Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Outcomes after pancreas retransplantation: is the juice worth the squeeze?

PURPOSE OF REVIEW: Pancreas retransplantations are rarely carried out, and their outcomes are still debatable because of a lack of studies and clinical series on this issue. RECENT FINDINGS: In general, pancreas retransplantations achieve similar or even higher patient survival than primary transplantations; however, it should be noted that this finding may be biased, as only healthier patients are selected for retransplantation. Graft survival in retransplantations is usually lower than that in primary transplantation, but this comparison may also be biased, as most retransplantations are solitary pancreas transplantations (which are known to have lower graft survival), whereas primary transplantations are mostly simultaneous kidney-pancreas transplantations. Technical loss is similar between primary pancreas transplantations and pancreas retransplantations, but the occurrence of surgical complications is greater in the latter. SUMMARY: This review summarizes the literature on pancreas retransplantations, comparing them with primary transplantations, and demonstrates that in selected patients in experienced centres, retransplantation can be a valid and effective option for returning the patient to an insulin-free state.

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.

Over 500 pancreas transplants by a single team in São Paulo, Brazil.

Pancreas transplantation (PT) remains a developing practice in Latin America. From 1996 to 2009, 506 PTs were performed by our team in the following categories: simultaneous pancreas-kidney (SPK), simultaneous deceased donor pancreas and living-donor kidney (SPLK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). Enteric drainage was preferred for SPK and bladder drainage for solitary PT or SPLK. Immunosuppression was with tacrolimus, mycophenolate mofetil, and steroids, and anti-lymphocytic drugs were used to induce solitary PT and SPLK. The series includes 254 SPK, 60 SPLK, 94 PAK, and 98 PTA. The one-yr patient survivals were 82% for SPK, 90% for SPLK, 95% for PTA, and 93% for PAK. The one-yr pancreas graft survivals were 70% for SPK, 86% for SPLK, 86% for PAK, and 77% for PTA. The one-yr kidney graft survivals were 77.5% for SPK and 89% for SPLK. This represents the largest reported PT series in Latin America. Results comparable to those of developed countries were achieved, with the exception of the SPK category. This has led our program to prioritize solitary PT and SPLK.

Pancreas transplantation outside the USA: an update.

PURPOSE OF REVIEW: Due to the extreme lack of an international registry of pancreas transplantation, the purpose of this review was to conduct an extensive collection of data on the activity of pancreas transplantation in non-United States areas. RECENT FINDINGS: Over 10 000 pancreas transplants were collected in non-US areas. These countries together account for annual activity of about 1100 pancreas transplants out of which 85% are simultaneous pancreas-kidney transplants. Europe stands with 6766 pancreas transplantation, followed by Latin America with 1945, Canada with 671, Oceania with 499, Asia with 222 and Africa with five. Adding this activity of pancreas transplantation to the US data, we reach the mark of about 32 000 pancreas transplants performed worldwide and the overall activity roughly 'jumps' to approximately 2300 procedures annually. SUMMARY: From the data collected in this article, it is possible to have a current dimension of the pancreas transplantation activity worldwide. This study should serve as a stimulus for the creation of a single international registry and guide future analysis and protocols in the pancreas transplantation field in different continents.

A machine learning prediction model for waiting time to kidney transplant.

BACKGROUND: Predicting waiting time for a deceased donor kidney transplant can help patients and clinicians to discuss management and contribute to a more efficient use of resources. This study aimed at developing a predictor model to estimate time on a kidney transplant waiting list using a machine learning approach. METHODS: A retrospective cohort study including data of patients registered, between January 1, 2000 and December 31, 2017, in the waiting list of São Paulo State Organ Allocation System (SP-OAS) /Brazil. Data were randomly divided into two groups: 75% for training and 25% for testing. A Cox regression model was fitted with deceased donor transplant as the outcome. Sensitivity analyses were performed using different Cox models. Cox hazard ratios were used to develop the risk-prediction equations. RESULTS: Of 54,055 records retrieved, 48,153 registries were included in the final analysis. During the study period, approximately 1/3 of the patients were transplanted with a deceased donor. The major characteristics associated with changes in the likelihood of transplantation were age, subregion, cPRA, and frequency of HLA-DR, -B and -A. The model developed was able to predict waiting time with good agreement in internal validation (c-index = 0.70). CONCLUSION: The kidney transplant waiting time calculator developed shows good predictive performance and provides information that may be valuable in assisting candidates and their providers. Moreover, it can significantly improve the use of economic resources and the management of patient care before transplant.

Disparity in the access to kidney transplantation for sensitized patients in the state of Sao Paulo-Brazil.

Highly sensitized (HS) patients accumulate on deceased donor kidney transplantation (DDKT) waitlists worldwide due to matching difficulty and inequity of allocation policies. Current situation of HS patients on KT waitlist in Brazil has not been published. All patients enrolled on the KT waitlist of the State of São Paulo from 2002 to 2017 were retrospectively assessed. Patients were divided into eight groups according to their degree of sensitization, PRA of 0%, >0-40%, >40-80%, >80-85%, >85-90%, >90-95%, >95-98% and > 98%. Cumulative incidence curves for transplantation or mortality/removal from waitlist were estimated by competing risk. Among 50,249 waitlisted candidates, 1247 prioritized, 2467 with age < 18 or > 75 years and 4152 submitted to living-donor KT were excluded from the analysis, remaining 42,383 patients. There were 29,664(70%) PRA 0%, 5611(13.2%) PRA > 0-40%, 3442(8.2%) PRA > 40-80%, 507(1.2%) PRA > 80-85%, 564(1.3%) PRA > 85-90%, 825(1.9%) PRA >90-95%, 859(2%) PRA > 95-98% and 911(2.2%) PRA > 98%. There was a progressive increase in the need of prioritization, waiting time for KT or on waitlist and time on dialysis as PRA increased (p < 0.001). Probability of DDKT clearly increased as PRA decreased so that PRA 0% candidates were much more likely to be transplanted compared to PRA > 98% patients(HR:13.02, p < 0.001). Waiting list mortality/removal was higher among PRA > 0-40%(HR1.05,p = 0.03), PRA > 90-95%(HR:1.10,p = 0.05), PRA > 95-98%(HR:1.26,p < 0.001) and PRA > 98%(HR:1.09,p = 0.05) patients compared to PRA zero candidates. HS patients in Sao Paulo-Brazil required greater prioritization due to lack of venous access, longer dialysis and waitlist times, lower probability of DDKT and higher rates of waitlist mortality/removal. We confirmed the disparity of access to KT among HS patients in Sao Paulo-Brazil, indicating the need of new strategies that optimize transplantation for this subcategory of patients.

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil.

INTRODUCTION: Liver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics. METHODS: We reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients' clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups. RESULTS: Almost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795). DISCUSSION: The new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.

Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation.

Antibody-mediated rejection (AMR) requires specific diagnostic tools and treatment and is associated with lower graft survival. We prospectively screened C4d in pancreas (n = 35, in 27 patients) and kidney (n = 33, in 21 patients) for cause biopsies. Serum amylase and lipase, amylasuria, fasting blood glucose (FBG) and 2-h capillary glucose (CG) were also analysed. We found that 27.3% of kidney biopsies and 43% of pancreatic biopsies showed C4d staining (66.7% and 53.3% diffuse in peritubular and interacinar capillaries respectively). Isolated exocrine dysfunction was the main indication for pancreas biopsy (54.3%) and was followed by both exocrine and endocrine dysfunctions (37.1%) and isolated endocrine dysfunction (8.6%). Laboratorial parameters were comparable between T-cell mediated rejection and AMR: amylase 151.5 vs. 149 U/l (P = 0.075), lipase 1120 vs. 1288.5 U/l (P = 0.83), amylasuria variation 46.5 vs. 61% (P = 0.97), FBG 69 vs. 97 mg/dl (P = 0.20) and 2-h CG maximum 149.5 vs. 197.5 mg/dl (P = 0.49) respectively. Amylasuria values after treatment correlated with pancreas allograft loss (P = 0.015). These data suggest that C4d staining should be routinely investigated when pancreas allograft dysfunction is present because of its high detection rate in cases of rejection.

Pancreas transplantation alone in children: a case report.

Pancreas transplantation (PT) is a relatively uncommon therapy for non-uremic type 1 diabetes, as the severity of diabetes must warrant the risk of immunosuppression. In pediatric diabetic patients, who are less likely to display uremia because of the duration of diabetes, there is very little experience with pancreas transplantation alone (PTA). This report describes a 13-yr-old male PTA recipient. This patient was initially diagnosed with type 1 diabetes mellitus at the age of four yr. Following a multidisciplinary evaluation, PTA was found to be indicated based on a history of severe labile diabetes and hypoglycemic unawareness resulting in frequent episodes of hypoglycemia and hospital admissions. Because of the failure of medical management of the patient's diabetes, a whole organ bladder and systemic drained PTA was performed. Immunosuppression included thymoglobulin, tacrolimus, mycophenolate mofetil, and steroids. Early outcome was uneventful and patient was discharged 12 d after surgery normoglycemic and insulin-free. An episode of acute rejection (Maryland grade II) 20-d post-transplant was successfully treated with corticosteroids. A second and more severe episode of rejection (Maryland grade IV) occurred 13 months post-transplant, requiring treatment with thymoglobulin and conversion from steroid to sirolimus. On tacrolimus, sirolimus, and mycophenolic acid, he remains euglycemic and insulin-free 38 months after PTA. His quality-of-life is judged to be superior to his insulin dependent state prior to transplantation. According to the medical literature, this is the youngest patient ever to undergo PTA.

Liver transplantation for neotropical polycystic echinococcosis caused by Echinococcus vogeli: a case report.

Neotropical polycystic echinococcosis (NPE) is a parasitic disease caused by cestodes of Echinococcus vogeli. This parasite grows most commonly in the liver, where it produces multiples cysts that cause hepatic and vessel necrosis, infects the biliary ducts, and disseminates into the peritoneal cavity, spreading to other abdominal and thoracic organs. In cases of disseminated disease in the liver and involvement of biliary ducts or portal system, liver transplantation may be a favorable option. We present a report of the first case of liver transplantation for the treatment of advanced liver NPE caused by E. vogeli.

Liver transplantation for neotropical polycystic echinococcosis caused by Echinococcus vogeli: a case report

Neotropical polycystic echinococcosis (NPE) is a parasitic disease caused by cestodes of Echinococcus vogeli. This parasite grows most commonly in the liver, where it produces multiples cysts that cause hepatic and vessel necrosis, infects the biliary ducts, and disseminates into the peritoneal cavity, spreading to other abdominal and thoracic organs. In cases of disseminated disease in the liver and involvement of biliary ducts or portal system, liver transplantation may be a favorable option. We present a report of the first case of liver transplantation for the treatment of advanced liver NPE caused by E. vogeli.

Transplante de pâncreas isolado (órgäo total) com drenagem vesical. Relato do primeiro caso do Brazil / Isoleted pancreas transplantation(total organ) with bladder drainage. First case reported in Brazil

O transplante de pâncreas representa, no momento, a única terapêutica capaz de determinar estado normoglicêmico constante em pacientes com diabetes mellitus do tipo 1 (DM1), sendo indicado particularmente nas formas graves da doença, geralmente traduzidas pelas complicações secundárias como a retinopatia, neuropatia e nefropatia. Sua indicação mais consagrada é em associação ao transplante renal para portadores de DM1 com insuficiência renal, correspondente a cerca de 85 por cento dos transplantes de pâncreas no mundo. O transplante de pâncreas após rim constitui outra indicação aceita, uma vez que o paciente submetido previamente ao transplante renal já se encontra sob o uso da imunossupressão. O transplante de pâncreas isolado permanece tema controverso, mas pode ser empregado em pacientes com DM instável ou com complicações secundárias da doença e função renal preservada. No presente artigo, relata-se o primeiro caso de transplante de pâncreas isolado empregando-se órgão total com drenagem vesical realizado no Brasil para o tratamento do DM instável.

Insuficiência hepática aguda da gravidez: experiência clínica com sete casos / Acute liver failure of pregnancy: clinical experience with seven cases

Objetivos: avaliar a dificuldade diagnóstica, o tratamento e seu resultado em casos de insuficiência hepática aguda da gravidez. Métodos: sete pacientes com insuficiência hepática aguda da gravidez admitidas em nosso Serviço nos últimos quatro anos foram estudadas com ênfase nos sintomas presentes, achados laboratoriais, curso clínico, complicaçöes maternas e sobrevida fetal. Resultados: a média de idade foi de 25,8 anos (sendo duas primigestas) com idade gestacional média de 30,1. Destas, quatro receberam diagnóstico final de esteatose hepática aguda da gravidez e três de colestase intra-hepática da gravidez. Os principais sinais e sintomas encontrados foram: anorexia, náusea, dor abdominal, icterícia e encefalopatia. Ocorreu morte materna em dois casos: uma paciente por falência hepática enquanto aguardava órgäo para transplante e outra por falência hepática, coagulopatia grave e choque hemorrágico após biopsia hepática. Uma paciente com esteatose hepática aguda evoluiu para cronicidade e encontra-se viva um ano após transplante hepático. Nos quatro casos restantes houve completa remissäo do quadro com as medidas de suporte, associadas à interrupçäo da gravidez. As mortalidades materna e fetal foram, respectivamente, 28,6 por cento e 57,1 por cento. Conclusöes: conclui-se, nesta experiência inicial, que a insuficiência hepática aguda da gravidez constitui evento clínico grave, de elevada mortalidade materno-fetal, e que seu pronto reconhecimento e encaminhamento para centros terciários especializados em fígado, além da imediata interrupçäo da gestaçäo, säo fatores decisivos para o sucesso do tratamento.

Linfoma das vias biliares: relato de dois casos / Extrahepatic lymphoma: report of two cases

A infiltracao linfomatosa das vias biliares extra hepaticas e entidade rara e constitui causa incomum de ictericia obstrutiva. Neste trabalho descrevemos dois casos: um corresponde a linfoma nao Hodgkin primario do ducto hepatico comum e o outro secundario a envolvimento do trato biliar por linfoma de Hodgkin. No primeiro caso foi efetuada resseccao da lesao estando a doente viva seis meses apos a intervencao com tratamento radio e quimioterapico. O segundo paciente faleceu apos drenagem externa da via biliar em quadro de choque septico antes que se pudesse iniciar o tratamento especifico.