Donor risk index does not predict graft survival after pancreas transplantation in Brazil.

BACKGROUND: Pancreas donor risk index (DRI) was developed by using large multicenter American data to predict the risk of adverse outcomes in pancreas transplantation based on donor and technical/logistical characteristics. AIM: The goal of this study was to evaluate the usefulness of the DRI in predicting graft survival in a Brazilian population of pancreas transplant recipients. METHOD: We conducted a retrospective analysis of the 570 procedures performed by the same surgical team between 1996 and 2011. Because of the lack of sufficient data for the calculation of DRI values, only 154 cases were studied (27%), of which 105 underwent simultaneous pancreas-kidney transplantation, 33 underwent pancreas after kidney transplantation, and 16 underwent pancreas transplantation alone. Donor cause of death was classified as cerebrovascular accident (CVA) and non-CVA. Graft origin was divided into three groups: local, if the graft was obtained in the metropolitan area of the city of São Paulo; regional, if collected in other cities of the state of São Paulo; and national, if obtained outside the state. RESULTS: Logistic regression analysis did not find a statistically significant association between DRI values and 1-year graft survival (odds ratio = 0.676; 95% confidence interval 0.152 to 3.014; P = .60). One-year graft survival calculated by the Kaplan-Meier method was 89.8% in transplants with DRI ≤ 1, 77.9% in those with 1 < DRI < 1.5, and 93.3% in those with DRI ≥ 1.5 (P = .106). CONCLUSION: The pancreas DRI model did not prove effective in predicting pancreas graft survival in a Brazilian sample of recipients.

Aortic clamping in pancreas transplantation: is there any harm to the transplanted kidney graft?

INTRODUCTION: Some special situations may require aortic clamping during pancreas transplantation (PT). The most important problem is ischemic injury to a previous transplanted kidney. We sought to demonstrate experience with aortic clamping in PT without special kidney allograft protection measures and its impact on kidney function. METHODS: Retrospective study that analyzed 6 patients who underwent PT (5 pancreas after kidney and 1 simultaneous pancreas-kidney) with aortic clamping. In all cases, the pancreas graft was placed on the right with retrocolic portal-enteric drainage. Serum creatinine was evaluated pre- and posttransplantation. RESULTS: The average clamping time was 19 minutes. The mean serum creatinine was 1.1, 1.15, 0.95, and 1.0, respectively, at pre and postoperative days 1 and 7 and at hospital discharge. Patient, kidney, and pancreatic graft survivals were 100%, 100%, and 83%, respectively. CONCLUSION: The need for aortic clamping in selected cases of PT did not seem to affect the transplanted kidney, even without protective measures, provided that the ischemic time was short.

Single-balloon enteroscopy for treating Roux-en-Y choledochojejunostomy stenosis after liver transplantation: a case report.

Endoscopic treatment of biliary tract complications after Roux-en-Y surgery is still a challenge. With balloon enteroscopy, we can reach previously inaccessible areas changing the management of biliopancreatic diseases in patients with surgically altered anatomy. We report a case of single-balloon enteroscopy plus endoscopic retrograde cholangiopancreatography for the treatment of a pinpoint stricture in a hepaticojejunal anastomosis after liver transplantation.

Use of enteroscopy for treating pancreatitis in a pancreas and kidney transplantation patient with Roux-en-Y portoenteric derivation--a case report.

In pancreas and kidney transplantations, the donor duodenum and pancreas are frequently anastomosed to the jejunum to allow exocrine drainage by creation of a Roux-en-Y jejunal loop. In this situation, those organs are relatively inaccessible using standard endoscopes. We present a case of the use of single-balloon enteroscopy in the treatment of cronic pancreatitis in the donor pancreas.

Liver transplantation in bearers of hepatitis B associated or not with delta hepatitis in the age of the new antiviral drugs: is hyperimmune globulin still necessary?

Hepatitis B (HBV) is a public health problem worldwide; one-third of the population has already been in contact with HBV, and 350 million people are chronic carriers of virus. The appearance of hyperimmune gamma globulin and antiviral drugs has allowed that group to undergone hepatic transplantation, achieving satisfactory results to prevent a relapse. But the use of hyperimmune gamma globulin has an extremely high cost, and combined therapies with new antiviral drugs seem to be a therapeutic alternative. We analyzed 21 patients with hepatitis B associated or not with Delta hepatitis over a mean follow-up period of 19.5 months, concluding that use of only nucleotide analogues has sufficient to achieve satisfactory results.

Analysis of reoperations and their impact on the results of pancreas transplantation.

BACKGROUND: Many factors, including the advances in surgical techniques and immunosuppression, have been brought significant improvement to graft and patient survivals of patients undergoing pancreatic transplantations. However, one third of these patients require reoperations (ReOps). PURPOSE: We sought to evaluate the distribution of ReOps in the early or late postoperative period and analyze their impact on patient and graft survivals. PATIENTS AND METHODS: This unicenter, retrospective study was performed using data from 182 patient charts after pancreas transplantation from January 2000 through December 2007. RESULTS: We performed 88 ReOps on 73 patients; 43 early and 41 late operations. The simultaneous pancreas-kidney transplantation group showed a greater incidence of premature ReOps. The group undergoing early ReOp showed a lower survival rate (87.2%) compared with the nonoperated group, but a similar survival rate (97.5%) to the late ReOp group. In relation to the survival of pancreatic grafts after 1 year, the early ReOp group showed inferior survival to the late ReOp group, both of which were significantly worse results then those of the group without ReOp. CONCLUSION: ReOps were related to the success of the procedure. When they were performed in the first 3 months they had a negative impact on patient and graft survival.

Simultaneous pancreas-kidney transplantation in a human immunodeficiency virus-positive recipient: a case report.

BACKGROUND: After the development of highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV), there has been increased interest in organ transplantation for this selected population. There is a lack of reports about pancreas transplant in HIV+ recipients. CASE REPORT: We report the case of a 43-year-old HIV+ man who presented with type 1 diabetes for 25 years and end-stage-renal disease. He underwent dialysis therapy for the prior 3 years. His CD4 count was 830 cells/mL and a negative viral load was achieved after 3 months of antiretroviral therapy. His nutritional status was favorable; no opportunistic infections had occurred. A simultaneous pancreas-kidney transplantation (SPKT) was performed from a 19-year-old deceased trauma victim. Pancreas implantation was enteric-portal drainage. No induction immunosuppression was used, but rather tacrolimus, sodium mycophenolate, and steroids. In the postoperative period, there was a delayed kidney graft function requiring hemodialysis for 14 days. On postoperative day 11, a kidney biopsy specimen showed mild rejection, which was successfully treated with steroids. The patient was discharged after 22 days; he was normoglycemic and insulin-independent with a serum creatinine value of 1.9 mg/dL. Currently, his outcome has been uneventful, without a readmission or opportunistic infections. After 5 months postoperation, the viral load is negative and the CD4 count is 460 cells/mL. The current serum creatinine level is 1.1 mg/dL; no insulin has been required. COMMENT: HIV has been considered to be an absolute contraindication to organ transplantation, because of the infection risk due to severe immunosuppression, to interactions between antiretroviral and immunosuppressive drugs, and to reluctance to offer an organ to a terminal patient. However, transplants in HIV+ patients have shown good results, when a patient has an acceptable CD4 level, a low viral load, and minimal antiretroviral therapy.

Prolactin-induced changes in protein expression in human pancreatic islets.

Ex vivo islet cell culture prior to transplantation appears as an attractive alternative for treatment of type 1 diabetes. Previous results from our laboratory have demonstrated beneficial effects of human prolactin (rhPRL) treatment on human islet primary cultures. In order to probe into the molecular events involved in the intracellular action of rhPRL in these cells, we set out to identify proteins with altered expression levels upon rhPRL cell treatment, using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). An average of 300 different protein spots were detected, 14 of which were modified upon rhPRL treatment (p<0.01), of which 12 were successfully identified using MS and grouped according to their biological functions. In conclusion, our study provides, for the first time, information about proteins that could be critically involved in PRL's action on human pancreatic islets, and facilitate identification of new and specific targets involved in islet cell function and proliferation.

No induction versus anti-IL2R induction therapy in simultaneous kidney pancreas transplantation: a comparative analysis.

UNLABELLED: The optimal immunosuppressive regimen for simultaneous kidney pancreas transplantation (SKPT) is still not established. We conducted a study to compare the safety and efficacy of no induction versus anti-IL-2 receptor induction protocols in SKPT recipients receiving the same maintenance regimen. METHODS: Sixty-three SKPT recipients were divided into two groups: no induction group (n = 42) and anti-IL-2 receptor induction group (n = 21). All patients were maintained on tacrolimus, mycophenolate mofetil, and prednisone. Primary endpoints were 1-year acute rejection incidence and patient and graft survivals. RESULTS: Demographic characteristics were similar between the groups. Acute rejection incidence at 1 year was equal in both groups (28.6%). Kidney and pancreas allograft survival in the no induction group were 78.6% and 76.2%, and in the anti-IL-2R induction group, 81% and 71.4%, respectively (P = NS). Patient survival was also similar: 83.3% in the no induction versus 85.7% in the anti-IL-2R induction group. Deaths due to sepsis were higher in the anti-IL-2R induction group, albeit not significantly. CONCLUSION: The use of a no-induction protocol in SKPT is safe and effective immunosuppression that also reduces transplantation costs.

Pancreas retransplantation: outcomes of 20 cases.

The objective of this paper was to evaluate our initial experience with pancreas retransplantation. From January 26, 1996 to February 2005, 285 pancreas transplantations were performed, including 20 (7%) retransplants. The causes of primary graft loss were graft thrombosis in 11 (55%, 7 venous and 4 arterial); 4 (20%) chronic rejections; 2 (10%) ischemia/reperfusion injury; 1 severe graft pancreatitis; 1 primary nonfunction; and 1 sepsis. Venous drainage was placed in the iliac vessels in 14 (70%), vena cava in 5 (25%), and portal drainage in 1. The exocrine drainage was vesical in 16 (80%) and enteric in 4 (20%). In 14 cases (70%), the primary graft was removed before and in 6 (30%) at the time of retransplantation. Immunosuppression was based on antilymphocyte induction, tacrolimus, mycophenolate mofetil, and steroids in all patients. One-year patient and graft survivals were 95% and 85%. In conclusion, pancreas retransplants were feasible with results comparable to a primary pancreas transplantation.

Influence of pancreas transplantation alone on native renal function.

Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) > or = 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were analyzed using Student's t-test (P < or = .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n = 5) or graft loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P < .001). There was also a 39.3% reduction among group 1 subjects (P = .003), including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4% reduction among group 2 (P = .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl < 70 mL/min show a significant risk of worsened renal function.

Diabetes mellitus: new therapeutic approaches to treat an old disease

Diabetes mellitus is a widespread disease whose frequency increases constantly and is expected to reach alarming levels by the year 2025. Introduction of insulin therapy represented a major breakthrough; however, a very strict regimen is required to maintain blood glucose levels within the normal range and to prevent or postpone chronic complications associated with this disease. Frequent hyper- and hypoglycemia seriously affect the quality of life of these patients. Reversion of this situation can only be achieved through whole organ (pancreas) transplant or pancreatic islet transplant, the former being a high-risk surgical procedure, while the latter is a much simpler and may be accomplished in only 20-40 min. The advantages and perspectives of islet cell transplantation will be discussed, in the light of tissue engineering and gene therapy. Ongoing research carried out in our laboratory, aimed at developing clinical cell and molecular therapy protocols for diabetes will also be focused

Enteric conversion after bladder drained pancreas transplantation experience of 14 cases.

The method of exocrine diversion in pancreas allograft continues to be controversial due to the advantages versus disadvantages of bladder versus enteric techniques. Bladder drainage (BD) exposes the patient to urological and metabolic problems that may require conversion to enteric drainage (ED). The purpose of this study was to review our initial experience of conversion from BD to ED for patients who underwent pancreas transplantation originally with bladder diversion. Among 114 pancreas transplantation performed with BD, from January 1996 to April 2003, 60 were simultaneous pancreas-kidney transplantation (SPKT), 35 were pancreas transplantation alone (PA), and 19 were pancreas after kidney transplantations (PAK). Twenty-three (20.2%) cases were excluded due to early death of the patient or the graft, yielding an analyses of 91 patients. Enteric conversion (EC) was performed in 14 (15.4%) patients with a mean follow-up of 15.7 months (range, 3-51 months) after transplantation including 8 (8.8%) SPKT, 4 (4.4%) PAK, and 2 (2.2%) PA. No surgical morbidity or mortality was observed related to EC. All patients had complete resolution of the initial problem with preservation of pancreatic function. EC represents an easy, safe procedure with low morbidity and mortality rates, representing the option of choice for patients with persistent urological or metabolic disturbances.

Glycemic control during pancreas transplantation: continous infusion versus bolus.

Pancreas transplantation is a method to restore endogenous insulin secretion in insulin-dependent diabetic patients. Because glycemia >150 mg/dL may harm pancreatic graft beta cells, early glucose control using insulin administration is recommended during transplantation. The aim of this study was to evaluate the benefits of strict glycemic control during pancreas transplantation by comparing two types of insulin and glucose administration: continuous infusion and bolus. Capillary glucose was measured every 30 minutes after anesthetic induction for pancreas transplantation alone or simultaneously with kidney transplantation. Intravenous regular insulin was administered for values >150 mg/dL or glucose for values <100 mg/dL. The following timepoints were evaluated: anesthetic induction, before pancreatic graft reperfusion, and the first 4 minutes after reperfusion. Pancreatic graft ischemia time was significantly lower in the bolus group (P <.02). Immediately after reperfusion, there was a small increase in glycemia with a decrease in subsequent measurements in both groups. No significant difference in glycemia was observed between the groups at any time. Induction values were greater than all other timepoints in both groups. Glycemic control is important; it was successfully obtained with both methods. The trend to decrease glucose after reperfusion suggest early graft function.

Anesthesia for pancreas transplantation alone or simultaneous with kidney.

Improvements in perioperative care, namely, organ preservation solutions, immunosuppression, and increased experience of surgical, anesthetic, and intensive care teams, have contributed to the success of pancreas transplantation. The objective of this study was to present data on anesthesia for pancreas transplantation alone (PTA) or simultaneous with kidney (SPKT), evaluating crystalloid, albumin and blood component infusions, graft ischemic times, and weights and ages of recipient. We evaluated patients undergoing SPKT (n=73), PTA (n=49), or SPKT with kidney living donor (n=8). Aggressive monitoring and therapy were used to avoid hypoperfusion, optimized with intravenous fluids, vasoative drugs, and correction of metabolic disturbances. Three SPKT patients were not extubated at the end of surgery. There were no other complications related to anesthesia in any patient. Although it is a high-risk surgery, PTA or SPKT is routine in our practice. Adequate perioperative care is important not only for the safety of the procedure but also for graft viability, contributing to a promising long-term treatment of insulin-dependent diabetic patients.

Tratamento da síndrome de Budd-Chiari com trombose de veia cava inferior por anastomose mesoatrial / Treatment of Budd-Chiari syndrome with venous cava thrombosis by mesoatrial shunt

A Síndrome de Budd-Chiari (SBC) é uma doença rara, ocorre com maior frequência nos adultos, não havendo predominância de sexo e é mais comum nos países do leste asiático. Relatamos o tratamento cirúrgico de paciente com SBC e trombose de veia cava. Paciente do sexo masculino, 29 anos, com Síndrome de Budd-Chiari consequente a trombose de veia cava inferior (VCI). Apresentava função hepática preservada, esplenomegalia, gastropatia congestiva com vários episódios de hemorragia digestiva alta e fígado com fibrose. Optou-se por realizar anastomose mesoatrial (AMA). Concluímos que AMA foi eficaz na descompressão hepática e resultou no desaparecimento dos sinais e sintomas da SBC além de ser seguida de melhora das provas de função hepática do paciente num seguimento de 8 meses

Microencapsulation and tissue engineering as an alternative treatment of diabetes

In the 70's, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.

Microencapsulation and tissue engineering as an alternative treatment of diabetes.

In the 70's, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.