胰腺与胰肾联合移植免疫抑制剂的应用

目前已公认胰腺与胰肾联合移植是治疗Ⅰ型糖尿病(IDDM)及其并发症的安全、有效方法。移植的最终目的是彻底根治IDDM，完全停用外源性胰岛素，消除或改善糖尿病并发症，提高生活质量。由于糖尿病病变的特殊性、移植胰排斥反应发生率和移植物丢失率高以及术后免疫抑制剂引起的副作用，如：高血压、高脂血症和移植后糖尿病(PTDM)等因素，胰腺与胰肾联合移植术后免疫抑制剂的选择与应用比单纯肾移植更复杂，涉及问题更多。本文就胰腺及胰肾联合移植术后免疫抑制的临床应用及进展作一概述。     

胰肾联合移植53例术后长期存活的临床观察

目的 分析53例胰肾联合移植长期存活情况及其影响因素.方法 回顾性分析2000年1月至2009年6月间施行的53例胰肾联合移植受者和移植物长期存活情况,分析受者死亡原因和移植物功能丧失原因.结果 3、5和8年受者存活率分别为90.1％、89.1％和80.0％,3、5和8年移植胰腺存活率分别为84.9％、84.8％和60.0％,3、5和8年移植肾存活率分别为83.0％、82.6％和53.3％.受者死亡原因分别为感染(4例)、移植肾功能丧失(2例)、心血管急症(1例)和脑卒中(1例).移植胰腺功能丧失的主要原因为带功能受者死亡、排斥反应和外科并发症.移植肾功能丧失的主要原因为排斥反应和带功能受者死亡.结论 胰肾联合移植治疗终末期糖尿病肾病远期效果良好,感染、排斥反应和外科并发症是受者死亡和移植物功能丧失的主要原因.     

临床胰腺和胰、肾联合移植的现状

由于胰腺外分泌处理和移植胰腺排斥反应难以诊断的特殊性，胰腺移植在移植总数和移植效果上曾远远落后于肾、心和肝等器官移植。直至近10余年，随着新型强效免疫抑制剂的临床应用、器官保存技术的改进和移植手术方式的日趋成熟，胰腺移植受者和移植胰腺的存活率均显著提高。胰、肾联合移植已成为治疗1型糖尿病、部分2型糖尿病合并尿毒症的有效方法。本文概述临床胰腺与胰、肾联合移植的现状与进展。     

胰肾联合移植的排斥反应

目的探讨胰肾联合移植术后的排斥反应。方法对我院施行的3例胰肾联合移植的病人，采用FK506 MMF Perid Zenapax四联免疫治疗方案，通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法，对激素不敏感者采用OKT3治疗。结果3例患者中有2例出现排斥反应，其发生率达66％；在出现排斥反应时，首先表现为低热、全身不适，尿量减少，血Cr、BUN升高，彩超示移植物血流阻抗升高，之后才是血糖升高。结论胰肾联合移植中，排斥反应与多种因素有关，移植肾对移植胰具有保护作用，肾脏可以作为监测胰腺排异的窗口，彩超检查可以作为筛选移植物排异反应的手段。     

移植合剂治疗胰腺移植排斥反应的实验研究

目的 :探讨移植合剂在胰腺移植排斥反应中的作用及其机理。 方法 :建立大鼠全胰十二指肠移植模型 ,使用移植合剂和环孢菌素A(cyclosporinA ,CsA)进行治疗 ,观察二者及二者结合应用后各鼠移植胰腺有功能存活时间 ,血清胰岛素水平 ,外周血T淋巴细胞亚群和胰、肝、肾的组织病理学改变。 结果 :移植合剂可以延长移植胰有功能存活时间 (P <0 0 5 ) ;对CD3+T细胞和CD8+T细胞有显著的抑制作用 (P <0 0 1) ;移植合剂与亚治疗量CsA合用后可以达到治疗量CsA的效果且无肝、肾毒性。 结论 :移植合剂对胰腺移植的排斥反应有抑制作用 ,而且与CsA具有一定的协同作用     

猪同种异体胰十二指肠移植门静脉回流肠内引流模型的实验研究

目的研究猪胰十二指肠移植治疗实验性Ⅰ型糖尿病的可行性及其意义。方法选四川当地杂种长白猪46头(体重25~32kg),分为供、受体2组(n=23),进行同种异体胰十二指肠移植手术。观察术后手术并发症,术前、术中及术后1、3、5及7d检测血糖、胰岛素及胰高血糖素水平,观察移植物存活及急性排斥反应情况。结果进行猪同种异体胰十二指肠移植23例,手术中因麻醉意外死亡1例,手术成功率为95.7%。发生手术并发症2例,其中静脉血栓形成1例(4.5%),十二指肠空肠吻合口漏1例(4.5%)。在切除胰腺30min内即可见血糖升高,术后第3d开始恢复至术前水平。胰岛素和胰高血糖素在切除胰腺30min内开始下降,术后第3d开始恢复到术前水平。手术后第1d开始出现排斥反应,并逐渐加重,第9d达到高峰,但未出现血糖、胰岛素及胰高血糖素水平变化和排斥反应的临床症状。结论猪胰十二指肠移植治疗Ⅰ型糖尿病效果确实、可靠,移植术后急性排斥反应是影响术后功能的主要因素。     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

胰、肾联合移植术式的选择

由于胰腺外分泌液的引流方式和移植胰腺排斥反应难以诊断的特殊性,胰、肾联合移植的总数和效果都远远落后于其它器官移植。直到最近十年,胰、肾联合移植的手术方式才趋向定型,成为治疗 1 型糖尿病合并尿毒症的最佳选择。在我国,胰、肾联合移植的经验积累十分有限,手术方式尚无统一标准,多数中心仅仅实施单一术式。因此,本文结合我们的经验,对胰腺与胰、肾联合移植手术选择的有关问题作一综述。一、胰、肾同期移植与肾移植后的胰腺移植胰、肾联合移植分为胰、肾同期移植(SPK)和肾移植后的胰腺移植(PAK),SPK的免疫学特点是胰腺和肾脏…     

移植肺病理学诊断标准及其进展

近年来,随着肺移植外科技术和术后管理经验的积累,我国肺移植例数逐步增长。肺移植术后移植肺可出现多种并发症,主要包括由移植肺缺血-再灌注损伤(IRI)等所致的原发性移植肺无功能(PGD)、急性与慢性排斥反应以及移植术后应用免疫抑制剂所致机体免疫力下降出现的机会性感染或淋巴组织异常增生等。移植肺并发症的确诊主要依据移植肺活组织检查(活检)。本文对移植肺病理学研究的简史、移植肺活检的主要方法及其病理学处理技术、肺移植术后主要并发症及其活检病理学诊断标准进行阐述,旨在为指导临床对上述并发症采取针对性的治疗方案提供参考。     

胰、肾联合移植六例报告

目的 探讨胰、肾联合移植治疗糖病合并糖尿病肾病的疗效。方法 回顾分析近期施行的6例胰、肾联合移植手术的方法、疗效及并发症的防治。结果 6例患者分别于移植胰腺恢复血液循环后23h、第9d、17h、19h、第5d及1．5h停用外源性胰岛素,移植肾功能于术后第2－4d恢复正常;术后并发症有排斥反应和血尿,其中1例术后5d发生加速性排斥反应,抗排斥治疗无效,于术后11d切除移植胰、肾,其余5例均痊愈出院。结论 胰、肾联合移植是治疗胰岛素依赖型糖尿病及达到胰岛素依赖期的非胰岛素依赖型糖尿病合并糖尿病合并糖尿病肾病的有效方法;加强围手术期管理术后减少各种并发症、取得良好疗效的有效措施。     

Preserved Endocrine Function in a Pancreas Transplant Recipient with Pancreatic Panniculitis and Antibody‐Mediated Rejection

Pancreas transplantation is an effective treatment option for patients with complicated diabetes mellitus. Pancreas allograft recipients are followed with laboratory markers such as serum amylase, lipase and glucose levels. Hyperglycemia may indicate severe acute rejection and has recently been associated with antibody‐mediated (humoral) rejection. In this report, we describe a unique case of a pancreas‐after‐kidney (PAK) transplant recipient with the rare presentation of pancreatic panniculitis, biopsy‐proven severe acute cellular and antibody‐mediated pancreas allograft rejection and surprisingly well‐preserved endocrine function despite treatment with high dose steroids. We discuss the clinicopathologic features of antibody‐mediated pancreas rejection, including the importance of correlating pancreas allograft biopsy, C4d staining and donor specific antibodies, to diagnose antibody‐mediated rejection and initiate the correct treatment.     

Exocrine drainage into the duodenum: a novel technique for pancreas transplantation.

Simultaneous pancreas-kidney transplantation is the treatment of choice for patients suffering from type 1 diabetes mellitus and end-stage renal failure secondary to diabetic nephropathy. Until 1995, about 90% of pancreas transplantations were performed with exocrine drainage into the bladder. Since then the proportion of pancreas transplants with enteric drainage increased steadily because of frequency of complications and long-term disadvantages of bladder drainage. However, the use of enteric drainage removes the opportunity to monitor pancreatic allograft function either by measuring urinary amylase or by carrying out biopsy via cystoscopy. We report a new technique of exocrine pancreatic drainage into the recipient duodenum. This modification places the pancreas graft including the duodenal anastomosis in a retroperitoneal location and, importantly, allows easy graft monitoring via gastroscopy.     

Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Kidney-pancreas transplantation for diabetic nephropathy

Pancreas transplantation is being performed with increasing frequency and increasing technical success. The availability of new immunosuppressant agents has been associated with a reduction in the previously high rates of allograft rejection in recipients of simultaneous pancreas-kidney transplants. These lower rejection rates have, in turn, led to changes in surgical techniques and a resurgence of interest in isolated pancreas transplantation--either in nonuremic patients or, more commonly, in patients who have already received a prior kidney transplant. Pancreas transplantation has emerged as an important option for the management of patients with type I diabetes mellitus and diabetic nephropathy.     

Evolution of pancreas transplant surgery

Background: Type 1 diabetes mellitus is a chronic condition often leading to disabling complications including retinopathy, neuropathy and cardiovascular disease which can be modified by intensive treatment with insulin. Such treatment, however, is associated with a restrictive lifestyle and risk of hypoglycaemic morbidity and mortality. Methods: This review examines the role of pancreas transplantation in patients with Type 1 diabetes mellitus. Results: Pancreas transplantation is currently the only proven option to achieve long‐term insulin independence, resulting in an improvement or stabilization of those diabetic related complications. The hazards of pancreas transplantation as a major operation are well known. Balancing the risks of a surgical procedure, with the benefits of restoring normoglycaemia remains an important task for the pancreas transplant surgeon. Pancreas transplantation is not an emergency operation to treat poorly managed and non‐compliant patients with debilitating complications. It is a highly specialized procedure which has evolved both in terms of the surgical technique, patient selection and assessment. Conclusion: Pancreas transplantation has emerged as the single most effective way to achieve normal glucose homeostasis in patients with Type 1 diabetes mellitus.     

Simultaneous pancreas-kidney transplantation: portal versus systemic venous drainage of the pancreas allografts

Simultaneous pancreas-kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end-stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group=17) received SPK transplantation with systemic venous drainage, and the second group (PV group=17) received pancreas allograft with portal drainage. A Roux-en-Y loop was performed in all the patients. Patient follow-up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.     

胰肾联合移植治疗Ⅰ型糖尿病合并终末期肾病

目的 探讨胰肾联合移植治疗Ⅰ型糖尿病合并终末期肾病的临床效果。方法 ８例Ⅰ型糖尿病合并终末期肾病的患者接受胰肾联合移植,平均年龄４３．４６岁,２例合并视网膜病变,双目失明,病史２～２２年。胰腺移植于右髂窝,胰腺外分泌经膀胱引流,肾脏移植于左髂窝。免疫抑制方案开始四联用药,以后三联用药继续治疗。结果 ８例虱其中７例术后即不需要应用胰岛素,空腹血糖可维持在正常范围,１例术后应用胰岛素４０ｄ后停用。１例     

Pancreas transplantation: a survey on indications, surgical techniques, immunosuppression, complications and outcome

Since its introduction in 1966, pancreas transplantation has undergone considerable progress. Refinements in surgical technique, better organ preservation solutions, and more potent immunosuppressive therapies have improved patient and graft-survival rates dramatically. Survival rates for patient and pancreas at 1 year approach 95 and 83 %, resp., for simultaneous pancreas and kidney transplantation, and 97 and 78 %, resp., for pancreas alone. US pancreas graft and patient survival rates do not significantly differ from the results of the European centers. However, there is still a hesitant acceptance of combined pancreas-kidney transplantation in Germany. Combined pancreas-kidney transplantation is nowadays the treatment of choice in carefully selected patients with type 1 insulin-dependent diabetes mellitus and end-stage renal failure. Many US centers even advocate combined transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation significantly improves quality of life and provides excellent long-term glycemic control which halts or even ameliorates secondary diabetic complications such as microangiopathy and neuropathy. In addition, there is increasing evidence that successful pancreas transplantation significantly prolongs patient survival mainly by a reduction of cardiovascular-related mortality. Current 10-year patient survival rate after SPK exceeds 70 %. For diabetics with end-stage renal disease there is no alternative treatment available with comparable live expectancy. However, morbidity and mortality after SPK is still higher than for kidney transplantation alone in the first year. Outcome of isolated pancreas transplantation is also improving but this technique is still restricted to non-uremic patients with severe diabetic complications or with brittle diabetes and severe impairment of quality of life.     

Pancreatic Transplantation

Pancreas transplantation is the only treatment of Type I diabetes that consistently establishes an insulin-independent, normoglycemic state. Currently long-term insulin-independence is achieved in > 80% of recipients of pancreas grafts placed simultaneous with the kidney and in > 70% of recipients of a pancreas after a kidney and non-uremic recipients of a pancreas alone. The penalty is immunosuppression, already obligatory for a kidney recipient, but the benefits are improved quality of life and the effect that perfect control of glycemia can have on secondary complications of diabetes.     

One Hundred Pancreas Transplants Performed in a Brazilian Institution

After decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for selected patients with type 1 diabetes mellitus. Between January 2001 and January 2008, 100 patients underwent pancreatic transplantation at our center: 88 simultaneous pancreas-kidney transplantation and 12 pancreas transplantations alone. Pancreas graft management of the exocrine drainage technique involved enteric drainage in 8 (all simultaneous pancreas-kidney) and the bladder in 92 cases. The recipient systemic venous system was used for the pancreas graft venous effluent in all cases. Our overall results have shown that the number of functioning pancreatic grafts was 64 of 100. Graft losses were: rejection (n = 8), venous thrombosis (n = 9), arterial thrombosis (n = 1), or surgical complications such as anastomotic leak (n = 3), perigraft infection (n = 10), pancreatitis of the graft (n = 5). Most cases of pancreatitis (80%) had preservation times exceeding 18 hours. Despite surgical and immunosuppressive complications, our impression was that pancreas transplantation was a highly effective therapy for diabetes mellitus. After 7 years of the program and 100 transplantations, we believe that there is a major role for transplantation in diabetes management.