新型温敏凝胶在精准肝段（亚肝段）切除术中的应用研究
发布时间：2018-08-24 09:01
【摘要】：目的 精准的肝段(亚肝段)切除术在肝癌的根治性治疗中具有巨大优势,越来越为外科医师所接受。鉴于目前精准肝段切除术的各种技术手段尚存在着不足,本实验制备了一种新型温敏凝胶,采用超声引导下将其推注入门静脉分支阻断目标肝段血流的办法,再根据缺血边界精准将目标肝段进行切除,并研究探索该方法的可行性、安全性。方法 首先制备不同浓度的泊洛沙姆407、吲哚菁绿混合溶液(P407-ICG),研究其胶凝温度并在大鼠身上观察其可逆性的阻断入肝血流效果。然后将18头健康雄性长白猪随机分为肝段切除组(segmental hepatectomy group, SH)和部分切除组(partial hepatectomy group, PH),其中SH组分为A、B两个亚组,每组均6头动物：SH-A亚组在术中超声引导下向肝脏左外叶下段、左中叶下段门静脉分支内分别推注3ml浓度为18%的P407-ICG溶液,随即目标肝段发生缺血改变,根据肝脏表面缺血线切除目标肝段;SH-B亚组在术中超声引导下向相同肝段的门静脉分支内注入3ml的ICG溶液染色,然后根据肝脏表面的染色边界行段切除术;PH组无法准确预知目标肝段边界,仅在肝脏相同部位按照规则边界行肝切除术。观察各组手术时间、术中出血量、术后并发症,取术前、术后即刻、术后3天和7天四个时间点监测血常规、肝功能、肾功能及血脂变化情况。术后7天再次开腹,观察肝脏及腹腔情况,留取肝、肾、心、肺等大器官行病理检查。另取6头健康雄性长白猪将P407-ICG溶液注入肝静脉、胆道、肝实质后观察溶解时间及病理改变,进行安全性研究。结果 浓度为16%、18%、20%(W/V)的P407-ICG溶液胶凝温度分别为29℃、26℃、22℃；0.3ml溶液注入大鼠门静脉后即刻变为凝胶状态完全阻断入肝血流,浓度越高推注阻力越大；三种浓度的凝胶分别于阻断5min、12min、15min后完全溶解,大鼠术后均长期存活,未见任何并发症。长白猪实验中SH-A亚组采用浓度为18%的P407-ICG溶液阻断门脉分支,该亚组与PH组所有动物均按计划完成手术,而SH-B亚组有2头动物未能按计划染色(2/6)；SH组手术时间较PH组延长(P0.05),组内A、B两亚组无差别(SH-A:118.5±10.2min, SH-B:120.8±7.4min, PH:98.0±8.9min);术中出血量SH组较PH组显著减少(P0.05),组内A、B两组无明显差别(SH-A:83.3±14.0ml, SH-B:86.7±12.9ml, PH:139.2±18.5ml);所有动物术后未见明显并发症。组间术后血生化及病理变化无差别。安全性研究结果：注入肝静脉的P407-ICG凝胶10.5±1.1min后完全溶解,注入肝总管的凝胶14.1±1.5min后完全溶解,注入肝实质的P407-ICG凝胶术后3天取标本行病理检查证实已完全吸收,且术后动物均未出现并发症及组织器官的病理改变。结论超声引导下向门静脉分支内推注18%P407-ICG溶液可暂时阻断目标肝段的血供,之后沿着肝脏表面缺血线可实现精准肝段(亚肝段)切除。该方法相比超声引导下穿刺门静脉后推注染色剂的方法成功率较高,且降低了肿瘤术中播散的风险,简单有效,同时安全可逆,为临床实现精准肝切除提供了新的技术手段。
[Abstract]:Objective Accurate hepatectomy has a great advantage in the radical treatment of hepatocellular carcinoma, which is accepted by surgeons more and more. In view of the deficiency of various techniques of precise hepatectomy, a new thermosensitive gel was prepared and injected into portal vein branch under the guidance of ultrasound. Methods Poloxamer 407, indocyanine green mixed solution (P407-ICG) of different concentrations was prepared to study the gel temperature and observe the reversible effect of blocking the hepatic blood flow in rats. 18 healthy male Landrace pigs were randomly divided into two groups: segmental hepatectomy group (SH) and partial hepatectomy group (PH), in which group SH was divided into two subgroups A and B. Each group had six animals: SH-A subgroup was guided by intraoperative ultrasound to the lower left lateral lobe of the liver and the lower portal vein branch of the left middle lobe. The target liver segment was resected according to the ischemic line of the liver surface; the SH-B subgroup was injected with 3 ml of ICG solution to the portal vein branch of the same segment under the guidance of intraoperative ultrasound, and then segmental resection was performed according to the staining boundary of the liver surface. The operation time, intraoperative bleeding volume, postoperative complications, blood routine, liver function, renal function and blood lipid were observed before operation, immediately after operation, 3 days and 7 days after operation. Six healthy male Landrace pigs were injected with P407-ICG solution into hepatic vein, biliary tract and liver parenchyma to observe the dissolution time and pathological changes. The results showed that the gelling temperature of P407-ICG solution was 29, 26, 22, and the gelling temperature of P407-ICG solution was 16%, 18%, 20% (W/V) respectively. In the Landrace White Pig experiment, the SH-A subgroup was blocked by P407-ICG solution with 18% concentration. The operation time of SH-B group was longer than that of PH group (P 0.05). There was no difference between A and B subgroups (SH-A: 118.5 + 10.2 min, SH-B: 120.8 + 7.4 min, PH: 98.0 + 8.9 min). The amount of bleeding in SH-B group was significantly less than that in PH group (P 0.05). There was no significant difference (SH-A: 83.3 [14.0] ml, SH-B: 86.7 [12.9] ml, PH: 139.2 [18.5] ml)]. There were no significant complications in all animals after operation. There was no difference in blood biochemical and pathological changes between groups. The specimens of liver parenchyma-penetrating P407-ICG gel were taken for pathological examination 3 days after operation, and no complications and pathological changes of tissues and organs were found in the animals after operation.Conclusion Ultrasound-guided injection of 18% P407-ICG solution into the portal vein branch can temporarily block the blood supply of the target liver segment, and then along the ischemic line of the liver surface can achieve sperm. Quasi-hepatectomy (sub-hepatectomy). Compared with ultrasound-guided puncture of portal vein, this method has a higher success rate, and reduces the risk of intraoperative dissemination of tumor. It is simple, effective, safe and reversible. It provides a new technical means for clinical accurate hepatectomy.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.7
，
本文编号：2200293
[Abstract]:Objective Accurate hepatectomy has a great advantage in the radical treatment of hepatocellular carcinoma, which is accepted by surgeons more and more. In view of the deficiency of various techniques of precise hepatectomy, a new thermosensitive gel was prepared and injected into portal vein branch under the guidance of ultrasound. Methods Poloxamer 407, indocyanine green mixed solution (P407-ICG) of different concentrations was prepared to study the gel temperature and observe the reversible effect of blocking the hepatic blood flow in rats. 18 healthy male Landrace pigs were randomly divided into two groups: segmental hepatectomy group (SH) and partial hepatectomy group (PH), in which group SH was divided into two subgroups A and B. Each group had six animals: SH-A subgroup was guided by intraoperative ultrasound to the lower left lateral lobe of the liver and the lower portal vein branch of the left middle lobe. The target liver segment was resected according to the ischemic line of the liver surface; the SH-B subgroup was injected with 3 ml of ICG solution to the portal vein branch of the same segment under the guidance of intraoperative ultrasound, and then segmental resection was performed according to the staining boundary of the liver surface. The operation time, intraoperative bleeding volume, postoperative complications, blood routine, liver function, renal function and blood lipid were observed before operation, immediately after operation, 3 days and 7 days after operation. Six healthy male Landrace pigs were injected with P407-ICG solution into hepatic vein, biliary tract and liver parenchyma to observe the dissolution time and pathological changes. The results showed that the gelling temperature of P407-ICG solution was 29, 26, 22, and the gelling temperature of P407-ICG solution was 16%, 18%, 20% (W/V) respectively. In the Landrace White Pig experiment, the SH-A subgroup was blocked by P407-ICG solution with 18% concentration. The operation time of SH-B group was longer than that of PH group (P 0.05). There was no difference between A and B subgroups (SH-A: 118.5 + 10.2 min, SH-B: 120.8 + 7.4 min, PH: 98.0 + 8.9 min). The amount of bleeding in SH-B group was significantly less than that in PH group (P 0.05). There was no significant difference (SH-A: 83.3 [14.0] ml, SH-B: 86.7 [12.9] ml, PH: 139.2 [18.5] ml)]. There were no significant complications in all animals after operation. There was no difference in blood biochemical and pathological changes between groups. The specimens of liver parenchyma-penetrating P407-ICG gel were taken for pathological examination 3 days after operation, and no complications and pathological changes of tissues and organs were found in the animals after operation.Conclusion Ultrasound-guided injection of 18% P407-ICG solution into the portal vein branch can temporarily block the blood supply of the target liver segment, and then along the ischemic line of the liver surface can achieve sperm. Quasi-hepatectomy (sub-hepatectomy). Compared with ultrasound-guided puncture of portal vein, this method has a higher success rate, and reduces the risk of intraoperative dissemination of tumor. It is simple, effective, safe and reversible. It provides a new technical means for clinical accurate hepatectomy.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.7
，
本文编号：2200293
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