Progress in experimental porcine small-bowel transplantation

Studies in large animals are needed to overcome technical complications, allograft rejection, and graft-vs-host disease, which are major problems that prevent clinical application of small-bowel transplantation. The small bowel was allografted heterotopically or orthotopically into 30 pigs with the use of cyclosporine, prednisone, and azathioprine. When cyclosporine was given orally to heterotopically transplantation recipients, rejection was frequent, and graft-vs-host disease caused one death. After 30 days of intravenous cyclosporine followed by oral administration, no rejection occurred. Graft-vs-host disease was mild or absent, and there were some long-term survivors. Technical failures were relatively infrequent, but death from sepsis, eg, intra-abdominal abscess, occurred in 17% (5/30). Anastomoses of donor superior mesenteric vein to recipient portal vein offered no advantages over systemic venous drainage. Although the high cyclosporine levels used would be intolerable in humans, these results indicate that successful small-bowel transplantation can be achieved with adequate immunosuppression in a large animal.     

Living-donor pancreas and small-bowel transplantation

Background: In contrast to renal and liver transplantation, only a limited number of pancreas and intestinal live-donor transplants have so far been reported. Patients: The vast majority of live segmental pancreas transplants have been performed at the University of Minnesota. From 1979 to 1993, a total of 78 solitary pancreas transplants – 28 after kidney and 49 pancreas transplants alone – were performed and, from 1994 to August 1999, 27 simultaneous pancreas/kidney transplants. For the first intestinal transplant, a segment of ileum from the mother was used in Boston in 1964. In 1970, 170 cm of jejuno-ileum from a human leukocyte antigen (HLA)- identical sister was removed and transplanted in New York. In 1988, an intestinal transplant from a haplotype-identical sister was performed at Kiel University, Germany. In the 1990s, a few more intestinal transplants from live donors were reported to the registry. Results: No death occurred among pancreas or intestinal donors. Altogether, seven pancreas donors required splenectomy and several donors required drainage of abscesses or fluid collections. Three of the 78 pancreas donors and at least two of the 27 pancreas/kidney donors required insulin post-donation. Twenty-seven of the solitary segmental pancreas transplants failed for technical reasons. Graft survival of technically successful pancreas transplants was 68% after 1 year and 38% after 10 years. Patient and renal allograft survival of combined kidney/pancreas transplants after 1 year was 100%, while 1-year pancreas survival was 84%. The first recipient of a live-donor intestinal transplant died only 12 h after surgery. The second case lived for 79 days and was able to eat for 6 weeks. A patient transplanted in 1988 lived for 4 years mainly on oral nutrition. Many of the live-donor intestinal transplants carried out in the 1990s became long-term survivors. Conclusion: Pancreas and small-bowel transplantation using organs from live donors is possible in experienced centers, with no donor mortality and excellent survival rates for recipients and grafts. Since abnormal glucose tolerance post-donation cannot be excluded with certainty and since, for the time being, there is no pancreas or small-bowel shortage in Europe, live donation of these organs should be restricted mainly to highly sensitized patients with a cross-match-negative relative or HLA-identical donor-intestinal recipient combinations. Received: 20 October 1999 Accepted: 27 October 1999     

Is rejection a diffuse or localized process in small-bowel transplantation?

Utilization of endoscopy to both visualize and selectively biopsy an intestinal allograft has become the standard for early recognition and treatment of intestinal allograft rejection. Despite the widespread acceptance of the need for selective mucosal biopsies, it has not been shown that the histological features of intestinal allograft rejection are either localized or occur as part of a more diffuse phenomenon within a tubular allograft.To resolve these issues, 88 ileoscopies were performed in 12 small-bowel allograft recipients and mucosal biopsy samples were obtained at 5, 10, and 15 cm, respectively, from the ileal stoma. Each mucosal biopsy was labeled, processed, and evaluated individually for the presence and severity of any evidence for allograft rejection.The data obtained suggest that intestinal allograft rejection is a diffuse process, and biopsies obtained randomly from an ileal graft are likely to demonstrate evidence of allograft rejection when such is present.     

A modified technique for small-bowel transplantation in the rat

The rat model for small-bowel transplantation is becoming increasingly popular. The currently accepted microsurgical technique, however, is complicated by extensive dissection in the donor rat vascular system requiring a great deal of manipulation of the vessels themselves, with consequent complications of thrombosis and vascular injury. We describe a procedure for small-bowel transplantation in the rat that simplifies the currently accepted technique. The peripheral portion of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is used as the vascular pedicle of the segment of bowel to be transplanted rather than the SMA with an aortic cuff and the portal vein as previously described. The SMA and SMV are anastomosed to recipient aorta and inferior vena cava respectively. The bowel extremities are exteriorized, thus leaving access to the lumen for further studies. All anastomoses are performed with interrupted 10-0 nylon sutures. The procedure was performed in 11 animals. Good revascularization of the transplant was defined as immediate filling of the transplant vasculature with normal (pink) appearing bowel. Eight of the recipients had excellent revascularization. Venous occlusion was the cause of early failure in the remaining three animals. All animals were killed, autopsies performed, and the anastomoses examined. The longest survivors were killed at 7 months. Biopsies were obtained immediately and at daily intervals. Early ultrastructural changes of rejection in the transplanted bowel were studied by electron microscopy. Changes in the microvasculature were seen early after transplantation. Immunologic changes were apparent only later in the course of rejection. We conclude that this technique is successful in achieving functional small-bowel transplants in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expedited handling of transplantation biopsies

The workload from the rapid handling of transplantation biopsies is increasing in many pathology laboratories. By using a novel tissue processor (the MED'LASS Paraffinator, F.R.G.) that employs continuously distilled acetone for tissue dehydration, it is possible to prepare high-quality hematoxylin-and-eosin sections in under 90 min. The slides are comparable to those processed by traditional methods and yield excellent results with special stains and immunohistochemical techniques.     

首例临床异体全小肠移植的围手术期处理

本文报告国内道例小肠移植的临床经过的转手术期处理。供体为男性，２８岁。受者为女性，３１岁，因慢性小肠结肠炎、反复肠梗阻及短肠综合征而接受小肠移植。移植肠长２５０ｃｍ，热缺血６分钟，冷缺血９小时４５分钟，行一期原位移植，未端回肠１０ｃｍ旷置作为观察窗。免疫抑制方案为环孢素Ａ、雷公藤、甲基强的松龙联合用药。受者术后经过顺利，现已９８天，移植肠功能在恢复中。     

Interest of screening biopsies in renal transplantation

Renal biopsy is an invaluable tool used for the monitoring of grafts and the management of their survival. Since 1993, thanks to research on biopsy tissues that enabled to distinguish the different types of rejection and to find markers of reversible or irreversible rejection, a classification of renal lesions has been established to achieve the regularly updated Banff classification. The last in date (2005) has defined the antibody-mediated chronic rejection, forsaken the term "chronic allograft nephropathy" and described a new class with interstitial fibrosis and tubular atrophy (IF/TA). Systematic or screening biopsies allow revealing infraclinical rejection lesions before any renal function degradation, better understanding of allograft nephropathy pathophysiology, confirming the diagnostic, but also displaying other more specific lesions that could benefit from a treatment. However, the interest of biopsies is limited by interpretation problems and risks for the patient.     

Protocol biopsies after kidney transplantation

Numerous studies have investigated features of allograft injury in renal biopsies obtained in stable kidney transplants. Evaluation of protocol biopsies has revealed a considerably high prevalence of subclinical acute rejection (SAR) and chronic allograft nephropathy (CAN) already in early phases after transplantation. The meanwhile well-established association of SAR and CAN in protocol biopsy with long-term allograft failure and the finding of superior allograft outcome after treatment of SAR in a randomized prospective study may point to clinical relevance of this procedure. In this review, potential benefits and risks associated with kidney allograft biopsy in stable renal transplant recipients are discussed.     

In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation

In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.     

Experimental small-bowel transplantation: alternative strategies for graft prolongation

Alternative combined immunosuppressive therapy was tested in canine orthotopic bowel transplantation. Despite sporadic long-term survival, cyclosporine is still questionably effective. Triple-drug therapy (cyclosporine, azathioprine, and prednisone) combined with antilymphocyte serum or with a short segment graft was effective in reducing the early postoperative mortality due to acute rejection but did not alter the long-term survival rate. There was no apparent relationship between the serum cyclosporine levels and survival. The long-term survivors (longer than 100 days) maintained relatively low serum trough levels of cyclosporine. These suggest that orthotopic bowel transplantation in the dog, and probably in the human as well, requires improved immunosuppressive regimens.     

原位心脏移植一例报告

给１例终末期扩张型心肌病患者施行了原位心脏移植术。供心总缺血时间３小时零２分钟，术中及术后顺利。术后采和环孢素Ａ、强的松及硫唑嘌呤三联免疫抑制治疗，术后第４天和第１７天发生排斥反应，经冲击逆转，患者至今存活已逾１年，未发生严重并发症，心功能由术前的Ⅳ级改善为Ⅱ级。认为供心心肌的保护、免疫抑制剂合理应用与毒副作用的防治以及感染的预防是移植成功的基础，强调在初开展这项工作的单位多学科密切配合，作好充分