肝动脉戴戒限流术联合肝脏分隔和门静脉结扎的二步肝切除术治疗巨块型肝癌的临床疗效

Clinical efficacy of hepatic artery ringed and restriction operation-associating liver partition and portal vein ligation for staged hepatectomy in the treatment of giant hepatocellular carcinoma

  • 摘要: 目的:探讨肝动脉戴戒限流术联合肝脏分隔和门静脉结扎的二步肝切除术(HARO-ALPPS)治疗巨块型肝癌的临床疗效。
    方法:采用回顾性描述性研究方法。收集2018年7月广西医科大学第一附属医院收治的1例45岁右肝巨块型肝癌男性患者的临床资料。患者一期行门静脉右支结扎+原位左右半肝隔离+肝右动脉戴戒限流术,二期行右半肝切除术。观察指标:(1) 一期手术及术后恢复情况。(2)二期手术及术后恢复情况。(3)术后病理学检查情况。(4)剩余肝脏体积(FLR)和肿瘤体积变化情况。(5)肝右动脉、肝固有动脉和肝左动脉围术期血流量变化情况。(6)门静脉左支、门静脉主干围术期血流量变化情况。(7)随访情况。采用门诊方式随访,了解患者预后情况。随访时间截至2019年2月。计数资料以绝对数表示。
    结果:(1)一期手术及术后恢复情况:患者顺利完成门静脉右支结扎+原位左、右半肝隔离 术+肝右动脉戴戒限流术。患者手术时间为376 min,术中出血量为400 mL。患者一期手术后炎症指标 (体温、白细胞、C反应蛋白、降钙素原),肝功能指标[总胆红素(TBil)、白蛋白(Alb)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、腹腔积液量、吲哚菁绿15 min滞留率、二期手术前终末期肝病模型(MELD)评分]经对症支持治疗后逐步好转,部分凝血酶原时间(PT)术后均在正常范围。患者术后无 ClavienDindo Ⅱ级及以上并发症。(2)二期手术及术后恢复情况:患者顺利完成右半肝切除术。患者手术时间为322 min,术中出血量约为900 mL;术中输注新鲜冰冻血浆约300 mL。患者二期手术后炎症指标(体温、C反应蛋白)、肝功能指标(Alb、ALT、AST)、腹腔积液量经对症支持治疗后逐步恢复至正常,WBC、降钙素原、TBil、PT均在正常范围。患者术后无Clavien-Dindo Ⅱ级及以上并发症。 (3)术后病理学检查情况:病理学检查为①肝细胞癌Ⅱ级,团片型,伴有肿瘤组织大片坏死,微脉管侵犯,M0期,肿瘤未累及肝包膜及外科切缘。周围肝组织Ishak评分:炎症3分,纤维化2分。②胆囊黏膜慢性炎症。③第8组淋巴结 2枚,均为反应性增生。④第12组淋巴结1枚,反应性增生。免疫组织化学染色检测为磷脂酰肌醇蛋白聚糖3、肝细胞标记、精氨酸酶1、转移抑制因子阳性,血管内皮生长因子弱阳性,细胞增殖指数(Ki67)阳性细胞约为10%,血管内皮细胞标记物CD34[<50条/高倍镜下(200倍放大)],胆管上皮标记物CK19和CK7、抑癌基因P21和P53阴性。(4)FLR和肿瘤体积变化情况:患者一期手术后第5、14天,FLR分别为565、580 mL;占标准肝体积比例分别为54%、57%;FLR与体质量比分别为0.96、0.98;FLR增长率分别为194%、202%;肿瘤体积一期手术后第5、14天分别为1 210、1 297 mL;肿瘤坏死区域体积一期手术后第5、14天分别为635、500 mL。患者一期手术后第5、14天行肝脏CT检查示肝动脉戴戒限流术成功,剩余肝脏增生明显血供良好。患者术前CT血管造影检查示右半肝肿瘤术前动脉血供丰富;一期手术后第5天CT血管造影检查确认肝右动脉戴戒部位,肿瘤血供逐渐减少;一期手术后第14天CT血管造影检查示肝肿瘤血供明显减少。患者二期手术后第7天肝脏CT检查示剩余肝脏血供良好,肝脏体积增长至829 mL。(5)肝右动脉、肝固有动脉和肝左动脉围术期血流量变化情况:①患者一期手术前,门静脉右支结扎前,门静脉右支结扎后并肝右动脉戴戒前,门静脉右支结扎后并肝右动脉戴戒后,一期手术后第1、3、5、7、10天的肝右动脉血流量分别为224.3,574.7,827.5,222.7,153.0、282.5、279.1、247.9、150.2 mL/min。患者二期手术中肝右动脉血流量为505.0 mL/min。②患者一期手术前,门静脉右支结扎前,门静脉右支结扎后并肝右动脉戴戒前,门静脉右支结扎后并肝右动脉戴戒后,一期手术后第1、3、5、7、10天的肝固有动脉血流量分别为399.7,793.5,830.5,1 075.4,784.7、821.2、722.8、467.4、555.4 mL/min。患者二期手术右半肝切除前,右半肝切除后,二期手术后第1、3、5、7天的肝固有动脉血流量分别为505.0、473.3、158.5、627.0、103.8、139.8 mL/min。③患者一期手术前,门静脉右支结扎前,门静脉右支结扎后并肝右动脉戴戒前,门静脉右支结扎后并肝右动脉戴戒后,一期手术后第1、3、5、7、10天的肝左动脉血流量分别为147.5,13.8,19.4,16.2,62.1、93.9、67.1、30.8、106.1 mL/min。患者二期手术右半肝切除前,右半肝切除后,二期术后第1、3、5、7天的肝左动脉血流量分别52.0、43.2、112.4、103.6、80.7、56.1 mL/min。(6)门静脉左支、门静脉主干围术期血流量变化情况:①患者一期手术前,门静脉右支结扎前,门静脉右支结扎后并肝右动脉戴戒后,一期手术后第1、3、5、7、10天门静脉左支血流量分别为552.6,181.2,412.2,320.0,1 777.7、1 284.7、749.5、484.2 mL/min。患者二期手术右半肝切除前,右半肝切除后,二期手术后第1、3、5、7天门静脉左支血流量分别为793.3,979.0,485.2、1 042.5、803.5、548.3 mL/min。②患者一期手术前,门静脉右支结扎前,门静脉右支结扎后并肝右动脉戴戒后,一期手术后第1、3、5、7、10天门静脉主干血流量分别为1 186.0,696.7,833.7,431.7、1 319.1、668.4、890.7、550.8 mL/min。二期手术右半肝切除前,右半肝切除后,二期手术后第1、3、5、7天门静脉主干血流量分别为846.4,937.4,891.2、1 671.0、2 697.8、1 230.0 mL/min。(7)随访情况:患者二期手术后随访6个月,患者一般情况好,肝功能Child A级,甲胎蛋白属于正常范围,肝脏增强CT检查示剩余肝脏增生,血供良好,无肿瘤复发。术后2个月剩余肝脏体积为727 mL。
    结论:HAROALPPS可安全、有效减少肝肿瘤的血供,增加肿瘤坏死,减少一期手术后肝动脉门静脉瘘的发生,保证剩余肝脏增生所需的血流供应。

     

    Abstract: Objective:To investigate the clinical efficacy of hepatic artery ringed and restriction operationassociating liver partition and portal vein ligation for staged hepatectomy (HAROALPPS) in the treatment of giant hepatocellular carcinoma.
    Methods:The retrospective and descriptive study was conducted. Clinical data of a 45yearold male patient with giant hepatocellular carcinoma who was admitted to the First Affiliated Hospital of Guangxi Medical University in July 2018 were collected. In the first stage operation, right portal vein ligation+ in situ liver partition + right hepatic artery ringed operation was performed on the patient. In the second stage operation , right hemihepatectomy was performed on the patient. Observation indicators: (1) surgical and postoperative situations of the first stage operation; (2) surgical and postoperative situations of the second stage operation; (3) postoperative pathological examination; (4) changes in future liver remnant (FLR) and tumor volume; (5) perioperative hemodynamic changes of right hepatic artery, proper hepatic artery and left hepatic artery; (6) perioperative hemodynamic changes of leftportal vein and main portal vein; (7) followup. Followup using outpatient examination was performed to detect the prognosis of patients up to February 2019. Count data were described as absolute number.
    Results:(1) Surgical and postoperative situations of the first stage operation: the patient underwent right portal vein ligation+ in situ liver partition+ right hepatic artery ringed operation successfully. The operation time and volume of intraoperative blood loss were 376 minutes and 400 mL. Inflammatory indicators including body temperature, white blood cells (WBC), Creactive protein, procalcitonin, and liver function indices including total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ascites, indocyanine green retention rate at15 min (ICG R15), score of model for endstage liver disease (MELD) before the second stage operation were improved after symptomatic supportive treatment. Prothrombin time (PT) was in the normal range after the first stage operation. There was no complication of ClavienDindo classificationⅡor above. (2) Surgical and postoperative situations of the second stage operation: the patient underwent right hemihepatectomy successfully. The operation time and volume of intraoperative blood loss were 322 minutes and 900 mL. The patient received 300 mL of fresh frozen plasma infusion. Inflammatory indicators including body temperature, Creactive protein, and liver function indices including Alb, ALT, AST, ascites, were recoved to normal level after symptomatic supportive treatment. WBC, procalcitonin, TBil, and PT were in the normal range. There was no complication of ClavienDindo classificationⅡ or above. (3) Postoperative pathological examination: ① Ⅱstage hepatocellular carcinoma was confirmed, masslike type, with tissue necrosis and microvascluar invasion. There was no distal metastasis and tumor did not invade liver capsule or surgical margin. Ishak score of surrounding tissues was 3 in the inflammation and 2 in the fibrosis. ② Chronic inflammation was detected in the gallbladder mucosa. ③ Reactive hyperplasia was found in the 2 lymph nodes of the group 8. ④ One in the group 12 lymph nodes showed reactive hyperplasia. Immunohistochemistry showed positive Glypican3, Hepatocyte, Arginase1, NM23, weakly positive vascular endothelial growth factor, and negative Ki67, vascular endothelial cell marker CD34, biliary epithelial marker CK19 and CK 7, tumor suppressor gene P21 and P23. (4) Changes in FLR and tumor volume: FLR was 565 mL and 580 mL at the 5th and 14th day after the first stage operation respectively, accounting for 54% and 57% of total liver volume. The FLR to body weight ratio was 0.96 and 0.98, and the growth rate of FLR was 194% and 202%. Tumor volume was 1 210 mL and 1 297 mL at the 5th and 14th day after the first stage operation respectively. Tumor necrosis volume was 635 mL and 500 mL at the 5th and 14th day after the first stage operation respectively. At the 5th and 14th day after the first stage operation, the liver CT examination showed that HARO was successfully underwent and the blood supply of remnant liver was good. Preoperative CT aothgraphy (CTA) examination showed that the right hepatic tumor had rich arterial blood supply. At the 5th day after the first stage operation, the CTA examination confirmed the ringed site of right hepatic artery, and the blood supply of the tumor gradually decreased. At the 14th day after the first stage operation, CTA examination showed significant decrease in the blood supply of liver tumors. Liver CT examination showed rich supply of the remnant liver and the liver volume of 829 mL at the 7th day after the second stage operation. (5) Perioperative hemodynamic changes of the right hepatic artery, proper hepatic artery and left hepatic artery. ① Blood flow of right hepatic artery was 224.3, 574.7, 827.5, 222.7, 153.0, 282.5, 279.1, 247.9 and 150.2 mL/min before the first stage operation, before right portal vein ligation, after right portal vein ligation and before right hepatic artery ringed and restriction, after right portal vein ligation and right hepatic artery ringed and restriction, at the 1st , 3th ,5th and 7th day after the first stage operation. Blood flow of right hepatic artery in the second stage operation was 505.0 mL/min. ② Blood flow of proper hepatic artery was 399.7, 793.5, 830.5, 1 075.4, 784.7.5, 821.2, 722.8, 467.4 and 555.4 mL/min before the first stage operation, before right portal vein ligation, after right portal vein ligation and before right hepatic artery ringed and restriction, after right portal vein ligation and right hepatic artery ringed and restriction, at the 1st , 3th ,5th and 7th day after the first stage operation. Blood flow of proper hepatic artery was 505.0, 473.3, 158.5, 627.0, 103.8 and 139.8 mL/min before right hepatectomy in the second stage operation, after right hepatectomy, at the 1st, 3th and 5th day after the second operation, respectively. ③ Blood flow of left hepatic artery was 147.5, 13.8, 19.4, 16.2, 62.1, 93.9, 67.1, 30.8 and 106.1 mL/min before the first stage operation, before right portal vein ligation, after right portal vein ligation and before right hepatic artery ringed and restriction, after right portal vein ligation and right hepatic artery ringed and restriction, at the 1st , 3th ,5th, 7th and 10th day after the first stage operation. Blood flow of left hepatic artery was 52.0, 43.2, 112.4, 103.6, 80.7 and 56.1 mL/min before right hepatectomy in the second stage operation, after right hepatectomy, at the 1st , 3th and 5th day after the second operation, respectively. (6) Perioperative hemodynamic changes of leftportal vein and main portal vein. ① Blood flow of left portal vein was 552.6, 181.2 , 412.2, 320.0, 1 777.7, 1 284.7, 749.5 and 484.2 mL/min before the first stage operation, before right portal vein ligation, after right portal vein ligation and right hepatic artery ringed and restriction, at the 1st, 3th ,5th, 7th and 10th day after the first stage operation, respectively. Blood flow of left portal vein was 793.3, 979.0, 485.2, 1 042.5, 803.5 and 548.3 mL/min before right hepatectomy in the second stage operation , after right hepatectomy, at the 1st , 3th , 5th and 7th day after the second operation respectively. ② Blood flow of main portal vein was 1 186.0, 696.7, 833.7, 431.7, 1 319.1, 668.4, 890.7, 550.8 mL/min before the first stage operation, before right portal vein ligation, after right portal vein ligation and right hepatic artery ringed and restriction, at the 1st , 3th ,5th, 7th and 10th day after the first stage operation, respectively. Blood flow of main portal vein was 846.4, 937.4, 891.2, 1 671.0, 2 697.8, and 1 230.0 mL/min before right hepatotectomy in the second stage operation , after right hepatectomy, at the 1st , 3th , 5th and 7th day after the second stage operation, respectively. (7) Follow up: the patient was followed up for 6 months and survived well, with Child A of liver function and normal alpha fetoprotein level. Liver contrast CT examination showed increase in the remnant liver, good blood supply, and no tumor recurrence. The FLR was 727 mL at the 2 months after operation.
    Conclusion:For patients with giant hepatocellular carcinoma, HAROALPPS can be performed to decrease blood supply of tumor, increase tumor necrosis area, and reduce the incidence of intrahepatic arteriovenous fistula, which ensure blood supply of remnant liver hyperplasia.

     

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