disease, yet with rising incidence globally. Most patients are not eligible for potentially curative surgical resection, and many patients with unresectable disease die within 12 months of diagnosis, primarily due to liver failure from the primary tumor. Recent prospective and retrospective studies indicate that local control of the primary tumor can be achieved with hypofractionated radiotherapy in patients with unresectable disease, translating into prolonged survival of these patients. During the time that these encouraging reports for radiotherapy have been published, numerous concurrent studies have also shown that intrahepatic cholangiocarcinoma is a molecularly diverse disease with multiple targetable genetic alterations and a complex tumor microenvironment. These biological insights have translated into new drug approvals for subsets of patients. We review the current knowledge about the biology and targeted treatment of intrahepatic cholangiocarcinoma and describe these developments in the context of modern radiotherapy.

PMID:37796645 | DOI:10.1097/PPO.0000000000000685
Comparison Between Contrast-Enhanced Computed Tomography and Contrast-Enhanced Magnetic Resonance Imaging With Magnetic Resonance Cholangiopancreatography for Resectability Assessment in Extrahepatic Cholangiocarcinoma

Fetched: November 3rd, 2023, 5:01am GMT by Jeongin Yoo

Korean J Radiol. 2023 Oct;24(10):983-995. doi: 10.3348/kjr.2023.0368.

ABSTRACT

OBJECTIVE: To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA).

MATERIALS AND METHODS: This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020. Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ).

RESULTS: No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all). The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754-0.841] vs. 0.753 [0.697-0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884).

CONCLUSION: CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.

PMID:37793669 | PMC:PMC10550738 | DOI:10.3348/kjr.2023.0368
The Clinical Features of Late Postoperative Cholangitis After Hepaticojejunostomy Brought on by Conditions other than Cancer Recurrence

Fetched: November 3rd, 2023, 5:01am GMT by Shinya Sakamoto

Am Surg. 2023 Nov 2:31348231212585. doi: 10.1177/00031348231212585. Online ahead of print.

ABSTRACT

PURPOSE: Postoperative cholangitis and anastomotic strictures (AS) are long-term complications of biliary-enteric anastomosis (BEA).

METHODS: We retrospectively reviewed data of patients who underwent bile duct resection with or without hepatectomy and investigated the risk factors for postoperative cholangitis, benign AS, and incidence of Clavien-Dindo (C-D) >Grade III complications.

RESULTS: Overall, data of 189 patients (115 men and 74 women) were retrospectively analyzed. The median patient age was 73 years. Thirty-five patients (18.5%) developed postoperative cholangitis, and 16 (8.4%) developed postoperative AS. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for cholangitis. The incidence of serious postoperative complications was 32.3%. Hypertension, preoperative biliary drainage, C-reactive protein-albumin ratio ≥.22, and bile duct resection with hepatectomy were potential risk factors for serious postoperative complications.

CONCLUSIONS: The incidence rates of postoperative cholangitis and AS after BEA were 18.5% and 8.4%, respectively. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for postoperative cholangitis.

PMID:37918444 | DOI:10.1177/00031348231212585
Measuring and imaging of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

Fetched: November 3rd, 2023, 5:01am GMT by Masafumi Minakawa

J Biomed Opt. 2023 Oct;28(10):107001. doi: 10.1117/1.JBO.28.10.107001. Epub 2023 Oct 31.

ABSTRACT

SIGNIFICANCE: Evaluation of biological chromophore levels is useful for detection of various skin diseases, including cancer, monitoring of health status and tissue metabolism, and assessment of clinical and physiological vascular functions. Clinically, it is useful to assess multiple different chromophores in vivo with a single technique or instrument.

AIM: To investigate the possibility of estimating the concentration of four chromophores, bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin from diffuse reflectance spectra in the visible region.

APPROACH: A new diffuse reflectance spectroscopic method based on the multiple regression analysis aided by Monte Carlo simulations for light transport was developed to quantify bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin. Three different experimental animal models were used to induce hyperbilirubinemia, hypoxemia, and melanogenesis in rats.

RESULTS: The estimated bilirubin concentration increased after ligation of the bile duct and reached around 18 mg/dl at 50 h after the onset of ligation, which corresponds to the reference value of bilirubin measured by a commercially available transcutaneous bilirubin meter. The concentration of oxygenated hemoglobin and that of deoxygenated hemoglobin decreased and increased, respectively, as the fraction of inspired oxygen decreased. Consequently, the tissue oxygen saturation dramatically decreased. The time course of melanin concentration after depilation of skin on the back of rats was indicative of the supply of melanosomes produced by melanocytes of hair follicles to the growing hair shaft.

CONCLUSIONS: The results of our study showed that the proposed method is capable of the in vivo evaluation of percutaneous bilirubin level, skin hemodynamics, and melanogenesis in rats, and that it has potential as a tool for the diagnosis and management of hyperbilirubinemia, hypoxemia, and pigmented skin lesions.

PMID:37915398 | PMC:PMC10616887 | DOI:10.1117/1.JBO.28.10.107001
Lightweight neural network for smart diagnosis of cholangiocarcinoma using histopathological images

Fetched: November 3rd, 2023, 5:01am GMT by Shubhadip Chakrabarti

Sci Rep. 2023 Nov 1;13(1):18854. doi: 10.1038/s41598-023-46152-6.

ABSTRACT

Traditional Cholangiocarcinoma detection methodology, which involves manual interpretation of histopathological images obtained after biopsy, necessitates extraordinary domain expertise and a significant level of subjectivity, resulting in several deaths due to improper or delayed detection of this cancer that develops in the bile duct lining. Automation in the diagnosis of this dreadful disease is desperately needed to allow for more effective and faster identification of the disease with a better degree of accuracy and reliability, ultimately saving countless human lives. The primary goal of this study is to develop a machine-assisted method of automation for the accurate and rapid identification of Cholangiocarcinoma utilizing histopathology images with little preprocessing. This work proposes CholangioNet, a novel lightweight neural network for detecting Cholangiocarcinoma utilizing histological RGB images. The histological RGB image dataset considered in this research work was found to have limited number of images, hence data augmentation was performed to increase the number of images. The finally obtained dataset was then subjected to minimal preprocessing procedures. These preprocessed images were then fed into the proposed lightweight CholangioNet. The performance of this proposed architecture is then compared with the performance of some of the prominent existing architectures like, VGG16, VGG19, ResNet50 and ResNet101. The Accuracy, Loss, Precision, and Sensitivity metrics are used to assess the efficiency of the proposed system. At 200 epochs, the proposed architecture achieves maximum training accuracy, precision, and recall of 99.90%, 100%, and 100%, respectively. The suggested architecture's validation accuracy, precision, and recall are 98.40%, 100%, and 100%, respectively. When compared to the performance of other AI-based models, the proposed system produced better results making it a potential AI tool for real world application.

PMID:37914815 | PMC:PMC10620203 | DOI:10.1038/s41598-023-46152-6
CT Texture Analysis and Node-RADS CT Score of Lymph Nodes in Patients With Perihilar Cholangiocarcinoma

Fetched: November 3rd, 2023, 5:01am GMT by Jakob Leonhardi

Anticancer Res. 2023 Nov;43(11):5089-5097. doi: 10.21873/anticanres.16709.

ABSTRACT

BACKGROUND/AIM: Texture analysis can provide quantitative imaging markers from computed tomography (CT) images. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of CT texture analysis and the Node-RADS classification to categorize and stage lymph nodes in patients with perihilar cholangiocarcinoma.

PATIENTS AND METHODS: Overall, 25 patients (n=9 females, 36%) with a mean age of 72.4±8.1 years were included. All patients were surgically resected and the lymph nodes were histopathologically analyzed. CT-texture analysis was performed with the Mazda package. All investigated lymph nodes were scored in accordance with the Node-RADS classification.

RESULTS: Regarding lymph node discrimination (N- versus N+), Node-RADS classification achieved an area under the curve (AUC) of 0.86 resulting in a sensitivity of 78% and a specificity of 86%. Multiple investigated texture features were different between negative and positive lymph nodes. The "S(0,1)SumVarnc" achieved the best AUC of 0.75 resulting in a sensitivity of 0.91 and a specificity of 0.67. Correlation analysis showed various statistically significant associations between CT texture features and Node-RADS score.

CONCLUSION: Several CT texture features and the Node-RADS score derived from preoperative staging CT were associated with the malignancy of the hilar lymph nodes and might aid for preoperative staging. This could change surgical treatment planning in hilar cholangiocarcinoma.

PMID:37909955 | DOI:10.21873/anticanres.16709
A 30-Month Survival Case of Undifferentiated Carcinoma of the Duodenum Treated by Pancreaticoduodenectomy

Fetched: November 2nd, 2023, 5:01am GMT by Masakazu Matsuda

Gan To Kagaku Ryoho. 2023 Sep;50(9):1001-1004.

ABSTRACT

The patient was an elderly man in his early 80s who was admitted to our hospital due to anemia and tarry stools. An upper gastrointestinal endoscopy revealed a type 2 tumor in the second portion of the duodenum. An endoscopic biopsy revealed poorly differentiated adenocarcinoma. We performed a pancreaticoduodenectomy because neither lymphadenopathy nor distant metastases were found. Macroscopic findings revealed that the lesion was mainly in the second portion of the duodenum, and there was no evidence of invasion of the main pancreatic duct, the bile duct, or the ampulla of Vater. Histologically, the tumor was composed of atypical cells with polymorphic or spindle-shaped nuclei proliferating in a scattered fashion, and immunohistological examinations showed weakly positive results for cytokeratin(CK)AE1/AE3 and CK20 and positive results for vimentin but negative results for CK7. The tumor was diagnosed as undifferentiated carcinoma of the duodenum(pT4N0M0, pStage ⅡB). The patient recovered enough to be discharged and was followed up without postoperative adjuvant chemotherapy. He maintained recurrence-free survival for 27 months, after which lymph node and lung metastases reoccurred. This is a rare case of undifferentiated carcinoma of the duodenum treated by curative resection with a relatively favorable prognosis.

PMID:37800297
A Novel Mouse Model of Intrahepatic Cholangiocarcinoma Induced by Azoxymethane

Fetched: November 2nd, 2023, 5:01am GMT by Yohei Shirakami

Int J Mol Sci. 2023 Sep 26;24(19):14581. doi: 10.3390/ijms241914581.

ABSTRACT

Cholangiocarcinoma is the second most common primary cancer of the liver and has a poor prognosis. Various animal models, including carcinogen-induced and genetically engineered rodent models, have been established to clarify the mechanisms underlying cholangiocarcinoma development. In the present study, we developed a novel mouse model of malignant lesions in the biliary ducts induced by the administration of the carcinogen azoxymethane to obese C57BLKS/J-db/db mice. A histopathological analysis revealed that the biliary tract lesions in the liver appeared to be an intrahepatic cholangiocarcinoma with higher tumor incidence, shorter experimental duration, and a markedly increased incidence in obese mice. Molecular markers analyzed using a microarray and a qPCR indicated that the cancerous lesions originated from the cholangiocytes and developed in the inflamed livers. These findings indicated that this is a novel mouse model of intrahepatic cholangiocarcinoma in the context of steatohepatitis. This model can be used to provide a better understanding of the pathogenic mechanisms of cholangiocarcinoma and to develop novel therapeutic strategies for this malignancy.

PMID:37834032 | PMC:PMC10572168 | DOI:10.3390/ijms241914581
Granulomatous peritoneal disease associated with oxaliplatin-based chemotherapy for ampullary adenocarcinoma: a case report

Fetched: November 2nd, 2023, 5:01am GMT by G Vermeersch

Acta Gastroenterol Belg. 2023 Jul-Sep;86(3):499-501. doi: 10.51821/86.3.11323.

ABSTRACT

Adenocarcinomas of the ampulla of Vater represent only 0.2% of all gastrointestinal cancers. Due to the low incidence no large clinical trials evaluating efficacy of treatments are available. Adjuvant therapy is often administered in patients with stage IB or higher. Oxaliplatin is considered as an effective and well tolerated therapeutic option. Adverse events associated with this therapy include cardio-, neuro-, nephrotoxicity and myelosuppression. Previously granulomatous pulmonary and liver manifestations have been described in oxaliplatin-based chemotherapy. In this report peritoneal manifestation of granulomatous disease associated with oxaliplatin is described for the first time. Sarcoidlike reactions may be misinterpreted as tumour progression or metastatic disease, and may consequently result in over-treatment.

PMID:37814569 | DOI:10.51821/86.3.11323
Biliary papillomatosis

Fetched: November 2nd, 2023, 5:01am GMT by F Gelders

Acta Gastroenterol Belg. 2023 Jul-Sep;86(3):483-485. doi: 10.51821/86.3.11733.

ABSTRACT

Biliary papillomatosis (BP) is a rare disorder of the biliary tract characterized by the presence of multiple papillary adenomas spread along the biliary tree. Although benign, it carries a significant risk of malignant transformation. Due to low sensitivity and specificity of conventional radiologic modalities, the diagnosis as well as estimation of disease extent is difficult. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreaticography (ERCP) are superior although direct peroral cholangioscopy (POC) is currently the most accurate diagnostic method. Mainly because it provides more detailed information and makes targeted histological diagnosis possible. The treatment of biliary papillomatosis consists of surgical resection, liver transplantation (LT) or a combination of both. Unfortunately, the recurrence rate after radical surgery without LT remains high due to the diffuse distribution of the disease.

PMID:37814564 | DOI:10.51821/86.3.11733
Combined hepatocellular-cholangiocarcinoma containing both large and small duct type cholangiocarcinoma: report of a case

Fetched: November 2nd, 2023, 5:01am GMT by H Wang

Zhonghua Bing Li Xue Za Zhi. 2023 Oct 8;52(10):1047-1049. doi: 10.3760/cma.j.cn112151-20230110-00020.

ABSTRACT

第5版WHO消化系统肿瘤分类提出，肝内胆管癌（intrahepatic cholangiocarcinoma，ICC）存在大胆管型和小胆管型两种组织病理学亚型，但并未提及两种亚型可否在单一肿瘤中同时性发生。此外，认为发生于混合型肝细胞-胆管癌（combined hepatocellular-cholangiocarcinoma，CHC）的胆管癌成分多为小胆管型。本文报道1例65岁男性原发性肝脏CHC，胆管癌部分同时存在大胆管型和小胆管型组织学成分。提示多组织亚型ICC合并发生的可能性，以及CHC中胆管癌成分的多样性和异质性，丰富对肝癌形态学及其发生的认识。.

PMID:37805401 | DOI:10.3760/cma.j.cn112151-20230110-00020
Prognosis value of microscopic bile duct invasion in hepatocellular carcinoma: A multicenter study

Fetched: November 2nd, 2023, 5:01am GMT by Qizhen Huang

Cancer Med. 2023 Nov 1. doi: 10.1002/cam4.6650. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection.

PATIENTS AND METHODS: Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI-MVI-), microscopic bile duct invasion alone (MiBDI+MVI-), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI-MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan-Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models.

RESULTS: A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI- was similar to that of MiBDI-MVI- (p > 0.05) but better than MiBDI+MVI+, MiBDI-MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were.

CONCLUSIONS: Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection.

PMID:37909228 | DOI:10.1002/cam4.6650
Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal

Fetched: November 2nd, 2023, 5:01am GMT by Serrena Singh

Dev Cell. 2023 Oct 23:S1534-5807(23)00522-1. doi: 10.1016/j.devcel.2023.10.004. Online ahead of print.

ABSTRACT

The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.

PMID:37909044 | DOI:10.1016/j.devcel.2023.10.004
Tumour origin, diagnostic accuracy and histopathological evaluation in patients with periampullary cancer: nationwide cohort study

Fetched: November 1st, 2023, 5:00am GMT by Johannes Byrling

BJS Open. 2023 Sep 5;7(5):zrad104. doi: 10.1093/bjsopen/zrad104.

ABSTRACT

BACKGROUND: The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in the literature. During the 2010s, a standardized histopathological protocol for pancreatoduodenectomy specimens based on axial slicing was adopted in Sweden. The present study sought to provide information about periampullary cancers with regard to tumour types in curative and noncurative settings, preoperative diagnostic accuracy and the impact of a standardized evaluation of the surgical specimen on diagnosis, R status and lymph node assessment.

METHODS: Data from patients diagnosed with periampullary cancer from 2010 to 2019 were retrieved from the Swedish National Registry for Pancreatic and Periampullary Cancer.

RESULTS: Among non-curative patients, 3704 (83.6 per cent) were diagnosed with pancreatic ductal adenocarcinoma. Among patients treated with pancreatoduodenectomy, diagnosis was pancreatic ductal adenocarcinoma in 1380 (50.0 per cent), distal cholangiocarcinoma in 284 (10.3 per cent), ampullary cancer in 376 (13.6 per cent), duodenal cancer in 160 (5.8 per cent) and other diagnoses in 560 (20.3 per cent) patients. The preoperative diagnosis corresponded to the postoperative in 1177 (67.5 per cent) patients for pancreatic ductal adenocarcinoma, 162 (37.4 per cent) patients for distal cholangiocarcinoma, 220 (61.3 per cent) patients for ampullary cancer and 120 (53.6 per cent) patients for duodenal cancer. A higher rate of pancreatic ductal adenocarcinoma was seen in surgical specimens who underwent standardized evaluation, from 56.8 per cent to 64.3 per cent (P = 0.003). After standardization, higher rates of R1 resection (31.7 per cent versus 44.6 per cent, P < 0.001) and N1 stage (62.1 per cent versus 77.0 per cent, P < 0.001) were found.

CONCLUSION: The proportion of pancreatic ductal adenocarcinoma was higher in patients in a non-curative setting compared with patients who underwent surgery. The rate of misdiagnosis for periampullary cancers was confirmed to be high. Thus, it should be taken into account when preoperative oncological treatment is considered. Standardized evaluation of the surgical specimen has increased pancreatic ductal adenocarcinoma, R1 and N1 rates.

PMID:37864577 | PMC:PMC10590063 | DOI:10.1093/bjsopen/zrad104
The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

Fetched: October 31st, 2023, 5:01am GMT by Kosuke Mima

Gut Microbes. 2023 Dec;15(2):2269623. doi: 10.1080/19490976.2023.2269623. Epub 2023 Oct 30.

ABSTRACT

Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one's life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations.

PMID:37902043 | DOI:10.1080/19490976.2023.2269623
Impact of preoperative self-expandable metal stent on benign hepaticojejunostomy anastomotic stricture after pancreaticoduodenectomy

Fetched: October 31st, 2023, 5:01am GMT by Takafumi Mie

DEN Open. 2023 Oct 28;4(1):e307. doi: 10.1002/deo2.307. eCollection 2024 Apr.

ABSTRACT

OBJECTIVES: Hepaticojejunostomy anastomotic stricture (HJAS) is a serious adverse event of pancreaticoduodenectomy. Preoperative biliary drainage with a self-expandable metal stent (SEMS) is often performed before pancreaticoduodenectomy. The purpose of this study is to evaluate the risk factors and impact of preoperative SEMS placement on developing benign HJAS after pancreaticoduodenectomy.

METHODS: We retrospectively analyzed consecutive patients who underwent pancreatoduodenectomy at our institution between July 2014 and June 2020. Risk factors for benign HJAS were identified using univariate and multivariate logistic regression analysis. We also compared outcomes of preoperative biliary drainage using SEMS and non-SEMS.

RESULTS: Of the 626 included patients, benign HJAS occurred in 36 patients (5.8%). The median follow-up time was 36.7 months (interquartile range, 25.4-57.4 months). Multivariate logistic regression analysis revealed that lack of preoperative biliary drainage, preoperative bile duct diameter <5 mm, and former or current smoking were independent predictors of benign HJAS. In the preoperative biliary drainage group, the rate of preoperative bile duct diameter <5 mm was significantly lower in the SEMS group than in the non-SEMS group (2.0% vs. 12.8%, p = 0.04).

CONCLUSIONS: Preoperative biliary drainage with SEMS may be useful to maintain bile duct diameter ≥5 mm and to reduce benign HJAS as a result.

PMID:37900615 | PMC:PMC10612468 | DOI:10.1002/deo2.307
Ruptured cystic artery pseudoaneurysm after self-expandable metal stent placement for malignant biliary obstruction

Fetched: October 31st, 2023, 5:01am GMT by Takafumi Mie

DEN Open. 2023 Oct 26;4(1):e304. doi: 10.1002/deo2.304. eCollection 2024 Apr.

ABSTRACT

We report a case of ruptured cystic artery pseudoaneurysm after self-expandable metal stent placement for malignant biliary obstruction. A 78-year-old woman on palliative care after chemotherapy for unresectable pancreatic head cancer presented with obstructive jaundice. Imaging revealed a dilated common bile duct and an enlarged gallbladder with cystic wall thickening. Endoscopic retrograde cholangiopancreatography was performed and a fully-covered self-expandable metal stent was placed in the bile duct, leading to resolution of jaundice. She presented with hematochezia 7 days later. Contrast-enhanced computed tomography revealed a cystic artery pseudoaneurysm with extravasation of contrast into a blood-filled gallbladder. Hemostasis was achieved after emergent transcatheter arterial embolization. Rupture of cystic artery pseudoaneurysm should be raised as a differential diagnosis for hemobilia after self-expandable metal stent placement, particularly in cases accompanied by inflamed gallbladders.

PMID:37900613 | PMC:PMC10602019 | DOI:10.1002/deo2.304
Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology

Fetched: October 31st, 2023, 5:01am GMT by Federico Mocchegiani

World J Gastroenterol. 2023 Oct 14;29(38):5361-5373. doi: 10.3748/wjg.v29.i38.5361.

ABSTRACT

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

PMID:37900587 | PMC:PMC10600795 | DOI:10.3748/wjg.v29.i38.5361
The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy

Fetched: October 31st, 2023, 5:01am GMT by Yasunori Yoshimi

Ann Surg Oncol. 2023 Oct 29. doi: 10.1245/s10434-023-14406-2. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy.

METHODS: We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G).

RESULTS: R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G.

CONCLUSIONS: Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

PMID:37899414 | DOI:10.1245/s10434-023-14406-2
Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)

Fetched: October 31st, 2023, 5:01am GMT by Siqi Yang

Int J Oncol. 2023 Dec;63(6):137. doi: 10.3892/ijo.2023.5585. Epub 2023 Oct 27.

ABSTRACT

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy originating from the epithelial system of the bile ducts, and its incidence in recent years is steadily increasing. The immune microenvironment of CCA is characterized by diversity and complexity, with a substantial presence of cancer‑associated fibroblasts and immune cell infiltration, which plays a key role in regulating the distinctive biological behavior of cholangiocarcinoma, including tumor growth, angiogenesis, lymphangiogenesis, invasion and metastasis. Despite the notable success of immunotherapy in the treatment of solid tumors in recent years, patients with CCA have responded poorly to immune checkpoint inhibitor therapy. The interaction of tumor cells with cellular components of the immune microenvironment can regulate the activity and function of immune cells and form an immunosuppressive microenvironment, which may cause ineffective immunotherapy. Therefore, the components of the tumor immune microenvironment appear to be novel targets for immune therapies. Combination therapy focusing on immune checkpoint inhibitors is a promising and valuable first‑line or translational treatment approach for intractable biliary tract malignancies. The present review discusses the compositional characteristics and regulatory factors of the CCA immune microenvironment and the possible immune escape mechanisms. In addition, a summary of the advances in immunotherapy for CCA is also provided. It is hoped that the present review may function as a valuable reference for the development of novel immunotherapeutic strategies for CCA.

PMID:37888583 | PMC:PMC10631767 | DOI:10.3892/ijo.2023.5585
Safety and Efficacy of Hepatic Artery Embolization in Heavily Treated Patients with Intrahepatic Cholangiocarcinoma: Analysis of Clinicopathological and Radiographic Parameters Associated with Better Overall Survival

Fetched: October 31st, 2023, 5:01am GMT by Sara Velayati

Curr Oncol. 2023 Oct 18;30(10):9181-9191. doi: 10.3390/curroncol30100663.

ABSTRACT

The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4-18.5) and 4 months (CI = 95%, 2.09-5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC.

PMID:37887563 | PMC:PMC10605490 | DOI:10.3390/curroncol30100663
Computational identification and exploration of novel FGFR tyrosine kinase inhibitors for the treatment of cholangiocarcinoma

Fetched: October 29th, 2023, 5:01am GMT by Amanpreet Kaur

J Biomol Struct Dyn. 2023 Oct 28:1-12. doi: 10.1080/07391102.2023.2274975. Online ahead of print.

ABSTRACT

Tyrosine kinase inhibitors are a specific drug class revolutionizing cancer treatment. FGFR (Fibroblast Growth Factor Receptor) is a member of the receptor tyrosine kinase family that has been involved in various alterations which have been increasingly recognized as critical molecular drivers in cholangiocarcinoma, a malignant tumor originating from bile duct epithelial cells. The paper focuses on stepwise computational investigations for the discovery of novel inhibitors of FGFR using pharmacophore modeling, virtual screening, docking, ADMET analysis, molecular dynamics, and knowledge-based structure-activity relationship. To begin with, we have considered a library of 120314868 compounds from the ZINC 15 database through pharmacophore modeling, which was narrowed down to 110 having binding affinity >-8.0 kcal mol^-1. The 110 compounds were analyzed using virtual screening and compared with the FDA-approved drug pemigatinib, which provided the 34 hits with binding affinities >-6.5 kcal mol^-1. Finally, the top 4 hits were considered for docking, and ADMET property analysis for drug-likeness. MD and MM-GBSA analysis were performed to predict the binding free energy of these chemicals and determine their stability. To gain insight into the structure and binding interactions of these compounds, knowledge-based SAR analyses were performed using their electrostatic potential maps computed with DFT. Several techniques were employed to build improved inhibitors based on these SAR, and they were then analyzed utilizing ADMET, MD studies, and MM-GBSA analyses. Finally, the results suggested that the identified four compounds and developed inhibitors from this current work can be employed effectively as prospective FGFR inhibitors for treating Cholangiocarcinoma.Communicated by Ramaswamy H. Sarma.

PMID:37897189 | DOI:10.1080/07391102.2023.2274975
Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors

Fetched: October 29th, 2023, 5:01am GMT by Mohamed O Radwan

Biomolecules. 2023 Sep 28;13(10):1465. doi: 10.3390/biom13101465.

ABSTRACT

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

PMID:37892147 | PMC:PMC10604226 | DOI:10.3390/biom13101465
Treatment of Ampullary Adenocarcinoma

Fetched: October 27th, 2023, 5:01am GMT by Dong Woo Shin

Korean J Gastroenterol. 2023 Oct 25;82(4):159-170. doi: 10.4166/kjg.2023.110.

ABSTRACT

The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.

PMID:37876255 | DOI:10.4166/kjg.2023.110
Variations of the hepatic artery and bile duct in patients with pancreaticobiliary maljunction: Impact on postoperative outcomes

Fetched: October 26th, 2023, 5:01am GMT by Shunya Takada

J Hepatobiliary Pancreat Sci. 2023 Nov;30(11):1241-1248. doi: 10.1002/jhbp.1381. Epub 2023 Oct 25.

ABSTRACT

PURPOSE: Preoperative comprehension of the anatomical variations of the hepatic artery and bile duct is essential for safe laparoscopic surgery for pancreaticobiliary maljunction (PBM). This study aimed to investigate the impact of anatomical variations of the hepatic artery and bile duct on surgical technique and postoperative complications.

METHODS: We conducted a retrospective review of patients with PBM who underwent laparoscopic surgery at our institution between January 2014 and December 2022 to investigate anatomical variations in the hepatic artery and bile duct, surgical technique, and postoperative complications.

RESULTS: We included 112 patients with PBM, with a median age of 4 years (interquartile range, 0-55). Overall, 29 of 112 patients had an aberrant right hepatic artery (ARHA) running ventral to the common hepatic duct (CHD), and they underwent hepaticojejunostomy on the ventral side of the ARHA. Additionally, eight of 112 patients had an aberrant posterior hepatic duct (APHD), which was joined to the CHD in all but one case. The presence of APHD was associated with postoperative bile leak occurrence.

CONCLUSION: Performing hepaticojejunostomy ventral to the ARHA is important to prevent complications. Furthermore, APHD may be a risk factor for postoperative bile leak and requires careful bile duct plasty.

PMID:37876298 | DOI:10.1002/jhbp.1381
Using immunovascular characteristics to predict very early recurrence and prognosis of resectable intrahepatic cholangiocarcinoma

Fetched: October 23rd, 2023, 5:01am GMT by Ying Xu

BMC Cancer. 2023 Oct 19;23(1):1009. doi: 10.1186/s12885-023-11476-z.

ABSTRACT

OBJECTIVE: To predict the very early recurrence (VER) of patients with intrahepatic cholangiocarcinoma (ICC) based on TLSs and MVI status, and further perform prognosis stratifications.

METHODS: A total of 160, 51 ICC patients from two institutions between May 2012 and July 2022 were retrospectively included as training, external validation cohort. Clinical, radiological and pathological variables were evaluated and collected. Univariate and multivariate analysis were applied to select the significant factors related to VER of ICC. The factors selected were combined to perform stratification of overall survival (OS) using the Kaplan-Meier method with the log-rank test.

RESULTS: Overall, 39 patients (24.4%) had VER, whereas 121 (75.6%) did not (non-VER group). In the training cohort, the median OS was 40.5 months (95% CIs: 33.2-47.7 months). The VER group showed significantly worse OS than the non-VER group (median OS: 14.8, 95% CI:11.6-18.0 months vs. 53.4, 34.3-72.6 months; p<0.001), and it was confirmed in the validation cohort (median OS: 22.1, 95% CI: 8.8-35.4 months vs. 40.1, 21.2-59.0 months; p = 0.003). According to the univariate analysis, four variables were significantly different between the VER group and non-VER group (TLSs status, p = 0.028; differentiation, p = 0.023; MVI status, p = 0.012; diameter, p = 0.028). According to the multivariate analysis, MVI-positive status was independently associated with a higher probability of VER (odds ratio [OR], 2.5; 95% CIs,1.16-5.18; p = 0.018), whereas intra-tumoral TLSs-positive status was associated with lower odds of VER (OR, 0.43; 95% CIs, 0.19-0.97; p = 0.041). Based on the TLSs and MVI status, patients of ICC were categorized into four groups: TLSs-positive and MVI-negative (TP/MN); TLSs-negative and MVI-negative (TN/MN); TLSs-positive and MVI-positive (TP/MP), TLSs-negative and MVI-positive groups (TN/MP). In the training cohort, the four groups could be correlated with OS significantly (p<0.001), and it was confirmed in the validation cohort (p<0.001).

CONCLUSION: Intra-tumoral TLSs and MVI status are independent predictive factors of VER after surgery, based on which immunovascular stratifications are constructed and associated with OS significantly of resectable intrahepatic cholangiocarcinoma.

PMID:37858111 | PMC:PMC10588260 | DOI:10.1186/s12885-023-11476-z
Endoscopic treatment of obstructive jaundice in patients with Klatskin tumor

Fetched: October 23rd, 2023, 5:01am GMT by A V Kachmazova

Khirurgiia (Mosk). 2023;(4):55-60. doi: 10.17116/hirurgia202304155.

ABSTRACT

OBJECTIVE: To improve treatment outcomes in patients with Klatskin tumor and obstructive jaundice by using of endoscopic bilioduodenal stenting.

MATERIAL AND METHODS: There were 1904 transpapillary interventions between August 2017 and February 2022. Endoscopic bilioduodenal stenting was performed in 250 patients including 25 (10%) ones with Klatskin tumor.

RESULTS: Bilioduodenal plastic and self-expanding stents were installed in 19 (76%) and 6 (24%) patients, respectively. In Klatskin tumor type I, 11 patients (44%) underwent bilioduodenal stenting of common hepatic duct with plastic stent; 5 (20%) patients with Klatskin tumor type II received self-expanding stents. In case of tumor type IIIA, 3 (12%) patients underwent stenting of the right lobar duct with plastic stent. Four (16%) patients with Klatskin tumor type III B underwent stenting of the left lobar duct. Two 2 (8%) patients with Klatskin tumor type IV underwent bilateral bilioduodenal stenting with plastic and bifurcation self-expanding stents. Peroral cholangioscopy using the SpyGlass DS system was performed in 4 (16%) patients. No intraoperative complications were identified. One (4%) patient developed gastrointestinal bleeding in 2 postoperative days after retrograde intervention that did not require surgery. Moreover, 1 (4%) patient with distal dislocation of plastic bilioduodenal stent required redo bilioduodenal stenting. Three (12%) patients died from multiple organ failure despite adequate biliary decompression, and 22 (88%) patients were discharged in 8±5 days after retrograde intervention.

CONCLUSION: Bilioduodenal stenting as minimally invasive and physiological method was highly effective for obstructive jaundice in patients with Klatskin tumor. Peroral cholangioscopy using the SpyGlass system provides effective and safe direct visualization of the biliary tract, as well as biopsy for morphological verification and prescription of chemotherapy in patients with intraductal growth of tumor.

PMID:37850895 | DOI:10.17116/hirurgia202304155
Automated 3D liver segmentation from hepatobiliary phase MRI for enhanced preoperative planning

Fetched: October 23rd, 2023, 5:01am GMT by Namkee Oh

Sci Rep. 2023 Oct 17;13(1):17605. doi: 10.1038/s41598-023-44736-w.

ABSTRACT

Recent advancements in deep learning have facilitated significant progress in medical image analysis. However, there is lack of studies specifically addressing the needs of surgeons in terms of practicality and precision for surgical planning. Accurate understanding of anatomical structures, such as the liver and its intrahepatic structures, is crucial for preoperative planning from a surgeon's standpoint. This study proposes a deep learning model for automatic segmentation of liver parenchyma, vascular and biliary structures, and tumor mass in hepatobiliary phase liver MRI to improve preoperative planning and enhance patient outcomes. A total of 120 adult patients who underwent liver resection due to hepatic mass and had preoperative gadoxetic acid-enhanced MRI were included in the study. A 3D residual U-Net model was developed for automatic segmentation of liver parenchyma, tumor mass, hepatic vein (HV), portal vein (PV), and bile duct (BD). The model's performance was assessed using Dice similarity coefficient (DSC) by comparing the results with manually delineated structures. The model achieved high accuracy in segmenting liver parenchyma (DSC 0.92 ± 0.03), tumor mass (DSC 0.77 ± 0.21), hepatic vein (DSC 0.70 ± 0.05), portal vein (DSC 0.61 ± 0.03), and bile duct (DSC 0.58 ± 0.15). The study demonstrated the potential of the 3D residual U-Net model to provide a comprehensive understanding of liver anatomy and tumors for preoperative planning, potentially leading to improved surgical outcomes and increased patient safety.

PMID:37848662 | PMC:PMC10582008 | DOI:10.1038/s41598-023-44736-w
Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts

Fetched: October 23rd, 2023, 5:01am GMT by Theerayut Thongrin

Open Vet J. 2023 Sep;13(9):1150-1166. doi: 10.5455/OVJ.2023.v13.i9.11. Epub 2023 Sep 30.

ABSTRACT

BACKGROUND: Individual host susceptibility is believed to be a risk factor in the interaction between the host and the parasite. Since studying time series in humans is limited, animal models are replaced.

AIM: This study aims to explore and compare the pattern of inflammatory cell types along the biliary tract and their association with proliferative lesions in the early development of cholangiocarcinoma from susceptible and nonsusceptible animal models.

METHODS: Thirty male Syrian golden hamsters and 30 BALB/c mice, serving as the susceptible and nonsusceptible animal models, were used in this comparative study. The animals were infected with 50 Opisthorchis viverrini metacercariae via gastric intubation. At days 1, 2, 7, 14, 28, and 56 postinfection (p.i.), five animals were randomly selected from each group and humanely sacrificed. The hepatobiliary tissues were collected and processed for histopathological study. Histochemical and immunohistochemical staining were applied to differentiate the inflammatory cell types. Kruskal-Wallis and Mann-Whitney tests were applied to assess all semi-quantitative and quantitative variables. The correlation between each variable was also analyzed using Spearman rank at a p-value < 0.05.

RESULTS: The results demonstrated that mice had different patterns of infiltrating cell types when compared to hamsters. This suggested that the cellular response to the infection in mice occurred earlier than that in hamsters. The response in mice reached its peak at D7 to D14 and then rapidly declined at D28. In contrast, although the inflammatory response in hamsters started slowly, the response reached the peak at D28 and maintained a high level until D56. Significant differences in the number of inflammatory cells between mice and hamsters were seen at D1 (p = 0.047), D7 (p = 0.049), D28 (p = 0.040), and D56 (p < 0.040).

CONCLUSION: The inflammatory responses to O. viverrini infection in the nonsusceptible animal model occurred and declined earlier while the response in the susceptible animal model occurred later in a gradual manner. Both rodents are suitable animal models for the studies of opisthorchiasis susceptibility.

PMID:37842106 | PMC:PMC10576576 | DOI:10.5455/OVJ.2023.v13.i9.11
Cartilage oligomeric matrix protein overexpression is an independent poor prognostic indicator in patients with intrahepatic cholangiocarcinoma

Fetched: October 23rd, 2023, 5:01am GMT by Khaa Hoo Ong

Sci Rep. 2023 Oct 14;13(1):17444. doi: 10.1038/s41598-023-43006-z.

ABSTRACT

Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker.

PMID:37838792 | PMC:PMC10576746 | DOI:10.1038/s41598-023-43006-z
Clinical Significance of Sphingosine 1-phosphate Receptor 2 and Takeda G Protein-coupled Receptor 5 in Extrahepatic Cholangiocarcinoma Patients

Fetched: October 23rd, 2023, 5:01am GMT by Hayeon Kim

J Gastrointestin Liver Dis. 2023 Sep 29;32(3):371-376. doi: 10.15403/jgld-4841.

ABSTRACT

BACKGROUND AND AIMS: In biliary epithelial cells, two bile acid receptors, sphingosine 1-phosphate receptor 2 (S1PR2) and Takeda G protein-coupled receptor 5 (TGR5) have been reported to trigger cell proliferation, as well as neoplastic cell invasiveness. In this study, we aimed to investigate the clinical significance of S1PR2/ TGR5 expression in extrahepatic cholangiocarcinoma (CCA) patients.

METHODS: Patients who underwent surgical resection of extrahepatic CCA at Korea University Guro Hospital between 2002 and 2018 were included. Data on immunohistochemical staining and H-score of S1PR2 and TGR5 were evaluated using digital image analysis.

RESULTS: A total of 115 cases of invasive CCA were analyzed. The H-score of S1PR2 showed a decrease in invasive CCA (p=0.052) but that of TGR5 showed a significant increase (p=0.02). Overall survival and disease-free survival were significantly lower in the low S1PR2 expression group (p<0.05) than in the control group; however, TGR5 expression was not significant (p=0.096). In multivariate analysis, low S1PR2 was only significant for poor prognosis.

CONCLUSION: Low S1PR2 level was the only independent poor prognostic factor in patients with resected extrahepatic CCA.

PMID:37774230 | DOI:10.15403/jgld-4841
PD-1 blockade and radiotherapy combination for advanced Epstein-Barr virus-associated intrahepatic cholangiocarcinoma: a case report and literature review

Fetched: October 23rd, 2023, 5:01am GMT by Chun-Xu Liao

Front Immunol. 2023 Sep 11;14:1239168. doi: 10.3389/fimmu.2023.1239168. eCollection 2023.

ABSTRACT

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.

PMID:37753076 | PMC:PMC10518395 | DOI:10.3389/fimmu.2023.1239168
CT imaging features of bile duct stent complications

Fetched: October 23rd, 2023, 5:01am GMT by Nga T Nguyen

Clin Imaging. 2023 Nov;103:109986. doi: 10.1016/j.clinimag.2023.109986. Epub 2023 Sep 21.

ABSTRACT

Biliary stents have been widely used to treat both malignant and benign biliary obstruction. Biliary stenting serves as a temporary measure to maintain ductal patency and promote bile drainage. Biliary decompression can help relieve clinical symptoms of pain, obstructive jaundice, pruritis, fat malabsorption, and failure to thrive and prevent disease progression, such as secondary biliary cirrhosis and end-stage liver failure. Endoscopic placement of biliary endoprosthesis is a minimally invasive procedure well tolerated by most patients but is not without problems. Multiple early and late complications have been reported in the literature and Computed Tomography (CT) is the most used modality to assess normal positions and evaluate patients suspected of stent complications. The aim of this article is to provide a review various of biliary stent related complications, as seen on CT. Current literature on risk factors, diagnosis and management is also discussed.

PMID:37742411 | DOI:10.1016/j.clinimag.2023.109986
Bariatric Surgery and Risk of Hospitalization for Gastrointestinal Cancers in the USA: a Propensity Score Matched Analysis of National Inpatient Sample Study

Fetched: October 21st, 2023, 5:01am GMT by Ali Esparham

Obes Surg. 2023 Oct 20. doi: 10.1007/s11695-023-06883-x. Online ahead of print.

ABSTRACT

BACKGROUND: There are some concerns about the higher risk of certain gastrointestinal (GI) cancers in patients with a history of bariatric metabolic surgery (BMS). The current study aimed to investigate the association of BMS with GI cancer hospital admission including esophageal, gastric, colorectal, small intestinal, liver, gallbladder, bile duct, and pancreatic cancers.

METHODS: The analysis utilized the US national inpatient sample (NIS) data from 2016 to 2020, employing ICD-10 codes. A propensity score matching in a 3:1 ratio was done to match the BMS and non-BMS groups.

RESULTS: A total of 328,369 patients with a history of BMS and 4,989,154 with obesity and without a history of BMS were included in this study. BMS was independently associated with a higher risk of gastric and pancreatic cancers hospital admission (OR: 1.69 (CI 95%: 1.42-2.01) and OR: 1.46 (CI 95%: 1.27-1.68)), respectively. In addition, BMS was independently associated with a lower risk of colorectal and liver cancer hospital admission (OR: 0.57 (CI 95%: 0.52-0.62) and OR: 0.72 (CI 95%: 0.52-0.98)), respectively. Besides, esophageal, gallbladder, bile duct, and small intestinal cancer were not significantly different between the two groups. In patients with GI cancer, although the BMS group had significantly lower total charges and length of hospital stay compared to the non-BMS group, the rate of in-hospital mortality was not significantly different.

CONCLUSION: The current study showed that bariatric surgery may be associated with a higher risk of gastric and pancreatic cancer and a lower risk of colorectal and liver cancer hospital admission. Further research is needed to explore this association.

PMID:37861878 | DOI:10.1007/s11695-023-06883-x
Multi-institutional review of adverse events associated with irreversible electroporation in the treatment of locally advanced pancreatic cancer

Fetched: October 19th, 2023, 5:01am GMT by Kyle Stephens

Surgery. 2023 Oct 16:S0039-6060(23)00609-8. doi: 10.1016/j.surg.2023.08.042. Online ahead of print.

ABSTRACT

BACKGROUND: Irreversible electroporation is a novel approach for treating locally advanced pancreatic adenocarcinoma. However, this ablative technique is not without risk and has the potential to precipitate adverse events. The aim of this study was to delineate risk factors that increase this risk, as well as to elucidate the risk profile associated with irreversible electroporation in the setting of locally advanced pancreatic adenocarcinoma.

METHODS: A review of our prospective multi-institutional database from December 2015 to March 2022 of patients with locally advanced pancreatic adenocarcinoma who underwent irreversible electroporation was analyzed for adverse events. These were then compared with a control population of patients undergoing pancreatectomy for adenocarcinoma.

RESULTS: Adverse events occurred in 51 patients of the 201 patients treated with irreversible electroporation compared with 78 of the 200 patients treated with pancreatectomy. The irreversible electroporation group had a significantly greater incidence of postoperative ascites in stage 3C patients. The most common complications in the irreversible electroporation group were infectious (n = 13), gastrointestinal bleed (n = 11), and ascites (n = 7). Multivariate analysis demonstrated increased risk of severe (grade ≥3) adverse events in the irreversible electroporation cohort who received high dose, neoadjuvant radiation (hazard ratio, 2.4; 95% confidence interval, 1.4-5.4), irreversible electroporation electrodes bracketing the superior mesenteric artery, superior mesenteric vein, and portal venous vein (hazard ratio, 1.9; 95% confidence interval, 1.3-3.4), and who had a bile duct stent in place for >6 months (hazard ratio, 1.7; 95% confidence interval, 1.2-5.6). There were similar rates of 90-day mortality in both groups, irreversible electroporation 2.4% vs pancreatectomy 2.8%.

CONCLUSION: This study revealed a 25% rate of adverse events associated with irreversible electroporation in locally advanced pancreatic adenocarcinoma, which was significantly less (P = .004) than the 39% rate of adverse events associated with pancreatectomy in early-stage disease. Certain unique adverse events in the irreversible electroporation group have been established and should be understood in the care of these patients.

PMID:37852831 | DOI:10.1016/j.surg.2023.08.042
A case of congenital biliary dilatation without pancreaticobiliary maljunction, so-called Type Ib according to Todani's classification

Fetched: October 19th, 2023, 5:01am GMT by Yusuke Kiyoshita

Clin J Gastroenterol. 2023 Oct 18. doi: 10.1007/s12328-023-01873-z. Online ahead of print.

ABSTRACT

Congenital biliary dilatation (CBD) is a congenital malformation of focal dilatation of the extrahepatic bile ducts, including the common bile duct, and is often associated with pancreaticobiliary maljunction (PBM). In this article, we report a CBD case that presented with focal dilation of the common bile duct without PBM (Todani's classification type Ib). The patient was a 32-year-old man who visited a doctor with a chief complaint of abdominal distension. Computed tomography revealed cystic dilatation of the common bile duct, and the patient was referred to our institution. Magnetic resonance cholangiopancreatography showed cystic dilatation of the common bile duct with a maximum diameter of 7 cm; however, evaluating the presence of PBM was challenging. Endoscopic ultrasonography showed small gallstones and debris in the dilated common bile duct and no thickening of the gallbladder wall. Endoscopic retrograde cholangiopancreatography revealed no PBM or markedly elevated bile amylase levels. Based on these findings, the patient was diagnosed with Todani Type Ib CBD. Since this patient did not have pancreatobiliary reflux, it was unclear whether the risk of developing biliary tract cancer was high, and since the treatment was highly invasive, the decision was to follow up without surgical treatment.

PMID:37851209 | DOI:10.1007/s12328-023-01873-z
Gastric cancer simultaneously complicated with extrahepatic bile duct metastasis and portal vein tumor thrombus: a case report

Fetched: October 18th, 2023, 5:01am GMT by Naohiko Otsuka

Surg Case Rep. 2023 Oct 17;9(1):182. doi: 10.1186/s40792-023-01764-y.

ABSTRACT

BACKGROUND: Gastric cancer metastatic to the extrahepatic bile duct or accompanied by portal vein tumor thrombus (PVTT) is rare. To our knowledge, there have been no cases complicated with both of these factors.

CASE PRESENTATION: A 72-year-old man presented with icterus and melena. A biochemical blood test showed abnormal values for hepatobiliary enzymes and a tumor marker, and abdominal computed tomography scan revealed wall thickening of the lower bile duct with intra- and extra-hepatic bile duct dilatation and PVTT. A biopsy of the lower bile duct during endoscopic retrograde cholangiopancreatography demonstrated a moderately differentiated tubular adenocarcinoma. Moreover, gastroduodenoscopy showed a type 3 tumor at the lesser curvature of the gastric antrum, and an endoscopic biopsy demonstrated a moderately differentiated tubular adenocarcinoma. We diagnosed concomitant gastric cancer and distal bile duct accompanied by PVTT, and pancreatoduodenectomy with combined resection of the portal vein was performed. The resected specimen revealed a tumor in the lesser curvature of the gastric antrum and circumferential wall thickening in the lower bile duct. In pathological findings, infiltration of a moderately differentiated tubular adenocarcinoma from the mucosal layer to the subserosal layer of the stomach was observed. In contrast, a moderately differentiated tubular adenocarcinoma demonstrating the same histological type as the gastric cancer had spread not to the mucosal layer but mainly to the fibromuscular layer of the lower bile duct. Immunohistochemical staining showed identical patterns between gastric cancer and the bile duct tumor: negativity for cytokeratin 7 (CK7), and positivity for CK19 and 20. Therefore, the final diagnosis was extrahepatic bile duct metastasis from gastric cancer with PVTT. Unfortunately, multiple liver metastases occurred in the early postoperative period and chemotherapy was conducted, but the patient died 12 months after the surgery.

CONCLUSIONS: In the diagnosis of extrahepatic bile duct metastasis, immunohistochemical staining of gastric cancer and the bile duct tumor was essential and helpful as decisive evidence.

PMID:37847321 | PMC:PMC10581976 | DOI:10.1186/s40792-023-01764-y
Autophagy impairment in human bile duct carcinoma cells

Fetched: October 17th, 2023, 5:01am GMT by Simonetta Petrungaro

Front Physiol. 2023 Sep 29;14:1249264. doi: 10.3389/fphys.2023.1249264. eCollection 2023.

ABSTRACT

Bile duct epithelial cells, named cholangiocytes, may undergo a neoplastic transformation leading to cholangiocarcinoma. The role autophagy plays in cancer is still debated and few information are available in cholangiocarcinoma. We report in vitro data, at least in part validated in vivo,i ndicating that autophagy is impaired in intrahepatic cholangiocarcinoma cells, as compared to healthy cholangiocytes, evaluated through LC3II and p62 Western blot analyses. Autophagy impairment was found to be associated with low expression of TFEB protein and high expression of three proteins i.e., c-FLIP, caspase-10 and cleaved BCLAF-1, as compared to healthy cholangiocytes. We highlight biological effects of autophagy impairment in cholangiocarcinoma showing that autophagy induction, via rapamycin, as well as caspase inhibition, via Q-VD-OPh, are able to reduce proliferation marker PCNA level, colony size and protein content of cultured cholangiocarcinoma cells. The increased protein expression of p62, c-FLIP, caspase-10 observed in vitro in cholangiocarcinoma cells was paralleled by significant increase at gene expression levels in vivo; in fact, significant increase of transcript levels of p62, c-FLIP and caspase-10 was observed in 34 biopsies from human cholangiocarcinoma patients compared to 9 biopsies from 9 healthy controls, as reported in the GEPIA2 public database. The significant increase of p62 level in cholangiocarcinoma was found as a relatively uncommon finding in solid cancers, since it was also found in only 7 cancer types out of 31 cancer types investigated, including melanoma and hepatocarcinoma. In conclusion, we present data suggesting a molecular machinery controlling autophagy in cholangiocytes and autophagy impairment in cholangiocarcinoma.

PMID:37841311 | PMC:PMC10570450 | DOI:10.3389/fphys.2023.1249264
Intraductal papillary neoplasm of the bile duct with metachronous development in the downstream bile duct after radical resection

Fetched: October 16th, 2023, 5:01am GMT by Taito Ito

Clin J Gastroenterol. 2023 Oct 14. doi: 10.1007/s12328-023-01867-x. Online ahead of print.

ABSTRACT

We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection.

PMID:37837506 | DOI:10.1007/s12328-023-01867-x
Utility of Covered Self-Expanding Metal Stents for Biliary Drainage during Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Cancer

Fetched: October 15th, 2023, 5:01am GMT by Masaru Furukawa

J Clin Med. 2023 Sep 28;12(19):6245. doi: 10.3390/jcm12196245.

ABSTRACT

OBJECTIVES: We aimed to compare the utility of covered self-expanding metal stents (CSEMSs) with that of plastic stents (PSs) for biliary drainage during neoadjuvant chemotherapy in patients with borderline resectable pancreatic cancer.

METHODS: Forty patients with borderline resectable pancreatic cancer underwent biliary stenting during neoadjuvant chemotherapy at Hiroshima University Hospital. PSs and CSEMSs were placed in 19 and 21 patients, respectively. Two gemcitabine-based regimens for chemotherapy were used. Treatment outcomes and postoperative complications were compared between both groups.

RESULTS: The incidence of recurrent biliary obstruction was significantly lower in the CSEMS group (0% vs. 47.4%, p < 0.001), and the median time to recurrent biliary obstruction in the PS group was 47 days. There was no difference in the incidence of other complications such as non-occlusive cholangitis, pancreatitis, and cholecystitis between the two groups. Delays in the chemotherapy schedule due to stent-related complications were significantly frequent in the PS group (52.6% vs. 4.8%, p = 0.001). There was no significant difference in the incidence of postoperative complications between the two groups.

CONCLUSIONS: CSEMSs may be the best choice for safely performing neoadjuvant chemotherapy for several months in patients with borderline resectable pancreatic cancer with bile duct stricture.

PMID:37834889 | PMC:PMC10573529 | DOI:10.3390/jcm12196245
Understanding Barriers to Enrollment in Adjuvant Clinical Trials: Insights into Patient Eligibility Criteria from the Adjuvant S-1 for Cholangiocarcinoma Trial (JCOG1202, ASCOT)

Fetched: October 13th, 2023, 5:01am GMT by Divya Sood

Ann Surg Oncol. 2023 Nov;30(12):6967-6969. doi: 10.1245/s10434-023-14272-y. Epub 2023 Sep 8.

NO ABSTRACT

PMID:37684366 | DOI:10.1245/s10434-023-14272-y
EUS-Guided Choledochoduodenostomy after Failed Endoscopic Retrograde Cholangiopancreatography in Distal Malignant Biliary Obstruction

Fetched: October 12th, 2023, 5:01am GMT by Isabel Tarrio

GE Port J Gastroenterol. 2023 Mar 13;30(Suppl 1):65-73. doi: 10.1159/000528808. eCollection 2023 Sep.

ABSTRACT

INTRODUCTION: Malignant biliary obstruction drainage is essential, since jaundice is associated with morbidity and mortality. Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended procedure for biliary drainage, with percutaneous biliary drainage being the classic alternative in cases of unsuccessful ERCP. Recently, endoscopic ultrasound-guided biliary drainage has been emerged as a new option, with EUS-guided choledochoduodenostomy (EUS-CDS) being considered an effective and safe method in the drainage of distal obstructions of the common bile duct.

AIM: The aim of the study was to evaluate the efficacy and safety of EUS-CDS performed in patients with distal malignant biliary obstructions, after failed ERCP.

METHODS: Single-center retrospective cohort study between July 2017 and June 2022 including all consecutive patients submitted to EUS-CDS in our center. The primary outcomes were "technical success" and "clinical success," defined as "resolution of jaundice or improvement in total serum bilirubin level above 50% at 7th day and above 75% at 30th day after the procedure." Secondary outcomes were procedure-related adverse events, endoscopic reintervention, and survival time.

RESULTS: EUS-CDS was performed in 20 patients (65.0% male; median age 76 years). The most frequent etiology for the biliary obstruction was pancreatic adenocarcinoma (n = 17; 85.0%), and most patients presented at advanced stages of cancer (12/60% in stages III or IV). ERCP failure was mainly due to the presence of obstruction in the duodenal lumen (n = 11; 55.0%). Fully covered metallic stents were used in all patients, mostly HotAxios^TM (n = 15; 75.0%). The technical success rate was 100%, and the clinical success rate was 89.5% (n = 17/19) at 7th day and 93.3% (n = 14/15) at 30th day. Four patients (20.0%) developed cholangitis within the first 30 days after the procedure; there were no late complications, and no patient died as a complication of the procedure. In 2 patients (10.0%), endoscopic reintervention was necessary due to stent migration, incidentally detected. Median survival was 93 days (minimum 5-maximum 751).

CONCLUSION: EUS-CDS was effective in biliary decompression of malignant obstructions of the common bile duct, with high clinical success and a favorable safety profile.

PMID:37818398 | PMC:PMC10561318 | DOI:10.1159/000528808
Utility and diagnostic accuracy of intraoperative frozen sections in hepato-pancreato-biliary surgical pathology

Fetched: October 12th, 2023, 5:01am GMT by Archana Rastogi

Langenbecks Arch Surg. 2023 Oct 9;408(1):390. doi: 10.1007/s00423-023-03124-8.

ABSTRACT

BACKGROUND AND PURPOSE: Hepato-pancreato-biliary (HPB) surgeries are one of the most challenging and complex procedures. Intraoperative frozen section (IFS) diagnosis plays a pivotal role in management decisions. Comprehensive large cohort studies evaluating utility of IFS in HPB malignancies are lacking. This study aimed to evaluate the accuracy of frozen section analysis and to analyse discrepancies and impact of IFS on the surgical decisions.

PATIENTS AND METHODS: This was a retrospective study of IFS received for the HPB specimens between years 2009 and 2021. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity. Indications, disagreements and impact on the surgical management were analysed.

RESULTS: A total of 1008 specimens were evaluated: bile duct margin (279; 27.7%), gallbladder (203; 20.1%), liver lesions (125 cases; 12.4%), lymph nodes (147; 14.6%), pancreatic margin (120; 11.9%) and deposits (134; 13.3%). IFS were diagnosed as negative for malignancy (805; 79.9%), positive for dysplasia (8; 0.8%), suspicious for malignancy (6; 0.6%) and positive for malignancy (189; 18.8%). The overall diagnostic accuracy was 98.4%, and the discordant rate was 1.6%. The sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 99.4%, 97.5% and 98.6% respectively. The most important reason of discordant results was technical, followed by interpretational and sampling errors.

CONCLUSION: The study demonstrates high diagnostic accuracy (98.4%) of IFS in a large dataset of HPB specimens. This comprehensive analysis apprises of the indications, errors and the impact of IFS diagnosis on subsequent HPB surgical management.

PMID:37814143 | DOI:10.1007/s00423-023-03124-8

PubMed - Cholangiocarcinoma

In vitro and in vivo pharmacokinetics, disposition, and drug-drug interaction potential of tinengotinib (TT-00420), a promising investigational drug for treatment of cholangiocarcinoma and other solid tumors

Fetched: December 5th, 2023, 5:01am GMT by Shumao Ni

Eur J Pharm Sci. 2023 Dec 2:106658. doi: 10.1016/j.ejps.2023.106658. Online ahead of print.

ABSTRACT

Early-stage clinical evaluation of tinengotinib (TT-00420) demonstrated encouraging preliminary efficacies in multiple types of refractory cancers, including fibroblast growth factor receptors (FGFR) inhibitors relapsed cholangiocarcinoma (CCA), castrate-resistant prostate cancer (CRPC), and HR+/HER2- breast cancer and triple negative breast cancer (TNBC). To further evaluate drug-like properties of the drug candidate, it is imperative to understand its metabolism and pharmacokinetic properties. This manuscript presented the investigation results of in vitro permeability, plasma protein binding, metabolic stability, metabolite identification, and drug-drug interaction of tinengotinib. Preclinical ADME (absorption, distribution, excretion, and metabolism) studies in rats and dogs was also conducted using a radioactive labeled tinengotinib, [¹⁴C]tinengotinib. Tinengotinib was found to have high permeability and high plasma protein binding and equally distributed between blood and plasma. There were no unique metabolites in human liver microsomes and tinengotinib showed moderate hepatic clearance. Tinengotinib is neither a potential inhibitor nor an inducer of P450 enzymes at clinically relevant concentrations, and unlikely to cause drug-drug interactions when used in combination with other drugs mediated by a key transporter, either as victim or perpetrator. Taken together, tinengotinib demonstrated a minimal risk of clinically relevant drug-drug interactions. Tinengotinib showed good oral bioavailability and dose-dependent exposures in both rat and dog after oral administration. The total radioactivity was largely distributed in the gastrointestinal system and liver, and tinengotinib could not easily pass through the blood-brain barrier. The major drug-related component in rat and dog plasma was unchanged drug (>89%) with primary route of elimination via feces (>93% of the dose) and minor via renal excretion (<4% of the dose). Tinengotinib metabolism is mediated largely by CYP3A4, with minor contributions from CYP2D6 and CYP2C8. Major metabolic pathways include oxidation, oxidative cleavage of the morpholine ring, glucuronide and glutathione conjugations. The overall preclinical pharmacokinetics profile supported the selection and development of tinengotinib as a clinical candidate.

PMID:38048851 | DOI:10.1016/j.ejps.2023.106658
NIPBL::NACC1 Fusion Hepatic Carcinoma

Fetched: December 5th, 2023, 5:01am GMT by Erika Hissong

Am J Surg Pathol. 2023 Dec 4. doi: 10.1097/PAS.0000000000002159. Online ahead of print.

ABSTRACT

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.

PMID:38047392 | DOI:10.1097/PAS.0000000000002159
Circulating tumour cell enumeration, biomarker analyses, and kinetics in patients with colorectal cancer and other GI malignancies

Fetched: December 5th, 2023, 5:01am GMT by Walla Malkawi

Front Oncol. 2023 Nov 17;13:1305181. doi: 10.3389/fonc.2023.1305181. eCollection 2023.

ABSTRACT

OBJECTIVE: Most of the work in terms of liquid biopsies in patients with solid tumors is focused on circulating tumor DNA (ctDNA). Our aim was to evaluate the feasibility of using circulating tumor cells (CTCs) in peripheral blood samples from patients with advanced or metastatic gastrointestinal (GI) cancers.

METHODS: In this prospective study, blood samples were collected from each patient in 2 AccuCyte^® blood collection tubes and each tube underwent CTC analysis performed utilizing the RareCyte^® platform. The results from both tubes were averaged and a total of 150 draws were done, with 281 unique reported results. The cadence of sampling was based on convenience sampling and piggybacked onto days of actual clinical follow-ups and treatment visits. The CTC results were correlated with patient- and tumor-related variables.

RESULTS: Data from a total of 59 unique patients were included in this study. Patients had a median age of 58 years, with males representing 69% of the study population. More than 57% had received treatment prior to taking blood samples. The type of GI malignancy varied, with more than half the patients having colorectal cancer (CRC, 54%) followed by esophageal/gastric cancer (17%). The least common cancer was cholangiocarcinoma (9%). The greatest number of CTCs were found in patients with colorectal cancer (Mean: 15.8 per 7.5 ml; Median: 7.5 per 7.5 ml). In comparison, patients with pancreatic cancer (PC) had considerably fewer CTCs (Mean: 4.2 per 7.5 ml; Median: 3 per 7.5 ml). Additionally, we found that patients receiving treatment had significantly fewer CTCs than patients who were not receiving treatment (Median 2.7 versus 0.7). CTC numbers showed noteworthy disparities between patients with responding/stable disease in comparison to those with untreated/progressive disease (Median of 2.7 versus 0). When CTCs were present, biomarker analyses of the four markers human epidermal growth factor receptor 2 (HER2)/programmed death-ligand 1 (PD-L1)/Kiel 67 (Ki-67)/epidermal growth factor receptor (EGFR) was feasible. Single cell sequencing confirmed the tumor of origin.

CONCLUSION: Our study is one of the first prospective real-time studies evaluating CTCs in patients with GI malignancies. While ctDNA-based analyses are more common in clinical trials and practice, CTC analysis provides complementary information from a liquid biopsy perspective that is of value and worthy of continued research.

PMID:38044994 | PMC:PMC10693413 | DOI:10.3389/fonc.2023.1305181
Locally invasive cholangiocarcinoma causing gastric outlet obstruction in heterotaxy syndrome: A case report and review of literature

Fetched: December 5th, 2023, 5:01am GMT by Wanyang Qian

Radiol Case Rep. 2023 Nov 22;19(2):531-534. doi: 10.1016/j.radcr.2023.10.050. eCollection 2024 Feb.

ABSTRACT

Heterotaxy syndrome is a disease of embryo development resulting in abnormal distribution of thoracic and abdominal organs across the left-right axis. In this case, A 77-year-old gentleman was admitted with gastric outlet obstruction secondary to cholangiocarcinoma. This is on a background of heterotaxy syndrome, specifically situs ambiguus. The patient's anatomical variations included a right-sided stomach, midline liver, and asplenia. Due to variant anatomy and risk of aspiration; endoscopy was abandoned in favor of surgical bypass via a gastrojejunostomy. Although technically challenging, complex upper abdominal surgery in heterotaxy syndrome has been described in the literature. Variations in anatomy observed in heterotaxy syndrome may render patients ineligible for resection of cholangiocarcinoma and increase the risk of complications. Careful preoperative planning with imaging and meticulous intraoperative dissection is required.

PMID:38044905 | PMC:PMC10686879 | DOI:10.1016/j.radcr.2023.10.050
Correlation of vein-rich tumor microenvironment of intrahepatic cholangiocarcinoma with tertiary lymphoid structures and patient outcome

Fetched: December 4th, 2023, 5:01am GMT by Noriteru Doi

Mod Pathol. 2023 Dec 1:100401. doi: 10.1016/j.modpat.2023.100401. Online ahead of print.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer composed of large-duct and small-duct types. Understanding the tumor immune microenvironment and its related vascular system is important for developing novel and efficient therapies. We focused on tertiary lymphoid structure (TLS) as a hallmark of antitumor immunity and investigated the clinicopathological significance of TLSs and the influence of vascular microenvironment on TLS formation in iCCAs. We examined 261 iCCA cases clinicopathologically and analyzed the vascular system using immunohistochemistry. Single-cell (102,685 cells) and bulk RNA (33 iCCA cases) sequencing analyses were performed using datasets downloaded from public databases, and endothelial cell characteristics in iCCA tissues and functional networks related to the tumor microenvironment were bioinformatically examined. High densities of both intratumoral and peritumoral TLS were significantly associated with prolonged survival only in large-duct type iCCA. Multivariate analyses showed that peritumoral TLS was a prognostic factor for the large-duct type. TLS-rich iCCA had a significantly higher vein density and tumor-infiltrating T cell count than TLS-poor iCCA. Both the presence of TLSs and high vein endothelial cells in iCCA tissues were significantly associated with molecular networks representing active immune responses in transcriptomic analysis. Vein density was a prognostic factor in patients with large-duct and small-duct types. This suggests that TLS formation is involved in a microenvironment with high vein density, which represents an antitumor-directed immune microenvironment.

PMID:38043787 | DOI:10.1016/j.modpat.2023.100401
Update on the risk factors for opisthorchiasis and cholangiocarcinoma in Thailand

Fetched: December 4th, 2023, 5:01am GMT by Sattrachai Prasopdee

Parasites Hosts Dis. 2023 Nov;61(4):463-470. doi: 10.3347/PHD.23032. Epub 2023 Nov 28.

ABSTRACT

This study aimed to identify the recent risk factors for Opisthorchis viverrini infection and cholangiocarcinoma (CCA) to improve disease prevention. The participants were divided into the following 3 groups based on their health status: healthy control (nonOV and nonCCA), those with O. viverrini infection (OV), and those with CCA. A questionnaire was used to explore their lifestyle and behaviors. Multivariate logistic regression and backward elimination were used to identify the significant risk factors. The results showed that the significant risk factors for both O. viverrini infection and CCA were age>50 years (odd ratio (OR)=8.44, P<0.001, 95% confidence intervals (CI) 2.98-23.90 and OR=43.47, P=0.001, 95% CI 14.71-128.45, respectively) and raw fish consumption (OR=8.48, P< 0.001, 95% CI 3.18-22.63 and OR=3.15, P=0.048, 95% CI 1.01-9.86, respectively). A history of O. viverrini infection was identified as an additional risk factor for CCA (OR=20.93, P=0.011, 95% CI 2.04-215.10). This study provided an update on the risk factors for O. viverrini infection and CCA. Asymptomatic patients with O. viverrini infection, particularly those>50 years old, should be carefully monitored to prevent CCA.

PMID:38043542 | DOI:10.3347/PHD.23032
Corrigendum to "Comprehensive in-silico analysis of chaperones identifies CRYAB and P4HA2 as potential therapeutic targets and their small molecular inhibitors for the treatment of Cholangiocarcinoma" [Comput. Biol. Med. 166 (2023) 107572]

Fetched: December 3rd, 2023, 5:01am GMT by Manju Nidagodu Jayakumar

Comput Biol Med. 2023 Dec 1:107756. doi: 10.1016/j.compbiomed.2023.107756. Online ahead of print.

NO ABSTRACT

PMID:38042714 | DOI:10.1016/j.compbiomed.2023.107756
From evidence to clinical practice: Bridging the gap of new liver cancer therapies in Latin America

Fetched: December 3rd, 2023, 5:01am GMT by Federico Piñero

Ann Hepatol. 2023 Nov 30:101185. doi: 10.1016/j.aohep.2023.101185. Online ahead of print.

ABSTRACT

The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.

PMID:38042481 | DOI:10.1016/j.aohep.2023.101185
Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial

Fetched: December 2nd, 2023, 5:01am GMT by Cullen M Taniguchi

Lancet Oncol. 2023 Dec;24(12):1387-1398. doi: 10.1016/S1470-2045(23)00478-3.

ABSTRACT

BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma.

METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete.

FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT.

INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results.

FUNDING: Galera Therapeutics.

PMID:38039992 | DOI:10.1016/S1470-2045(23)00478-3
A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease

Fetched: December 2nd, 2023, 5:01am GMT by Mireia Mato Prado

Exp Hematol Oncol. 2023 Dec 1;12(1):101. doi: 10.1186/s40164-023-00458-3.

ABSTRACT

Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases. We performed miRNA discovery by global profiling of 800 miRNAs using the NanoString nCounter platform in prospectively collected bile samples from malignant (n = 43) and benign (n = 14) pancreaticobiliary disease. Differentially expressed miRNAs were validated by RT-qPCR and further assessed in an independent validation cohort of bile from malignant (n = 37) and benign (n = 38) pancreaticobiliary disease. MiR-148a-3p was identified as a discriminatory marker that effectively distinguished malignant from benign pancreaticobiliary disease in the discovery cohort (AUC = 0.797 [95% CI 0.68-0.92]), the validation cohort (AUC = 0.772 [95% CI 0.66-0.88]), and in the combined cohorts (AUC = 0.752 [95% CI 0.67-0.84]). We also established a two-miRNA signature (miR-125b-5p and miR-194-5p) that distinguished PDAC from CCA (validation: AUC = 0.815 [95% CI 0.67-0.96]; and combined cohorts: AUC = 0.814 [95% CI 0.70-0.93]). Our research stands as the largest, multicentric, global profiling study of miRNAs in the bile from patients with pancreaticobiliary disease. We demonstrated their potential as clinically useful diagnostic tools for the detection and differentiation of malignant pancreaticobiliary disease. These bile miRNA biomarkers could be developed to complement current approaches for diagnosing pancreaticobiliary cancers.

PMID:38041102 | PMC:PMC10693033 | DOI:10.1186/s40164-023-00458-3
Locoregional therapy combined with systemic therapy (LRT + ST) for unresectable and metastatic intrahepatic cholangiocarcinoma: a systematic review and meta-analysis

Fetched: December 2nd, 2023, 5:01am GMT by Mengqi Zhang

Radiol Oncol. 2023 Nov 30;57(4):419-429. doi: 10.2478/raon-2023-0059. eCollection 2023 Dec 1.

ABSTRACT

BACKGROUND: The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and safety of locoregional therapy combined with systemic therapy (LRT + ST) compared with only ST in unresectable and metastatic iCCA by performing a systematic literature review and meta-analysis.

METHODS: A comprehensive search was performed in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 3, 2022. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).

RESULTS: Ten retrospective cohort studies with 3,791 unresectable or metastatic iCCA patients were enrolled in this study, including 1,120 who received ablation, arterially directed therapy (ADT), or external beam radiation therapy (EBRT) combined with ST. The meta-analysis showed that the LRT + ST group had a better OS (HR = 0.51; 95% CI =0.41-0.64; p value < 0.001), PFS (HR = 0.40, 95% CI = 0.22-0.71, p value = 0.002) and ORR (RR = 1.68; 95% CI = 1.17-2.42; p value = 0.005). Subgroup analysis showed that both ST combined with ADT (HR = 0.42, 95% CI = 0.31-0.56, p value < 0.001) and EBRT (HR = 0.67, 95% CI = 0.63-0.72, p value < 0.001) could improve OS. Neutropenia, thrombocytopenia, anemia, anorexia, and vomiting did not show significant differences between the groups (p value > 0.05).

CONCLUSIONS: Compared with only ST, LRT + ST improved survival outcomes for unresectable and metastatic iCCA patients without increasing severe AEs, which can further provide a basis for guidelines.

PMID:38038416 | PMC:PMC10690746 | DOI:10.2478/raon-2023-0059
Should lymphadenectomy performed routinely in patients with primary intrahepatic cholangiocarcinoma undergoing curative hepatectomy? A retrospective cohort study with propensity-score matching analysis

Fetched: December 1st, 2023, 5:01am GMT by Shan Huang

BMC Surg. 2023 Nov 30;23(1):364. doi: 10.1186/s12893-023-02255-5.

ABSTRACT

BACKGROUND: The benefit of routine lymphadenectomy (LD) in improving outcomes for patients with primary intrahepatic cholangiocarcinoma (ICC) undergoing curative hepatectomy remains unclear.

MATERIALS AND METHODS: This study enrolled 269 consecutive patients who underwent liver resection for primary ICC from January 2009 to July 2020 in West China Hospital. The association of the nodal status with disease-free survival (DFS) and overall survival (OS) was analyzed using the Cox proportional hazards model and 1:1 propensity score matching (PSM) analysis.

RESULTS: Seventy-five (27.9%) patients underwent curative liver resection combined with LD (LD+ group), while 194 (72.1%) patients received curative liver resection without LD (LD- group and Nx group). Among the LD+ group, metastatic disease was present in 36 patients (48%, N1 group) and absent in 39 patients (N0 group). During the follow-up period, 116 patients (43.1%) experienced tumor recurrence and 101 patients (37.5%) died due to recurrence. Multivariate analysis revealed that lymph node metastasis (N1, HR 3.682, 95% CI 1.949-6.957, p < 0.001) was associated with worse OS, while LD+ status (HR 0.504, 95% CI 0.298-0.853, p = 0.011) was associated with improved OS. Adjuvant therapy was a protective factor for both DFS (HR 0.602, 95% CI, 0.447-0.810, p = 0.001) and OS (HR 0.683, 95% CI 0.484-0.963, p = 0.030). After 1:1 PSM, the LD+ patients (n = 74) displayed similar 1-, 3- and 5-year DFS rates (40.0, 7.9 and 7.9% vs. 29.0, 13.7 and 13.7%, p = 0.741) and OS rates (56.0, 26.6 and 22.2% vs. 58.9, 25.6, and 16.4%, p = 0.644) to the LD- patients (n = 74). Additionally, among the 75 LD+ patients, 48 patients underwent hepatic hilar lymphadenectomy (HHL), and 27 patients underwent extended hepatic hilar lymphadenectomy (EHL). Both DFS (p = 0.504) and OS (p = 0.215) were similar between the HHL and EHL groups.

CONCLUSION: Routine LD and adjuvant therapy may contribute to improved OS according to the crude analysis. LD could provide accurate staging without excessive risk and guide adjuvant therapy based on the tumor stage, potentially resulting in better survival. These results suggest that a routine LD should be considered during curative hepatectomy for ICC.

PMID:38036995 | PMC:PMC10688469 | DOI:10.1186/s12893-023-02255-5
Prognostic model for oversurvival and tumor-specific survival prediction in patients with advanced extrahepatic cholangiocarcinoma: a population-based analysis

Fetched: December 1st, 2023, 5:01am GMT by Yu Zhang

BMC Gastroenterol. 2023 Nov 30;23(1):422. doi: 10.1186/s12876-023-03017-6.

ABSTRACT

BACKGROUND: The prognosis of patients with extrahepatic cholangiocarcinoma (ECCA) must be determined with precision. However, the usual TNM staging system has the drawback of ignoring age, adjuvant therapy, and gender and lacks the ability to more correctly predict patient prognosis. Therefore, we determine the risk factors of survival for patients with advanced ECCA patients and developed brand-new nomograms to forecast patients with advanced ECCA's overall survival (OS) and cancer-specific survival (CSS).

METHOD: From the Epidemiology and End Results (SEER) database, patients with advanced ECCA were chosen and randomly assigned in a ratio of 6:4 to the training and validation subgroups. The cumulative incidence function (CIF) difference between groups was confirmed by applying Gray's and Fine test and competing risk analyses. Next, the cancer-specific survival (CSS) and overall survival (OS) nomograms for advanced ECCA were developed and validated.

RESULTS: In accordance with the selection criteria, 403 patients with advanced ECCA were acquired from the SEER database and then split at random into two groups: a training group (n = 241) and a validation group (n = 162). The 1-, 2-, and 3-year cancer-specific mortality rates were 58.7, 74.2, and 78.0%, respectively, while the matching mortality rates for the competition were 10.0, 13.8, and 15.0%. Nomograms were generated for estimating OS and CSS, and they were assessed using the ROC curve and the C-index. The calibration curves showed that there was a fair amount of agreement between the expected and actual probabilities of OS and CSS. Additionally, greater areas under the ROC curve were seen in the newly developed nomograms for OS and CSS when compared to the 7th AJCC staging system. The advanced ECCA patients were divided into groupings with an elevated risk and those with a low risk and the Kaplan-Meier method was used for the survival analysis, which showed that survival time was shorter in the high-risk group than in the low-risk group.

CONCLUSION: The proposed nomograms have good predictive ability. The nomograms may can help doctors determine the prognosis of patients with advanced ECCA as well as provide more precise treatment plans for them.

PMID:38036949 | PMC:PMC10691049 | DOI:10.1186/s12876-023-03017-6
Spatial multimodal analysis revealed tertiary lymphoid structures as a risk stratification indicator in combined hepatocellular-cholangiocarcinoma

Fetched: December 1st, 2023, 5:01am GMT by Xiaojie Gan

Cancer Lett. 2023 Nov 28:216513. doi: 10.1016/j.canlet.2023.216513. Online ahead of print.

ABSTRACT

The microenvironment created by tertiary lymphoid structures (TLSs) can support and regulate immune responses, affecting the prognosis and immune treatment of patients. Nevertheless, the actual importance of TLSs for predicting the prognosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients remains unclear. Herein, using spatial transcriptomic analysis, we revealed that a gene signature of TLSs specific to cHCC-CCA was associated with high-intensity immune infiltration. Then, a novel scoring system was developed to evaluate the distribution and frequency of TLSs in intra-tumoral and extra-tumoral regions (iTLS and eTLS scores) in 146 cHCC-CCA patients. iTLS score was positively associated with promising prognosis, likely due to the decreased frequency of suppressive immune cell like Tregs, and the ratio of CD163⁺ macrophages to macrophages in intra-tumoral TLSs via imaging mass cytometry, while improved prognosis is not necessarily indicated by a higher eTLS score. Overall, this study highlights the potential of TLSs as a prognostic factor and an indicator of immune therapy in cHCC-CCA.

PMID:38036041 | DOI:10.1016/j.canlet.2023.216513
IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma

Fetched: December 1st, 2023, 5:01am GMT by Wei R Ng

J Surg Case Rep. 2023 Nov 22;2023(11):rjad621. doi: 10.1093/jscr/rjad621. eCollection 2023 Nov.

ABSTRACT

A man in his 70s presented to the emergency department with painless obstructive jaundice. Initial blood test results show a predominantly cholestatic picture with elevated tumour markers, and imaging findings are concerning for a pancreatic head neoplasm or cholangiocarcinoma with involvement of the entire common bile duct. The patient underwent staging laparoscopy and biopsies including peritoneal washing, but did not identify any features of malignancy. Immunoglobulin G and immunoglobulin G4 testing were subsequently tested and shown to be elevated. The provisional diagnosis of immunoglobulin G4-related sclerosing cholangitis was made, and steroid treatment was empirically started. Treatment with steroids was successful, with complete resolution of symptoms and abnormal imaging findings and near complete resolution of liver function test results after 1 month.

PMID:38034909 | PMC:PMC10684043 | DOI:10.1093/jscr/rjad621
Biliary adenofibroma: a precursor lesion of intrahepatic cholangiocarcinoma

Fetched: December 1st, 2023, 5:01am GMT by Mayur Parkhi

Autops Case Rep. 2023 Nov 13;13:e2023453. doi: 10.4322/acr.2023.453. eCollection 2023.

ABSTRACT

Biliary adenofibroma (BAF) is an uncommon liver tumor with a high propensity for malignant transformation. The histomorphology of BAF with malignant transformation can show a spectrum of changes ranging from benign, dysplastic to frank malignancy. Thus, the diagnosis of BAF imposes the pursuit of dysplasia/ malignancy focus. We presented a case of intrahepatic cholangiocarcinoma arising from BAF in a 49-year-old woman with detailed histomorphology. We also performed a PubMed database search and tabulated all previously reported cases of BAF with dysplasia/ malignant transformation. A statistic comparison of age, sex ratio, size of the tumor, and survival following complete resection between BAFs with and without dysplasia/ malignancy from the retrieved data is presented. Our analysis did not highlight any statistically significant difference between BAFs with and without dysplasia/ malignancy in age, sex ratio, tumor size, and survival following complete surgical resection. Our study highlights the histopathology and immunohistochemistry of a case of BAF with malignant transformation and highlights the importance of this diagnosis in management. Further longitudinal studies on a larger cohort of patients are required to validate our findings.

PMID:38034524 | PMC:PMC10688199 | DOI:10.4322/acr.2023.453
Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis

Fetched: December 1st, 2023, 5:01am GMT by Zhitao Chen

Front Microbiol. 2023 Nov 14;14:1288525. doi: 10.3389/fmicb.2023.1288525. eCollection 2023.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies.

MATERIALS AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms.

RESULTS: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment.

CONCLUSION: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

PMID:38033576 | PMC:PMC10682188 | DOI:10.3389/fmicb.2023.1288525
A Novel Bifidobacterium/Klebsiella Ratio in Characterization Analysis of the Gut and Bile Microbiota of CCA Patients

Fetched: November 30th, 2023, 5:01am GMT by Ningning Zhang

Microb Ecol. 2023 Nov 30;87(1):5. doi: 10.1007/s00248-023-02318-3.

ABSTRACT

Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.

PMID:38030815 | PMC:PMC10687116 | DOI:10.1007/s00248-023-02318-3
8-Chloroadenosine Induces ER Stress and Apoptotic Cell Death in Cholangiocarcinoma Cells

Fetched: November 30th, 2023, 5:01am GMT by Jomnarong Lertsuwan

Anticancer Res. 2023 Dec;43(12):5425-5436. doi: 10.21873/anticanres.16746.

ABSTRACT

BACKGROUND/AIM: Cholangiocarcinoma is a lethal cancer, and current chemotherapeutic drugs are not very effective. Recent studies reported that cholangiocarcinoma cells were sensitive to adenosine. One adenosine analog, 8-chloroadenosine (8-CA), was shown to be more potent than adenosine and induced apoptosis in leukemia cells. This study examined effects of 8-CA in cholangiocarcinoma cells and immortalized cholangiocytes.

MATERIALS AND METHODS: Cell growth was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell invasion was examined by transwell assay. Cell cycle and cell death were evaluated by flow cytometry. Colorimetric absorbance assay was used to assessed RNA and protein synthesis as well as mitochondrial membrane potential. Protein levels were examined by western blot analysis. Animal experiment was performed in Balb/cAJcl-Nu mice.

RESULTS: 8-CA reduced cholangiocarcinoma cell growth, prevented colony formation and caused endoplasmic reticulum stress and cell-cycle arrest. Eventually, apoptosis was induced. However, treatment with 8-CA did not interfere with RNA synthesis or protein synthesis and did not alter mitochondrial membrane potential. Combination of 8-CA with several chemotherapeutic drugs in vitro was less effective than 8-CA alone and the drugs alone, except for the combination of 8-CA with hydroxychloroquine, which had an additive effect on RMCCA-1 cells. However, further in vivo study showed that treatment with 8-CA alone inhibited tumor growth more than treatment with a combination of 8-CA with hydroxychloroquine.

CONCLUSION: 8-Chloroadenosine inhibited CCA cells by inducing endoplasmic reticulum stress and apoptosis. In vivo study showed that 8-CA inhibited cholangiocarcinoma tumor growth better when administered alone as compared to a combination with hydroxychloroquine.

PMID:38030206 | DOI:10.21873/anticanres.16746
Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy

Fetched: November 30th, 2023, 5:01am GMT by Ankur Pandey

Eur J Radiol. 2023 Nov 18;170:111196. doi: 10.1016/j.ejrad.2023.111196. Online ahead of print.

ABSTRACT

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters.

OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score.

METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index.

RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10^-6 mm²/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction.

CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model.

CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

PMID:38029705 | DOI:10.1016/j.ejrad.2023.111196
$Permalink for 'Proton beam stereotactic body radiotherapy and hypofractionated therapy with pencil beam scanning is safe and effective for advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A single center experience'$
Proton beam stereotactic body radiotherapy and hypofractionated therapy with pencil beam scanning is safe and effective for advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A single center experience

Fetched: November 30th, 2023, 5:01am GMT by Alexander H Yang

J Radiosurg SBRT. 2023;9(1):43-52.

ABSTRACT

BACKGROUND: Proton beam therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation and useful for Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We present a single center experience in HCC and iCCA treated with Pencil Beam Scanning (PBS) PBT.

METHODS: Forty-four consecutive patients (22 patients in each group) receiving PBT were included and reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy (SBRT) using PBS. Tumor size was approximated by clinical target volume (CTV). Outcomes were evaluated with Kaplan-Meier and liver toxicity was determined by MELD-Na and albumin-bilirubin (ALBI) grade.

RESULTS: Median follow up was 38.7 months, fourteen (35%) had multifocal disease and median CTV was 232.5cc. Four (9%) and 40 (91%) patients received SBRT and hypofractionated radiation, respectively. Two year overall survival was statistically higher for HCC (entire group: 68.9% months [95% CI: 61.3 - 76.3%]; iCCA: 49.8% [95% CI: 38.5% - 61.1%]; HCC: 89.4% [95% CI: 82.3 - 96.5%]; P <0.005). There was no statistical difference in progression-free survival or freedom from local failure. Biologically Equivalent Dose (BED) was greater than or equal to 80.5Gy in 37 (84%) patients. All iCCA patients had stable or improved ALBI grade following treatment. ALBI grade was stable in 83% of HCC patients and average MELD-Na score remained stable. Tumor size, pretreatment liver function, and total radiation dose were not associated with liver toxicity.

CONCLUSIONS: PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis in this advanced population with large tumors.

PMID:38029012 | PMC:PMC10681150
Intrahepatic cholangiocarcinoma initially diagnosed as adenocarcinoma of unknown primary with hepatoduodenal ligament lymph node metastases: A case report

Fetched: November 30th, 2023, 5:01am GMT by Sangik Noh

Oncol Lett. 2023 Nov 8;27(1):7. doi: 10.3892/ol.2023.14140. eCollection 2024 Jan.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) with regional lymph node metastases, which lacks a well-delineated liver mass, may be misdiagnosed as a carcinoma of unknown primary (CUP) origin. The present study reports the case of a 69-year-old man initially diagnosed with CUP, who was incidentally found to have abdominal lymphadenopathy during ultrasonography (US). The clinical course from the time of lymphadenectomy and CUP diagnosis to iCCA detection after long-term follow-up is reported. A patient with a history of hypertensive renal disease presented with an incidental finding of enlarged abdominal lymph nodes in the perihepatic region on US. Abdominal contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed two enlarged lymph nodes in the hepatoduodenal ligament. Exploratory laparotomy and lymphadenectomy were performed for diagnostic and therapeutic purposes, respectively. Poorly differentiated metastatic adenocarcinoma positive for cytokeratin 7 and negative for cytokeratin 20 was identified in two of the 22 lymph nodes. Postoperatively, a positron emission tomography/CT (PET/CT) scan was performed, which failed to locate the primary site. The diagnosis of CUP was confirmed based on clinical, radiological and histopathological characteristics. A sequential abdominal CT scan 48 months after lymphadenectomy revealed a faintly enhancing, intraductal polypoid mass with localized ductal dilatation in liver segment 3. MRI and PET/CT confirmed a mass in the left lobe of the liver. US-guided percutaneous needle biopsy confirmed the presence of moderately differentiated adenocarcinoma. The patient refused surgical treatment because of general weakness caused by Coronavirus disease 2019 infection. The patient received radical radiotherapy and underwent left hepatectomy after recovery of their performance status. Histopathological examination of the surgical specimen demonstrated prevailing fibrosis and mucin accumulation, with scattered cancer cells observed focally in the resected liver specimen owing to the effect of the radiotherapy. Consequently, a definitive diagnosis of primary adenocarcinoma of the intrahepatic bile duct was confirmed. The present report may improve understanding of the pathophysiology and clinical progression of iCCA, with a specific focus on the intraductal growth subtype.

PMID:38028185 | PMC:PMC10664074 | DOI:10.3892/ol.2023.14140
Hsa_circ_0050900 affects ferroptosis in intrahepatic cholangiocarcinoma cells by targeting hsa‑miR-605‑3p to regulate SLC3A2

Fetched: November 30th, 2023, 5:01am GMT by Xiangtian Shi

Oncol Lett. 2023 Nov 6;27(1):2. doi: 10.3892/ol.2023.14135. eCollection 2024 Jan.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary tumor with high aggressiveness. The role of circular RNA (circRNA) in ICC remains to be explored. The present study aimed to investigate whether hsa_circ_0050900 affected ferroptosis in ICC cells by regulating hsa-microRNA (miR)-605-3p/solute carrier family 3 member 2 (SLC3A2). Human ICC cells were cultured and hsa_circ_0050900 expression was evaluated by reverse transcription-quantitative PCR. hsa_circ_0050900 was knocked down and ferroptosis inhibitor ferrostatin-1 was added to HuCCT-1 cells. Following knockdown or overexpression of hsa-miR-605-3p, Fe²⁺, reactive oxygen species (ROS), glutathione peroxidase 4 and SLC3A2 levels were assessed using iron and ROS assay kit or RT-qPCR and western blotting, respectively. Cell function experiments were performed to examine proliferation and migration abilities. Dual-luciferase reporter gene and argonaute2-RNA immunoprecipitation assay verified the relationship among hsa_circ_0050900, hsa-miR-605-3p, and SLC3A2. hsa_circ_0050900 was derived from actinin alpha 4 gene and was elevated in ICC cells. Among HuCCT-1, QBC-939, HCCC-9810, and RBE cell lines, the highest expression was in HuCCT-1 cells. Inhibition of hsa_circ_0050900 inhibited proliferation and migration by facilitating ICC cell ferroptosis. hsa-miR-605-3p expression was elevated after knocking down hsa_circ_0050900 and hsa-miR-605-3p was negatively regulated by hsa_circ_0050900. In addition, hsa-miR-605-3p targeted SLC3A2. Overexpression of hsa-miR-605-3p regulated SLC3A2 to promote ICC cell ferroptosis and inhibit proliferation and migration. Taken together, knockdown of hsa_circ_0050900 inhibited SLC3A2 expression via sponging hsa-miR-605-3p to promote ICC cell ferroptosis, and finally suppressed proliferation and migration. The present study suggested that hsa_circ_0050900 was a potential therapeutic target for ICC.

PMID:38028176 | PMC:PMC10665981 | DOI:10.3892/ol.2023.14135
Metabolomic analyses uncover an inhibitory effect of niclosamide on mitochondrial membrane potential in cholangiocarcinoma cells

Fetched: November 30th, 2023, 5:01am GMT by Thanaporn Kulthawatsiri

PeerJ. 2023 Nov 22;11:e16512. doi: 10.7717/peerj.16512. eCollection 2023.

ABSTRACT

BACKGROUND: Niclosamide is an oral anthelminthic drug that has been used for treating tapeworm infections. Its mechanism involves the disturbance of mitochondrial membrane potential that in turn inhibits oxidative phosphorylation leading to ATP depletion. To date, niclosamide has been validated as the potent anti-cancer agent against several cancers. However, the molecular mechanisms underlying the effects of niclosamide on the liver fluke Opisthorchis viverrini (Ov)-associated cholangiocarcinoma (CCA) cell functions remain to be elucidated. The aims of this study were to investigate the effects of niclosamide on CCA cell proliferation and on metabolic phenoconversion through the alteration of metabolites associated with mitochondrial function in CCA cell lines.

MATERIALS AND METHODS: The inhibitory effect of niclosamide on CCA cells was determined using SRB assay. A mitochondrial membrane potential using tetramethylrhodamine, ethyl ester-mitochondrial membrane potential (TMRE-MMP) assay was conducted. Liquid chromatography-mass spectrometry-based metabolomics was employed to investigate the global metabolic changes upon niclosamide treatment. ATP levels were measured using CellTiter-Glo^® luminescent cell viability assay. NAD metabolism was examined by the NAD⁺/NADH ratio.

RESULTS: Niclosamide strongly inhibited CCA cell growth and reduced the MMP of CCA cells. An orthogonal partial-least square regression analysis revealed that the effects of niclosamide on suppressing cell viability and MMP of CCA cells were significantly associated with an increase in niacinamide, a precursor in NAD synthesis that may disrupt the electron transport system leading to suppression of NAD⁺/NADH ratio and ATP depletion.

CONCLUSION: Our findings unravel the mode of action of niclosamide in the energy depletion that could potentially serve as the promising therapeutic strategy for CCA treatment.

PMID:38025687 | PMC:PMC10676079 | DOI:10.7717/peerj.16512
Pathologic features and clinical treatment of sarcomatoid intrahepatic cholangiocarcinoma

Fetched: November 30th, 2023, 5:01am GMT by Xiaoli Xie

Intractable Rare Dis Res. 2023 Nov;12(4):267-270. doi: 10.5582/irdr.2023.01094.

ABSTRACT

The current study examined sarcomatoid intrahepatic cholangiocarcinoma (S-iCCA). S-iCCA was a more aggressive subtype of intrahepatic cholangiocarcinoma (iCCA). Early detection and complete resection of tumors are very important. Reported here is a case of S-iCCA, and the diagnosis and treatment of S-iCCA are discussed. The patient underwent a tumor resection and was treated with chemotherapy and molecularly targeted drugs after surgery. The clinical pathologic features and treatment of S-iCCA are discussed based on the literature. An immunohistochemical examination revealed positivity for cytokeratin 7 (CK7), CK-pan, vimentin, and CK19 and negativity for hepatocyte paraffin 1 (HepPar-1) in sarcomatoid cells. This case suggests that the particular molecular characteristics of sarcomatoid cells have great clinical diagnostic value, and comprehensive treatment of S-iCCA based on surgery is described.

PMID:38024583 | PMC:PMC10680159 | DOI:10.5582/irdr.2023.01094
An overview of recent treatment options for primary sclerosing cholangitis

Fetched: November 30th, 2023, 5:01am GMT by Ioanna Mousavere

Ann Gastroenterol. 2023 Nov-Dec;36(6):589-598. doi: 10.20524/aog.2023.0834. Epub 2023 Oct 30.

ABSTRACT

Primary sclerosing cholangitis (PSC) is a chronic hepatic dysfunction characterized by inflammatory and tissue-degenerative strictures of the biliary tree, leading to cirrhosis and cholangiocarcinoma. The pathophysiological mechanisms involve immune-mediated responses. Numerous treatment modalities targeting the inflammatory aspects have been suggested, but a consensus on the best treatment option is lacking. This study aims to review the most up-to-date treatment options for PSC.

PMID:38023975 | PMC:PMC10662072 | DOI:10.20524/aog.2023.0834
TGFβ-induced circLTBP2 predicts a poor prognosis in intrahepatic cholangiocarcinoma and mediates gemcitabine resistance by sponging miR-338-3p

Fetched: November 30th, 2023, 5:01am GMT by Corentin Louis

JHEP Rep. 2023 Sep 5;5(12):100900. doi: 10.1016/j.jhepr.2023.100900. eCollection 2023 Dec.

ABSTRACT

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.

METHODS: Transforming growth factor β (TGFβ)-regulated circRNAs were identified by dedicated microarrays in human HuCC-T1 iCCA cell line, and their clinical relevance was evaluated in independent cohorts of patients. Gain and loss of function of circLTBP2 combined with functional tests was performed in vitro and in vivo in mice. RNA pulldown, microRNA sequencing, and RNA immunoprecipitation were performed to explore the sponging activity of circLTBP2.

RESULTS: CircLTBP2 (has_circ_0032603) was identified as a novel TGFβ-induced circRNA in several cholangiocarcinoma cell lines. CircLTBP2 promotes tumour cell proliferation, migration, and resistance to gemcitabine-induced apoptosis in vitro and tumour growth in vivo. Mechanistically, circLTBP2 acts as a competitive RNA regulating notably the activity of the tumour suppressor microRNA miR-338-3p, leading to the overexpression of its pro-metastatic targets. The restoration of miR-338-3p levels in iCCA cells reversed the pro-tumourigenic effects driven by circLTBP2, including the resistance to gemcitabine-induced apoptosis. In addition, circLTBP2 expression predicted a reduced survival, as detected in not only tumour tissues but also serum extracellular vesicles isolated from patients with iCCA.

CONCLUSIONS: CircLTBP2 is a novel effector of the pro-tumourigenic arm of TGFβ and a clinically relevant biomarker easily detected from liquid biopsies in iCCA.

IMPACT AND IMPLICATIONS: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with limited therapeutic options. Opening the field to new concepts is urgently needed to improve the survival of patients. Here, we evaluated the role and the clinical relevance of circular RNA. We report that TGFβ-induced circLTBP2 contributes to CCA carcinogenesis and may constitute a clinically relevant prognostic biomarker detected in liquid biopsies.

PMID:38023605 | PMC:PMC10665948 | DOI:10.1016/j.jhepr.2023.100900
Short-term and long-term clinical outcomes of combined major vessel resection for hilar cholangiocarcinoma: a propensity score analysis

Fetched: November 30th, 2023, 5:01am GMT by Yaoqun Wang

Ann Surg Treat Res. 2023 Nov;105(5):319-332. doi: 10.4174/astr.2023.105.5.319. Epub 2023 Oct 31.

ABSTRACT

PURPOSE: In the treatment of hilar cholangiocarcinoma (HCCA), combined resection of important hepatic vessels remains controversial. The purpose of this study was to compare the postoperative complications and prognosis of combined and non-combined major vessel resections in patients undergoing radical resection for HCCA.

METHODS: In this study, patients with HCCA who underwent curative resection between January 2007 and December 2018 were retrospectively enrolled. Postoperative complications and prognosis between the groups were compared using propensity score-matching (PSM) analysis.

RESULTS: There were 310 patients included in this study. The portal vein resection (PVR) and hepatic artery resection (HAR) groups had a higher incidence of postoperative complications than the control group. Patients in the HAR group had an increased risk of abdominal and pleural effusion after surgery. Patients who underwent combined PVR had better overall survival (OS; P = 0.020) and disease-free survival (DFS; P = 0.020). After curative-intent resection, patients in the HAR group had improved OS (P = 0.027) and DFS (P = 0.023). The postoperative complications of combined vascular resection (VR) did not worsen long-term survival for patients.

CONCLUSION: In patients with HCCA, combined VR improved prognosis. The postoperative complications of combined VR do not worsen patient survival. Therefore, radical surgical resection is recommended.

PMID:38023434 | PMC:PMC10648609 | DOI:10.4174/astr.2023.105.5.319
A nomogram based on ultrasonographic features and clinical indicators for differentiating mass-forming intrahepatic cholangiocarcinoma and liver metastatic colorectal adenocarcinoma

Fetched: November 30th, 2023, 5:01am GMT by Wuyongga Bao

Front Oncol. 2023 Oct 31;13:1245686. doi: 10.3389/fonc.2023.1245686. eCollection 2023.

ABSTRACT

OBJECTIVE: This study aimed to develop and validate a nomogram based on ultrasonographic features and clinical indicators to differentiate mass-forming intrahepatic cholangiocarcinoma (MF-ICC) from hepatic metastatic colorectal adenocarcinoma.

MATERIALS AND METHODS: A total of 343 patients with pathologically confirmed MF-ICC or metastatic colorectal adenocarcinoma were enrolled between October 2018 and July 2022. Patients were randomly assigned to training and validation sets at a ratio of 7:3. Preoperative ultrasound features and clinical indicators were retrieved. Univariate logistic regression analysis was employed to select relevant features. Multivariate logistic regression analysis was used to establish a predictive model, which was presented as a nomogram in training sets. The model's performance was assessed in terms of discrimination, calibration, and clinical usefulness.

RESULTS: The study included 169 patients with MF-ICC and 174 with liver metastatic colorectal adenocarcinoma, assigned to training (n=238) and validation (n=105) cohorts. The nomogram incorporated ultrasound features (tumor size, lesion number, echogenicity, tumor necrosis, and rim arterial phase hyperenhancement) and clinical information (serum levels of CEA, CA19-9, CA125). The nomogram demonstrated promising performance in differentiating these two entities in both training and validation sets, with an AUC value of 0.937 (95%CI: 0.907,0.969) and 0.916 (95%CI: 0.863,0.968), respectively. The Hosmer-Lemeshow test and calibration curves confirmed good consistency between predictions and observations. Additionally, decision curve analysis confirmed the nomogram's high clinical practicability.

CONCLUSION: The nomogram based on ultrasound features and clinical indicators demonstrated good discrimination performance in differentiating MF-ICC from metastatic colorectal adenocarcinoma, which may enhance clinical decision-making process in managing these challenging diagnostic scenarios.

PMID:38023257 | PMC:PMC10644673 | DOI:10.3389/fonc.2023.1245686
Dramatic response and acquired resistance to savolitinib in advanced intrahepatic cholangiocarcinoma with MET amplification: a case report and literature review

Fetched: November 30th, 2023, 5:01am GMT by Kexun Zhou

Front Oncol. 2023 Nov 2;13:1254026. doi: 10.3389/fonc.2023.1254026. eCollection 2023.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive disease with limited treatment options. Despite substantial efforts to explore better regimens, gemcitabine-based chemotherapy has been the standard first-line treatment for decades. With the growing field of precision medicine, biomarker-guided treatments are gaining popularity. MET alteration is a frequent occurrence in various cancer types, making it a promising target.

CASE PRESENTATION: A 53-year-old man visited our hospital with a complaint of upper abdominal pain. Advanced CCA was diagnosed based on the biopsy of the metastatic lymph nodes and immunohistochemistry. Next-generation sequencing revealed MET amplification. As the patient was intolerant to traditional chemotherapy, savolitinib (a c-MET inhibitor) was administered. Partial response was achieved, and the treatment was well tolerated. After 1 year, the patient developed progressive disease, to which the emergence of epidermal growth factor receptor amplification may have contributed.

CONCLUSION: Our study verified the therapeutic value of a c-MET inhibitor in advanced CCA-harboring MET amplification and provides an alternative strategy for patients who are intolerant to chemotherapy.

PMID:38023194 | PMC:PMC10652553 | DOI:10.3389/fonc.2023.1254026
Improved Diagnosis of Adjacent Organ Invasion of Extrahepatic Cholangiocarcinoma by Adding Arterial and Delayed Phases

Fetched: November 30th, 2023, 5:01am GMT by Eisuke Mukaida

Cureus. 2023 Oct 24;15(10):e47568. doi: 10.7759/cureus.47568. eCollection 2023 Oct.

ABSTRACT

PURPOSE: To clarify the role of dynamic computed tomography (CT) in diagnosing extrahepatic cholangiocarcinoma (eCCA) involving adjacent organs.

MATERIAL AND METHODS: We retrospectively analyzed patients diagnosed with eCCA in Iwate Medical University Hospital (Morioka, Japan) during January 2011-December 2021 who underwent dynamic contrast-enhanced CT before biliary intervention, surgery, or chemotherapy. For surgical cases, two radiologists independently reviewed CT images in the portal, dual (adding arterial phase), and triple (adding delayed phase) phases. The mean attenuations of the abdominal aorta, portal vein (PV), hepatic parenchyma, pancreatic parenchyma, and eCCA were measured. The biliary segment-wise longitudinal tumour extent, arterial and PV invasion, organ invasion (liver, pancreas, and duodenum), and regional lymph node metastasis were assessed on a five-point scale. Image performances were compared using the sensitivity, specificity, and area under the curve (AUC).

RESULTS: We included 120 patients (mean age, 71.7 ± 8.9; 84 males). The PV and liver differed most from the bile duct tumour in the portal phase. The abdominal aorta and pancreas differed most from eCCA in the arterial phase. For 80 patients evaluated on the five-point scale, adding phases increased the AUC for pancreatic, duodenal, and arterial invasion for each observer (observer 1, 0.79-0.93, p<0.01, 0.71-0.86, p = 0.04, 0.74-0.99, p = 0.02; observer 2, 0.88-0.96, p = 0.01, 0.73-0.94, p<0.01, 0.80-0.99 p = 0.04; respectively). The AUC for biliary segment-wise longitudinal tumor extent, hepatic, and PV invasion remained unchanged with additional phases.

CONCLUSIONS: Portal-phase information is sufficient to evaluate the segmental extent of bile duct and liver/PV invasion. Arterial- and delayed-phase information can help evaluate pancreatic, duodenal, and arterial invasion.

PMID:38022347 | PMC:PMC10665762 | DOI:10.7759/cureus.47568
Single-cell RNA sequencing reveals cancer stem-like cells and dynamics in tumor microenvironment during cholangiocarcinoma progression

Fetched: November 30th, 2023, 5:01am GMT by Jihye L Golino

Front Cell Dev Biol. 2023 Nov 10;11:1250215. doi: 10.3389/fcell.2023.1250215. eCollection 2023.

ABSTRACT

Cholangiocarcinoma is a malignancy of the bile ducts that is driven by activities of cancer stem-like cells and characterized by a heterogeneous tumor microenvironment. To better understand the transcriptional profiles of cancer stem-like cells and dynamics in the tumor microenvironment during the progression of cholangiocarcinoma, we performed single-cell RNA analysis on cells collected from three different timepoints of tumorigenesis in a YAP/AKT mouse model. Bulk RNA sequencing data from TCGA (The Cancer Genome Atlas program) and ICGC cohorts were used to verify and support the finding. In vitro and in vivo experiments were performed to assess the stemness of cancer stem-like cells. We identified Tm4sf1high malignant cells as cancer stem-like cells. Across timepoints of cholangiocarcinoma formation in YAP/AKT mice, we found dynamic change in cancer stem-like cell/stromal/immune cell composition. Nevertheless, the dynamic interaction among cancer stem-like cells, immune cells, and stromal cells at different timepoints was elaborated. Collectively, these data serve as a useful resource for better understanding cancer stem-like cell and malignant cell heterogeneity, stromal cell remodeling, and immune cell reprogramming. It also sheds new light on transcriptomic dynamics during cholangiocarcinoma progression at single-cell resolution.

PMID:38020927 | PMC:PMC10667919 | DOI:10.3389/fcell.2023.1250215
LAMC2 is a potential prognostic biomarker for cholangiocarcinoma

Fetched: November 30th, 2023, 5:01am GMT by Khaa Hoo Ong

Oncol Lett. 2023 Oct 30;26(6):533. doi: 10.3892/ol.2023.14120. eCollection 2023 Dec.

ABSTRACT

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-βsignaling pathway' and 'platelet-derived growth factor receptor-β signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.

PMID:38020294 | PMC:PMC10655064 | DOI:10.3892/ol.2023.14120
Editorial: Advances in chemotherapy-resistant hepatocellular carcinoma

Fetched: November 30th, 2023, 5:01am GMT by Shui Liu

Front Med (Lausanne). 2023 Nov 13;10:1325304. doi: 10.3389/fmed.2023.1325304. eCollection 2023.

NO ABSTRACT

PMID:38020167 | PMC:PMC10679682 | DOI:10.3389/fmed.2023.1325304
The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma

Fetched: November 30th, 2023, 5:01am GMT by Chiyu Cai

Scand J Gastroenterol. 2023 Nov 29:1-11. doi: 10.1080/00365521.2023.2286193. Online ahead of print.

ABSTRACT

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

PMID:38018772 | DOI:10.1080/00365521.2023.2286193
Association between high expression of intratumoral fibroblast activation protein and survival in patients with intrahepatic cholangiocarcinoma

Fetched: November 29th, 2023, 5:01am GMT by Yuhei Waki

BMC Gastroenterol. 2023 Nov 28;23(1):415. doi: 10.1186/s12876-023-03012-x.

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to exhibit protumorigenic effects. Among the well-known CAF markers such as smooth muscle actin (SMA) and fibroblast activation protein (FAP), high expression of SMA in the peritumoral stroma has been reported to be a prognostic factor in various cancers. However, the effect of high FAP expression in intrahepatic cholangiocarcinoma (IHCC) has not been fully clarified. We evaluated the expression of CAF markers, focusing on FAP expression in the peripheral and intratumoral regions, to clarify the association with survival in patients with IHCC.

METHODS: The study cohort comprised 37 patients who underwent curative resection for IHCC. The FAP expressions were evaluated in the peripheral and intratumoral regions of the resected tissues. Clinicopathological factors and survival outcomes were investigated between patients with high versus low FAP expression. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival and relapse-free survival.

RESULTS: The median area percentages of FAP expression in the peripheral and intratumoral regions were 15.5% and 17.8%, respectively. High FAP expression in the intratumoral region was significantly associated with worse overall survival and disease-free survival than low FAP expression in the intratumoral region. Multivariate analysis identified high intratumoral FAP expression as a risk factor for worse overall survival (hazard ratio, 2.450; p = 0.049) and relapse-free survival (hazard ratio, 2.743; p = 0.034).

CONCLUSIONS: High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.

PMID:38017374 | PMC:PMC10683315 | DOI:10.1186/s12876-023-03012-x
Revealing the role of necroptosis microenvironment: FCGBP + tumor-associated macrophages drive primary liver cancer differentiation towards cHCC-CCA or iCCA

Fetched: November 29th, 2023, 5:01am GMT by Chun Wang

Apoptosis. 2023 Nov 28. doi: 10.1007/s10495-023-01908-3. Online ahead of print.

ABSTRACT

Previous research has demonstrated that the conversion of hepatocellular carcinoma (HCC) to intrahepatic cholangiocarcinoma (iCCA) can be stimulated by manipulating the tumor microenvironment linked with necroptosis. However, the specific cells regulating the necroptosis microenvironment have not yet been identified. Additionally, further inquiry into the mechanism of how the tumor microenvironment regulates necroptosis and its impact on primary liver cancer(PLC) progression may be beneficial for precision therapy. We recruited a single-cell RNA sequencing dataset (scRNA-seq) with 34 samples from 4 HCC patients and 3 iCCA patients, and a Spatial Transcriptomic (ST) dataset including one each of HCC, iCCA, and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Quality control, dimensionality reduction and clustering were based on Seurat software (v4.2.2) process and batch effects were removed by harmony (v0.1.1) software. The pseudotime analysis (also known as cell trajectory) in the single cell dataset was performed by monocle2 software (v2.24.0). Calculation of necroptosis fraction was performed by AUCell (v1.16.0) software. Switch gene analysis was performed by geneSwitches(v0.1.0) software. Dimensionality reduction, clustering, and spatial image in ST dataset were performed by Seurat (v4.0.2). Tumor cell identification, tumor subtype characterization, and cell type deconvolution in spot were performed by SpaCET (v1.0.0) software. Immunofluorescence and immunohistochemistry experiments were used to prove our conclusions. Analysis of intercellular communication was performed using CellChat software (v1.4.0). ScRNA-seq analysis of HCC and iCCA revealed that necroptosis predominantly occurred in the myeloid cell subset, particularly in FCGBP + SPP1 + tumor-associated macrophages (TAMs), which had the highest likelihood of undergoing necroptosis. The existence of macrophages undergoing necroptosis cell death was further confirmed by immunofluorescence. Regions of HCC with poor differentiation, cHCC-CCA with more cholangiocarcinoma features, and the tumor region of iCCA shared spatial colocalization with FCGBP + macrophages, as confirmed by spatial transcriptomics, immunohistochemistry and immunofluorescence. Pseudotime analysis showed that premalignant cells could progress into two directions, one towards HCC and the other towards iCCA and cHCC-CCA. Immunofluorescence and immunohistochemistry experiments demonstrated that the number of macrophages undergoing necroptosis in cHCC-CCA was higher than in iCCA and HCC, the number of macrophages undergoing necroptosis in cHCC-CCA with cholangiocarcinoma features was more than in cHCC-CCA with hepatocellular carcinoma features. Further investigation showed that myeloid cells with the highest necroptosis score were derived from the HCC_4 case, which had a severe inflammatory background on pathological histology and was likely to progress towards iCCA and cHCC-CCA. Switchgene analysis indicated that S100A6 may play a significant role in the progression of premalignant cells towards iCCA and cHCC-CCA. Immunohistochemistry confirmed the expression of S100A6 in PLC, the more severe inflammatory background of the tumor area, the more cholangiocellular carcinoma features of the tumor area, S100A6 expression was higher. The emergence of necroptosis microenvironment was found to be significantly associated with FCGBP + SPP1 + TAMs in PLC. In the presence of necroptosis microenvironment, premalignant cells appeared to transform into iCCA or cHCC-CCA. In contrast, without a necroptosis microenvironment, premalignant cells tended to develop into HCC, exhibiting amplified stemness-related genes (SRGs) and heightened malignancy.

PMID:38017206 | DOI:10.1007/s10495-023-01908-3
Diagnostic accuracy and interobserver agreement of cholangioscopy for indeterminate biliary strictures: A single-center experience

Fetched: November 29th, 2023, 5:01am GMT by Sebastian Manuel Milluzzo

Dig Liver Dis. 2023 Nov 27:S1590-8658(23)01035-6. doi: 10.1016/j.dld.2023.11.017. Online ahead of print.

ABSTRACT

BACKGROUND AND STUDY AIMS: Characterization of indeterminate biliary strictures (IDBS) still represents a major challenge. Digital single-operator cholangioscopy (DSOC) could potentially overcome limits of conventional biopsy and brush sampling. The aim of this study was to compare diagnostic accuracy of visual evaluation and DSOC-guided biopsies to conventional trans-papillary sampling techniques and to evaluate the inter-observer agreement (IOA) on visual diagnosis.

PATIENTS AND METHODS: All consecutive patients undergoing DSOC-guided biopsy after conventional sampling techniques for IDBS during a six-year period were retrospectively evaluated. Final diagnosis was based on histological evaluation of the surgical specimen if available or a clinical follow-up of at least 6 months. For IOA, 20-second DSOC clips were retrospectively reviewed by 6 experts and 6 trainees and classified according to the Monaco Classification.

RESULTS: Thirty-five patients underwent DSOC for IDBS in the study period; 14 patients (F = 9) with a median age of 64 years (range 53-76) met the study aim. After DSOC, strictures location was changed in three patients (additional yield of 21.4 %). Intraductal DSOC-guided biopsy were technically successful in all cases, with an adequacy of 92.8 %. No adverse events were recorded. Final diagnosis was benign disease in five cases and cholangiocarcinoma in the others. For IOA, 29 videos were evaluated with almost perfect agreement for final diagnosis (kappa 0.871; agreement 93.1, p <0.001), although overall accuracy of DSOC visual finding was 73.6 % and 64.4 % for experts and trainees, respectively.

CONCLUSIONS: DSOC could improve diagnostic accuracy for IDBS, since it showed high sensitivity for visual finding and high specificity for DSOC guided-biopsy. Visual diagnosis seems reliable for diagnosis using the Monaco Classification.

PMID:38016895 | DOI:10.1016/j.dld.2023.11.017
Circulating oncometabolite 2-hydroxyglutarate (2HG) as a potential biomarker for isocitrate dehydrogenase (IDH1/2) mutant cholangiocarcinoma

Fetched: November 29th, 2023, 5:01am GMT by Cha Len Lee

Mol Cancer Ther. 2023 Nov 28. doi: 10.1158/1535-7163.MCT-23-0460. Online ahead of print.

ABSTRACT

Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate. IDH1/2 mutations preferentially convert αKG to R-2-hydroxyglutarate (R2HG), resulting in R2HG accumulation in tumor tissues. We investigated circulating 2-hydroxyglutate (2HG) as potential biomarkers for patients with IDH-mutant (IDHmt) cholangiocarcinoma (CCA). R2HG and S-2-hydroxyglutarate (S2HG) levels in blood and tumor tissues were analyzed in a discovery cohort of IDHmt glioma and CCA patients. Results were validated in cohorts of CCA and clear cell renal cell carcinoma (ccRCC) patients. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for IDHmt glioma patients, while circulating rRS was elevated in IDHmt CCA patients. There were overlap distributions of circulating R2HG and total 2HG (t2HG) in both IDHmt and wild-type (IDHwt) CCA patients, while there was minimal overlap in rRS values between IDHmt and IDHwt CCA patients. Using the rRS cut-off value of 1.5, the sensitivity of rRS was 90% and specificity was 96.8%. Circulating rRS is significantly increased in IDHmt CCA patients compare to IDHwt CCA patients. Circulating rRS is a sensitive and specific surrogate biomarker for IDH1/2 mutations in CCA. It can potentially be used as a tool for monitoring IDH-targeted therapy.

PMID:38015561 | DOI:10.1158/1535-7163.MCT-23-0460
Utilization of Radiomics Features Extracted From Preoperative Medical Images to Detect Metastatic Lymph Nodes in Cholangiocarcinoma and Gallbladder Cancer Patients: A Systemic Review and Meta-analysis

Fetched: November 29th, 2023, 5:01am GMT by Mohammad Mirza-Aghazadeh-Attari

J Comput Assist Tomogr. 2023 Nov 27. doi: 10.1097/RCT.0000000000001557. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to determine the methodological quality and evaluate the diagnostic performance of radiomics features in detecting lymph node metastasis on preoperative images in patients with cholangiocarcinoma and gallbladder cancer.

METHODS: Publications between January 2005 and October 2022 were considered for inclusion. Databases such as Pubmed/Medline, Scopus, Embase, and Google Scholar were searched for relevant studies. The quality of the methodology of the manuscripts was determined using the Radiomics Quality Score and Quality Assessment of Diagnostic Accuracy Studies 2. Pooled results with corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Liard method (random-effect model). Forest plots were used to visually represent the diagnostic profile of radiomics signature in each of the data sets pertaining to each study. Fagan plot was used to determine clinical applicability.

RESULTS: Overall sensitivity was 0.748 (95% CI, 0.703-0.789). Overall specificity was 0.795 (95% CI, 0.742-0.839). The combined negative likelihood ratio was 0.299 (95% CI, 0.266-0.350), and the positive likelihood ratio was 3.545 (95% CI, 2.850-4.409). The combined odds ratio of the studies was 12.184 (95% CI, 8.477-17.514). The overall summary receiver operating characteristics area under the curve was 0.83 (95% CI, 0.80-0.86). Three studies applied nomograms to 8 data sets and achieved a higher pooled sensitivity and specificity (0.85 [0.80-0.89] and 0.85 [0.71-0.93], respectively).

CONCLUSIONS: The pooled analysis showed that predictive models fed with radiomics features achieve good sensitivity and specificity in detecting lymph node metastasis in computed tomography and magnetic resonance imaging images. Supplementation of the models with biological correlates increased sensitivity and specificity in all data sets.

PMID:38013233 | DOI:10.1097/RCT.0000000000001557
ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells

Fetched: November 28th, 2023, 5:01am GMT by Anghui Peng

Cell Death Dis. 2023 Nov 27;14(11):777. doi: 10.1038/s41419-023-06309-7.

ABSTRACT

p63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples. We further established genetically modified iCCA cell lines in which p63 was overexpressed or knocked down to study the protein function/function of p63 in iCCA. We found that cells overexpressing p63, but not p63 knockdown counterparts, displayed increased proliferation, migration, and invasion. Transcriptome analysis showed that p63 altered the iCCA transcriptome, particularly by affecting cell adhesion-related genes. Moreover, chromatin accessibility decreased at p63 target sites when p63 binding was lost and increased when p63 binding was gained. The majority of the p63 bound sites were located in the distal intergenic regions and showed strong enhancer marks; however, active histone modifications around the Transcription Start Site changed as p63 expression changed. We also detected an interaction between p63 and the chromatin structural protein YY1. Taken together, our results suggest an oncogenic role for p63 in iCCA.

PMID:38012140 | PMC:PMC10682000 | DOI:10.1038/s41419-023-06309-7
Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016

Fetched: November 28th, 2023, 5:01am GMT by Bertille Comoz

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