Department of Pathology, University of Helsinki and Helsinki University Hospital, HUSLAB, 00029 Helsinki, Finland.
Transplantation and Liver Surgery Clinic, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.
World J Gastroenterol. 2017 Sep 7;23(33):6147-6154. doi: 10.3748/wjg.v23.i33.6147.
To investigate markers for high-grade dysplasia for the optimal timing of liver transplantation in patients with primary sclerosing cholangitis (PSC).
Earlier data support a dysplasia-carcinoma sequence, even low- to high-grade dysplasia, in PSC-associated cholangiocarcinoma (CCA). Surveillance using endoscopic retrograde cholangiography (ERC) and brush cytology aims to detect cases of biliary dysplasia, and liver transplantation is an option in cases with suspicion of malignancy in brushing. This study investigated markers to identify patients with high-grade biliary dysplasia for optimal timing in early liver transplantation. Patients undergoing surveillance using ERC and brush cytology during 2008-2014 and who were diagnosed with biliary dysplasia in explanted liver or CCA until February 2016 were included in the study. Demographic data, cholangiography findings, laboratory values, cytological morphology and DNA ploidy were analysed.
Thirty PSC patients had biliary neoplasia in the explanted liver during the study period. Sixteen of these patients had low-grade dysplasia, 10 patients had high-grade dysplasia, and 4 patients had CCA. Fifteen PSC patients diagnosed with CCA were not transplanted. Patients with low-grade dysplasia were younger. Alkaline phosphatase or carcinoembryonic antigen values did not differ between groups during surveillance, but carbohydrate antigen 19-9 was higher in CCA patients. No difference in PSC duration, ERC scores, suspicious cytology, or ploidy analysis was found between groups. No difference was observed between fibrosis stage in explanted livers. Low- and high-grade dysplasia could not be differentiated before liver transplantation based on liver enzymes, tumour markers, ERC scores, brush cytology or DNA ploidy.
Repeated suspicion of neoplasia in brush cytology should be an indication for evaluations of liver transplantation prior to the development of CCA.
探讨原发性硬化性胆管炎（PSC）患者发生高级别上皮内瘤变（dysplasia）的标志物，以确定肝移植的最佳时机。
早期数据支持 PSC 相关胆管癌（CCA）存在从低级别到高级别上皮内瘤变-癌的演变过程。经内镜逆行胰胆管造影（ERC）和刷检细胞学检查进行监测的目的是检测胆管上皮内瘤变，并且在刷检怀疑有恶性时进行肝移植。本研究通过检测标志物来识别具有高级别胆道上皮内瘤变的患者，以确定早期肝移植的最佳时机。纳入 2008 年至 2014 年期间接受 ERC 和刷检细胞学监测且在肝移植时确诊为胆道上皮内瘤变或 CCA 的患者，对其临床资料、胆管影像学表现、实验室检查、细胞学形态学和 DNA 倍体进行分析。
研究期间，30 例 PSC 患者的肝内存在胆管肿瘤。其中 16 例为低级别上皮内瘤变，10 例为高级别上皮内瘤变，4 例为 CCA。15 例确诊为 CCA 的患者未进行肝移植。低级别上皮内瘤变患者更年轻。在监测期间，碱性磷酸酶或癌胚抗原水平在各组之间无差异，但 CCA 患者的糖类抗原 19-9 水平更高。各组之间的 PSC 病程、ERC 评分、可疑细胞学表现或倍体分析无差异。各组的肝内纤维化分期无差异。基于肝酶、肿瘤标志物、ERC 评分、刷检细胞学或 DNA 倍体，无法在肝移植前区分低级别和高级别上皮内瘤变。
刷检反复怀疑有肿瘤时，应进行肝移植评估，以防止 CCA 的发生。
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