食管空肠两层半吻合在胃癌根治术中应用的安全性:一项前瞻性多中心单臂研究

Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy:A prospective,multi-center,single arm trial

目的探讨食管空肠两层半吻合在根治性全胃切除术中应用的安全性。方法本研究是由郑州大学附属肿瘤医院普通外科自2021年6月发起的一项前瞻性、多中心、单臂队列研究(研究名称:CRAFT研究,临床注册号:NCT05282563),参与的中心包括南阳市中心医院、驻马店市中心医院、洛阳市中心医院、河南理工大学第一附属医院、河南大学第一附属医院、漯河市中心医院、鹤壁市人民医院、商丘市第一人民医院、安阳市肿瘤医院、平顶山市第一人民医院和郑州大学附属郑州中心医院。病例入组标准:(1)术前胃镜确诊胃腺癌;(2)术前影像学评估可行R0切除;(3)术前评估无手术禁忌证;(4)术中计划行食管空肠吻合;(5)患者自愿参加本次研究,签署知情同意书;(6)体力状况美国东部肿瘤协作组(ECOG)评分0~1;(7)美国麻醉师协会(ASA)评分Ⅰ~Ⅲ。病例排除标准:(1)上腹部手术史(腹腔镜胆囊切除史除外);(2)胃部手术史(内镜黏膜下剥离术和内镜下黏膜切除术除外);(3)妊娠或哺乳期妇女;(4)胃癌合并症(穿孔、出血、梗阻)行急诊手术者;(5)5年内出现过或同时患有其他恶性肿瘤;(6)患者6个月内发生过动脉栓塞性疾病,如心绞痛、心肌梗死、脑血管意外等;(7)合并有其他疾病或精神状态异常,可能影响到患者参与研究。病例剔除标准:(1)无法完成根治性胃癌切除术;(2)术中未行食管空肠端侧吻合;(3)无法行食管空肠吻合口加固。食管空肠吻合口加固方法:开腹手术使用倒刺线或3-0可吸收缝线,连续全层加固吻合口1周然后进行吻合口浆肌层包埋1周,每周平均缝合6~8针。腹腔镜手术,自吻合口前壁偏左侧采用逆时针全层缝合加固,缝合至吻合口右后方时,向右侧牵拉空肠残端,适当翻转吻合口继续完成后壁加固,缝合间距5 mm左右。全层缝合1周后继续逆时针缝合完成浆肌层包埋。根据纳入、排除和剔除标准,连续入组自2021年6月开始,于以上12个中心接受胃癌根治术并于术中行食管空肠两层半吻合的患者临床病理及围手术期资料。主要观察食管空肠吻合的安全性指标(吻合口相关并发症发生情况及相关处理),次要观察指标包括手术情况(手术时间、术中出血量等)、术后恢复(术后排气时间、进食时间、住院天数)及随访情况(生活质量采用Visick评估)。结果截至2022年9月,共457例患者纳入研究,其中男355例,女102例,年龄(60.8±10.1)岁,体质指数(23.7±3.2)kg/m2;肿瘤位于胃上部294例、胃中部139例、胃下部24例;肿瘤直径(4.3±2.2)cm。所有患者均顺利完成手术,经腹手术352例,经腹食管裂孔手术25例,胸腹联合手术80例;近端胃切除48例,全胃切除409例。全腹腔镜53例(11.6%)、腹腔镜辅助189例(41.4%),开放手术215例(47.0%)。术中中位出血量200(10~1350)ml,手术时间(215.6±66.7)min,食管空肠吻合口加固时间(7.3±3.9)min,其中腔镜下加固时间(17.6±1.7)min;开腹加固时间(6.0±1.2)min。术后排气时间(3.1±1.1)d,术后中位造影时间6(4~13)d,术后进食中位时间7(2~14)d,术后住院(15.8±6.7)d。共有184例(40.3%)患者出现术后并发症,食管空肠吻合口并发症发生率为2.2%(10/457),其中4例(0.9%)吻合口漏(亚临床漏和临床漏各2例),均经保守治疗治愈;另6例(1.3%)为吻合口狭窄,2例分别于术后21 d、46 d经内镜下球囊扩张治愈,其余4例改变饮食方式后好转。全组均无术后吻合口出血的发生。非吻合口并发症发生率为38.1%(174/457)。中位随访时间10(3~18)个月,术后3个月生活质量Visick分级,Ⅰ级89.1%(407/457),Ⅱ级7.9%(36/457),Ⅲ级2.6%(12/457),Ⅳ级0.4%(2/457)。结论胃癌根治术中应用食管空肠两层半吻合安全有效。

Objective To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods This prospective,multi-center,single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021(CRAFT Study,NCT05282563).Participating institutions included Nanyang Central Hospital,Zhumadian Central Hospital,Luoyang Central Hospital,First Affiliated Hospital of Henan Polytechnic University,First Affiliated Hospital of Henan University,Luohe Central Hospital,the People's Hospital of Hebi,First People's Hospital of Shangqiu,Anyang Tumor Hospital,First People's Hospital of Pingdingshan,and Zhengzhou Central Hospital Affiliated to Zhengzhou University.Inclusion criteria were as follows:(1)gastric adenocarcinoma confirmed by preoperative gastroscopy;(2)preoperative imaging assessment indicated that R0 resection was feasible;(3)preoperative assessment showed no contraindications to surgery;(4)esophagojejunostomy planned during the procedure;(5)patients volunteered to participate in this study and gave their written informed consent;(6)ECOG score 0–1;and(7)ASA score I–III.Exclusion criteria were as follows:(1)history of upper abdominal surgery(except laparoscopic cholecystectomy);(2)history of gastric surgery(except endoscopic submucosal dissection and endoscopic mucosal resection);(3)pregnancy or lactation;(4)emergency surgery for gastric cancer-related complications(perforation,hemorrhage,obstruction);(5)other malignant tumors within 5 years or coexisting malignant tumors;(6)arterial embolism within 6 months,such as angina pectoris,myocardial infarction,and cerebrovascular accident;and(7)comorbidities or mental health abnormalities that could affect patients'participation in the study.Patients were eliminated from the study if:(1)radical gastrectomy could not be completed;(2)end-to-side esophagojejunal anastomosis was not performed during the procedure;or(3)esophagojejunal anastomosis reinforcement was not possible.Double and a half layered esophagojejunal anastomosis was performed as follows:(1)Open surgery:the full thickness of the anastomosis is continuously sutured,followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures.The anastomosis is sutured with an average of six to eight stitches.(2)Laparoscopic surgery:the anastomosis is strengthened by counterclockwise full-layer sutures.Once the anastomosis has been sutured to the right posterior aspect of the anastomosis,the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall.The suture interval is approximately 5 mm.After completing the full-thickness suture,the anastomosis is embedded in the seromuscular layer.Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed.The primary outcome was safety(e.g.,postoperative complications,and treatment).Other studied variables included details of surgery(e.g.,surgery time,intraoperative bleeding),postoperative recovery(postoperative time to passing flatus and oral intake,length of hospital stay),and follow-up conditions(quality of life as assessed by Visick scores).Result[1]From June 2021 to September 2022,457 patients were enrolled,including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2.The tumors were located in the upper stomach in 294 patients,mid stomach in 139;and lower stomach in 24.The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies.Neoadjuvant chemotherapy was administered to 85 patients.Other organs were resected in 85 patients.The maximum tumor diameter was 4.3±2.2 cm,number of excised lymph nodes 28.3±15.2,and number of positive lymph nodes five(range one to four.As to pathological stage,83 patients had Stage I disease,128 Stage II,237 Stage III,and nine Stage IV.[2]The studied surgery-related variables were as follows:The operation was successfully completed in all patients,352 via a transabdominal approach,25 via a transhiatus approach,and 80 via a transthoracoabdominal approach.The whole procedure was performed laparoscopically in 53 patients(11.6%),189(41.4%)underwent laparoscopic-assisted surgery,and 215(47.0%)underwent open surgery.The median intraoperative blood loss was 200(range,10–1350)mL,and the operating time 215.6±66.7 minutes.The anastomotic reinforcement time was 2(7.3±3.9)minutes for laparoscopic-assisted surgery,17.6±1.7 minutes for total laparoscopy,and 6.0±1.2 minutes for open surgery.[3]The studied postoperative variables were as follows:The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6(range,4–13)days.The median time to postoperative oral intake was 7(range,2–14)days,and the postoperative hospitalization time 15.8±6.7 days.[4]The safety-related variables were as follows:In total,there were 184(40.3%)postoperative complications.These comprised esophagojejunal anastomosis complications in 10 patients(2.2%),four(0.9%)being anastomotic leakage(including two cases of subclinical leakage and two of clinical leakage;all resolved with conservative treatment);and six patients(1.3%)with anastomotic stenosis(two who underwent endoscopic balloon dilation 21 and 46 days after surgery,the others improved after a change in diet).There was no anastomotic bleeding.Non-anastomotic complications occurred in 174 patients(38.1%).All patients attended for follow-up at least once,the median follow-up time being 10(3–18)months.Visick grades were as follows:Class I,89.1%(407/457);Class II,7.9%(36/457);Class III,2.6%(12/457);and Class IV 0.4%(2/457).Conclusion Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.