新辅助化疗联合腹腔镜辅助胃癌根治术治疗进展期胃癌的疗效分析

Clinical efficacy of neoadjuvant chemotherapy combined with laparoscopy-assisted radical gastrectomy for advanced gastric cancer

目的探讨新辅助化疗联合腹腔镜辅助胃癌根治术治疗进展期胃癌的临床疗效。方法采用回顾性队列研究方法。收集2012年1月至2015年6月华中科技大学同济医学院附属协和医院收治的112例进展期胃癌患者的临床资料。根据患者意愿决定是否行新辅助化疗。42例行新辅助化疗联合腹腔镜辅助胃癌根治术患者设为新辅助化疗＋腹腔镜手术组，70例仅行腹腔镜辅助胃癌根治术，未行新辅助化疗患者设为腹腔镜手术组。新辅助化疗＋腹腔镜手术组采用FOLFOX6方案行新辅助化疗，术前完成2～4个周期的化疗，完成后约4周行手术治疗。根据实体瘤的疗效评价标准（RECIST）将新辅助化疗疗效分为完全缓解、部分缓解、疾病稳定、疾病进展。临床反应率=[（完全缓解病例数＋部分缓解病例数）／可测量病例数]X100％，疾病控制率=[（完全缓解病例数＋部分缓解病例数＋疾病稳定病例数）／可测量病例数]×100％。化疗期间观察患者不良反应，按照WHO抗癌药物常见不良反应分级标准分为0、Ⅰ、Ⅱ、Ⅲ、Ⅳ级。根据肿瘤部位选择远端或全胃切除术。观察指标：（1）新辅助化疗疗效及不良反应分级。（2）手术情况。（3）术后恢复情况。（4）预后情况。采用门诊和电话方式进行随访，了解患者术后生存及肿瘤复发、转移情况。随访时间截至2015年12月。正态分布的计量资料以x±s表示，组间比较采用t检验。计数资料比较采用爿。检验和非参数检验。结果（1）新辅助化疗疗效及不良反应情况：42例新辅助化疗＋腹腔镜手术组患者中12例患者获得临床降期。其中完全缓解2例，部分缓解16例，疾病稳定20例，疾病进展4例；临床反应率为42．9％（18／42），疾病控制率为90．5％（38／42）。0、Ⅰ、Ⅱ、Ⅲ、Ⅳ级不良反应分别为5、23、12、2、0例，均经积极对症处理后好转，无新辅助化疗相关死亡发生。（2）手术情况：新辅助化疗＋腹腔镜手术组和腹腔镜手术组患者中分别有3例和11例行姑息性手术；手术切缘R。切除例数分别为34例和44例，R．或R：切除例数分别为5例和15例，两组比较，差异有统计学意义（χ^2=4．066，P〈0．05）。（3）术后恢复情况：新辅助化疗＋腹腔镜手术组和腹腔镜手术组患者术后胃肠功能恢复时间分别为（3．1±1．2）d和（2．8±0．9）d，术后住院时间分别为（13±4）d和（13±4）d，术后并发症例数中切口感染分别为4例和5例，肺部感染分别为3例和2例，胸腔积液分别为1例和2例，吻合口瘘分别为0例和1例，吻合口出血分别为1例和0例，胃排空障碍分别为0例和1例，十二指肠残端瘘分别为1例和1例，肠梗阻分别为0例和1例，腹腔感染分别为1例和1例，腹腔出血分别为0例和1例，淋巴漏分别为0例和1例，血栓形成分别为1例和0例。两组患者术后胃肠功能恢复时间、术后住院时间、术后并发症例数比较，差异均无统计学意义（t=1．114，0．416，χ^2=0．457，P〉0．05）。112例患者中，103例获得术后随访。随访时间为6—45个月，中位随访时间为22个月。随访期间，新辅助化疗＋腹腔镜手术组和腹腔镜手术组患者分别有5例和11例死亡，9例和17例肿瘤复发、转移。结论进展期胃癌行腹腔镜辅助胃癌根治术前行新辅助化疗是安全可行的，可有效降低进展期胃癌临床分期，提高R0切除率。

Objective To explore the clinical efficacy of neoadjuvant chemotherapy combined with laparoscopy-assisted radical gastrectomy for advanced gastric cancer. Methods The retrospective cohort study was adopted. The clinical data of 112 patients with advanced gastric cancer who were admitted to the Wuhau Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2012 to June 2015 were collected. The neoadjuvant chemotherapy was selectively performed based on patients＇ decisions. Of 112 patients, 42 receiving neoadjuvant chemotherapy combined with laparoscopy-assisted radical gastrectomy （NCLAG） were al｜ocated into the NCLAG group and 70 receiving laparoscopy-assisted radical gastrectomy （LAG） without neoadjuvant chemotherapy were allocated into the LAG group. Patients in the NCLAG group underwent LAG at 4 weeks after neoadjuvant chemotherapy of 2-4 cycles FOLFOX6 regimen. The efficacy of neoadjuvant chemotherapy was divided into the complete remission （CR） , partial remission （PR） , stable disease （SD） and progressive disease （PD） based on the Response Evaluation Criteria in Solid Tumors （RECIST）. Clinical response rate = [ （number of patients with CR ＋ number of patients with PR）/number of measurable patients] x 100% ,disease control rate = [ （number of patients with CR ＋ number of patients with PR ＋ number of patients with SD）/number of measurable patients ] × 100%. The adverse reactions were observed during neoadjuvant chemotherapy and were divided into the grade 0, Ⅰ, Ⅱ, Ⅲ, and Ⅳ based on the grading standards for common adverse drug reactions of anticancer drugs issued by World Health Organization （WHO）. The distal or total gastrectomy was selected according to tumor location. Observation indicators included （1） efficacy of neoadjuvant chemotherapy and grading of adverse reaction, （2） surgical situations, （ 3 ） postoperative recovery, （4） prognosis. The follow-up of outpatient examination and telephone interview was performed to detect the survival of patients and tumors recurrence and metastasis up to December 2015. The measurement data with normal distribution was presented as x±s. The comparison between groups was evaluated with the t test, and the count data were analyzed using the chi-square test and nonparametric test. Results （1） Efficacy of neoadjuvant chemotherapy and adverse reaction： of 42 patients in the NCLAG group, 12 had tumor down-staging, and 2, 16, 20 and 4 had respectively CR, PR, SD and PD, with the clinical response rate of 42.9% （18/42） and disease control rate of 90.5% （38/42）. Five, 23, 12, 2 and 0 patients had respectively grade 0, Ⅰ, Ⅱ,Ⅲ, and IV of adverse reactions and were improved after symptomatic treatment, without occurrence of chemotherapy-related death. （2） Surgical situations ： number of patients with palliative operation, number of patients with R0 resection and with Rl or R2 reseetion were 3,34 , 5 in the NCLAG group and 11, 44, 15 in the LAG group, respectively, with signifieant difference between the 2 groups （χ^2 = 4. 066, P 〈 0.05 ）. （ 3 ） Postoperative recovery ： recovery time of gastrointestinal function and duration of hospital stay were respectively （ 3.1±1.2 ） days and （ 13±4 ） days in the NCLAG group and （2.8 ±0.9） days and （13 ＋4）days in the LAG group. Four, 3, 1,0, 1, 0, 1, 0, 1, 0, 0 and 1 patients in the NCLAG group and 5, 2, 2, 1, 0, 1, 1, 1, 1, 1, 1, and 0 patients in the LAG group were respeetively complicated with incisional infection, pulmonary infection, pleural effusion, anastomotic fistula, anastomotie hemorrhage, delayed gastric emptying, duodenal stump fistula, intestine obstruction, intraperitoneal infeetion, intraperitoneal hemorrhage, endolymphatic leakage and thrombosis. There were no significant differences in the recovery time of gastrointestinal function, duration of hospital stay and number of patients with eomplieations between the 2 groups （t = 1. 114, 0. 416, χ^2=0. 457, P 〉0.05）. Of 112 patients, 103 were followed up for a median time of 22 months （ranges, 6-45 months） , 5 in the NCLAG group and 11 in the LAG group were dead, 9 in the NCLAG group and 17 in the LAG group had tumors recurrence and metastasis. Conclusion Neoadjuvant chemotherapy is safe and feasible after LAG for advanced gastric cancer, and it can effeetively reduce the clinical stage of gastrie cancer and improve the R0 resection rate.