【摘要】：目的 精準(zhǔn)的肝段(亞肝段)切除術(shù)在肝癌的根治性治療中具有巨大優(yōu)勢(shì),越來越為外科醫(yī)師所接受。鑒于目前精準(zhǔn)肝段切除術(shù)的各種技術(shù)手段尚存在著不足,本實(shí)驗(yàn)制備了一種新型溫敏凝膠,采用超聲引導(dǎo)下將其推注入門靜脈分支阻斷目標(biāo)肝段血流的辦法,再根據(jù)缺血邊界精準(zhǔn)將目標(biāo)肝段進(jìn)行切除,并研究探索該方法的可行性、安全性。方法 首先制備不同濃度的泊洛沙姆407、吲哚菁綠混合溶液(P407-ICG),研究其膠凝溫度并在大鼠身上觀察其可逆性的阻斷入肝血流效果。然后將18頭健康雄性長白豬隨機(jī)分為肝段切除組(segmental hepatectomy group, SH)和部分切除組(partial hepatectomy group, PH),其中SH組分為A、B兩個(gè)亞組,每組均6頭動(dòng)物：SH-A亞組在術(shù)中超聲引導(dǎo)下向肝臟左外葉下段、左中葉下段門靜脈分支內(nèi)分別推注3ml濃度為18%的P407-ICG溶液,隨即目標(biāo)肝段發(fā)生缺血改變,根據(jù)肝臟表面缺血線切除目標(biāo)肝段;SH-B亞組在術(shù)中超聲引導(dǎo)下向相同肝段的門靜脈分支內(nèi)注入3ml的ICG溶液染色,然后根據(jù)肝臟表面的染色邊界行段切除術(shù);PH組無法準(zhǔn)確預(yù)知目標(biāo)肝段邊界,僅在肝臟相同部位按照規(guī)則邊界行肝切除術(shù)。觀察各組手術(shù)時(shí)間、術(shù)中出血量、術(shù)后并發(fā)癥,取術(shù)前、術(shù)后即刻、術(shù)后3天和7天四個(gè)時(shí)間點(diǎn)監(jiān)測(cè)血常規(guī)、肝功能、腎功能及血脂變化情況。術(shù)后7天再次開腹,觀察肝臟及腹腔情況,留取肝、腎、心、肺等大器官行病理檢查。另取6頭健康雄性長白豬將P407-ICG溶液注入肝靜脈、膽道、肝實(shí)質(zhì)后觀察溶解時(shí)間及病理改變,進(jìn)行安全性研究。結(jié)果 濃度為16%、18%、20%(W/V)的P407-ICG溶液膠凝溫度分別為29℃、26℃、22℃；0.3ml溶液注入大鼠門靜脈后即刻變?yōu)槟z狀態(tài)完全阻斷入肝血流,濃度越高推注阻力越大；三種濃度的凝膠分別于阻斷5min、12min、15min后完全溶解,大鼠術(shù)后均長期存活,未見任何并發(fā)癥。長白豬實(shí)驗(yàn)中SH-A亞組采用濃度為18%的P407-ICG溶液阻斷門脈分支,該亞組與PH組所有動(dòng)物均按計(jì)劃完成手術(shù),而SH-B亞組有2頭動(dòng)物未能按計(jì)劃染色(2/6)；SH組手術(shù)時(shí)間較PH組延長(P0.05),組內(nèi)A、B兩亞組無差別(SH-A:118.5±10.2min, SH-B:120.8±7.4min, PH:98.0±8.9min);術(shù)中出血量SH組較PH組顯著減少(P0.05),組內(nèi)A、B兩組無明顯差別(SH-A:83.3±14.0ml, SH-B:86.7±12.9ml, PH:139.2±18.5ml);所有動(dòng)物術(shù)后未見明顯并發(fā)癥。組間術(shù)后血生化及病理變化無差別。安全性研究結(jié)果：注入肝靜脈的P407-ICG凝膠10.5±1.1min后完全溶解,注入肝總管的凝膠14.1±1.5min后完全溶解,注入肝實(shí)質(zhì)的P407-ICG凝膠術(shù)后3天取標(biāo)本行病理檢查證實(shí)已完全吸收,且術(shù)后動(dòng)物均未出現(xiàn)并發(fā)癥及組織器官的病理改變。結(jié)論超聲引導(dǎo)下向門靜脈分支內(nèi)推注18%P407-ICG溶液可暫時(shí)阻斷目標(biāo)肝段的血供,之后沿著肝臟表面缺血線可實(shí)現(xiàn)精準(zhǔn)肝段(亞肝段)切除。該方法相比超聲引導(dǎo)下穿刺門靜脈后推注染色劑的方法成功率較高,且降低了腫瘤術(shù)中播散的風(fēng)險(xiǎn),簡單有效,同時(shí)安全可逆,為臨床實(shí)現(xiàn)精準(zhǔn)肝切除提供了新的技術(shù)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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.7
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本文編號(hào)：2200293