Marichez A, Raymond A A, Boubaddi M, Toussaint N, Le Bail B, Belleannée G, Di Tommaso S, Dupuy J W, Dourthe C, Decraecker M, Saltel F, Laurent C, Chiche L
Department of Hepato-bilio-pancreatic Surgery and Liver Transplantation, Haut-Lévêque Hospital, Bordeaux University Hospital, Bordeaux, France.
Inserm UMR 1312, Bordeaux Institute of Oncology (BRIC), University of Bordeaux, Bordeaux, France.
Ann Surg Oncol. 2025 Jul 16. doi: 10.1245/s10434-025-17811-x.
Extrahepatic cholangiocarcinoma (eCCA) includes perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA), classified on the basis of tumor location. However, the oncological and molecular characteristics of these subtypes remain uncertain. We compared their oncological outcomes and investigated potential proteomic differences based on tumor location.
A single-center retrospective study was conducted on 204 patients who underwent surgical resection for eCCA between 2007 and 2023. Clinicopathological data were collected, and overall survival (OS) and disease-free survival (DFS) were compared. Prognostic factors were identified using multivariate analyses with a stepwise Cox proportional hazards model. For molecular analysis, 60 proteomic assays were performed in triplicate using 20 resected eCCA samples.
No significant differences were observed between pCCA (n = 113) and dCCA (n = 91) in terms of severe morbidity or postoperative mortality. Patients with dCCA had a higher R0 resection rate compared with those with pCCA (79.1% versus 48.7%, p < 0.001). Furthermore, lymph node positivity was more frequent in dCCA (61.5% versus 29.2%, p < 0.001), whereas microvascular and perineural invasion were more prevalent in pCCA. Despite these clinicopathological differences, no significant differences were observed in 5-year OS (43.1% versus 48.3%, p = 0.57) or 5-year DFS (37.6% versus 32.8%, p = 0.46). Tumor location was not identified as an independent prognostic factor. Proteomic analysis identified 686 proteins with significantly differential expression between the two subtypes. However, principal component analysis failed to clearly separate pCCA and dCCA samples.
Our study reinforces the view that pCCA and dCCA, despite clinicopathological variations, exhibit comparable long-term oncological outcomes. Tumor location was not identified as an independent prognostic factor, emphasizing the need for an integrated approach in future studies of targeted therapies for eCCA.
肝外胆管癌（eCCA）包括肝门部胆管癌（pCCA）和远端胆管癌（dCCA），根据肿瘤位置进行分类。然而，这些亚型的肿瘤学和分子特征仍不明确。我们比较了它们的肿瘤学结局，并基于肿瘤位置研究了潜在的蛋白质组学差异。
对2007年至2023年间接受手术切除的204例eCCA患者进行了单中心回顾性研究。收集临床病理数据，并比较总生存期（OS）和无病生存期（DFS）。使用逐步Cox比例风险模型进行多变量分析以确定预后因素。对于分子分析，使用20个切除的eCCA样本进行了60次蛋白质组学检测，每次检测重复3次。
在严重并发症或术后死亡率方面，pCCA（n = 113）和dCCA（n = 91）之间未观察到显著差异。与pCCA患者相比，dCCA患者的R0切除率更高（79.1%对48.7%，p < 0.001）。此外，dCCA中淋巴结阳性更为常见（61.5%对29.2%，p < 0.001），而微血管和神经周围侵犯在pCCA中更为普遍。尽管存在这些临床病理差异，但5年OS（43.1%对48.3%，p = 0.57）或5年DFS（37.6%对32.8%，p = 0.46）方面未观察到显著差异。肿瘤位置未被确定为独立的预后因素。蛋白质组学分析确定了两种亚型之间有686种蛋白质表达存在显著差异。然而，主成分分析未能清晰区分pCCA和dCCA样本。
我们的研究强化了这样一种观点，即尽管pCCA和dCCA存在临床病理差异，但它们具有相似的长期肿瘤学结局。肿瘤位置未被确定为独立的预后因素，这强调了在未来eCCA靶向治疗研究中采用综合方法的必要性。
