Department of Hepato-Biliary-Pancreatic Surgery Osaka City University Graduate School of Medicine 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Department of Surgery, Minamitama Hospital, 3-10-1 Sandamachi, Hachioji, Tokyo 193-0832, Japan.
Asian Pac J Cancer Prev. 2020 Dec 1;21(12):3647-3654. doi: 10.31557/APJCP.2020.21.12.3647.
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.
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.
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.
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.
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肝内胆管结石患者行肝切除术后可并发胆管癌和继发性胆汁性肝硬化，是导致肝内胆管结石相关死亡的原因。本研究旨在确定肝内胆管结石患者行肝切除术后发生肝内胆管结石相关死亡和胆管癌的潜在危险因素，包括癌前病变如胆管上皮内瘤变（BilIN）和胆管内乳头状肿瘤。
方法：本研究纳入了 62 例因肝内胆管结石行肝切除且无胆管癌的患者，所有患者均有可供病理检查的手术标本。采用单因素和多因素分析方法来探讨肝内胆管结石患者发生胆管癌和肝内胆管结石相关死亡的危险因素。对 28 例存在 BilIN 病变的患者，采用免疫组化法检测 γ-H2AX 和 S100P 的表达。
结果：在本研究队列中，死亡原因为胆管癌、胆汁性肝硬化和其他疾病的患者分别有 5、3 和 7 例。肝脏萎缩、癌前病变、术后反复胆管炎和随访期间黄疸持续时间≥1 周是肝内胆管结石相关死亡的危险因素。多因素分析显示，肝脏萎缩和癌前病变是肝内胆管结石相关死亡的独立危险因素。单因素分析也显示肝脏萎缩或癌前病变是发生胆管癌的危险因素。在 28 例 BilIN 病变中，分别有 18 例和 14 例病变的 γ-H2AX 和 S100P 呈阳性表达。
结论：肝脏萎缩和伴有恶性转化的癌前病变不仅是肝内胆管结石患者行肝切除术后发生胆管癌的危险因素，也是发生肝内胆管结石相关死亡的危险因素，提示对于存在这些危险因素的患者，即使行肝切除术后也需要长期随访。
