Advanced gallbladder cancer with high tumor mutation burden: a case report and literature review.

Background: Gallbladder cancer (GBC) is a common malignant tumor of the biliary system. It is characterised by insidious onset, rapid progression and poor prognosis. Symptoms often indicate advanced or late-stage disease, with a 5-year survival rate of only 5-15%. Case Description: We present a case study of a patient with GBC who had a tumor mutation burden (TMB) of 32.5/MB (≥10 muts/MB). The patient received mFOLFIRINOX as first-line chemotherapy, which demonstrated significant efficacy. After stabilizing the disease, a sequential chemotherapy regimen was chosen. This regimen combined the immune checkpoint inhibitor (ICI) toripalimab (JS001), a humanised IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1), with S-1 therapy, an oral fluoropyrimidine derivative. However, this treatment did not provide any significant clinical benefit for the patient. Therefore, we hypothesise that combining immunotherapy with chemotherapy may be more effective as a first line treatment for high-TMB advanced GBC. This hypothesis needs to be validated in large-scale clinical studies. Conclusions: In summary, mFOLFIRINOX is a safe and effective first-line chemotherapy regimen for advanced GBC. The timing of combining immunotherapy with chemotherapy requires careful consideration. Further clinical trials involving immunotherapy in advanced GBC are necessary to identify biomarkers that can guide clinical decisions.

Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease.

Cholangiocarcinoma (CCA) represents a group of epithelial cell tumors classified based on their anatomic location along the biliary tree. This rare malignancy is often diagnosed at an advanced stage and deemed unresectable. Even for those patients who are surgical candidates, recurrence rates are high and survival rates low. The mainstay of therapy for advanced CCA remains cisplatin plus gemcitabine, with a median overall survival (mOS) under 12 months, although the TOPAZ-1 trial showed a survival benefit with the addition of programmed cell death ligand 1 (PD-L1) blockade. In recent years, molecular profiling has revealed a wealth of potentially targetable genetic alterations, including fibroblast growth factor receptor (FGFR) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, human epidermal growth factor receptor 2 (HER2) amplification and overexpression, and microsatellite instability (MSI). These discoveries have prompted numerous clinical trials employing drugs against these specific genetic changes. The foundation laid by early clinical studies and the landscape of ongoing trials are both summarized here. While the role of adjuvant therapy has yet to be defined in this disease, we emphasize the importance of employing targeted therapies in trials in the adjuvant and neoadjuvant spaces and discuss ways to overcome challenges due to low incidence of targetable mutations. Personalized medicine for this disease promises significant clinical benefit to patients, but further investigation is needed.

Targeting ERBB2/HER2 genetic alterations: an expanding therapeutic opportunity in gastrointestinal cancers.

HER2 amplification and/or activating variations of its protein, human epidermal growth factor receptor 2 (HER2), are associated with distinct clinical and pathological features in gastrointestinal tumors, including a worse overall prognosis and a higher incidence of metastastic lesions in the central nervous system. Notably, the role of HER2 as a therapeutic target continues to expand beyond the scope of breast and gastroesophageal tumors, now encompassing colorectal and biliary tract cancers (BTCs), among others. In parallel, there is a burgeoning array of therapeutic agents designed to inhibit the activity of the HER2 pathway, including monoclonal antibodies, orally available tyrosine kinase inhibitors, bispecific antibodies, and antibody-drug conjugate compounds. In this comprehensive review, we will explore the current body of evidence that supports the implementation of HER2-targeting strategies in the treatment of patients with gastric, esophageal, colorectal, and biliary tract tumors. We will also describe testing methods for HER2 status in clinical practice, including immunohistochemistry (IHC), and its correlation with next-generation sequencing-based techniques. Additionally, we will review the key treatment-related adverse events associated with specific anti-HER2 agents, emphasizing the need for early diagnosis and effective management. Furthermore, a critical aspect of this exploration is determining the optimal treatment sequencing among the available therapies, which will be pivotal in enhancing treatment outcomes.

Erratum: Preoperative immunological plasma markers TRAIL, CSF1, and TIE2 predict survival after resection for biliary tract cancer.

[This corrects the article DOI: 10.3389/fonc.2023.1169537.].

Wee1 inhibition by MK1775 potentiates gemcitabine through accumulated replication stress leading to apoptosis in biliary tract cancer.

Patients with advanced biliary tract cancer (BTC) have a poor prognosis, and novel treatments are needed. Gemcitabine, the standard of care for BTC, induces DNA damage; however, the ability of cancer cells to repair DNA dampens its effects. To improve the efficacy of gemcitabine, we combined it with MK1775, a Wee1 inhibitor that prevents activation of the G2/M checkpoint. BTC cell lines were treated with gemcitabine only or in combination with MK1775 to determine the therapeutic potential of BTC. Gemcitabine inhibited the growth and induced the apoptosis of four BTC cell lines to a greater extent when added with MK1775 than when added alone. The effects of the combination treatment were observed in both p53 wild-type and p53 mutant cell lines and were unaffected by knockdown of wild-type p53. The combination treatment increased the percentage of apoptotic cells and decreased the percentage of cells synthesizing DNA, suggesting that it caused DNA-damaged cells to accumulate and possibly die in S phase. It did not induce apoptosis when cells were arrested in mitosis using nocodazole. In a xenograft mouse model, gemcitabine plus MK1775 (but not either alone) inhibited the growth of tumors generated from inoculated BTC cells. Our results show that MK1775 highly enhances gemcitabine cytotoxicity in BTC regardless of p53 status. We suggest that the combination treatment elicits a DNA damage response and consequent apoptosis. Our preclinical study provides a basis for future clinical trials of gemcitabine plus MK1775 in patients with BTC.

Systemic treatment of patients with locally advanced or metastatic cholangiocarcinoma - an Austrian expert consensus statement.

Locally advanced or metastatic cholangiocarcinoma is an aggressive carcinoma with a dismal prognosis. For the first-line treatment of locally advanced or metastatic cholangiocarcinoma, cisplatin/gemcitabine has been the standard of care for more than 10 years. Its combination with the immune checkpoint inhibitor durvalumab resulted in an efficiency improvement in the phase III setting. Regarding the use of chemotherapy in the second line, positive phase III data could only be generated for FOLFOX. The evidence base for nanoliposomal irinotecan (Nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) is contradictory. After the failure of first-line treatment, targeted therapies can be offered if the molecular targets microsatellite instability-high (MSI-H), IDH1, FGFR2, BRAF V600E, and NTRK are detected. These targeted agents are generally preferable to second-line chemotherapy. Broad molecular testing should be performed, preferably from tumor tissue, at the initiation of first-line therapy to timely identify potential molecular targets.

Preoperative immunological plasma markers TRAIL, CSF1 and TIE2 predict survival after resection for biliary tract cancer.

Introduction: Systemic inflammatory markers have been validated as prognostic factors for patients with biliary tract cancer (BTC). The aim of this study was to evaluate specific immunologic prognostic markers and immune responses by analyzing preoperative plasma samples from a large prospectively collected biobank. Methods: Expression of 92 proteins representing adaptive and innate immune responses was investigated in plasma from 102 patients undergoing resection for BTC 2009-2017 (perihilar cholangiocarcinoma n=46, intrahepatic cholangiocarcinoma n=27, gallbladder cancer n=29), by means of a high-throughput multiplexed immunoassay. Association with overall survival was analyzed by Cox regression, with internal validation and calibration. Tumor tissue bulk and single-cell gene expression of identified markers and receptors/ligands was analyzed in external cohorts. Results: Three preoperative plasma markers were independently associated with survival: TRAIL, TIE2 and CSF1, with hazard ratios (95% confidence intervals) 0.30 (0.16-0.56), 2.78 (1.20-6.48) and 4.02 (1.40-11.59) respectively. The discrimination of a preoperative prognostic model with the three plasma markers was assessed with concordance-index 0.70, while the concordance-index of a postoperative model with histopathological staging was 0.66. Accounting for subgroup differences, prognostic factors were assessed for each type of BTC. TRAIL and CSF1 were prognostic factors in intrahepatic cholangiocarcinoma. In independent cohorts, TRAIL-receptor expression was higher in tumor tissue and seen in malignant cells, with TRAIL and CSF1 expressed by intra- and peritumoral immune cells. Intratumoral TRAIL-activity was decreased compared to peritumoral immune cells, while CSF1-activity was increased. The highest CSF1 activity was seen in intratumoral macrophages, while the highest TRAIL-activity was seen in peritumoral T-cells. Discussion: In conclusion, three preoperative immunological plasma markers were prognostic for survival after surgery for BTC, providing good discrimination, even compared to postoperative pathology. TRAIL and CSF1, prognostic factors in intrahepatic cholangiocarcinoma, showed marked differences in expression and activity between intra- and peritumoral immune cells.

Targeted therapies in advanced biliary tract cancers-a narrative review.

BACKGROUND AND OBJECTIVE: Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder cancer, are a relatively rare group of cancers with a poor prognosis. Over the past decade, the utilization of next-generation sequencing has led to the identification of multiple actionable somatic aberrations in BTCs. Subsequently, new therapies have been created to target these molecular alterations and have been incorporated into clinical practice. In this review, we outline therapies that have been previously studied, and those that are under investigation, to target genomic alterations with the goal of improving survival in patients with advanced disease. METHODS: A literature search was performed to identify phase I, II, and III trials of targeted therapies in patients with advanced BTCs published between January 1, 2010 and October 1, 2022. Medline (via PubMed) and ClinicalTrials.gov were searched for relevant studies and 415 trials were identified. The search strategy was performed using keywords including: biliary tract cancer, cholangiocarcinoma, gallbladder cancer, chemotherapy, targeted therapy, randomized trials, controlled trials, phase I, phase II, and phase III. Search results were imported into EndNote X 9.1. KEY CONTENT AND FINDINGS: Overall, immune checkpoint inhibitors, fibroblast growth factor receptor (FGFR) inhibitors, isocitrate dehydrogenase (IDH) inhibitors, and human epidermal growth factor receptor 2 (HER2)-directed therapies have all shown promising results with regard to efficacy in patients with advanced BTCs studied in clinical trials. A number of other agents have also been studied in early-phase trials. CONCLUSIONS: Targeted agents can improve survival in patients with advanced BTCs and have substantially increased the number of potential therapeutic options in patients with refractory disease. The therapeutic landscape of targeted therapies for patients with advanced BTCs continues to evolve based on improvements in detection of genomic alterations.

Comprehensive treatment of biliary tract tumors:from the perspective of evolution / 肿瘤

Biliary tract tumors are a class of highly malignant digestive system tumors.Although surgical treatment,chemotherapy,and targeted therapy have achieved good therapeutic effects.However,due to its complex biological characteristics,it is easy to develop drug resistance,and recurrence is still inevitable.More than 99.9％of the species that had ever appeared on earth have become extinct,and these species possess resistance to external selection pressures similar to tumor cells.The comprehensive treatment of biliary tract tumors should be designed from the perspective of natural evolution and species extinction.We compared the causes of species extinction with existing cancer treatments,which are expected to provide new ideas for fundamental and clinical research.

Progress research on immune checkpoint inhibitors for advanced biliary tract cancer treatment / 中国肿瘤临床

Biliary tract cancers(BTCs),encompassing gallbladder cancer and intra-and extra-hepatic cholangiocarcinoma,primarily manifest as highly invasive adenocarcinomas with a notably poor prognosis.BTCs typically initiate insidiously,and even surgically resectable patients confront a heightened risk of recurrence,with postoperative adjuvant chemotherapy offering limited survival benefits.For unresectable or metastatic BTCs,systemic antitumor drug therapy remains the primary treatment.Recently,significant progress has been made in the treat-ment of advanced BTCs with the emergence of immune checkpoint inhibitors(ICIs)and molecularly targeted drugs alongside traditional chemotherapy.This progress has substantially broadened clinical treatment options and improved patient prognoses.Combining first-line chemotherapy with immunotherapy has emerged as a favorable treatment strategy over conventional chemotherapy.Additionally,the com-bination of chemotherapy with immunotherapy,anti-angiogenic targeted therapy,dual immunotherapy,or dual immunotherapy has exhib-ited promising outcomes.Explorations into second-line immunotherapy have also been actively explored.This article provides an overview of the current status and recent advances in immunotherapy for advanced BTCs.

Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome.

Background: Biliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management. Methods: We obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing. Results: Among 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34-78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC. Conclusions: MSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan.

The Clinical Impact of Methylated Homeobox A9 ctDNA in Patients with Non-Resectable Biliary Tract Cancer Treated with Erlotinib and Bevacizumab.

Methylated homeobox A9 (meth-HOXA9) is tumor specific and has been suggested as a prognostic biomarker in several types of cancer. ctDNA measured as meth-HOXA9 may be a valuable biomarker in the decision-making process about last-line treatment of biliary tract cancer (BTC). The aim of the study was to investigate the clinical impact of meth-HOXA9 in plasma from patients receiving erlotinib and bevacizumab for late-stage BTC and to investigate the treatment effect and adverse events. Droplet digital PCR was applied to detect meth-HOXA9 in 39 patients. Response rates were registered according to RECIST (1.1) and adverse events according to Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE (4.0)). Endpoints were progression-free survival (PFS), overall survival (OS), response rate, and toxicity. A significant difference in PFS and OS between patients with increasing and non-increasing meth-HOXA9 was detected after one treatment cycle, hazard ratio (HR) 12.4 (p < 0.0001) and HR 2.75 (p = 0.04), respectively. The most common adverse events of erlotinib were fatigue, pain, and rash, and those of bevacizumab were bleeding and wounds. This study found meth-HOXA9 to be negatively associated with survival in patients with late-stage BTC. Hence, meth-HOXA9 may guide early discontinuation of ineffective treatment.

Efficacy and Safety of Anti-PD1/PDL1 in Advanced Biliary Tract Cancer: A Systematic Review and Meta-Analysis.

Background: Anti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given the scarce quantitative analyses of anti-PD1/PDL1 in aBTC, we thus did a meta-analysis to assess the benefits and risks of this emerging treatment strategy in patients with aBTC. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and meeting resources were searched for relevant studies. The main endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), any-grade adverse events (AEs), and grade 3-4 AEs. Results: Twenty-eight studies with 1,338 participants were included. The best curative effect was found in the anti-PD1/PDL1 combined with anti-CTLA4 and chemotherapy group (mPFS: 12.4 months; mOS: 16.0 months; ORR: 45.1%; DCR: 95.0%), followed by the anti-PD1/PDL1 plus chemotherapy group (mPFS: 8.2 months; mOS: 14.8 months; ORR: 36.3%; DCR: 84.6%), the anti-PD1/PDL1 plus antiangiogenesis group (mPFS: 4.9 months; mOS: 10.2 months; ORR: 17.5%; DCR: 68.7%), the anti-PD1/PDL1 plus anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) group (mPFS: 2.9 months; mOS: 8.3 months; ORR: 9.9%; DCR: 36.8%), and the anti-PD1/PDL1 monotherapy group (mPFS: 2.5 months; mOS: 7.6 months; ORR: 6.8%; DCR: 34.7%). Compared with anti-PD1-containing regimens, anti-PDL1-containing regimens achieved preferable mPFS (11.1 vs. 3.8 months), mOS (12.2 vs. 9.8 months), and ORR (23.7% vs. 17.4%), despite a similar DCR (61.1% vs. 61.3%). The mPFS, mOS, ORR, and DCR were 10.6 months, 15.8 months, 42.3%, and 88.6% of first-line anti-PD1/PDL1 and 3.0 months, 9.1 months, 11.6%, and 51.1% of second-line therapy or beyond, respectively. There were 80.6% and 34.0% of the patients suffering any-grade AEs and grade 3-4 AEs. Anti-PD1/PDL1 monotherapy might be considered as a safer alternative than combination regimens. Meanwhile, obvious toxicities in the first-line setting could not be neglected. Conclusions: Anti-PD1/PDL1 showed encouraging efficacy and acceptable safety profile in aBTC and, thus, could be an alternative treatment.

Liquid Biopsy from Bile-Circulating Tumor DNA in Patients with Biliary Tract Cancer.

Although liquid biopsy of blood is useful for cancer diagnosis and prediction of prognosis, diagnostic and prognostic value of ctDNA in bile fluid for BTCs are not clear yet. To determine whether liquid biopsy for circulating tumor DNA (ctDNA) can replace tissue biopsy when assessing somatic mutations in biliary tract cancers (BTCs). Bile samples were obtained from 42 patients with BTC. Matched formalin-fixed paraffin-embedded (FFPE) samples were obtained from 20 of these patients and matched plasma samples from 16 of them. Droplet digital PCR (ddPCR) was used for detection KRAS somatic mutation. KRAS mutations were identified in the bile ctDNA of 20 of 42 (48%) patients. Patients with mutant KRAS showed significantly worse survival than those with wild-type KRAS (2-year survival rates: 0% vs. 55.5%, respectively; p = 0.018). There was 80.0% mutational concordance between the paired bile ctDNA and FFPE samples, and 42.9% between the plasma and FFPE samples. On transcriptomic sequencing of one set of paired bile and FFPE samples, expression level of KRAS-associated signaling oncogenes in the bile and tissue samples showed a strong positive correlation (r = 0.991, p < 0.001). Liquid biopsy of bile reliably detect mutational variants within the bile ctDNA of BTC patients. These results suggest that bile is an effective biopsy fluid for ctDNA analysis.

Controlling nutritional status score as a prognostic marker to predict overall survival in resected biliary tract cancers.

BACKGROUND: The aim of our study was to explore the prognostic significance of the preoperative controlling nutritional status (CONUT) score and establish a nomogram to predict overall survival (OS) and to achieve a more accurate prognostic risk stratification. METHODS: Clinicopathological records of 371 patients who underwent surgical resection for biliary tract cancers (BTC) from December 2002 to December 2017 were reviewed retrospectively. The associations of the CONUT score with clinicopathological factors and OS were evaluated. Univariate and multivariable Cox regression analysis were used to screen out independent predictors. A nomogram was developed and validated to estimate OS. RESULTS: The CONUT score was an independent predictor of OS [hazard ratio 1.478, 95% confidence interval (CI), 1.078-2.025, P=0.015]. And patients with a high CONUT score tended to have a poor prognosis with poor differentiation (P=0.011) of tumor cells and longer hospital stays (P=0.046). Besides the CONUT score, carbohydrate antigen 19-9, surgical method, and the American Joint Committee on Cancer (AJCC; 7th edition) TNM stage were contained in the final prognostic model. An OS nomogram was generated to visually predict 1-, 3-, and 5-year OS. The C-index was 0.714 (95% CI, 0.673-0.755) and 0.679 (95% CI, 0.616-0.742) in the development and validation cohort respectively. The nomogram provided superior discriminative power than the AJCC TNM staging system. The nomogram also demonstrated good risk stratification power in the entire cohort of BTC patients as well as for both BTC and surgical method subgroups. CONCLUSIONS: The nomogram based on the CONUT score can predict OS in patients with BTCs, and it performed better than the AJCC TNM staging system.

Blood tests predict the therapeutic prognosis of anti-PD-1 in advanced biliary tract cancer.

Predictive prognostic markers for immunotherapy are crucial and desperately required for clinical precise medicine. This retrospective study aimed to assess the efficacy of anti-PD-1 (programmed cell death protein 1) treatment and find the therapeutic prognostic biomarkers in advanced biliary tract cancer (BTC). A total of 60 patients of advanced BTC who received at least one dose of anti-PD-1 therapy between June 2016 and October 2019 were recruited and followed up till April 2020. Systemic immune-inflammation index (SII) and neutrophils-to-lymphocytes ration (NLR) were obtained from the routine circulating hematologic analysis before treatment. Serum 45-Plex Panel cytokines were detected using multiplexed bead immunoassays. Logistic regression nomogram was used to construct the algorithm model for prognosis prediction. Of the 60 patients, the overall benefit rate (OBR) was 38.3%, the median progression free survival (PFS), and overall survival (OS) were 4.0 mo (95% confidence interval [CI]: 2.28-5.72) and 13.0 mo (95% CI: 8.05-17.95), respectively. High levels of SII (≥720), NLR (≥4.3) and cytokine IFN-inducible protein-10 (IP-10; ≥45 pg/ml) indicated worse OS. Those with high SII (≥720) and high IP-10 (≥45 pg/ml) also had shorter PFS. The nomogram algorithm combining above three independent factors (SII, IP-10, and macrophage inflammatory protein-1ß) had better efficacy in predicting OBR. Our study offers a simple, affordable, and noninvasive method to help physicians predict therapeutic response in BTC patients receiving anti-PD-1 antibody treatment.

Adjuvant Therapy for Resectable Biliary Tract Cancer: A Bayesian Network Analysis.

Background: Selecting proper postoperative adjuvant therapy is of great importance for prolonging overall survival (OS) of patients with biliary tract cancer (BTC). OS is commonly affected by high rate of postoperative recurrence and metastasis. Purpose: The present study aimed to identify the optimal adjuvant therapy for BTC patients. Method: A comprehensive search was carried out on Pubmed, Web of science, and Embase databases to acquire articles regarding BTC therapy approaches. Subsequently, the hazard ratio (HR) and its 95% confidence intervals (CIs) were applied to evaluate the efficacy of different adjuvant therapy regimens. The GemTc (GemTc.0.8-2) and R (R.3.6.0) software were employed to perform statistical analyses. Result: Data from 22 articles, including 14,646 patients, were quantitatively analyzed. The results showed that in terms of 5-year OS, gemcitabine (GEM) was considered as the optimal adjuvant therapy for BTC compared with chemoradiotherapy (CRT; HR = 0.59; 95% CI = 0.34-0.97), observation (OB; HR = 0.49; 95% CI = 0.33-0.73), and radiotherapy (RT; HR = 0.40; 95% CI = 0.22-0.71). Additionally, 5-fluorouracil (5-FU) exhibited improved efficacy compared with RT (HR = 0.52; 95% CI = 0.29-0.91) and OB (HR = 0.63; 95% CI = 0.43-0.92). When the efficacy of 5-FU was compared with that of GEM, the results showed that 5-FU (HR = 1.29) was more effective than GEM. Furthermore, CRT and RT prolonged positive resection margin (R+)-OS (HR = 0.69; 95% CI = 0.49-1.00) and positive lymph node-(N+)-OS (HR = 0.22; 95% CI = 0.074-0.66) in BTC patients. In terms of median recurrence-free survival (RFS) and 1-year OS, the differences were not statistically significant among different therapeutic interventions. Conclusion: The present study suggested that GEM could be used as a first-line adjuvant therapy for resected BTC patients. Additionally, CRT could be the optimal treatment approach for R+ and N+ patients.

Adequate tissue acquisition rate of peroral cholangioscopy-guided forceps biopsy.

BACKGROUND: Peroral cholangioscopy (POCS)-guided forceps biopsy is a method for diagnosing indeterminate biliary strictures and for the preoperative identification of the exact perihilar and distal margins of biliary tract cancer (BTC). However, POCS-guided forceps biopsy may result in an insufficient amount of specimen at times. Therefore, we evaluated the adequate tissue acquisition rate and the factors affecting the adequate tissue acquisition of POCS-guided forceps biopsy for the biliary tract. METHODS: Patients who underwent POCS-guided forceps biopsy for biliary disease between September 2016 and October 2018 at our hospital were enrolled retrospectively. We evaluated the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion and that for non-stenotic bile duct. In addition, the factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy were evaluated. RESULTS: We enrolled 47 patients with biliary disease and performed POCS-guided forceps biopsy for biliary lesion and POCS-guided forceps mapping biopsy for non-stenotic bile duct in 40 and 36 patients, respectively. The adequate tissue acquisition rates of POCS-guided forceps biopsy for biliary lesions and that for non-stenotic bile duct were 86.4%, and 68.9%, respectively. In the multivariate logistic regression analyses, age, and previous biliary stenting before POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. For non-stenotic bile duct, the location of the biliary lesion, endoscopic sphincterotomy (EST), and procedure time of POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps mapping biopsy. CONCLUSIONS: Previous biliary stenting was a factor affecting a low tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. In the POCS-guided forceps mapping biopsy, the location of the biliary lesion, EST, and procedure time were factors affecting tissue acquisition rates.