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Ⅲ期胃癌根治术后预后因素分析及淋巴结转移率对预后的预测价值(附995例报告)

Prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis: a report of 995 cases

摘要:

目的 探讨Ⅲ期胃癌根治术后预后因素及淋巴结转移率对预后的预测价值.方法 采用回顾性病例对照研究方法.收集2003年1月至2014年12月复旦大学附属中山医院收治的995例Ⅲ期胃癌患者的临床病理资料;男690例,女305例;平均年龄为61岁,年龄范围为20~75岁.根据患者术前辅助检查结果进行临床分期,早期胃癌行D1+淋巴结清扫术,进展期胃癌行标准的D2淋巴结清扫术,肿瘤侵犯浆膜行D2+淋巴结清扫术.观察指标:(1)治疗情况.(2)随访和生存情况.(3)术后预后因素分析.(4)分层分析:①肿瘤病理学N分期分层分析.②淋巴结清扫总数分层分析.③肿瘤病理学TNM分期分层分析.(5)受试者工作特征(ROC)曲线.采用门诊和电话方式进行随访,了解患者术后生存情况.随访时间截至2016年1月.总体生存时间定义为自手术日期至末次有效随访日期或患者死亡日期.正态分布的计量资料以Mean±SD表示.采用Kaplan-Meier法计算生存率和绘制生存曲线,采用Log-rank检验进行生存情况分析.采用COX比例风险模型进行单因素和多因素分析.采用ROC曲线及其曲线下面积(AUC)检验阳性淋巴结数目和淋巴结转移率预测患者预后的准确性.AUC比较采用Z检验.结果 (1)治疗情况:995例患者均行胃癌根治术,其中行远端胃切除术677例,行近端胃切除术85例,行全胃切除术233例;行D1+淋巴结清扫术117例,行D2或D2+淋巴结清扫术878例.995例患者淋巴结清扫数目为(27±12)枚,阳性淋巴结数目为(10±9)枚,淋巴结转移率为0.41±0.28.(2)随访和生存情况:995例患者均获得术后随访,随访时间为(35±32)个月.随访期间,995例患者术后1、3、5年总体生存率分别为77.9%、47.8%、36.2%.(3)术后预后因素分析.单因素分析结果显示:患者的性别、肿瘤组织学类型、脉管癌栓、肿瘤浸润深度、肿瘤病理学N分期、淋巴结清扫总数、淋巴结转移率、肿瘤病理学TNM分期是影响Ⅲ期胃癌根治术后预后的相关因素(风险比=0.817,1.486,1.268,2.173,1.957,1.737,3.357,2.169,95%可信区间为0.686~0.973,1.059~2.086,1.074~1.497,1.195 ~3.954,1.480 ~2.588,1.390~2.170,2.476~4.602,1.740~2.704,P<0.05).多因素分析结果显示:患者的性别、肿瘤组织学类型、肿瘤病理学N分期、淋巴结清扫总数、淋巴结转移率、肿瘤病理学TNM分期是影响Ⅲ期胃癌根治术后预后的独立因素(风险比=0.805,1.476,0.237,1.475,3.811,3.600,95%可信区间为0.673 ~0.963,1.049~2.087,0.083 ~0.678,1.140 ~1.909,2.259~6.428,1.317~9.839,P<0.05).(4)分层分析.995例患者术后1、3、5年总体生存率:淋巴结转移率≤0.1患者分别为93.7%、69.6%、60.5%,0.1<淋巴结转移率≤0.4患者分别为86.9%、60.6%、44.3%,淋巴结转移率>0.4患者分别为64.3%、28.9%、21.0%,3者生存情况比较,差异有统计学意义(x2=121.300,P<0.05);其中淋巴结转移率≤0.1分别与0.1<淋巴结转移率≤0.4、淋巴结转移率>0.4患者的生存情况比较,差异均有统计学意义(x2=7.580,65.320,P<0.05);0.1<淋巴结转移率≤0.4与淋巴结转移率>0.4患者生存情况比较,差异有统计学意义(x2=80.806,P<0.05).①肿瘤病理学N分期分层分析:132例N1期患者的淋巴结转移率平均值为0.09,将N1期患者淋巴结转移率分为≤0.1和>0.1两组.108例淋巴结转移率≤0.1患者术后1、3、5年总体生存率分别为92.2%、68.6%、59.1%.24例淋巴结转移率>0.1患者术后1、3、5年总体生存率分别为79.2%、32.8%、21.9%,两者生存情况比较,差异有统计学意义(x2=14.499,P<0.05).265例N2期患者的淋巴结转移率平均值为0.23,将N2期患者淋巴结转移率分为≤0.2和>0.2两组.138例淋巴结转移率≤0.2患者术后1、3、5年总体生存率分别为92.3%、73.8%、61.0%,127例淋巴结转移率>0.2患者术后1、3、5年总体生存率分别为76.5%、40.1%、22.2%,两者生存情况比较,差异有统计学意义(x2=42.536,P<0.05).598例N3期患者的淋巴结转移率平均值为0.56,将N3期患者淋巴结转移率分为≤0.4和>0.4两组.194例淋巴结转移率≤0.4患者术后1、3、5年总体生存率分别为88.5%、62.8%、47.0%,404例淋巴结转移率>0.4患者术后1、3、5年总体生存率分别为64.3%、29.8%、21.0%,两者生存情况比较,差异有统计学意义(xa=51.860,P<0.05).②淋巴结清扫总数分层分析:117例淋巴结清扫总数<15枚患者中仅7例淋巴结转移率≤0.1,所以将该亚组患者分为淋巴结转移率≤0.4和>0.4两组.44例淋巴结转移率≤0.4患者术后1、3、5年总体生存率分别为78.2%、40.0%、28.6%,73例淋巴结转移率>0.4患者术后1、3、5年总体生存率分别为78.1%、18.7%、12.9%,两者生存情况比较,差异有统计学意义(x2=4.727,P<0.05).③肿瘤病理学TNM分期分层分析:262例Ⅲa期胃癌患者中,230例淋巴结转移率≤0.4,术后1、3、5年总体生存率分别为88.5%、65.0%、54.3%;32例淋巴结转移率>0.4,术后1、3、5年总体生存率分别为77.5%、35.4%、29.5%,两者生存情况比较,差异有统计学意义(x2 =6.132,P<0.05).296例Ⅲb期胃癌患者中,200例淋巴结转移率≤0.4,术后1、3、5年总体生存率分别为84.4%、60.7%、42.7%;96例淋巴结转移率>0.4,术后1、3、5年总体生存率分别为59.9%、26.8%、21.7%,两者生存情况比较,差异有统计学意义(x2 =23.699,P<0.05).437例Ⅲc期胃癌患者中,133例淋巴结转移率≤0.4,术后1、3、5年总体生存率分别为84.7%、59.9%、38.7%;304例淋巴结转移率>0.4,术后1、3、5年总体生存率分别为64.0%、27.9%、18.3%,两者生存情况比较,差异有统计学意义(x2=36.215,P<0.05).(5)ROC曲线:分别以阳性淋巴结数目和淋巴结转移率绘制Ⅲ期胃癌根治术后患者总体生存率ROC曲线,其AUC分别为0.619(95%可信区间为0.588~0.649)和0.706(95%可信区间为0.677~0.734),两者比较,差异有统计学意义(Z=8.842,P<0.05).结论 患者性别、肿瘤组织学类型、肿瘤病理学N分期、淋巴结清扫总数、淋巴结转移率、肿瘤病理学TNM分期是影响Ⅲ期胃癌根治术后预后的独立因素;在相同肿瘤病理学N分期亚组、相同淋巴结清扫总数亚组、相同肿瘤病理学TNM分期亚组中,不同淋巴结转移率患者预后存在差异;与肿瘤病理学N分期比较,淋巴结转移率预测患者预后更准确.

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abstracts:

Objective To investigate the prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis.Methods The retrospective case-control study was conducted.The clinicopathological data of 995 patients with stage Ⅲ gastric cancer who were admitted to the Zhongshan Hospital of Fudan University between January 2003 and December 2014 were collected.There were 690 males and 305 females,aged from 20 to 75 years,with an average age of 61 years.After clinical staging according to results of preoperative accessory examinations,patients with early gastric cancer underwent D1+ lymphadenectomy,patients with advanced gastric cancer underwent D2 lymphadenectomy and patients with serosa invasion underwent D2+ lymphadenectomy.Observation indicators:(1) treatment situations;(2) follow-up and survival situations;(3) prognostic factors analysis after operation;(4) stratified analysis:① stratified analysis of tumor pathological N staging;② stratified analysis of number of lymph node dissected;③ stratified analysis of tumor pathological TNM staging;(5) receiver operating characteristic (ROC) curve.Patients were followed up using outpatient examination and telephone interview to detect postoperative survival up to January 2016.The overall survival time was from the operation data to last follow-up or time of death.Measurement data with normal distribution were represented as Mean±SD.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and Log-rank test was used for survival analysis.The COX proportional hazard model was used for univariate and multivariate analysis.The ROC curve and area under curve (AUC) were used to check the accuracy of number of positive lymph nodes and metastatic lymph node ratio for prognosis.Comparison of the AUC was analyzed by the Z test.Results (1) Treatment situations:of 995 patients underging gastrectomy,677 underwent distal gastrectomy,85 underwent proximal gastrectomy,233 underwent total gastrectomy.There were 117 undergoing D1+ lymphadenectomy and 878 undergoing D2 lymphadenectomy or D2+ lymphadenectomy.The number of lymph node dissected,number of positive lymph nodes,metastatic lymph node ratio were 27± 12,10± 9 and 0.41±0.28,respectively.(2) Follow-up and survival situations:995 patients were followed up for (35± 32)months.During the follow-up,the 1-,3-,5-year overall survival rates were 77.9%,47.8%,36.2%.(3) Prognostic factors analysis after operation:results of univariate analysis showed that sex,tumor histological type,vascular embolus,degree of tumor invasion,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were related factors affecting prognosis of radical gastrectomy for stage Ⅲ gasteric cancer (hazard ratio =0.817,1.486,1.268,2.173,1.957,1.737,3.357,2.169,95% confidence interval:0.686-0.973,1.059-2.086,1.074-1.497,1.195-3.954,1.480-2.588,1.390-2.170,2.476-4.602,1.740-2.704,P<0.05).Results of multivariate analysis showed that sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer (hazard ratio =0.805,1.476,0.237,1.475,3.811,3.600,95% confidence interval:0.673-0.963,1.049-2.087,0.083-0.678,1.140-1.909,2.259-6.428,1.317-9.839,P<0.05).(4) Stratified analysis:of the 995 patients,the postoperative l-,3-,5-year overall survival rates were 93.7%,69.6%,60.5% in the patients with metastatic lymph node ratio ≤ 0.1,86.9%,60.6%,44.3% in the patients with 0.1 < metastatic lymph node ratio ≤0.4 and 64.3%,28.9%,21.0% in the patients with metastatic lymph node ratio > 0.4,showing a statistically significant difference (x2 =121.300,P<0.05).There were statistically significant differences between patients with metastatic lymph node ratio ≤0.1 and patients with 0.1< metastatic lymph node ratio ≤0.4,between patients with metastatic lymph node ratio ≤0.1 and patients with metastatic lymph node ratio >0.4 (x2=7.580,65.320,P<0.05).There was a statistically significant difference between patients with 0.1 < metastatic lymph node ratio ≤0.4 and patients with metastatic lymph node ratio>0.4 (x2 =80.806,P<0.05).① Stratified analysis of tumor pathological N staging:the average metastatic lymph node ratio was 0.09 in the 132 stage N1 patients,who were divided into the patients with metastatic lymph node ratio ≤ 0.1 and > 0.1.The postoperative 1-,3-,5-year overall survival rates were 92.2%,68.6%,59.1% in the 108 patients with metastatic lymph node ratio ≤ 0.1 and 79.2%,32.8%,21.9% in the 24 patients with metastatic lymph node ratio >0.1,respectively,showing a statistically significant difference (x2 =14.499,P<0.05).The average metastatic lymph node ratio was 0.23 in the 265 stage N2 patients,who were divided into the patients with metastatic lymph node ratio ≤0.2 and >0.2.The postoperative 1-,3-,5-year overall survival rates were 92.3%,73.8%,61.0% in the 138 patients with metastatic lymph node ratio ≤0.2 and 76.5%,40.1%,22.2% in the 127 patients with metastatic lymph node ratio >0.2,respectively,showing a statistically significant difference (x2 =42.536,P<0.05).The average metastatic lymph node ratio was 0.56 in the 598 stage N3 patients,who were divided into the patients with metastatic lymph node ratio ≤0.4 and >0.4.The postoperative 1-,3-,5-year overall survival rates were 88.5%,62.8%,47.0% in the 194 patients with metastatic lymph node ratio ≤ 0.4 and 64.3%,29.8%,21.0% in the 404 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =51.860,P< 0.05).② Stratified analysis of number of lymph node dissected:7 of 117 patients with the number of lymph node dissected < 15 had metastatic lymph node ratio ≤0.1,who were divided into patients with metastatic lymph node ratio ≤0.4 and >0.4.The postoperative 1-,3-,5-year overall survival rates were 78.2%,40.0%,28.6% in the 44 patients with metastatic lymph node ratio ≤0.4 and 78.1%,18.7%,12.9% in the 73 patients with metastatic lymph node ratio>0.4,respectively,showing a statistically significant difference (x2 =4.727,P<0.05).③ Stratified analysis of tumor pathological TNM staging:of 262 patients with stage Ⅲa gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 88.5%,65.0%,54.3% in the 230 patients with metastatic lymph node ratio ≤0.4 and 77.5%,35.4%,29.5% in the 32 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =6.132,P<0.05).Of 296 patients with stage Ⅲb gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.4%,60.7%,42.7% in the 200 patients with metastatic lymph node ratio ≤ 0.4 and 59.9%,26.8%,21.7% in the 96 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2 =23.699,P<0.05).Of 437 patients with stage Ⅲ c gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.7%,59.9%,38.7% in the 133 patients with metastatic lymph node ratio ≤0.4 and 64.0%,27.9%,18.3% in the 304 patients with metastatic lymph node ratio >0.4,respectively,showing a statistically significant difference (x2=36.215,P< 0.05).(5) ROC curve:ROC curves of postoperative overall survival rates in patients with stage Ⅲ gastric cancer were drawn using the number of positive lymph nodes and metastatic lymph node ratio,of which AUC were 0.619 (95% confidence interval:O.588-0.649) and 0.706 (95% confidence interval:0.677-0.734),showing a statistically significant difference (Z=8.842,P<0.05).Conclusions Sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging are independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer.There is different prognosis of patients with different metastatic lymph node ratios in the subgroup of the same tumor pathological TNM staging,number of lymph node dissected,tumor pathological TNM staging.Compared with tumor pathological N staging,metastatic lymph node ratio has a more accurate predictive value for prognosis.

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作者: 周荣健 [1] 张恒 [1] 束平 [1] 王洪山 [1] 沈振斌 [1] 刘凤林 [1] 秦净 [1]
期刊: 《中华消化外科杂志》2019年18卷3期 250-258页 ISTICPKUCSCD
栏目名称: 论著
DOI: 10.3760/cma.j.issn.1673-9752.2019.03.010
发布时间: 2019-04-26
基金项目:
上海市科学技术委员会基金 上海市浦江人才计划 中山医院科研发展基金(2016ZSFZ60)Program of Shanghai Science and Technology Committee Shanghai Pujiang Talent Program Scientific Research and Development Foundation of Zhongshan Hospital
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