Sheng Shen

Background & Aims: ICC is a malignant tumor that originates from the intrahepatic bile ducts with insidious symptoms and a poor prognosis. Early diagnosis methods and therapeutic targets are urgently needed for ICC. Methods: We utilized a comprehensive set of analytical techniques to elucidate the role and mechanisms of DCDC2 in ICC. Our study included protein microarrays, transcriptome analysis, functional assays, immunofluorescence, dual-luciferase reporter assays, as well as xenograft models and humanized PBMC models. Results: Our study demonstrates that elevated levels of anti-DCDC2 autoantibodies in the serum of ICC patients indicate its potential utility as a diagnostic biomarker. Comprehensive in vitro and in vivo analyses reveal that DCDC2 promotes ICC proliferation, metastasis, and immune evasion. Mechanistically, DCDC2 stabilizes ENO1, resulting in enhanced AKT phosphorylation and increased expression of FGL1. Notably, elevated FGL1 levels significantly impair CD8⁺ T cell functionality via the FGL1-LAG3 axis. Conclusion: Our findings position anti-DCDC2 autoantibody as a promising diagnostic biomarker for ICC, associated with poor prognostic outcomes, and elucidate its critical role in tumor growth and immune evasion through its interaction with ENO1.

The human body comprises various tubular structures that have essential functions in different bodily systems. These structures are responsible for transporting food, liquids, waste, and other substances throughout the body. However, factors such as inflammation, tumors, stones, infections, or the accumulation of substances can lead to the narrowing or blockage of these tubular structures, which can impair the normal function of the corresponding organs or tissues. To address luminal obstructions, stenting is a commonly used treatment. However, to minimize complications associated with the long-term implantation of permanent stents, there is an increasing demand for biodegradable stents (BDS). Magnesium (Mg) metal is an exceptional choice for creating BDS due to its degradability, good mechanical properties, and biocompatibility. Currently, the Magmaris^® coronary stents and UNITY-B^TM biliary stent have obtained Conformité Européene (CE) certification. Moreover, there are several other types of stents undergoing research and development as well as clinical trials. In this review, we discuss the required degradation cycle and the specific properties (anti-inflammatory effect, antibacterial effect, etc.) of BDS in different lumen areas based on the biocompatibility and degradability of currently available magnesium-based scaffolds. We also offer potential insights into the future development of BDS.

Gallbladder cancer (GBC) is one of the lethal cancers with an extremely poor prognosis. In the recent 20 years, research on GBC has developed rapidly. Here we aim to perform a systematical bibliometric analysis on the current foci and status of GBC research. This study analyzes trends in GBC research and compares contributions from different countries and regions, institutions, and authors. All publications in GBC research from 2001 to 2021 in the Web of Science Core Collection (WoSCC) database were collected. Microsoft Excel 2010 and GraphPad Prism 9 were used to analyze publication data and publication trends. VOSviewer 1.6.17 was adapted to generate a visual network of keywords in surgical training research. A total of 3,323 publications were included. China was the most productive country, with the highest number of publications (n = 900, 27.08%). Shanghai Jiaotong University and Roa JC were the most productive institution and authors, contributing 215 and 89 publications, respectively. Keywords were classified into five clusters, each representing a key topic. The main clusters of GBC are related to surgery therapy, mechanism research-related study, and non-surgery therapy, while migration is the current hotspot of GBC research. The scientific progression of GBC research over the past two decades was comprehensively analyzed by this bibliometric study. Finding deeper mechanisms in the migration of GBC cells, new biomarkers, and highly effective nomograms will be the major problems and directions in the future.

Background: In this study, we aimed at elucidating the postoperative survival and prognostic factors in patients with biliary neuroendocrine neoplasm (NEN). Methods: Cases of biliary system NEN and adenocarcinoma from 1975 to 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A propensity score matching (PSM) method was used to adjust baseline differences in clinicopathological characteristics in our analysis. The Kaplan–Meier analysis was carried out for survival analysis. Results: A total of 233 patients with biliary system NEN were enrolled in this study, of which 119 patients’ lesions located in gallbladder, while the others’ located in bile duct. The postoperative overall survival of bile duct NEN is significantly longer than that of gallbladder NEN (P < 0.001). For gallbladder NENs, surgery method (P = 0.020) and lymph node metastasis (P = 0.018) were identified as independent prognostic factors. In terms of ampulla of vater (AOV) NENs, age (P = 0.017) and lymph node metastasis (P = 0.006) were identified as independent prognostic factors, while grade (P = 0.002) and lymph node metastasis (P = 0.036) were identified as independent prognostic factors for extrahepatic bile duct (EBD) NENs. PSM analysis indicated that patients with biliary duct NENs have a better postoperative prognosis than biliary duct adenocarcinoma. Conclusions: Patients with NEN have better overall survival than patients with adenocarcinoma. Gallbladder NEN has an adverse prognosis than that of biliary tract NEN. The pathological subtype, differentiation, lymph node metastasis, surgery method, and lymph node resection could affect the postoperative prognosis of the gallbladder and biliary tract NEN.

Cholangiocarcinoma (CCA) is one of the most lethal types of solid tumors worldwide. Lymph node metastasis is common in the early stage, which is associated with recurrence and reduced survival time after CCA resection. The molecular pathogenesis of CCA is complex and requires extensive investigation. It involves multiple genomic alterations and the dysregulation of signaling pathways. Biliverdin reductase B (BLVRB) is a non-redundant NAD(P)H-dependent biliverdin reductase that regulates cellular redox status by reducing biliverdin to bilirubin. This study aimed at describing the biological functions and molecular mechanisms of BLVRB in human CCA. Prognostic clinical data showed that low expression BLVRB was associated with poor prognosis and lymph node metastasis. BLVRB depletion accelerated epithelial-mesenchymal transition (EMT), cell migration and invasion. In contrast, BLVRB overexpression was associated with reduced EMT and cell migration and invasion in CCA. BLVRB suppression activated Notch signaling, and activated c-Notch enhanced EMT by upregulating Snail expression levels, thereby increasing cell migration and invasion in CCA. Our results identified an unexpected function of BLVRB in CCA migration and invasion through the regulation of Notch/Snail signaling.

Background: The clinical benefits and efficacies of adjuvant therapies for gallbladder cancer (GBC) have not been verified due to insufficient clinical evidence. Methods: Patients with resected nonmetastatic stage II–IV GBC were selected from the Surveillance, Epidemiology, and End Results database and distributed into nonchemotherapy and chemoradiotherapy (NCRT), chemotherapy (CT), and chemoradiotherapy (CRT) groups. Generalized propensity score and inverse probability of treatment weighting (IPTW) were used to reduce the imbalances between groups. Results: A total of 2,689 patients were enrolled, among whom 1,193 (44.4%) were classified as stage II, 1,371 (51.0%) as stage III, and 125 (4.6%) as stage IV GBC. A total of 1,703, 444, and 542 patients were placed in the NCRT, CT, and CRT groups, respectively. After the IPTW, there were no significant differences in overall survival (OS) between the 3 treatment groups (p > 0.05) in stage II GBC patients. In patients with stage III–IV GBC, the CT group exhibited a superior OS compared to the NCRT group (p < 0.001). In addition, the CRT group exhibited a superior OS compared to the CT (p < 0.001) and NCRT (p < 0.001) groups. For patients with stage III–IV tumors, a nomogram was constructed to predict the survival benefits of adjuvant therapies. Conclusion: Patients with stage II GBC may not benefit from adjuvant therapy, while patients with stage III–IV GBC were shown to benefit from chemotherapy and chemoradiotherapy. Furthermore, chemoradiotherapy exhibited a superior OS. Nevertheless, the results need to be explained in the context of retrospective studies.

Background This study was designed to investigate whether 3D laparoscopic common bile duct (LCBDE) could improve surgical outcomes in choledocholithiasis patients compared with 2D LCBDE. Method Propensity score-matched analysis was performed to balance the bias in baseline characteristic between two groups. Results 213 patients underwent 3D LCBDE and 212 patients receiving 2D LCBDE were enrolled in this study. The operation time and blood loss in 3D group were significantly less than that in 2D group. After propensity score matching, a total of 114 paired cases were selected from the two groups. The operation time and blood loss in 3D group remain significantly lower than in 2D group. In the end, the subgroup analysis based on abdominal adhesion level was performed and it was observed that for patients with adhesion level 1 and level 2, 3D surgery could obviously decrease the operation time and intraoperative blood loss. Conclusions 3D LCBDE would significantly reduce operation time, blood loss, and conversion rate to laparotomy in choledocholithiasis patients versus 2D LCBDE. For patients with abdominal adhesions level 1 and level 2, 3D LCBDE could provide better surgical outcomes than 2D LCBDE.