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Highlighting concerns about the acceptance of oncologic therapies with no proven benefit, this article compares the interpretation of the clinical trial results of several studies conducted to identify a better therapy for patients with biliary tract cancer.

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. [ABSTRACT FROM AUTHOR]

The article focuses on the advancements and challenges of immune checkpoint blockade (ICB) therapy in cancer treatment. Topics include the historical context and development of ICB, mechanisms of action and resistance, and the exploration of biomarkers and combination therapies to enhance efficacy and overcome treatment limitations.

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. [ABSTRACT FROM AUTHOR]

Background and aims: Sarcopenia has been associated with poor prognosis in patients with malignant tumors. However, its impact on the outcomes of patients with biliary tract cancer (BTC) undergoing surgical resection remains unclear and warrants further review. This study aims to summarize the available evidence on this issue. Methods: A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies up to March 10, 2024. We extracted data on overall survival (OS), recurrence free survival (RFS), and postoperative major complications from the included studies as the outcomes of interest. Following data synthesis and analysis, we assessed the heterogeneity and performed subgroup analyses. Additionally, the potential for publication bias was evaluated. Results: A total of 26 studies involving 4292 BTC patients were ultimately retrieved. The findings indicated that sarcopenia was significantly associated with reduced OS in BTC patients after surgery (adjusted HR: 2.03, 95% CI: 1.65–2.48, P < 0.001, I2 = 57.4%). Moreover, sarcopenia may also be linked to poorer RFS (adjusted HR: 2.15, 95% CI: 1.79–2.59, P < 0.001, I2 = 0%) and increased postoperative major complications (OR: 1.22, 95% CI 1.02–1.47, P = 0.033, I2 = 29.2%) as well. Notably, no significant publication bias was detected through funnel plots and Egger's tests. Conclusion: Sarcopenia is associated with poorer OS in BTC patients following surgery. Additionally, it may serve as a prognostic indicator for poorer RFS and increased postoperative major complications. Further studies are warrant to standardize existing definitions and validate these findings. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) starts in the epithelial tissue (lining of the bile duct and gallbladder). It is a type of aggressive cancer called adenocarcinoma that can spread to other tissues. Among all cases of biliary tract cancer, 50% is from GBC. It is a deadly cancer with a survival rate of 17.6% between 2007 and 2013. GBC is rarely found in the Western world, but it is commonly found in South Asia. In Southeast Asian countries, GBC plays a significant role in cancer-related morbidity and mortality. GBC incidence exhibits marked regional variability, a rare condition in the western population but having a higher frequency in India, especially the Indo-Gangetic belt and some northeast districts excluding Nagaland. This might be attributed to the differences in environmental factors and genetic predisposition modulating carcinogenesis. In GBC, only 10% of cases are identified in the early stages. The low rate of early detection is due to the lack of screening techniques and the aggressive characteristics of the tumor. Various risk factors are associated with GBC, for example, chronic cholecystitis with or without gallstones, obesity, exposure to heavy metals such as lead and arsenic, bacterial infection, congenital biliary cysts, and abnormal pancreaticobiliary duct junction. The risk factors can cause chronic gallbladder mucosa irritation, leading to dysplasia and neoplasia. GBC can form metaplasia to dysplasia in a time span of 5-15 years, then to carcinoma in situ, and finally to invasive cancer. Dysbiosis is responsible for various diseases, including cancer. Multiple triggers can cause dysbiosis, for example, environmental changes, inflammation, infection, medications, dietary changes, or genetic predisposition. Various researches show that Helicobacter pylori, human papillomavirus, Hepatitis B virus, and Hepatitis C virus microbial species can cause cancer. They are the major species responsible for 90% of infection-associated cancers. Various studies demonstrate that the strains of Salmonella and Helicobacter colonize are linked to developing GBC. While the mechanisms linking gut microbiota to GBC are not fully understood, several studies have suggested a potential association. According to a study, certain gut microbiomes, such as Fusobacterium nucleatum, found glut in GBC tissues, compared to adjacent normal tissues. By evaluating gut microbiome dysbiosis, we can see the potential link between gut microbiome dysbiosis and GBC; it may provide valuable insights into the development and progression of GBC. It could lead to the identification of new diagnostic markers and the development of novel therapeutic strategies. In GBC, the evaluation of gut microbiome dysbiosis (involving evaluating the composition, diversity, and functional capacity of the gut microbiome in patients) has emerged as a promising method for understanding the molecular mechanisms and identifying biomarkers for early prevention and detection of GBC and also investigating the possibility of any link between the gut microbiome and host immune response. In conclusion, evaluating gut microbiome dysbiosis in GBC is a promising direction for identifying potential early detection and prevention biomarkers. Additional investigation is therefore needed to determine the role of gut microbiome dysbiosis in the development and progression of GBC and to identify reliable biomarkers for clinical use. [ABSTRACT FROM AUTHOR]