腹腔镜胃癌根治术的临床疗效分析(附4 435例报告)

Clinical effect analysis of laparoscopic radical gastrectomy for gastric cancer: a report of 4 435 cases

目的探讨腹腔镜胃癌根治术的发展趋势、安全性及临床疗效。方法采用回顾性描述性研究方法。收集2008年1月至2017年12月福建医科大学附属协和医院收治的4 435例行腹腔镜胃癌根治术患者的临床病理资料;男3 263例,女1172例;年龄为(61±11)岁,年龄范围为12~93岁。依据患者手术时间,以5年为截点将4435例患者分为两个时期:前期(2008—2012年)1 588例和后期(2013—2017年)2 847例。观察指标:(1)临床病理资料。(2)术中和术后情况。(3)术后并发症情况。(4)随访和生存情况。采用门诊、登门拜访、信件及电话等方式由专人进行术后随访。术后前2年每3个月随访1次,术后2年以后每6个月随访1次,记录患者的生存情况,生存时间定义为自手术时间至末次随访时间,或死亡时间,或随访数据库截至时间(如失访、死于其他疾病等)。随访时间截至2018年6月。正态分布的计量资料以Mean±SD表示,组间比较采用t检验;偏态分布的计量资料以M(范围)表示。计数资料以频数或百分比表示,组间比较采用χ2检验。采用一元线性回归进行线性分析。采用Kaplan-Meier法计算生存率并绘制生存曲线,Log-rank检验进行生存情况分析。结果(1)临床病理资料:4 435例患者中,男3263例,占73.574%(3263/4435),女1 172例,占26.426%(1172/4435)。4 435例患者TNM分期:早期胃癌(均为T1期)1133例;进展期胃癌3 302例,其中T2期518例,T3期1 431例,T4a期1 353例。线性回归分析显示:腹腔镜胃癌根治术例数与手术年份呈线性相关(R2=0.911,P<0.05),腹腔镜胃癌根治术例数逐年上升。前期患者的性别(男),肿瘤部位(胃上部、胃中部、胃下部、>2个部位),肿瘤直径,病理学类型(分化型、未分化型),pT分期(pT1、pT2、pT3、pT4a期),pN分期(pN0、pN1、pN2、pN3a、pN3b期),pTNM分期(ⅠA、ⅠB、ⅡA、ⅡB、ⅢA、ⅢB、ⅢC期)分别为1 204例,383、302、714、189例,(4.8±2.7)cm,361、1 227例,382、193、418、595例,588、212、255、318、215例,325、137、150、172、253、267、284例;后期患者的上述指标分别为2 059例,807、530、1 128、382例,(4.3±2.6)cm,976、1 871例,751、325、1 013、758例,1 138、444、505、486、274例,616、258、378、322、528、443、302例,两期患者上述指标比较,差异均有统计学意义(χ^2=6.411,15.699,t=10.946,χ^2=57.801,90.437,26.502,98.773,P<0.05)。(2)术中和术后情况:前期手术患者术中出血量,术中输血,消化道重建方式(B-Ⅰ式吻合、B-Ⅱ式吻合、残胃Roux-en-Y吻合、食管-残胃吻合、食管Roux-en-Y吻合),淋巴结清扫数目,术后首次进食流质食物时间,术后首次进食半流质食物时间,术后住院时间分别为(120±75)mL,38例,599、122、0、32、835例,(32±13)枚,(4.5±1.7)d,(8.6±2.5)d,(13.0±7.3)d;后期手术患者上述指标分别为(104±68)mL,17例,441、673、21、18、1 694例,(37±15)枚,(4.1±1.5)d,(7.9±2.8)d,(12.3±7.6)d,两期患者上述指标比较,差异均有统计学意义(t=2.169,χ^2=26.843,397.185,t=-10.764,2.125,3.347,2.779,P<0.05)。进一步线性回归分析显示:患者人均淋巴结清扫数目与手术年份呈线性相关(R2=0.826,P<0.05),人均淋巴结清扫数目呈逐年上升趋势。(3)术后并发症情况:4 435例患者中,690例发生术后并发症,并发症发生率为15.558%(690/4 435),其中前期242例,后期448例,两期比较,差异无统计学意义(χ^2=0.191,P>0.05);8例因术后严重并发症死亡,病死率为0.180%(8/4 435),其中前期5例,后期3例,两期比较,差异无统计学意义(χ^2=2.485,P>0.05)。4 435例患者中,561例发生Ⅰ~Ⅱ级并发症,发生率为12.649%(561/4435),129例发生Ⅲ~Ⅴ级并发症,发生率为2.909%(129/4 435);前期发生Ⅰ~Ⅱ级和Ⅲ~Ⅴ级并发症分别为196例和46例,后期分别为365例和83例,两期患者Ⅰ~Ⅱ级和Ⅲ~Ⅴ级并发症发生情况比较,差异均无统计学意义(χ^2=0.211,0.001,P>0.05)。(4)随访和生存情况:4 435例患者中,4 250例获得术后随访(前期1 465例、后期2 785例),随访时间为1~123个月,中位随访时间为37个月;患者5年累积生存率为63.9%,Ⅰ、Ⅱ、Ⅲ期患者5年生存率分别为91.8%、80.2%和39.5%,3者生存情况比较,差异有统计学意义(χ^2=810.146,P<0.05)。前期和后期患者5年累积生存率分别为60.8%和66.7%,两者生存情况比较,差异有统计学意义(χ^2=17.887,P<0.05)。TNM分期分层分析显示:前期患者ⅠA、ⅠB、ⅡA、ⅡB、ⅢA、ⅢB、ⅢC期5年累积生存率分别为92.7%、85.6%、79.4%、74.5%、58.1%、37.6%、18.9%,后期患者分别为95.6%、90.4%、87.6%、79.5%、52.7%、41.2%、19.5%,两期患者各TNM分期生存情况比较,差异均无统计学意义(χ^2=0.414,2.575,2.872,2.119,0.632,0.972,2.212,P>0.05)。结论腹腔镜胃癌根治术的手术量呈逐年上升趋势,且患者人均淋巴结清扫数目逐年增加,患者术后恢复不断改善,具有良好的安全性和临床疗效。

Objective To investigate the development trend, safety and clinical effects of laparoscopic radical gastrectomy (LRG) for gastric cancer. Methods The retrospective and descriptive study was conducted. The clinicopathological data of 4435 patients with gastric cancer who underwent LRG in the Fujian Medical University Union Hospital between January 2008 and December 2017 were collected. There were 3263 males and 1172 females, aged (61±11)years, with a range of 12-93 years. According to the operation time, 4435 patients were divided into two periods, including 1 588 patients of the early period (2008-2012) and 2847 patients of the later period (2013-2017). Observation indicators:(1) the clinicopathological data of patients;(2) intraoperative and postoperative situations;(3) postoperative complications;(4) follow-up and survival situations. Follow-up using outpatient examination, visit to home, mail and telephone interview was performed to detect survival of patients once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively up to June 2018. Survival time was from operation time to the last follow-up, death or deadline of follow-up database such as loss to follow-up or death of other diseases. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as frequency or percentage, comparison between groups was analyzed using the chi-square test. Linear analysis was done using the unitary linear regression. The survival rate and survival curve were respectively calculated and drawn by the Kaplan-Meier method, and Log-rank test was used for survival analysis. Results (1) The clinicopathological data of patients: there were 3263 males and 1172 females of the 4435 patients, accounting for 73.574%(3 263/4 435) and 26.426%(1172/4435), respectively. TNM staging of the 4435 patients: 1133 cases were detected early gastric cancer (T1 stage) and 3302 cases were detected advanced gastric cancer including 518, 1431, 1353 in T2, T3 and T4a stages respectively. Linear regression analysis showed a linear correlation between the cases of LRG and operation year (R2=0.911, P<0.05) and a gradually increasing in cases of LRG. The sex (male), cases with tumor at upper stomach, middle stomach, lower stomach,>2 regions (tumor location), tumor diameter, cases with undifferentiated and differentiated tumor (pathological types), cases in pT1, pT2, pT3, pT4a stages (pT staging), in pN0, pN1, pN2, pN3a, pN3b stages (pN staging), in ⅠA,ⅠB,ⅡA,ⅡB,ⅢA,ⅢB,ⅢC stages (pTNM staging ) were 1 204, 383, 302, 714, 189,(4.8±2.7)cm, 361, 1 227, 382, 193, 418, 595, 588, 212, 255, 318, 215, 325, 137, 150, 172, 253, 267, 284 in patients of the early period, and 2 059, 807, 530, 1128, 382,(4.3±2.6) cm, 976, 1871, 751, 325, 1013, 758, 1138, 444, 505, 486, 274, 616, 258, 378, 322, 528, 443, 302 in patients of the later period, with statistically significant differences between patients of the two periods (χ^2=6.411, 15.699, t=10.946,χ^2=57.801, 90.437, 26.502, 98.773, P<0.05).(2) Intraoperative and postoperative situations: the volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with BillrothⅠ, BillrothⅡ, residual stomach Roux-en-Y anastomosis, esophagogastric anastomosis, esophageal Roux-en-Y anastomosis of digestive tract reconstruction, number of lymph nodes dissected, time for initial fluid diet intake, time for initial semi-fluid diet intake, duration of postoperative hospital stay were (120±75)mL, 38, 599, 122, 0, 32, 835, 32±13,(4.5±1.7)days,(8.6±2.5)days,(13.0±7.3)days in patients of the early period,(104±68)mL, 17, 441, 673, 21, 18, 1 694, 37±15,(4.1±1.5)days,(7.9±2.8)days,(12.3±7.6)days in patients of the later period, showing statistically significant differences between patients of the two periods (t=2.169,χ^2=26.843, 397.185, t=-10.764, 2.125, 3.347, 2.779, P<0.05). Further linear regression analysis showed a linear correlation between the average number of lymph nodes dissected and operation year (R2=0.826, P<0.05) and a gradually increasing in average number of lymph nodes dissected.(3) Postoperative complications: 690 of 4 435 patients had postoperative complications, with an incidence rate of 15.558%(690/4 435), including 242 patients of the early period and 448 of the later period, showing no statistically significant difference (χ^2=0.191, P>0.05). Eight patients died of severe postoperative complications, with a death rate of 0.180%(8/4 435), including 5 of the early period and 3 of the later period, showing no statistically significant difference (χ^2=2.485, P>0.05). Of 4 435 patients, 561 had stage Ⅰ-Ⅱ complications, with an incidence rate of 12.649%(561/4 435), 129 had stage Ⅲ-Ⅳ complications, with an incidence rate of 2.909%(129/4 435). There were 196 and 46 patients of the early period with stage Ⅰ-Ⅱ complications and stage Ⅲ-Ⅳ complications, 365 and 83 of the later period with stage Ⅰ-Ⅱ complications and stage Ⅲ-Ⅳ complications, showing no statistically significant difference between patients of the two periods (χ^2=0.211, 0.001, P>0.05).(4) Follow-up and survival situations: 4 250 of 4 435 patients including 1 465 of the early period and 2 785 of the later period were followed up for 1-123 months, with a median time of 37 months. The 5-year cumulative survival rate was 63.9%. The 5-year cumulative survival rate was 91.8%, 80.2% and 39.5% in the stage Ⅰ,Ⅱ,Ⅲ patients, respectively, showing a statistically significant difference (χ^2=810.146, P<0.05). The 5-year cumulative survival rate was 60.8% and 66.7% in patients of the early and later period, respectively with a statistically significant difference (χ^2=17.887, P<0.05). Stratified analysis of TNM staging: the 5-year cumulative survival rates of stage ⅠA,ⅠB,ⅡA,ⅡB,ⅢA,ⅢB,ⅢC patients in the early period were 92.7%, 85.6%, 79.4%, 74.5%, 58.1%, 37.6%, 18.9% and 95.6%, 90.4%, 87.6%, 79.5%, 52.7%, 41.2%, 19.5% in patients of the later period, with no statistically significant difference (χ^2=0.414, 2.575, 2.872, 2.119, 0.632, 0.972, 2.212, P>0.05). Conclusions Surgical volume of the LRG has shown an increasing trend year by year, and the number of lymph nodes dissected and postoperative recovery of patients are improving. LRG is a safe procedure with acceptable clinical efficacy for gastric cancer.