新的血管生成抑制剂

脑死亡供体的供肝比活体供肝行肝移植术后原发性移植肝无功能的发生率高。目前已有报道,在鼠的模型实验中,脑死亡供体的供肝微循环受到破坏。为了阐明在肝移植中脑死亡供体的供肝活力降低的机制,在原位肝移植手术前后,通过活体内的荧光显微镜和电子显微镜对肝的微循环和组织形态学进行评估。     

肝移植供肝获取和修整的临床研究

目的 总结肝移植供肝获取和修整的临床经验.方法 分析2004年8月～2007年12月共126例快速肝肾联合获取及105个供肝修整的资料,105个供肝均用于原位肝移植术.结果 126例供肝、肾热缺血时间为1～8.5 min,平均4min.肝肾联合切取手术时间19～28 min,平均22.5 min.105个供肝修整时间38～102 min,平均51 min;冷缺血时间5.5～13 h,平均8 h;有8例供肝存在动脉变异.结论 供肝获取和修整应强调器官灌注和动脉修整技术,预防供体因素导致的出血,注意与受体手术组配合.     

活体右半肝移植肝中静脉取舍选择与供受者的安全性

目的 根据术前CT评估供体残余肝脏比例(RLV%)和评估移植物重量与受者体重比(GRWR),参考肝中静脉解剖情况等因素制定术前肝中静脉(MHV)切取分配方案,研究这种分配方案对活体肝移植供、受体安全的影响,并为今后临床工作提供参考.方法 同一外科小组连续73例活体右半肝肝移植病例按术前肝中静脉分配方案,切取肝中静脉28例,不切取肝中静脉45例.对供受者性别、年龄、体重、手术时间及失血量等基本资料,移植物重量、无肝期、供肝冷保存时间、围术期供受者存活率、小肝综合征发生率以及供受者术后肝功能恢复情况等移植物相关资料进行比较.结果 两组供者术中均未输注血制品,术后均无死亡及小肝综合征发生病例.1例受体术后6 d出现移植肝急性肝坏死转尸体肝移植后痊愈,1例发生小肝综合征保守治疗后痊愈,受者围手术期死亡1例(术后30 d),死亡原因为全身播散性感染并发呼吸功能衰竭旭肝功能已恢复正常.切取MHV组与不切取MHV组之间受者年龄、供体体重小于受体病例所占比例、实际GRWR、移植物重量、移植物冷保存时间、受体术后ALT最高值问差异有统计学意义.结论 这种以术前CT评估供者残肝比例和评估GRWR为分类标准,重点参考MHV解剖因素的MHV取舍方案对供、受者均是安全的.     

猪肝移植时无心跳供体耐受热缺血时间的实验研究

目的探讨心脏停搏供体猪肝移植时供肝耐受无心跳热缺血损伤的安全时限。方法建立小型猪原位肝移植动物模型并按移植前供肝经历心脏停搏时间0,15,30,45 min分为四组。观测肝移植术后各组肝功能、肝脏病理和肝脏能量代谢改变。结果肝脏能量代谢等指标的改变在供肝无心跳热缺血时间30 min前是可逆的,随无心跳热缺血时间的延长逐渐向不可逆演变。结论在本实验条件下,小型猪心脏停搏供体肝移植时供肝耐受无心跳热缺血损伤的安全时限约为30min。     

脑死亡对大鼠肝移植后早期移植肝损伤的影响

目的:探讨脑死亡状态对大鼠供肝肝移植后早期肝脏损伤的影响.方法:Wistar大鼠80只随机分为活体大鼠供肝肝移植组(L组)和脑死亡大鼠供肝肝移植组(B组).L组仅建立活体大鼠供肝的二袖套法原位肝移植模型,B组供体大鼠建立脑死亡模型后切取供肝行二袖套法原位肝移植.监测脑死亡模型建立过程中大鼠血压和心率变化,观察肝移植术后受体6 h、24 h存活率,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、透明质酸(HA)和肿瘤坏死因子-α(TNF-α)水平,电镜观察肝脏形态变化,TUNEL法测定肝组织细胞凋亡情况.结果:B组供体大鼠脑死亡模型建立后血压和心率与L组比较,差异有统计学意义(P=0.001.L组和B组6 h和24 h生存率差异无统计学意义(P＞0.05).与L组比较,B组ALT、AST、TNF-α和HA水平均升高(P＜0.05),肝细胞形态学损伤重、凋亡率高(P＜0.05)、Kupffer细胞显著活化.结论:供体脑死亡可以加重脑死亡供肝移植后早期肝脏损伤,其机制可能和脑死亡供体血压、心率的改变以及Kupffer细胞的活化有关.     

供肝的切取与修整技巧

目的 探讨肝移植术供肝的选择，切取和修整方法，方法 2001-12/2002-04月第四军医大学西京医院进行3例全肝移植术，供肝来源于颅脑外伤死亡的患者，根据国内外供体处理经验，采用合适的方法灌洗，切取供体肝脏，经修整后移植给受体，结果 3例供肝的热缺血时间分别为3，1.5和1min，切取时间分别为28，25和21min，肝脏保存时间分别为7.5,6.5和7.9h，术后1wk内肝脏功能恢复正常。结论 供肝的灌洗，修整及保存都是肝移植术中应重视的问题，我们设计的供肝处理方法，在实际应用中取得满意的效果，为移植手术的成功提供了可靠的保证。     

肝移植术后早期肝动脉阻力指数增高的相关因素分析

目的:探讨肝移植术后早期超声检查中影响肝动脉阻力指数增高的相关因素.方法:对83例在我院行肝移植术患者的资料进行回顾性分析,按术后72h内超声监测肝动脉阻力指数结果分为阻力指数正常组和阻力指数增高组,对比分析两组供体年龄、受体年龄、受体性别、冷缺血时间、手术因素(包括手术方式、手术时间、热缺血时间、无肝期时间)等相关因素.结果:83例患者中18例(22%)出现肝动脉阻力指数增高,65例(78%)肝动脉阻力指数正常.阻力指数增高组和正常组相比,受体年龄及冷缺血时间的平均值有统计学意义(P<0.05),供体年龄、受体性别及手术因素等两组比差异无统计学意义(P>0.05).结论:肝移植术后早期肝动脉阻力指数一过性增高是较常见的现象,与受体年龄偏大及供肝冷缺血时间过长有关.     

四种不同肝移植手术方式的选择

目的探讨4种不同肝移植手术方式的优缺点及适应证。方法对实施成人尸体全肝移植的135例患者分别采用4种不同术式:A组(22例)采用经典原位肝移植,B组(79例)采用改良背驮式,C组(18例)采用经典背驮式肝移植,D组(16例)采用改良的经典原位肝移植,所有患者术中均未行体外静脉转流,回顾性分析135例患者的术中、术后情况。结果各组间手术时间、无肝期时间和术中出血量差异具有显著性(P<0.05),术后一过性肾功能损害的发生率C组较其他各组显著降低(P<0.05),手术后近期生存率及血管并发症各组间差异无显著性。结论应针对患者具体情况选择不同手术方式,对于一些肿瘤患者或有上腹部手术史的患者,采用改良的经典原位肝移植可以缩短手术时间,尤其是无肝期时间,减少手术难度和术中出血量,改善患者预后。     

边缘供肝在肝移植中的应用研究

边缘供肝一般是指肝移植后存在原发性移植肝无功能或功能低下以及迟发性移植物失活风险的肝移植供体.广泛地讲,边缘供肝主要包括两大类型,第一种是有可能带来高风险的技术性并发症和功能障碍的供肝,如脂肪肝、无心跳供肝、老年供肝、劈裂式供肝以及长缺血时间供肝;第二种类型是有可能给受体传染疾病或肿瘤的供肝,如血清学病毒抗体阳性的供体、患有恶性肿瘤的供体、有细菌感染的供体等.近年来,由于理想供肝的严重短缺,边缘供肝逐渐被人们重视起来.大量的文献研究表明,合理地利用边缘供肝可以得到满意的效果.本文就边缘供肝在肝移植中的作用及效果做一综述.     

老年大鼠供肝应用的实验研究

目的 研究老年大鼠供肝的应用,并探讨老年大鼠肝移植供体年龄限制.方法 采用肝动脉重建二袖套原位肝移植技术,建立大鼠原位肝移植模型,供受体均为雄性Wistar大鼠,受体鼠龄均为5月,根据供体鼠龄分组,A～E组供体鼠龄分别为5、17、20、23、26月,每组12例.检测术后第1、3、7天血清丙氨酸转氨酶(ALT)水平,并观察组织病理学变化和术后3月存活率.结果 B、C和D组肝移植术后第1天和第3天ALT与A组比较差异均有显著性(P<0.05),第7天差异无显著性(P>0.05),肝功能恢复延迟,肝功能于术后第7天趋于稳定.老年大鼠移植肝植入前组织病理学表现存在轻度肝纤维化,老年大鼠肝细胞数目减少,脂褐素数量增加.E组术后ALT增高(P<0.05),肝功能损伤不可恢复,3月存活率为0.结论 供体年龄是影响老年供肝移植疗效的重要因素之一,鼠龄低于23月的老年大鼠移植肝可恢复功能.

Abstract：

Objective To investigate the application of donor livers from aging rats, and discuss the age limit of the donor rats liver transplantation. Methods Arterialized, two-cuff technique orthotopic liver transplantation was performed in male Wistar rats. All the recipient rats were 5 months old, and the ages of the donor rats were 5 (group A), 17 (group B), 20 (group C), 23 (group D), and 26 (group E) months (n=12). The postoperative function recovery and pathological changes of the liver grafts were evaluated by serum alanine aminotransferase (ALT) detection and histopathological examination, and the 3-month survival rate of the rats was observed. Results Aging liver grafts in groups B, C, and D caused early elevation of ALT peak level and aggravation of liver tissue damage, and the liver graft recovery was delayed until postoperative day 7. Mild liver fibrosis, reduced hepatocytes and pigment deposition were observed in the liver grafts before the transplantation. Compared with the other groups, the rats in group E showed significantly increased ALT levels after the transplantation (P<0.05), with failure of liver graft function recovery and significantly reduced 3-month survival rate (0%, P<0.05). Conclusion The donor age of the rats is a crucial factor to affect the outcome of the liver grafts. Grafts obtained from rats younger than 23 months allow better functional recovery of the liver.     

U-74389G PRETREATMENT ATTENUATING WARM ISCHEMIA INJURY IN LIVER TRANSPLANTATION

Objective To investigate the protective role of lazaroid U-74389G pretreatment against warm ischemia injury of rat liver transplantation from non-heart-beating donors. Methods Rat othortopic liver transplantation was perfomed in 4 groups (N-45, N-60, pN-45 and pN-60 ), according to pretreatment with U-74389G or not, and the non-heart-beating time 45rain or 60rain before donor liver harvested. Survival rates, liver functions, MDA values and graft pathology of each group were compared. Results The one-week survival rates of Group N-45, N-60 , pN-45 and pN-60 were25% (2/8), 0% (0/8), 58.3% (7/12) and 33.3% ( 4/12 ), respectively. U-74389G pretreatment significantly increased survival rate of rat liver trans-plantation from non-heart-beating donors, but also improved liver functions and graft pathologies, as well as decreased MDA expression. Conclusion U-74389G pretreatment could attenuate warm ischemia reperfusion injury of rat liver transplantation from non-heart-beating donors.     

Outcomes of adult-to-adult living donor liver transplantation: a single center experience

Background Since January 2002, adult-to-adult living donor liver transplantation （AALDLT） has gained increasing popularity in China in response to the shortage of cadaveric donor livers. This study presents a detailed analysis of the outcomes of AALDLT in a single center.
Methods A total of 70 patients underwent AALDLT at our center between January 2002 and January 2007. Among these, 67 patients received a right lobe graft without the middle hepatic vein and 3 patients received dual grafts. Three-dimensional volumetric computed tomography, magnetic resonance imaging with angiography and cholangiography were performed preoperatively. Recipient operation time, intraoperative transfusion requirement, length of intensive care unit stay, length of hospital stay, liver function tests, coagulation tests and surgical outcomes were routinely investigated throughout this study.
Results All donors survived the procedure with an overall complication rate of 15.3%. Overall recipient 1-year survival and complication rates were 87.1% and 34.2%, respectively. Among the 70 cases, average graft recipient weight ratio was 0.94% （0.72%-1.43%） and average graft volume/standard liver volume ratio was 46.42% （31.74%-71.68%）. All residual liver volumes exceeded 35%. Liver function and coagulation recovered rapidly within the first 7 days after transplantation.
Conclusions AALDLT is a safe procedure for the donors and an effective therapy for patients with end-stage liver disease. Patient selection and timely decision-making for transplantation are essential in achieving good outcomes. With accumulation of experience in surgery and clinical management, timely feedback and proper modification, we foresee better outcomes in the future.     

Early experiences on living donor liver transplantation in China: multicenter report

Background Because of the lack of brain death laws in China, the proportion of cadaveric organ donation is low. Many patients with end-stage liver disease die waiting for a suitable donor. Living donor liver transplantation （LDLT） would reduce the current discrepancy between the number of patients on the transplant waiting list and the number of available organ donors. We describe the early experience of LDLT in the mainland of China based on data from five liver transplant centers. Methods Between January 2001 and October 2003, 45 patients with end-stage liver disease received LDLT at five centers in China. The indication and timing, surgical techniques and complications, nonsurgical issues including rejection, infection, and advantages of LDLT in the series were reviewed. Actuarial patient and graft survival rates were calculated by using the Kaplan-Meier product-limit estimate. Statistical analysis was completed by using SPSS 10.0. Results All LDLT recipients were cirrhotic patients, except for one man with fulminant hepatic failure. Among the 45 cases of LDLT, 35 （77.8%） were performed in one center （the First Affiliated Hospital of Nanjing Medical University）. The overall 1 and 3 year survival rate of the recipients was 93.1% and 92.0%, respectively. Of the 45 LDLT donors, there were 3 cases of biliary leakage, 2 subphrenic collections, 1 fat liquefaction around the incision and 1 biliary peritonitis after T tube removal. All donors recovered completely. Conclusions LDLT provides an excellent approach to addressing the problem of donor shortage in China even though the operation is complicated, uncompromising and difficult with respect to the safety of the donors and receptors. Despite early technical hurdles having been overcome, perfection of technique is still necessarily. At present, LDLT is a good choice for the patients with irreversible liver disease.     

大鼠肝移植并发症的预防

目的探讨如何从手术操作过程中,减少大鼠原位肝移植术的并发症。方法采用二套管法共行大鼠原位肝移植术72次,其中24次为大鼠心脏停搏供体肝移植,热缺血时间分别为15、30和45min不等。结果术后受体的主要并发症为出血、血栓形成、感染和胆道梗阻;而对于心脏停掉供体肝移植,受体更易产生原发性移植肝无功能。结存减少游离肝脏时的机械损伤、防止血管套管的扭曲或成角、提高吻合口质量、以及缩短无肝期时间是预防并发症的关键。     

104例成人间活体肝移植肝动脉重建

目的 探讨成人间活体肝移植的肝动脉重建技术的经验.方法 自2002年1月至2007年8月,四川大学华西医院施行了104例成人间右半肝活体肝移植,包括98例不含中肝静脉(MHV)的右半供肝肝移植及6例双供肝肝移植(双亲属左半供肝1例,亲属右半肝加亲属左半肝3例,亲属右半肝加尸体左半肝2例),104例受者中男86例,女18例,年龄18～63岁(中位年龄38岁),在供受体间肝动脉的重建中,61例供体右肝动脉与受体肝右动脉吻合,15例与受体肝固有动脉吻合,此外与受体左肝动脉吻合7例,与受体肝总动脉吻合3例,与受体肠系膜上动脉发出的副右肝动脉吻合8例,供体右肝动脉与受体肝总动脉自体大隐静脉间置搭桥5例,受体腹主动脉与供体右肝动脉自体大隐静脉搭桥2例,用尸体冷冻保存髂血管行受体腹主动脉与供体右肝动脉搭桥3例,供体肝动脉直径1.5～2.5 mm,分别采用8-0和9-0 Prolene无损伤血管缝线在手术显微放大镜下完成肝动脉重建.结果 104例成人间右半肝活体肝移植,术后1、7 d发生肝动脉血栓形成2例(1.9%),采用自体大隐静脉肾下腹主动脉至供体右肝动脉搭桥术,恢复供肝血流,痊愈出院.1例1个月后发生肝动脉血栓形成,随访期无临床症状未行处理.术后和随访期末发现肝动脉狭窄、肝动脉假性动脉瘤等并发症.全部病例获得随访,随访时间2～60个月,1、2和3年实际生存率分别为89.3%、76.0%和69.3%.结论 根据供受体动脉解剖情况选择最适宜的重建位置和方式,采用显微外科技术是减少围手术期肝动脉并发症保证供肝存活的关键.     

Non-heart-beating organ donors as a source of kidneys for transplantation: a chart review

BACKGROUND: Organ transplantation is the treatment of choice for patients with end-stage organ failure, but the supply of organs has not increased to meet demand. This study was undertaken to determine the potential for kidney donation from patients with irremediable brain injuries who do not meet the criteria for brain death and who experience cardiopulmonary arrest after withdrawal of ventilatory support (controlled non-heart-beating organ donors). METHODS: The charts of 209 patients who died during 1995 in the Emergency Department and the intensive care unit at the Foothills Hospital in Calgary were reviewed. The records of patients who met the criteria for controlled non-heart-beating organ donation were studied in detail. The main outcome measure was the time from discontinuation of ventilation until cardiopulmonary arrest. RESULTS: Seventeen potential controlled non-heart-beating organ donors were identified. Their mean age was 62 (standard deviation 19) years. Twelve of the patients (71%) had had a cerebrovascular accident, and more than half (10 [59%]) did not meet the criteria for brain death because one or more brain stem reflexes were present. At the time of withdrawal of ventilatory support, the mean serum creatinine level was 71 (29) mumol/L, mean urine output was 214 (178) mL/h, and 9 (53%) patients were receiving inotropic agents. The mean time from withdrawal of ventilatory support to cardiac arrest was 2.3 (5.0) hours; 13 of the 17 patients died within 1 hour, and all but one died within 6 hours. For the year for which charts were reviewed, 33 potential conventional donors (people whose hearts were beating) were identified, of whom 21 (64%) became donors. On the assumption that 40% of the potential controlled non-heart-beating donors would not in fact have been donors (25% because of family refusal and 15% because of nonviability of the organs), there might have been 10 additional donors, which would have increased the supply of cadaveric kidneys for transplantation by 48%. INTERPRETATION: A significant number of viable kidneys could be retrieved and transplanted if eligibility for kidney donation was extended to include controlled non-heart-beating organ donors.     

Studies on post-transplant dyslipidemia in kidney transplant patients

This study was performed to retrospectively compare changes in the levels of total cholesterol, non-HDL cholesterol, triglycerides, and immunosuppressive drugs, cyclosporine A and steroids in patients with living-relation renal transplants with those from non-heart-beating donors. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. We evaluated 13 cases of kidney transplants from living-relation donors during the same period. The immunosuppressants used included mainly cyclosporine A as well as mycophenolate mofetil or azathioprine, steroid and ALG, or basiliximab. Over-night fasting lipids (total cholesterol, triglycerides and HDL cholesterol) were studied before renal transplantation and repeated after renal transplantation at 1, 3, 6 and 12 months. The levels of total cholesterol and triglycerides remained in the normal range before transplantation. However, the levels of total cholesterol increased siginificantly 1 and 3 months after transplantation from non-heart-beating donors and remained at higher levels up to 12 months after transplantation. A similar pattern in the levels of triglycerides was observed. The levels of HDL cholesterol remained unchanged and stayed in the normal range before and 1, 3, 6, and 12 months after transplantation from non-heart-beating donors. On the other hand, significant increases in non-HDL cholesterol were observed 3 and 6 months after transplantation from non-heart-beating donors. After transplantation from living-relation donors, levels of total cholesterol, triglycerides, and non-HDL cholesterol remained unchanged and remained in the normal range up to 12 months after transplantation. Although there were no significant differences in the total dosage of cyclosporine A between the patients with living-relation donors and those with non-heart-beating donors, a significant increase in the total dosage of methylprednisolone was observed in patients with non-heart-beating donors compared with those in the patients with living-relation donors. Renal function recovery in patients with living-relation donors was better than in those with non-heart-beating donors. These results may suggest that significant increases in total cholesterol, especially non-HDL cholesterol and triglycerides, were probably partly due to an increased use of immunosuppressants, steroids. It is necessary to aggressively control post-transplant hyperlipidemia and important to reduce or withdraw steroids in the selected, low-risk recipients as early as possible from the viewpoint of preventing post-transplant hyperlipidemia.     

Hepatic venous outflow reconstruction in adult right lobe living donor liver transplantation without middle hepatic vein

Background It is difficult and challenging to reconstruct hepatic venous outflow in adult right lobe living donor liver transplantation (LDLT) without the middle hepatic vein (MHV). Excessive perfusion of the portal vein and venous outflow obstruction will lead to acute congestion of the graft, ultimately resulting in primary nonfunction. Although various reconstruction patterns have been explored in many countries, there is currently no clear consensus. In this study we describe a technique to prevent “chocking” of the graft at the outflow anastomosis with the inferior vena cava (IVC) in LDLT using right lobe graft without the MHV. Methods A retrospective analysis was conducted on clinical data from 55 recipients undergoing LDLT using right lobe grafts without the MHV or reconstruction of hepatic venous outflow. The donor’s right hepatic vein (RHV) was anastomosed with a triangular opening of the recipient IVC; the inferior right hepatic vein (IRHV), if large enough, was anastomosed directly to the IVC. The great saphenous vein (GSV) was used for reconstruction of significant MHV tributaries.Results No deaths occurred in any of the donors. Of the 55 recipients, complications occurred in 6, including hepatic vein stricture (1 case), small-for-size syndrome (1), hepatic artery thrombosis (1), intestinal bleeding (1), bile leakage (1), left subphrenic abscess and pulmonary infection (1). A total of three patients died, one from small-for-size syndrome and two from multiple system organ failure. Conclusions The multiple-opening vertical anastomosis was reconstructed with hepatic vein outflow. This technique alleviates surgical risk of living donors, ensures excellent venous drainage, and prevents vascular thromboses and primary nonfunction.