Han Jiagang, Wang Zhenjun, Dai Yong, Li Xiaorong, Qian Qun, Wang Guiying, Wei Guanghui, Zeng Weigen, Ma Liangang, Zhao Baocheng, Wang Yanlei, Yang Kaiyan, Ding Zhao, Hu Xuhua
Department of General Surgery, Beijing Chaoyang Hosptial, Capital Medical University, Beijing 100020, China.
Department of General Surgery, Beijing Chaoyang Hosptial, Capital Medical University, Beijing 100020, China. Email:
Zhonghua Wei Chang Wai Ke Za Zhi. 2018 Nov 25;21(11):1233-1239.
To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer.
This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541).
(1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×10/L, platelet ≥ 80×10/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent.
(1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon.
The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05).
Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.
评估自膨式金属支架（SEMS）置入后，新辅助化疗在完全性梗阻性左半结肠癌择期手术前应用的安全性和可行性。
本前瞻性、多中心、开放标签试验经首都医科大学附属北京朝阳医院伦理委员会批准（2016-ke-161-1），并在Clinicaltrials.gov注册（NCT02972541）。
（1）年龄18至75岁；（2）病理确诊为腺癌；（3）临床表现及影像学检查确诊为左半结肠癌，距肛缘距离>15 cm；（4）影像学检查评估为可切除癌，无远处转移；（5）东部肿瘤协作组（ECOG）评分≤1或卡氏功能状态评分（KPS）>70，表明能耐受新辅助化疗及手术；（6）过去6个月内未接受过化疗或放疗；（7）骨髓系统及肝肾功能：血红蛋白≥90 g/L，中性粒细胞≥1.5×10⁹/L，血小板≥80×10⁹/L，总胆红素≤1.5×正常上限（ULN），血清转氨酶≤2.5×ULN，血清肌酐≤1.0×ULN，内生肌酐清除率>50 ml/min；（8）签署知情同意书。
（1）多原发性结直肠癌；（2）拒绝手术；（3）SEMS置入前出现腹膜炎或肠穿孔；（4）注册数据审核人员证实不符合条件。根据纳入标准，2015年12月至2017年12月期间，前瞻性纳入了来自首都医科大学附属北京朝阳医院（n = 31）、山东大学齐鲁医院（n = 14）、中南大学湘雅三医院（n = 13）、武汉大学中南医院（n = 2）、河北医科大学第四医院（n = 2）的62例因完全性梗阻性左半结肠癌在SEMS置入后择期手术前行新辅助化疗的连续患者。根据研究者的临床经验和患者偏好，将患者分为新辅助化疗组和择期手术组。择期手术组患者在SEMS置入后1至2周内接受手术，不进行新辅助化疗。新辅助化疗组患者在SEMS置入后1至2周内接受2周期CapeOX或3周期mFOLFOX6新辅助化疗，然后在完成新辅助化疗后3周内接受手术。采用Student t检验、卡方分析或Fisher确切概率法分析比较两组间的数据，包括基本临床信息、手术情况和术后并发症。记录新辅助化疗期间的不良反应。由外科医生使用视觉模拟量表评估手术难度，范围为1至10，其中1表示最低手术难度，10表示最高手术难度。
本研究共纳入38例男性和24例女性，平均年龄（64.8±8.8）岁。两组间临床基线数据无显著差异（均P>0.05），但新辅助化疗组SEMS与手术之间的平均时间间隔显著更长[（61.6±13.5）天 vs.（10.4±5.2）天，t = A16.679，P<0.001]。两组均未发生支架移位。择期手术组有3例患者发生穿孔；新辅助化疗组有1例患者发生穿孔，1例患者发生梗阻；所有这些患者均接受了急诊手术。新辅助化疗的不良反应主要为1级和2级，除1例3级腹泻患者外。与择期手术组患者相比，新辅助化疗组患者的造口率显著更低[4.8%（1/21） vs. 34.1%（14/41），χ² = 6.538，P = 0.011]，腹腔镜手术率更高[71.4%（15/21） vs. 36.6%（15/41），χ² = 6.751，P = 0.009]，平均手术时间更短（147分钟 vs. 178分钟，t = -3.255，P = 0.002），平均术中出血量更少（47 ml vs. 127 ml，t = -4.129，P<0.001），手术难度更低（3.3 vs. 5.6，t = -5.091，P<0.001），平均术后排气时间更短（56.2小时 vs. 69.0小时，t = -2.891，P = 0.006），平均术后住院时间更短（8.5天 vs. 13.5天，t = -2.246，P = 0.028）。两组间手术部位感染率和吻合口漏率无显著差异（均P>0.05）。
SEMS置入后择期手术前行新辅助化疗是治疗梗阻性左半结肠癌的一种相对安全可行的方法，与传统择期手术相比，造口更少，腹腔镜手术更多，手术时间更短, 出血量更少，手术难度更低，术后恢复更快。
