【作者】 叶锋；

【导师】 郑树森；

【作者基本信息】 浙江大学 ， 外科学（普外）， 2016， 博士

【摘要】 第一部分ValtracTM结肠内旁路在开腹低位直肠癌保肛手术中的应用目的：评估ValtracTM结肠内旁路(ValtracTM-secured intracolonic bypass, VIB)在开腹低位直肠癌保肛手术中应用的安全性和有效性,并且与袢式回肠造口(Loop ileostomy, LI)比较两者的有效性和并发症。方法：记录并收集从2002年1月到2006年5月,浙江大学附属第一医院肛肠外科83例择期行低位直肠癌保肛手术资料,他们分别施行了VIB或LI保护吻合口,回顾性分析他们的一般情况、临床资料和手术相关数据。结果：44例(53.0%)施行了VIB,39例(47.0%)施行了LI。所有患者均无临床吻合口漏发生。经统计学分析,两组的一般情况和临床资料无显著性差异。VIB组的术后住院时间和住院费用(12.5±6.3d,2.5±0.7万元)小于LI组(21.3±5.8d,3.5±0.9万元),统计学上差异有显著性(P<0.05)。LI组：造口皮炎5例(12.8%),出血1例(2.6%)和回纳后肠梗阻2例(5.1%)；V1B组发生吻合环完整下移导致排出困难2例(4.5%)。术后吻合环松动时间为14±3(12-16)d.结论：VIB在开腹低位直肠癌保肛手术应用是一种安全有效的但有时间限制性的粪便转流技术。第二部分ValtracTM结肠内旁路在腹腔镜辅助低位直肠癌保肛手术中的应用及其微创价值目的：评估ValtracTM结肠内旁路(ValtracTM-secured intracolonic bypass, VIB)在腹腔镜辅助低位直肠癌保肛手术中应用的安全性和有效性,并且与袢式回肠造口LI(Loop ileostomy, LI)比较两者的有效性和并发症。方法：记录并收集从2010年5月到2013年5月,浙江大学附属第一医院肛肠外科43例择期行腹腔镜辅助低位直肠癌保肛手术资料,他们分别施行了VIB或LI保护吻合口,回顾性分析他们的一般情况、临床资料和手术相关数据。结果：24例(55.8%)施行了VIB,19例(44.2%)施行了LI。两组的一般情况和临床资料无显著性差异。但是VIB组的直肠肿块距肛缘距离(7.5cm; inter-quartile range [IQR] 7.0-9.5cm)大于LI组(6.0cm; IQR 6.0-7.0cm).根据直肠肿块距肛缘距离的差异,两组的比较进行相应的统计学调整。调整之后,VIB组的术后住院时间和住院费用(7.0d,4.8万元)小于LI组(14.0d,6.3万元)。(P<0.001)。统计学上差异有显著性。所有患者均无临床吻合口漏发生。LI组：造口皮炎2(10.5%)例,出血1(5.3%)例和回纳后切口感染2(10.5%)例；VIB组无旁路相关并发症发生。术后吻合环松动时间为14.1±3.2d。结论：VIB,因为避免了肠造口,作为腹腔镜辅助直肠癌手术的好伙伴,更增加了其微创价值,是安全有效的但有时间限制性的粪便转流技术。第三部分利用脂肪族聚酯(聚乙丙交酯)制备新型结肠内旁路器目的：应用脂肪族聚酯(聚乙丙交酯,Poly lactic-co-glycolic acid, PLGA)制造出新型结肠内旁路器(New intracolonic bypass device, NIBD).测定新结肠内旁路系统的密闭性和体内脱落时间。方法：PLGA以乙交酯(GA)和L-丙交酯(L-LA)两种单体,按一定配比开环共聚而成。设计、改良结肠内旁路器的结构和形状,并采用注塑机加工成型NIBD.体外实验测定其自降解性和密闭性,动物实验测定其密闭性和体内脱落时间。结果：通过开环共聚的方法成功制备了目标产物PLGA,初步设定了满足粪便转流要求的结肠内旁路器结构雏形,并应用该材料制备了NIBD.其体外降解时间较ValtracTM吻合环延长,其体外密闭性试验压力约为20kPa,体内脱落时间大约4周。结论：以PLGA为材料制造出NIBD,新结肠内旁路系统有合适的密闭性、自降解特性和其体内脱落时间大约4周,符合粪便转流要求。第四部分新型结肠内旁路器保护低位直肠吻合口的动物实验研究目的：通过动物实验比较新结肠内旁路器((New intracolonic bypass device, NIBD,应用了新材料和新结构)和ValtracTM结肠内旁路(ValtracTM-secured intracolonic bypass, VIB)装置的安全性和有效性。方法：以巴马小型猪为实验对象,随机分为两组。均施行手术切断再吻合直肠,并分别行NIBD或VIB保护低位吻合口。收集并比较两组的一般情况、手术、术后吻合口及结肠内旁路器的密闭性和脱落等资料。结果：VIB组和NIBD组分别为10例。本组中1例VIB组术后第3天死亡,可能与术中严重污染相关。NIBD组0例死亡。两组各有1例低位直肠吻合口裂开,但无临床有症状吻合口漏发生。两组术前术后体重、肠道清洁度、术中不良事件、术后进食、排便、死亡率、切口和活动方式等指标差异无统计学意义。但是NIBD组手术时间(108.8±35.5mmin)长；术后第3,4周测漏试验阳性率[1/10(10.0%),5/10(50.0%)]低,术后第3,4周旁路脱落率[1/10(10.0%),4/10(40.0%)]低,与V1B组{83.5±20.0mmin,[8/9(88.8%),9/9(100.0%)],[7/9(77.7%),9/9(100.0%)]}的差异有统计学意义(P<0.05),NIBD组术后旁路器脱落时间为30.8±5.5d,长于VIB组(18.1±6.0 d),两组差异有统计学意义(P<0.05)。术后病理显示,NIBD吻合口炎症反应轻,肌层完整,而VIB吻合口炎症反应重,肌层断裂。结论：动物实验显示NIBD在保护低位直肠吻合口中,安全有效,保护时间比VIB延长,但是操作时间长。更多还原

【Abstract】 PART I Use of ValtracTM-secured intracolonic bypass to protect the low rectal anastomosis in open anterior resectionObjective:To assess the efficacy and safety of the ValtracTM-secured intracolonic bypass (VIB) in protecting low rectal anastomosis and to compare the efficacy and complications of VIB with those of loop ileostomy (LI).Method:From January 2002 to April 2006,83 patients with rectal cancer who underwent elective low anterior resection received VIB or LI. Demographics, clinical features, and operative data were recorded.Result:Forty-four patients (53.0%) received a VIB and 39 patients (47.0%) a LI. The demographics and clinical features of the groups were similar. None of the patients developed clinical anastomotic leakage. Longer overall postoperative hospital stay (21.3±5.8 days) and higher costs incurred (3.5±0.9 ten-thousand Yuan) were observed in the LI group than in the VIB group (12.5±6.3 days,2.5±0.7 ten-thousand Yuan; P<0.05). Stoma-related complications in the LI group included dermatitis (12.8%), bleeding (2.6%), and intestinal obstruction after stoma closure (5.1%). No complications were observed in the VIB group except for the ValtracTM ring discharging en bloc, which compromised fecal evacuation in two cases (4.5%). The mean time to ValtracTM ring loosening was 14 ± 3 (12-16) days.Conclusion:The VIB procedure is a safe, effective, but time-limited, diverting technique to protect an elective low colorectal anastomosisPART II Use and mini-invasive value of ValtracTM-secured intracolonic bypass in laparoscopic-assisted rectal cancer resectionObjective:To assess the efficacy and safety of the ValtracTM-secured intracolonic bypass (VIB) in protecting laparoscopic-assisted low rectal anastomosis and to compare the efficacy and complications of VIB with those of loop ileostomy (LI).Methods:Medical records of the 43 patients with rectal cancer who underwent elective laparoscopic-assisted low anterior resection and received VIB procedure or LI between May 2010 and May 2013 were retrospectively analyzed, including the patients’ demographics, clinical features, and operative data.Result:Twenty-four patients (55.8%) received a VIB and 19 patients (44.2%) a LI procedure. Most of the demographics and clinical features of the groups, including Dukes stages, were similar. However, the median distance of the tumor edge from the anus verge in the VIB group was significantly longer (7.5cm; inter-quartile range [IQR] 7.0-9.5cm) than that of the LI group (6.0cm; IQR 6.0-7.0cm). None of the patients developed clinical anastomotic leakage. The comparisons between the LI and the VIB groups were adjusted for the significant differences in the tumor level of the groups. After adjustment, the LI group experienced longer overall postoperative hospital stay (14.0 days, IQR:12.0-16.0 days; P<0.001) and incurred higher costs (6.3 ten-thousand Yuan, IQR:3.7-4.2 ten-thousand Yuan) than the VIB group (7.0 days,4.8 ten-thousand Yuan; P<0.05). Stoma-related complications in the ileostomy group included dermatitis (2,10.5%), stoma bleeding (1,5.3%), and wound infection after closure (2,10.5%). No BAR-related complications occurred. The mean time to ValtracTM ring loosening was 14.1±3.2 days.Conclusion:The VIB procedure, as a good partner with the laparoscopic-assisted rectal cancer resection, appears to be a safe and effective, but time-limited, diverting technique to protect an elective low colorectal anastomosis.PART Ⅲ Synthesis of Poly (lactic-co-glycolic acid) elastomers and manufacture of new intracolonic bypass deviceObjective:To develop and manufacture a new type of intracolonic bypass device (NIBD) by polylactic-co-glycolic acid (PLGA), and to detect the air-tightness and loosing time of the NIBD.Method:PLGA was synthesized via bulk ring-opening polymerization with GA and L-LA (80:20) as raw materials. The mould was modified on the basis of original design model, and the NIBD was manufactured by injection molding with PLGA. The air-tightness and self-degradability of the NIBD was tested in vitro and in vivo experiment. The loosening time of the NIBD was detected in vivo experiment.Result:The target product PLGA was successfully synthesized and the NIBD was manufactured with PLGA. The air tight test pressure of new intracolonic bypass system was more than 20kPa and its self-degrading time was longer than that of ValtracTM ring in vitro experiment. Its loosening time is about 4 weeks in vivo experiment.Conclusion:The NIBD was successfully manufactured with PLGA. The air-tightness, self-degradability, and loosing time of the new intracolonic bypass system was competent for fecal diverting.PART IV Animal study of new intracolonic bypass device to protect the rectal anastomosisObjective:To compare the safety and efficacy of the new intracolonic bypass device (NIBD) with those of ValtracTM introcolonic bypass (VIB).Method:A total of 20 Bama minipigs were randomized to two groups with the NIBD and VIB to protect the lower rectal anastomosis. The general condition, anastomosis, and time of bypass loosing were recorded and compared between two groups.Result:10 minipigs (50.0%) received a NIBD and 10 minipigs (50.0%) a VIB. Only 1 minipig in VIB was dead at 3 days postoperatively, and none in NIBD. One in each group showed anastomotic dehiscence, but none of the minipigs developed clinical anastomotic leakage. The pre-operative and post-operative weight, bowel preparation, intra-operative adverse events postoperative eating, post-operative defecation time, mortality, wound infection, and uncommon activity of two groups were similar. Longer operative time (108.8±35.5min) was observed in NIBD group than in VIB group (83.5±20.0min, P<0.05). The Methylene leak test showed that the lower leak rate at 3-week post-operatively (1/10,10.0%) and at 4-week post-operatively (5/10,50.0%) were observed in NIBD group than in VIB group [8/9(88.8%),9/9(100.0%); P<0.05]. Also, the lower bypass dropping rate at 3-week post-operatively (1/10,10.0%) and at 4-week post-operatively (4/10,40.0%) were observed in NIBD group (10%,40%) than in VIB group [7/9(77.7%),9/9(100.0%); P<0.05]. The dropping time of NIBD (30.8±5.5d) was longer than that of VIB (18.1±6.0d) (P<0.05).By the pathologic test 5-week postoperatively, the serious inflammation reaction and the raptured muscle layer at the site of VIB anastomosis were observed; otherwise, the mild inflammation reaction and complete muscle layer at the site of NIBD anastomosis.Conclusion:The animal experience showed that the NIBD appeared to be a safe and effective diverting technique to protect a low rectal anastomosis, with longer protective time, but longer operative time than those of VIB.更多还原