食管癌新辅助化疗与食管手术间隔时期的临床影响

Clinical effect of interval between neoadjuvant chemotherapy and esophageal operation in patients with esophageal cancer

目的 食管癌患者新辅助化疗与手术的最佳间隔时间现在没有一个准确的定论。本研究的目的在于探究新辅助化疗后食管癌手术时机的选择对临床结局的影响,包括围手术期情况及生存期。方法 本研究回顾性研究了2017年1月—2018年12月在郑州大学第一附属医院进行新辅助化疗且进行食管切除手术的患者182例,依据从完成新辅助化疗到接受手术治疗的时间间隔分为0~40天的短间隔组及40天以上的长间隔组。单因素分析患者的年龄、性别、肿瘤位置、BMI、新辅助化疗方案、手术时机、术后住院时间、术后并发症、肿瘤组织学类型、TNM分期、分化程度、病理退缩情况等一般及临床病理因素,利用Kaplan-Meier绘制生存曲线,并应用Cox回归进行单因素,多因素生存分析。结果 本研究共纳入182名患者,其中长间隔组有117例患者,短间隔组有65例患者。利用单因素分析分析两组患者一般资料发现仅术前合并症(P=0.032)的差异存在统计学意义,其余性别、年龄、肿瘤位置等差异均无统计学意义(P>0.05)。另外,本研究发现术中出血量、手术时间等差异均无统计学意义(P>0.05)。根据患者的临床病理资料进行单因素分析后发现两组患者在TNM分期、切缘情况、脉管及神经侵犯的差异均无统计学意义(P>0.05)。长间隔组和间隔组的病理完全缓解率分别为33.8%(26/117)和22.2%(22/65),长间隔组的病理完全缓解率相对短间隔组有提高的趋势,但是差异无统计学意义(P=0.239)。经单因素及多因素Cox回归分析后发现手术间隔时间对生存期无明显影响(HR=1.249,95%CI=0.792~1.971,P=0.339),影响生存期的主要因素是ypT分期(HR=1.220,95%CI=1.014~1.469,P=0.035)及R0切除(HR=4.344,95%CI=1.041~18.122,P=0.044)。结论 延长手术间隔时间并不会影响到病理反应,也不会对术后并发症和总生存率产生影响。所以,延长手术间隔时间并不会得到额外的益处,可以依据患者的实际临床情况选择手术时机。

Objective There is no accurate conclusion on the optimal interval between neoadjuvant chemotherapy and surgery for patients with esophageal cancer.The purpose of this study was to explore the influence of surgical timing on the clinical outcome of esophageal cancer after neoadjuvant chemotherapy, including perioperative condition and survival time.Methods This study retrospectively studied 182 patients who underwent neoadjuvant chemotherapy and esophagectomy in the First affiliated Hospital of Zhengzhou University from January 2017 to December 2018,and divided them into a short interval group of 0-40 days and a long interval group of more than 40 days according to the time interval from completion of neoadjuvant chemotherapy to surgical treatment.Single factor analysis of patient’s age, sex, tumor location, BMI,neoadjuvant chemotherapy scheme, operation time, postoperative hospital stay time, postoperative complications, tumor histologic types, TNM stages, differentiation degree, such as general pathology back conditions and clinical pathologic factors, using the Kaplan Meier-survival curve, and Cox regression was used to the single factor, multivariate survival analysis.Results A total of 182 patients were included in this study, including 117 patients in the long interval group and 65 patients in the short interval group.In the univariate analysis of the general data of the two groups, there was only significant difference in preoperative complications(P=0.032).There was no significant difference in sex, age and tumor location between the two groups(P>0.05).In addition, there was no significant difference in intraoperative blood loss and operation time(P>0.05).According to the clinicopathological data of the patients, univariate analysis showed that there was no significant difference in TNM stage, incisal margin, vascular and nerve invasion between the two groups(P>0.05).The pathological complete remission rates of the long interval group and the interval group were 33.8%(26/117) and 22.2%(22/65),respectively.The pathological complete remission rate of the long interval group was higher than that of the short interval group, but the difference was not statistically significant(P=0.239).After univariate and multivariate Cox regression analysis, it was found that the operative interval had no significant effect on survival(HR=1.249,95% CI=0.792-1.971,P=0.339).The main factors affecting survival were ypT stage(HR=1.220,95% CI=1.014-1.469,P=0.039) and R0 resection(HR=4.344,95% CI=1.041-18.122,P=0.044).Conclusion Prolonging the interval of operation does not affect the pathological reaction, nor does it affect the postoperative complications and overall survival rate.Therefore, prolonging the interval of surgery will not get additional benefits, and the timing of operation can be chosen according to the actual clinical conditions of patients.