Experomental and clinical studies to increase curability and safety of surgery for hilar cholangiocarcinoma

提高肝门部胆管癌手术治愈率和安全性的实验和临床研究

• 批准号: 04404050
• 负责人: NIMURA Yuji
• 金额: $ 12.48万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404050/
• 关键词: Hilar cholangiocarcinoma; Obstructive Jaundice; Hepatectomy; Liver failure; Portal vein embolization; Biliary drainage; Cholangitis; Caudate lobe; 肝再生能; 胆道ドレナージ; xanthine oxidase; 肝虚血; histo chemistry; 虚血再潅流障害; xanthine oxiclase; histochemi

*Clinical Research*(1) Preoperative accurate diagnosis of cancer extent was achievable using cholangiography throgh biliary drainage catheter, percutaneous transhepatic cholangioscopy, selective angiography, pcrcutaneous transhepatic portography and hepatic venography. This, in turn led to rational surgical prcoedures. (2) Perineural lnvasion proved to have a profound impact on survival of the patients with bile duct carcinoma, indicating that thorough skeletonization resection is essential for curative intent. (3) We developed a new approach of percutaneous transhepatic portal vein cmbolization, the ipsilateral approach, which made it possible to embolize the right or left trisegment portal vein. Portal vein cmbolization had the potential to increase safety of and to extend indication of major hepatectomy for hilar cholangiocarcinoma. (4) Technique of multiple selective biliary for hilar cholangiocarcinoma was well established by the direct anterior approach under fluoroscopic control … More . This aggressive drainage was essential for preventing and/or treating segmental cholangitis in patients with malignant biliary obstruction at the hepatic confluence.*Experimental Research*The following resukts were demonstrated experimentally using rats or mioe. (1) External bilisry drainage, unlike internal drainage, does not suppress regcenration of cholestatic liver after partial hepatectomy. (2) Biliary infection, especially associated with obstructive jaundice, injures hepatic mitochondrial function markedly. Biliary drainage is definitely effective in improving the impaierd function. (3) Under a condition of selective biliary obstruction, hepatic mitochondrial function is decreased also in the non-cholestatic lobe, as well as the cholestatic lobc. This implies that biliary drainage of the entire biliary system is beneficial. (4) An application of lipid emulsion to total parenteral nutrition is useful for hepatic regeneration after partial hepatectomy. (5) Portal branch ligation induces hepatocyte proliferation in the non-ligated lobe in a way similar to partial hepatectomy, from the viewpoint of changes in DNA polymerases and mitochondrial gene expression. (6) Portal branch ligation induces hepatocyte proliferation in the non-ligated lobe, irrespective of obstructive jaundice. (7) An increment in IL-10 production in the liver is involved in the protective effect of dibutyryl cAMP on inflammatory liver injury. Less

*临床研究*(1)术前经胆管引流管胆道造影、经皮肝穿胆管镜、选择性血管造影、经皮肝穿门脉造影、肝静脉造影均可准确诊断癌变范围。这反过来又导致了合理的手术程序。(2)神经周围侵犯对胆管癌患者的生存有很大影响，提示彻底的骨架化切除是治疗的关键。(3)提出了一种新的经皮肝穿门静脉栓塞术--同侧门静脉栓塞术，使右、左三段门静脉栓塞术成为可能。门静脉栓塞术有可能提高肝门部胆管癌行肝大部切除术的安全性和扩大手术适应证。(4)建立了透视控制下直接前入路…治疗肝门部胆管癌的多选择胆道技术。更多。这种积极的引流对于预防和/或治疗肝汇部恶性胆道梗阻患者的节段性胆管炎是必不可少的。*实验研究*以下结果是用大鼠或小鼠实验证实的。(1)胆道外引流与内引流不同，不抑制肝部分切除后胆汁淤积性肝的再生。(2)胆道感染，尤其是与梗阻性黄疸相关的胆道感染对肝脏线粒体功能有明显损害。胆道引流对改善受损功能肯定有效。(3)在选择性胆道梗阻条件下，非胆汁淤积叶和胆汁淤积叶的肝线粒体功能也降低。这意味着整个胆道系统的胆汁引流是有益的。(4)脂肪乳剂应用于全肠外营养有利于肝部分切除后的肝再生。(5)从DNA聚合酶和线粒体基因表达的变化来看，门静脉分支结扎诱导未结扎肝叶肝细胞增殖的方式与肝部分切除相似。(6)门静脉分支结扎可诱导未结扎肝叶肝细胞增殖，与梗阻性黄疸无关。(7)二丁酰cAMP对炎性肝损伤的保护作用与肝脏IL-10生成增加有关。较少

项目成果

Bhuiya MMR,Nimura Y,et al: "Clinicopathologic studies on perineural invasion of bile duct carcinoma." Ann Surg. 215. 344-349 (1992)

Bhuiya MMR，Nimura Y，等人：“胆管癌神经周围浸润的临床病理学研究。”

Bhuiya MMR: "Clinicopathologic factors influencing survival of patients with bile duct carcinoma:Multivariate statistical analysis" World Journal of Surgery. 17. 653-657 (1993)

Bhuiya MMR：“影响胆管癌患者生存的临床病理因素：多变量统计分析”世界外科杂志。

Kanai M,Nimura Y, et al.: "Preoperative intrahepatic segmental cholangitis in patients with advanced carcinoma involving the hepatic hilus." Surgery. 119. 498-504 (1996)

Kanai M、Nimura Y 等人：“累及肝门的晚期癌患者的术前肝内节段性胆管炎。”

Arai T,Nimura Y,et al.: "IL-10 is involved in the protective effect of dibutyryl cyclic adenosine monophosphate on endotoxin-induced inflammatory liver injury" Journal of Immunology. 155. 5743-5749 (1995)

Arai T、Nimura Y 等人：“IL-10 参与二丁酰环单磷酸腺苷对内毒素诱导的炎症性肝损伤的保护作用”《免疫学杂志》。

Kato S,Nimura Y,et al: "Hepatic recovery after biliary drainage in experimental obstructive jaundice complicated by biliary infection." Hepato-Gastroenterology. 41. 217-221 (1994)

Kato S，Nimura Y，等：“实验性梗阻性黄疸并发胆道感染胆道引流后的肝脏恢复。”