Boyd Sonja, Mustonen Harri, Tenca Andrea, Jokelainen Kalle, Arola Johanna, Färkkilä Martti A
a Department of Pathology , University of Helsinki, and Helsinki University Hospital , Helsinki , Finland.
b University of Helsinki and Department of Surgery, Helsinki University Hospital , Helsinki , Finland.
Scand J Gastroenterol. 2017 Feb;52(2):242-249. doi: 10.1080/00365521.2016.1250281. Epub 2016 Nov 3.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to bile duct strictures and fibrosis, and predisposing to cholangiocarcinoma (CCA). Biliary dysplasia is a known precursor of CCA. In our unit, PSC patients undergo regular surveillance with ERC and brush cytology (BC), and liver transplantation is an option in case with biliary dysplasia. We evaluated the risk factors for biliary dysplasia and CCA based on ERC imaging, BC and liver function tests.
Seven hundred and eighty-eight ERCs were performed with BC for 447 PSC patients. ERC images were evaluated using the modified Amsterdam score, neutrophilic inflammation was assessed in BC, and liver function tests were collected. Ploidy analysis with DNA flow cytometry was performed in cases with advanced PSC or previous suspicious BC/aneuploidy. The endpoint was either a benign disease course (follow-up for ≥2.4 years after the latest ERC), benign histology, biliary dysplasia or CCA.
Benign disease course was seen in 424/447 (including 23 cases with biliary dysplasia), and CCA in 17 (3.8%) patients. Gallbladder carcinoma/carcinoma in situ was diagnosed in three patients. Advanced ERC findings, male gender, suspicious BC, aneuploidy in flow cytometry, inflammation, and elevation of ALP, bilirubin, ALT, AST, GGT, CEA and CA19-9 represented significant risk factors for CCA in univariate analysis.
PSC patients with advanced bile duct disease and elevated liver enzymes, CEA or CA19-9, inflammation or suspicious BC are most likely to develop CCA. These patients may benefit from surveillance with BC if early liver transplantation is possible.
原发性硬化性胆管炎(PSC)是一种慢性胆汁淤积性肝病,可导致胆管狭窄和纤维化,并易患胆管癌(CCA)。胆管发育异常是已知的CCA前驱病变。在我们科室,PSC患者接受定期的内镜逆行胰胆管造影(ERC)和刷检细胞学检查(BC),对于出现胆管发育异常的患者可选择肝移植。我们基于ERC成像、BC和肝功能检查评估了胆管发育异常和CCA的危险因素。
对447例PSC患者进行了788次ERC检查并同时进行BC检查。使用改良的阿姆斯特丹评分评估ERC图像,在BC检查中评估中性粒细胞炎症,并收集肝功能检查结果。对晚期PSC或既往BC检查可疑/非整倍体的病例进行DNA流式细胞术倍性分析。终点指标为良性病程(最近一次ERC检查后随访≥2.4年)、良性组织学、胆管发育异常或CCA。
447例患者中424例病程呈良性(包括23例胆管发育异常),17例(3.8%)患者发生CCA。3例患者诊断为胆囊癌/原位癌。在单因素分析中,ERC检查结果为晚期、男性、BC检查可疑、流式细胞术非整倍体、炎症以及碱性磷酸酶(ALP)、胆红素、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、癌胚抗原(CEA)和糖类抗原19-9(CA19-9)升高是CCA的显著危险因素。
患有晚期胆管疾病且肝酶、CEA或CA19-9升高、有炎症或BC检查可疑的PSC患者最有可能发生CCA。如果有可能早期进行肝移植,这些患者可能会从BC监测中获益。