Delayed Recurrence of Gall Bladder Cancer as Port-site Metastases with Occult Primary Detected on Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography: A Tale of Two Cases

Fetched: December 5th, 2023, 5:01am GMT by Parneet Singh

Indian J Nucl Med. 2023 Jul-Sep;38(3):273-275. doi: 10.4103/ijnm.ijnm_17_23. Epub 2023 Oct 10.

ABSTRACT

Laparoscopic cholecystectomy is a fairly common procedure and is currently considered the gold standard for cholecystectomy. However, the laparoscopic procedure in the presence of gall bladder cancer (GBC) is associated with the risk of port-site metastasis (PSM). Furthermore, in few cases, GBC remains occult even on postoperative histopathology and presents with PSM remotely. Here, we describe two such cases of GBC with occult primary who presented with PSM and also defined the role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography in the management of such cases.

PMID:38046970 | PMC:PMC10693369 | DOI:10.4103/ijnm.ijnm_17_23
Liver Mass as First-Time Diagnosis of Sarcomatoid Anaplastic Thyroid Carcinoma: A Rare Malignancy Presenting at an Unexpected Body Site

Fetched: December 5th, 2023, 5:01am GMT by Abdulla Kamashki

Am J Case Rep. 2023 Dec 2;24:e941838. doi: 10.12659/AJCR.941838.

ABSTRACT

BACKGROUND Anaplastic thyroid carcinomas are aggressive malignancies associated with poor clinical outcomes and challenges in diagnosis. While local/regional disease in the neck is the most usual site of biopsy, in some cases, distant metastases may be the site of initial investigation. CASE REPORT A 66-year-old woman with a clinical concern for diffuse metastatic malignancy of unknown primary presented to the Emergency Department (ED) with jaundice and shortness of breath. Recent laboratory test results revealed an elevated CA 19-9. Urinalysis revealed hematuria, proteinuria, and hyperbilirubinemia. She had a computed tomography (CT) scan of the chest, abdomen, and pelvis revealing diffuse involvement of the liver, lungs, adrenals, kidneys, thyroid, pancreas, gallbladder, and brain, but had not yet had a biopsy for definitive diagnosis. An ultrasound-guided liver biopsy was evaluated for cytological features, histological features, and pattern of immunostaining. The cytomorphological histological features were concerning for a high-grade malignancy. Immunohistochemical evaluation revealed that the lesion was positive for CK-AE1/AE3, BRAF, CK7, GATA3, SATB2, PAX8, and TTF-1, but the lesion was not reactive to the following stains: napsin, CK20, CDX2, PCEA, calcitonin, ER and thyroglobulin. The patient was diagnosed with a sarcomatoid anaplastic thyroid carcinoma and died within a few days after diagnosis. CONCLUSIONS This case illustrates that unanticipated specific diagnoses of widely metastatic anaplastic thyroid carcinoma are feasible when integration of patient history, clinical setting, imaging findings, clinical laboratory results, cytomorphology, histomorphology, and results of ancillary immunohistochemical testing are thoughtfully pursued and synthesized.

PMID:38041397 | DOI:10.12659/AJCR.941838
First-in-Humans PET Imaging of KRASG12C Mutation Status in Non-Small Cell Lung and Colorectal Cancer Patients Using [18F]PFPMD

Fetched: December 5th, 2023, 5:01am GMT by Xiang Li

J Nucl Med. 2023 Dec 1;64(12):1880-1888. doi: 10.2967/jnumed.123.265715.

ABSTRACT

Kirsten rat sarcoma (KRAS) mutations are an important marker for tumor-targeted therapy. In this study, we sought to develop a KRAS^G12C oncoprotein-targeted PET tracer and to evaluate its translational potential for noninvasive imaging of the KRAS^G12C mutation in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) patients. Methods: [¹⁸F]PFPMD was synthesized on the basis of AMG510 (sotorasib) by attaching a polyethylene glycol chain to the quinazolinone structure. The binding selectivity and imaging potential of [¹⁸F]PFPMD were verified by cellular uptake, internalization, and blocking (H358: KRAS^G12C mutation; A549: non-KRAS^G12C mutation) studies, as well as by a small-animal PET/CT imaging study on tumor-bearing mice. Five healthy volunteers were enrolled to assess the safety, biodistribution, and dosimetry of [¹⁸F]PFPMD. Subsequently, 14 NSCLC or CRC patients with or without the KRAS^G12C mutation underwent [¹⁸F]PFPMD and [¹⁸F]FDG PET/CT imaging. The SUVmax of tumor uptake of [¹⁸F]PFPMD was measured and compared between patients with and without the KRAS^G12C mutation. Results: [¹⁸F]PFPMD was obtained with a high radiochemical yield, radiochemical purity, and stability. The protein-binding assay showed that [¹⁸F]PFPMD selectively binds to the KRAS^G12C protein. [¹⁸F]PFPMD uptake was significantly higher in H358 than in A549 and was decreased by pretreatment with AMG510 (H358 vs. A549: 3.22% ± 0.28% vs. 2.50% ± 0.25%, P < 0.05; block: 2.06% ± 0.13%, P < 0.01). Similar results were observed in tumor-bearing mice on PET imaging (H358 vs. A549: 3.93% ± 0.24% vs. 2.47% ± 0.26% injected dose/g, P < 0.01; block: 2.89% ± 0.29% injected dose/g; P < 0.05). [¹⁸F]PFPMD was safe in humans and was excreted primarily by the gallbladder and intestines. The whole-body effective dose was comparable to that of [¹⁸F]FDG. The accumulation of [¹⁸F]PFPMD in KRAS^G12C mutation tumors was significantly higher than that in non-KRAS^G12C mutation tumors (SUVmax: 3.73 ± 0.58 vs. 2.39 ± 0.22, P < 0.01) in NSCLC and CRC patients. Conclusion: [¹⁸F]PFPMD is a safe and promising PET tracer for noninvasive screening of the KRAS^G12C mutation status in NSCLC and CRC patients.

PMID:37827842 | DOI:10.2967/jnumed.123.265715
Comparative Genomic Analysis and Clinical Outcomes of BRAF-mutated Advanced Biliary Tract Cancers

Fetched: December 5th, 2023, 5:01am GMT by Tin-Yun Tang

Clin Cancer Res. 2023 Dec 1;29(23):4853-4862. doi: 10.1158/1078-0432.CCR-23-1926.

ABSTRACT

PURPOSE: BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC.

EXPERIMENTAL DESIGN: We analyzed two nonoverlapping cohorts. We examined the genomic landscape of BRAF-mutated iCCA in a "genomic cohort" [187 class I, 82 class II, 113 class III BRAF mutants and 8,026 wildtype (WT)]. We also analyzed median progression-free survival (PFS) and overall survival (OS) on first-line chemotherapy in a separate multi-institutional "clinical cohort" of patients with BTC (including iCCA and extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer; 41 class I, 32 class II+III BRAF mutants and 1,042 WT).

RESULTS: In the entire BTC clinical cohort, the median PFS was shorter for class I [HR, 2.11 (P < 0.001)] and class II+III [HR, 1.72 (P = 0.007)] as compared with BRAF WT. OS was also shorter in class I [HR, 2.04 (P = 0.011)] and class II+III [HR, 1.86 (P = 0.002)] as compared with BRAF WT. In the iCCA subgroup, class I alterations were mutually exclusive with FGFR2, IDH1/2, ERBB2, and KRAS mutations. Class II+III mutations appear to be mutually exclusive with FGFR2 and KRAS.

CONCLUSIONS: In BTC, all classes of BRAF mutations are associated with a worse prognosis. BRAF mutations occur in 5% of iCCA subgroup and may be mutually exclusive with other targetable mutations.

PMID:37773629 | DOI:10.1158/1078-0432.CCR-23-1926
Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map

Fetched: December 1st, 2023, 5:02am 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
Large Cell Neuroendocrine Carcinoma of the Gallbladder: Where Survival Is a Rare Entity - Case Report and Review of the Literature

Fetched: December 1st, 2023, 5:02am GMT by Samyak Dhruv

Case Rep Gastroenterol. 2023 Nov 16;17(1):333-338. doi: 10.1159/000534520. eCollection 2023 Jan-Dec.

ABSTRACT

INTRODUCTION: Carcinoma of the gallbladder is extremely rare, papillary adenocarcinoma comprises 90% of these cases. Although neuroendocrine neoplasms (NENs) comprise 0.5% of the cases of gallbladder cancer, the incidence is rising. NEN is classified into a well-differentiated neuroendocrine tumor and poorly differentiated neuroendocrine cancer (NEC). Histologically, NEC is small-cell or large-cell carcinoma. We present the extremely rare case, 15th in the literature to be precise, of large cell neuroendocrine carcinoma of the gallbladder.

CASE PRESENTATION: A 72-year-old male presented to the emergency department with constipation and right upper quadrant pain for 3 months. Computed tomography scan of the abdomen demonstrated an ill-defined 7.2 × 4.9 cm hypodense lesion in the gallbladder fossa with extension into the liver. Histopathological and immunohistochemical analysis of the biopsy specimen confirmed the diagnosis of large cell neuroendocrine carcinoma of the gallbladder. He was started on palliative chemotherapy.

CONCLUSION: The plethora of tumors present in the gallbladder necessitates a search for risk factors for gallbladder neoplasia, and underscores the need to more carefully examine the nature of "asymptomatic gallstones." Further studies may reveal subclasses of cholelithiasis, gallbladder morphology, or imaging to define which patients should be followed more carefully, and may clarify additional risk factors for cancer of the gallbladder.

PMID:38020465 | PMC:PMC10653706 | DOI:10.1159/000534520
Immunohistochemical expression of TROP‑2 (TACSTD2) on the urothelial carcinoma of the urinary bladder and other types of cancer

Fetched: December 1st, 2023, 5:02am GMT by Mahmoud Abbas

Oncol Lett. 2023 Oct 23;26(6):527. doi: 10.3892/ol.2023.14114. eCollection 2023 Dec.

ABSTRACT

In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma in situ, the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.

PMID:38020299 | PMC:PMC10644361 | DOI:10.3892/ol.2023.14114
Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and risk of 14 lifestyle-related cancers in the UK Biobank prospective cohort study

Fetched: December 1st, 2023, 5:02am GMT by Fiona C Malcomson

BMC Med. 2023 Nov 28;21(1):407. doi: 10.1186/s12916-023-03107-y.

ABSTRACT

BACKGROUND: The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based recommendations which aim to reduce cancer risk. This study investigated associations between adherence, assessed using a standardised scoring system, and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with aspects of lifestyle in the UK.

METHODS: We used data from 94,778 participants (53% female, mean age 56 years) from the UK Biobank. Total adherence scores (range 0-7 points) were derived from dietary, physical activity, and anthropometric data. Associations between total score and cancer risk (all cancers combined; and prostate, breast, colorectal, lung, uterine, liver, pancreatic, stomach, oesophageal, head and neck, ovarian, kidney, bladder, and gallbladder cancer) were investigated using Cox proportional hazard models, adjusting for age, sex, deprivation index, ethnicity, and smoking status.

RESULTS: Mean total score was 3.8 (SD 1.0) points. During a median follow-up of 8 years, 7296 individuals developed cancer. Total score was inversely associated with risk of all cancers combined (HR: 0.93; 95%CI: 0.90-0.95 per 1-point increment), as well as breast (HR: 0.90; 95%CI: 0.86-0.95), colorectal (HR: 0.90; 95%CI: 0.84-0.97), kidney (HR: 0.82; 95%CI: 0.72-0.94), oesophageal (HR: 0.84; 95%CI: 0.71-0.98), ovarian (HR: 0.76; 95%CI: 0.65-0.90), liver (HR: 0.78; 95%CI: 0.63-0.97), and gallbladder (HR: 0.70; 95%CI: 0.53-0.93) cancers.

CONCLUSIONS: Greater adherence to lifestyle-based recommendations was associated with reduced risk of all cancers combined and of breast, colorectal, kidney, oesophageal, ovarian, liver, and gallbladder cancers. Our findings support compliance with the Cancer Prevention Recommendations for cancer prevention in the UK.

PMID:38012714 | PMC:PMC10683228 | DOI:10.1186/s12916-023-03107-y
The role of subspecialized radiologist reviews in preoperative conference for hepato-pancreato-biliary disease

Fetched: December 1st, 2023, 5:02am 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
Bariatric Surgery and Risk of Hospitalization for Gastrointestinal Cancers in the USA: a Propensity Score Matched Analysis of National Inpatient Sample Study

Fetched: December 1st, 2023, 5:02am GMT by Ali Esparham

Obes Surg. 2023 Dec;33(12):3797-3805. doi: 10.1007/s11695-023-06883-x. Epub 2023 Oct 20.

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
Deciphering Target Protein Cascade in Salmonella typhi Biofilm using Genomic Data Mining, and Protein-protein Interaction

Fetched: November 24th, 2023, 5:02am GMT by Aditya Upadhyay

Curr Genomics. 2023 Oct 27;24(2):100-109. doi: 10.2174/1389202924666230815144126.

ABSTRACT

BACKGROUND: Salmonella typhi biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the S. typhi outbreak has turned into a fatal disease typhoid. S. typhi infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of S. typhi.

OBJECTIVE: The study aimed to identify a cascade of target proteins in S. typhi biofilm condition with the help of genomic data mining and protein-protein interaction analysis.

METHODS: The goal of this study was to notice some important pharmacological targets in S. typhi. using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease.

RESULTS: In this study, we identified 15 potential target proteins that are critical for S. typhi biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of S. typhi. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence.

CONCLUSION: All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in S. typhi is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.

PMID:37994324 | PMC:PMC10662377 | DOI:10.2174/1389202924666230815144126
Durvalumab: A Review in Advanced Biliary Tract Cancer

Fetched: November 24th, 2023, 5:02am 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
FASN promotes gallbladder cancer progression and reduces cancer cell sensitivity to gemcitabine through PI3K/AKT signaling

Fetched: November 22nd, 2023, 5:02am GMT by Haihong Cheng

Drug Discov Ther. 2023 Nov 18;17(5):328-339. doi: 10.5582/ddt.2023.01036. Epub 2023 Sep 22.

ABSTRACT

Lipid metabolism plays an important role in the growth and development of tumors. However, the role of lipid metabolism in gallbladder cancer (GBC) has not been clearly clarified. Here, we demonstrated that fatty acid synthase (FASN), a key enzyme in de novo fatty acid biosynthesis, had upregulated expression in GBC samples both at protein and mRNA levels. Analysis of clinical data indicated the association between elevated FASN expression and poorer histology grades. Furthermore, FASN activity impairment through FASN knockdown or treatment with orlistat resulted in the inhibition of cell proliferation and migration, as well as increased sensitivity to gemcitabine. Both FASN knockdown and orlistat treatment induced cell apoptosis. Mechanistically, impairment of FASN activity suppressed the activation of the PI3K/AKT signaling pathway, which led to increased cell apoptosis and sensitivity to gemcitabine. These findings were also validated through nude mouse xenograft models, thus highlighting the potential of targeting FASN as a clinical treatment strategy. Collectively, the present study underscores the crucial role of FASN in the progression of gallbladder cancer via the PI3K/AKT pathway.

PMID:37743521 | DOI:10.5582/ddt.2023.01036
YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation

Fetched: November 14th, 2023, 5:02am GMT by Xuesong Bai

Cancer Sci. 2023 Nov;114(11):4299-4313. doi: 10.1111/cas.15953. Epub 2023 Sep 12.

ABSTRACT

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and involved in the carcinogenesis of various malignancies. However, the functions and mechanisms of m6A in gallbladder cancer (GBC) remain unclear. In this study, we investigated the role and underlying mechanism of the RNA-binding protein YT521-B homology domain-containing family protein 2 (YTHDF2), an m6A reader, in GBC. Herein, we detected that YTHDF2 was remarkably upregulated in GBC tissues compared to normal gallbladder tissues. Functionally, YTHDF2 overexpression promoted the proliferation, tumor growth, migration, and invasion of GBC cells while inhibiting the apoptosis in vitro and in vivo. Conversely, YTHDF2 knockdown induced opposite results. Mechanistically, we further investigated the underlying mechanism by integrating RNA immunoprecipitation sequencing (RIP-seq), m6A-modified RIP-seq, and RNA sequencing, which revealed that death-associated protein kinase 3 (DAPK3) is a direct target of YTHDF2. YTHDF2 binds to the 3'-UTR of DAPK3 mRNA and facilitates its degradation in an m6A-dependent manner. DAPK3 inhibition restores the tumor-suppressive phenotype induced by YTHDF2 deficiency. Moreover, the YTHDF2/DAPK3 axis induces the resistance of GBC cells to gemcitabine. In conclusion, we reveal the oncogenic role of YTHDF2 in GBC, demonstrating that YTHDF2 increases the mRNA degradation of the tumor suppressor DAPK3 in an m6A-dependent way, which promotes GBC progression and desensitizes GBC cells to gemcitabine. Our findings provide novel insights into potential therapeutic strategies for GBC.

PMID:37700438 | PMC:PMC10637062 | DOI:10.1111/cas.15953
Endoscopic Ultrasound-Guided Naso-gallbladder Drainage Using a Dedicated Catheter for Acute Cholecystitis After Transpapillary Metal Stent Placement for Malignant Biliary Obstruction

Fetched: November 11th, 2023, 5:01am GMT by Tadahisa Inoue

Dig Dis Sci. 2023 Dec;68(12):4449-4455. doi: 10.1007/s10620-023-08135-5. Epub 2023 Oct 13.

ABSTRACT

BACKGROUND: Acute cholecystitis is a significant adverse event after self-expandable metal stent (SEMS) placement for malignant biliary obstruction (MBO); however, no appropriate treatment strategy has been established for its management.

AIMS: This study aimed to examine the feasibility and utility of endoscopic ultrasound-guided naso-gallbladder drainage (EUS-NGBD) for the management of acute cholecystitis occurring after SEMS placement.

METHODS: This retrospective study investigated consecutive patients with acute cholecystitis after SEMS placement for unresectable MBO, in whom EUS-NGBD was attempted. The study outcomes included technical success, clinical success, procedure time, adverse event, and cholecystitis recurrence, associated with the procedure.

RESULTS: During the study period, EUS-NGBD was performed for SEMS-related acute cholecystitis in 30 patients with MBO. The technical and clinical success rates were 96.7% (29/30) and 96.6% (28/29), respectively. The median procedure time was 15 min, and rate of procedure-related adverse event was 3.3% (1/30). The median duration from the procedure to tube removal was 9 days. No adverse events were observed after removal. The median hospitalization duration after the procedure was 14 days, and the median duration to the (re-)start of chemotherapy from cholecystitis onset was 13 days. The median overall survival after EUS-NGBD was 123 days, and the rate of cholecystitis recurrence until death was 4.2% (1/28).

CONCLUSIONS: This study demonstrated that EUS-NGBD possesses good technical and clinical feasibility with an acceptable adverse event rates and short hospitalization and chemotherapy withdrawal period. Therefore, EUS-NGBD may be a good option for the treatment of SEMS-related cholecystitis in patients with MBO.

PMID:37831399 | DOI:10.1007/s10620-023-08135-5
Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis

Fetched: November 9th, 2023, 5:02am GMT by Ya-Fei Hu

Biomol Biomed. 2023 Nov 3;23(6):1096-1107. doi: 10.17305/bb.2023.9582.

ABSTRACT

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient's OS. Unfavorable pathological features of the neoplasm are the main determinants.

PMID:37724922 | PMC:PMC10655887 | DOI:10.17305/bb.2023.9582
Annals of Surgical Oncology Practice Guidelines Series: Management of Primary Liver and Biliary Tract Cancers

Fetched: November 9th, 2023, 5:02am GMT by Samantha M Ruff

Ann Surg Oncol. 2023 Dec;30(13):7935-7949. doi: 10.1245/s10434-023-14255-z. Epub 2023 Sep 11.

ABSTRACT

Primary cancers of the liver and biliary tract are rare and aggressive tumors that often present with locally advanced or metastatic disease. For patients with localized disease amenable to resection, surgery typically offers the best chance at curative-intent therapy. Unfortunately, the incidence of recurrence even after curative-intent surgery remains high. In turn, patients with hepatobiliary cancers commonly require multimodality therapy including a combination of resection, systemic therapy (i.e., targeted therapy, cytotoxic chemotherapy, immunotherapy), and/or loco-regional therapies. With advancements in the field, it is crucial for surgical oncologists to remain updated on the latest guidelines and recommendations for surgical management and optimal patient selection. Given the complex and evolving nature of treatment, this report highlights the latest practice guidelines for the surgical management of hepatobiliary cancers.

PMID:37691030 | DOI:10.1245/s10434-023-14255-z
Surgical Management Of Feline Biliary Tract Disease: Decision-making and techniques

Fetched: November 9th, 2023, 5:02am GMT by Daniel Low

J Feline Med Surg. 2023 Nov;25(11):1098612X231206846. doi: 10.1177/1098612X231206846.

ABSTRACT

PRACTICAL RELEVANCE: Diseases of the hepatobiliary system are not uncommon in first-opinion practice. The anatomy of the feline hepatobiliary tract differs from that of dogs and may predispose cats to inflammatory hepatobiliary disease. Case management can be challenging, and the prognosis is variable and dependent on the underlying disease process.

CLINICAL CHALLENGES: Biliary tract disease in the cat has non-specific clinical signs that overlap with those of diseases of other body systems. Diagnostic tests of the hepatobiliary system are widely available, but interpretation of results can be challenging. Deciding on medical or surgical management can also be challenging; for example, various degrees of cholestasis may be seen with different diseases and disease severities, and will influence the decision to manage the patient medically or surgically. Surgery is indicated in cases of bile peritonitis, severe cholestasis, focal neoplasia or disease that is refractory to medical management. Intensive perioperative and postoperative management, with 24 h hospitalisation facilities, is essential.

AUDIENCE: This review article is written for the small animal general/primary care practitioner, with an emphasis on decision-making in the surgical management of feline hepatobiliary disease.

EVIDENCE BASE: Evidence available in the published literature is reviewed and presented, and the inherent limitations are discussed.

PMID:37933545 | DOI:10.1177/1098612X231206846
Cholecystokinin to enhance the safety of ablation of liver tumors adjacent to the gallbladder

Fetched: November 7th, 2023, 5:02am GMT by Michael J Margron

J Vasc Interv Radiol. 2023 Nov 4:S1051-0443(23)00799-6. doi: 10.1016/j.jvir.2023.10.031. Online ahead of print.

ABSTRACT

This retrospective case review describes the potential for intravenous cholecystokinin (CCK) to improve the safety margin between hepatic tumor and gallbladder for hepatic tumor ablation. Eight patients with primary hepatic neoplasms adjacent to the gallbladder underwent CCK administration prior to ablation. Gallbladder volume and contact area measurements were made before and after CCK administration to assess the degree of contraction. The planned ablation was successful in 7 (88%) patients after CCK administration, although 5 (63%) patients also had hydrodissection. After CCK, the median gallbladder volume reduction was 22% and tumor contact area with the gallbladder was reduced by 20%. There was no evidence for CCK-related adverse events (AEs). CCK administration prior to ablation of hepatic neoplasms abutting the gallbladder is a safe and simple method that may be an adjunct to needle decompression or hydrodissection of the gallbladder.

PMID:37931845 | DOI:10.1016/j.jvir.2023.10.031
Next generation sequencing uncovers multiple miRNAs associated molecular targets in gallbladder cancer patients

Fetched: November 7th, 2023, 5:02am GMT by Rahul Saxena

Sci Rep. 2023 Nov 4;13(1):19101. doi: 10.1038/s41598-023-44767-3.

ABSTRACT

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.

PMID:37925508 | PMC:PMC10625549 | DOI:10.1038/s41598-023-44767-3
Radiosynthesis, preclinical evaluation and pilot clinical PET imaging study of a 18F-labeled tracer targeting fibroblast activation protein

Fetched: November 4th, 2023, 5:01am GMT by Lilan Fu

Bioorg Chem. 2023 Dec;141:106878. doi: 10.1016/j.bioorg.2023.106878. Epub 2023 Sep 22.

ABSTRACT

Fibroblast activation protein (FAP) is a promising molecular target for imaging in various types of cancers. Several ¹⁸F-labeled FAP inhibitor (FAPI) tracers have been evaluated in clinical study. However, these tracers display high physiological uptake in gallbladder and bile duct system. To overcome the limitation, we herein designed a novel radiotracer named ¹⁸F-FAPTG. ¹⁸F-FAPTG was produced with a non-decay-corrected radiochemical yield of 24.0 ± 6.0% and 22.0 ± 7.0% for manual and automatic synthesis, respectively. ¹⁸F-FAPTG exhibited high hydrophilicity and stability in vitro. The studies of cellular uptake, internalization, efflux properties and competitive binding to FAP of ¹⁸F-FAPTG indicated that the tracer showed high specificity, rapid internalization and low cellular efflux in FAP-positive cells. Biodistribution studies and microPET in mice bearing FAP-positive xenografts demonstrated extremely low uptake in the majority of other organs and main excretion of ¹⁸F-FAPTG through the urinary system. Furthermore, compared to ¹⁸F-FAPI-42, ¹⁸F-FAPTG showed significantly lower uptake in gallbladder, higher tumor uptake and longer tumor retention. In the pilot clinical study, ¹⁸F-FAPTG PET/CT demonstrated favorable tumor-to-background ratios in most organs and clearly displayed the malignant lesions. Our findings indicated that ¹⁸F-FAPTG had an advantage over ¹⁸F-FAPI-42 in PET imaging for cancers located in gallbladder the bile duct system. Thus, ¹⁸F-FAPTG could be an alternative to the currently available FAPI tracers.

PMID:37774434 | DOI:10.1016/j.bioorg.2023.106878
A nomogram predicting the outcome of gallbladder cancer patients with different target organ metastases

Fetched: November 4th, 2023, 5:01am GMT by Z-P Xu

Eur Rev Med Pharmacol Sci. 2023 Oct;27(20):10016-10030. doi: 10.26355/eurrev_202310_34182.

ABSTRACT

OBJECTIVE: Gallbladder cancer (GBC) is a highly aggressive malignancy that is associated with a high mortality rate globally. Unfortunately, distant metastases are often detected at the time of diagnosis. Therefore, we investigated the survival outcomes of gallbladder cancer patients with different metastases targeting organs, analyzed their prognosis, and explored their hidden clinical value.

PATIENTS AND METHODS: Through data screening, a total of 398 patients with GBC with different target organ metastases were analyzed retrospectively, including patients with solitary bone metastasis, solitary liver metastasis, solitary lung metastasis, and multiple organ metastases. The survival results of different variables were plotted as Kaplan-Meier survival curves. Univariate and multivariate Cox regression models were used to screen study variables and identify independent prognostic factors. Finally, a nomogram was established to systematically evaluate the prognosis of patients with multiple organ metastasis.

RESULTS: In the patient cohort, thirteen (3.3%) had solitary bone metastasis, 290 (72.9%) had solitary liver metastasis, 22 (5.5%) had solitary lung metastasis, and 73 (18.3%) had multiple organ metastases (including liver, lung, bone and brain metastases). Multivariate Cox analysis showed that the overall survival (OS) of patients with solitary lung metastasis was significantly better than that of patients with other organ metastasis (p = 0.038), while the difference in tumor cancer-specific survival (CSS) of this factor was not statistically significant (p > 0.05). Surgery and chemotherapy were independent prognostic protective factors for OS and CSS. The OS-related models exhibited a C-index of 0.74 (95% CI: 0.71-0.77), while the CSS-related models showed a slightly lower C-index of 0.73 (0.70-0.76). Both the OS- and CSS-related clinical prediction models had good accuracy.

CONCLUSIONS: This study shows that different target organ metastases may affect the OS of patients with distant metastatic GBC. Patients receiving palliative surgery, primary site resection, radical surgery, and chemotherapy have significant survival benefits in terms of OS and CSS.

PMID:37916372 | DOI:10.26355/eurrev_202310_34182
The utility of systemic immune inflammatory index in discriminating between gallbladder cancer and xanthogranulomatous cholecystitis: A single-tertiary center experience

Fetched: November 3rd, 2023, 5:02am GMT by Hilmi Anil Dincer

Medicine (Baltimore). 2023 Oct 27;102(43):e35805. doi: 10.1097/MD.0000000000035805.

ABSTRACT

Xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) are rare diseases with several similarities. This study aimed to evaluate the utility of the systemic immune inflammatory index (SII), a novel index that more accurately depicts inflammatory and immunological balance, in distinguishing between XGC and GBC. This retrospective study included 33 XGC, 22 GBC patients diagnosed according to histopathological findings and 33 age-sex-matched healthy controls at Hacettepe University Faculty of Medicine, General Surgery Department. The demographic, clinical and laboratory findings were recorded. Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio and SII were calculated from preoperative complete blood count parameters. The receiver operating characteristic curve was performed to evaluate the utility of SII in differentiating GBC and XGC. A P value < .05 was accepted as statistically significant. The preoperative neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio and SII were significantly higher in patients with GBC compared to XGC patients and healthy controls (P < .001, P = .001, P = .001, P < .001, respectively). When receiver operating characteristic analysis was made, the optimal cutoff value of SII was 640 for differential diagnosis of XGC and GBC preoperatively with a sensitivity of 77.3% and a specificity of 66.7%, among which the positive likelihood ratio was 2.32, and Youden index was 0.44 (P = .006). The positive predictive value was 60.7%, the negative predictive value was 81.5%, and the diagnostic accuracy was 79.9%. SII may be a valuable, practical, and affordable method to differentiate between XGC and GBC, in addition to clinical and radiological signs, prior to surgery. When supported by prospective trials with a larger study population, distinguishing GBC from XGC using SII preoperatively may lead to a change in the management practice of GBC.

PMID:37904388 | PMC:PMC10615518 | DOI:10.1097/MD.0000000000035805
Melanoma of the gallbladder

Fetched: November 3rd, 2023, 5:02am GMT by Paweł Bojar

Folia Med Cracov. 2023 Jul 30;63(2):77-92. doi: 10.24425/fmc.2023.145915.

ABSTRACT

Melanoma is a highly malignant neoplasm with the most typical primary locations in the skin and eyeball and rarely reported in the other organs, including the gallbladder. More commonly metastases of melanoma of various primary sites to the gallbladder are observed. However, generally melanoma of the gallbladder is a rare entity with only 217 cases reported in the literature up to date. The paper summarizes knowledge on epidemiology, symptoms, laboratory and imaging findings, morphology, treatment options, and outcome of patients with both primary and metastatic melanoma to the gallbladder.

PMID:37903381 | DOI:10.24425/fmc.2023.145915
An incidental traditional serrated adenoma of the gallbladder: A case report

Fetched: November 3rd, 2023, 5:02am GMT by Emilio I Abecia Martínez

Rev Esp Patol. 2023 Oct-Dec;56(4):271-274. doi: 10.1016/j.patol.2022.12.002. Epub 2023 Feb 9.

ABSTRACT

Serrated lesions outside the low digestive tract are scarce, with only two traditional serrated adenomas (TSA) reported in the gallbladder, with limited information about the serrated pathway outside the colon. Our case was an incidental finding in a patient undergoing surgery to treat a cholecystitis, when a polypoid lesion was observed. The epithelium formed gland structures with ectopic crypts, serrated slits and eosinophilic cytoplasm. MUC4 and MUC5A were positive, but mismatch repair proteins (MSI) retained nuclear staining. BRAF showed a not mutated profile and NRAS/KRAS was inconclusive due to the absence of remaining tissue. MSI and CpG island (CIMP), the most common genetic hallmarks of the serrated pathway, have been proven in gallbladder carcinomas, although serrated polyps are not recognized as premalignant precursors. Hereby we report one TSA of the gallbladder without the usual genetic drivers. A larger evidence is needed to improve the diagnosis and management.

PMID:37879824 | DOI:10.1016/j.patol.2022.12.002
Melanoma of the gallbladder

Fetched: November 3rd, 2023, 5:02am GMT by A Boca

Acta Gastroenterol Belg. 2023 Jul-Sep;86(3):505-506. doi: 10.51821/86.3.12020.

NO ABSTRACT

PMID:37814572 | DOI:10.51821/86.3.12020
Pre and post treatment quality of life among patients of hepatobiliary and pancreatic cancers in North India: A prospective study

Fetched: November 3rd, 2023, 5:02am GMT by Ermeen Khurshied Wani

J Cancer Res Ther. 2023 Jul-Sep;19(5):1109-1114. doi: 10.4103/jcrt.jcrt_225_21.

ABSTRACT

CONTEXT: Studies reporting quality of life (QOL) measures alongside conventional measures of effectiveness of interventions and outcome are essential.

AIMS: We aimed to compare QOL and mental well-being in hepatobiliary and pancreatic cancer patients before and after receiving treatment.

SETTINGS AND DESIGN: This was a hospital-based prospective study.

METHODS AND MATERIALS: The study was conducted in North India for a period of 1 year. QOL was assessed in 118 patients using the Functional Assessment of Cancer Therapy-Hepatobiliary Scale and Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Level 1 Cross-Cutting Symptom Measure-Adult was used to assess the psychiatric domains of subjects.

STATISTICAL ANALYSIS USED: The data were analyzed using MS Excel and SPSS version 23. Statistical significance between QOL scores at baseline and 12 weeks was evaluated by Student's t-test. Pre- and post-Cronbach's alpha reliability coefficient was also calculated.

RESULTS: 59.4% of subjects were females and 40.6% were males. Carcinoma gallbladder was the predominant cancer (2/3^rd) followed by carcinoma pancreas (1/3^rd). Both pre- and posttreatment reliability coefficients showed values ≥ 0.75, indicating that the questionnaire reliably measured different domains of health-related QOL, both on generic and disease-specific scales. Using paired t-test, a significant difference was observed only in the physical (P = 0.001) and functional (P = 0.0002) domains. There was a slight increase in proportion of patients demonstrating improvement in severity of depression and anxiety at 6-12 weeks and the number of patients experiencing moderate symptoms of sleep disorders and somatic disorders. The number of patients experiencing severe symptoms of anger decreased posttreatment.

CONCLUSIONS: QOL is amenable to improvement with timely interventions including counseling.

PMID:37787271 | DOI:10.4103/jcrt.jcrt_225_21
Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer

Fetched: November 2nd, 2023, 5:02am GMT by Xing He

J Transl Med. 2023 Oct 12;21(1):717. doi: 10.1186/s12967-023-04589-3.

ABSTRACT

BACKGROUND: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC.

METHODS: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance.

RESULTS: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors.

CONCLUSIONS: Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.

PMID:37828574 | PMC:PMC10571407 | DOI:10.1186/s12967-023-04589-3
Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma

Fetched: November 2nd, 2023, 5:02am GMT by Hanrui Shao

BMC Med Genomics. 2023 Oct 11;16(1):240. doi: 10.1186/s12920-023-01663-z.

ABSTRACT

BACKGROUND: Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms.

METHODS: The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database.

CONCLUSIONS: We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC.

PMID:37821907 | PMC:PMC10566037 | DOI:10.1186/s12920-023-01663-z
The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

Fetched: November 1st, 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
EUS-guided gallbladder drainage for malignant biliary obstruction: a new paradigm but not so new

Fetched: November 1st, 2023, 5:01am GMT by Faisal Kamal

Gastrointest Endosc. 2023 Nov;98(5):774-775. doi: 10.1016/j.gie.2023.07.040.

NO ABSTRACT

PMID:37863570 | DOI:10.1016/j.gie.2023.07.040
Primary Undifferentiated Gallbladder Carcinoma With SMARCA4 Deletion: A Case Report and Review of the Literature

Fetched: October 31st, 2023, 5:02am GMT by Deng Xiaoxu

Int J Surg Pathol. 2023 Oct 29:10668969231206575. doi: 10.1177/10668969231206575. Online ahead of print.

ABSTRACT

Background. Undifferentiated gallbladder carcinoma is a rare type of cancer with poor prognosis, due to the absence of specific clinical manifestations, and the final diagnosis depends on pathological and immunohistochemical examinations. However, only a few reports of SMARCA4-deficient undifferentiated gallbladder tumor have been published to date. Therefore, we report the diagnosis and treatment of an undifferentiated gallbladder carcinoma with SMARCA4 deficiency. Case Presentation. A 65-year-old woman with undifferentiated gallbladder carcinoma was treated using traditional Chinese medicine and underwent palliative surgery in our hospital. The postoperative pathology showed SMARCA4-deficient undifferentiated gallbladder carcinoma with metastasis to the abdominal lymph nodes. Conclusions. This case report contributes to the limited literature regarding undifferentiated carcinoma without SMARCA4 in the gallbladder.

PMID:37899615 | DOI:10.1177/10668969231206575
Intracholecystic Papillary-tubular Neoplasm (ICPN) of the Gallbladder: A Case Report Focusing on an Unexpected Pathological Finding

Fetched: October 28th, 2023, 5:02am GMT by Antonio Pesce

Recent Pat Anticancer Drug Discov. 2023 Oct 25. doi: 10.2174/0115748928256837231012151452. Online ahead of print.

ABSTRACT

BACKGROUND: Intracholecystic papillary neoplasms (ICPNs) represent a rare benign entity characterized by intraluminal polypoid lesions in the gallbladder. The incidence of ICPNs ranges from 0.4% to 0.61% in all gallbladder specimens.

CASE PRESENTATION: In this report, we present a case of a young Caucasian woman who underwent elective laparoscopic cholecystectomy due to gallbladder polyps. The histological examination revealed the presence of an intracholecystic papillary neoplasm (ICPN) with a tubulopapillary growth pattern, exhibiting gastric morphology and displaying both low and high-grade dysplasia. A thorough review of the existing literature was conducted, with a specific focus on the histological features.

CONCLUSION: A comprehensive understanding of neoplastic polyps of the gallbladder is still limited. Pathological examination of these lesions is crucial for identifying key features that can influence patient outcomes and survival.

PMID:37885107 | DOI:10.2174/0115748928256837231012151452
FOXQ1 promotes pancreatic cancer cell proliferation, tumor stemness, invasion and metastasis through regulation of LDHA-mediated aerobic glycolysis

Fetched: October 28th, 2023, 5:02am GMT by Changhao Wu

Cell Death Dis. 2023 Oct 24;14(10):699. doi: 10.1038/s41419-023-06207-y.

ABSTRACT

Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial-mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients' poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.

PMID:37875474 | PMC:PMC10598070 | DOI:10.1038/s41419-023-06207-y
A rare case of urothelial carcinoma metastasizing to the gallbladder wall with manifestations as acute cholecystitis

Fetched: October 27th, 2023, 5:02am GMT by A Berková

Klin Onkol. 2023 Fall;36(4):401-404. doi: 10.48095/ccko2023401.

ABSTRACT

BACKGROUND: Metastasis to the gallbladder is very rare. This case report highlights a rare cause of acute cholecystitis, which should be considered by the surgeon and other treating physicians in the differential diagnosis of patients with urothelial carcinoma.

CASE: We report the case of a 73 year-old man with follow-up oncology care. He was diagnosed with infiltrating urothelial carcinoma in 2019, received neoadjuvant chemotherapy, and subsequently underwent radical cystectomy with ureteroileostomy in April 2020. Histology confirmed complete regression of bladder cancer, the lymphonodes were also free of tumour infiltration. In July 2021, the patient was examined for intermittent abdominal pain, predominantly of the right upper quadrant. On clinical examination, the gallbladder hydrops was palpable and a positive Murphy's sign was present. Due to the signs of acute cholecystitis, the patient was indicated for acute cholecystectomy. Gallbladder histology revealed metastatic involvement of the gallbladder wall by urothelial carcinoma.

CONCLUSION: If patients with bladder cancer present with intermittent right subcostal pain or signs of acute cholecystitis and diagnostic imaging shows a thickened gallbladder wall, clinicians and radiologists should consider the possibility of metastatic origin of lesion.

PMID:37877533 | DOI:10.48095/ccko2023401
Dosimetry of [18F]TRACK, the first PET tracer for imaging of TrkB/C receptors in humans

Fetched: October 24th, 2023, 5:01am GMT by Alexander Thiel

EJNMMI Radiopharm Chem. 2023 Oct 23;8(1):33. doi: 10.1186/s41181-023-00219-x.

ABSTRACT

BACKGROUND: Reduced expression or impaired signalling of tropomyosin receptor kinases (Trk receptors) are found in a vast spectrum of CNS disorders. [¹⁸F]TRACK is the first PET radioligand for TrkB/C with proven in vivo brain penetration and on-target specific signal. Here we report dosimetry data for [¹⁸F]TRACK in healthy humans. 6 healthy participants (age 22-61 y, 3 female) were scanned on a General Electric Discovery PET/CT 690 scanner. [¹⁸F]TRACK was synthesized with high molar activities (Am = 250 ± 75 GBq/µmol), and a dynamic series of 12 whole-body scans were acquired after injection of 129 to 147 MBq of the tracer. Images were reconstructed with standard corrections using the manufacturer's OSEM algorithm. Tracer concentration time-activity curves (TACs) were obtained using CT-derived volumes-of-interest. Organ-specific doses and the total effective dose were estimated using the Committee on Medical Internal Radiation Dose equation for adults and tabulated Source tissue values (S values).

RESULTS: Average organ absorbed dose was highest for liver and gall bladder with 6.1E-2 (± 1.06E-2) mGy/MBq and 4.6 (± 1.18E-2) mGy/MBq, respectively. Total detriment weighted effective dose EDW was 1.63E-2 ± 1.68E-3 mSv/MBq. Organ-specific TACs indicated predominantly hepatic tracer elimination.

CONCLUSION: Total and organ-specific effective doses for [¹⁸F]TRACK are low and the dosimetry profile is similar to other ¹⁸F-labelled radio tracers currently used in clinical settings.

PMID:37870640 | PMC:PMC10593718 | DOI:10.1186/s41181-023-00219-x
Metastatic Colon Cancer Presenting as Gallbladder Perforation: Highlighting the Diagnostic Challenges and Clinical Implications

Fetched: October 24th, 2023, 5:01am GMT by Sagar Nagpal

ACG Case Rep J. 2023 Oct 19;10(10):e01167. doi: 10.14309/crj.0000000000001167. eCollection 2023 Oct.

ABSTRACT

Gallbladder perforation is an uncommon occurrence that demands prompt surgical intervention, typically observed in the context of acute cholecystitis. In this article, we present an extraordinary case of gallbladder gangrene and perforation, originating from metastasis of colon cancer. The patient's presentation included an incidental discovery of colon cancer, which was indicated by histopathology of the gall bladder. This case report aims to shed light on the intricate relationship between gallbladder pathology and metastatic colon cancer, emphasizing the need for vigilant evaluation and comprehensive management strategies.

PMID:37868363 | PMC:PMC10586845 | DOI:10.14309/crj.0000000000001167
Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor

Fetched: October 23rd, 2023, 5:02am GMT by Qianwen Wang

Front Immunol. 2023 Sep 29;14:1173520. doi: 10.3389/fimmu.2023.1173520. eCollection 2023.

ABSTRACT

BACKGROUND: Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy.

CASE PRESENTATION: We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated β-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC.

CONCLUSION: chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

PMID:37841278 | PMC:PMC10570427 | DOI:10.3389/fimmu.2023.1173520
Squamous cell carcinoma of the cystic duct: A case report and literature review

Fetched: October 23rd, 2023, 5:02am GMT by Hui-Jun Wang

Medicine (Baltimore). 2023 Oct 13;102(41):e35430. doi: 10.1097/MD.0000000000035430.

ABSTRACT

RATIONALE: Pure squamous cell carcinoma (SCC) of the gallbladder is a rare malignant biliary tract tumor predominantly found in the body and neck of the gallbladder. However, its occurrence in the cystic duct is even rarer. Given its rarity, no established guidelines or consensus currently exist regarding the treatment of pure SCC of the gallbladder. We report an unusual case of SCC originating from the cystic duct with the intent of providing insights into the therapeutic approach for this type of malignancy.

PATIENT CONCERNS: A male patient presented to our hospital with acute cholecystitis. Unexpectedly, imaging revealed gallbladder malignancy.

DIAGNOSES: Pathologic examination after surgery confirmed SCC of the cystic duct.

INTERVENTIONS: Despite elevated bilirubin levels, we were able to exclude hilar involvement, enabling radical tumor resection. Intraoperatively, we discovered that the tumor was located in the cystic duct, a site associated with a high likelihood of invasion into neighboring organs. The tumor demonstrated a predominantly exophytic growth pattern, which prompted us to refrain from extending the resection range, thereby striking a balance between complete tumor removal and surgical trauma. We performed liver wedge resection only to ensure a negative resection margin while preserving the anatomical structure to the greatest extent possible. Postoperative recovery was rapid and uncomplicated. Pathological examination confirmed pure SCC, which led us to initiate a regimen of nab-paclitaxel and cisplatin, which is known to be effective in other organ SCCs. Remarkably, the patient experienced a rare and severe posttreatment cardiovascular event. Consequently, we switched the patient to a chemotherapy regimen of gemcitabine and cisplatin, which ultimately yielded positive clinical outcomes.

OUTCOMES: no evidence of tumor recurrence was observed within 1 year after surgery.

LESSONS: The diagnosis and therapeutic strategy for rare tumors such as gallbladder SCC should be meticulously tailored based on their unique characteristics to optimize postoperative patient outcomes.

PMID:37832089 | PMC:PMC10578676 | DOI:10.1097/MD.0000000000035430
Acute cholecystitis in old adults: the impact of advanced age on the clinical characteristics of the disease and on the surgical outcomes of laparoscopic cholecystectomy

Fetched: October 23rd, 2023, 5:02am GMT by Cho Eun Lee

BMC Gastroenterol. 2023 Sep 25;23(1):328. doi: 10.1186/s12876-023-02954-6.

ABSTRACT

BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established.

METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis.

RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3.

CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.

PMID:37749524 | PMC:PMC10521416 | DOI:10.1186/s12876-023-02954-6
Is ultrasonography accurate for the diagnosis of gallbladder polyps? A review of cholecystectomy specimens from patients diagnosed with gallbladder polyps over a 14-years period

Fetched: October 23rd, 2023, 5:02am GMT by Anna González Costa

Cir Esp (Engl Ed). 2023 Oct;101(10):701-707. doi: 10.1016/j.cireng.2023.02.009. Epub 2023 Sep 23.

ABSTRACT

INTRODUCTION: Incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the capacity to become malignant, from true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are >6-10 mm, growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. Most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyse whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason.

METHODS: Retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study has been approved by the Clinical Research Ethics Committee of our hospital.

RESULTS: We included 124 patients in our study. An elective laparoscopic cholecystectomy was performed in all of them. The mean age was 55,4 years and 61% were women. Of all patients, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2,4%). All of them were tubular adenomas. The rest of patients were false positives (97,6%). The adenoma size was 11, 6 and 5 mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms.

CONCLUSION: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. Validation of other complementary tests for the diagnosis of gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries.

PMID:37748643 | DOI:10.1016/j.cireng.2023.02.009
Risk factors for early and late cholecystitis after covered metal stent placement for distal biliary obstruction

Fetched: October 23rd, 2023, 5:02am GMT by Tatsuya Ishii

J Hepatobiliary Pancreat Sci. 2023 Oct;30(10):1180-1187. doi: 10.1002/jhbp.1350. Epub 2023 Sep 12.

ABSTRACT

BACKGROUND: Cholecystitis is a major adverse event after self-expandable metallic stent placement for distal biliary obstruction (DBO). Covered self-expandable metallic stent (CSEMS) is being increasingly used, but few studies have investigated risk factors for cholecystitis limited to CSEMS. The present study aimed to identify risk factors for cholecystitis after CSEMS.

METHODS: Patients who underwent initial CSEMS placement for DBO between November 2014 and September 2021 were enrolled and followed-up until death, recurrent biliary obstruction, cholecystitis, or until March 2022. Cholecystitis within 30 days of CSEMS was defined as early cholecystitis and after 30 days as late cholecystitis.

RESULTS: Cholecystitis occurred in 51 of 339 patients (15%) after CSEMS. Forty-one patients (80.4%) had early cholecystitis, and 10 (19.6%) had late cholecystitis. Multivariate logistic regression analysis revealed that the maximum diameter of the common bile duct (CBD) (per 1 mm increase) (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.76-1.00; p = .044), gallbladder stones (OR: 3.63; 95% CI: 1.62-8.10; p = .002), and tumor involvement in the cystic duct (CD) (OR: 4.87; 95% CI: 2.16-11.00; p < .001) were significant independent risk factors associated with early cholecystitis. No significant risk factors were identified for late cholecystitis.

CONCLUSIONS: A smaller CBD diameter, gallbladder stones, and tumor involvement in the CD were identified as risk factors for early cholecystitis development after CSEMS.

PMID:37698322 | DOI:10.1002/jhbp.1350
Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study

Fetched: October 22nd, 2023, 5:01am GMT by F C Yang

Zhonghua Wai Ke Za Zhi. 2023 Oct 1;61(10):863-870. doi: 10.3760/cma.j.cn112139-20230202-00047.

ABSTRACT

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ²=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ²=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ²=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

PMID:37653988 | DOI:10.3760/cma.j.cn112139-20230202-00047
Impact of hepatitis B virus infection on the risk of gallbladder polyps: a cohort study

Fetched: October 18th, 2023, 5:02am GMT by Nam Hee Kim

Korean J Intern Med. 2023 Nov;38(6):844-853. doi: 10.3904/kjim.2023.197. Epub 2023 Oct 18.

ABSTRACT

BACKGROUND/AIMS: We aimed to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains an important risk factor for gallbladder polyps (GBPs) in the current context of reduced prevalence of these infections.

METHODS: The cohort included 392,913 asymptomatic adults who underwent abdominal ultrasonography (US).

RESULTS: The prevalence of GBP sized ≥ 5 mm, ≥ 10 mm, and overall (< 5, 5-9 and ≥ 10 mm) was 2.9%, 0.1%, and 12.8%, respectively. The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis C antibody (anti-HCV) positivity was 3.2%, 26.7%, and 0.1%, respectively. The GBP risk was significantly increased in HBsAg-positive individuals, with an adjusted odds ratio of 1.66 (95% confidence interval, 1.49-1.85) for GBP ≥ 5 mm, 2.39 (1.53-3.75) for GBP ≥ 10 mm, and 1.49 (1.41-1.59) for overall, whereas there was no significant association between anti-HCV positivity and GBP risk. The GBP risk did not increase significantly in individuals who tested negative for HBsAg but positive for HBcAb.

CONCLUSION: The presence of HBsAg may be an independent risk factor for GBP development in the current context of a indecreasing prevalence of HBsAg positivity. A more comprehensive evaluation of GBP during abdominal US surveillance of HBsAg-positive individuals may be necessary.

PMID:37848340 | PMC:PMC10636554 | DOI:10.3904/kjim.2023.197
Effective treatment of gallbladder neuroendocrine carcinoma with nivolumab

Fetched: October 17th, 2023, 5:01am GMT by Shinichiro Kanda

Clin Case Rep. 2023 Oct 11;11(10):e8040. doi: 10.1002/ccr3.8040. eCollection 2023 Oct.

ABSTRACT

An 89-year-old patient with gallbladder neuroendocrine neoplasms (GB-NENs) and lung cancer metastasis underwent nivolumab monotherapy, resulting in tumor shrinkage. Surgery and adjuvant nivolumab showed efficiency despite low expression of PD-L1.

PMID:37841882 | PMC:PMC10568049 | DOI:10.1002/ccr3.8040
Clinicopathological characteristics of extrahepatic biliary neuroendocrine neoplasms in the gallbladder, extrahepatic biliary tract, and ampulla of Vater: A single-center cross-sectional study

Fetched: October 17th, 2023, 5:01am GMT by Young Mok Park

Ann Hepatobiliary Pancreat Surg. 2023 Nov 30;27(4):380-387. doi: 10.14701/ahbps.23-045. Epub 2023 Oct 16.

ABSTRACT

BACKGROUNDS/AIMS: In 2019, the grading and staging system for neuroendocrine neoplasms (NENs) was significantly changed. In this study, we report the clinicopathological characteristics and surgical outcomes of patients with extrahepatic biliary NENs who underwent curative resection with or without adjuvant treatment.

METHODS: We retrospectively reviewed a database of 16 patients who developed NENs, neuroendocrine carcinoma (NEC), and mixed endocrine non-endocrine neoplasms (MiNENs) after curative resection. Among them, eight patients had ampulla of Vater (AoV) tumors, and eight patients had non-AoV tumors.

RESULTS: G1 and G2 were more frequently observed in the AoV group than in the non-AoV group (12.5% and 62.5%, respectively). In contrast, NEC and MiNEN were more common in the non-AoV group (50.0%). High Ki-67 index (> 20%) and perineural invasion (PNI) were more frequently observed in the non-AoV group. Advanced age (> 65 years), mitotic count > 20 per 2 mm², and Ki-67 index > 20% were strongly correlated with patient survival (p = 0.018, 0.009, and 0.044, respectively). Advanced age (> 65 years) and mitotic count > 20 per 2 mm² were significantly correlated with disease recurrence (p = 0.033 and 0.010, respectively).

CONCLUSIONS: AoV and non-AoV tumors had significant differences in the histologic grade, Ki67, and PNI. Patients with non-AoV tumors had an increased risk for survival and recurrence than those in the AoV group. For extrahepatic biliary NENs, early detection of tumors, adequate surgery, and aggressive adjuvant treatment for high-risk patients are important to achieve long-term survival and prevent disease recurrence.

PMID:37840317 | DOI:10.14701/ahbps.23-045
Global epidemiological trends and variations in the burden of gallbladder cancer

Fetched: October 14th, 2023, 5:01am GMT by Srineil Vuthaluru

J Surg Oncol. 2023 Nov;128(6):980-988. doi: 10.1002/jso.27450.

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is a rare but lethal malignancy with a dismal prognosis. The aim of this study is to analyze the burdens and trends of GBC across the world based on geography, socioeconomic development (based on human development index [HDI]), and gender.

METHODS: GLOBOCAN 2020 database was used to extract data (2020-2040) relating to the incidence and mortality of GBC across the world.

RESULTS: Asia had the highest burden of GBC with India and China contributing to majority of the absolute burden. The burden of GBC by age standardized rate was highest in Latin America (Bolivia and Chile) and Southeast Asia (Bangladesh and Nepal). Medium HDI countries had a higher mortality rate compared to very high HDI countries. Females had a higher predilection for GBC across different regions and socioeconomic groups. GBC burden is expected to significantly increase across the world by 2040 with variable trends across different regions, age groups, and genders.

CONCLUSION: The global burden of GBC will significantly increase over the next two decades with marked regional and demographic variations. The results of this study will empower national and global health leaders to develop policies to address the increasing burden of this lethal malignancy.

PMID:37818916 | DOI:10.1002/jso.27450
Comment on "Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study"

Fetched: October 13th, 2023, 5:02am GMT by Chu-Yue Zhang

Ann Surg Oncol. 2023 Nov;30(12):7397. doi: 10.1245/s10434-023-14257-x. Epub 2023 Sep 3.

NO ABSTRACT

PMID:37661224 | DOI:10.1245/s10434-023-14257-x
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
Robots to Improve Surgery for All

Fetched: October 11th, 2023, 5:02am GMT by Leslie Mertz

IEEE Pulse. 2022 Nov-Dec;13(6):6-11. doi: 10.1109/MPULS.2022.3227808.

ABSTRACT

Surgeons around the world are now using robot-assisted tech to help them perform minimally invasive operations ranging from hernia repair and gall bladder removal to knee replacement and cancer-related colectomy, often manipulating the surgical tools from a computer console some distance from the patient. With names like da Vinci, Aquabeam, and Mako, robotic surgical technologies are becoming more common. As an example, industry powerhouse Intuitive reported in late 2021 that the number of surgical procedures using its robotic da Vinci system had topped 10 million globally [1].

PMID:37815945 | DOI:10.1109/MPULS.2022.3227808
Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS)

Fetched: October 10th, 2023, 5:03am GMT by Devica S Umans

Br J Surg. 2023 Nov 9;110(12):1877-1882. doi: 10.1093/bjs/znad318.

ABSTRACT

BACKGROUND: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP).

METHODS: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up.

RESULTS: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life.

CONCLUSION: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

PMID:37811814 | PMC:PMC10638543 | DOI:10.1093/bjs/znad318
Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study

Fetched: October 10th, 2023, 5:03am GMT by Masahiro Iseki

Surgery. 2023 Nov;174(5):1145-1152. doi: 10.1016/j.surg.2023.05.019. Epub 2023 Aug 18.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater.

METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors.

RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031).

CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

PMID:37599194 | DOI:10.1016/j.surg.2023.05.019
Percutaneous transhepatic cholangioscopy for benign and malignant biliary disease using a novel short single-operator cholangioscope

Fetched: October 10th, 2023, 5:03am GMT by A K Uribe Rivera

Surg Endosc. 2023 Oct;37(10):7774-7783. doi: 10.1007/s00464-023-10337-x. Epub 2023 Aug 14.

ABSTRACT

BACKGROUND: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases.

METHODS: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023.

RESULTS: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis.

CONCLUSIONS: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients.

PMID:37580582 | DOI:10.1007/s00464-023-10337-x
The significance of countable and treatable metastatic liver disease in patients with gallbladder carcinoma after curative-intent surgery: A 10-year experience in China

Fetched: October 10th, 2023, 5:03am GMT by Tian-Run Lv

Cancer Med. 2023 Sep;12(18):18503-18515. doi: 10.1002/cam4.6450. Epub 2023 Aug 10.

ABSTRACT

OBJECTIVE: Our study was performed to evaluate the significance of countable and treatable metastatic liver disease (CTMLD) in patients with gallbladder carcinoma (GBC) after curative-intent surgery.

METHODS: Resected GBC patients between September 2010 and January 2021 were reviewed. Comparative analyses between patients with CTMLD and those without it were performed. A propensity score matching analysis was conducted for further validation.

RESULTS: A total of 326 resected GBC patients were identified (33 with CTMLD). A significantly higher preoperative CA199 level was detected in those with CTMLD (p = 0.0160). Significantly higher incidences of major hepatectomy (p = 0.0010), lymph node metastasis (p < 0.0001), direct liver invasion (p < 0.0001), moderate to poor differentiation status (p < 0.0001), and T3-4 disease (p < 0.0001) were detected in patients with CTMLD. Even sharing comparable surgical margin status, patients with CTMLD still shared a significantly higher recurrence rate (93.9% vs. 57.3%, p < 0.0001) as well as a significantly higher recurrence rate within 6 months after surgery (63.6% vs. 14.7%, p < 0.0001). A significantly worse overall survival (median survival time: 12 vs. 33 months, p < 0.0001) or disease-free survival (median recurrence-free time: 6 vs. 30 months, p < 0.0001) was acquired in patients with CTMLD. After matching, a significantly higher early recurrence rate was still detected. Adjuvant chemotherapy seemed to have survival benefit for patients with CTMLD.

CONCLUSION: CTMLD was an indicator of advanced disease and served as an independent predictor of early recurrence among resected GBC patients. Whether curative-intent surgery is superior to nonsurgical treatment among GBC patients with CTMLD remains to be explored in future prospective studies.

PMID:37563921 | PMC:PMC10557855 | DOI:10.1002/cam4.6450
Increased 68Ga-FAPI Activity in Primary Small Cell Neuroendocrine Carcinoma of the Gallbladder

Fetched: October 6th, 2023, 5:02am GMT by Longlan Chen

Clin Nucl Med. 2023 Nov 1;48(11):1003-1005. doi: 10.1097/RLU.0000000000004855. Epub 2023 Sep 18.

ABSTRACT

Primary small cell neuroendocrine carcinomas are extremely rare heterogeneous neoplasms. We present 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of small cell neuroendocrine carcinoma of the gallbladder in a 57-year-old woman. This rare gallbladder small cell neuroendocrine carcinoma demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This demonstrates the potential value of 68 Ga-FAPI PET/CT for evaluation of gallbladder small cell neuroendocrine carcinoma.

PMID:37796160 | DOI:10.1097/RLU.0000000000004855
Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome

Fetched: October 6th, 2023, 5:02am GMT by Mohamed Rezk

Front Immunol. 2023 Sep 18;14:1243946. doi: 10.3389/fimmu.2023.1243946. eCollection 2023.

ABSTRACT

INTRODUCTION: The development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples.

METHODS: Stored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization.

RESULTS: PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2-specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative.

DISCUSSION: SKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.

PMID:37795104 | PMC:PMC10546397 | DOI:10.3389/fimmu.2023.1243946
Gallbladder primary well-differentiated neuroendocrine tumor: A misdiagnosed case

Fetched: October 5th, 2023, 5:01am GMT by Nouha Dammak

Int J Surg Case Rep. 2023 Oct;111:108882. doi: 10.1016/j.ijscr.2023.108882. Epub 2023 Oct 1.

ABSTRACT

INTRODUCTION: Gallbladder (GB) Well-Differentiated (WD) Neuroendocrine Tumor (NET) are extremely rare tumors. They represent only about 0.5 % of all Neuroendocrine Neoplasms (NENs). Most GB-NETs are diagnosed after cholecystectomy. They are often misdiagnosed and have good prognosis.

CASE PRESENTATION: We share our experience of a 42-year-old woman operated on for symptomatic cholelithiasis. We discover on the anatomopathological piece that it was a Grade 1 NET of the GB. Staging scans and octreotide-scans were normal: there is no distant or nodal metastasis. This tumor was classified as T1bN0M0. After multidisciplinary team discussion, additional treatment is deemed unnecessary. She didn't receive any treatment after the surgery. At one year after the cholecystectomy, she is symptom free and there is no sign of recurrence.

DISCUSSION: The diagnosis of GB-WD NET is difficult at the first evaluation. Surgical management for GB cancer has shown increased survival rates, a similar strategy seems reasonable for GB-NETs. Patients with Grade,1 well-differentiated GB-NETS have an excellent prognosis overall.

CONCLUSION: Research is required to facilitate earlier diagnosis and to develop management guidelines for GB-NETs.

PMID:37793232 | PMC:PMC10551650 | DOI:10.1016/j.ijscr.2023.108882
Clinical significance of extrahepatic bile duct resection for T2 gallbladder cancer using data from the Japanese Biliary Tract Cancer Registry between 2014 and 2018

Fetched: October 5th, 2023, 5:01am GMT by Hiroyuki Kato

J Hepatobiliary Pancreat Sci. 2023 Oct 4. doi: 10.1002/jhbp.1379. Online ahead of print.

ABSTRACT

PURPOSE: The present study aimed to determine whether concomitant extrahepatic bile duct resection (EHBDR) improves the prognosis of patients with T2 gallbladder cancer (GBC).

METHODS: Between 2014 and 2018, 4947 patients with GBC were registered in the National Biliary Tract Cancer Registry in Japan. This included 3804 patients (76.9%) who underwent curative-intent surgical resection; 1609 of these patients had pT2 GBC with no distant metastasis. Of the 1609 patients with GBC, 520 underwent EHBDR and 1089 did not. We compared the patients' backgrounds and disease-specific survival rates between the groups.

RESULTS: The frequency of lymph node metastasis was significantly higher in the EHBDR group than in the non-EHBDR group (38.2% vs. 20.7%, p < .001). In the entire cohort, however, there was no significant difference in disease-specific survival between the two groups (76% vs. 79%, p = .410). The EHBDR group had a significantly higher incidence of postoperative complications (Clavien-Dindo classification grade = 3) (32.4% vs. 11.7%, p < .001). When we focused on the survival of only T2N1 patients who underwent gallbladder bed resection, the prognosis was significantly improved for the EHBDR group (5-year survival rate: 64% vs. 54%, p = .017). The non-EHBDR group was subcategorized into two groups: D2 dissection and D1 dissection or sampling, and survival curves were compared between these subgroups. Although the EHBDR group tended to have a favorable prognosis compared to the D2 group, this difference was not significant (p = .167). However, the EHBDR group had a significantly greater prognosis than the D1 dissection or sampling group (5 year-survival rate: 64 vs. 49%, p = .027).

CONCLUSIONS: The EHBDR may improve the prognosis of patients with T2 gall bladder cancer with lymph node metastases; however, its indication should be carefully determined because of the increased risk of postoperative complications.

PMID:37792631 | DOI:10.1002/jhbp.1379
Expression of ER, PR, and HER-2 Neu and correlation with tumor markers in gall bladder carcinoma

Fetched: October 4th, 2023, 5:03am GMT by Rishit Mani

J Cancer Res Ther. 2023 Jul-Sep;19(5):1279-1287. doi: 10.4103/jcrt.jcrt_1754_21.

ABSTRACT

BACKGROUND: Females having a large proportion of gallbladder carcinoma (GBC) and a higher incidence of gallstones pointed toward the role of sex hormones in GBC development. In this study, we evaluated the expression of Estrogen receptor (ER), Progesterone receptor (PR), and Her2/neu and their correlation with tumor markers and clinicopathological parameters in the GBC.

METHODS: A total of 50 patients of GBC and 42 patients in control group undergoing surgery for other conditions were taken. The patient's biopsy sample's paraffin block was tested for ER, PR, and Her2/neu expression by immunohistochemistry.

RESULTS: ER and PR had no significant expression in GBC and control group, but Her2/neu had 16% expression in GBC, significantly associated with the degree of differentiation with 62.5% (n-5) being well-differentiated; 75% of Her2/neu positive were in stages III and IV. Her2/neu did not correlate with tumor markers despite expression.

CONCLUSIONS: Her2/neu amplification is a small step in validating that option so it could be included in the treatment and prognostication of GBC.

PMID:37787296 | DOI:10.4103/jcrt.jcrt_1754_21
Clinical Outcome and Patterns of Failure in Patients with Solitary Plasmacytoma Treated with Radical Radiotherapy

Fetched: October 4th, 2023, 5:03am GMT by A Biswas

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S109. doi: 10.1016/j.ijrobp.2023.06.073.

ABSTRACT

PURPOSE/OBJECTIVE(S): We intended to assess the patterns of care and failure in patients with solitary plasmacytoma (SP), treated at our institute from 2011-21.

MATERIALS/METHODS: Data pertaining to the management of patients with SP was abstracted by retrospective chart review. Progression free survival (PFS) and overall survival (OS) were defined as the time intervals from the date of diagnosis to the date of progression (local, systemic or both) and death or last follow up, respectively. PFS and OS were analyzed by Kaplan Meier method.

RESULTS: Atotal of 72 patients were diagnosed with SP (61-bone plasmacytoma; 11-extramedullary plasmacytoma) in between 2011 and 2021. The median age at diagnosis was 52 years. The male: female ratio was 2.27. The ECOG PS were 0, 1, 2, 3, and 4 in 1, 46, 11, 10, and 3 patients, respectively. The median diameter of the lesion was 6.7 cm (range 2.3-18.4 cm). The median M protein was 0.375 g/dl (range 0.63-5.3 g/dl). On bone marrow examination, 8 and 64 patients had no and minimal marrow involvement, respectively (median bone marrow plasma cells 4%). Radical radiotherapy (RT) was administered in 71 patients, the techniques being 2D-conventional in 35, 3D-conformal in 14, IMRT in 8 and VMAT in 5 patients (details not available in 9). The median RT dose was 45 Gy in 25 fractions over 5 weeks (range 45-50 Gy). In addition, 5(7%) patients underwent surgery prior to RT and 6(8.5%) patients received systemic chemotherapy. After RT, the median quantum of symptom relief was 75% (range 0-100%). The best response to RT was CR, PR, SD and PD in 41(57.7%),18(25.4%),3(4.2%) and 4(5.6%) patients, respectively (response assessment could not be done in 5). Local control with primary RT was achieved in 58(81.7%) patients. No RT related grade 3/4 acute or late toxicity was reported. The median follow up was 48.3 months (range 1.3-141.6 months). A total of 28(39.4%) patients experienced disease progression (systemic in 15, local in 7 and both in 6), out of which 13 could be successfully salvaged with further systemic chemotherapy (mostly bortezomib, lenalidomide/pomalidomide and dexamethasone based) with or without local treatment. On progression to multiple myeloma, 9 patients underwent high dose chemotherapy(melphalan) followed by autologous stem cell transplant. Nine (12.7%) patients died, the causes being COVID-19 infection in 1, surgical complications in 1, PD in 2, second malignancies in 3 and unknown in 2. The actuarial rates of PFS & OS were 58.4% & 92.5% at 3 years and 50.3% & 89.4% at 5 years, respectively. Metachronous second malignancies were noted in 4 patients (B-ALL-1, lung cancer-1, metastatic carcinoma cervix-1, metastatic carcinoma gall bladder-1).

CONCLUSION: In patients with SP, radical RT with a modest dose (45-50 Gy) leads to satisfactory symptom relief, response and local control. Close to 40% patients eventually progress to multiple myeloma, out of which 50% can be successfully salvaged with further systemic chemotherapy. The 5-year OS approaches 90% in this cohort.

PMID:37784287 | DOI:10.1016/j.ijrobp.2023.06.073
Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma

Fetched: October 4th, 2023, 5:03am GMT by Rikita I Hatia

Cancer Epidemiol Biomarkers Prev. 2023 Oct 2;32(10):1338-1347. doi: 10.1158/1055-9965.EPI-23-0388.

ABSTRACT

BACKGROUND: It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States.

METHODS: We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor.

RESULTS: Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively.

CONCLUSIONS: In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals.

IMPACT: The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.

PMID:37540502 | DOI:10.1158/1055-9965.EPI-23-0388
Research progress on the pharmacological effects and chemical constituents of Pien Tze Huang and its potential Q-markers

Fetched: October 3rd, 2023, 5:02am GMT by Zhaomin Dong

Chin J Nat Med. 2023 Sep;21(9):658-669. doi: 10.1016/S1875-5364(23)60400-5.

ABSTRACT

Pien Tze Huang (PTH) was documented as an imperial prescription composed of Notoginseng Radix, Calculus Bovis, Snake Gallbladder, and Musk. It is famous in China and Asian countries due to its excellent effects in heat clearing, detoxifying, swelling reduction, and pain relieving. Modern pharmacological studies demonstrate that PTH shows excellent effects against various inflammatory diseases, liver diseases, and cancers. This review summaries the pharmacological effects, clinical applications, and mainchemical components of PTH. More importantly, its potential quality markers (Q-markers) were then analyzed based on the "five principles" of Q-markers under the guidance of Traditional Chinese Medicine theory, including transfer and traceability, specificity, efficacy, compatibility, and measurability. As a result, ginsenosides Rb1, ginsenoside Rg1, ginsenoside Rd, ginsenoside Re, notoginsenoside R1, dencichine, bilirubin, biliverdin, taurocholic acid, and muscone are considered as the Q-markers of PTH. These findings will provide guidance and assistance for the construction of a quality control system for PTH.

PMID:37777316 | DOI:10.1016/S1875-5364(23)60400-5
Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved

Fetched: October 3rd, 2023, 5:02am GMT by Junke Wang

Langenbecks Arch Surg. 2023 Sep 28;408(1):382. doi: 10.1007/s00423-023-03119-5.

ABSTRACT

BACKGROUND: The metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined.

METHODS: From January 2007 to January 2018, 144 advanced GBC patients (T2-4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS).

RESULTS: The optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195-2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463-0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148-2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589-0.892) were independent prognostic factors for GBC (all P<0.05).

CONCLUSIONS: LNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

PMID:37770780 | PMC:PMC10539180 | DOI:10.1007/s00423-023-03119-5
Cholecystitis induced by Yttrium-90 radioembolization of advanced liver tumors: prospective evaluation of a management algorithm in 197 consecutive patients

Fetched: September 29th, 2023, 5:02am GMT by Robert Damm

Acta Radiol. 2023 Oct;64(10):2783-2790. doi: 10.1177/02841851231189490. Epub 2023 Jul 31.

ABSTRACT

BACKGROUND: Cholecystitis is a rare but dolorous complication after Y90-radioembolization of liver malignancies.

PURPOSE: To decide the occlusion of the cystic artery (CA) to prevent cholecystitis after Y90 radioembolization using an algorithm.

MATERIAL AND METHODS: In 130 patients, the gallbladder was at risk of embolization as the right liver lobe was targeted. Precautionary measures (e.g. coil occlusion of the cystic artery) were decided by enhancement of the gallbladder in pre-treatment Tc99m-MAA SPECT/CT and performed directly before Y90 radioembolization. In non-enhancing cases, the CA was left open. The outcome was determined by clinical symptoms of acute or chronic cholecystitis as well as imaging and laboratory parameters. Findings were additionally classified according to the Tokyo Guidelines of acute cholecystitis.

RESULTS: Only 16 patients demonstrated enhancement of the gallbladder in Tc99m-MAA SPECT/CT. Including additional indications from angiographic findings, prophylactic measures were scheduled in 22 patients (standard of care). Thus, 121 patients were at risk of non-target embolization to the gallbladder during Y90 microsphere administration (investigative arm). Four cases (3.0%) of cholecystitis occurred by clinical presentation: two patients with onset of acute symptoms within 48 h after Y90 radioembolization ("embolic cholecystitis") and two patients with late onset of symptoms ("radiogenic cholecystitis"). The incidence of cholecystitis was not significantly more frequent without indication of precautionary measures (investigative cohort 2.9% vs. standard of care 4.7%; P = 0.53).

CONCLUSION: The overall incidence of cholecystitis after Y90 radioembolization is low. Determination of cystic artery intervention using Tc99m-MAA SPECT/CT successfully balances the incidence of symptomatic cholecystitis with unnecessary vessel occlusion.

PMID:37525508 | DOI:10.1177/02841851231189490
An audit of the adequacy of first-time ultrasound reports in patients with non-acute gallbladder wall thickening: Need for gallbladder reporting and data system

Fetched: September 28th, 2023, 5:03am GMT by Maninder Kaur

Indian J Gastroenterol. 2023 Oct;42(5):741-743. doi: 10.1007/s12664-023-01397-x.

NO ABSTRACT

PMID:37421574 | DOI:10.1007/s12664-023-01397-x
The value of the preoperative Naples prognostic score in predicting prognosis in gallbladder cancer surgery patients

Fetched: September 27th, 2023, 5:02am GMT by Jie Yang

World J Surg Oncol. 2023 Sep 25;21(1):303. doi: 10.1186/s12957-023-03198-0.

ABSTRACT

PURPOSE: The Naples prognostic score (NPS) is a comprehensive prognostic model that includes inflammatory and nutrition-related indicators and is increasingly used as a prognostic score for various malignant tumors. Given its predictive effect on prognosis in patients with gallbladder cancer, it is currently unclear. This study aimed to investigate the role of preoperative NPS in predicting prognosis in gallbladder cancer surgery patients.

PATIENTS AND METHODS: A retrospective analysis was performed for 135 patients who underwent radical surgery for gallbladder cancer without preoperative treatment between March 2011 and January 2020. NPS was calculated by measuring the preoperative total cholesterol value, serum albumin value, neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). They were then divided into 3 groups (groups 0, 1, and 2) based on NPS scores. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Plot time-dependent receiver operating characteristic (ROC) curves to compare the prognostic value of scoring systems. Finally, a nomogram model was developed with independent prognostic factors.

RESULTS: Multivariate analysis showed that NPS was an independent risk factor affecting OS (HR = 3.417, p < 0.05). The time-dependent ROC curve results showed that NPS had a better predictive value on survival prognosis than other indicators. The nomogram constructed according to independent factors such as NPS has a good predictive ability for OS.

CONCLUSION: As a simple and reliable tool, the NPS has important predictive value in the survival prognosis of gallbladder cancer patients. The nomogram model constructed by NPS will help determine prognosis and make individualized treatment decisions.

PMID:37743468 | PMC:PMC10519127 | DOI:10.1186/s12957-023-03198-0
Sister Mary Joseph nodule can be the only clinical sign of advanced gallbladder carcinoma

Fetched: September 26th, 2023, 5:02am GMT by Akihiko Kida

Gastrointest Endosc. 2023 Oct;98(4):655-656. doi: 10.1016/j.gie.2023.06.033. Epub 2023 Jun 26.

NO ABSTRACT

PMID:37380004 | DOI:10.1016/j.gie.2023.06.033
A Retrospective Analysis of Biliary Tract Cancer Patients Presented to the Molecular Tumor Board at the Comprehensive Cancer Center Munich

Fetched: September 26th, 2023, 5:02am GMT by Danmei Zhang

Target Oncol. 2023 Sep;18(5):767-776. doi: 10.1007/s11523-023-00985-3. Epub 2023 Aug 18.

ABSTRACT

BACKGROUND AND OBJECTIVE: With the rising importance of precision oncology in biliary tract cancer (BTC), the aim of this retrospective single-center analysis was to describe the clinical and molecular characteristics of patients with BTC who underwent comprehensive genomic profiling (CGP) and were discussed in the CCCMunich^LMU molecular tumor board (MTB).

PATIENTS AND METHODS: In this single-center observational study, we included BTC patients with intrahepatic cholangiocarcinoma (iCCA), extrahepatic CCA (eCCA), and gallbladder cancer (GB), who had been discussed in the institutional MTB from May 29, 2017, to July 25, 2022. Patients were followed up until 31 January 2023. Data were retrospectively collected by review of medical charts, and MTB recommendation.

RESULTS: In total, 153 cases were registered to the MTB with a median follow-up of 15 months. Testing was successful in 81.7% of the patients. CGP detected targetable alterations in 35.3% of our BTC patients (most commonly ARID1A/ERBB2/IDH1/PIK3CA/BRAF-mutations and FGFR2-fusions). Recommendations for molecularly guided therapy were given in 46.4%. Of those, treatment implementation of targeted therapy followed in 19.4%. In patients receiving the recommended treatment, response rate was 57% and median overall survival was 19 months (vs 8 months in the untreated cohort). The progression-free survival ratio of 1.45 suggest a clinical benefit of molecularly guided treatment.

CONCLUSIONS: In line with previous work, our series demonstrates feasibility and clinical utility of comprehensive genomic profiling in BTC patients. With the growing number of targeted agents with clinical activity in BTC, CGP should become standard of care in the management of this group of patients.

PMID:37594677 | PMC:PMC10517894 | DOI:10.1007/s11523-023-00985-3
Prophylactic EUS-guided gallbladder drainage in patients with malignant biliary obstruction and cystic duct orifice involvement: Need more answers!

Fetched: September 26th, 2023, 5:02am GMT by Mithu Bhowmick

Gastrointest Endosc. 2023 Oct;98(4):675. doi: 10.1016/j.gie.2023.04.2069.

NO ABSTRACT

PMID:37734818 | DOI:10.1016/j.gie.2023.04.2069
Well-Differentiated Neuroendocrine Tumor of the Gallbladder with Paraganglioma-Like Features: a Potential Mimicker of Gallbladder Paraganglioma

Fetched: September 22nd, 2023, 5:03am GMT by Alessandro Vanoli

Endocr Pathol. 2023 Sep;34(3):358-360. doi: 10.1007/s12022-023-09784-y. Epub 2023 Aug 21.

NO ABSTRACT

PMID:37599339 | DOI:10.1007/s12022-023-09784-y
Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells

Fetched: September 22nd, 2023, 5:03am GMT by Zeyu Wang

Chin Med J (Engl). 2023 Sep 20;136(18):2210-2220. doi: 10.1097/CM9.0000000000002675. Epub 2023 Jul 24.

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated.

METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry.

RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 .

CONCLUSION: ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.

PMID:37488674 | PMC:PMC10508381 | DOI:10.1097/CM9.0000000000002675
Drug resistance and new therapies in gallbladder cancer

Fetched: September 21st, 2023, 5:01am GMT by Yuxin Sun

Drug Discov Ther. 2023 Sep 15;17(4):220-229. doi: 10.5582/ddt.2023.01013. Epub 2023 Aug 17.

ABSTRACT

Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves as a primary treatment option in cases where surgery is not feasible. However, the emergence of chemoresistance poses a significant challenge to the effectiveness of chemotherapy, ultimately resulting in a poor prognosis. Despite extensive research on mechanisms of chemotherapeutic resistance in oncology, the underlying mechanisms of chemoresistance in GBC remain poorly understood. In this review, we present the findings from the last decade on the molecular mechanisms of chemotherapeutic resistance in GBC. We hope that these insights may provide novel therapeutic and experimental targets for further investigations into this lethal disease.

PMID:37587052 | DOI:10.5582/ddt.2023.01013
ASO Author Reflections: Precision in Gallbladder Cancer Care: Present Challenges and Future Directions

Fetched: September 21st, 2023, 5:01am GMT by Sebastian Mellado

Ann Surg Oncol. 2023 Oct;30(11):6601-6602. doi: 10.1245/s10434-023-14062-6. Epub 2023 Aug 7.

NO ABSTRACT

PMID:37548834 | DOI:10.1245/s10434-023-14062-6
Patient Experiences After Aborted Cancer Surgery: A Qualitative Study

Fetched: September 21st, 2023, 5:01am GMT by Lena Stevens

Ann Surg Oncol. 2023 Oct;30(11):6844-6851. doi: 10.1245/s10434-023-14046-6. Epub 2023 Aug 4.

ABSTRACT

BACKGROUND: Surgical resection is a necessary component of curative-intent treatment for most solid-organ cancers but is occasionally aborted, most often due to occult metastatic disease or unanticipated unresectability. Despite its frequency, little research has been performed on the experiences, care needs, and treatment preferences of patients who experience an aborted cancer surgery.

METHODS: Semistructured interviews of patients who had previously experienced an aborted cancer surgery were conducted, focusing on their recalled experiences and stated preferences. All interviews were audio recorded, transcribed, and coded by two independent researchers by using NVivo 12. An integrative approach to qualitative analysis was used-both inductive and deductive methods-and iteratively identifying themes until saturation was reached.

RESULTS: Fifteen patients with an aborted cancer surgery participated in the interviews. Cancer types included pancreatic (n = 9), cholangiocarcinoma (n = 3), hepatocellular carcinoma (n = 1), gallbladder (n = 1), and neuroendocrine (n = 1). The most common reasons for aborting surgery included local tumor unresectability (n = 8) and occult metastatic disease (n = 7). Five subthemes that characterized the patient experience following an aborted cancer surgery emerged, including physical symptoms, emotional responses, impact on social and life factors, coping mechanisms, and support received.

CONCLUSIONS: This qualitative study characterizes the impact of aborted cancer surgery on multiple domains of quality of life: physical, emotional, social, and existential. These results highlight the importance of developing patient-centered interventions that focus on enhancing quality of life after aborted cancer surgery.

PMID:37540329 | DOI:10.1245/s10434-023-14046-6
Identification of gallbladder cancer by direct near-infrared measurement of deuterated chloroform-extracted organic phase from human bile

Fetched: September 21st, 2023, 5:01am GMT by Yunjung Kim

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Dec 15;303:123139. doi: 10.1016/j.saa.2023.123139. Epub 2023 Jul 11.

ABSTRACT

A simple near-infrared (NIR) spectroscopic scheme enabling direct measurement of organic phase extracted from human bile with no spectral interference from the extraction solvent was demonstrated for identification of gallbladder (GB) cancer. This scheme is used to recognize the different lipid contents in bile samples from GB cancer patients using NIR spectroscopy for disease identification. To this end, the extraction solvent should provide an absorption-free NIR region to observe peaks of related metabolite. For this purpose, deuterated chloroform (CDCl3) is uniquely suited as an extraction medium because it has few absorption peaks in the 4380-4100 cm^-1 range, where intense peaks for lipids and cholesterol are located. This exploratory study used 37 bile samples (obtained from five normal subjects and nine GB polyp, 11 gallstone, six hepatocellular carcinoma (HCC), and six GB cancer patients). The transmission NIR spectra of the organic phases extracted using CDCl3 in a commercial glass vial were directly measured. The peak intensities of the GB cancer samples were lower than those of the other samples, and the differences were statistically significant, with a confidence interval greater than 99.0%. The lower lipid and cholesterol contents in the organic phases of the GB cancer samples were effectively identified in the corresponding NIR spectra. Therefore, the proposed NIR scheme is simpler and faster than the previous infrared (IR) measurement approach that requires solvent drying to highlight the buried metabolite peaks under a solvent absorption band.

PMID:37463552 | DOI:10.1016/j.saa.2023.123139
Analysis of the Extent of Liver Oncological Extended Resection for Incidental Gallbladder Cancer: How Much Is Too Much?

Fetched: September 21st, 2023, 5:01am GMT by Eduardo A Vega

Ann Surg Oncol. 2023 Oct;30(11):6594-6600. doi: 10.1245/s10434-023-13861-1. Epub 2023 Jul 17.

ABSTRACT

BACKGROUND: Liver resection is pivotal in treating incidental gallbladder cancer (IGBC). However, the adequate volume of liver resection remains controversial.

METHODS: A cross-sectional retrospective analysis was performed on resected IGBC patients between 1999 and 2018. Morbidity was evaluated according to the Clavien-Dindo classification. The theoretical volume of a 2-cm and 1.5-cm wedge liver resection was calculated (105 cm³ and 77.5 cm³, respectively) and used as reference. Overall survival (OS) was estimated using Kaplan-Meier and Cox regression analyses.

RESULTS: Among 111 patients re-resected for IGBC, 84 provided sufficient data to calculate liver resection volume. Patients with a resection volume ≥ 105 cm³ had a higher rate of overall morbidity (P = 0.001) and length of stay (P = 0.012), with no difference in mortality. There was no significant difference in OS according to residual cancer or T-category. A resection volume ≥ 77.5 cm³ was more frequent in T ≥ 3 than in T1-2 patients (P = 0.026), and residual cancer was higher (P = 0.041) among patients with ≥ 77.5 cm³ resected. Cox multivariate regression showed that residual cancer (HR = 11.47, P < 0.001), perineural/lymphovascular invasion (HR = 2.48, P = 0.021), and Clavien-Dindo ≥ IIIa morbidity (HR = 5.03, P = 0.003) predict worse OS, but not liver volume resection.

CONCLUSION: There are no significant differences in OS based on resected liver volume of IGBC, when R0 is achieved. There is a significant difference in morbidity and length of stay when liver wedges are ≥ 105 cm³, which is lost when analyzed by Clavien-Dindo ≥ IIIa. A 77.5-105 cm³ resection is indicated in ≥ T3 patients, minimizing morbidity risk, while addressing concerns of overall survival.

PMID:37460736 | DOI:10.1245/s10434-023-13861-1
Tumor mutation burden in gastro-entero-pancreatic-neuroendocrine neoplasms

Fetched: September 19th, 2023, 5:02am GMT by Sun Young Jeong

J Gastrointest Oncol. 2023 Aug 31;14(4):1707-1714. doi: 10.21037/jgo-22-1190. Epub 2023 Jul 10.

ABSTRACT

BACKGROUND: As rare tumors, there are limited treatment options for neuroendocrine neoplasms (NENs). Recently, microsatellite instability (MSI) and tumor mutation burden (TMB) have been emerging as potential biomarkers in various tumors. However, there is a lack of research on the use of these biomarkers in gastro-entero-pancreatic (GEP)-NENs.

METHODS: We analyzed 31 patients diagnosed with GEP-NEN between 2013 to 2022. The TMB and MSI analyses using next-generation sequencing (NGS) were performed for all patients. The TruSightTM Oncology 500 assay from Illumina was used as the NGS panel.

RESULTS: Out of the 31 patients analyzed, the most frequent primary origin was the pancreas (12 patients, 38.7%), followed by the stomach (4 patients, 12.9%), gallbladder (4 patients, 12.9%), rectum (7 patients, 22.6%), small bowel (2 patients, 6.5%), and bile duct (1 patient, 3.2%). Among these patients, 19 (61.3%) were diagnosed with well-differentiated neuroendocrine tumors, with grade 2 being the most common (15 patients, 48.4%), followed by grade 3 (3 patients, 9.7%) and grade 1 (1 patient, 3.2%). Neuroendocrine carcinoma was confirmed in 12 patients (38.7%). The median number of metastases was 2.0 [interquartile range (IQR), 1.0-3.0], and the liver was the most common site of metastasis (23 patients, 74.2%). The median TMB was 4.7 (IQR, 3.1-6.3) mutations/Mb, and all tumors were classified as microsatellite stability (MSS). Only one patient had a high TMB (266.4 mutations/Mb), which was a grade 3 neuroendocrine tumor originating from the pancreas. The TMB value did not vary depending on the primary tumor site or World Health Organization (WHO) grade.

CONCLUSIONS: This analysis showed that, despite very low incidence, there are GEP-NENs with high TMB. For precision medicine, testing for MSI and TMB is needed for this tumor type.

PMID:37720428 | PMC:PMC10502559 | DOI:10.21037/jgo-22-1190
Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer

Fetched: September 19th, 2023, 5:02am GMT by Sarun Juengpanich

Nat Commun. 2023 Sep 14;14(1):5699. doi: 10.1038/s41467-023-41389-1.

ABSTRACT

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

PMID:37709778 | PMC:PMC10502062 | DOI:10.1038/s41467-023-41389-1
Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection

Fetched: September 16th, 2023, 5:02am GMT by Jiasheng Cao

Cancer Med. 2023 Aug;12(16):16744-16755. doi: 10.1002/cam4.6297. Epub 2023 Jun 27.

ABSTRACT

BACKGROUND: The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC.

METHODS: We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease-free survival (DFS), surgery-related outcomes, and surgical approaches were collected.

RESULTS: A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p < 0.001). There was no significance in OS (p = 0.790), DFS (p = 0.580), and surgery-related outcomes (all p > 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery-related outcomes between different TTT groups of incidental GBC patients (all p > 0.05).

CONCLUSIONS: Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery-related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

PMID:37366278 | PMC:PMC10501227 | DOI:10.1002/cam4.6297
COVID-19 and Malignancy: What is the Association? A Case Report and Review of the Literature

Fetched: September 15th, 2023, 5:02am GMT by Safi Alqatari

Med Arch. 2023;77(3):237-240. doi: 10.5455/medarh.2023.77.237-240.

ABSTRACT

BACKGROUND: After more than two years since Coronavirus disease 2019 (COVID-19) was first identified as a global pandemic, we still observe a variety of clinical presentations. From asymptomatic carriers to severely ill patients. Most patients infected with COVID-19 present with respiratory symptoms.

OBJECTIVE: However, case reports of different presentations were published, none of them highlighted the potential of COVID-19 to facilitate the manifestation of hidden malignancy, particularly, gallbladder carcinoma.

CASE PRESENTATION: In this report, we present a case of a 77-year-old Saudi lady with multiple comorbidities, presented with an acute confusional state after one month of having asymptomatic COVID-19 infection. Significantly, she was completely functional prior to her presentation and did not manifest any symptoms such as weight loss or fever. Her clinical assessment demonstrated severe abdominal tenderness and guarding on palpation. Computed tomography scans of the abdomen showed perforated gallbladder cancer.

CONCLUSION: Among multiple clinical presentations related to COVID-19 infection, gastrointestinal manifestations are the most common extrapulmonary symptoms, ranging from mild to more severe symptoms. Acute abdomen with perforated viscus should be kept in mind as a differential diagnosis when dealing with COVID-19 infected patients who present with severe abdominal pain. The current case report highlights one of unusual presentations of COVID-19 infection.

PMID:37700926 | PMC:PMC10495138 | DOI:10.5455/medarh.2023.77.237-240
Gallbladder Emulating Hepatic Haemangioma On Gastrointestinal Bleed Scan

Fetched: September 14th, 2023, 5:02am GMT by Kinza Abdul Hye

J Pak Med Assoc. 2023 Aug;73(8):1747-1748. doi: 10.47391/JPMA.23-60.

ABSTRACT

Tc-99m labelled erythrocyte scan is a sensitive method for detection of gastrointestinal (GI) bleed and liver haemangioma but false positive results can occur, as in this case gallbladder is visualized which is not a common finding. Single‑photon emission computed tomography/computed tomography (SPECT-CT) is helpful to avoid such false‑positive results.

PMID:37697780 | DOI:10.47391/JPMA.23-60
Gallbladder cancer mimicking perihilar cholangiocarcinoma-considerable rate of postoperative reclassification with implications for prognosis

Fetched: September 14th, 2023, 5:02am GMT by Lynn E Nooijen

World J Surg Oncol. 2023 Sep 11;21(1):286. doi: 10.1186/s12957-023-03171-x.

ABSTRACT

BACKGROUND: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3-15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA.

METHODS: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009-May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan-Meier method.

RESULTS: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15-25 months) for patients with pCCA and 17 months (95% CI 11-23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3-17 months) compared 17 months (95% CI 15-19 months) for patients with pCCA (p = 0.010).

CONCLUSIONS: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies.

PMID:37697321 | PMC:PMC10494342 | DOI:10.1186/s12957-023-03171-x
DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP

Fetched: September 12th, 2023, 5:01am GMT by Jie Huang

Cancer Immunol Immunother. 2023 Oct;72(10):3203-3216. doi: 10.1007/s00262-023-03484-6. Epub 2023 Jul 8.

ABSTRACT

BACKGROUND: Although disc large associated protein family (DLGAP5) has been reported to be involved in a variety of tumor pathologic processes, its expression and mechanism in gallbladder cancer (GBC) are still uncertain. Macrophages were divided into M1 and M2 macrophages. TAM is more closely defined as M2 polarized macrophages, which plays a key role in cancer progression.

OBJECTIVE: To clarify the role of disc large associated protein family (DLGAP5) in gallbladder cancer (GBC) progression and investigate the mechanism.

METHODS: Differential genes in 10 normal paracancer tissues and 10 GBC tissues in GSE139682 from NCBI-GEO were analyzed by R language. Bioinformation analysis and clinical sample analysis were performed to detect DLGAP5 expression in GBC and its correlation with prognosis. CCK-8, EDU, transwell, wound closure, and Immunoblot were performed to detect its effects on the function of GBC cells. GST-pulldown showed the direct interact between DLGAP5 and cAMP. Macrophage polarization assay was further conducted to detect the effects of DLGAP5 on macrophage M2 polarization. The tumor growth assays were further conducted to confirm its role in mice.

RESULTS: Biological analysis and clinical samples confirmed that DLGAP5 was increased in GBC and strongly related to poor prognosis in patients with GBC. After overexpression of DLGAP5 in GBC cell lines, such as GBC-SD and NOZ cells, cell proliferation and migration were enhanced, and macrophages were polarized to M2. However, after DLGAP5 is knocked down, there is opposite effect. Mechanistically, DLGAP5 promotes the growth and migration of GBC-SD and NOZ cells and the M2 polarization of THP-1-derived macrophages by activating cyclic adenosine monophosphate (cAMP) pathway. In vivo, GBC-SD with DLGAP5 knockdown was subcutaneously injected into nude mice. It was found that after DLGAP5 knockdown, both tumor volume and tumor were reduced, and indicators related to proliferation and M2 polarization decreased.

CONCLUSION: Our study shows that DLGAP5 is significantly elevated in GBC and is strongly related to poor prognosis in patients with GBC. DLGAP5 promotes GBC proliferation, migration, and M2 polarization of macrophages through cAMP pathway, which provides a theoretical basis for the treatment of GBC and may become a promising therapeutic target.

PMID:37421434 | DOI:10.1007/s00262-023-03484-6
Exocrine pancreatic cancer as a second primary malignancy: A population-based study

Fetched: September 9th, 2023, 5:01am GMT by Mee Joo Kang

Ann Hepatobiliary Pancreat Surg. 2023 Sep 8. doi: 10.14701/ahbps.23-053. Online ahead of print.

ABSTRACT

BACKGROUNDS/AIMS: Although cancer survivors are at higher risk of developing second primary malignancies, cancer surveillance strategies for them have not yet been established. This study aimed to identify first primary cancers that had high risks of developing second primary exocrine pancreatic cancer (EPC).

METHODS: Data on individuals diagnosed with primary cancers between 1993 and 2017 were obtained from the Korea Central Cancer Registry. The standardized incidence ratios (SIRs) of second primary EPCs were analyzed according to the primary tumor sites and follow-up periods.

RESULTS: Among the 3,205,840 eligible individuals, 4,836 (0.15%) had second primary EPCs, which accounted for 5.8% of the total EPC patients in Korea. Between 1 and 5 years after the diagnosis of first primary cancers, SIRs of second primary EPCs were increased in patients whose first primary cancers were in the bile duct (males 2.99; females 5.03) in both sexes, and in the small intestine (3.43), gallbladder (3.21), and breast (1.26) in females. Among those who survived 5 or more years after the diagnosis of first primary cancers, SIRs of second primary EPCs were elevated in patients whose first primary cancers were in the bile duct (males 2.61; females 2.33), gallbladder (males 2.29; females 2.22), and kidney (males 1.39; females 1.73) in both sexes, and ovary (1.66) and breast (1.38) in females.

CONCLUSIONS: Survivors of first primary bile duct, gallbladder, kidney, ovary, and female breast cancer should be closely monitored for the occurrence of second primary EPCs, even after 5 years of follow-up.

PMID:37680115 | DOI:10.14701/ahbps.23-053
Clinical features and outcomes analysis of Gallbladder neuroendocrine carcinoma

Fetched: September 9th, 2023, 5:01am GMT by Man Jiang

J Cancer Res Ther. 2023 Aug;19(4):910-916. doi: 10.4103/jcrt.jcrt_1959_21.

ABSTRACT

PURPOSE: Gallbladder neuroendocrine carcinoma (GB-NEC) is an uncommon and highly malignant tumor. This research aimed to investigate the clinical characteristics and prognostic factors of GB-NEC.

MATERIALS AND METHODS: Our survey of case reports from January 2000 to May 2022 screened a total of 84 patients with complete data who received surgical resection for gallbladder NEC. Log-rank generated survival curves using the Kaplan-Meier method for univariate survival analysis. To identify GB-NEC independent prognostic indicators for overall survival (OS), univariate and multivariate Cox proportional hazard analyses were conducted.

RESULTS: These patients consisted of 25 men and 59 women, with an average age of 60 (range 29-85). Patients under 60 years old made up 44% of the population, while patients over 60 made up 56%. Fifty-three tumors were advanced pathologic TNM stage III and IV. After surgery, 44 patients underwent chemotherapy or radiotherapy. The median OS of 84 patients with GB-NEC was 16.8 months. In univariate and multivariate analysis, tumor size (diameter ≥5 cm), TNM tumor stage, and the receipt of postoperative adjuvant chemotherapy are independent factors influencing the prognosis of patients with GB-NEC.

CONCLUSION: Tumor size (diameter ≥5 cm) and TNM tumor stage were independently related to a shorter OS. An enhanced OS was independently linked to receiving postoperative adjuvant chemotherapy.

PMID:37675716 | DOI:10.4103/jcrt.jcrt_1959_21
The Demographic and Clinicopathological Characteristics of Hepatopancreatobiliary Cancers From a Specialized Center in India

Fetched: September 8th, 2023, 5:01am GMT by Puja Sahai

Cureus. 2023 Aug 6;15(8):e43026. doi: 10.7759/cureus.43026. eCollection 2023 Aug.

ABSTRACT

Introduction Hepatopancreatobiliary (HPB) cancers are a distinct group requiring specialized multidisciplinary care. The present study was an analysis of HPB cancers. Methods The institutional data for two years from 2017 to 2018 was retrieved from the hospital-based cancer registry (HBCR) database in Excel format (Microsoft^® Corp., Redmond, WA). The demographic details, method of diagnosis, tumor characteristics, and disease extent of the patients with HPB primary sites were retrospectively analyzed. Results Out of the 1417 patients with HPB malignancies, 1193 were analyzed. Most of the patients at our center hailed from North India. The distribution of HPB cancers was as follows: hepatocellular carcinoma (HCC) (n=717, 60.1%), gallbladder (GB) (n=230, 19.3%), periampullary carcinoma (n=76, 6.37%), head of the pancreas (HOP) (n=55, 4.61%), extrahepatic bile duct (EBD) (n=53, 4.44%), intrahepatic bile duct (IBD) (n=32, 2.68%), and body of the pancreas (BOP) (n=30, 2.52%). The most common disease presentation of HPB cancers was in the seventh and sixth decades of life. Male predominance was seen in all HPB cancers except in GB with a higher incidence in females. The predominant cause of chronic liver disease (CLD) with HCC was viral-related (53.7%) with hepatitis B virus (HBV) (34.3%) higher than hepatitis C virus (HCV) (19.2%) followed by non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) (24.8%) and then alcohol. Adenocarcinoma was the most common morphology in pancreatobiliary malignancies. The disease presentation was locoregional in 63.4% of HCC, 69.7% of periampullary carcinoma, and 50.9% of HOP cases. The patients with EBD and IBD cancers presented commonly with locoregional disease extent in 60.4% and 62.5%, respectively. Perihilar subsite was more commonly detected (71.7%) as compared to the distal one in the patients with EBD cancers. The patients with GB cancers (GBC) presented with distant metastases in 53.5% and locoregional disease in 33%. Distant metastases were present in 76.7% of the patients with BOP cancers. The liver was a common site of distant metastases in GB, periampullary, and pancreatic cancers. Conclusions The present study highlights the characteristics and the variations in disease presentation in different primary tumor sites of HPB cancers. In view of the common locoregionally advanced disease presentation of HCC, the patients with CLD need surveillance for the early detection of lesions. As the patients with HPB cancers show advanced disease presentation, effective locoregional and systemic therapies are needed.

PMID:37674951 | PMC:PMC10479249 | DOI:10.7759/cureus.43026
Exploring the Chemical and Biological Potential of Jamun (Syzygium cumini (L.) Skeels) Leaves: A Comprehensive Review

Fetched: September 7th, 2023, 5:02am GMT by Neeraj Kumari

Chem Biodivers. 2023 Sep;20(9):e202300479. doi: 10.1002/cbdv.202300479. Epub 2023 Sep 6.

ABSTRACT

Leaves of jamun collected as agro by-produce during the cultivation of jamun is traditionally used as ayurvedic medicine to treat diabetes, gall bladder stones and other ailments. Most of the beneficial effects of jamun leaves are associated with phytochemicals found in jamun leaves such as gallic acid, tannins, mallic acid, flavonoids, essential oils, jambolin, ellagic acid, jambosine, antimellin and betulinic acid. Jamun possess curative activities like anticancer, antidiabetic, antifertility, anti-inflammatory, antidiarrheal, antimicrobial, antinociceptive, antioxidant, antiradiation, chemotherapeutic, and gastroprotective. The main goal of this review article is to provide information on the nutritional content, phytochemical composition and health promoting properties of jamun leaves. The review of literature based on the phytochemical composition and health promoting benefits of the jamun leaves, suggests that leaves can be used as potential constituent in the formulation of pharmacological drugs. From the review literature it is found that clinical, in-vivo, in-vitro studies are still required to check the health promoting effects of jamun leaves extracts on humans.

PMID:37667613 | DOI:10.1002/cbdv.202300479
A case of malignant ascites of neuroendocrine carcinoma of the gallbladder diagnosed by endoscopic ultrasound-guided fine-needle aspiration

Fetched: September 5th, 2023, 5:02am GMT by Mihoko Ishikawa

Diagn Cytopathol. 2023 Oct;51(10):658-661. doi: 10.1002/dc.25199. Epub 2023 Jul 28.

NO ABSTRACT

PMID:37501588 | DOI:10.1002/dc.25199
Adjuvant chemoradiotherapy vs chemotherapy for resectable biliary tract cancer: a propensity score matching analysis based on the SEER database

Fetched: September 5th, 2023, 5:02am GMT by Yueting Zhu

Eur J Med Res. 2023 Sep 1;28(1):310. doi: 10.1186/s40001-023-01299-w.

ABSTRACT

BACKGROUND: Although the role of adjuvant chemotherapy (CT) for resectable biliary tract cancer (BTC) is gradually recognized, the benefit of adjuvant chemoradiotherapy (CRT) is still controversial. Our study is designed to compare the prognosis of CRT versus CT in BCT patients.

METHODS: Clinicopathologic characteristics of patients with operable gallbladder cancer (GBCA), intrahepatic bile duct cancer (IHBDC), or extrahepatic bile duct cancer (EHBDC) were obtained from the Surveillance, Epidemiology and End Results (SEER) database (2004-2015). Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Selection bias were reduced by propensity-score matching (PSM). Kaplan-Meier analysis was used to estimate the survival time.

RESULTS: Within 922 patients, 53.9% received adjuvant CRT, and 46.1% received adjuvant CT. Multivariate analysis showed age, primary tumor site, T stage, N stage, tumor size, number of removed lymph nodes, and treatment were independent risk factors for OS. Similar improvement of CRT on survival was identified by PSM in the matched cohort compared with CT (28.0 months vs. 25.0 months, p = 0.033), particularly in GBCA cohort (25.0 months vs. 19.0 months, p = 0.003). Subgroup analysis indicated CRT improved outcomes of patients with age ≥ 60, female, lymph nodes positive, tumor size ≥ 5 cm, and none removed lymph node diseases.

CONCLUSION: Adjuvant CRT correlated with improved survival in patients with resected BTC compared with adjuvant CT, particularly in GBCAs. In addition, patients with age ≥ 60, female, lymph nodes positive, tumor size ≥ 5 cm, and none removed lymph node diseases may receive more benefits from adjuvant CRT.

PMID:37658421 | PMC:PMC10472568 | DOI:10.1186/s40001-023-01299-w
Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma

Fetched: September 2nd, 2023, 5:02am GMT by Yunfeng Li

Cancer Med. 2023 Aug;12(15):16076-16086. doi: 10.1002/cam4.6261. Epub 2023 Jun 21.

ABSTRACT

BACKGROUND: Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment.

METHODS: We retrospectively reviewed 113 BTC patients who underwent curative-intent surgery and had available tumor sequencing data. Disease-free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS.

RESULTS: Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04-0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51-5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups.

CONCLUSIONS: Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.

PMID:37341068 | PMC:PMC10469713 | DOI:10.1002/cam4.6261
Pemetrexed and Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer Who Failed Gemcitabine-containing Chemotherapy: A Phase II Single-arm Prospective Study

Fetched: September 2nd, 2023, 5:02am GMT by Sung Hee Lim

Anticancer Res. 2023 Sep;43(9):4161-4167. doi: 10.21873/anticanres.16607.

ABSTRACT

BACKGROUND/AIM: No standard treatment is currently recommended for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin. We aimed to evaluate the efficacy and safety of a pemetrexed and erlotinib combination in patients with BTC previously treated with gemcitabine.

PATIENTS AND METHODS: This phase II, open-label, single-arm study enrolled patients with BTC who had previously failed gemcitabine-based first-line chemotherapy. Patients were treated with pemetrexed as a 500 mg/m² intravenous infusion on day 1 for three weeks and erlotinib 100 mg daily until disease progression or unacceptable toxicity. The primary endpoint was the overall response rate (ORR).

RESULTS: The study enrolled 20 patients with BTC, including 12 (60%) with intrahepatic cholangiocarcinoma (IHCC), 3 (15%) with extrahepatic cholangiocarcinoma (EHCC), and 5 (25%) with gallbladder cancer (GBC). The ORR was 5%, and the disease control rate (DCR) was 55%. As of the cutoff point of March 31, 2023, the median progression-free survival (PFS) was 2.3 months [95% confidence interval (CI)=0.00-4.74] and the median overall survival (OS) was 5.6 months (95%CI=2.28-8.87). Patients with EHCC showed longer PFS and OS compared to patients with IHCC or GBC, but the differences were not significant. A baseline CEA greater than the upper normal limit was the only significant prognostic factor for a worse OS rate. The only treatment-related adverse event (TRAE) with severity grade ≥3 was anemia (5%).

CONCLUSION: Salvage chemotherapy with pemetrexed plus erlotinib was well-tolerated and showed marginal clinical activity in BTC patients after failure to gemcitabine-based chemotherapy.

PMID:37648323 | DOI:10.21873/anticanres.16607
Effect of different surgical options on the long-term survival of stage I gallbladder cancer: a retrospective study based on SEER database and Chinese Multi-institutional Registry

Fetched: September 1st, 2023, 5:02am GMT by Zuhong Ji

J Cancer Res Clin Oncol. 2023 Oct;149(13):12297-12313. doi: 10.1007/s00432-023-05116-z. Epub 2023 Jul 11.

ABSTRACT

BACKGROUND: Gallbladder cancer (GC) is a uncommon and highly malignant tumor. This study compared the effects of simple cholecystectomy (SC) and extended cholecystectomy (EC) on the long-term survival of stage I GC.

METHODS: Patients with stage I GC between 2004 and 2015 in the SEER database were selected. Meanwhile, this study collected the clinical information of patients with stage I GC admitted to five medical centers in China between 2012 and 2022. Using clinical data from patients in the SEER database as a training set to construct a nomogram, which was validated in Chinese multicenter patients. Long-term survival between SC and EC were distinguished using propensity score matching (PSM).

RESULTS: A total of 956 patients from the SEER database and 82 patients from five Chinese hospitals were included in this study. The independent prognostic factors were age, sex, histology, tumor size, T stage, grade, chemotherapy and surgical approach by multivariate Cox regression analysis. We developed a nomogram based on these variables. The nomogram has been proved to have good accuracy and discrimination in internal and external validation. The cancer-specific survival (CSS) and overall survival of patients receiving EC were better than those of SC before and after the propensity score match. The interaction test showed that EC was associated with better survival in patients aged ≥ 67 years (P = 0.015) and in patients with T1b and T1NOS (P < 0.001).

CONCLUSION: A novel nomogram to predict CSS in patients with stage I GC after SC or EC. Compared with SC, EC for stage I GC had higher OS and CSS, especially in specific subgroups (T1b, T1NOS, and age ≥ 67 years).

PMID:37432456 | DOI:10.1007/s00432-023-05116-z
ELF3 suppresses gallbladder cancer development through downregulation of the EREG/EGFR/mTOR complex 1 signalling pathway

Fetched: September 1st, 2023, 5:02am GMT by Takeharu Nakamura

J Pathol. 2023 Sep;261(1):28-42. doi: 10.1002/path.6144. Epub 2023 Jun 22.

ABSTRACT

The prognosis of gallbladder cancer (GBC) remains poor, and a better understanding of GBC molecular mechanisms is important. Genome sequencing of human GBC has demonstrated that loss-of-function mutations of E74-like ETS transcription factor 3 (ELF3) are frequently observed, with ELF3 considered to be a tumour suppressor in GBC. To clarify the underlying molecular mechanisms by which ELF3 suppresses GBC development, we performed in vivo analysis using a combination of autochthonous and allograft mouse models. We first evaluated the clinical significance of ELF3 expression in human GBC tissues and found that low ELF3 expression was associated with advanced clinical stage and deep tumour invasion. For in vivo analysis, we generated Pdx1-Cre; Kras^G12D ; Trp53^R172H ; Elf3^f/f (KPCE) mice and Pdx1-Cre; Kras^G12D ; Trp53^R172H ; Elf3^wt/wt (KPC) mice as a control and analysed their gallbladders histologically. KPCE mice developed larger papillary lesions in the gallbladder than those developed by KPC mice. Organoids established from the gallbladders of KPCE and KPC mice were analysed in vitro. RNA sequencing showed upregulated expression of epiregulin (Ereg) in KPCE organoids, and western blotting revealed that EGFR/mechanical targets of rapamycin complex 1 (mTORC1) were upregulated in KPCE organoids. In addition, ChIP assays on Elf3-overexpressing KPCE organoids showed that ELF3 directly regulated Ereg. Ereg deletion in KPCE organoids (using CRISPR/Cas9) induced EGFR/mTORC1 downregulation, indicating that ELF3 controlled EGFR/mTORC1 activity through regulation of Ereg expression. We also generated allograft mouse models using KPCE and KPC organoids and found that KPCE organoid allograft tumours exhibited poorly differentiated structures with mTORC1 upregulation and mesenchymal phenotype, which were suppressed by Ereg deletion. Furthermore, EGFR/mTORC1 inhibition suppressed cell proliferation and epithelial-mesenchymal transition in KPCE organoids. Our results suggest that ELF3 suppresses GBC development via downregulation of EREG/EGFR/mTORC1 signalling. EGFR/mTORC1 inhibition is a potential therapeutic option for GBC with ELF3 mutation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

PMID:37345534 | DOI:10.1002/path.6144
Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers

Fetched: August 30th, 2023, 5:01am GMT by Sini Takala

Scand J Surg. 2023 Sep;112(3):147-156. doi: 10.1177/14574969231181228. Epub 2023 Jun 28.

ABSTRACT

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies.

METHODS: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland.

RESULTS: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up.

CONCLUSIONS: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

PMID:37377127 | DOI:10.1177/14574969231181228
Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis

Fetched: August 29th, 2023, 5:01am GMT by Giorgio Frega

Cells. 2023 Aug 19;12(16):2098. doi: 10.3390/cells12162098.

ABSTRACT

BACKGROUND: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.

METHODS: Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible.

RESULTS: A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs-15 studies), perihilar-distal CCAs (p/dCCAs-7 studies), and gallbladder cancer (GBC-5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively.

CONCLUSION: From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.

PMID:37626908 | PMC:PMC10453268 | DOI:10.3390/cells12162098
A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada

Fetched: August 29th, 2023, 5:01am GMT by Ravi Ramjeesingh

Curr Oncol. 2023 Jul 25;30(8):7132-7150. doi: 10.3390/curroncol30080517.

ABSTRACT

Biliary tract cancers (BTC) are rare and aggressive tumors with poor prognosis. Radical surgery offers the best chance for cure; however, most patients present with unresectable disease, and among those receiving curative-intent surgery, recurrence rates remain high. While other locoregional therapies for unresectable disease may be considered, only select patients may be eligible. Consequently, systemic therapy plays a significant role in the treatment of BTC. In the adjuvant setting, capecitabine is recommended following curative-intent resection. In the neoadjuvant setting, systemic therapy has mostly been explored for downstaging in borderline resectable tumours, although evidence for its routine use is lacking. For advanced unresectable or metastatic disease, gemcitabine-cisplatin plus durvalumab has become the standard of care, while the addition of pembrolizumab to gemcitabine-cisplatin has also recently demonstrated improved survival compared to chemotherapy alone. Following progression on gemcitabine-cisplatin, several chemotherapy combinations and biomarker-driven targeted agents have been explored. However, the optimum regimen remains unclear, and access to targeted agents remains challenging in Canada. Overall, this article serves as a practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease.

PMID:37622998 | PMC:PMC10453186 | DOI:10.3390/curroncol30080517
Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention

Fetched: August 29th, 2023, 5:01am GMT by Enrique Almanza-Aguilera

Semin Cancer Biol. 2023 Oct;95:103-119. doi: 10.1016/j.semcancer.2023.08.001. Epub 2023 Aug 4.

ABSTRACT

Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms.

PMID:37543179 | DOI:10.1016/j.semcancer.2023.08.001
Isolated IgG4-related cholecystitis mimicking an advanced gallbladder cancer: Don't fall into the trap

Fetched: August 29th, 2023, 5:01am GMT by Arthur Marichez

Dig Liver Dis. 2023 Sep;55(9):1297-1298. doi: 10.1016/j.dld.2023.05.031. Epub 2023 Jun 12.

NO ABSTRACT

PMID:37316364 | DOI:10.1016/j.dld.2023.05.031
Short- and long-term outcomes of laparoscopic radical gallbladder resection for gallbladder carcinoma: A multi-institutional retrospective study in Japan

Fetched: August 29th, 2023, 5:01am GMT by Takuya Minagawa

J Hepatobiliary Pancreat Sci. 2023 Aug;30(8):1046-1054. doi: 10.1002/jhbp.1342. Epub 2023 Jun 12.

ABSTRACT

BACKGROUND/PURPOSE: Laparoscopic resection of gallbladder carcinomas remains controversial. This study aimed to evaluate the surgical and oncological outcomes of laparoscopic procedures for suspected gallbladder carcinoma (GBC).

METHODS: In this retrospective study, data regarding suspected GBC treated with laparoscopic radical cholecystectomy before 2020 in Japan, was included. Patient characteristics, surgical procedure details, surgical outcomes, and long-term outcomes were analyzed.

RESULTS: Data of 129 patients with suspected GBC who underwent laparoscopic radical cholecystectomy were retrospectively collected from 11 institutions in Japan. Among them, 82 patients with pathological GBC were included in the study. Laparoscopic gallbladder bed resection was performed in 114 patients and laparoscopic resection of segments IVb and V was performed in 15 patients. The median operation time was 269 min (range: 83-725 min), and the median intraoperative blood loss was 30 mL (range: 0-950 mL). The conversion and postoperative complication rates were 8% and 2%, respectively. During the follow-up period, the 5-year overall survival rate was 79% and the 5-year disease-free survival rate was 87%. Recurrence was detected in the liver, lymph nodes, and other local tissues.

CONCLUSION: Laparoscopic radical cholecystectomy is a treatment option with potential favorable outcomes in selected patients with suspected GBC.

PMID:37306108 | DOI:10.1002/jhbp.1342
Cell Surface B2m-Free Human Leukocyte Antigen (HLA) Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?

Fetched: August 27th, 2023, 5:01am GMT by Mepur H Ravindranath

Biomolecules. 2023 Jul 28;13(8):1178. doi: 10.3390/biom13081178.

ABSTRACT

Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, bronchi, epidermis, esophagus, breast, stomach, ilium, colorectum, gall bladder, urinary bladder, seminal vesicles ovarian epithelia, endometrium, thymus, spleen, and lymphocytes. They are upregulated on immune cells upon activation by proinflammatory cytokines, anti-CD3 antibodies, antibiotics (e.g., ionomycin), phytohemagglutinin, retinoic acid, and phorbol myristate acetate. Their density on the cell surface remains high as long as the cells remain in an activated state. After activation-induced upregulation, the Face-2 molecules undergo homo- and hetero-dimerization (Face-3 and Face-4). Alterations in the redox environment promote dimerization. Heterodimerization can occur among and between the alleles of different haplotypes. The glycosylation of these variants differ from that of Face-1, and they may occur with bound exogenous peptides. Spontaneous arthritis occurs in HLA-B27+ mice lacking B2m (HLA-B27+ B2m-/-) but not in HLA-B27+ B2m+/- mice. The mice with HLA-B27 in Face-2 spontaneous configuration develop symptoms such as changes in nails and joints, hair loss, and swelling in paws, leading to ankyloses. Anti-HC-specific mAbs delay disease development. Some HLA-I polyreactive mAbs (MEM series) used for immunostaining confirm the existence of B2m-free variants in several cancer cells. The upregulation of Face-2 in human cancers occurs concomitantly with the downregulation of intact HLAs (Face-1). The HLA monomeric and dimeric variants interact with inhibitory and activating ligands (e.g., KIR), growth factors, cytokines, and neurotransmitters. Similarities in the amino acid sequences of the HLA-I variants and HLA-II β-chain suggest that Face-2 could be the progenitor of both HLA classes. These findings may support the recognition of these variants as a neo-HLA class and proto-HLA.

PMID:37627243 | PMC:PMC10452486 | DOI:10.3390/biom13081178

Trials - Gall Bladder Cancer

Phase 1/2 Trial of Radiotherapy in Combination With TTI-101 in Patients With Borderline Resectable Pancreatic Cancer

Posted: November 21st, 2023, 3:00am GMT

Conditions: Pancreatic Cancer
Interventions: Drug: TTI-101
Sponsors: University of Colorado, Denver; Tvardi Therapeutics, Incorporated
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
STALL vs Sole Local Wound Infiltration in Laparoscopic Cholecystectomy - Double-blinded Randomized Controlled Trial

Posted: November 8th, 2023, 3:00am GMT

Conditions: Cholelithiasis; Cholecystitis; Gallbladder Cancer
Interventions: Procedure: single transversus abdominis laparoscopy-guided plane block; Procedure: local trocar site ropivacaine infiltration
Sponsors: Helsinki University Central Hospital
Not yet 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
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
Tumor-Derived FGF19

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

Conditions: Colorectal Cancer; Breast Cancer; Healthy
Sponsors: University of Central Florida
Recruiting
Effect of Intravenous Lignocaine Infusion on Intraoperative End Tidal Desflurane Concentration Requirements

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

Conditions: Cholelithiases; Appendicitis; Ovarian Cysts
Interventions: Drug: Lignocaine; Drug: Placebo
Sponsors: Universiti Kebangsaan Malaysia Medical Centre
Completed
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
Comparison of Al18F-NOTA-LM3 With 68Ga-DOTATATE and 68Ga-NODAGA-LM3 PET/CT in Patients With Well-differentiated Neuroendocrine Tumors

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

Conditions: Neuroendocrine Tumors
Interventions: Diagnostic Test: Al18F-NOTA-LM3; Diagnostic Test: 68Ga-DOTATATE; Diagnostic Test: Al18F-NOTA-LM3; Diagnostic Test: 68Ga-NODAGA-LM3
Sponsors: Peking Union Medical College Hospital
Recruiting
Improving Surgeon Performance Measures for Robot-Assisted Surgery

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

Conditions: Surgery
Interventions: Procedure: Robotic Surgery
Sponsors: Memorial Sloan Kettering Cancer Center
Recruiting
Envafolimab Combined With GEMOX in First-line Treatment of Advanced GBC

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

Conditions: Gallbladder Cancer
Interventions: Drug: Envafolimab+Gemox
Sponsors: Eastern Hepatobiliary Surgery Hospital
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
Effects of Dexamethasone on Common Bile Duct Cannulation Time

Posted: July 14th, 2023, 2:00am 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
A Clinical Study of a Preoperative Translational Therapy for Unresectable Gallbladder Cancer

Posted: June 26th, 2023, 2:00pm GMT

Condition: Unresectable Gallbladder Cancer
Intervention: Drug: Carrilizumab plus GEMOX
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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
Addition of Everolimus to Standard of Care in Carcinoma Gallbladder

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

Condition: Gallbladder Cancer
Interventions: Drug: Everolimus 10 mg; Drug: Standard of care
Sponsor: Banaras Hindu University
Recruiting
DETERMINE Trial Treatment Arm 4: Trastuzumab in Combination With Pertuzumab in Adult, Teenage/Young Adult and Paediatric Patients With Cancers With HER2 Amplification or Activating Mutations

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

Conditions: Solid Tumor; Haematological Malignancy; Colorectal Neoplasms; Urinary Bladder Neoplasm; Gallbladder Neoplasms; Salivary Gland Neoplasm; Lung Neoplasm; Pancreatic Neoplasm; Ovarian Neoplasms; Prostatic Neoplasm; Skin Neoplasm
Interventions: Drug: Trastuzumab; Drug: Pertuzumab
Sponsors: Cancer Research UK; University of Manchester; University of Birmingham; Royal Marsden NHS Foundation Trust; Hoffmann-La Roche
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
Combination of Gemcitabine, Albumin-paclitaxel , Sintilimab and Bevacizumab in Unresectable Gallbladder Cancer

Posted: March 7th, 2023, 3:00pm GMT

Conditions: Gallbladder Cancer; Initially Unresectable; the First Line Treatment
Intervention: Drug: Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab
Sponsor: Lu Wang, MD, PhD
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
Deep Learning Radiogenomics For Individualized Therapy in Unresectable Gallbladder Cancer

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

Condition: Gallbladder Cancer
Intervention: Diagnostic Test: CT scan
Sponsors: Postgraduate Institute of Medical Education and Research, Chandigarh; Radiological Society of North America
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
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
A Study of RC108-ADC in Subjects With Advanced Digestive System Malignant Tumor

Posted: November 29th, 2022, 3:00pm GMT

Conditions: Digestive Cancer
Interventions: Drug: RC108
Sponsors: RemeGen Co., Ltd.
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
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
Pressurized Intraperitoneal Aerosolized Nab-Paclitaxel in Combination With Gemcitabine and Cisplatin for the Treatment of Biliary Tract Cancer Patients With Peritoneal Metastases

Posted: March 17th, 2022, 2:00pm GMT

Conditions: Distal Bile Duct Adenocarcinoma; Gallbladder Carcinoma; Intrahepatic Cholangiocarcinoma; Metastatic Malignant Neoplasm in the Peritoneum; Stage IV Distal Bile Duct Cancer AJCC v8; Stage IV Intrahepatic Bile Duct Cancer AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Stage IVB Gallbladder Cancer AJCC v8
Interventions: Drug: Cisplatin; Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Sponsors: City of Hope Medical Center; National Cancer Institute (NCI)
Recruiting
To Evaluate Efficacy and Safety of TT-00420 as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors

Posted: February 23rd, 2022, 3:00am GMT

Conditions: Advanced Solid Tumor; Cholangiocarcinoma; Biliary Tract Cancer; HER2-negative Breast Cancer; Triple Negative Breast Cancer; Small-cell Lung Cancer; Bladder Cancer; Prostate Cancer; Thyroid Cancer; Gastric Cancer; Gallbladder Cancer
Interventions: Drug: TT-00420; Drug: Combination Product: Atezolizumab; Drug: Combination Product: Nab-Paclitaxel
Sponsors: TransThera Sciences (Nanjing), Inc.
Recruiting
Tissue Procurement and Natural History Study of Neuroendocrine Neoplasms (NENs) Including Adrenocortical Carcinoma (ACC)

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

Conditions: Neuroendocrine Tumors; Carcinoma, Neuroendocrine
Sponsors: National Cancer Institute (NCI)
Recruiting
Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer

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

Conditions: Biliary Tract Cancer (CCA); Intrahepatic Cholangiocarcinoma; Hilar Cholangiocarcinoma; Distal Cholangiocarcinoma; Gall Bladder Carcinoma
Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Capecitabine
Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Recruiting
Comprehensive Genomic Profiling Combined With Real Life Data of "The German-Registry of Incidental Gallbladder Carcinoma"

Posted: February 3rd, 2022, 3:00am GMT

Conditions: Gallbladder Carcinoma
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Active, not recruiting
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

Posted: November 8th, 2021, 3:00am GMT

Conditions: Anal Melanoma; Bladder Melanoma; Cervical Melanoma; Esophageal Melanoma; Gallbladder Melanoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Mucosal Melanoma of the Urinary System; Oral Cavity Mucosal Melanoma; Penile Mucosal Melanoma; Rectal Melanoma; Recurrent Mucosal Melanoma; Sinonasal Mucosal Melanoma; Stage II Vulvar Cancer AJCC v8; Stage III Vulvar Cancer AJCC v8; Stage IV Vulvar Cancer AJCC v8; Urethral Melanoma; Vaginal Melanoma; Vulvar Melanoma
Interventions: Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Placebo Administration; Procedure: Positron Emission Tomography
Sponsors: National Cancer Institute (NCI)
Suspended
Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types

Posted: August 11th, 2021, 2:00pm GMT

Conditions: Bile Duct Cancer; Gall Bladder Cancer; Breast Cancer; Neuroendocrine Tumors; Ovarian Cancer; Pancreatic Adenocarcinoma; Soft Tissue Sarcoma; Vulvar Cancer; Prostate Cancer
Interventions: Drug: Atezolizumab; Drug: Tivozanib
Sponsors: University of Florida; Genentech, Inc.; Aveo Oncology Pharmaceuticals
Suspended
Combination Immunotherapy in Rare Cancers Under InvesTigation

Posted: July 21st, 2021, 2:00pm GMT

Conditions: Advanced Biliary Tract Cancer; Neuroendocrine Tumors; Female Reproductive System Neoplasm; MSI-H Solid Malignant Tumor
Interventions: Drug: Ipilimumab; Drug: Nivolumab
Sponsors: Olivia Newton-John Cancer Research Institute; Bristol-Myers Squibb
Recruiting
The ID- RFA Trial: A Trial of Intraductal Radio-frequency Ablation (ID-RFA) Plus Biliary Stenting Versus Biliary Stenting Alone for the Treatment of Malignant Biliary Obstruction.

Posted: June 28th, 2021, 2:00pm GMT

Condition: Malignant Biliary Obstruction
Interventions: Procedure: Intraductal Radio-Frequency Ablation; Device: Biliary Stent Placement
Sponsors: University Hospitals Dorset NHS Foundation Trust; The Christie NHS Foundation Trust
Recruiting
Low Dose ICG for Biliary Tract and Tumor Imaging

Posted: June 28th, 2021, 2:00am GMT

Conditions: Cholecystitis; Hepatocellular Carcinoma; Liver Metastases
Interventions: Drug: Indocyanine green; Device: PINPOINT Endoscopic Fluorescence
Sponsors: University of Florida; Society of University Surgeons
Completed
Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels

Posted: June 18th, 2021, 2:00pm GMT

Conditions: Metastatic Cancer; Foregut Carcinoid Tumor; Gastric Adenocarcinoma; Gallbladder Adenocarcinoma; Liver Cancer; GI Cancer; GI Carcinoma; Lung Cancer
Interventions: Drug: Standard of Care Chemotherapy; Procedure: Video-Assisted Thoracic Surgery (VATS); Procedure: Lobectomy; Radiation: Consolidative Radiation; Radiation: Ablation Treatment; Procedure: Resection or Excision; Procedure: Peritonectomy; Other: Transarterial Radioembolization
Sponsors: University of Chicago
Not yet recruiting
Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes

Posted: June 1st, 2021, 2:00pm GMT

Conditions: Cancer Pain; Visceral Pain; Gastrointestinal Neoplasms; Cancer of Gastrointestinal Tract; Small Intestine Cancer; Pancreas Cancer; Liver Cancer; Colon Cancer; Biliary Tract Cancer; Stomach Cancer; Rectum Cancer; Peritoneal Cancer; Gastrointestinal Cancer Metastatic; Gastrointestinal Cancers - Anus; Gastrointestinal Cancers - Stomach; Gastrointestinal Cancers - Colorectal; Gastrointestinal Cancers - Small Intestine; Small Intestine Cancer Stage III; Small Intestine Cancer Stage IV; Small Intestine Cancer, Recurrent; Pancreas Cancer, Stage III; Pancreas Cancer, Stage IV; Pancreas Cancer, Metastatic; Pancreas Cancer, Recurrent; Liver Cancer Stage IIIa; Liver Cancer Stage IIIb; Liver Cancer Stage IIIc; Liver Cancer Stage IV; Colon Cancer Stage III; Colon Cancer Stage IV; Stomach Cancer Stage III; Stomach Cancer Stage IV; Stomach Cancer Recurrent; Rectum Cancer, Recurrent; Gastrointestinal Cancers - Liver; Anal Cancer; Anal Cancer Stage III; Anal Cancer Stage IV; Anal Cancer Recurrent; Anal Cancer Metastatic; Anal Cancer, Stage IIIA; Anal Cancer, Stage IIIB; Appendix Cancer; Ampullary Cancer; Bile Duct Cancer; Bile Duct Cancer Stage III; Bile Duct Cancer Stage IV; Bile Duct Cancer Stage IVA; Bile Duct Cancer Stage IVB; Bile Duct Cancer Recurrent; Carcinoid Tumor; Carcinoid Tumor of Pancreas; Carcinoid Tumor of Large Intestine; Carcinoid Tumor of GI System; Carcinoid Tumor of Colon; Carcinoid Tumor of Liver; Carcinoid Tumor of Cecum; Carcinoid Tumor of Ileum; Carcinoid Tumor of Rectum; Carcinoid Tumor of the Small Bowel; Carcinoid Tumor of the Stomach; Large Intestine Cancer; Esophagus Cancer; Esophagus Cancer, Stage III; Esophagus Cancer, Stage IV; Esophagus Cancer, Recurrent; Gallbladder Cancer; Gallbladder Cancer Stage III; Gallbladder Cancer Stage IV; Gastric (Stomach) Cancer; Neuroendocrine Tumor; Peritoneum Cancer; Rectal Cancer; Esophagus Cancer, Stage I; Esophagus Cancer, Stage II; Gallbladder Cancer Stage I; Gallbladder Cancer Stage II; Bile Duct Cancer Stage I; Bile Duct Cancer Stage II
Intervention: Device: PICO G2 4k
Sponsors: Cedars-Sinai Medical Center; National Cancer Institute (NCI)
Recruiting
A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)

Posted: June 1st, 2021, 2:00am GMT

Conditions: Advanced Solid Tumours
Interventions: Drug: RXC004; Drug: RXC004; Drug: RXC004; Biological: Denosumab; Biological: Pembrolizumab
Sponsors: Redx Pharma Plc; Merck Sharp & Dohme LLC
Active, not recruiting
EUS-Guided Choledochoduodenostomy Versus ERCP for Primary Biliary Decompression in Distal Malignant Biliary Obstruction

Posted: May 24th, 2021, 2:00am GMT

Conditions: Malignant Biliary Obstruction
Interventions: Procedure: Biliary drainage
Sponsors: Mansoura University
Recruiting
New Prospective Expanded German Registry of Incidental Gallbladder Carcinoma (PERSUASION)- a Permanent Platform Including All Kind of Biliary Tract Cancers (BTC)

Posted: May 21st, 2021, 2:00am GMT

Conditions: Biliary Tract Cancer; Neoadjuvant, Adjuvant and 1st Line
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Recruiting
Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors

Posted: February 8th, 2021, 3:00am GMT

Conditions: Advanced Solid Tumor; Cholangiocarcinoma; HER2-negative Breast Cancer; Triple Negative Breast Cancer; Bladder Cancer; Small-cell Lung Cancer; Prostate Cancer; Thyroid Cancer; Sarcoma; Gastric Cancer; Gallbladder Cancer
Interventions: Drug: TT-00420; Combination Product: Nab-Paclitaxel
Sponsors: TransThera Sciences (Nanjing), Inc.
Active, not recruiting
A Dual Channel Supraglottic Airway Device (LMA Gastro) for Oxygenation in Patients Undergoing ERCP

Posted: February 5th, 2021, 3:00am GMT

Conditions: Bile Duct Carcinoma; Gallbladder Carcinoma; Pancreatic Ductal Adenocarcinoma
Interventions: Procedure: Endoscopic Retrograde Cholangiopancreatography; Procedure: Endoscopic Retrograde Cholangiopancreatography
Sponsors: M.D. Anderson Cancer Center; National Cancer Institute (NCI)
Completed
18F-DOPA II - PET Imaging Optimization

Posted: January 13th, 2021, 3:00pm GMT

Conditions: Congenital Hyperinsulinism; Neuroblastoma; Parkinson Disease; Lewy Body Disease; Neuroendocrine Tumors; Brain Tumor
Interventions: Drug: 18F-DOPA; Drug: Furosemide Injection
Sponsor: University of Alberta
Recruiting
A Trial to Learn Whether Regorafenib in Combination With Nivolumab Can Improve Tumor Responses and How Safe it is for Participants With Solid Tumors

Posted: January 11th, 2021, 3:00am GMT

Conditions: Solid Tumors
Interventions: Drug: Regorafenib, (Stivarga, BAY73-4506); Drug: Nivolumab (Opdivo)
Sponsors: Bayer; Bristol Myers Squibb Co. and Ono Pharmaceutical Co., Ltd
Active, not recruiting
Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies

Posted: November 24th, 2020, 3:00am GMT

Conditions: Metastatic Cancer; Solid Tumor
Interventions: Drug: Sym021; Drug: Sym022; Drug: Sym023; Drug: Irinotecan Hydrochloride
Sponsors: Symphogen A/S
Active, not recruiting
Feasibility Study of Multi-Platform Profiling of Resected Biliary Tract Cancer

Posted: September 23rd, 2020, 2:00pm GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer; Intrahepatic Cholangiocarcinoma; Perihilar Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Hilar Cholangiocarcinoma; Distal Bile Duct Cancer
Intervention: Diagnostic Test: Multi-Platform Profiling with Organoid Drug Sensitivity Screening and ctDNA Monitoring
Sponsors: University of Washington; Natera, Inc.; SEngine Precision Medicine, Inc.
Recruiting
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer

Posted: September 22nd, 2020, 2:00pm GMT

Conditions: Stage II Gallbladder Cancer AJCC v8; Stage IIA Gallbladder Cancer AJCC v8; Stage IIB Gallbladder Cancer AJCC v8; Stage III Gallbladder Cancer AJCC v8; Stage IIIA Gallbladder Cancer AJCC v8; Stage IIIB Gallbladder Cancer AJCC v8
Interventions: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Procedure: Lymphadenectomy; Procedure: Partial Hepatectomy
Sponsors: ECOG-ACRIN Cancer Research Group; National Cancer Institute (NCI)
Recruiting
Behavioral Weight Loss Program for Cancer Survivors in Maryland

Posted: September 1st, 2020, 2:00am GMT

Conditions: Breast Cancer; Prostate Cancer; Melanoma (Skin); Endometrial Cancer; Gallbladder Cancer; Rectal Cancer; Kidney Cancer; Bladder Cancer
Interventions: Behavioral: Written Weight Loss Material; Behavioral: Weight Loss App; Behavioral: Behavioral Lifestyle Weight Loss Intervention (Coaching)
Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Maryland Cigarette Restitution Fund
Completed
PLATON - Platform for Analyzing Targetable Tumor Mutations (Pilot-study)

Posted: July 23rd, 2020, 2:00pm GMT

Conditions: Hepatocellular Cancer; Cholangiocarcinoma; Gallbladder Cancer; Pancreatic Cancer; Oesophageal Cancer; Stomach Cancer
Intervention: Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid
Sponsors: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest; Roche Pharma AG
Recruiting
A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

Posted: July 10th, 2020, 2:00am GMT

Conditions: HER2-amplified Biliary Tract Cancers
Interventions: Drug: ZW25 (Zanidatamab)
Sponsors: Jazz Pharmaceuticals; BeiGene, Ltd.
Active, not recruiting
Hepatobiliary Tumors Tissue Samples Acquisition

Posted: June 24th, 2020, 2:00pm GMT

Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma; Gallbladder Cancer; Biliary Tract Cancer; Liver Cancer; Precancerous Condition; Benign Hepatobiliary Disease; Healthy, no Evidence of Disease
Interventions: Other: Gene expression analysis; Other: Genomic analysis; Other: Protein expression analysis; Other: Proteomic profiling; Other: Polymerase chain reaction; Other: Mass spectrometry; Other: Immunohistochemistry; Other: Metabolomics profiling; Other: Methylation and epigenetic analysis; Other: Liquid biopsy analysis; Other: Laboratory biomarker analysis
Sponsors: Peking Union Medical College Hospital; OrigiMed; GeneCast Biotechnology Co., Ltd.; YuceBio Technology Co., Ltd.; Geneplus-Beijing Co. Ltd.
Recruiting
Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers

Posted: June 12th, 2020, 2:00pm GMT

Conditions: Colorectal Carcinoma; Gastric Adenocarcinoma; GEJ Adenocarcinoma; Esophageal Adenocarcinoma; Cholangiocarcinoma; Gallbladder Carcinoma
Interventions: Drug: tucatinib; Drug: trastuzumab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: capecitabine; Drug: pembrolizumab
Sponsors: Seagen Inc.
Recruiting
The Incidence of Gallstones After Gastric Cancer Surgery

Posted: January 31st, 2020, 3:00pm GMT

Conditions: Gallstones; Gastric Cancer
Interventions: Procedure: Resection
Sponsors: Hepatopancreatobiliary Surgery Institute of Gansu Province
Recruiting
Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers

Posted: December 26th, 2019, 3:00pm GMT

Condition: Advanced Biliary Tract Cancer
Intervention: Drug: Toripalimab plus Lenvatinib
Sponsors: Peking Union Medical College Hospital; Shanghai Junshi Bioscience Co., Ltd.
Recruiting
Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

Posted: November 15th, 2019, 3:00pm GMT

Conditions: Advanced Colorectal Carcinoma; Metastatic Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Stage II Colon Cancer; Stage II Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Esophageal Cancer; Pancreatic Cancer; Bile Duct Cancer; Gastric Cancer; Gall Bladder Cancer; Small Bowel Adenocarcinoma
Interventions: Biological: Bevacizumab; Drug: Dasatinib; Drug: Fluorouracil; Drug: Leucovorin; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Other: Quality-of-Life Assessment
Sponsor: Anne Noonan
Recruiting
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies

Posted: August 28th, 2019, 2:00pm GMT

Conditions: Cholangiocarcinoma; Gallbladder Carcinoma; Malignant Solid Neoplasm; Stage III Gallbladder Cancer AJCC v8; Stage III Hilar Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Gallbladder Cancer AJCC v8; Stage IV Hilar Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
Interventions: Drug: Avelumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Hypofractionated Radiation Therapy; Drug: Peposertib
Sponsors: National Cancer Institute (NCI)
Recruiting
Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC

Posted: August 26th, 2019, 2:00am GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer
Interventions: Drug: M7824; Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin
Sponsors: EMD Serono Research & Development Institute, Inc.; Merck KGaA, Darmstadt, Germany
Terminated
M7824 Monotherapy in Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer)

Posted: February 7th, 2019, 3:00am GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer
Interventions: Drug: M7824
Sponsors: EMD Serono Research & Development Institute, Inc.; Merck KGaA, Darmstadt, Germany
Completed
Adoptive Transfer of Tumor Infiltrating Lymphocytes for Biliary Tract Cancers

Posted: January 11th, 2019, 3:00pm GMT

Conditions: Biliary Tract Cancer; Cholangiocarcinoma; Biliary Tract Neoplasms
Intervention: Biological: Tumor Infiltrating Lymphocytes (TIL)
Sponsor: Udai Kammula
Recruiting
A Study of the Efficacy and Safety of Chemotherapy Combined With Toripalimab in Advanced Biliary Tract Cancer

Posted: January 8th, 2019, 3:00am GMT

Conditions: Biliary Tract Cancer
Interventions: Drug: GS+Toripalimab
Sponsors: Shanghai Zhongshan Hospital; Shanghai Junshi Bioscience Co., Ltd.; OrigiMed
Completed
Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers

Posted: December 7th, 2018, 3:00am GMT

Conditions: Stage III Distal Bile Duct Cancer AJCC v8; Stage III Gallbladder Cancer AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IIIA Distal Bile Duct Cancer AJCC v8; Stage IIIA Gallbladder Cancer AJCC v8; Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8; Stage IIIB Distal Bile Duct Cancer AJCC v8; Stage IIIB Gallbladder Cancer AJCC v8; Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Distal Bile Duct Cancer AJCC v8; Stage IV Gallbladder Cancer AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Stage IVA Gallbladder Cancer AJCC v8; Stage IVB Gallbladder Cancer AJCC v8; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma; Unresectable Intrahepatic Cholangiocarcinoma
Interventions: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Nab-paclitaxel
Sponsors: SWOG Cancer Research Network; National Cancer Institute (NCI)
Active, not recruiting
A Study to Evaluate Safety, Tolerability and Preliminary Efficacy of FP-1305 in Cancer Patients (MATINS)

Posted: November 7th, 2018, 3:00am GMT

Conditions: Cancer
Interventions: Biological: FP-1305 (bexmarilimab)
Sponsors: Faron Pharmaceuticals Ltd
Completed
The Relationship Between Triceps Skinfold and Overall Survival of Pancreas, Bile Duct, Gallbladder Cancer

Posted: August 20th, 2018, 2:00pm GMT

Conditions: Pancreas Cancer; Cholangiocarcinoma; Gallbladder Cancer
Intervention: Other: Measurement of triceps skinfold thickness
Sponsor: Samsung Medical Center
Recruiting
Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

Posted: June 14th, 2018, 2:00pm GMT

Conditions: Any Solid Tumors Progressed After a Prior Immunotherapy; Cervical Cancer; Adenoid Cystic Carcinoma; Squamous Cell Carcinoma of Head and Neck; Mesothelioma; Gall Bladder Cancer; Thymic Carcinoma; Non-Small Cell Squamous Lung Cancer; Bladder Cancer; Ovarian Cancer; Pancreatic Cancer; Colon Cancer; Leiomyosarcoma; Head and Neck Squamous Cell Carcinoma; Thymoma; Urothelial Carcinoma
Interventions: Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Sponsors: VM Oncology, LLC
Recruiting
Pembrolizumab in Biliary Tract Cancer

Posted: August 24th, 2017, 2:00am GMT

Conditions: Biliary Tract Cancer; Metastatic Cancer; Advanced Cancer; Gallbladder Cancer
Interventions: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Gemcitabine
Sponsors: European Organisation for Research and Treatment of Cancer - EORTC
Completed
Atezolizumab With or Without Cobimetinib in Treating Patients With Metastatic Bile Duct Cancer That Cannot Be Removed by Surgery or Gallbladder Cancer

Posted: June 28th, 2017, 2:00am GMT

Conditions: Gallbladder Carcinoma; Metastatic Cholangiocarcinoma; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Cholangiocarcinoma
Interventions: Drug: Atezolizumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Cobimetinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
Point of Care 3D Ultrasound for Various Applications: A Pilot Study

Posted: July 13th, 2016, 2:00am GMT

Conditions: Appendicitis; Evidence of Cholecystectomy; Gallstones; Pregnancy, Ectopic; Aortic Aneurysm; Kidney Stones; Intrauterine Pregnancy; Diverticulitis; Abdominal Injuries; Tumors; Pancreatitis; Digestive System Diseases; Gastrointestinal Diseases; Intraabdominal Infections; Intestinal Diseases; Pregnancy; Vascular Disease; Uterine Fibroids; Ovarian Cysts; Uterine Abnominalies; Bladder Abnominalies; Testicular Abnominalies; Polyps
Sponsors: Duke University; Wallace H. Coulter Foundation
Recruiting
Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors

Posted: October 1st, 2015, 2:00am GMT

Conditions: Advanced Solid Tumors
Interventions: Drug: DS-8201a (DP1); Drug: DS-8201a (DP2); Drug: DS-8201a (DP)
Sponsors: Daiichi Sankyo Co., Ltd.; Daiichi Sankyo, Inc.; AstraZeneca
Active, not recruiting
Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

Posted: November 19th, 2014, 3:00am GMT

Conditions: Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific
Interventions: Procedure: radionuclide imaging; Procedure: positron emission tomography; Other: laboratory biomarker analysis; Other: pharmacological study; Drug: Cu 64 anti-CEA monoclonal antibody M5A IV
Sponsors: City of Hope Medical Center; National Cancer Institute (NCI)
Active, not recruiting
Integrated Cancer Repository for Cancer Research

Posted: December 16th, 2013, 3:00pm GMT

Conditions: Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma; Breast Cancer; Leukemia; Melanoma; Sarcoma; Unknown Primary Tumor; Multiple Myeloma; Ovarian Cancer; Endometrial Cancer; Vaginal Cancer; Neuroendocrine Tumors; Plasma Cell Dyscrasia; Healthy Control
Sponsors: University of Nebraska
Recruiting
ADH-1, Gemcitabine Hydrochloride & Cisplatin in Treating Metastatic Pancreatic or Biliary Tract Cancer

Posted: April 5th, 2013, 2:00am GMT

Conditions: Ampulla of Vater Adenocarcinoma; Gallbladder Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Stage III Ampulla of Vater Cancer; Stage III Intrahepatic Cholangiocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Hilar Cholangiocarcinoma; Stage IIIB Gallbladder Cancer; Stage IIIB Hilar Cholangiocarcinoma; Stage IV Ampulla of Vater Cancer; Stage IVA Gallbladder Cancer; Stage IVA Hilar Cholangiocarcinoma; Stage IVA Intrahepatic Cholangiocarcinoma; Stage IVA Pancreatic Cancer; Stage IVB Gallbladder Cancer; Stage IVB Hilar Cholangiocarcinoma; Stage IVB Intrahepatic Cholangiocarcinoma; Stage IVB Pancreatic Cancer
Interventions: Drug: ADH-1; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis
Sponsors: University of Nebraska; Adherex Technologies, Inc.; National Cancer Institute (NCI)
Completed

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Rare Cancer News & Clinical Trials » Gall Bladder Cancer

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