Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.
Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
Clin Rev Allergy Immunol. 2020 Feb;58(1):134-149. doi: 10.1007/s12016-019-08764-7.
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.
胆管癌（CCA）是原发性硬化性胆管炎（PSC）患者最常见的恶性肿瘤，死亡率很高。尽管 PSC 中 CCA 的发病机制在很大程度上尚不清楚，但炎症驱动的癌变伴随着各种遗传和表观遗传异常是潜在因素。大多数 CCA 病例源自主要狭窄（DS），其定义为胆总管直径<1.5mm 或肝内胆管直径<1.0mm 的狭窄。在 PSC 患者中，突然出现黄疸、疼痛、疲劳、瘙痒、体重减轻或肝功能恶化时，应怀疑 CCA 并利用各种诊断方式进行评估。然而，早期识别 PSC 中的 CCA 仍然是一个主要挑战。重要的是，30-50%的 PSC 患者在诊断 PSC 后的第一年就出现 CCA，随后每年的发病率为每 100 人 0.5-1.5 例，几乎是普通人群的 10-1000 倍。累积 5 年、10 年和终生发病率分别为 7%、8-11%和 9-20%。当诊断出 PSC 相关的 CCA 时，大多数肿瘤无法切除，也没有有效的药物可用。鉴于治疗效果不佳，监测和管理有发生 CCA 风险的 PSC 患者非常重要。这些患者包括患有大导管 PSC 且可能同时患有溃疡性结肠炎的老年男性。因此，应更加关注具有这些临床特征的患者，尤其是在 PSC 诊断后的第一年。相比之下，在儿科或女性 PSC 患者、小导管 PSC 或同时患有克罗恩病的患者中，CCA 较少见。最近，发现抗体糖蛋白 2 等新的生物标志物与 PSC 患者发生 CCA 的风险增加有关。在此，我们综述了有关 PSC 相关 CCA 的发病机制、发病率、临床特征和危险因素的文献，重点介绍了各种诊断方式。
