Experience in human segmental pancreas transplantation

Pancreas transplantation in the United Kingdom was initiated just over a decade ago and interest further developed with the introduction of ductal injection techniques and cyclosporin. However, graft losses associated with technical problems remain a significant problem, and experiences over the last year with other units initiating programs suggest progress continues to be slow.

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Resumen El transplante pancreático fué iniciado en el Reino Unido hace exactamente una década mediante el transplante de la totalidad del páncreas y del duodeno; este procedimiento resultaba en complicaciones mayores tales como sepsis, escape de las anastomosis y trombosis. La introducción de la técnica de inyección ductal y de la ciclosporina dió origen a nuestro estudio piloto de transplante de páncreas en humanos. Este informe presenta nuestra experiencia con el programa de transplante segmentario de páncreas combinado con transplante renal.Nuestra técnica consiste en el transplante renal cadavérico simultáneo con el transplante pancreático segmentario intraperitoneal sobre los vasos ilíacos externos, con obliteración ductal por medio de la inyección de un polímero natural y altamente purificado del Latex (polisopreno). La inmunosupresión se realiza con ciclosporina (15 mg/kg) y prednisolona (20 mg/ diarios). Solo uno de los 10 primero transplantes segmentarios ha muerto por un infarto miocárdico agudo que ocurrió 35 días después del transplante, cuando tanto el riñon como el páncreas transplantados se encontraban funcionando. Todos los transplantes segmentarios exhibieron función inicial que permitió descontinuar la insulina exógena, pero dos transplantes perdieron su función dentro de los primero 7 días y otros dos fallaron en el curso de las primeras 6 semanas. Así, de ocho transplantes exitosamente establecidos desde el punto de vista técnico, 4 han funcionado por más de un año, y dos de ellos se encuentran funcionando dos años después del transplante. De nueve pacientes que sobreviven entre 4 y 28 meses después del transplante, solo un alotransplante renal se ha perdido por rechazo vascular irreversible; los otros ocho funcionan satisfactoriamente, aun cuando dos presentan evidencia histológica de rechazo vascular.El hecho de que continuemos perdiendo entre el 15 y el 20% de los transplantes segmentarios en la fase inmediata, a los dos o tres días del procedimiento por preservación inadecuada o por trombosis vascular es indicativo de lo inadecuado de nuestra técnica; sin embargo, la causa de la falla después de este período inicial es difícil de determinar. En conclusión, las pérdidas de los transplantes pancreáticos asociados a factores de orden técnico siguen siendo un problema significativo y las experiencias del último año junto con las de otras unidades que han iniciado programas de transplante sugieren que el progreso continua siendo lento.

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Résumé Les premières transplantations pancréatiques au Royaume-Uni remontent à un peu plus de 10 ans; elles ont bénéficié d'un intérêt accru avec l'avénement des méthodes d'occlusion canalaire et la cyclosporine. Cependant, les échecs de greffes dus à des raisons techniques constituent toujours un obstacle majeur et l'expérience acquise l'année dernière avec d'autres groupes impliqués dans de nouveaux protocoles laisse à penser que les progrès dans ce domaine restent lents.

     

Experience with 53 portal–duodenal drained solitary pancreas transplants

Systemic–enteric drainage is currently the most common technique for pancreas transplantation (PT). A novel alternative technique, portal–duodenal drainage (PDD), has potential physiological benefits and provides improved monitoring of the pancreatic graft. The current study describes 53 solitary PT procedures (43 pancreas after kidney and 10 pancreas transplant alone) using the PDD technique over the last three yr. This method resulted in one‐yr patient survival at 96% and 83% graft survival. There were five cases (9.4%) of thrombosis, in which transplantectomy and two‐layer closure of the native duodenum were performed. No fistulas were observed. Here, we demonstrate that the PDD technique in PT was as safe and effective as current techniques in clinical use.     

Cardiovascular risk factors in diabetic patients with renal transplants

There is a progressive increase in cardiovascular events post-renal transplantation and diabetes mellitus (DM) is one of the major cardiovascular risk factors. The objective of this study was to analyze the prevalence of cardiovascular risk factors and nonfatal cardiovascular events among renal transplant recipients, according to the status of their carbohydrate metabolism. We studied 214 renal transplant recipients, among whom 18% diabetic and 82% were nondiabetic. The 16% prevalence of cardiovascular events were higher among the posttransplantation DM (PTDM) group (33%) compared with the other groups, 19% in pre-renal transplantation DM, 17% in altered baseline glycemia, and 13% in normal patients. Diabetic renal transplant recipients showed a greater prevalence of pretransplantation ischemic cardiopathy when they were older and had a higher pretransplantation body mass index (BMI) a heavier smoking habit, significantly increased microinflammation markers, and a greater need for antihypertensive and hypolipidemic treatment. Renal transplant recipients with altered baseline glycemia show greater BMI after transplantation, as well as higher Hb1Ac than patients with normoglycemia.     

Pancreatitis in childhood. Experience with 49 patients.

Pancreatitis in children is not common but can be associated with severe morbidity rates. We have treated 49 children with pancreatitis over the past 12 years ranging in age from 1 month to 18 years. One third of the patients had biliary tract disease as an etiology, with nearly half of these being related to underlying hematologic disease, usually sickle cell anemia. Another third of the pancreatitis was due to trauma, and one third of these were related to child abuse. Other etiologies were systemic disease (6 patients), congenital anomalies (8 patients), and idiopathic (3 cases). Eighty-two per cent of the patients presented with abdominal pain, but four children, all less than 4 years old, presented with an abdominal mass. Twenty-nine patients required 33 operations for pancreatitis. Fifteen of the 16 patients with biliary tract disease and all patients with congenital anomalies required operation. Six of the 16 patients with trauma required operation and none of those with systemic disease. As in adults ultrasonographic examination and CT scan are most important in the diagnosis; medical treatment consists of intravenous (I.V.) fluids, nasogastric suction, and total parenteral nutrition (TPN), and risk factors can help predict the severity of the disease while amylase alone is not related to severity. Different from adults, in children an etiology can usually be determined. The common etiologies, biliary tract disease, trauma, and congenital anomalies frequently require operation.     

Living-related donor transplants should be performed with caution in patients with focal segmental glomerulosclerosis

The success rates of living-related donor (LRD) transplants are clearly superior to those obtained with cadaver donors. However, caution should be exercised when considering LRD transplantation for a condition which has an increased chance of recurring after transplantation and causing ultimate graft failure. The recurrence rate of focal segmental glomerulosclerosis (FSGS) in the allograft is 20%–40%, with graft failure resulting in 40%–50% of these cases. However, these figures may be an underestimation of the true rate of recurrence of FSGS. Once a first transplant fails due to recurrent disease, the risk of recurrence in the second transplant approaches 80%. Subgroups of patients at high risk for recurrence have been identified. In patients not at high risk for recurrent FSGS, the use of a LRD should be considered, provided that the donor and recipient and their families have been informed that the disease may recur and lead to graft failure. In patients at high risk for recurrence, a LRD transplant should be avoided. Hopefully, future development of a simple and reliable test to predict the likelihood of recurrence will enable us to counsel and advise our patients with FSGS about the wisdom or dangers of proceeding with a LRD transplant.     

Over 500 solitary pancreas transplants in nonuremic patients with brittle diabetes mellitus

BACKGROUND: A pancreas transplant alone (PTA) in a nonuremic patient with brittle diabetes mellitus remains a rare procedure because the tradeoff for insulin independence is lifelong immunosuppression. METHODS: Herein we report our results at the University of Minnesota of 513 PTAs from December 17, 1966, through December 31, 2006. Of these recipients, 87% had previously experienced hypoglycemic unawareness and 23% experienced coma and/or seizures. These transplants spanned four immunosuppressive eras: pre-cyclosporine A (pre-CsA) era (16%), CsA era (23%), tacrolimus (TAC) era (47%), and calcineurin-inhibitor (CNI)-free era (14%). RESULTS: The overall patient survival rate at 1 year posttransplant was about 95%; at 5 years, it was 90%. The pancreas graft survival rate at 1 year increased significantly from the pre-CsA era (31%) to the TAC era (75%), thanks to a significant decline in immunologic and technical failures. The CNI-free protocol, because of its high infection and hematologic infection rate, did not further improve outcome. Risk factors for subsequent kidney failure (13% at 5 years posttransplant) were serum creatinine levels>1.5 mg/dl at the time of the pancreas transplant and recipient age<30 years. CONCLUSIONS: A technically successful PTA is currently the only treatment option that allows nonuremic patients with brittle diabetes to become insulin-independent in the long term.     

Outcomes of pancreas transplants for patients with type 2 diabetes mellitus

BACKGROUND: The objective of this study was to examine how effectively pancreas transplants provide long-term glucose control in patients with type 2 diabetes mellitus (DM). We used guidelines from the American Diabetes Association (ADA) and the World Health Organization (WHO) to appropriately classify recipients with type 2 DM (vs. type 1 DM). RESULTS: From 1994 through 2002, a total of 17 patients with type 2 DM underwent a pancreas transplant at our center. Mean recipient age was 52.5 yr. The mean age at diabetes onset was 35.7 yr; mean duration, 16.8 yr. Most recipients had one or more secondary complications related to their diabetes: retinopathy (94%), neuropathy (76%), or nephropathy (65%). At the time of their transplant, three (18%) were on oral hypoglycemic agents alone and 14 (82%) were on insulin therapy. Of the 17 transplants, seven (41%) were a simultaneous pancreas-kidney transplant (SPK); four (24%), pancreas after kidney transplant (PAK); and six (35%), pancreas transplant alone (PTA). One recipient died during the perioperative period because of aspiration. The other 16 recipients became euglycemic post-transplant and had a functional graft at 1 yr post-transplant (patient and graft survival rates, 94%). Now, with a mean follow-up of 4.3 yr post-transplant, the patient survival rate is 71%. The four additional deaths were because of sepsis (n = 2), suicide (n = 1), and unknown cause (n = 1). All four of these recipients were insulin-independent at the time of death, although one was on an oral hypoglycemic agent. Of the 12 recipients currently alive, 11 remain euglycemic without requiring insulin therapy or oral hypoglycemic agents; one began insulin therapy 1.2 yr post-transplant (current daily dose, 60 units). CONCLUSION: These findings suggest that pancreas transplants can provide excellent glucose control in recipients with type 2 DM. All 16 (94%) of our recipients whose transplant was technically successful were rendered euglycemic. Long-term results were comparable with those seen in transplant recipients with type 1 DM.     

Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients--a two-year follow-up

We have investigated the metabolic effects of segmental (neoprene-injected) pancreas transplantation versus whole (enteric-diverted) pancreas transplantation. Seventeen uremic insulin-dependent diabetes mellitus (IDDM) patients received a simultaneous pancreaticorenal transplant: in a prospective, randomized study, 9 patients received a segmental neoprene-injected graft (group A) while 8 patients received a total pancreaticoduodenal graft, with enteric diversion (group B). The immunosuppressive therapy was based on ALG, CsA, azathioprine, and steroids. Three months after surgery, patients were submitted to the following metabolic investigation: i.v. and oral glucose tolerance tests, Hba1, i.v. arginine test, and a 24-hr metabolic profile. The OGTT, HbA1, and metabolic profile were repeated 12 and 24 months after transplantation. At 3 months after transplantation, the OGTT showed delayed insulin secretion and higher blood glucose levels in group A. Serum insulin levels after IVGTT or arginine were higher in group B than in group A. OGTT at 12 and 24 months were unchanged in group B, while in group A a higher incidence of impaired glucose tolerance (IGT) and diabetes mellitus response were observed. HbA1 and blood glucose levels during the 24-hr profile showed good metabolic control in both groups at 3, 12, and 24 months. We can conclude that both the segmental and total pancreas transplantation restore a good metabolic control in IDDM patients, though a higher incidence of IGT and DM responses were observed after OGTT in the patients receiving a segmental graft. These abnormalities do not seem to interfere with metabolic control in everyday life. These results seem to be the consequence of the different B cell masses transplanted with these two techniques.     

Quality of life in diabetic recipients of kidney transplants is better with the addition of the pancreas

The present study is an evaluation of the quality of life of 32 patients following successful pancreatic transplantation. These patients were studied at from 6 months to 5 years post-transplantation. Over one-half of them were beyond the 21/2-yr mark. A questionnaire was developed that focused on symptoms of neuropathy, enteropathy, and retinopathy. All of the patients evaluated had completely normal carbohydrate metabolism, as evidenced by normal fasting blood sugars and hemoglobin A1C levels. Twenty-one of the 32 patients had symptomatic neuropathy pre-operatively, and 11 of these reported substantial subjective improvement. Eight remained unchanged and 2 became worse. Twenty-four patients had symptoms of enteropathy and 23 noted improvement post-transplantation. Retinopathy symptoms were not improved, but there was a suggestion that after 3 or 31/2 yr progression did not occur as rapidly as earlier. Virtually all of the patients had mood improvements and considerably less fatigue. We have determined that the risk of the procedure when receiving simultaneous renal and pancreas grafts is not significantly greater than that associated with a kidney transplant alone. Patients who are not uremic, either those with a successful kidney graft or those preuremic patients, are better candidates if symptoms are present. The risk of immunosuppression is insignificant in those patients who already have a successful renal transplant and are already on immunosuppressant drugs. Pancreatic transplantation can substantially improve the quality of life in diabetic patients, and should be considered as a therapeutic measure.     

急性重症胆管炎49例治疗体会

目的探讨急性重症胆管炎的临床特点及其治疗方法。方法对我院1992年1月～2007年3月收治的急性重症胆管炎49例的临床资料进行回顾性分析。结果本组行急诊手术治疗37例,非手术治疗12例。死亡5例。其中,死于较复杂的手术术后3例,死于非手术治疗2例。死亡原因均为脏器功能衰竭。余者均治愈。结论急性重症胆管炎应首选手术治疗。损伤控制性手术理念有助于选择该病的最佳治疗方法。