胆道系统疾病的肝脏移植治疗

胆道系统疾病始终是选择肝脏移植治疗的诸多病种中的一个重要适应证,其在病例选择及适应证方面主要包括:先天性胆道闭锁、易恶变的胆道疾病、胆道恶性肿瘤、原发性胆汁性肝硬化和继发性胆汁性肝硬化等病变,且这些疾病各有其适应证.胆道系统疾病行肝脏移植手术的时机包括:当肝脏移植为疾病治疗的唯一手段或唯一有效手段时;肝脏移植为疾病外科治疗的方法之一时.虽然国内外目前尚无一个统一标准用于胆道疾病行肝脏移植术前的评估,但首先应是明确诊断;其次要确定胆道疾病患者目前是否急需行肝脏移植以及急需的程度;再者要患者家属了解肝脏移植的整个过程,知道其存在的危险、移植的价值以及术后终身服用免疫抑制剂等.本文通过笔者的经验和实例分析胆道系统疾病肝脏移植手术的相关问题.     

Pediatric liver transplantation in 31 consecutive children

Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements.
Methods Thirty-one children （≤18 years old） underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old （ranged from 5 months to 18 years） with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson＇s disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard （without venovenous bypass）, 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug （FK506, steroid, and mycophenolate mofetil） immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months.
Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus （HBV） or hepatitis C virus （HCV） infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.
Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients＇ age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The     

原位肝脏移植术后早期胆道并发症诊断与治疗

目的探讨原位肝移植术后胆道并发症的发生原因及防治措施。方法回顾性研究2002年7月-2005年1月该组肝脏移植32例原位肝移植的临床资料。结果该组32例肝脏移植受体中有6例发生胆道并发症，其中3例术后3d内出现单纯胆漏，给予小号导管置入T管周边引流，均在8d后未见胆漏。1例经影像学诊断肝动脉吻合口狭窄经介入置入支架扩张后，胆道并发症好转，肝功能恢复。1例术后1周出现霉菌感染，给予相应治疗，因出现肝昏迷多脏器功能衰竭死亡。1例术后第3天出现无胆汁，B超示肝内外胆管扩张，行T管造影术。发现T管胆管内的上支行成活瓣，随在介入下置入超滑导丝效果欠佳，第2天在超滑导丝的基础上置入4F管，引流通畅，肝功能快速恢复。结论手术技术不佳、移植物冷热缺血的时间不宜过长及胆管的血液供应不良是肝移植术后发生胆道少并发症的重要因素，联合应用胆道造影术和核磁共振胆管成像能了解胆道今新．有助干胆省犊窑与胆漏的论断．及时采用放射介入技术处理胆道并发症可取得良好疗效。     

肝移植术后肝内弥漫性胆管狭窄的再次肝移植治疗

目的 探讨肝移植术后肝内弥漫性胆管狭窄行再次肝移植治疗的临床经验.方法回顾性分析中山大学附属第一医院2001年1月至2009年12月施行的53例再次肝移植患者的临床资料,其中因首次肝移植术后肝内胆管弥漫性狭窄行再次肝移植手术患者20例(20/53).分析其预后及影响因素.结果 20例术后肝内胆管弥漫性狭窄的发生时间为首次肝移植术后3～16个月,平均6.3个月.胆道狭窄的类型包括肝内弥漫性胆管狭窄16例,肝内外胆管多发性狭窄者4例;20例患者术前均经介入及其他综合治疗无效,行再次肝脏移植.行再次肝移植20例患者中,14例获治愈.6例死于围手术期合并症,其中严重腹腔感染和多脏器衰竭3例,胆瘘 2例,血管合并症(肝动脉栓塞)1例.术后随访1～5年,平均1.8 年;术后1、6个月和1年的累计生存率分别为80.0%、75.0%和70.0%.结论 再次肝移植是挽救肝内弥漫性胆管狭窄无法介人治疗或介入治疗失败的最终治疗手段;把握最佳手术时机和提高手术技巧,以及有效防治围手术期感染是提高该类患者生存率的关键.

Abstract：

Objective To investigate the feasibility and management of retransplantation for diffuse biliary strictures occurring after initial liver transplantation.Methods The clinical data of 53 consecutive liver retransplantation patients at our hospital from January 2001 to December 2009 were collected and analyzed retrospectively. Among them, 20 (37.7%) were due to diffuse biliary strictures.Results Diffuse biliary strictures appeared at 3-16 months after initial transplantation. The mean time was 6.3 months. The specific types included intra-hepatic diffuse biliary strictures (n=16) and multi-strictures involving both intra- & extra-hepatic biliary ducts (n=4). Retransplantation was performed after a failure of intervention or/and other comprehensive treatments. Among them, 14 were cured and 6 died from peri-operative complications including serious abdominal infection & MODS (multiple organ dysfunction syndrome) (n=3, 50%), biliary fistula (n=2, 33.3%) and hepatic artery embolism (n=1, 16.7%). These patients were followed up for a mean time of 1.8 years (range:1-5 years). The accumulative survival rates at 1, 3 and 6 months were 80.0%, 75.0% and 70.0% respectively.Conclusions Liver retransplantation is the ultimate treatment for diffuse biliary strictures after liver transplantation. The survival rate is associated with operative timing, surgical techniques and peri-operative management.     

肝移植术后缺血型胆道病变的预防和治疗

目的探讨原位肝移植术后缺血型胆道病变（ITBL）的发生原因及防治措施.方法回顾性研究从1999年2月至2004年8月间212例次原位肝移植患者的临床资料,总结原位肝移植术后发生ITBL的情况.结果共发生缺血型胆道病变14例（6.6%）,其中肝门部胆管病变5例,肝内外胆管多发病变6例,肝内胆管多发病变3例.供肝冷保存时间超过10 h,供受体ABO血型不符,术后肝动脉病变及原发病为重型乙型病毒性肝炎的ITBL发生率分别为9.8%（10/102）、22.2%（2/9）、40%（2/5）及14.6%（7/48）.14例患者采用内科保守、内镜、外科及再次肝移植治疗,7例治愈,4例病情改善,1例无效、1例死亡.治疗有效率为78.6%（11/14）,治愈率为50%（7/14）,与ITBL相关的病死率为7.1%（1/14）,与ITBL相关的移植物失功率为23%（3/14）.结论尽量避免供受体ABO血型不符和供肝冷保存时间过长,及时处理术后肝动脉病变是预防原位肝移植术后发生ITBL的有效措施.根据胆管树的病变情况选择合适的治疗方法,是原位肝移植术后ITBL患者获得良好疗效的关键.     

Emergencies in rheumatology

Rheumatological conditions can sometimes present as emergencies. These can occur due to the disease process or may be iatrogenic. Some of the important articular emergencies are septic arthritis, acute polyarthritis and atlanto-axial dislocation. Classical polyarteritis nodosa may present with massive gastro-intestinal bleeding, intestinal perforation or acute pancreatitis. Adult respiratory distress syndrome, bilateral pneumonitis and diffuse alveolar haemorrhage due to systemic lupus erythematosus or systemic necrotising vasculitis and ventilatory failure due to polymyositis are some of the respiratory emergencies. Scleroderma is well known to cause renal crisis which can be fatal if not diagnosed and managed promptly. Microscopic polyangiitis and Wegener's granulomatosis may cause rapidly progressive renal failure. Cerebrovascular accident, cortical vein thrombosis, seizures and acute psychosis are important neurological complications of rheumatic disease. Cardiac emergencies include tamponade, acute myocarditis and acute myocardial infarction. Vision can be threatened in Behcet's disease, temporal arteritis and seronegative spondylarthritis. Catastrophic antiphospholipid syndrome is a devastating emergency. The management of above emergencies includes critical care, immunosuppression when indicated and withdrawal of the offending drug. Anticoagulants have to be used in the management of antiphospholipid syndrome. A good understanding of these conditions is of paramount importance for proper management.     

Adult-to-adult living donor liver transplantation for fulminant hepatic failure

The outcome of fulminant hepatic failure without timely liver transplantation is poor. We describe a 19-year-old woman with fulminant hepatic failure due to acute hepatitis B infection who received a living donor liver transplant from her sister. The donor's recovery was uneventful, allowing hospital discharge on Day 6. Two months after transplantation the recipient developed a biliary stricture requiring surgery. One year after transplantation, her liver function was normal.     

Biliary complications in orthotopic liver transplantation: mechanism, diagnosis and treatment

Biliary complications(BC) are a major cause of morbidity in liver transplant recipients with an incidence of 10～30% following orthotopic liver transplantation(OLT), and a mortality rate of up to 10%. The most common biliary complications are bile leaks, biliary strictures, ampullary dysfunction, and stones. Leaks predominate in the early posttransplant period; while stricture formation typically develops gradually over time. Risk factors for biliary complications comprise technical failure, T-tube-related c...     

肝移植术后胆道狭窄及胆漏的微创治疗

目的探讨肝移植术后胆道狭窄及胆漏微创治疗的价值.方法对17例肝移植术后胆道狭窄及胆漏的患者,应用十二指肠镜逆行胆道造影（ERCP）、胆管狭窄部扩张、塑料内支架置入、经皮经肝胆管内外引流或联合经皮腹腔胆汁湖引流等微创方法治疗,评价其治疗效果.结果17例肝移植术后黄疸患者经造影证实：胆管吻合口狭窄9例,其中合并胆漏3例;肝门部胆管狭窄4例,其中合并胆漏1例;移植肝肝内胆管弥漫性狭窄4例;行ERCP加胆管扩张及塑料内支架置入8例,经皮经肝胆管造影、胆管内外引流管置入9例,对合并胆漏的4例联合进行了经皮腹腔胆汁湖引流,13例非胆管弥漫性狭窄的患者治疗有效、黄疸消退,胆漏愈合,4例移植肝肝内胆管弥漫性狭窄患者治疗无效.结论肝移植术后胆管非弥漫性狭窄及胆漏的微创治疗安全、有效,但对于移植肝肝内胆管弥漫性狭窄尚无有效的微创治疗手段.     

地市级医院开展肝移植的经验（附11例报告）

目的：总结在地市级医院开展临床肝移植的经验,方法：从1999年12月－2001年4月间对4例肝炎后终末期肝硬化,4例原发性肝癌,1例肝癌术后肝功能衰竭,1例肝豆状核变性患者施行了原位肝移植,对1例慢性肾功能衰竭合并肝硬化患者施行肝肾联合移植。结果：全组成功9例,围手术期死亡2例,直接死亡原因：脑出血1例,急性呼吸窘迫综合征（ARDS）1例,最长已存活超过9个月。结论：在地市级医院开展肝移植初期专业队伍建设非常重要,应精心组织,分工明确;宙时应严格掌握适应证,选择条件较好的受体;围手术期的严密监测与正确处理是肝移植成功的关键。     

Liver transplantation for hepatitis C virus related liver disease

Liver transplantation is a useful treatment for end stage liver disease of all aetiologies but recurrent disease presents an ongoing challenge, particularly for hepatitis C virus (HCV) where recurrence is almost universal. Immunosuppression is needed for all patients after transplantation and should be tailored to the individual patient, with particular problems being noted for those with HCV. The longer term effects of immunosuppression, particularly renal failure and the adverse effects of certain treatments on the liver graft, have become more important as survival improves and results are studied for longer periods after transplantation.     

Transplantation of multiple abdominal viscera

Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus-associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival.     

Liver retransplantation: a single-centre experience

Background The curative effect of liver transplantation for patients with end-stage liver disease was encouraging in recent years and the 5-year patient survival rate can reach up to 70%. However, some patients might lose grafts due to a variety of reasons, including bile duct complications, vascular complications, primary non-function, graft rejection and disease recurrence etc. Liver retransplantation （re-LT） was the only available means for those patients whose initial grafts had failed, but the inferior outcomes of re-LT compared to primary liver transplantation （PLT） continue to be a major concern. This study aimed to analyze the indications for re-LT, optimal timing of re-LT, and strategies to improve the survival rate after re-LT.
Methods From January 2001 to December 2006, we performed 738 liver transplants and 39 re-LT （5.3%） at our center. A retrospective analysis was performed to identify factors （indication for re-LT, preoperative score of model for end-stage liver disease （MELD）, interval to re-LT from primary liver transplantation, methods of vascular and biliary reconstruction and common causes of death） associated with survival.
Results Mean follow-up period was 1.8 years （1 to 5 years）. Patients with MELD score less than 20 were better than those whose MELD score was 〉20 and MELD score〉30 （1-year survival, 80.0% versus 50.0% and 3/5）. The perioperative survival rate of patients who received re-LT at an interval of more than 30 days and less than 8 days after the initial transplantation was higher than those who received retransplantation between 8 to 30 days following the first operation （88.5% and 74.3% versus 50.0%）. The main causes of death were infection （60.0%）, multiple organ failure （20.0%）, vascular complications （10.0%） and biliary fistula （10.0%） in perioperative period. The overall patient survival rate of 1-month, 6-month and 1-year was 80.0%, 76.7% and 66.7%, respectively.
Conclusions Our study suggested the favorable results aft     

1449例肝脏移植患者病种统计分析

目的对近五年某院肝移植患者进行疾病归类,了解不同性别和年龄段行肝脏移植患者的情况,为医院临床管理提供数据参考,对预防治疗有一定的指导作用。方法利用医院统计报表数据进行分析,采用疾病分类ICD-10和手术编码ICD-9-CM-3进行分类。所有数据均利用办公软件Excel分析处理。结果 2006年1月-2010年12月因终末期肝病行肝脏移植1449例患者中男性多于女性患者,男女性别比为5.11∶1;酒精性肝硬化患者100%为男性;肝炎后肝硬化患者644人,占肝脏移植人数的44.44%,肝移植患者平均年龄51.2.岁；50岁-59岁肝移植患者占肝脏移植的52．17％。10岁以下患者100％为先天性胆道闭锁患者。肝移植1年、3年、5年生存率分别为83．1％、72．9％、69．3％。结论肝移植是终末期肝病治疗的最佳手段。预防治疗策略是预防进展至终末期肝病的有效方法。戒酒是首要措施。中年人要成为医疗预防工作的重点对象。     

Motor neurone disease

Motor neurone disease (MND), or amyotrophic lateral sclerosis (ALS), is a neurodegenerative disorder of unknown aetiology. Progressive motor weakness and bulbar dysfunction lead to premature death, usually from respiratory failure. Confirming the diagnosis may initially be difficult until the full clinical features are manifest. For all forms of the disease there is a significant differential diagnosis to consider, including treatable conditions, and therefore specialist neurological opinion should always be sought. Clear genetic inheritance has been demonstrated in a minority of patients with familial ALS but elucidation of the biological basis of genetic subtypes is also providing important information which may lead to treatments for sporadic forms of the disease. In the absence of curative or disease modifying therapy, management is supportive and requires a multidisciplinary approach. If, as seems likely, complex inherited and environmental factors contribute to the pathogenesis of MND, future treatment may involve a combination of molecular based treatments or restoration of cellular integrity using stem cell grafts.     

No longer a biological waste product: umbilical cord blood

Haematopoietic stem cell transplantation is an accepted curative therapy for many cancers and inherited non-malignant diseases, including bone marrow failure syndromes, haemoglobinopathies, and inborn errors of metabolism. Stem cells can be used from the bone marrow or blood of matched siblings or appropriately matched unrelated volunteers, but many patients do not have a suitably matched donor. Umbilical cord blood (UCB) has been successfully used as an alternative stem cell source. It has the advantage of tolerance for a degree of human leukocyte antigen (HLA) incompatibility not possible with adult bone marrow, resulting in greater likelihood of finding an appropriate match. UCB is also stored fully tested and cryopreserved, leading to rapid availability. Greatest clinical experience in UCB transplants has been in treating paediatric leukaemia. Results using well matched UCB grafts are equivalent or better than with unrelated bone marrow transplant. Cell dose and the degree of HLA matching are critical determinants in the success of UCB transplant. The use of UCB in older children and adult patients has been limited by the fixed, low cell dose available in a UCB unit, relative to recipient weight. This can be overcome by strategies such as using two or more UCB units. Early animal studies suggest that UCB may have the potential to differentiate into other cell types, including nervous tissue, and may in future play a role in the treatment of disorders such as Alzheimer disease and Parkinson disease.     

Marginal grafts increase early mortality in liver transplantation

CONTEXT AND OBJECTIVE: Expanded donor criteria (marginal) grafts are an important solution for organ shortage. Nevertheless, they raise an ethical dilemma because they may increase the risk of transplant failure. This study compares the outcomes from marginal and non-marginal graft transplantation in 103 cases of liver transplantation due to chronic hepatic failure. DESIGN AND SETTING: One hundred and three consecutive liver transplantations to treat chronic liver disease performed in the Liver Transplantation Service of Hospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo between January 2001 and March 2006 were retrospectively analyzed. METHODS: We estimated graft quality according to a validated scoring system. We assessed the pre-transplantation liver disease category using the Model for End-Stage Liver Disease (MELD), as low MELD (< 20) or high MELD (>or= 20). The parameters for marginal and non-marginal graft comparison were the one-week, one-month and one-year recipient survival rates, serum liver enzyme peak, post-transplantation hospital stay and incidence of surgical complications and retransplantation. The significance level was 0.05. RESULTS: There were no differences between the groups regarding post-transplantation hospital stay, serum liver enzyme levels and surgical complications. In contrast, marginal grafts decreased overall recipient survival one month after transplantation. Furthermore, low-MELD recipients of non-marginal grafts showed better one-week and one-month survival than did high-MELD recipients of marginal livers. After the first month, patient survival was comparable in all groups up to one year. CONCLUSION: The use of marginal graft increases early mortality in liver transplantation, particularly among high-MELD recipients.     

肝移植术后胆道并发症的病因及诊治进展

肝移植术后胆道并发症(BC)做为肝移植术后影响肝移植远期疗效的重要并发症业已引起临床和研究人员的重视。胆道并发症是指具有临床表现,有影像学依据,需要进行手术或介入性治疗的胆道狭窄、梗阻及胆瘘等,其发生与外科操作、缺血再灌注损伤、供肝保存性损伤等因素有关。该文对BC的病因及诊治进展予以综述,以期进一步开展BC的临床和实验研究。     

Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia

The demand for liver transplantation in the Kingdom of Saudi Arabia (KSA) is associated with the country’s high burden of liver disease. Trends in the epidemiology of liver transplantation indications among recipients in KSA have changed over 20 years. Non-alcoholic steatohepatitis has eclipsed the hepatitis C virus in the country due to the effective treatment strategies for HCV. Risk factors for NASH, like type 2 diabetes mellitus, obesity, and hyperlipidemia, are becoming a major concern and a leading indication for liver transplantation in the KSA. There is also a significantly increased prevalence and incidence of genetic adult familial liver diseases in KSA. New immunosuppressive agents and preservation solutions, improved surgical capabilities, and early disease recognition and management have increased the success rate of liver transplant outcome but concerns about the side effects of immunosuppressive therapy can jeopardise long-term survival outcomes. Despite this, indications for liver transplantation continue to increase, resulting in ongoing challenges to maximize the number of potential donors and reduce patient mortality rate while expecting to get transplanted. The Saudi Center of Organ Transplant is the recognized National Organ Donation Agency for transplantation, which renders important support for procurement and allocation of organs. This guidance document aims to help healthcare providers in managing patients in the liver transplant setting.