淋巴结转移阴性胃癌的预后影响因素分析

Prognostic factors of lymph node-negative metastasis gastric cancer

目的探讨淋巴结转移阴性（pN0）胃癌患者的预后影响因素。方法回顾性收集1980年5月至2012年8月期间中国医科大学附属第一医院肿瘤外科连续收治行胃癌根治术的pN0胃癌患者的临床资料。病例纳入标准：（1）病理明确诊断为胃腺癌；（2）术后病理证实为T1a-4bN0M0期胃癌；（3）淋巴结检取总数≥15枚。排除术后1月内死亡者、因其他疾病死亡者和残胃癌以及随访资料不全或失访者。对可能影响pN0期胃癌患者预后的临床因素进行单因素分析，并将有意义的变量纳入Cox比例风险回归模型中进一步行多因素分析，最终得出pN0胃癌患者的独立预后因素。随后采用同样的方法对影响pNn进展期胃癌（浸润深度≥T2）患者预后的因素进行分析。结果610例pN0胃癌患者入组，其中男性441例，女性169例，年龄19．0—83．0（56．4±11．0）岁。行D1淋巴结清扫45例，D2淋巴结清扫543例，D3淋巴结清扫22例。进展期胃癌384例。全组610例患者随访时间1-372（中位数32）月，期间死亡90例（14．8％），中位生存时间277．7（95％CI：257．6～297．8）月，术后1、3、5年生存率分别为96．5％、87．0％和83．2％。单因素分析结果显示，肿瘤直径、浸润深度、大体分型、淋巴结清扫方式、淋巴管癌栓与预后有关（均P〈0．05）。肿瘤直径〉4cm患者的5年生存率明显低于直径≤4cm者（75．6％比87．8％，P=0．000）；浸润深度T1a、T1b、T2、T3、T4期患者5年生存率分别为98．4％、92．8％、84．2％、61．0％和31．4％，差异有统计学意义（P=0．000）：大体分型中，早期胃癌患者5年生存率为96．0％，Borrmann Ⅰ～Ⅳ型胃癌5年生存率依次为100．0％、83．4％、73．7％及68．9％，差异有统计学意义（P=0．000）；淋巴结清扫D1、D2及D3患者术后5年生存率依次为100．0％、83．3％及58．7％，差异有统计学意义（P=0．005）；淋巴管癌栓阳性者5年生存率低于阴性者（69．4％比86．9％，P=0．000）。多因素分析结果显示，大体分型[Borrmann Ⅱ／早期胃癌：HR（95％CI）=15．129（3．284—69．699），Borrmann Ⅲ／早期胃癌：HR（95％CI）=14．613（3．292。64．875）．Borrmann Ⅳ／早期胃癌：HR（95％CI）=15．430（2．778～85．718），BomnannV／早期胃癌：HR（95％CI）=12．604（1．055。150．642）；P=0．025]和淋巴管癌栓阳性[HR（95％CI）=3．241（2．056～5．108），P=0．000]是影响pN0胃癌患者的独立预后因素。pN0进展期胃癌患者的多因素分析结果显示，浸润深度较深[T3／T2期：HR（95％ CI）=1．520（0．888～2．601），T4/T2期：HR（95％CI）=2．235（1．227～4．070）；P=0．0311与淋巴管癌栓阳性[HR（95％CI）=3．065（1．930～4．868），P=0．000]是影响pN0进展期胃癌患者预后的独立危险因素。结论淋巴管癌栓阳性和大体分型差提示pN0胃癌患者预后不良，可以作为评估预后的有效指标；而对于pN0进展期胃癌患者，浸润深度和淋巴管癌栓对预后评估的帮助更大。

Objective To investigate the prognostic factors of patients with lymph node-negative metastasis gastric cancer （pN0）. Methods Clinicopathological data of patients with pN0 gastric cancer who underwent radical operation at the Department of Surgical Ontology, The First Hospital of China Medical University from May 1980 to August 2012 were collected and analyzed retrospectively. Inclusion criteria： （1） Patients were diagnosed as gastric adenocarcinoma; （2） Postoperative pathology confirmed Tla to 4bNOM0 gastric cancer; （3） Total number of harvested lymph node was more than 15. The patients, who died within 1 month after the operation, died of other diseases, had remnant gastric cancer, or had incomplete follow-up data, were excluded. Univariate analysis was used to analyze the clinical factors that may influence the prognosis of patients with stage pN0 gastric cancer, then, those significant variables were entered into the Cox＇s proportional hazards regression model for multivariate analysis to obtain the independent prognostic factors for patients with pN0 gastric cancer finally. Furthermore, the prognosis of patients with pN0 advanced gastric cancer （invasive depth i〉 T2） were analyzed using the same method. Results A total of 610 patients with pN0 gastric cancer were enrolled in the study, including 441 males and 169 females with age ranging from 19 to 83 （mean 56.4 ± 11.0） years, D1 lymph node dissection in 45 cases, D2 lymph node dissection in 543 cases, D3 lymph node dissection in 22 cases, and 384 cases of advanced gastric cancer. The overall followed-up was 1 to 372 （median 32） months. Ninety cases （14.8%） were dead during the follow-up. The median survival was 277.7 （95% CI：257.6 to 297.8） months, and the 1-, 3-, 5-year survival rates were 96.5%, 87%, 83.2%. Univariate analysis showed that tumor diameter, depth of invasion, gross type, lymph node dissection and lymph vessel cancer embolus were related to the prognosis （all P 〈 0.05）. The 5-year survival rate of patients with tumor diameter 〉 4 cm was significantly lower than those with tumor diameter ≤ 4 cm （75.6% vs. 87.8%, P=0.000）. The 5-year survival rates of T1a, T1b, T2, T3 and T4 were 298.4%, 92.8%, 84.2%, 61.0% and 31.4% respectively, and the difference was statistically significant （P = 0.000）. In gross type, 5-year survival rate of early gastric cancer was 96.0% , and of Borrmann Ⅰ to Ⅳ type gastric cancer was 100% , 83.4% , 73.7% and 68.9% respectively, whose difference was statistically significant （P=0.000）. The 5-year survival rates in patients undergoing lymph node dissection D1, D2 and D3 were 100%, 83.3% and 58.7%, and the difference was significant （P= 0.005）. The 5-year survival rate of patients with positive lymphatic cancer embolus was lower than those with negative ones （69.4% vs. 86.9%, P= 0.000）. Multivariate analysis showed that the gross type [Borrmann ll/early gastric cancer： HR （95% CI） = 15.129 （3.284 to 69.699）, Borrmannm/early gastric cancer： HR（95% CI） = 14.613 （3.292 to 64.875）, BorrmannlV/ early gastric cancer： HR （95% CI） = 15.430 （2.778 to 85.718）,BorrmannV/early gastric cancer： HR （95%CI）= 12.604 （1.055 to 150.642）, P=0.025] and the positive lymphatic cancer embolus [HR （95% CI） = 3.241 （2.056 to 5.108）, P= 0.0001 were the independent prognostic factors of patients with pN0 gastric cancer. For pN0 patients with advanced gastric cancer, multivariate analysis showed that the depth of invasion [stage T3/stage T2： HR（95%CI）= 1.520 （0.888 to 2.601）, stage Td/stage T2： HR （95%CI） = 2.235 （1.227 to 4.070）; P=0.031] and the positive lymphatic cancer embolus [HR （95%CI） = 3.065 （1.930 to 4.868）; P=0.000] were the independent risk factors influencing the prognosis. Conclusions Positive lymphatic cancer embolus and worse gross pattern indicate poorer prognosis of patients with pN0 gastric cancer, which may be used as effective markers in evaluating the prognosis. As for pN0 advanced gastric cancer, invasion depth and positive lymphatic cancer embolus can play a more important role in the prediction.