Objective: To explore the value of a new modified T3 sub-staging for the prognosis evaluation in gallbladder cancer patients. Methods: This is a retrospective case-series study. The clinical data of patients with pathologically confirmed stage T3 gallbladder cancer who were admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively analyzed. A total of 190 patients were enrolled in this study, 67 males and 123 females, with an age (M(IQR)) of 63(14) years (range:17 to 88 years). The stage T3 was divided into four sub-stages according to the site of tumor invasion: (1) T3a:tumor perforates the serosa,but not invading the liver and one other adjacent structure; (2) T3b:tumor perforates the serosa and invades one other adjacent structure,but not the liver; (3) T3c:tumor perforates the serosa and invades the liver,but not one other adjacent structure; (4) T3d:tumor perforates the serosa,invades the liver and one other adjacent structure. To evaluate the application value of this modified sub-staging,the Kaplan-Meier method was used to draw the survival curve,univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results: According to the modified T3 sub-staging method,34 patients (17.9%) were in stage T3a,24 cases(12.6%) were in stage T3b, 97 cases (51.1%) were in stage T3c, and 35 cases (18.4%) were in stage T3d. The median survival time of patients in stages T3a,T3b,T3c and T3d after radical resection was 72.0 months, 32.0 months, 12.0 months and 10.0 months, respectively. The 1-, 3-, and 5-year survival rates of patients in stage T3a, T3b, T3c and T3d were 79.4%, 53.3%, and 53.3%; 79.2%, 44.6%, and 26.0%;49.5%,27.5%,and 18.1%;42.9%,15.9%, and 15.9% (χ2=18.349,P<0.01),respectively. Univariate analysis showed that gallbladder stones,pathological differentiation,perineural invasion, N stage,postoperative adjuvant therapy and modified T3 substage were factors affecting patient prognosis(all P<0.05). Cox multivariate analysis showed that modified sub-stages with T3c (HR=2.043, 95%CI:1.176 to 3.549) and T3d(HR=2.419, 95%CI:1.284 to 4.555), accompanied by gallbladder stones (HR=1.661,95%CI:1.150 to 2.398),pathological differentiation with poorly differentiated(HR=1.709,95%CI:1.198 to 2.438), and the N stage with N1 and N2(HR=1.602, 95%CI:1.090 to 2.355, 2.714, 95%CI: 1.621 to 4.544) were independent prognostic risk factors for patients in stage T3,while postoperative adjuvant chemotherapy(HR=0.351) was a protective factor for prognosis. There was no statistically significant difference in survival between patients with stage T3a and T3b who underwent hepatic wedge resection and liver segment or major resection (P=0.402). For patients with stage T3c and T3d with liver invasion,the survival difference after hepatic wedge resection and segmental or major resection was statistically significant (P=0.008). Conclusion: The modified T3 sub-staging system based on the depth and direction of tumor invasion maybe helpful to further stratify the prognosis of patients with gallbladder cancer.
目的： 探讨基于AJCC第8版TNM分期中T3分期提出的改良亚分期在评估胆囊癌预后中的价值。 方法： 本研究为回顾性病例系列研究。回顾性分析2011年1月至2021年12月西安交通大学第一附属医院肝胆外科收治的经病理学检查证实的190例T3期胆囊癌患者的临床和病理学资料。男性67例，女性123例，年龄为［M（IQR）］63（14）岁（范围：17~88岁）。根据肿瘤侵犯部位划分为4个亚分期：（1）T3a：侵透全层，未侵犯肝脏或其余组织器官；（2）T3b：侵透全层并侵犯一个周围组织器官，未侵犯肝脏；（3）T3c：侵透全层并侵犯肝脏，未侵犯周围组织器官；（4）T3d：侵透全层并同时侵犯肝脏及一个周围组织器官。使用Kaplan-Meier法绘制生存曲线，单因素生存分析采用Log-rank检验，多因素分析采用Cox比例风险回归模型。 结果： 依据改良T3亚分期方法：T3a期34例（17.9%），T3b期24例（12.6%），T3c期97例（51.1%），T3d期35例（18.4%）。T3a期、T3b期、T3c期、T3d期患者根治性切除术后的中位生存时间分别为72.0、32.0、12.0、10.0个月，T3a期患者1、3、5年总体生存率分别为79.4%、53.3%、53.3%，T3b期患者1、3、5年总体生存率分别为79.2%、44.6%、26.0%，T3c期患者1、3、5年总体生存率分别为49.5%、27.5%、18.1%，T3d期患者1、3、5年总体生存率分别为42.9%、15.9%、15.9%，组间总体生存率的差异有统计学意义（χ2=18.349，P<0.01）。单因素分析结果显示，胆囊结石、病理学分化、神经浸润、N分期、术后辅助治疗及改良T3亚分期为患者的预后因素（P值均<0.05）。Cox多因素分析结果显示，改良亚分期为T3c期（HR=2.043，95%CI：1.176~3.549）及T3d期（HR=2.419，95%CI：1.284~4.555）、有胆囊结石（HR=1.661，95%CI：1.150~2.398）、病理学分化为低分化（HR=1.709，95%CI：1.198~2.438）、N分期为N1期及N2期（HR=1.602，95%CI：1.090~2.355、2.714，95%CI：1.621~4.544）为T3期患者的独立预后不良因素，而术后辅助化疗（HR=0.351）为独立预后保护性因素（P值均<0.05）。T3a期及T3b期患者行肝脏楔形切除与肝段或以上切除术后患者的生存差异无统计学意义（P=0.402），伴有肝脏侵犯的T3c期及T3d期患者行肝脏楔形切除与行肝段或以上切除术后患者的生存差异有统计学意义（P=0.008）。 结论： 依据肿瘤浸润深度及侵犯方向提出的改良T3亚分期可能有助于进一步对胆囊癌患者进行预后分层。.