Prospective assessment of probe-based confocal laser endomicroscopy under direct cholangioscopic visualization for biliary strictures that could not be definitively diagnosed using endoscopic retrograde cholangiopancreatography (with video).

The definitive diagnosis of patients with indeterminate biliary strictures remains challenging. Probe-based confocal laser endomicroscopy (pCLE) provides real-time histological assessment of bile duct tissues. Since no previous studies have evaluated the efficacy of pCLE under direct cholangioscopic visualization for biliary strictures that cannot be definitively diagnosed through endoscopic retrograde cholangiopancreatography using fluoroscopy, we prospectively assessed the feasibility and safety of this procedure in three cases. pCLE findings were obtained in three cases, providing accurate diagnoses. Additionally, no adverse event was reported. pCLE under direct cholangioscopic visualization for indeterminate biliary strictures might be feasible and safe, even though these strictures were not previously diagnosed using endoscopic retrograde cholangiopancreatography. Further studies with more cases are warranted to clarify the effectiveness of pCLE under direct cholangioscopic visualization.

Exploring the impact of durvalumab on biliary tract cancer: insights from real-world clinical data.

INTRODUCTION: This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes. METHODS: A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies. RESULTS: Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052). CONCLUSION: This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Chemotherapy combined with regorafenib and immune checkpoint inhibitors as a first-line treatment for patients with advanced biliary tract cancer: a single arm phase II trial.

Objective: This study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC). Methods: In this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions. Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%). Conclusion: The combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.

Evolving therapeutic landscape of advanced biliary tract cancer: from chemotherapy to molecular targets.

Biliary tract cancer, the second most common type of liver cancer, remains a therapeutic challenge due to its late diagnosis and poor prognosis. In recent years, it has become evident that classical chemotherapy might not be the optimal treatment for patients with biliary tract cancer, especially after failure of first-line therapy. Finding new treatment options and strategies to improve the survival of these patients is therefore crucial. With the rise and increasing availability of genetic testing in patients with tumor, novel treatment approaches targeting specific genetic alterations have recently been proposed and have demonstrated their safety and efficacy in numerous clinical trials. In this review, we will first consider chemotherapy options and the new possibility of combining chemotherapy with immune checkpoint inhibitors in first-line treatment. We will then provide an overview of genomic alterations and their potential for targeted therapy especially in second-line therapy. In addition to the most common alterations such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, fibroblast growth factor receptor 2 (FGFR2) fusions, and alterations, we will also discuss less frequently encountered alterations such as BRAF V600E mutation and neurotrophic tyrosine kinase receptor gene (NTRK) fusion. We highlight the importance of molecular profiling in guiding therapeutic decisions and emphasize the need for continued research to optimize and expand targeted treatment strategies for this aggressive malignancy.

Phase I/II study of nivolumab plus lenvatinib for advanced biliary tract cancer (JCOG1808/NCCH1817, SNIPE).

BACKGROUND: Although cisplatin plus gemcitabine and other combinations have improved the survival of advanced biliary tract cancer (BTC), high unmet medical needs remain. This study aimed to assess the efficacy and safety of nivolumab plus lenvatinib in the second-line treatment for advanced BTC. PATIENTS AND METHODS: Nivolumab (240 mg) was administered biweekly. Phase I determined the recommended phase II dose of lenvatinib (20 mg or 14 mg). In phase II, the primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The planned sample size was 32 patients with a power of 80%, a one-sided alpha error of 5%, threshold ORR of 10%, and expected ORR of 30%. RESULTS: In phase I, the recommended dose of lenvatinib was determined to be 20 mg in six patients, with one dose-limiting toxicity (myocarditis). In phase II, we enrolled 26 patients. ORR, DCR, and median OS and PFS were 9.4% [90% confidence interval (CI) 2.6% to 22.5%], 53.1% (95% CI 34.7% to 70.9%), and 6.4 months (95% CI 4.9-9.7 months) and 2.5 months (95% CI 1.5-4.1 months), respectively. No response was observed in patients with the usage of antibiotics. The grade 3 or 4 adverse events were hypertension (59.4%) and biliary tract infection (37.5%). Rash (28.1%) and hypothyroidism (21.9%) were observed as immune-mediated adverse events of any grade. CONCLUSIONS: Nivolumab plus lenvatinib had a manageable safety in advanced BTC, but its efficacy in the second-line treatment was limited.

Exceptional sustained long-term complete response to Tepotinib in a MET-amplified advanced intrahepatic biliary tract cancer failing Durvalumab plus Cisplatin and Gemcitabine.

BACKGROUND: Biliary tract cancers (BTCs) are a diverse group of malignancies with varied genetic backgrounds. The prevalence of intrahepatic cholangiocarcinoma (iCC) is increasing, particularly in Western countries. Despite advancements in treatments, the prognosis for BTC remains poor. Recent molecular profiling has revealed that up to 40% of iCC cases have targetable genetic alterations. MET amplification, although rare, presents a significant target for therapy. CASE PRESENTATION: A 25-year-old female with a history of ulcerative colitis presented with shoulder pain and a positron emission tomography-computed tomography (PET-CT) scan revealed an enlarged liver and multiple metastases. Histopathological analysis diagnosed poorly differentiated adenocarcinoma. First-line therapy with Cisplatin, Gemcitabine, and Durvalumab resulted in disease progression. Molecular profiling identified a TP53 mutation and MET amplification. Based on these findings, Tepotinib was initiated. Tepotinib treatment led to a significant reduction in tumor size and normalization of CA 19-9 levels within 2 months, achieving a complete metabolic remission lasting up to 17 months. The treatment was well tolerated with minimal side effects. DISCUSSION: MET-amplified BTCs are exceedingly rare, and evidence for targeted treatment is limited. This case demonstrates the efficacy of Tepotinib in a young patient with MET-amplified iCC, showing a long-term response and suggesting a potential new standard treatment option for this molecularly defined entity. This case also highlights the aggressive nature of MET-amplified tumors and the need for targeted second-line therapies. CONCLUSION: Tepotinib showed remarkable efficacy in treating MET-amplified intrahepatic cholangiocarcinoma, underscoring the importance of molecular profiling in BTCs and suggesting a potential new therapeutic approach for this rare cancer subtype.

[18F]FDG PET/CT in Benign and Malignant Diseases Involving the Biliary Tract.

Role of FDG PET/CT in evaluation of biliary tract diseases remains relatively unexplored. PET/CT with FDG helps in evaluation of both infective / inflammatory as well as neoplastic diseases as increased glucose utilization is observed in both the conditions. In this article, we describe the spectrum of FDG PET/CT findings in various diseases affecting the biliary tract. Role of FDG PET/CT in neoplastic diseases involving the biliary duct has been described at the time of staging and response evaluation; in characterization of the intrahepatic mass (abscess v/s cholangiocarcinoma). In addition, we have discussed about the false positive FDG uptake along the biliary duct stent, which interfere with scan interpretation. Few of the benign conditions described are Langerhans cell histiocytosis and IgG4 related disease involving the biliary duct and adenomyomatosis and Xanthogranulomatous cholecystitis involving the gall bladder.

Efficacy and safety of camrelizumab combined with chemotherapy in the treatment of advanced biliary malignancy and associations between peripheral blood lymphocyte subsets and clinical outcomes.

BACKGROUND: Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. METHODS: 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. RESULTS: The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. CONCLUSIONS: Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

Cost-effectiveness analysis of immune checkpoint inhibitors as first-line therapy in advanced biliary tract cancer.

Aim: To assess the cost-effectiveness of immune checkpoint inhibitors as first-line treatments for advanced biliary tract cancer (BTC).Methods: This pharmacoeconomic evaluation employed the fractional polynomial network meta-analysis and partitioned survival model. Costs and utilities were collected from the literature and databases. Sensitivity analyses were used to examine uncertainties.Results: The incremental cost-effectiveness ratios (ICERs) of first-line treatment strategies were $761,371.37 per quality-adjusted life-year (QALY) or $206,222.53/QALY in the US and $354,678.79 /QALY or $213,874.22/QALY in China, respectively. The sensitivity analysis results were largely consistent with the base case.Conclusion: From the US and Chinese payer perspectives, adding durvalumab or pembrolizumab to chemotherapy is unlikely to be cost effective in the first-line setting for advanced BTC.

[Box: see text].

Anatomical classification of advanced biliary tract cancer predicts programmed cell death protein 1 blockade efficacy.

Background: Immune checkpoint blockade (ICB)-based immunotherapy has inspired new hope for advanced biliary tract cancer (BTC) treatment; however, there are no prior studies that primarily focus on different anatomical types of unresectable BTCs reacting differently to ICB. Methods: We retrospectively collected data on advanced BTC patients who received anti-programmed cell death protein 1 (anti-PD1) therapy from two affiliated hospitals of Sun Yat-Sen university. The effects of anti-PD1 were compared for different anatomical sites. The GSE32225 and GSE132305 datasets were used to further analyze differences in the immune microenvironments between intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Results: A total of 198 advanced BTC patients were enrolled in this study, comprising 142 patients with ICC and 56 with other cancer types ("Others" group), including ECC and gallbladder cancer. In the anti-PD1 treated patients, the ICC group (n = 90) achieved longer median progression-free survival (mPFS) (9.5 vs. 6.2 months, p = 0.02) and median overall survival (mOS) (15.1 vs. 10.7 months, p = 0.02) than the Others group (n = 26). However, chemotherapy did not show different effects between the two groups (mOS: 10.6 vs. 12.1 months, p = 0.20; mPFS: 4.9 vs. 5.7 months, p = 0.83). For the first-line anti-PD1 therapy, the ICC group (n = 70) achieved higher mOS (16.0 vs. 11.8 months, p = 0.04) than the Others group (n = 19). Moreover, most chemokines, chemokine receptors, major histocompatibility complex molecules, immunostimulators, and immunoinhibitors were stronger in ICC than ECC; furthermore, CD8+ T cells and M1 macrophages were higher in ICC than ECC for most algorithms. The immune differential genes were mainly enriched in antigen processing and presentation as well as the cytokine receptors. Conclusions: This study shows that the efficacy of anti-PD1 therapy was higher in ICC than in other types of BTCs. Differences in the immune-related molecules and cells between ICC and ECC indicate that ICC could benefit more from immunotherapy.

Targeted therapy with polymeric nanoparticles in PBRM1-mutant biliary tract cancers: Harnessing DNA damage repair mechanisms.

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10 % of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

Safety of pressurized intraperitoneal aerosolized chemotherapy in biliary cancer patients with peritoneal metastases.

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

[Box: see text].

The HALP score as a prognostic factor in metastatic biliary cancer.

BACKGROUND: Biliary tract cancers are serious diseases and new biomarkers may be useful for the optimal management and prediction of these cases. This study aimed to evaluate the prognostic significance of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a novel composite marker, in patients with metastatic biliary tract cancer. METHODS: Patients with biliary tract cancers were analyzed retrospectively. Laboratory values, patient and disease characteristics, and survival rates were evaluated. The diagnostic impact of the HALP score was assessed with regression analyses. RESULTS: The study included 106 individuals with metastatic biliary tract cancer. Based on the median HALP score, ≥ 2.22 was considered a high score and < 2.22 was considered low. The overall average survival time was found to be 11.4 months. Patients with low HALP scores had median overall survival of 9.5 months, while those with high HALP scores had median overall survival of 15.9 months. In multivariate analysis, Eastern Cooperative Oncology Group performance status, CA19-9 level, and HALP score remained significant predictors of overall survival. CONCLUSION: The HALP score appears to be a useful prognostic marker in patients with metastatic biliary tract cancer.

Multimodal Convolutional Neural Network-Based Algorithm for Real-Time Detection and Differentiation of Malignant and Inflammatory Biliary Strictures in Cholangioscopy: a Proof of Concept Study with Video.

BACKGROUND AND AIMS: Deep learning algorithms gained attention for detection (CADe) of biliary tract cancer (BTC) in digital single-operator cholangioscopy (dSOC). We developed a multimodal convolutional neural network (CNN) for detection (CADe) characterization and discriminating (CADx) between malignant, inflammatory and normal biliary tissue in raw dSOC videos. In addition, clinical metadata was included in the CNN algorithm to overcome limitations of image-only models. METHODS: Based on dSOC videos and images of 111 patients (total of 15,158 still frames), we developed and validated a real-time CNN-based algorithm for CADe and CADx. We established an image-only model and metadata injection approach. In addition, we validated frame-wise and case-based predictions on complete dSOC video sequences. Model embeddings were visualized and class-activation maps highlighted relevant image regions. RESULTS: The concatenation-based CADx approach achieved a per-frame AUC of 0.871, sensitivity of 0.809 (95% CI: [0.784-0.832]), specificity of 0.773 [0.761-0.785], PPV of 0.450 [0.423-0.467], and NPV of 0.946 [0.940-0.954] with respect to malignancy on 5,715 test frames from complete videos of 20 patients. For case-based diagnosis using average prediction scores, six out of eight malignant cases and all twelve benign cases were identified correctly. CONCLUSION: Our algorithm distinguishes malignant and inflammatory bile duct lesions in dSOC videos, indicating the potential of CNN-based diagnostic support systems for both, CADe and CADx. The integration of non-image data can improve CNN based support systems, targeting current challenges in the assessment of biliary strictures.

Epidemiological, clinical and microbiological characteristics of patients with biliary tract diseases with positive bile culture in a tertiary hospital.

PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.

Casual effects of type 1 diabetes mellitus on site-specific digestive cancers: a Mendelian randomisation analysis.

Objective: Despite several observational studies attempting to investigate the potential association between type 1 diabetes mellitus (T1DM) and the risk of digestive cancers, the results remain controversial. The purpose of this study is to examine whether there is a causal relationship between T1DM and the risk of digestive cancers. Methods: We conducted a Mendelian randomisation (MR) study to systematically investigate the effect of T1DM on six most prevalent types of digestive cancers (oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer). A total of 1,588,872 individuals were enrolled in this analysis, with 372,756 being the highest number for oesophageal cancer and 3,835 being the lowest for pancreatic cancer. Multiple MR methods were performed to evaluate the causal association of T1DM with the risk of six site-specific cancers using genome-wide association study summary data. Sensitivity analyses were also conducted to assess the robustness of the observed associations. Results: We selected 35 single nucleotide polymorphisms associated with T1DM as instrumental variables. Our findings indicate no significant effect of T1DM on the overall risk of oesophageal cancer (OR= 0.99992, 95% CI: 0.99979-1.00006, P= 0.2866), stomach cancer (OR=0.9298,95% CI: 0.92065-1.09466, P= 0.9298), hepatocellular carcinoma (OR= 0.99994,95% CI: 0.99987-1.00001, P= 0.1125), biliary tract cancer (OR=0.97348,95% CI: 0.8079-1.1729, P= 0.7775)), or pancreatic cancer (OR =1.01258, 95% CI: 0.96243-1.06533, P= 0.6294). However, we observed a causal association between T1DM and colorectal cancer (OR=1.000, 95% CI: 1.00045-1.0012, P<0.001), indicating that T1DM increases the risk of colorectal cancer. We also performed sensitivity analyses, which showed no heterogeneity or horizontal pleiotropy. For the reverse MR from T1DM to six digestive cancers, no significant causal relationships were identified. Conclusions: In this MR study with a large number of digestive cancer cases, we found no evidence to support the causal role of T1DM in the risk of oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, we found a causal positive association between T1DM and colorectal cancer. Further large-scale prospective studies are necessary to replicate our findings.

Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort.

BACKGROUND: Combined Immuno-chemotherapy consisting of gemcitabine, cisplatin and the programmed death-ligand one inhibitor durvalumab (GCD) is the new standard of care for patients with biliary tract cancers (BTC) based on positive results of the TOPAZ-1 study. OBJECTIVE: We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort. METHODS: Patients with BTC treated with GCD from 9 German centers were included. Clinicopathological baseline parameters, overall survival (OS), response rate and adverse events (AEs) were retrospectively analyzed. The prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. RESULTS: A total of 165 patients treated with GCD between 2021 and 2024 were included in the study. Median OS and median progression-free survival were 14 months (95% CI 10.3-17.7) and 8 months (95% CI 6.8-9.2), respectively. The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, mOS was significantly shorter in patients with gall bladder cancer (GB-CA) with 9 months (95% CI 5.5-12.4; p = 0.02). In univariate analyses age ≥70 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1, status post cholecystectomy, GB-CA and high baseline CRP values were significantly associated with OS. ECOG PS ≥ 1 and GB-CA remained independent prognostic factors for OS in multivariable cox regression analysis. AEs have been reported in 130 patients (78.8%), including 149 grade 3-4 AEs (25.5%). One patient died of severe infectious pneumonia. Immune-related (ir)AEs occurred in 17 patients (10.3%), including 9 grade 3-4 irAEs (2.2%), which led to treatment interruption in 4 patients. CONCLUSIONS: Immuno-chemotherapy in patients with BTC was feasible, effective and safe in a real-life scenario. Our results were comparable to the phase 3 clinical trial results (TOPAZ-1). Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

Evaluating the frequency and risk factors of multidrug-resistant bacteria in biliary samples.

Background and Objectives: This study aimed to evaluate the frequency of multidrug-resistant (MDR) bacteria in biliary samples, MDR-bacteria risk factors, and the relationship between MDR-bacteria positivity and some clinical outcomes. Materials and Methods: The study was conducted between May 2018 and May 2023, including patients over the age of 18 who had positive culture results in biliary samples. The frequency of MDR-bacteria in biliary samples was evaluated. Risk factors for MDR bacteria were assessed using univariate and multivariate analyses. MDR and non-MDR groups were compared inappropriate empirical antibiotic treatment, total antibiotic treatment duration, length of stay, and in-hospital mortality. Results: 342 microorganisms were isolated from 202 patients. Escherichia coli was the most commonly (37.2%) isolated Gram-negative microorganism, and Enterococcus spp. was the most commonly (70.2%) isolated Gram-positive microorganism. The incidence of MDR microorganisms was 42.3%. Gastrointestinal malignancy (OR: 1.96; 95% CI, 1.03-3.71) and previous antibiotic use (OR: 2.26; 95% CI, 1.09-4.68) were independent risk factors for MDR-bacteria. In the MDR group, inappropriate empirical antibiotic treatment (56.6% vs. 41%, p = 0.091), total antibiotic treatment duration (13 vs. 8 days, p = 0.054), length of stay (24 vs. 15 days, p = 0.001), and in-hospital mortality (27.3% vs. 22.3%, p = 0.416) were higher compared to the non-MDR group. Conclusion: MDR-bacteria positivity is associated with inappropriate antibiotic treatment, prolonged hospitalization, and increased mortality. Screening, antibiotic prophylaxis, and empirical treatment approaches should be carefully performed in patients with malignancy and recent antibiotic use, which are significant risk factors for MDR-bacteria.