Precancerous Lesions and Liver Atrophy as Risk Factors for Hepatolithiasis-Related Death after Liver Resection for Hepatolithiasis.

Toru Miyazaki,Kenjiro Kimura,Daisuke Shirai,Norifumi Kawada,Takatsugu Yamamoto,Ryosuke Amano,Atsushi Ishihara,Shoji Kubo,Shogo Tanaka,Jun Tsuchi,Kohei Nishio,Kenichi Wakasa,Shigekazu Takemura,Shimpei Eguchi,Hiroji Shinkawa,Go Ohira,Masahiko Kinoshita

doi:10.31557/apjcp.2020.21.12.3647

Abstract

Background:Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. Methods:The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. Results:In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. Conclusions:Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors.

Highlights

Albeit a benign disease, hepatolithiasis can lead to cholangiocarcinoma and secondary biliary cirrhosis due to repeated cholangitis and stones (Kubo et al, 1995; Kim et al, 2015a; Suzuki et al, 2018)
The following variables were included in the present study: age (10 years), history of cholecystectomy, history of choledocho-enterostomy, serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9), preoperative cholangitis, stone location, bile duct stenosis, bile duct dilatation, type of surgical procedure, biliary reconstruction, liver atrophy of affected segment(s) defined as more than 50% reduction in liver volume on computed tomography (CT) or magnetic resonance imaging (MRI) (Ham, 1979), precancerous lesions (BilIN and IPNB), residual stones after surgery, stone recurrence, jaundice for ≥1 week during the follow-up period, and postoperative repeated cholangitis
8 of 62 patients died of hepatolithiasis-related causes including cholangiocarcinoma and secondary biliary cirrhosis

Summary

Introduction

Hepatolithiasis can lead to cholangiocarcinoma and secondary biliary cirrhosis due to repeated cholangitis and stones (Kubo et al, 1995; Kim et al, 2015a; Suzuki et al, 2018). Biliary intraepithelial neoplasia (BilIN) and intraductal neoplasm of the bile duct (IPNB), which are considered as precancerous or early cancerous lesions (WHO, 2019), are observed in hepatolithiasis, primary sclerosing cholangitis, and occupational cholangiocarcinoma caused. Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. Conclusions: Liver atrophy and precancerous lesions with malignant transformation were risk factors for subsequent cholangiocarcinoma and hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors

Methods

Results

Conclusion