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成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值

张博瀚, 宋九林, 蒋利, 杨俭, 吕涛, 黄斌, 吴泓, 杨家印, 严律南

张博瀚, 宋九林, 蒋利, 等. 成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值[J]. 中华消化外科杂志, 2020, 19(2): 196-203. DOI: 10.3760/cma.j.issn.1673-9752.2020.02.013
引用本文: 张博瀚, 宋九林, 蒋利, 等. 成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值[J]. 中华消化外科杂志, 2020, 19(2): 196-203. DOI: 10.3760/cma.j.issn.1673-9752.2020.02.013
Zhang Bohan, Song Jiulin, Jiang Li, et al. Application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma[J]. Chinese Journal of Digestive Surgery, 2020, 19(2): 196-203. DOI: 10.3760/cma.j.issn.1673-9752.2020.02.013
Citation: Zhang Bohan, Song Jiulin, Jiang Li, et al. Application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma[J]. Chinese Journal of Digestive Surgery, 2020, 19(2): 196-203. DOI: 10.3760/cma.j.issn.1673-9752.2020.02.013

成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值

基金项目: 十三五国家科技重大专项(2017ZX10203205-005-002);四川大学华西医院学科卓越发展1.3.5工程项目(ZY2017308)

Application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma

  • 摘要:

    目的:探讨成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植治疗肝细胞癌的应用价值。
    方法:采用回顾性描述性研究方法。收集2019年10月四川大学华西医院收治的1例行成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植受者的临床病理资料;男性肝细胞癌受者,年龄为46岁,体质量为66 kg,身高为171 cm,血型为A型Rh阳性。移植物1来自女性活体供者,年龄为23岁,体质量为50 kg,身高为150 cm,血型为A型Rh阳性。移植物2来自男性脑死亡捐献者,年龄为44岁,血型为A型Rh阳性。手术在3个手术间施行,2个手术间同时施行移植物1和移植物2的切取手术,第3个手术间施行受者肝脏游离,当移植物的体外拼接接近完成时,完整取出受者肝脏,并施行肝移植。观察指标:(1)活体供者及受者的手术及术后恢复情况。(2)受者病肝术后病理学检查情况。(3)随访情况。采用门诊方式进行随访,随访内容包括肝细胞癌复发监测、移植肝功能监测、免疫抑制剂 监测调整、胆道血管并发症监测、排斥反应及药物不良反应等。受者需终生定期随访,最近一次随访时间为2019年12月4日。计数资料采用绝对数或百分比表示。
    结果:(1)活体供者及受者的手术及术后恢复情况:活体供者手术时间为315 min,术中出血量约200 mL,术中输入自体回收血量约200 mL,术后第 6天出院,无并发症发生。受者顺利完成改良背驼式肝移植。移植物1取自活体供者不含肝中静脉的肝右叶,质量410 g。移植物2取自脑死亡捐献者肝左外叶,质量400 g,拼接后的供者移植物质量与受者体质量比为1.2%。受者手术时间为815 min,无肝期时间为60 min,术中出血量约1 500 mL,术中输血量为1 800 mL。住院期间受者体温正常。术后第1天受者白细胞(WBC)和中性粒细胞百分比达到峰值(分别为17.15×109/L和91.7%),后逐渐降低,采用哌拉西林钠舒巴坦钠抗感染,术后第7天WBC和中性粒细胞百分比均降至正常范围(分别为7.90×109/L和70.9%),停用抗菌药物。住院期间,受者白蛋白(Alb)为31.0~41.4 g/L,受者总胆红素(TBil)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、凝血酶原时间、国际标准化比值肝功能指标均逐渐下降至正常范围,肌酐和肾小球滤过率肾功能指标均在正常范围。术后第10天受者全身状况良好,康复出院。(2)受者病肝术后病理学检查情况:①中分化肝细胞癌,肿瘤包膜欠完整,未侵及肝被膜,周围肝组织呈乙型病毒性肝炎后结节性肝硬化改变,肝门断端未见肿瘤累及;②慢性胆囊炎伴胆固醇沉积;③腹腔淋巴结1枚,呈反应性增生。免疫组织化学染色检测提示乙型肝炎表面抗原(10%细胞为阳性)、乙型肝炎核心抗原阴性。(3)随访情况:受者2019年11月19日复查肿瘤标志物,甲胎蛋白 2.92 μg/L、异常凝血酶原16 AU/L,结合腹部彩色多普勒超声检查的阴性结果提示肿瘤无复发。受者 2019年12月3日复查肝功能:TBil 8.6 μmol/L,ALT 23 IU/L,AST 28 IU/L,Alb 44.0 g/L;他克莫司血药浓度4.2 μg/L,调整吗替麦考酚酯至250 mg 2次/d,其余治疗不变(他克莫司2 mg 1次/d,西罗莫司1 mg 1次/d);无症状、体征及检查结果提示胆道血管并发症、排斥反应及药物不良反应等。
    结论:成人活体供者肝右叶联合脑死亡捐献者肝左外叶的双供肝活体肝移植安全、有效,可以作为治疗超出米兰标准肝细胞癌患者的次优方案。

    Abstract:

    Objective:To investigate the application value of dualgraft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma (HCC).
    Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a male 46yearold patient with HCC who underwent dualgraft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death at the West China Hospital of Sichuan University in October 2019 were collected. He weighed 66 kg and was 171 cm in height. His blood type was A Rh-positive. Graft one was from a female 23-year-old living donor who had a bodyweight of 50 kg, a height of 150 cm, and blood type of A Rh-positive; graft two was from a male 44yearold brain death donor with the blood type of A Rh-positive. The surgery was performed in three operating rooms, graft one and graft two were obtained simultaneously in two operating rooms, and the recipient′s liver was dissected in the third operating room. When the in vitro splicing of the liver was almost completed, surgeons entirely removed the recipient′s liver and started to transplant the new one. Observation indicators: (1) surgical situations and postoperative recovery of the living donor and the recipient; (2) postoperative pathological examination of the recipient′s liver; (3) Follow-up. Follow-up was conducted by outpatient examinations, including monitoring of HCC recurrence, monitoring of new liver function, monitoring and adjustment of immunosuppressive agents, detection of biliary vascular complications, rejection and adverse drug reactions. Regular lifelong Follow-up was required for recipients, with the latest Follow-up on December 4, 2019. Count data were expressed as absolute numbers or percentages.
    Results:(1) Surgical situations and postoperative recovery of the living donor and the recipient: operation time, volume of intraoperative blood loss, volume of intraoperative infusion of autologous blood of the living donor were 315 minutes, 200 mL, 200 mL, respectively. The living donor was discharged from hospital on the sixth day after surgery without any complications. The recipient underwent modified piggyback liver transplantation successfully. Graft one was from the right segment free of the middle hepatic vein in the living donor, with a weight of 410 g. Graft two was from the left lateral segment in the donor after brain death, with a weight of 400 g. The graft from donors to recipient weight ratio was 1.2% after splicing. The operation time, duration of anhepatic phase, volume of intraoperative blood loss, volume of intraoperative blood transfusion were 815 minutes, 60 minutes, 1 500 mL, 1 800 mL, respectively. The recipient′s temperature was normal during hospitalization. On the first postoperative day, the level of white blood cell and neutrophilic granulocyte percentage of the recipient reached a peak (17.15×109/L and 91.7%, respectively) and then gradually decreased. After antiinfective treatment with piperacillin sodium and sulbactam sodium, both of the two indicators returned to normal on the seventh day after surgery (7.90×109/L and 70.9%, respectively), and the antibiotic was discontinued. During the hospitalization, the level of albumin of the recipient fluctuated in 31.0-41.4 g/L, the liver function parameters including total bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international normalized ratio gradually returned to normal levels, and the renal function parameters including creatinine and estimated glomerular filtration rate remained within the normal range. On the tenth day after surgery, the recipient was in good condition and discharged from the hospital. (2) Postoperative pathological examination of the recipient′s liver: ① results of the pathological examination showed moderately differentiated HCC with incomplete tumour capsule and no invasion of the liver capsule. The surrounding liver tissues showed hepatitis Brelated nodular cirrhosis, and no tumor involvement was detected at the broken end of the hilum. ② The gallbladder presented chronic cholecystitis accompanied by cholesterol deposition, and one abdominal lymph node showed reactive hyperplasia. The immunohistochemical staining showed 10% positive HBsAg and negative HBcAg. (3) Follow-up: the tumor markers of the recipient were tested on November 19, 2019, including αfetoprotein (2.92 μg/L) and abnormal prothrombin (16 AU/L). Together with the negative result of abdominal colour doppler ultrasound, they collectively indicated no HCC recurrence in the recipient. The liver function parameters including total bilirubin (8.6 μmol/L), alanine aminotransferase (23 IU/L), aspartate aminotransferase (28 IU/L) and albumin (44.0 g/L) of the recipient tested on December 3, 2019, were all in normal levels. Blood concentration of tacrolimus was 4.2 μg/L . The drug dose of mycophenolate mofetil dispersible tablets was adjusted to 250 mg given twice daily, and the drug dose of others was unchanged (tacrolimus 2 mg, once daily; sirolimus 1mg, once daily). No symptoms, signs or examination results indicated biliary vascular complications, rejection or adverse drug reactions.
    Conclusion:Dualgraft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death is safe and effective, which can be used as a suboptimal treatment for patients with HCC beyond Milan criteria.

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