Efficacy and safety of endoscopic nasobiliary drainage versus percutaneous transhepatic cholangial drainage in the treatment of advanced hilar cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy and safety of Endoscopic Nasobiliary Drainage (ENBD) and Percutaneous Transhepatic Cholangiography Drainage (PTCD) in patients with advanced Hilar Cholangiocarcinoma (HCCA) through a meta-analysis of clinical studies. METHODS: We searched Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, Scopus, and Web of Science, for relevant literatures on PTCD and ENBD for advanced HCCA clinical trials. Two investigators independently screened the literatures, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). The primary endpoint was the success rate of biliary drainage operation, while secondary endpoints included Total Bilirubin (TBIL) change, acute pancreatitis, biliary tract infection, hemobilia, and other complications. R software was used for data analysis. RESULTS: A comprehensive database search, based on predefined inclusion and exclusion criteria, yielded 26 articles for this study. Analysis revealed that PTCD had a significantly higher success rate than ENBD [OR (95% CI) = 2.63 (1.98, 3.49), Z=6.70, P<0.05]. PTCD was also more effective in reducing TBIL levels post-drainage [SMD (95%CI) =-0.13 (-0.23, -0.03), Z=-2.61, P<0.05]. While ENBD demonstrated a lower overall complication rate [OR (95%CI) = 0.60 (0.43, 0.84), Z=-2.99, P<0.05], it was associated with a significantly lower incidence of post-drainage biliary hemorrhage compared to PTCD [OR=3.02, 95%CI: (1.94-4.71), Z= 4.89, P<0.01]. CONCLUSIONS: This meta-analysis compares the efficacy and safety of ENBD and PTCD for palliative treatment of advanced HCCA. While both are effective, PTCD showed superiority in achieving successful drainage, reducing TBIL, and lowering the incidence of acute pancreatitis and biliary infections. However, ENBD had a lower risk of post-drainage bleeding. Clinicians should weigh these risks and benefits when choosing between ENBD and PTCD for individual patients. Further research is needed to confirm these findings and explore long-term outcomes.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study.

Background: The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. Methods: A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. Results: The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. Conclusions: The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.

Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma.

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Clinical practice of basin-shaped hepaticojejunostomy following hilar resection of stage III/IV hilar cholangiocarcinoma.

BACKGROUND: Radical surgery for Bismuth type III/IV hilar cholangiocellular carcinoma, which was usually considered unresectable, seems to improve prognosis by increasing the surgical curability rate. However, the dilemma of multiple billiary stumps and high postoperative complication rate caused by hepato-enteric anastomosis has been the main impediment. Thus, we practiced and introduce a new technique called "basin-shaped" hepaticojejunostomy to improve the treatment. METHODS: Thirty-two cases with Bismuth type III/IV hilar cholangiocarcinoma admitted to our department from Aug. 2013 to Dec. 2015 and who underwent hilar resection and resection segment 4(or plus resection segment 1) were reconstructed by "basin-shaped" hepaticojejunostomy. The clinical data were collected and analyzed. RESULTS: All patients underwent successful R0 high hilar resection following basin-shaped hepaticojejunostomy and were discharged from the hospital without severe postoperative complications. The average operation time for hepato-enteric anastomosis was 42.1 ± 8.5 min. The postoperative bile leakage rate was 3.1% (1/32), and the biliary infection rate was 6.2% (2/32). Within a median follow-up of 25.6 months, none of the patients developed local recurrence around the hepato-enteric anastomosis. CONCLUSIONS: For patients with Bismuth type III/IV hilar cholangiocellular carcinoma who underwent resection segment 4(or plus resection segment 1), basin-shaped hepaticojejunostomy was a safe, simple and valid method for bile duct reconstruction, with a relatively low incidence of postoperative complications.

Long Non-Coding RNA MALAT1 Interacts With miR-204 to Modulate Human Hilar Cholangiocarcinoma Proliferation, Migration, and Invasion by Targeting CXCR4.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in many kinds of cancers. However, the exact effects and molecular mechanisms of MALAT1 in human hilar cholangiocarcinoma (HCCA) progression are still unknown. Here, we investigated the role of MALAT1 in human HCCA cell lines and clinical tumor samples in order to determine the function of this lncRNA. In our research, lncRNA-MALAT1 was specifically upregulated in HCCA tissues and cell lines, and was associated with pathological T stage, a larger tumor size, and perineural invasion. Knockdown of MALAT1 inhibited the proliferation, migration, and invasion of human HCCA cell. In addition, chemokine receptor-4 (CXCR4) was involved in MALAT1 induced human HCCA growth, migration, and invasion. By using online tools and a series of mechanistic analysis, we also demonstrated that miR-204-dependent CXCR4 regulation was required in MALAT1 modulating HCCA cell growth, migration and invasion. Taken together, our data indicated that MALAT1 might play an oncogenic role in HCCA through miR-204-dependent CXCR4 regulation, and could be regarded as a therapeutic target in HCCA. J. Cell. Biochem. 118: 3643-3653, 2017. © 2017 Wiley Periodicals, Inc.