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Background: The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed. Method: A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias. Result: The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P <.05 in all the subtypes) where the multi‐metastasis and distant lymph node (dLN) only always indicated the worst and best prognosis, respectively. Chemotherapy presented the most significant survival impact with the lowest hazard ratio by multivariate cox model and still provided a survival improvement after PSM (all P <.001) in all subtypes. However, the median months manifested different between patients with and without chemotherapy among the subtypes (ICC, from 5 to 9; PHCC, from 6 to 10; AVC, from 4 to 9; GBC, from 6 to 7; DCC from 6 to 8). Conclusion: We provided a landscape about the detailed DM mode of the advanced BTC in a large population, found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported TIMs play an important role in tumors progression or regression, but the effect of TIMs in biliary tract cancer remains unclear. The aim of this study is to investigate the prognostic value of tumor infiltrating mast cells (TIMs) and its influence on gemcitabine-based adjuvant chemotherapy (ACT) benefits in biliary tract cancer patients after surgery.Methods: TIMs were evaluated by immunohistochemical staining of tryptase in 250 patients with resected gallbladder carcinoma (GBC) or extrahepatic bile duct carcinoma (EBDC) from Zhongshan Hospital. The relationships between TIMs and clinicopathological factors and postoperative prognosis were analyzed respectively.Results: High TIMs infiltration was significantly correlated with prolonged overall survival (OS). Furthermore, multivariate analysis indicated TNM stage and TIMs as independent prognostic factors for OS. Patients with high TIMs infiltration appeared to significantly benefit from Gemcitabine-based ACT in the discovery and validation cohorts. Spearman analysis identified that TIMs infiltration were positively correlated with anti-tumor CD8+ T cells.Conclusion: TIMs infiltration is an independent favorable prognostic factor in GBC and EBDC patients, which could better stratify patients with different prognosis and predict benefit from gemcitabine-based ACT. [ABSTRACT FROM AUTHOR]

Abstract: CD133+ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133+ tumor cells. Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133+ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As2O3 effectively induces CD133+ gallbladder carcinoma cells apoptosis. Treatment with As2O3 reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As2O3 on cells through activation of AKT signaling pathways. Collectively, As2O3 effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As2O3-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma. [Copyright &y& Elsevier]