A Nomogram in Predicting Risks of Intrahepatic Cholangiocarcinoma After Partial Hepatectomy for Hepatolithiasis.

BACKGROUND: Hepatolithiasis is associated with the development of intrahepatic cholangiocarcinoma (ICC). This study sought to investigate risk factors of ICC for hepatolithiasis after partial hepatectomy (PH) and to develop a model for predicting ICC risk. METHODS: Data on consecutive patients who underwent PH for hepatolithiasis at the Eastern Hepatobiliary Surgery Hospital between January 2009 and December 2011 were reviewed. Independent risk factors of ICC identified by Cox regression model were used to develop a nomogram in predicting ICC after PH for hepatolithiasis. RESULTS: Of 2056 patients, 168 developed ICC at a median follow-up of 7.2 years. The cumulative incidences of ICC at 3, 5, and 8 years after PH for hepatolithiasis were 3.0%, 6.5%, and 12.9%, respectively. Independent risk factors of ICC were identified to be a long duration of hepatolithiasis-related symptoms (hazard ratio, 1.088 [95% confidence interval, 1.057-1.120]), metabolic syndrome (2.036 [1.210-3.425]), a high neutrophil-to-lymphocyte ratio (1.250 [1.009-2.816] for 3-5 vs ≤3; 1.538 [1.048-2.069] for ≥5 vs ≤3), hepatic atrophy (1.711 [1.189-2.462]), segmental intensity differences (1.513 [1.052-2.176]), persistent biliary strictures (2.825 [1.480-5.391]), and residual stone disease (2.293 [1.511-3.481]). By incorporating these factors, a constructed nomogram showed a concordance index of 0.721 to predict ICC. The calibration plots demonstrated good agreement between observed and predicted morbidities. The optimal cutoff point for the nomogram was 48 in differentiating between high and low-risk of ICC. CONCLUSIONS: A nomogram for predicting ICC after PH for hepatolithiasis was constructed based on risk factors of developing ICC. Patients with a nomogram point of ≥48 were predicted to have a high risk of ICC.

Mesenchymal stem cells promote chemoresistance by activating autophagy in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a type of cancer that is difficult to cure; chemoresistance of cholangiocarcinoma cells affect the prognosis of patients who cannot be treated with surgery. The mechanism underlying this chemoresistance remains unknown. Mesenchymal stem cells (MSCs) are known to be important components of the tumor microenvironment. In the present study, a large number of MSCs were observed to infiltrate the tumor sites of ICC; thus, MSCs were isolated from ICC tumor tissues. It was revealed that herpesvirus entry mediator (HVEM) was overexpressed in ICC­MSCs. The present study then investigated the role of HVEM­overexpressing MSCs in the chemoresistance of cholangiocarcinoma cells. It was demonstrated that HVEM­overexpressing MSCs could support cell survival of chemotherapeutic cholangiocarcinoma cells and inhibited their apoptosis. Further investigations revealed that HVEM­overexpressing MSCs could secrete IL­6 and also activated AMPK/mTOR­dependent autophagy of cholangiocarcinoma cells. Thus, it was concluded that ICC­MSC­induced autophagy is the primary cause of chemoresistance in ICC.