RESUMEN
INTRODUCTION: Variceal hemorrhage from sinistral portal hypertension has never been reported as a complication of live pancreas donation. CASE REPORT: We present a 68-year-old patient who underwent a simultaneous live-donor laparoscopic segmental pancreatectomy and nephrectomy for the purposes of donating to her daughter. Her postoperative course was significant for an episode of acute pancreatitis with a pseudocyst formation. More than a decade later, she presented with variceal hemorrhage from sinistral portal hypertension, which after a diagnostic work-up, prompted a laparoscopic splenectomy. DISCUSSION: Sinistral portal hypertension is a long-term complication of live-donor pancreas donation.
Asunto(s)
Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/etiología , Hipertensión Portal/etiología , Trasplante de Páncreas , Pancreatectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Recolección de Tejidos y Órganos/efectos adversos , Anciano , Várices Esofágicas y Gástricas/cirugía , Femenino , Hemorragia Gastrointestinal/cirugía , Humanos , Hipertensión Portal/cirugía , Páncreas/cirugía , Pancreatitis/etiología , Complicaciones Posoperatorias/cirugía , Esplenectomía/métodos , Recolección de Tejidos y Órganos/métodosRESUMEN
Insulin independence after total pancreatectomy and islet autotransplant (TPIAT) for chronic pancreatitis is limited by a high rate of postprocedure beta cell apoptosis. Endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are increased by dipeptidyl peptidase 4 inhibitor therapy (sitagliptin) may protect against beta cell apoptosis. To determine the effect of sitagliptin after TPIAT, 83 adult TPIAT recipients were randomized to receive sitagliptin (n = 54) or placebo (n = 29) for 12 months after TPIAT. At 12 and 18 months after TPIAT, participants were assessed for insulin independence; metabolic testing was performed with mixed meal tolerance testing and frequent sample intravenous glucose tolerance testing. Insulin independence did not differ between the sitagliptin and placebo groups at 12 months (42% vs. 45%, p = 0.82) or 18 months (36% vs. 44%, p = 0.48). At 12 months, insulin dose was 9.0 (standard error 1.7) units/day and 7.9 (2.2) units/day in the sitagliptin and placebo groups, respectively (p = 0.67) and at 18 months 10.3 (1.9) and 7.1 (2.6) units/day, respectively (p = 0.32). Hemoglobin A1c levels and insulin secretory measures were similar in the two groups, as were adverse events. In conclusion, sitagliptin could be safely administered but did not improve metabolic outcomes after TPIAT.
Asunto(s)
Diabetes Mellitus/terapia , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Células Secretoras de Insulina/patología , Trasplante de Islotes Pancreáticos/efectos adversos , Pancreatectomía/efectos adversos , Fosfato de Sitagliptina/uso terapéutico , Adulto , Glucemia , Femenino , Hemoglobina Glucada , Rechazo de Injerto/etiología , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Trasplante AutólogoRESUMEN
To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients.
Asunto(s)
Rechazo de Injerto/epidemiología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Trasplante de Páncreas , Adulto , Femenino , Estudios de Seguimiento , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Antígenos HLA-C/inmunología , Antígenos HLA-DQ/inmunología , Antígenos HLA-DR/inmunología , Humanos , Incidencia , Masculino , Minnesota/epidemiología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Donantes de TejidosRESUMEN
Defective glucagon secretion during hypoglycemia after islet transplantation has been reported in animals and humans with type 1 diabetes. To ascertain whether this is true of islets from nondiabetic humans, subjects with autoislet transplantation in the intrahepatic site only (TP/IAT-H) or in intrahepatic plus nonhepatic (TP/IAT-H+NH) sites were studied. Glucagon responses were examined during stepped hypoglycemic clamps. Glucagon and symptom responses during hypoglycemia were virtually absent in subjects who received islets in the hepatic site only (glucagon increment over baseline = 1 ± 6, pg/mL, mean ± SE, n = 9, p = ns; symptom score = 1 ± 1, p = ns). When islets were transplanted in both intrahepatic + nonhepatic sites, glucagon and symptom responses were not significantly different than Control Subjects (TP/IAT-H + NH: glucagon increment = 54 ± 14, n = 5; symptom score = 7 ± 3; control glucagon increment = 67 ± 15, n = 5; symptom score = 8 ± 1). In contrast, glucagon responses to intravenous arginine were present in TP/IAT-H recipients (TP/IAT: glucagon response = 37 ± 8, n = 7). Transplantation of a portion of the islets into a nonhepatic site should be seriously considered in TP/IAT to avoid posttransplant abnormalities in glucagon and symptom responses to hypoglycemia.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Glucagón/metabolismo , Hipoglucemia/metabolismo , Trasplante de Islotes Pancreáticos/fisiología , Islotes Pancreáticos/patología , Adulto , Arginina/metabolismo , Arginina/uso terapéutico , Autoinjertos/fisiología , Glucemia/metabolismo , Péptido C/sangre , Femenino , Humanos , Hipoglucemia/sangre , Hipoglucemia/terapia , Insulina/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Pancreatectomía , Enfermedades Pancreáticas/cirugía , Enfermedades Pancreáticas/terapia , Conductos Pancreáticos/patología , Pancreatitis/terapia , Resultado del TratamientoRESUMEN
PURPOSE: The purposes of this study were to study and compare clinical and functional outcomes after simultaneous deceased donor pancreas and kidney transplantation (SPK DD), simultaneous deceased donor pancreas and living donor kidney transplantation (SPK DL), and simultaneous living donor pancreas and kidney transplantation (SPK LL). METHODS: From January 1, 1996 to September 1, 2005, 8918 primary, simultaneous pancreas and kidney transplantation (SPK) procedures were reported to the International Pancreas Transplant Registry. Of these, 8764 (98.3%) were SPK DD, 115 (1.3%) were SPK DL, and 39 (0.4%) were SPK LL. We compared these 3 groups with regard to several endpoints including patient and pancreas and kidney graft survival rates. RESULTS: The 1-year and 3-year patient survival rates for SPK DD were 95% and 90%, 97% and 95% for SPK DL, and 100% and 100% for SPK LL recipients, respectively (P ≥ .07). The 1-year and 3-year pancreas graft survival rates for SPK DD were 84% and 77%, 83% and 71% for SPK DL, and 90% and 84% for SPK LL recipients, respectively (P ≥ .16). The 1-year and 3-year kidney graft survival rates for SPK DD were 92% and 84%, 94% and 86% for SPK DL, and 100% and 89% for SPK LL recipients, respectively (P ≥ .37). CONCLUSIONS: Patient survival rates and graft survival rates for pancreas and kidney were similar among the 3 groups evaluated in this study.
Asunto(s)
Trasplante de Riñón , Trasplante de Páncreas , Adulto , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sistema de Registros , Tasa de SupervivenciaRESUMEN
In patients with type 1 diabetes mellitus (T1DM) complicated by severe hypoglycemic episodes, fear of hypoglycemia can significantly impact daily life. We evaluated whether restoration of glycemic awareness and prevention of hypoglycemia by islet allotransplant could reduce fear and improve health status. We conducted a comprehensive evaluation of patient-based outcomes in 48 T1DM subjects screened for allogeneic islet transplant alone (ITA) and 27 subjects who received an ITA. A battery of generic health status and diabetes-specific measures were used to assess ITA at evaluation, six months, and then annually after ITA. Allogeneic islet transplant was associated with a reduction in behaviors adopted in avoiding hypoglycemia (p Value < 0.001) and attenuation in concerns about hypoglycemic episodes (p Value < 0.001). Changes in hypoglycemia fear tracked most closely with insulin use. While there was a trend toward global improvement in health as measured by the EQ-5D (p Value = 0.002) and in depression symptoms as measured by the Beck (p Value = 0.003), physical health remained unchanged following ITA. Our findings support the socioemotional benefits of ITA during the five years after ITA, which to some extent remains dependent on preservation of islet graft function.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Hipoglucemia/prevención & control , Trasplante de Islotes Pancreáticos , Adulto , Glucemia/análisis , Femenino , Estudios de Seguimiento , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Periodo Posoperatorio , Pronóstico , Factores de Tiempo , Trasplante HomólogoRESUMEN
The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3)/kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3)/kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.
Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/citología , Páncreas/cirugía , Pancreatectomía/métodos , Pancreatitis Crónica/terapia , Adolescente , Adulto , Anciano , Peso Corporal , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pancreatitis , Vena Porta/patología , Curva ROC , Factores de Riesgo , Trombosis , Resultado del Tratamiento , Adulto JovenRESUMEN
Islet autotransplant (IAT) may ameliorate postsurgical diabetes following total pancreatectomy (TP), but outcomes are dependent upon islet mass, which is unknown prior to pancreatectomy. We evaluated whether preoperative metabolic testing could predict islet isolation outcomes and thus improve assessment of TPIAT candidates. We examined the relationship between measures from frequent sample IV glucose tolerance tests (FSIVGTT) and mixed meal tolerance tests (MMTT) and islet mass in 60 adult patients, with multivariate logistic regression modeling to identify predictors of islet mass ≥2500 IEQ/kg. The acute C-peptide response to glucose (ACRglu) and disposition index from FSIVGTT correlated modestly with the islet equivalents per kilogram body weight (IEQ/kg). Fasting and MMTT glucose levels and HbA1c correlated inversely with IEQ/kg (r values -0.33 to -0.40, p ≤ 0.05). In multivariate logistic regression modeling, normal fasting glucose (<100 mg/dL) and stimulated C-peptide on MMTT ≥4 ng/mL were associated with greater odds of receiving an islet mass ≥2500 IEQ/kg (OR 0.93 for fasting glucose, CI 0.87-1.0; OR 7.9 for C-peptide, CI 1.75-35.6). In conclusion, parameters obtained from FSIVGTT correlate modestly with islet isolation outcomes. Stimulated C-peptide ≥4 ng/mL on MMTT conveyed eight times the odds of receiving ≥2500 IEQ/kg, a threshold associated with reasonable metabolic control postoperatively.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/prevención & control , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/metabolismo , Pancreatectomía , Pancreatitis Crónica/cirugía , Complicaciones Posoperatorias/prevención & control , Adulto , Péptido C/análisis , Femenino , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Cuidados Preoperatorios , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Trasplante AutólogoRESUMEN
Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥ 30 (HR 1.87, p = 0.005), donor Cr ≥ 2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.
Asunto(s)
Rechazo de Injerto/epidemiología , Trasplante de Páncreas , Sistema de Registros , Medición de Riesgo/métodos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Obtención de Tejidos y Órganos/normas , Insuficiencia del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n=440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n=151); high-level tacrolimus (TAC, 8-12 µg/L) and low-level sirolimus (SIR, 3-7 µg/L) (TACH/SIRL, n=149) or low-level TAC (3-7 µg/L) and high-level SIR (8-12 µg/L) (TACL/SIR(H) , n=140). Median follow-up was â¼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TACH/SIRL and TACL/SIRH) and chronic rejection (38%, 35% and 31% in CSA/MMF, TACH/SIRL and TACL/SIRH). Rates of new-onset diabetes mellitus were higher with TACH/SIRL (p=0.04), and rates of anemia were higher with TACH/SIRL and TACL/SIRH (p=0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.
Asunto(s)
Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Prednisona/uso terapéutico , Adulto , Ciclosporina/uso terapéutico , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Complicaciones Posoperatorias , Estudios Prospectivos , Sirolimus/uso terapéutico , Esteroides/uso terapéutico , Tacrolimus/uso terapéutico , Factores de Tiempo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
While it is known that islet cell mass increases considerably after birth, general uncertainty surrounds the source of new beta cells in humans. Chronic pancreatitis (CP) presents a natural injury model for studying postnatal beta-cell regeneration in the human pancreas. In this report, we present histological evidence from human CP pancreases to support the theory that islet neogenesis can occur from ductal precursor cells after birth. Three young patients (ages 16, 12, and 28 years) underwent total pancreatectomy for the management of CP followed by islet isolation and autologous transplantation to prevent or minimize postsurgical diabetes. In all cases, the pancreases had extensive fibrosis, a rock-like consistency, and calcifications in the ducts. During islet isolations, we observed the unusual release of islets with many ductal fragments. In histopathological evaluation of these pancreases, solid cords of cells sometimes formed islet like structures intraductally or extending from ductal structures. Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon, and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both ß-cells and α-cells. Labeling for Ki67 to demonstrate mitotic activity showed frequent labeling of duct epithelial cells and of some periductal cells. Using insulin and wide-spectrum cytokeratin double immunofluorescent labeling, we found insulin-positive cells to be present within the ductal lumens, among the cytokeratin-positive ductal epithelium, and extending from the ductal epithelium into surrounding connective tissues, providing evidence for a ductal origin of islet neogenesis.
Asunto(s)
Islotes Pancreáticos/embriología , Páncreas/patología , Conductos Pancreáticos/citología , Pancreatitis Crónica/patología , Adolescente , Adulto , Niño , Femenino , Fibrosis , Humanos , Islotes Pancreáticos/citología , Masculino , Páncreas/cirugía , Pancreatectomía , Pancreatitis Crónica/cirugía , Índice de Severidad de la EnfermedadRESUMEN
The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell depleting antibodies (TCDAb) and TNF-α inhibition (TNF-α-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-α-i (group 2; n = 20); CITR recipients given TCDAb without TNF-α-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50%) and group 2 (50%) were comparable to outcomes in PTA (group 5: 52%; p>>0.05) but significantly higher than in group 3 (0%; p = 0.001) and group 4 (20%; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-α-i.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Inmunoterapia , Trasplante de Islotes Pancreáticos , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/cirugía , HumanosRESUMEN
The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long-term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times.
Asunto(s)
Agencias Internacionales , Trasplante de Páncreas , Sistema de Registros , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.
Asunto(s)
Autoanticuerpos/inmunología , Rechazo de Injerto/diagnóstico , Trasplante de Páncreas/inmunología , Guías de Práctica Clínica como Asunto , Rechazo de Injerto/inmunología , HumanosRESUMEN
INTRODUCTION: Despite significant advances, widespread applicability of islet cell transplantation remains elusive. Refinement of current islet isolation protocols may improve transplant outcomes. Islet purification by magnetic separation has shown early promise. However, surgical protocols must be optimized to maximize the incorporation of paramagnetic microparticles (MP) within a greater number of islets. This study explores the impact of MP concentration and infusion method on optimizing MP incorporation within islets. METHODS: Five porcine pancreata were procured from donors after cardiac death. Splenic lobes were isolated and infused with varying concentrations of MP (8, 16, and 32 × 10(8) MP/L of cold preservation solution) and using one of two delivery techniques (hanging bag versus hand-syringe). After procurement and infusion, pancreata were stored at 0°C to 4°C during transportation (less than 1 hour), fixed in 10% buffered formalin, and examined by standard magnetic resonance imaging (MRI) and histopathology. RESULTS: T2*-weighted MRI showed homogeneous distribution of MP in all experimental splenic lobes. In addition, histologic analysis confirmed that MP were primarily located within the microvasculature of islets (82% to 85%), with few MP present in acinar tissue (15% to 18%), with an average of five to seven MP per islet (within a 5-µm thick section). The highest MP incorporation was achieved at a concentration of 16 × 10(8) MP/L using the hand-syringe technique. CONCLUSION: This preliminary study suggests that optimization of a surgical protocol, MP concentrations, and applied infusion pressures may enable more uniform distribution of MP in the porcine pancreas and better control of MP incorporation within islets. These results may have implications in maximizing the efficacy of islet purification by magnetic separation.
Asunto(s)
Trasplante de Islotes Pancreáticos/métodos , Microesferas , Animales , Islotes Pancreáticos/patología , Imagen por Resonancia Magnética , PorcinosRESUMEN
BACKGROUND: Calcineurin inhibitors (CNI) are the basis of contemporary immunosuppression in clinical pancreas transplantation (PT). Nevertheless, CNI toxicities, especially nephrotoxicity, have stimulated the search for CNI-sparing protocols. We performed a retrospective analysis of 25 PT patients with progressive CNI toxicities that were switched to a daclizumab (DAC)-based maintenance regimen. METHODS: From 2003 to 2007, 25 PT patients with progressive CNI toxicity (predominantly nephrotoxicity) were identified and switched from CNI to monthly DAC maintenance therapy. The DAC group was compared with matched control subjects (1:1) by transplant type and number, age, year of transplant, and duct management. RESULTS AND CONCLUSIONS: Results showed improved graft survival rates and decreased immunologic loss rates at 1, 3, and 5 years in the DAC group compared with the control group. There was no difference in patient survival rate between the 2 groups. Analysis demonstrates that DAC maintenance therapy is safe and effective for PT patients experiencing CNI toxicities. A randomized trial to compare DAC- and CNI-based regimens is needed in CNI-intolerant patients, with particular attention to the impact on renal function and patient morbidity (eg, infection rates).
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Páncreas/inmunología , Adulto , Anticuerpos Monoclonales Humanizados , Daclizumab , Estudios de Seguimiento , Supervivencia de Injerto/inmunología , Humanos , Subunidad alfa del Receptor de Interleucina-2/inmunología , Trasplante de Riñón/inmunología , Trasplante de Riñón/estadística & datos numéricos , Persona de Mediana Edad , Trasplante de Páncreas/mortalidad , Reoperación/estadística & datos numéricos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion. METHODS: Human pancreata were obtained from brain-dead donors. Porcine pancreata were procured by en bloc viscerectomy from heparinized donation after cardiac death donors and were either preserved by either two-layer method (TLM) or PSF. Following procurement, organs were transported to a 1.5-T magnetic resonance (MR) system for (31)P nuclear magnetic resonance spectroscopy to investigate their bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI. RESULTS: Human and porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i) levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were almost undetectable in porcine organs preserved with TLM. When human or porcine organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those observed in rat pancreata. CONCLUSION: The methods developed for human and porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This elevates ATP levels during preservation and may improve islet isolation outcomes while enabling the use of marginal donors, thus expanding the usable donor pool.
Asunto(s)
Preservación de Órganos/métodos , Trasplante de Páncreas/métodos , Páncreas/patología , Animales , Muerte , Diabetes Mellitus Tipo 1/cirugía , Humanos , Islotes Pancreáticos/anatomía & histología , Trasplante de Islotes Pancreáticos/métodos , Angiografía por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Soluciones Preservantes de Órganos , Páncreas/anatomía & histología , Ratas , PorcinosRESUMEN
Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the large dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in low islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from donors after cardiac death and preserved by either TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from several regions of the pancreas were sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries and significantly less autolysis/cell death relative to regions not exposed to persufflation or to tissues preserved with TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.
Asunto(s)
Preservación de Órganos/métodos , Páncreas/patología , Animales , Anticoagulantes/farmacología , Aorta/citología , Sustitutos Sanguíneos , Capilares/citología , Capilares/patología , Muerte Celular , Diabetes Mellitus Tipo 1/cirugía , Eutanasia , Fluorocarburos , Humanos , Trasplante de Islotes Pancreáticos/métodos , Arteria Mesentérica Superior/citología , Soluciones Preservantes de Órganos , Consumo de Oxígeno , Páncreas/irrigación sanguínea , Páncreas/citología , Páncreas/fisiología , PorcinosRESUMEN
BACKGROUND: The cost of islet procurement from donor pigs is increased by the use of organs that produce low yields. We developed an assessment system using dithizone-stained pig pancreas biopsies to enable the preselection of donor organs. METHODS: Pig pancreas biopsy slices were soaked in dithizone solution. The islets were evaluated before islet isolation by converting the islet counts (IC) to islet equivalents (IE), and then determining the IE/cm(2), IE/IC, % islets >150 microm, and % islets >200 microm. These parameters were evaluated in 3 different areas of the pancreas (duodenal, splenic, and connecting lobe; n = 42 each). Stepwise multivariate linear regression analysis was performed to assess for correlations with islet yield and decide which area of the pancreas had the most predictive value. To identify other predictors, including donor and islet isolation variables, we performed binary logistic regression analysis with significant variables from the univariate analysis (n = 67). For this analysis, the pigs were categorized into high (n = 23) and low (n = 44) yield groups. RESULTS: Stepwise multivariate linear regression analysis revealed that IE/cm(2) of the splenic lobe significantly predicted islet yield. Binary logistic regression analysis indicated that the IE/mm(2) of the splenic lobe was the only parameter that significantly correlated with successful pig islet isolations (P = .01; odds ratio 3.605). Variables associated with donor and islet isolation, such as age, gender, ischemic time, or enzyme lot, were not significantly correlated with islet yield. CONCLUSION: Our study suggests that the islet distribution of splenic lobe biopsies can be a reliable predictor of islet yield from pig pancreata.
Asunto(s)
Islotes Pancreáticos/citología , Páncreas/anatomía & histología , Envejecimiento/fisiología , Animales , Biopsia/métodos , Peso Corporal , Separación Celular/métodos , Femenino , Masculino , Tamaño de los Órganos , Páncreas/citología , Conductos Pancreáticos/citología , Análisis de Regresión , PorcinosRESUMEN
BACKGROUND: Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation. METHODS: Five porcine kidneys were procured using a donation after cardiac death (DCD) model. The renal artery and renal vein were cannulated and the kidney connected to a custom-made hypothermic machine perfusion (HMP) system equipped with an inline oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8 degrees C, and the perfusion parameters and partial oxygen pressures (pO(2)) were measured to calculate WOOCR. RESULTS: Without an inline oxygenator, the pO(2) of the perfusion solution at the arterial inlet and venous outlet diminished to near 0 within minutes. However, once adequate oxygenation was provided, a significant pO(2) difference was observed and used to calculate the WOOCR. The WOOCR was consistently measured from presumably healthy kidneys, and results suggest that it can be used to differentiate between healthy and purposely damaged organs. CONCLUSIONS: Custom-made HMP systems equipped with an oxygenator and inline oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a promising approach for the real-time quality assessment of kidneys and other organs during preservation before transplantation.