残胃上的癌术后病理分期标准的探索性研究

Pathological staging criteria for carcinoma in the remnant stomach： an exploratory study

目的探讨TRM病理分期标准对于残胃上癌变病灶评估应用的可行性。方法回顾性收集1992年3月至2017年12月期间在北京大学人民医院接受治疗的91例残胃上癌变（CRS）患者的临床病理数据。根据阳性淋巴结数目与清扫淋巴结数目之比（阳性淋巴结比率）获得R分期，用R分期替换pN分期即获得TRM分期。分别将R分期和N分期纳入预后因素分析模型，并通过对比TRM分期和TNM分期（UICC第7版）系统的生存曲线、c-index及其95%置信区间（CI），比较两组分期系统预测预后的准确性。c-index值越高，代表预测准确性越高。结果91例CRS患者男性77例，女性14例，发病年龄（65.2 ± 10.4）岁。初次手术与CRS发病时间间隔中位数为156（6～600）月。49例（53.8%）原发疾病为良性，42例（46.2%）为恶性。获取淋巴结总数（RLN）中位数为8（0～38）枚，其中64例（70.3%）RLN≤15枚。50例（54.9%）发生了淋巴结转移。pN分期：N0期41例，N1期14例，N2期19例，N3期17例；R分期：R0期41例，R1期4例，R2期19例，R3期27例。TNM分期结果为：Ⅰ期13例，Ⅱ期25例，Ⅲa期10例，Ⅲb期23例，Ⅲc期6例；对应的TRM分期结果为：Ⅰ期13例，Ⅱ期24例，Ⅲa期4例，Ⅲb期18例，Ⅲc期18例。单因素分析结果显示，肿瘤直径≥7 cm（HR= 2.696，95% CI：1.307～5.563，P= 0.007）、T3～4期（HR=4.350，95% CI：1.949～9.707，P= 0.000）、N2～3期（HR= 1.883，95% CI：1.167～3.038，P= 0.009）、R2～3期（HR= 1.642，95% CI：1.026～ 2.628，P= 0.039）、TNM Ⅲ～Ⅳ期（HR= 2.448，95%CI：1.490～4.021，P= 0.000）和TRM Ⅲ～Ⅳ期（HR= 2.504，95%CI：1.515～4.137，P= 0.000）分期均与患者预后有关。将肿瘤直径、pT分期和pN分期纳入Cox多因素分析发现，pT分期（HR= 5.507，95%CI：2.254～13.454，P= 0.000）和pN分期（HR= 1.698，95%CI：1.022～2.789，P= 0.041）是本组CRS患者总体生存的独立危险因素。用R分期代替pN分期，与肿瘤直径及pT分期一并纳入Cox多因素分析，结果显示，R分期并不是本组CRS预后的独立危险因素（HR= 1.622，95%CI：0.866～2.329，P= 0.164）。绘制生存曲线发现，以阳性淋巴结个数为基础的pN分期和TNM分期，各分期组间的曲线分层更为清晰。本组CRS患者TNM分期的总体生存c-index指数为0.813（95%CI：0.732～0.826），TRM分期的c-index指数为0.809（95%CI：0.741～0.847），两种分期指数之间差异无统计学意义（P= 0.693）。原发恶性疾病组TNM分期的总体生存率c-index指数为0.774（95%CI：0.589～0.901），TRM分期的c-index指数为0.761（95%CI：0.596～0.912），两种分期指数之间差异无统计学意义（P= 0.881）。结论TRM分期对于CRS切除标本的评价效果并不优于TNM分期。

Objective To explore the prognostic value of the tumor-ratio-metastasis （TRM） staging system for carcinoma in the remnant stomach （CRS）. Methods Clinicopathological data a 91 CRS patients who underwent surgery at Peking University People＇s Hospital between March 1992 and December 2017 were retrospectively analyzed. According to the ratio of metastatic lymph node to dissected lymph node, the R staging was obtained, and the pN staging was replaced by the R staging to create the TRM staging. To compare the predictive accuracy of TRM and tumor-node-metastasis （TNM, UICC version 7）, the R staging and pN staging were included in the prognostic factor analysis model, and the survival curve, c-index, and 95% confidence interval （CI） of the TRM staging and TNM staging system were compared. A higher c-index value means higher prediction accuracy. Results Of 91 CRS patients, 77 were male and 14 were female with the mean onset age of （65.2±10.4） years. The mean interval from the first operation to CRS onset was 156（6-600） months. The primary diseases of 49（53.8%） cases were benign and of42（46.2%）cases were malignant. The median number of retrieved lymph node （RLN） was 8 （0-38）, and 64 patients （70.3%） had an RLN ≤ 15. Lymph node metastasis occurred in 50 patients （54.9%）. pN staging result was as follows： 41 cases in NO stage, 14 in N1 stage, 19 in N2 stage, and 17 in N3 stage. R staging result was as follows： 41 cases irL R0 stage, 4 in R1 stage, 19 in R2 stage, and 27 in R3 stage. TNM staging result was as follows： 13 cases in stage I , 25 in stage Ⅱ , 10 in stage Ilia, 23 in stage rob, and 6 in stage Ⅲc. TRM staging result was as follows： 13 cases in stage I , 24 in stage Ⅱ , and 4 in stage liIa, 18 in stage rob, and 18 in stage Ⅲc. Univariate analysis showed that tumor diameter ≥ 7 cm （FIR= 2.696, 95%CI： 1.307-5.563, P = 0.007）, T3-4 stage （HR= 4.350, 95%CI： 1.949-9.707, P = 0.000）, N2-3 stage （HR= 1.883, 95%CI： 1.167-3.038, P -- 0.009）, R2-3 stage（HR= 1.642, 95%C1： 1.026-2.628, P = 0.039）, TNM Ⅲ-IV stage （HR=2.448, 95%CI：1.490-4.021, P=0.O00）, and TRM Ⅲ-IV stage （HR= 2.504, 95%CI：1.515-4.137, P = 0.000） were related to prognosis. Tumor diameter, pT staging, and pN staging were included in the Cox multivariate analysis, and the result showed that pT staging （h＇R = 5.507, 95%CI：2.254-13.454, P=0.000） and pN staging （HR = 1.698, 95%CI：1.022-2.789, P= 0.041 ） were independent risk factors for overall survival of CRS in this group. While R staging replaced pN staging and was included in the Cox multivariate analysis together with tumor diameter anti pT staging, the result showed that R staging was not an independent risk factor for CRS in this group （HR=1.622, 95%CI：0.866-2.329, P= 0.164）. Survival curve revealed pN and TNM staging systems provided better stratified curves according to each staging than R and TRM staging systems. The overall survival c-index of TNM and TRM staging systems was 0.813 （95%CI：0.732-0.826） and 0.809 （95%CI：0.741-0.847） respectively, and no significant difference in predictive accuracy was found （P= 0.693）. In 42 patients with primary malignance, the overall survival c-index of TNM and TRM staging systems was 0.774（95%C1： 0.589-0.901） and 0.761（95%CI：0.596-0.912） respectirely, and there was no significant difference in predictive accuracy as well （P= 0.881 ）. Conclusion FRM staging is not superior to TNM staging （7th UICC） in evaluating the resected samples of CRS.