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1.
Ann Surg ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916985

RESUMEN

OBJECTIVE: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past five decades. BACKGROUND: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. METHODS: A single-center retrospective review of 2,500 pancreas transplants performed over >50 years in bivariate and multivariable models. Transplants were divided into six eras; outcomes are presented for the entire cohort and by era. RESULTS: All measures of patient and graft survival improved progressively through the six transplant eras. The overall death censored (DC) pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year DC pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. CONCLUSIONS: Pancreas outcomes have significantly improved over time via sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

2.
Ann Surg ; 276(3): 441-449, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35762611

RESUMEN

OBJECTIVE: To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. METHODS: TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. RESULTS: Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. CONCLUSIONS: QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatitis Crónica , Adulto , Femenino , Hemoglobina Glucada , Humanos , Insulina , Masculino , Pancreatectomía , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/cirugía , Calidad de Vida , Trasplante Autólogo , Resultado del Tratamiento
3.
Am J Transplant ; 21(2): 776-786, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32678932

RESUMEN

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children-digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.


Asunto(s)
Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Enfermedades Pancreáticas , Pancreatitis Crónica , Niño , Humanos , Pancreatectomía , Pancreatitis Crónica/cirugía , Trasplante Autólogo
4.
Am J Gastroenterol ; 112(4): 643-649, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28169284

RESUMEN

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.


Asunto(s)
Diabetes Mellitus/epidemiología , Instituciones de Salud , Trasplante de Islotes Pancreáticos/métodos , Pancreatectomía/métodos , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/epidemiología , Trasplante Autólogo/métodos , Enfermedad Aguda , Adulto , Péptido C/metabolismo , Estudios de Cohortes , Diabetes Mellitus/tratamiento farmacológico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Pancreatitis/metabolismo , Pancreatitis/cirugía , Pancreatitis Crónica/metabolismo , Complicaciones Posoperatorias/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
5.
Clin Transplant ; 31(10)2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28787529

RESUMEN

Arterial fistulas and pseudoaneurysms are rarely described significant arterial complications associated with pancreas transplantation that sometimes present with herald or catastrophic bleeding. We herein describe our institutional case series with a focus on management and outcomes. Of 2256 pancreas transplants, 24 arterial complications were identified in 23 recipients. Chart review was performed to describe the clinical characteristics, treatments, and outcomes of the complications (pseudoaneurysm, arterial enteric/cystic/ureteric fistula, or arteriovenous fistula). Of these 23 patients, 57% had a failed allograft at the time of the complication. Nine patients underwent primary surgical repair of 10 complications, 13 were treated by endovascular methods, and one patient by medical management. In total, 3 embolized patients rebled, 2 of which had failed allografts prior to treatment. Of those with graft function that were treated by embolization alone, all retained graft function. Diagnosis of arterial complications requires a high degree of suspicion and should involve early systemic angiography to evaluate the pancreatic vasculature. Management can be endovascular or surgical and should be individualized. We report our center's evolution from a predominantly surgical to endovascular approach as a definitive vs stabilizing therapy, with selective coiling mostly reserved for well-defined peripheral lesions in patients with a functioning allograft.


Asunto(s)
Fístula Arteriovenosa/etiología , Rechazo de Injerto/etiología , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
6.
Clin Transplant ; 31(9)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28636074

RESUMEN

Recent changes to pancreas graft allocation policy have increased the number of organs available for regional and distant sharing, which results in a corresponding increase in preservation time. We sought to systematically assess the impact of cold ischemia time (CIT) on outcomes post-transplant. A retrospective review of 1253 pancreas transplants performed at a single transplant center was performed to correlate CIT to transplant outcomes. The rate of technical failure (TF) increased with 20+ hours of CIT, with a 2.7-fold to 6.2-fold increased rate of TF for pancreas after kidney (PAK), simultaneous pancreas and kidney (SPK), and pancreas transplants overall. Long-term graft survival was best with <12 hours of CIT; graft failure increased 1.2-fold to 1.4-fold with 12-24 hours of CIT and 2.2-fold with 24+ hours. CIT had less influence on the pancreas transplant alone category than either SPK or PAK and had markedly more influence on grafts from older (age >25 years) and overweight (body mass index >25) donors. In the final analysis, grafts with <12 hours of CIT performed the best overall, and strategies that reduce CIT (such as early allocation, pre-recovery cross-matching, and chartered flights for organs) should be considered whenever possible.


Asunto(s)
Isquemia Fría/efectos adversos , Supervivencia de Injerto , Preservación de Órganos/efectos adversos , Trasplante de Páncreas , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Fría/estadística & datos numéricos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Preservación de Órganos/métodos , Preservación de Órganos/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo
7.
J Pediatr Gastroenterol Nutr ; 64(3): 440-445, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28231072

RESUMEN

OBJECTIVES: Fear of diabetes and major surgery may prohibit referral of young children severely affected by pancreatitis for total pancreatectomy with islet autotransplant (TPIAT). We evaluated outcomes in our youngest TPIAT recipients, 3 to 8 years of age at surgery. METHODS: Medical records were reviewed for 17 children (9 girls) ages 8 years or younger undergoing TPIAT from 2000 to 2014. Most (14/17) had genetic risk factors for pancreatitis. Since 2006, TPIAT recipients were followed prospectively with health questionnaires including assessments of pain and narcotic use, and scheduled hemoglobin A1c (HbA1c) and mixed-meal tolerance tests (6 mL/kg Boost HP) before surgery, and at regular intervals after. Patients are 1 to 11 years post-TPIAT (median 2.2 years). Data are reported as median (25th, 75th percentile). RESULTS: All had relief of pain, with all 17 patients off narcotics at most recent follow-up. Hospitalization rates decreased from 5.0 hospitalization episodes per person-year of follow-up before TPIAT, to 0.35 episodes per person-year of follow-up after TPIAT. Fourteen (82%) discontinued insulin, higher than the observed insulin independence rate of 41% in 399 patients older than 8 years of age undergoing TPIAT over the same interval (P = 0.004). Median post-TPIAT HbA1c was 5.9% (5.6%, 6.3%), and within patient post-TPIAT mean HbA1c was ≤6.5% for all but 2 patients. CONCLUSIONS: Young children with severe refractory chronic pancreatitis may be good candidates for TPIAT, with high rates of pain relief and insulin independence, and excellent glycemic control in the majority.


Asunto(s)
Dolor Abdominal/etiología , Trasplante de Islotes Pancreáticos/métodos , Pancreatectomía/métodos , Pancreatitis Crónica/cirugía , Dolor Abdominal/diagnóstico , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Dimensión del Dolor , Pancreatitis Crónica/complicaciones , Estudios Prospectivos , Trasplante Autólogo , Resultado del Tratamiento
8.
Clin Gastroenterol Hepatol ; 14(9): 1317-23, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26965843

RESUMEN

BACKGROUND & AIMS: Therapeutic options are limited for patients with recurrent acute pancreatitis who have intractable symptoms despite maximal endoscopic and medical treatment, but equivocal or no morphologic or functional evidence of chronic pancreatitis. We performed a prospective observational cohort study to determine the efficacy of total pancreatectomy with islet autotransplantation (TPIAT) for these patients. METHODS: We collected data from all patients undergoing TPIAT at the University of Minnesota from 2007 through 2013; 49 patients (42 female; mean age, 32.8 ± 7.8 years) had a diagnosis of recurrent acute pancreatitis not provoked by intervention, with negative or equivocal findings from nondiagnostic imaging or pancreatic function tests for chronic pancreatitis, and intractable pain between episodes. Data on insulin use, narcotic requirements, pain scores, and health-related quality of life were collected before TPIAT; 3 months, 6 months, and 1 year afterward; and then yearly. RESULTS: All 49 patients studied required narcotics before TPIAT (45 daily users and 4 intermittent users); 2 had insulin-treated diabetes. At 1 year after TPIAT, 22 out of 48 patients (46%) reported no use of narcotic pain medications (P < .001 vs baseline). Health-related quality of life score, measured by the physical and mental component summary score, increased by approximately 1 standard deviation from the population mean (P < .001 for the physical component summary; P = .019 for the mental component summary). At 1 year after TPIAT, 21 out of 48 patients (45%) were insulin independent; their mean percent glycosylated hemoglobin A1c at 1 year after TPIAT was 6.0% ± 0.9% (5.2% ± 0.6% pre-TPIAT). CONCLUSIONS: Patients with recurrent acute pancreatitis but lacking clear chronic pancreatitis benefit from TPIAT, with outcomes similar to those previously described for patients with chronic pancreatitis (improved quality of life and reduced narcotic use). For these patients who have otherwise limited surgical treatment options, TPIAT can be considered when medical and endoscopic therapies have failed.


Asunto(s)
Islas Genómicas , Pancreatectomía/métodos , Pancreatitis Aguda Necrotizante/cirugía , Trasplante Autólogo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Minnesota , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto Joven
9.
Pancreatology ; 16(4): 555-62, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27134135

RESUMEN

BACKGROUND/OBJECTIVES: Total pancreatectomy and islet autotransplant (TP-IAT) is a potential treatment for children with severe refractory chronic pancreatitis. Cultures from the resected pancreas and final islet preparation are frequently positive for microbes. It is unknown whether positive cultures are associated with adverse outcomes in pediatric patients. METHODS: We reviewed the medical records of children (n = 86) who underwent TP-IAT from May 2006-March 2015 with emphasis on demographics, previous pancreatic interventions, culture results, islet yield, hospital days, posttransplant islet function, and posttransplant infections. We compared outcomes in patients with positive (n = 57) and negative (n = 29) cultures. RESULTS: Patients with positive cultures had higher rates of previous pancreas surgery (P = 0.007) and endoscopic retrograde cholangiopancreatography (P < 0.0001). Positive cultures were not associated with posttransplant infections (P = 1.00) or prolonged hospital length of stay (P = 0.29). Patients with positive final islet preparation culture showed increased rates of graft failure at 2 years posttransplant (P = 0.041), but not when adjusted for islet mass transplanted (P = 0.39). CONCLUSIONS: Positive cultures during pediatric TP-IATs do not increase the risk of posttransplant infections or prolong hospital length of stay. Endocrine function depends on islet mass transplanted.


Asunto(s)
Contaminación de Medicamentos , Infecciones/etiología , Trasplante de Islotes Pancreáticos/efectos adversos , Soluciones Farmacéuticas/efectos adversos , Adolescente , Autoinjertos , Niño , Preescolar , Colangiopancreatografia Retrógrada Endoscópica , Femenino , Rechazo de Injerto , Humanos , Incidencia , Infecciones/epidemiología , Tiempo de Internación , Masculino , Pancreatectomía , Pruebas de Función Pancreática , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Resultado del Tratamiento
10.
Ann Surg ; 262(4): 610-22, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26366540

RESUMEN

OBJECTIVE: Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS: In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS: In our patients, the duration (mean ±â€ŠSD) of CP before their TP-IAT was 7.1 ±â€Š0.3 years and narcotic usage of 3.3 ±â€Š0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (≥5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS: This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatectomía , Pancreatitis Crónica/cirugía , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Narcóticos/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
11.
Curr Diab Rep ; 15(10): 67, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26275441

RESUMEN

A total pancreatectomy and islet autotransplant (TPIAT) offers substantial pain relief and improved quality of life for children who are severely affected by chronic or recurrent acute pancreatitis and for whom the usual medical and endoscopic therapies have failed. The pancreas is entirely resected, and the pancreatic islets are isolated from the pancreas and infused back into the patient's liver. Because this is an autologous transplant, no immunosuppression is required. Over several months, the islets engraft in the liver; the patient is then slowly weaned off insulin therapy. Slightly more than 40 % of patients become and remain insulin independent, yet even among patients who remain on insulin, most have some islet function, permitting easier diabetes control. The majority of patients experience pain relief, with significant improvements in health-related quality of life. A TPIAT should be considered for children who are significantly disabled by chronic pancreatitis.


Asunto(s)
Trasplante de Islotes Pancreáticos , Niño , Diabetes Mellitus/cirugía , Humanos , Pancreatectomía/efectos adversos , Pancreatitis/cirugía , Calidad de Vida , Trasplante Autólogo
12.
Ann Surg ; 260(1): 56-64, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24509206

RESUMEN

OBJECTIVE: Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients. BACKGROUND: Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long-term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, whereas islet autotransplantation (IAT) potentially can prevent or minimize TP-related diabetes. METHODS: Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012. RESULTS: Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P < 0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (P = 0.032), lack of prior Puestow procedure (P = 0.018), lower body surface area (P = 0.048), higher islet equivalents (IEQ) per kilogram body weight (P = 0.001), and total IEQ (100,000) (P = 0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT: (1) male sex, (2) lower body surface area, and (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (odds ratio = 2.62; P < 0.001). CONCLUSIONS: Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The ß-cell function is dependent on islet yield. Total pancreatectomy and islet autotransplantation is an effective therapy for children with painful pancreatitis that failed medical and/or endoscopic management.


Asunto(s)
Dolor Abdominal/terapia , Trasplante de Islotes Pancreáticos/métodos , Pancreatectomía/métodos , Pancreatitis Crónica/cirugía , Cuidados Posoperatorios/métodos , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Adolescente , Niño , Colangiopancreatografia Retrógrada Endoscópica , Endosonografía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Minnesota/epidemiología , Dimensión del Dolor , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Calidad de Vida , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada por Rayos X , Trasplante Autólogo , Resultado del Tratamiento
13.
Xenotransplantation ; 21(6): 574-81, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25040217

RESUMEN

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15-20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement as use of an intraductal infusion is not common practice.


Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/citología , Páncreas/citología , Trasplante Heterólogo , Animales , Separación Celular/métodos , Frío , Humanos , Porcinos , Trasplante Heterólogo/métodos
14.
Xenotransplantation ; 21(5): 473-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24986758

RESUMEN

Porcine islet xenotransplantation is emerging as a potential alternative for allogeneic clinical islet transplantation. Optimization of porcine islet isolation in terms of yield and quality is critical for the success and cost-effectiveness of this approach. Incomplete pancreas distention and inhomogeneous enzyme distribution have been identified as key factors for limiting viable islet yield per porcine pancreas. The aim of this study was to explore the utility of magnetic resonance imaging (MRI) as a tool to investigate the homogeneity of enzyme delivery in porcine pancreata. Traditional and novel methods for enzyme delivery aimed at optimizing enzyme distribution were examined. Pancreata were procured from Landrace pigs via en bloc viscerectomy. The main pancreatic duct was then cannulated with an 18-g winged catheter and MRI performed at 1.5-T. Images were collected before and after ductal infusion of chilled MRI contrast agent (gadolinium) in physiological saline. Regions of the distal aspect of the splenic lobe and portions of the connecting lobe and bridge exhibited reduced delivery of solution when traditional methods of distention were utilized. Use of alternative methods of delivery (such as selective re-cannulation and distention of identified problem regions) resolved these issues, and MRI was successfully utilized as a guide and assessment tool for improved delivery. Current methods of porcine pancreas distention do not consistently deliver enzyme uniformly or adequately to all regions of the pancreas. Novel methods of enzyme delivery should be investigated and implemented for improved enzyme distribution. MRI serves as a valuable tool to visualize and evaluate the efficacy of current and prospective methods of pancreas distention and enzyme delivery.


Asunto(s)
Separación Celular/métodos , Enzimas/administración & dosificación , Trasplante de Islotes Pancreáticos/métodos , Imagen por Resonancia Magnética , Trasplante Heterólogo/métodos , Animales , Femenino , Distribución Aleatoria , Porcinos
15.
Curr Diab Rep ; 12(5): 580-6, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22777430

RESUMEN

For patients with severe chronic pancreatitis refractory to medical interventions, total pancreatectomy can be considered to relieve the root cause of pain. The goal of a simultaneous islet autotransplant is to prevent or minimize the otherwise inevitable surgical diabetes. Islet autotransplant can successfully preserve some endogenous islet function in the majority of recipients, which mediates protection against brittle diabetes. Most maintain reasonably good glycemic control, while 30 %-40 % successfully discontinue insulin therapy. With islet autotransplants reaching a wider clinical audience, refinements in islet isolation techniques and strategies to protect islet grafts post-transplant may further improve the success of this procedure.


Asunto(s)
Diabetes Mellitus/etiología , Diabetes Mellitus/terapia , Trasplante de Islotes Pancreáticos/métodos , Humanos , Pancreatectomía/efectos adversos , Pancreatitis Crónica/cirugía
16.
Curr Opin Organ Transplant ; 17(1): 100-5, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22186094

RESUMEN

PURPOSE OF REVIEW: Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the very important risk factors for short-term survival of a pancreas transplant, there is not a lot of information available about factors that distinguish short-term from long-term graft function. RECENT FINDINGS: The analysis of 18,159 pancreas transplants from the International Pancreas Transplant Registry, performed from 25 July 1978 to 31 December 2005, showed an improvement not only in short-term but also in long-term graft function. Most recent 5-year, 10-year and 20-year graft function for transplants with the appropriate follow-up time showed 80, 68 and 45%, respectively, for simultaneous pancreas/kidney transplants; 62, 46 and 16%, respectively, for pancreas after kidney; and 59, 39 and 12%, respectively, for pancreas transplants alone. Important factors influencing long-term function were factors that described the quality of the deceased donor. Pancreas transplants in younger or African-American recipients showed a higher risk of graft failure. Anti-T-cell induction therapy had a significant impact on long-term survival in solitary transplants. SUMMARY: With a careful donor selection, not only short-term but also long-term pancreas graft function and, therefore, good metabolic control can be achieved for the diabetic patient.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Supervivencia de Injerto , Trasplante de Riñón , Trasplante de Páncreas , Insuficiencia Renal/cirugía , Toma de Decisiones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/complicaciones , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/metabolismo , Secreción de Insulina , Donadores Vivos , Modelos Logísticos , Diálisis Renal/efectos adversos , Insuficiencia Renal/etiología , Insuficiencia Renal/terapia , Factores de Tiempo , Resultado del Tratamiento , Listas de Espera
17.
Curr Opin Organ Transplant ; 17(1): 106-15, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22240639

RESUMEN

PURPOSE OF REVIEW: More than 160 living donor segmental pancreas/islet transplants have been done since the first in 1977, more than three-quarters at one institution. We review this three-decade experience to project future application. Initially, living donor pancreas transplants were done because the results with deceased donors were poor. As the results with deceased donors improved, the incentive to do living donor transplants declined but never disappeared. A living donor simultaneous pancreas-kidney transplant in a uremic diabetic can correct diabetes and pre-empt dialysis with one operation, obviating the high mortality rate of waiting for a deceased donor. Solitary pancreas transplant candidates with preformed human leukocyte antigen antibodies but a negative cross match to a living donor volunteer also benefit. RECENT FINDINGS: The technical failure rate of living donor pancreas transplants was high in the initial cases (>1/3), nearly double that for deceased donors, but has since declined to nearly zero. Living donor segmental pancreatectomy has little surgical morbidity (currently done laparoscopically) with only a small risk for diabetes by strict selection criteria. living donor and deceased donor graft survival rates are equivalent. Islet allografts have been done from three living donors, the last one successfully, showing the potential for further application. SUMMARY: The incentives for living donor transplants are to eliminate long-wait times for a deceased donor organ and to improve outcomes. With both the incentive is high, but either by itself is sufficient. As the number of pancreas transplant candidates increase, so will wait times for a deceased donor organ. For this reason, living donor pancreas/islet transplant volume will likely increase in the years to come.


Asunto(s)
Diabetes Mellitus/etiología , Trasplante de Riñón , Donadores Vivos , Trasplante de Páncreas , Pancreatectomía/efectos adversos , Cadáver , Diabetes Mellitus/prevención & control , Humanos , Trasplante de Riñón/métodos , Trasplante de Páncreas/métodos , Pancreatectomía/métodos , Trasplante Homólogo , Listas de Espera
18.
Clin Gastroenterol Hepatol ; 9(9): 793-9, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21683160

RESUMEN

BACKGROUND & AIMS: Total pancreatectomy (TP) and islet autotransplant (IAT) have been used to treat patients with painful chronic pancreatitis. Initial studies indicated that most patients experienced significant pain relief, but there were few validated measures of quality of life. We investigated whether health-related quality of life improved among pediatric patients undergoing TP/IAT. METHODS: Nineteen consecutive children (aged 5-18 years) undergoing TP/IAT from December 2006 to December 2009 at the University of Minnesota completed the Medical Outcomes Study 36-item Short Form (SF-36) health questionnaire before and after surgery. Insulin requirements were recorded. RESULTS: Before TP/IAT, patients had below average health-related quality of life, based on data from the Medical Outcomes Study SF-36; they had a mean physical component summary (PCS) score of 30 and mental component summary (MCS) score of 34 (2 and 1.5 standard deviations, respectively, below the mean for the US population). By 1 year after surgery, PCS and MCS scores improved to 50 and 46, respectively (global effect, PCS P < .001, MCS P = .06). Mean scores improved for all 8 component subscales. More than 60% of IAT recipients were insulin independent or required minimal insulin. Patients with prior surgical drainage procedures (Puestow) had lower yields of islets (P = .01) and greater incidence of insulin dependence (P = .04). CONCLUSIONS: Quality of life (physical and emotional components) significantly improve after TP/IAT in subsets of pediatric patients with severe chronic pancreatitis. Minimal or no insulin was required for most patients, although islet yield was reduced in patients with previous surgical drainage operations.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatectomía , Pancreatitis Crónica/terapia , Calidad de Vida/psicología , Trasplante Autólogo , Centros Médicos Académicos , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Minnesota , Resultado del Tratamiento
19.
Lancet ; 373(9677): 1808-17, 2009 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-19465236

RESUMEN

Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have been in progress, yet this surgical procedure still remains the treatment of choice for diabetic patients with end-stage renal failure. Many improvements have been made in the surgical techniques and immunosuppressive regimens, both of which have contributed to an increasing number of indications for pancreas transplantation. This operation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure and lifelong immunosuppression. The various indications, categories, and outcomes of patients having a pancreas transplant are discussed, particularly with reference to the effect on long-term diabetic complications.


Asunto(s)
Complicaciones de la Diabetes/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Páncreas , Enfermedad Coronaria/etiología , Enfermedad Coronaria/prevención & control , Complicaciones de la Diabetes/etiología , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Fallo Renal Crónico/etiología , Morbilidad , Trasplante de Páncreas/efectos adversos , Trasplante de Páncreas/inmunología , Trasplante de Páncreas/métodos , Trasplante de Páncreas/tendencias , Selección de Paciente , Calidad de Vida , Tasa de Supervivencia , Obtención de Tejidos y Órganos , Inmunología del Trasplante , Resultado del Tratamiento
20.
Curr Diab Rep ; 10(5): 326-31, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20680524

RESUMEN

Chronic pancreatitis is a rare disease in childhood. However, when severe, a total pancreatectomy may be the only option to relieve pain and restore quality of life. An islet autotransplant performed at the time of pancreatectomy can prevent or minimize the postsurgical diabetes that would otherwise result from pancreatectomy alone. In this procedure, the resected pancreas is mechanically disrupted and enzymatically digested to separate the islets from the surrounding exocrine tissue, and the isolated islets are infused into the portal vein and engraft in the liver. Because patients are receiving their own tissue, no immunosuppression is required. Islet autotransplant is successful in two thirds of children-these patients are insulin independent or require little insulin to maintain euglycemia. Factors associated with a more successful outcome include a younger age at transplant (<13 years), more islets transplanted, and lack of prior surgical procedures on the pancreas (partial pancreatectomy or surgical drainage procedures).


Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Niño , Humanos , Insulina/farmacología , Pruebas de Función Hepática , Manejo del Dolor , Páncreas/efectos de los fármacos , Páncreas/cirugía , Pancreatitis Crónica/terapia , Trasplante Autólogo , Resultado del Tratamiento
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