脑死亡儿童供肝成人移植临床分析

目的 探讨脑死亡儿童供肝成人移植的临床可行性,总结1例脑死亡儿童供肝成人移植的临床体会.方法 受者为39岁女性,诊断为原发性肝癌,肝炎后肝硬化(失代偿期).供者为脑肿瘤脑死亡的8岁儿童,供肝采用快速联合脏器切取方法获取.手术方式为经典原位肝移植.术后常规给予免疫抑制、防治感染、护肝、支持等治疗.结果 移植手术历时6 h.术后无严重并发症发生,受者健康存活,门诊随访肝功能正常.结论 儿童供肝成人移植技术是可行的.系统化的供肝评估、良好的手术技巧及完善的术后处理是确保手术成功的关键.

Abstract：

Objective To explore clinical feasibility of liver transplant from child of brain death to adult, to summarize the clinical experiences that a child of brain death transplants liver to an adult. Methods The recipient was a 39-year-old woman patient with primary hepatic carcinoma and posthepatitis cirrhosis (decompensation stage); while the donor was a 8-old-year child of brain death because of brain neoplasms. Donated liver was gained by the method of en bloc multivisceral procurement in a short time; the operative method was classic orthotopic liver transplantation. The postoperative managements included immunosuppression, prevention of infection, hepatic protection, and other relevant supports etc. Results The transplantation operative duration was 6 hours, after which not only did the recipient survive but also her body functioned well including the liver part, with no severe postoperative complications. Conclusions The technology of transplanting livers from children to adults is feasible. The key to ensure the success of transplant operation is systematic preoperative evaluation, excellent operative technique, and perfect postoperative treatment.     

供肝短缺形势下的我国肝移植策略

近5年来我国肝移植发展非常迅速,然而,供肝短缺成为制约临床肝移植发展的瓶颈。因此,拓展供肝来源成为目前肝移植临床的重点。活体肝移植在尸体供肝受限的情况下可以很好地扩展供肝来源,且活体供肝具有活力强、冷缺血时间短等优势;劈裂式肝移植可增加15％～28％的供肝数量,有望成为解决供肝短缺的主要手术方式之一;脑死亡供者在西方国家是移植器官的主要来源,在我国亦有广大的应用前景,但脑死亡供者器官移植刚刚起步,有许多问题亟待研究;此外,边缘供肝,包括脂肪变性肝脏、HBsAg阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间超过14h的盱脏等均可用以缓解日益突出的供肝短缺矛盾。     

无心跳供肝大鼠肝移植模型的手术操作技巧探讨

目的建立一个稳定的无心跳供肝大鼠原位肝移植模型。方法在Kamada"二袖套法"的基础上进行改良,根据供肝获取前经历无心跳热缺血时间不同分为10min(R10组)、20min(R20组)和30min(R30组)3组,比较各组术后1周大鼠存活率。结果供体手术时间约30min(不含热缺血时间)。供肝冷保存时间均为1h。肝上下腔静脉吻合时间12～22min(平均15min),门静脉和肝下下腔静脉套管分别约需2min和1min。无肝期时间14～24min(平均19min),受体总手术时间50～65min(平均60min)。大鼠术后24h内死亡视为手术失败,共计12例死亡。R10组、R20组和R30组手术成功率分别为95%(19/20)、80%(16/20)和65%(13/20),术后1周生存率分别为95%(18/19)、81%(13/16)和54%(7/13)。结论在Kamada"二袖套法"基础上进行改良的大鼠无心跳供肝肝移植模型能很好地模拟临床无心跳供肝肝移植。大鼠肝脏能耐受30min以内的热缺血时间,移植术后短期存活结果满意,长期存活率尚需进一步研究。     

无心跳供体中供肝微循环的动态变化

目的 探讨不同热缺血时间下大鼠无心跳供体肝组织微循环的变化规律，预测供肝耐受热缺血的安全时限。方法 实验动物按供肝热缺血时间分别为0、15、30、45、60min，随机分为5组。然后按各组条件分别作原位肝移植．对肝移植术后各组血清透明质酸(HA)的水平进行动态检测，以及观察肝组织微循环超微结构的动态变化。结果 在热缺血30min以内，移植肝组织复流后能逐渐恢复至正常的微循环结构和功能。热缺血45min，复流后大部分肝血窦腔可逐渐恢复通畅。但部分血窦仍充满较多的膜浆泡和血细胞积滞；热缺血45min以前各组术后3d血清HA可基本恢复。热缺血60min，复流后内皮细胞损伤不但不能恢复，且出现加重、扩大趋势。结论 供肝经受30min以内热缺血损伤，肝组织微循环的变化处在可复性阶段。45min的热缺血时间可能县供肝微循环功能耐受热缺血损伤的极限．热缺血60min以后．呈现不可逆性的微循环障碍．     

儿童供肝成人肝移植四例临床分析

<正>肝移植是目前治疗终末期肝病唯一有效的方法,但供器官短缺限制了器官移植事业的发展。根据中国人体器官分配与共享计算机系统分配原则:12岁的器官捐献者供肝优先分配给12岁的肝移植等待者,但当本地区无合适的儿童受者时,儿童供肝可以分配给病情危重且供肝质量或体积在可耐受范围内的成人受者~([1])。在供肝功能良好且无肝硬化和脂肪变性等病理改变时,一般将移植物与受者体质量比(graft to     

肝移植中应用边缘供肝的相关研究新进展

供肝短缺是当今制约临床肝移植发展的主要问题。临床上经常遇到脂肪肝供体、高龄供体、乙肝表面抗原阳性供体、冷缺血时限较长等边缘供肝（marginal donor）问题。我们就近年来国外有关边缘供肝在临床肝移植的应用及效果的最新进展做一综述。总体上说边缘供肝可以扩大供肝来源且疗效确切。     

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

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1500 mL,术中输血量为1800 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2.92μg/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 8.6μmol/L,ALT 23 IU/L,AST 28 IU/L,Alb 44.0 g/L;他克莫司血药浓度4.2μg/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。     

活体供肝肝移植

肝移植已成为治疗终末期肝病的有效方法，但供肝的缺乏是目前移植领域里尚未解决最大的非免疫学障碍，活体供肝肝移植为解决这一问题提供了新的途径。     

活体肝移植的供肝切取技术

为缓解肝移植中的尸体供肝不足问题，探讨活体供肝的供肝切除方法。供者男４例，女４例，年龄１９－４６岁，平均３３．１岁。其中５例切取肝脏Ⅱ，Ⅲ段，３例切取Ⅱ，Ⅲ，Ⅳ段术中用Ｂ型超垢波引导确定切肝界线，应用超声切割器切开肝实质，切肝过程不阻断肝脏血流，术中用自体血回输装置收集出血并再利用。     

大鼠两种不同供肝对原位肝移植术中和术后影响的比较

目的　比较正常 (HB)和心跳停搏 (NHB)供肝对大鼠原位肝移植术中和术后的影响。方法　雄性SD大鼠随机分成HB和NHB两组 ;NHB组又分别设心跳停搏 30min(HNB - 30 )和 4 5min(NHB - 4 5 )两组。每组各行原位肝移植 5 0、30和 30次。结果　HB和NHB组冷缺血、无肝期、肝下下腔静脉 (IVC)阻断、受体手术时间分别为 (6 9.76± 1.5 2 )min和 (70 .32± 1.5 3)min、(16 .4 6± 0 .96 )min和(16 .4 0± 0 .73)min、(2 2 .5 6± 1.73)min和 (2 2 .75± 1.16 )min、(89.38± 3.75 )min和 (90 .5 8± 3.76 )min ;术后受体苏醒和主动饮水时间分别为 (5 .4 3± 3.88)min和 (5 4 .0 6± 5 .99)min、(43.0 4± 10 .19)min和(12 6 .79± 15 .0 2 )min ;受体术后鼻粘膜出血率分别为 4 .17%和 92 .6 8% ;受体第 1周体重下降幅度分别为 (6 .15± 1.92 ) %和 (9.6 2± 1.80 ) % ;第 2周体重增加幅度分别为 (7.4 4± 2 .5 9) %和 (3.16± 1.0 4 ) %。HB组近期死因分别为原发性移植肝无功能 (PGF)、麻醉过深、肺部感染和肝上下腔静脉 (SVC)吻合口漏 ;而NHB组分别为PNF、麻醉过深、无肝期较长 (>17min)和再灌注后供肝渗血 ;HB和NHB - 30、NHB - 4 5组术后 1周存活率分别为 90 %、5 0 %和 30 %。结论　NHB较HB术中操作更复杂 ,更需     

Liver transplantation using elderly donors: a risk factor analysis

Kim DY, Moon J, Island ER, Tekin A, Ganz S, Levi D, Selvaggi G, Nishida S, Tzakis AG. Liver transplantation using elderly donors: a risk factor analysis.
Clin Transplant 2011: 25: 270–276. © 2010 John Wiley & Sons A/S. Abstract: Survival after liver transplantation is negatively impacted by use of elderly deceased donors, but excluding them would increase waiting times and waiting list mortality. We reviewed our experience with liver transplantation (LT) utilizing livers from deceased donors 65 yr of age and older to identify those factors that impact graft survival. All adult patients (≥18 yr old) who underwent primary LT using deceased donor livers from donors aged ≥65 yr between February 1995 and November 2003 were included. With multivariate analysis we found four unfavorable characteristics significantly associated with higher post‐transplant graft failure rate. These characteristics are hepatitis C as an etiology of liver disease, Model for End‐Stage Liver Disease score >20, serum glucose level of donor >200 mg/dL at the time of liver recovery, and skin incision to aortic cross‐clamp time >40 minutes in the donor surgery. The five‐yr estimated graft survival rates having 0, 1, 2, 3, and 4 unfavorable characteristics were 100%, 82.0%, 81.7%, 39.3%, and 25.0%, respectively (p < 0.05). Our data demonstrated good graft survival can be achieved in LT using elderly donor liver allografts with appropriate patient selection, donor blood glucose management and efficient liver recovery with minimal manipulation of the liver during donor surgery.     

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2–11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan–Meier analysis, the presence of DGF was associated with lower graft survival (log‐rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617–11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.     

Lung transplantation from donation after cardiac death (non-heart-beating) donors

Although lung transplantation is a well-accepted treatment for advanced lung diseases, donor shortage remains a significant limiting factor resulting in an increasing number of deaths of people on waiting lists. Recently, some transplant centers have begun to use lungs retrieved from donors after circulatory arrest. This review outlines the relevant published experimental data and clinical experiences with lung transplantation from donation after cardiac-death donors (DCDs) or non-heart-beating donors (NHBDs). Techniques for lung preservation and ex vivo lung assessment of DCD (NHBD) lungs are reviewed, and aspects of primary graft dysfunction after DCD (NHBD) lung transplantation are discussed. This review was submitted at the invitation of the editorial committee.     

Liver transplantation for HBsAg‐positive recipients using grafts from HBsAg‐positive deceased donors

This study reports our experience using deceased donor liver grafts from HBsAg‐positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg‐positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26–64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(?) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46–76) at LT. Post‐LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow‐up period was 25.5 months (range: 14–82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV‐unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow‐up biopsies. This experience shows that LT using grafts from deceased HBsAg‐positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.     

Outcome of transplantation using kidneys from controlled (Maastricht category 3) non-heart-beating donors

BACKGROUND: Many renal transplant centres are reluctant to use kidneys from non-heart-beating (NHB) donors because of the high incidence of primary non-function and delayed graft function reported in the literature. Here, we report our favourable experience of using kidneys from Maastricht category 3 donors (controlled NHB donors). MATERIALS AND METHODS: From January 1996 to June 2002, 42 renal transplants using kidneys from 25 controlled NHB donors were undertaken at our centre. The rates of primary non-function, delayed graft function (DGF), rejection and long-term graft and patient survival were compared with those of 84 recipients of grafts from heart-beating (HB donors) transplanted contemporaneously. RESULTS: Primary non-function did not occur in recipients of grafts from NHB donors but was seen in two grafts from HB donors. DGF occurred in 21 of 42 (50%) kidneys from NHB donors and 14 of 84 (17%) kidneys from HBD donars (p < 0.001). The acute rejection rates in the two groups were similar (33% for grafts from NHB donors vs. 40% from HB donors). By 1 month after transplantation, there was no significant difference in serum creatinine concentration between the two groups. Over a median follow-up period of 32 months (range 2-75 months), the actuarial graft survival rates at 1, 3 and 5 yr after transplantation were 84, 80 and 74% for recipients of kidneys from NHB donors, compared with 89, 85 and 80% for kidneys from HB donors. CONCLUSION: Controlled NHB donors are a valuable and under-used source of kidneys for renal transplantation. The outcome for recipients of kidney allografts from category 3 NHB donors is similar to that seen in recipients of grafts from conventional HB cadaveric donors.     

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes.
Clin Transplant 2011: 25: 255–264. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Delayed graft function (DGF) is more common in recipients of kidney transplants from donation after cardiac death (DCD) donors compared to donation after brain death (DBD) donors. Methods: Single‐center retrospective study to evaluate the impact of DGF on controlled (Maastricht category III) DCD donor kidney transplant outcomes. Results: From 10/01 to 6/08, 578 adult deceased donor kidney transplants were performed including 70 (12%) from DCD and 508 (88%) from DBD donors. Mean follow‐up was 36 months. DCD donor kidney transplants had significantly greater rates of DGF (57% DCD vs. 21% DBD, p < 0.0001)) and acute rejection (29% DCD vs. 16% DBD, p = 0.018) compared to DBD donor kidney transplants, but patient and graft survival rates were similar. DBD donor kidney transplants with DGF (n = 109) had significantly greater rates of death‐censored graft loss (12.5% DCD vs. 31% DBD), primary non‐function (0 DCD vs. 10% DBD) and higher 2 year mean serum creatinine levels (1.4 DCD vs. 2.7 mg/dL DBD) compared to DCD donor kidney transplants with DGF (n = 40, all p < 0.04). On univariate analysis, the presence of acute rejection and older donor age were the only significant risk factors for death‐censored graft loss in DCD donor kidney transplants, whereas DGF was not a risk factor. Conclusion: Despite higher rates of DGF and acute rejection in DCD donor kidney transplants, subsequent outcomes in DCD donor kidney transplants with DGF are better than in DBD donor kidney transplants experiencing DGF, and similar to outcomes in DCD donor kidney transplants without DGF.     

Hepatic grafts from live donors: donor morbidity for 470 cases of live donation

Living donor-morbidity was evaluated in 470 consecutive cases of living donor liver transplantation carried out from June 1990 to May 1999 at Kyoto University. Grafting was categorized into 4 groups according to the resection lines; left lateral segmentectomy (S2 + 3, n = 282, R1), extended left lateral segmentectomy without middle hepatic vein (MHV) (S2 + 3 + part4, n = 45, R2), left lobectomy with MHV (S2 + 3 + 4, n = 99, R3) and right lobectomy without MHV (S5 + 6 + 7 + 8, n = 43, R4). Intraoperative blood loss and operation duration were less for left lateral segmentectomy, but no significant difference was observed between left lobectomy and right lobectomy. The length of postoperative hospital stays was comparable among all groups except for the group with right lobe grafting. The AST values at the peak and at POD 7 were significantly elevated for right lobectomy, but the AST value normalized within one month in the majority of the cases. The close follow-up of donors with more than 1000 ml intraoperative bleeding, and of those donors who stayed in hospital for more than 30 days, the close follow-up, furthermore, of those donors with AST values higher than 100 IU/L AST after one month, revealed complete recovery. Biliary leakage was the most common and annoying complication after donor operations, especially in for right lobe grafting, but all donors recovered completely with conservative or minimal invasive therapy. The two cases of re-operation due to adhesive mechanical ileus we encountered were resolved completely. Finally, no donor-operation related death was noted. In conclusion, the morbidity of living donors is low or minimal even for right lobectomy, the most extended procedure, and complete recovery can be expected in all cases. Received: 24 November 1999/Accepted: 13 March 2000