Search Results (87)

Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors to calculate the risk ratios (RR) and reported post-estimation marginal effects. Coefficient estimates, variance inflation factors, and Pearson’s goodness-of-fit test statistics were used to check for multicollinearity and model fit, respectively. We also performed a reclassification analysis by modeling Klatskin tumors (PCC) as extrahepatic (ECC), reclassifying them as intrahepatic (ICC), and comparing the corresponding changes in estimates. Results. Regression analysis revealed an increased risk of death in patients with ICC (RR = 2.05, 95% CI 1.11–3.78) and PCC (RR = 2.03, 95% CI 0.97–4.24) compared to those with DCC. When PCC was analyzed as an ECC, the ICC revealed an RR of 1.52 (95% CI 0.84–2.73). Further reclassification of PCC showed an RR of 2.04 for ICC (95% CI: 1.53–3.53). The adjusted marginal effects saw a reduction in the death probability for both ICC and ECC. However, post hoc analyses revealed insufficient evidence for differences between the reclassified models. Conclusions. Patients with DCC had slightly better prognosis compared to ICC and PCC. We found no differences in survival between ICC and ECC (combining DCC and PCC). The decrease in mortality risk due to reclassification in both groups was not confirmed statistically. Future studies should focus on statistical evidence when referring to the Will Rogers phenomenon, instead of inferring from raw comparisons. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation remain the cornerstone treatments for those with resectable disease, endoscopic techniques have emerged as versatile tools for diagnosis, therapy, and palliation. In recent years, there have been major advancements in endoscopic therapies, including radiofrequency ablation (RFA), intraluminal brachytherapy (ILBT), and photodynamic therapy (PDT). The current narrative review serves to provide an overview of current and emerging endoscopic strategies for CCA, emphasizing diagnostic capabilities, therapeutic approaches, palliative interventions, and future directions. Full article

Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article

The pharmacological treatment of cholangiocarcinoma (CCA) is often hampered by tumor resistance. Improving our understanding of this issue is crucial for developing strategies that can overcome drug refractoriness. We have established and characterized two novel human cell sublines derived from extrahepatic CCA EGI-1 cells that are resistant to cisplatin and 5-fluorouracil (5-FU). Migration and proliferation were analyzed using holographic microscopy. The expression of genes involved in drug uptake and efflux was determined by RT-qPCR. Cross-resistance to commonly used antitumor drugs was assayed using the MTT test. EGI-1 sublines resistant to cisplatin (CR) or 5-FU (FR) exhibited more than a three-fold increase in resistance to cisplatin and 5-FU, respectively, and showed reduced proliferation, migration, and colony-formation rates, along with an altered cell cycle compared to wild-type cells, while retaining tumorigenic capacity. The analysis of the transportome showed downregulation of uptake transporters and upregulation of the export pumps MRP3/4. EGI-1 cells with acquired resistance to 5-FU demonstrated cross-resistance to irinotecan and gemcitabine, while cisplatin-resistant cells showed decreased sensitivity to 5-FU and platinum derivatives. These resistant cell lines offer valuable models for investigating the molecular basis of chemoresistance in CCA, providing a robust platform for the development and evaluation of novel therapeutic strategies. Full article

The 26th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Saskatoon, Saskatchewan, on 17–18 October 2024. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with hepatocellular and biliary tract cancers. Specialists from the fields of medical and radiation oncology, interventional radiology, pathology and laboratory medicine, and general and hepatobiliary surgery participated in presentations and discussions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular and biliary tract cancers. Full article

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. Race also significantly impacts disparities in healthcare utilization and clinical outcomes. Our study focused on the impact of race on admission, clinical outcomes, and disposition of cholangiocarcinoma. Methods: We performed a retrospective analysis of cholangiocarcinoma-related hospital admissions, using the National Inpatient Sample for the year 2022. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, and Other. The data analysis was performed using STATA/BE version 18.5. Univariable and multivariable logistic regression models were applied to evaluate the relationship between race and clinical and healthcare utilization outcomes. Results: In 2022, 7479 hospitalizations were recorded for cholangiocarcinoma in the United States. Among these, 65.99% were White, 13.27% Hispanic, and 10.13% African American. There was a statistically significant difference in gender distribution across racial groups (p < 0.001), with males comprising the majority in all groups. Males outnumbered females in all racial groups except among the Hispanic group. Significant racial disparities in mortality were observed, with White patients showing a mortality rate of 6.69%, compared to higher rates among African American (9.76%), Native American (8.51%), and Asian or Pacific Islander (8.09%) patients, while Hispanic (5.04%) and Other (5.88%) groups had lower rates (p < 0.001). Conclusions: The study underscores the racial disparities among cholangiocarcinoma hospitalizations, with African American, Native American, and Asian patients facing disproportionately higher mortality and poorer in-hospital outcomes compared to White patients. This analysis highlights the healthcare strategies and policy reforms to promote equitable treatment by mitigating these disparities and to improve cholangiocarcinoma outcomes. Full article

Background: Bone metastasis (BM) prevalence is underreported in biliary tract cancers (BTC). This study aimed to assess BM prevalence in a real-world BTC population, alongside examining its relationship to prognosis and genomic alterations. Methods: Patients with histology-proven BTC as reviewed at a university cancer centre between January 2019 and August 2022 were assessed. Data extracted from records included BTC subtype, molecular profiling and systemic anti-cancer therapy (SACT) use. Stratification by BTC subtype and metastasis sites occurred. Median overall survival (mOS) was defined as time from relapse or metastases to death. Survival analysis was conducted using the Cox Proportional Hazard model. Results: Of 197 patients, 74 (37.6%) had intrahepatic and 67 (34%) had extrahepatic cholangiocarcinoma. Thirty-four patients had BM (17.3%), with 14 identified at initial diagnosis. OS was not influenced by bone (HR 1.15; p = 0.48) or liver metastases (HR 1.09; p = 0.6). Stratifying for age and gender, no significant difference in OS was observed. Actionable alterations were equally likely in patients with (52.4%) and without BM (58.5%). Age of BTC onset (<65 or ≥65) did not significantly influence prevalence of actionable alterations. Patients receiving matched, targeted SACT had a mOS of 29.9 months, compared to 13.3 months in those with actionable alterations but no SACT matching (HR 0.35; p < 0.005). Conclusions: In advanced BTC, BM do not affect OS. Across all cohorts, actionable alterations improved OS when treated with matched SACT. Full article

Introduction: Biliary tract cancers (BTC) comprise a heterogeneous group of malignancies, including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The main determinants of prognosis in BTC are the stage of the disease and the eligibility for curative treatment. Additionally, liver functional capacity is also one of the factors influencing survival in biliary tract cancers. The age–bilirubin–INR–creatinine (ABIC) score has been previously shown to predict prognosis in hepatic diseases. The aim of our study is to demonstrate the relationship between the ABIC score and prognosis in BTC. Materials and Methods: In this study, a retrospective analysis was performed on 41 patients with non-metastatic BTC and 73 patients with metastatic BTC who were followed up in our clinic between 2003 and 2025. All patients were ≥18 years old at the time of diagnosis, and BTC was pathologically confirmed. The ABIC score was calculated separately for each group. A threshold value for the ABIC score was determined using Receiver Operating Characteristic (ROC) analysis, and based on this threshold, patients were divided into low and high ABIC score groups. Both the relationship between the ABIC score and prognosis and the other factors affecting prognosis were investigated. Results: In the non-metastatic BTC group, the cutoff value for the ABIC score was 6.89. The median survival time of patients with a high ABIC score was significantly shorter. In the metastatic BTC group, the cutoff value for the ABIC score was 7.41. Similarly, in this group, patients with a high ABIC score had a significantly shorter median survival time. Additionally, in the non-metastatic BTC group, tumor localization and stage were prognostic factors affecting survival, while in the metastatic BTC group, CEA and first-line chemotherapy were the prognostic factors influencing overall survival. Conclusions: We demonstrate that the ABIC score is a prognostic factor determining median survival in both non-metastatic and metastatic BTC patients. Full article

Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3–4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases. Full article

Cholangiocarcinoma (CCA) represents approximately 3% of all gastrointestinal cancers and is a highly heterogeneous and aggressive malignancy originating from the epithelial cells of the biliary tree. CCA is classified by anatomical location into intrahepatic (iCCA), extrahepatic (eCCA), gallbladder cancer (GBC), and ampullary cancers. Although considered a rare tumor, CCA incidence has risen globally, particularly due to the increased diagnosis of iCCA. Genomic and immune profiling studies have revealed significant heterogeneity within CCA, leading to the identification of molecular subtypes and actionable genetic alterations in 40–60% of cases, particularly in iCCA. Among these, FGFR2 rearrangements or fusions (7–15%) and IDH1 mutations (10–20%) are common in iCCA, while HER2 amplifications/overexpression are more frequent in eCCA and GBC. The tumor-immune microenvironment (TIME) of CCAs plays an active role in the pathogenesis and progression of the disease, creating a complex and plastic environment dominated by immune-suppressive populations. Among these, cancer-associated fibroblasts (CAFs) are a key component of the TIME and are associated with worse survival due to their role in maintaining a poorly immunogenic landscape through the deposition of stiff extracellular matrix and release of pro-tumor soluble factors. Improved understanding of CCA tumor biology has driven the development of novel treatments. Combination therapies of cisplatin and gemcitabine with immune checkpoint inhibitors (ICIs) have replaced the decade-long standard doublet chemotherapy, becoming the new standard of care in patients with advanced CCA. However, the survival improvements remain modest prompting research into more effective ways to target the TIME of CCAs. As key mechanisms of immune evasion in CCA are uncovered, novel immune molecules emerge as potential therapeutic targets. Current studies are exploring strategies targeting multiple immune checkpoints, angiogenesis, and tumor-specific antigens that contribute to immune escape. Additionally, the success of ICIs in advanced CCA has led to interest in their application in earlier stages of the disease, such as in adjuvant and neoadjuvant settings. This review offers a comprehensive overview of the immune biology of CCAs and examines how this knowledge has guided clinical drug development, with a focus on both approved and emergent treatment strategies. Full article

Background/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004–2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan–Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson–Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6–2.7) and HR 2.94 (95% CI 2.3–3.8)) and ECC (HR 2.1 (95% CI 1.8–2.5) and HR 3 (95% CI 2.4–3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor. Full article

Background: Obstructive jaundice is a common health challenge in daily clinical practice caused by a heterogeneous group of benign and malignant conditions in or around extrahepatic bile ducts. This study aimed to investigate the causes of obstructive jaundice, analyze the age and sex distribution, and report the locations of obstruction. Methods: This was a retrospective study of electronic records of patients diagnosed with obstructive jaundice in the Hadhramout region in Yemen. Results: This study analyzed the data of 303 patients (mean age: 57 ± 17.99 years; range: 18–95 years); 60.40% (n = 183) were female, and 39.60% (n = 120) were male. The highest prevalence was found in middle-aged adults (n = 112, 36.96%), followed by the old (n = 101, 33.33%). Common bile duct (CBD) stones were the most common cause of obstructive jaundice (n = 175, 57.8%), followed by CBD stricture (n = 58, 19.1%), carcinoma of the head of the pancreas (n = 35, 11.6%), cholangiocarcinoma (n = 21, 6.9%), and external compression of the CBD (n = 2, 0.7%). CBD stones, cholangiocarcinoma, and ampulla of Vater masses were more prevalent in females (30.9%, 3.8%, and 2.2%, respectively) than in males (25.8%, 2.9%, and 1.7%, respectively). In contrast, CBD stricture and carcinoma of the pancreas were more frequent in males, occurring in 12.1% and 7.1% of male patients, respectively, compared to 7.9% and 4.9% in female patients. The primary obstruction site was the CBD (n = 254, 83.8%), followed by the head of the pancreas (n = 30, 9.9%), and the ampulla of Vater (n = 13, 4.3%). Conclusions: Obstructive jaundice predominantly affects middle-aged adults followed by the old-aged patients predominantly in females. The most common cause of obstructive jaundice was CBD stones, followed by CBD stricture, while carcinoma of the head of the pancreas was the most common malignant cause, followed by cholangiocarcinoma. Distal CBD is the most common anatomical location of obstructive jaundice. Full article

Background and Aims: Pancreaticobiliary maljunction (PBMJ) has a long common channel (CC) that causes pancreaticobiliary reflux (PBR), which has been implicated in gallstones, cholangiocarcinoma, and pancreatitis. By contrast, PBR has occurred in cases with normal and longer CCs than normal but shorter than PBMJ. This pathophysiology has been primarily reported in adults and rarely in children. We sometimes observe this pathophysiology in children with pancreatitis and cholelithiasis. Herein, we report the clinical figures on the diagnosis of children with PBR in normal and relatively long CCs. Patients and Methods: This study included seven children who complained of refractory pancreatitis and cholelithiasis diagnosed with PBR in normal and relatively long CCs at our institution from August 2018 to September 2024. We measured the lengths of their CCs and sphincter of Oddi muscles via endoscopic retrograde cholangiopancreatography (ERCP) and cholangiography. In addition, amylase and lipase levels in bile juice were measured. Results: All seven children demonstrated elevated amylase and lipase levels in bile juice obtained from gallbladder drainage and/or the common bile duct. ERCP and cholangiography indicated 2.2–5.5-mm lengths of CCs in their cases, which are normal lengths in two cases and relatively longer (0.3–1.1 mm: mean 0.6 mm) than the normal upper limit of CC in children in five cases, with their CCs shorter than the sphincters of Oddi. All children underwent extrahepatic bile duct resection and bilio–jejunal anastomosis, demonstrating no clinical symptom recurrence postoperatively. Conclusions: Some children with cholelithiasis and pancreatitis exhibit normal and relatively long CCs, causing PBR and inducing gastrointestinal diseases. Careful investigation by ERCP and cholangiography focused on the CC length, and pancreatic enzyme level assessments in bile juice are useful for diagnosing PBR in children with cholelithiasis and refractory pancreatitis. Full article

Cholangiocarcinoma is a malignant tumor that emerges in the intrahepatic or extrahepatic bile ducts. Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs. In this study, we undertook a preliminary exploration of the mechanism through which DOR inhibits the viability of human cholangiocarcinoma cells (Mz-ChA-1) via transcriptome analysis and molecular validation at the cellular level. The results indicated that DOR could suppress the growth and proliferation of Mz-ChA-1 cells in a dose-dependent manner. Moreover, it significantly diminished their migration and invasion abilities. Cell cycle analysis disclosed arrest in the G1 phase, accompanied by an increase in p21 expression and a decrease in the levels of the cyclin E1 and CDK2 proteins. Additionally, DOR induced apoptosis via the ROS-triggered mitochondrial pathway. This was attested by an elevation in the BAX/BCL-2 ratio, the activation of caspase 3/7 and the cleavage of PARP1. These mechanistic insights underscore DOR’s potential as a therapeutic agent against cholangiocarcinoma Full article

Background: Post-hepatectomy liver failure (PHLF) is a serious complication following hepatic resection for Klatskin tumors, significantly affecting patient prognosis. Identifying reliable preoperative and early postoperative predictors of PHLF can help optimize patient outcomes and guide surgical planning. Method: We conducted a retrospective review of 34 patients who underwent hemi-hepatectomy for extrahepatic cholangiocarcinoma at Kosin University Gospel Hospital between April 2019 and April 2024, and at Chonnam National University Hwasun Hospital between September 2017 and April 2024. Demographics, laboratory data, and volumetric measurements including spleen volume, were analyzed to assess their roles in predicting PHLF. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive value of these factors. Results: Elevated preoperative glucose levels and reduced future liver remnant to spleen ratio (FLR/SV) were significantly associated with an increased risk of PHLF. Additionally, elevated postoperative day 1 total bilirubin (POD 1 TB) was identified as a key postoperative predictor of PHLF. Multivariable analysis confirmed the significance of these factors, with FLR/SV, preoperative glucose, and POD 1 TB demonstrating good discriminative ability in ROC analysis, with AUC values of 0.779, 0.782, and 0.786 respectively. Conclusion: Preoperative glucose control, evaluation of FLR/SV, and early postoperative monitoring of TB are useful for improving outcomes in patients undergoing major hepatectomy for Klatskin tumors. Full article