545 results on '"David E.R. Sutherland"'
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2. Commentary
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Paul F. Gores M.D. and David E.R. Sutherland
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Medicine - Published
- 1993
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- View/download PDF
3. Entrapment of Cultured Pancreas Islets in Three-Dimensional Collagen Matrices
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Seh-Huang Chao, Madhusudan V. Peshwa, David E.R. Sutherland M.D., Ph.D., and Wei-Shou Hu
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Medicine - Abstract
In vitro culture of islets of Langerhans decreases their immunogenecity, presumably by eliminating passenger leukocytes and other Ia+ presenting cells within the islets. Islets cultivated in petri dishes either at 37°C or at 25°C gradually disintegrate during culture in a time-dependent manner which is related to the free-floating condition of the islets. Also, a fraction of the islets disperse as single cells and beta-cell aggregates or adhere to the bottom of the culture dishes. Thus, the retrieval rate of transplantable islets is dampened due to their disintegration and spontaneous dispersion in conventional petri dish cultures. Entrapment of freshly harvested islets of Langerhans in a three-dimensional collagen matrix was studied as an alternative method for islet cultivation. The contraction of collagen fibrils during in vitro culture counteracts the dispersion of islets and helps in maintaining their integrity while in culture. It was observed that the entrapped islets maintain satisfactory morphology, viability, and capability of glucose-dependent insulin secretion for over 2 wk. The oxygen consumption rate and glucose metabolism of these islets was not deranged when entrapped in collagen. Also, the retrieval of islets is easier and more efficient than that observed in conventional culture systems. Our results indicate that culture of islets in three-dimensional collagen gels can potentially develop into an ideal system applicable to clinical transplantation of cultured islets or beta-cell aggregates.
- Published
- 1992
- Full Text
- View/download PDF
4. Intraportal Islet Autotransplantation Independently Improves Quality of Life After Total Pancreatectomy in Patients With Chronic Refractory Pancreatitis
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Srinath Chinnakotla, Gregory J. Beilman, David Vock, Martin L. Freeman, Varvara Kirchner, Ty B. Dunn, Timothy L. Pruett, Stuart K. Amateau, Guru Trikudanathan, Sarah J. Schwarzenberg, Elissa Downs, Matthew Armfield, Karthik Ramanathan, David E.R. Sutherland, and Melena D. Bellin
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Adult ,Glycated Hemoglobin ,Male ,Pancreatectomy ,Treatment Outcome ,Pancreatitis, Chronic ,Islets of Langerhans Transplantation ,Quality of Life ,Humans ,Insulin ,Female ,Surgery ,Transplantation, Autologous - Abstract
To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT).TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear.TP-IAT patients at our center1 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.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 for5 years after TP-IAT for 42.7% and for10 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 ( P0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P0.001). 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.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.
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- 2022
5. Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis
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Elissa M. Downs, Melena D. Bellin, Jessica Diaz, David E.R. Sutherland, Bernhard J. Hering, Srinath Chinnakotla, Joshua J. Wilhelm, Appakalai N. Balamurugan, Zachary Swanson, Sarah Jane Schwarzenberg, Marie Cook, and James S. Hodges
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endocrine system ,medicine.medical_specialty ,Total pancreatectomy ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,030230 surgery ,Transplantation, Autologous ,Gastroenterology ,Islets of Langerhans ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Pancreatitis, Chronic ,Diabetes mellitus ,Internal medicine ,Isolation techniques ,Humans ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,Child ,Transplantation ,geography ,geography.geographical_feature_category ,business.industry ,Pancreatic Diseases ,Islet ,medicine.disease ,Autotransplantation ,medicine.anatomical_structure ,Pancreatitis ,business ,Pancreas ,Pancreatic fibrosis - Abstract
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 (
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- 2021
6. How Durable Is Total Pancreatectomy and Intraportal Islet Cell Transplantation for Treatment of Chronic Pancreatitis?
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David E.R. Sutherland, Timothy L. Pruett, Srinath Chinnakotla, Arzu Petersen, Sarah Jane Schwarzenberg, Hawa M. Ali, Guru Trikudanathan, Varvara A. Kirchner, Martin L. Freeman, Melena D. Bellin, Steven J. Mongin, and Gregory J. Beilman
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Adult ,Male ,medicine.medical_specialty ,Abdominal pain ,Adolescent ,SF-36 ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Young Adult ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Pancreatitis, Chronic ,Diabetes mellitus ,medicine ,Humans ,Child ,Survival analysis ,Aged ,Pain Measurement ,Islet cell transplantation ,geography ,geography.geographical_feature_category ,business.industry ,Middle Aged ,medicine.disease ,Islet ,Survival Analysis ,Surgery ,Transplantation ,Logistic Models ,Treatment Outcome ,030220 oncology & carcinogenesis ,Quality of Life ,Pancreatitis ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Background A total pancreatectomy and intraportal islet cell autotransplant (TPIAT) is increasingly being offered to patients with chronic pancreatitis (CP). The benefits include removal of the root cause of pain and amelioration of diabetes. However, the long-term durability of this operation remains unclear. Study Design Of the 742 patients who have undergone a TPIAT at our center, 215 who did so between 1998 and 2008 now have at least 10 years of follow-up time and were eligible for this single-center observational study. Our outcomes measures included abdominal pain relief, narcotic use, islet graft function (subdivided into 3 groups: insulin independence; partial graft function, defined by C-peptide level > 0.6 mg/dL; and no function, defined by C-peptide level Results The 10-year actuarial survival rate was 72%. A BMI > 30 kg/m2 (p = 0.04) predicted 10-year mortality. The rates of pain relief were 82% at 10 years and 90% at 15 years. Narcotic use declined with time: the rates were 50% at 5 years and 37% at 10 years. At 10 years, the rate of insulin independence was 20%; the rate of partial graft function, 32%. Transplantation of islet equivalents/kg > 4,000 was the strongest predictor of islet graft function at 10 years. Pediatric patients were more likely to have islet function than adults (p = 0.01). Health-related quality of life continued to improve at 10 years, even in patients on narcotics. Conclusions This represents the first and largest series to examine long-term outcomes (10 years or more) in TPIAT patients. In our series, this dual procedure produced durable pain relief and sustained islet graft function, even past 10 years postoperatively.
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- 2019
7. Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function
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David E.R. Sutherland, John S. Najarian, Hassan N. Ibrahim, Oscar K. Serrano, Richard Spong, Timothy L. Pruett, Arthur J. Matas, Ty B. Dunn, Varvara A. Kirchner, Raja Kandaswamy, Erik B. Finger, Srinath Chinnakotla, William D. Payne, and Kristen J. Gillingham
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medicine.medical_specialty ,Type 1 diabetes ,business.industry ,Specific time ,Cancer ,medicine.disease ,Graft function ,Kidney transplant ,Clinical trial ,Internal medicine ,Long term outcomes ,Medicine ,Skin cancer ,business - Abstract
An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years. For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%. Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%. DD recipients had lower PS(P 3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender. New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant. Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%. To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.
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- 2021
8. Dorsal Pancreas Agenesis in an Organ Donor: To Accept or to Discard for Transplantation?
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David E.R. Sutherland, Diethard Monbaliu, Karlien Eggermont, Jacques Pirenne, Julie De Beule, Laurens J. Ceulemans, and Rainer W.G. Gruessner
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Transplantation ,medicine.medical_specialty ,business.industry ,MEDLINE ,lcsh:Surgery ,lcsh:RD1-811 ,medicine.disease ,Surgery ,Agenesis ,Organ Donation and Procurement ,medicine ,business ,Dorsal pancreas - Abstract
ispartof: TRANSPLANTATION DIRECT vol:7 issue:1 ispartof: location:United States status: published
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- 2020
9. History of pancreas transplantation
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Rainer W.G. Gruessner and David E.R. Sutherland
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medicine.medical_specialty ,business.industry ,Total pancreatectomy ,medicine.medical_treatment ,Autopsy ,Sequela ,Pancreas transplantation ,medicine.disease ,Clinical onset ,Surgery ,medicine.anatomical_structure ,Diabetes mellitus ,Medicine ,business ,Pancreas ,Subcutaneous tissue - Abstract
On December 20, 1893, 3 years after von Mering and Minkowski showed that total pancreatectomy in dogs resulted in diabetes mellitus,1 Dr. P. Watson Williams in Bristol, England, grafted three fragments of a pancreas obtained from a freshly slaughtered sheep into the subcutaneous tissue of a 15-year-old boy in extremis, 5 months after clinical onset of diabetes.2 The recipient died 3 days later, not of complications from the unsuccessful transplant but of unrelenting acidosis, a sequela of basically untreated diabetes. At autopsy, the recipient’s own pancreas was shriveled and sections showed little but fibrous stroma. According to Williams, the history and the postmortem examination left little doubt that the patient had “pancreatic diabetes” a case that “presented all the conditions that might lead one to hope for beneficial results from successful grafting of the pancreas, if anything can be hoped for in this direction at all.” He was not discouraged, and further stated that “failure was possibly due to obtaining the graft from a sheep that had been killed by bleeding....If ever I felt justified again in resorting to pancreatic grafts in a similar case, I should obtain them from a living animal anesthetized or dispense with the anesthetic altogether.”
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- 2020
10. Contributors
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Peter Abrams, Joel T. Adler, Rodolfo Alejandro, Mohamed Alibashe-Ahmed, Ana Alvarez, Takayuki Anazawa, Axel Andres, Barbara Antonioli, Alan Apete, David A. Axelrod, Lionel Badet, David Baidal, Kaylene Barrera, Pierre-Yves Benhamou, Thierry Berney, Alain Gerald Bertoni, Federico Bertuzzi, Ugo Boggi, Caroline Bonner, Adel Bozorgzadeh, Julien Branchereau, Jonathan Bromberg, George W. Burke, Fanny Buron, Robert Caiazzo, Rossana Caldara, Stephanie S. Camhi, Diego Cantarovich, Massimo Cardillo, D. Castanares-Zapatero, Pierre Cattan, Suresh Rama Chandran, Erin Chang, Linda Chen, Mikael Chetboun, Pratik Choudhary, Gaetano Ciancio, Maria Pia Cicalese, Antonio Citro, C. Collienne, Caterina Conte, Claire Counter, Khaled Z. Dajani, Carly M. Darden, Francesco De Cobelli, Eelco J.P. de Koning, Hector De Leon, Nathalie Delalleau, Laura DiChiacchio, Jason B. Doppenberg, Cinthia B. Drachenberg, Erica Dugnani, Ty B. Dunn, Marten A. Engelse, Ahmed Farag, Alan Farney, Anne Elizabeth Farrow, Ibrahim Fathi, Jose Figueiro, Anneliese Flatt, Georgia Fousteri, Jonathan A. Fridell, Peter J. Friend, Giacomo Gastaldi, Valery Gmyr, Javier Gonzalez, Jeevan Prakash Gopal, Frans K. Gorus, Masafumi Goto, Mitsukazu Gotoh, Michel Greget, Dominique Grenet, Paolo Antonio Grossi, Rainer W.G. Gruessner, Angelika C. Gruessner, David I. Harriman, Wayne J. Hawthorne, Jarl Hellman, Brenda Lee Holbert, Thomas Hubert, Sara Iacopi, Marco Infante, Peter Jacob, Paul Johnson, Raja Kandaswamy, Georges Karam, Dixon B. Kaufman, W.F. Kendall Jr, Clark D. Kensinger, Norma S. Kenyon, Julie Kerr-Conte, Delphine Kervella, Laurence Kessler, Romain Kessler, Bart Keymeulen, Olle Korsgren, Sandrine Lablanche, Muhaib Lakhani, Neeraj Lalwani, P.F. Laterre, Michael C. Lawrence, Frances Tangherlini Lee, Roger Lehmann, Elina Linetsky, Barbara Ludwig, Torbjörn Lundgren, Xunrong Luo, SriGita Madiraju, Paola Maffi, Paola Magistretti, Kristell Le Mapihan, James F. Markmann, Geert Martens, Paulo N. Martins, Francesco Antonio Mazzotta, Kavya Chitra Mekala, Raffaella Melzi, Alessia Mercalli, Paolo Monti, Mahmoud Morsi, Irene Mosca, M. Mourad, Anand S. Rathnasamy Muthusamy, Rita Nano, Bashoo Naziruddin, Christian Noel, John O’Callaghan, Jon S. Odorico, Anne Olland, E.C. Opara, Giuseppe Orlando, Nathalia Padilla, John C. Papadimitriou, Vassilios E. Papalois, Klearchos K. Papas, Gianni Pasquetti, François Pattou, Silvia Pellegrini, Nadine Pernin, Vittorio Grazio Perrone, Lorenzo Piemonti, Rutger Ploeg, John A. Powelson, Alberto Pugliese, Shanthini K. Rajan, Karthik V. Ramanathan, Violeta Raverdy, Robert R. Redfield, John Renz, Michael R. Rickels, Charles G. Rickert, Camillo Ricordi, Jeffrey Rogers, Joseph R. Scalea, Jesse D. Schold, Hanne Scholz, Antonio Secchi, Oscar K. Serrano, A.M. James Shapiro, Sidharth Sharma, Edward Sharples, James A.M. Shaw, Sanjay Sinha, Carlo Socci, Jean-Paul G. Squifflet, Peter G. Stock, Robert J. Stratta, David E.R. Sutherland, Manfredi Tesauro, Olivier Thaunat, Julien Thévenet, Christoph Troppmann, Marie-Christine Vantyghem, Francesco Vendrame, Massimo Venturini, Rodrigo Vianna, Fabio Vistoli, Bengt von Zur-Mühlen, X. Wittebole, Anne Wojtusciszyn, Arya Zarinsefat, and Asha Zimmerman
- Published
- 2020
11. Total Pancreatectomy With Intraportal Islet Autotransplantation as a Treatment of Chronic Pancreatitis in Patients With CFTR Mutations
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Jordan M. Dunitz, David E.R. Sutherland, Sarah Jane Schwarzenberg, Ty B. Dunn, Louise Berry, Melena D. Bellin, Timothy L. Pruett, Gregory J. Beilman, Srinath Chinnakotla, Joshua J. Wilhelm, and Kristin P. Colling
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Cystic Fibrosis Transmembrane Conductance Regulator ,Transplantation, Autologous ,Gastroenterology ,Cystic fibrosis ,Young Adult ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Endocrinology ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Child ,Retrospective Studies ,geography ,geography.geographical_feature_category ,Hepatology ,business.industry ,Insulin ,Middle Aged ,medicine.disease ,Islet ,Autotransplantation ,Treatment Outcome ,Child, Preschool ,030220 oncology & carcinogenesis ,Mutation ,Etiology ,Pancreatitis ,Female ,030211 gastroenterology & hepatology ,Complication ,business - Abstract
OBJECTIVES Chronic pancreatitis (CP) is an infrequent but debilitating complication associated with CFTR mutations. Total pancreatectomy with islet autotransplantation (TPIAT) is a treatment option for CP that provides pain relief and preserves β-cell mass, thereby minimizing the complication of diabetes mellitus. We compared outcomes after TPIAT for CP associated with CFTR mutations to CP without CTFR mutations. METHODS All TPIATs performed between 2002 and 2014 were retrospectively reviewed: identifying 20 CFTR homozygotes (cystic fibrosis [CF] patients), 19 CFTR heterozygotes, and 20 age-/sex-matched controls without CFTR mutations. Analysis of variance and χ tests were used to compare groups. RESULTS Baseline demographics were not different between groups. Postoperative glycosylated hemoglobin and C-peptide levels were similar between groups, as were islet yield and rate of postoperative complications. At 1 year, 40% of CF patients, 22% of CFTR heterozygotes, and 35% of control patients were insulin independent. CONCLUSION Total pancreatectomy with islet autotransplantation is a safe, effective treatment option for CF patients with CP, giving similar outcomes for those with other CP etiologies.
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- 2018
12. Living Donor Pancreas Transplants: Donor Selection and Risk Minimization
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David E.R. Sutherland, Raja Kandaswamy, Oscar K. Serrano, and Bodhisatwa Sengupta
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Waiting time ,Transplantation ,medicine.medical_specialty ,Hepatology ,Donor selection ,business.industry ,Immunology ,030230 surgery ,Living donor ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Highly sensitized ,Nephrology ,Donation ,medicine ,030211 gastroenterology & hepatology ,Pancreas ,business ,Biochemical markers - Abstract
In this study, our goal was to analyze nearly 4 decades of experience since the first living donor pancreas transplant in 1979, focusing on what constitutes optimal donor selection and ideal post donation follow-up. When combined with a living donor kidney transplant, a living donor pancreas transplant offers patients with concurrent renal failure and diabetes the option of a single procedure: a living donor simultaneous pancreas-kidney (SPK) transplant. Living donor SPK transplants not only can reduce the waiting time in areas where it is long but also, for highly sensitized patients, can electively identify a donor with a negative crossmatch. Although living donor pancreas (and simultaneous pancreas-kidney) transplants were initially performed open, they evolved to laparoscopic procedures in 1999. The technical failure rates have improved over the years. Guidelines for reducing donor morbidity have incorporated the use of biochemical markers and stricter donor selection criteria. Predonation assessment of donors’ beta-cell mass may help identify those at risk of developing diabetes. Living donor pancreas transplants can be performed safely and with good outcomes; they remain an important option for highly sensitized transplant candidates and can reduce waiting time in areas where it is long. For donors, stringent selection criteria, robust predonation counseling, and meticulous postdonation follow-up are essential.
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- 2017
13. Total Pancreatectomy With Islet Autotransplantation Resolves Pain in Young Children With Severe Chronic Pancreatitis
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Srinath Chinnakotla, Joshua J. Wilhelm, Gregory J. Beilman, Ty B. Dunn, Megan G. Berger, Marie Cook, Sarah Jane Schwarzenberg, Melena D. Bellin, Kaustav Majumder, Martin L. Freeman, Gregory P. Forlenza, Michael Murati, Timothy L. Pruett, and David E.R. Sutherland
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Abdominal pain ,geography ,medicine.medical_specialty ,geography.geographical_feature_category ,business.industry ,medicine.medical_treatment ,General surgery ,Gastroenterology ,030230 surgery ,medicine.disease ,Islet ,Autotransplantation ,Surgery ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Pediatrics, Perinatology and Child Health ,Pancreatectomy ,medicine ,Pancreatitis ,030211 gastroenterology & hepatology ,medicine.symptom ,Pancreatitis, chronic ,business - Abstract
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 w
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- 2017
14. Total Pancreatectomy With Islet Autotransplantation Improves Quality of Life in Patients With Refractory Recurrent Acute Pancreatitis
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David E.R. Sutherland, Melena D. Bellin, Martin L. Freeman, Tossapol Kerdsirichairat, Srinath Chinnakotla, Ty B. Dunn, Mustafa A. Arain, Timothy L. Pruett, Gregory J. Beilman, Sarah Jane Schwarzenberg, and David R. Radosevich
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medicine.medical_specialty ,Hepatology ,SF-36 ,Narcotic ,business.industry ,medicine.medical_treatment ,Gastroenterology ,medicine.disease ,Article ,Autotransplantation ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,030220 oncology & carcinogenesis ,Pancreatectomy ,medicine ,Pancreatitis ,030211 gastroenterology & hepatology ,Intractable pain ,Prospective cohort study ,business - Abstract
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 P 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 A 1c 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.
- Published
- 2016
15. HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival
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Harriet Noreen, Ty B. Dunn, E. Rudolph, Erik B. Finger, David E.R. Sutherland, David Mauer, and Raja Kandaswamy
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Adult ,Graft Rejection ,Male ,0301 basic medicine ,medicine.medical_specialty ,Opportunistic infection ,Minnesota ,medicine.medical_treatment ,HLA-C Antigens ,Histocompatibility Testing ,Human leukocyte antigen ,030230 surgery ,Pancreas transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,HLA-DQ Antigens ,Internal medicine ,medicine ,HLA-B Antigens ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Prospective Studies ,Retrospective Studies ,Transplantation ,HLA-A Antigens ,business.industry ,Incidence ,Graft Survival ,HLA-DR Antigens ,Prognosis ,medicine.disease ,Tissue Donors ,Histocompatibility ,HLA-A ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Female ,Pancreas Transplantation ,Pancreas ,business ,Follow-Up Studies - Abstract
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.
- Published
- 2016
16. Microbial contamination of transplant solutions during pancreatic islet autotransplants is not associated with clinical infection in a pediatric population
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Martin L. Freeman, Sameer Gupta, Kaustav Majumder, Timothy L. Pruett, Gregory J. Beilman, Sarah Jane Schwarzenberg, David E.R. Sutherland, Srinath Chinnakotla, Joshua J. Wilhelm, Ty B. Dunn, James S. Hodges, Megan G. Berger, and Melena D. Bellin
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Graft Rejection ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,030230 surgery ,Infections ,Gastroenterology ,03 medical and health sciences ,Pancreatectomy ,Postoperative Complications ,0302 clinical medicine ,Pancreatitis, Chronic ,Internal medicine ,medicine ,Humans ,Pancreatitis, chronic ,Autografts ,Child ,Retrospective Studies ,Cholangiopancreatography, Endoscopic Retrograde ,geography ,Endoscopic retrograde cholangiopancreatography ,geography.geographical_feature_category ,Hepatology ,medicine.diagnostic_test ,business.industry ,Incidence ,Incidence (epidemiology) ,Retrospective cohort study ,Length of Stay ,medicine.disease ,Islet ,Surgery ,Pancreatic Function Tests ,Pharmaceutical Solutions ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,Pancreatitis ,Female ,030211 gastroenterology & hepatology ,Drug Contamination ,business ,Pancreas - Abstract
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 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.
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- 2016
17. Evolution of Living Donor Nephrectomy at a Single Center
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Arthur J. Matas, Ty B. Dunn, Erik B. Finger, William D. Payne, David E.R. Sutherland, Raja Kandaswamy, Timothy L. Pruett, Oscar K. Serrano, David M. Vock, Ananta S Bangdiwala, John S. Najarian, and Varvara A. Kirchner
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Male ,Time Factors ,medicine.medical_treatment ,030232 urology & nephrology ,030230 surgery ,Kidney ,Single Center ,Nephrectomy ,Body Mass Index ,Cohort Studies ,Postoperative Complications ,0302 clinical medicine ,Robotic Surgical Procedures ,Living Donors ,Long term outcomes ,Postoperative Period ,Intraoperative Complications ,Laparoscopy ,Kidney transplantation ,Pain, Postoperative ,Surgical approach ,medicine.diagnostic_test ,Graft Survival ,Delayed Graft Function ,Treatment Outcome ,Tissue and Organ Harvesting ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,Universities ,Minnesota ,Patient Readmission ,Living donor nephrectomy ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,Minimally Invasive Surgical Procedures ,Blood Transfusion ,Probability ,Transplantation ,business.industry ,Length of Stay ,medicine.disease ,Kidney Transplantation ,Surgery ,business - Abstract
The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes.All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques.We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P0.001) and heavier (P0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P0.001). All 3 LDN modalities required a longer operative time (P0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P0.001) and reduced the incidence of intraoperative complications (P0.001) and hospital length of stay (P0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (30 day, P0.001) and long-term (30 day, P0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]).In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.
- Published
- 2016
18. Long-term Outcomes for Living Pancreas Donors in the Modern Era
- Author
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Bernhard J. Hering, Abhinav Humar, Melena D. Bellin, Arthur J. Matas, Rainer W.G. Gruessner, Ty B. Dunn, Erik B. Finger, Raja Kandaswamy, David E.R. Sutherland, Timothy L. Pruett, Aleksandra Kukla, and Varvara A. Kirchner
- Subjects
Adult ,Male ,medicine.medical_specialty ,Blood transfusion ,Adolescent ,Minnesota ,medicine.medical_treatment ,Splenectomy ,030230 surgery ,Diabetes Complications ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Risk Factors ,Diabetes mellitus ,Outcome Assessment, Health Care ,Living Donors ,medicine ,Humans ,Blood Transfusion ,Young adult ,Life Style ,Pancreas ,Transplantation ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Graft Survival ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Treatment Outcome ,Quality of Life ,Pancreatitis ,Female ,030211 gastroenterology & hepatology ,Pancreas Transplantation ,business ,Body mass index - Abstract
Background Living donor segmental pancreas transplants (LDSPTx) have been performed selectively to offer a preemptive transplant option for simultaneous pancreas-kidney recipients and to perform a single operation decreasing the cost of pancreas after kidney transplant. For solitary pancreas transplants, this option historically provided a better immunologic match. Although short-term donor outcomes have been documented, there are no long-term studies. Methods We studied postdonation outcomes in 46 segmental pancreas living donors. Surgical complications, risk factors (RF) for development of diabetes mellitus (DM) and quality of life were studied. A risk stratification model (RSM) for DM was created using predonation and postdonation RFs. Recipient outcomes were analyzed. Results Between January 1, 1994 and May 1, 2013, 46 LDSPTx were performed. Intraoperatively, 5 (11%) donors received transfusion. Overall, 9 (20%) donors underwent splenectomy. Postoperative complications included: 6 (13%) peripancreatic fluid collections and 2 (4%) pancreatitis episodes. Postdonation, DM requiring oral hypoglycemics was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%) donors. RSM with three predonation RFs (oral glucose tolerance test, basal insulin, fasting plasma glucose) and 1 postdonation RF, greater than 15% increase in body mass index from preoperative (Δ body mass index >15), predicted 12 (100%) donors that developed postdonation DM. Quality of life was not significantly affected by donation. Mean graft survival was 9.5 (±4.4) years from donors without and 9.6 (±5.4) years from donors with postdonation DM. Conclusions LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using RSM and predonation counseling on life style modifications postdonation.
- Published
- 2016
19. Evolution of Islet Transplantation for the Last 30 Years
- Author
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Alan C. Farney, Emmanuel C. Opara, and David E.R. Sutherland
- Subjects
Blood Glucose ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Economic shortage ,Pancreas transplantation ,History, 21st Century ,Islets of Langerhans ,03 medical and health sciences ,Endocrinology ,Diabetes Mellitus ,Internal Medicine ,medicine ,Isolation techniques ,Animals ,Humans ,Hypoglycemic Agents ,Insulin ,Intensive care medicine ,geography ,geography.geographical_feature_category ,Hepatology ,business.industry ,Critical factors ,Immunosuppression ,Recovery of Function ,History, 20th Century ,Islet ,Transplantation ,Treatment Outcome ,surgical procedures, operative ,030104 developmental biology ,Human pancreas ,Diffusion of Innovation ,business ,Biomarkers ,Immunosuppressive Agents - Abstract
In this article, we will review the changes that have occurred in islet transplantation at the birth of Pancreas 30 years ago. The first attempts at β-cell replacement in humans, pancreas and islet transplantation, were performed in the 1960s and 1970s. Although pancreas transplantation has been an accepted treatment for severe labile diabetes predating the emergence of the journal, allogeneic islet transplantation remains experimental. Current investigations within islet transplantation focus to improve islet function after transplantation. Improving islet viability during isolation, exploring ways to increase engraftment, and protection from the host immune system are some of the goals of these investigative efforts. The major barriers to clinical islet transplantation are shortage of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. It is generally accepted that islet encapsulation is an immunoisolation tool with good potential to address the first 2 of those barriers. We have therefore devoted a major part of this review to the critical factors needed to make it a clinical reality. With improved islet isolation techniques and determination of the best site of engraftment as well as improved encapsulation techniques, we hope that islet transplantation could someday achieve routine clinical use.
- Published
- 2016
20. Total Pancreactectomy with Islet Autotransplant Failure: Now What?
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David E.R. Sutherland, Ty B. Dunn, K. Louise Berry, Timothy L. Pruett, Varvara A. Kirchner, and Melena D. Bellin
- Subjects
Transplantation ,geography ,medicine.medical_specialty ,geography.geographical_feature_category ,Hepatology ,business.industry ,Insulin ,medicine.medical_treatment ,General surgery ,Immunology ,Pancreas transplantation ,Islet ,medicine.disease ,Gastroenterology ,Therapeutic approach ,Quality of life ,Nephrology ,Internal medicine ,medicine ,Risk of mortality ,Pancreatitis ,Endocrine system ,Surgery ,business - Abstract
Total pancreatectomy with islet cell autotransplant (TPIAT) is a definitive therapeutic approach to pain management for patients with chronic pancreatitis that is non-responsive to maximum medical management. Total pancreatectomy (TP) results in brittle diabetes unless islet cell autotransplant (IAT) is concomitantly performed. Even with IAT, about 30 % of patients will require long-term basal-bolus insulin therapy due to significant endocrine insufficiency. The focus of this review is on the utility of whole organ pancreas transplantation toward improving quality of life, and decreasing the risk of mortality and overall cost of care for the subset of patients who experience endocrine and exocrine deficiency after pancreatic resection.
- Published
- 2015
21. Outcomes of Pancreas Retransplantation
- Author
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E. Rudolph, David E.R. Sutherland, Ty B. Dunn, Erik B. Finger, Raja Kandaswamy, and Nikolaos Chandolias
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Adult ,Graft Rejection ,Male ,Reoperation ,medicine.medical_specialty ,Time Factors ,Databases, Factual ,Minnesota ,Technical failure ,Kaplan-Meier Estimate ,Risk Assessment ,Postoperative Complications ,Risk Factors ,Humans ,Medicine ,Transplantation ,business.industry ,Patient Selection ,General surgery ,Graft Survival ,Treatment Outcome ,medicine.anatomical_structure ,Female ,Registry data ,Pancreas Transplantation ,business ,Pancreas - Abstract
Pancreas retransplantation is associated with increased rates of technical failure and rejection compared to other organ transplants. As such, it is not routinely done, and outcomes are mostly known through registry data. Here we analyze the outcomes of primary versus retransplant for all pancreas transplants done in our program over nearly 35 years.Donor and recipient characteristics and outcomes data were prospectively gathered and recorded in our institutional database. Outcomes of primary and retransplants were reported overall, and then subgrouped by number (second, third, fourth). An in-depth analysis of transplants done after 2003 was included. Rates of technical failure, 1 year acute rejection, graft survival, and patient survival were compared.Two thousand one hundred forty-five pancreas transplants were performed at our institution between 1978 and 2012. Four hundred fifteen of these were retransplants. Improvements were seen in technical failure rates and graft survival for both primary and retransplants over time. There were no significant differences in technical failure or patient survival for primary versus retransplants overall, or by transplant number (second, third, fourth). Modern era retransplants had more acute rejection in the first year after transplantation. Retransplants (vs primary) had decreased mid-term death censored graft survival. Transplant type continues to be an important driver of outcome.Retransplant outcomes have improved over time, yet increased rejection and immunologic graft loss rates remain associated with pancreas retransplantation. In contrast, risk of technical failure and patient death for primary versus retransplants are similar. Therefore, pancreas retransplantation in highly selected candidates should be considered in experienced centers.
- Published
- 2015
22. Significant arterial complications after pancreas transplantation-A single-center experience and review of literature
- Author
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David E.R. Sutherland, Kunal Yadav, Jafar Golzarian, Erik B. Finger, Shamar Young, Ty B. Dunn, and Raja Kandaswamy
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Arteriovenous fistula ,030230 surgery ,Pancreas transplantation ,Single Center ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Pseudoaneurysm ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Risk Factors ,medicine ,Humans ,Embolization ,Prospective Studies ,Retrospective Studies ,Surgical repair ,Transplantation ,medicine.diagnostic_test ,business.industry ,Graft Survival ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,surgical procedures, operative ,Angiography ,Arteriovenous Fistula ,Female ,Radiology ,Pancreas Transplantation ,business ,Complication ,Follow-Up Studies - Abstract
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. This article is protected by copyright. All rights reserved.
- Published
- 2017
23. Assessment of β-Cell Mass and α- and β-Cell Survival and Function by Arginine Stimulation in Human Autologous Islet Recipients
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Lindsey D. Bogachus, Timothy L. Pruett, Melena D. Bellin, Michael R. Rickels, David E.R. Sutherland, R. Paul Robertson, Susan D. Parazzoli, Appakalai N. Balamurugan, Gregory J. Beilman, Christian Schuetz, Mary-Elizabeth Patti, Elizabeth Oseid, and Ty B. Dunn
- Subjects
Adult ,Male ,endocrine system ,medicine.medical_specialty ,Arginine ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,030209 endocrinology & metabolism ,Stimulation ,Biology ,Glucagon ,03 medical and health sciences ,0302 clinical medicine ,Insulin-Secreting Cells ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,geography ,geography.geographical_feature_category ,Insulin ,medicine.disease ,Islet ,Transplantation ,Endocrinology ,Glucagon-Secreting Cells ,Pancreatitis ,Female ,Immunology and Transplantation ,Function (biology) - Abstract
We used intravenous arginine with measurements of insulin, C-peptide, and glucagon to examine β-cell and α-cell survival and function in a group of 10 chronic pancreatitis recipients 1–8 years after total pancreatectomy and autoislet transplantation. Insulin and C-peptide responses correlated robustly with the number of islets transplanted (correlation coefficients range 0.81–0.91; P < 0.01–0.001). Since a wide range of islets were transplanted, we normalized the insulin and C-peptide responses to the number of islets transplanted in each recipient for comparison with responses in normal subjects. No significant differences were observed in terms of magnitude and timing of hormone release in the two groups. Three recipients had a portion of the autoislets placed within their peritoneal cavities, which appeared to be functioning normally up to 7 years posttransplant. Glucagon responses to arginine were normally timed and normally suppressed by intravenous glucose infusion. These findings indicate that arginine stimulation testing may be a means of assessing the numbers of native islets available in autologous islet transplant candidates and is a means of following posttransplant α- and β-cell function and survival.
- Published
- 2014
24. Total Pancreatectomy and Islet Autotransplantation in Children for Chronic Pancreatitis
- Author
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Melena D. Bellin, Selwyn M. Vickers, J. J. Wilhelm, Martin L. Freeman, Ty B. Dunn, Gregory J. Beilman, Appakalai N. Balamurugan, Timothy L. Pruett, Bernhard J. Hering, Jose M. Jimenez-Vega, Sarah Jane Schwarzenberg, David M. Radosevich, Srinath Chinnakotla, Barbara Bland, David E.R. Sutherland, and Marie Cook
- Subjects
Male ,medicine.medical_specialty ,Abdominal pain ,Time Factors ,Adolescent ,Minnesota ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Severity of Illness Index ,Transplantation, Autologous ,Article ,Endosonography ,Pancreatectomy ,Postoperative Complications ,Pancreatitis, Chronic ,medicine ,Humans ,Pancreatitis, chronic ,Child ,Pain Measurement ,Retrospective Studies ,Cholangiopancreatography, Endoscopic Retrograde ,Postoperative Care ,business.industry ,Incidence ,Odds ratio ,medicine.disease ,Autotransplantation ,Abdominal Pain ,Surgery ,Transplantation ,Treatment Outcome ,Quality of Life ,Pancreatitis ,Female ,Puestow procedure ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Follow-Up Studies - Abstract
Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients.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.Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012.Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P0.001). 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; P0.001).Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The β-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.
- Published
- 2014
25. Metabolic Assessment Prior to Total Pancreatectomy and Islet Autotransplant: Utility, Limitations and Potential
- Author
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R. Lundberg, David E.R. Sutherland, Appakalai N. Balamurugan, David M. Radosevich, Peggy Ptacek, Melena D. Bellin, Antoinette Moran, Timothy L. Pruett, Ty B. Dunn, Srinath Chinnakotla, Joshua J. Wilhelm, Gregory J. Beilman, R. P. Robertson, and Bernhard J. Hering
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Total pancreatectomy ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Logistic regression ,Body weight ,Transplantation, Autologous ,Gastroenterology ,Article ,Fasting glucose ,Islets of Langerhans ,Pancreatectomy ,Postoperative Complications ,Risk Factors ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,Preoperative Care ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Prospective Studies ,Transplantation ,geography ,geography.geographical_feature_category ,C-Peptide ,business.industry ,Glucose Tolerance Test ,Prognosis ,Islet ,medicine.disease ,Diabetes Mellitus, Type 1 ,Endocrinology ,Metabolic control analysis ,Female ,business ,Follow-Up Studies - Abstract
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 (
- Published
- 2013
26. A Composite Risk Model for Predicting Technical Failure in Pancreas Transplantation
- Author
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David E.R. Sutherland, Arthur J. Matas, Raja Kandaswamy, David M. Radosevich, Ty B. Dunn, Srinath Chinnakotla, Erik B. Finger, and Timothy L. Pruett
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,Tissue and Organ Procurement ,medicine.medical_treatment ,Technical failure ,Pancreas transplantation ,Single Center ,Risk Assessment ,Gastroenterology ,Article ,Risk model ,Risk Factors ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Registries ,Treatment Failure ,Risk factor ,Survival rate ,Retrospective Studies ,Transplantation ,business.industry ,Retrospective cohort study ,Middle Aged ,United States ,Surgery ,Survival Rate ,Female ,Pancreas Transplantation ,business ,Risk assessment ,Follow-Up Studies - Abstract
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 =
- Published
- 2013
27. Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation
- Author
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Martin L. Freeman, Timothy L. Pruett, Ty B. Dunn, Melena D. Bellin, Yu Kuei Lin, David E.R. Sutherland, Timothy B. Gardner, R. Matthew Walsh, Samuel J. Kesseli, Tyler Stevens, David A. Axelrod, Matthew Wagar, Min K. Jung, Sushela Chaidarun, Kerrington D. Smith, Betul Hatipoglu, and Gregory J. Beilman
- Subjects
Adult ,Male ,endocrine system ,medicine.medical_specialty ,animal structures ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Transplantation, Autologous ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pancreatectomy ,Postoperative Complications ,Recurrence ,Diabetes mellitus ,Pancreatitis, Chronic ,medicine ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Insulin ,Pancreatitis, chronic ,Glycemic ,Retrospective Studies ,Glycated Hemoglobin ,geography ,geography.geographical_feature_category ,Hepatology ,C-Peptide ,business.industry ,Gastroenterology ,Retrospective cohort study ,medicine.disease ,Islet ,Autotransplantation ,Surgery ,Transplantation ,Treatment Outcome ,Pancreatitis ,030220 oncology & carcinogenesis ,Acute Disease ,030211 gastroenterology & hepatology ,Female ,Health Facilities ,business - Abstract
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.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.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-peptide2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.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.
- Published
- 2016
28. A New Enzyme Mixture to Increase the Yield and Transplant Rate of Autologous and Allogeneic Human Islet Products
- Author
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David E.R. Sutherland, Gopalakrishnan Loganathan, David M. Radosevich, Melena D. Bellin, James V. Harmon, Joshua J. Wilhelm, Klearchos K. Papas, Sajjad M. Soltani, Bernhard J. Hering, M. Tiwari, Appakalai N. Balamurugan, Takeshi Yuasa, Takayuki Anazawa, and Robert C. McCarthy
- Subjects
Adult ,Male ,endocrine system ,Allogeneic transplantation ,endocrine system diseases ,Minnesota ,Islets of Langerhans Transplantation ,Thermolysin ,Transplantation, Autologous ,Article ,Andrology ,Islets of Langerhans ,Young Adult ,Clostridium histolyticum ,Endopeptidases ,medicine ,Humans ,Transplantation, Homologous ,Bacillaceae ,Tissue Survival ,Transplantation ,geography ,Chi-Square Distribution ,geography.geographical_feature_category ,biology ,Middle Aged ,biology.organism_classification ,Islet ,medicine.disease ,Microbial Collagenase ,Treatment Outcome ,Microbial collagenase ,Multivariate Analysis ,Immunology ,Tissue and Organ Harvesting ,Collagenase ,Regression Analysis ,Pancreatitis ,Female ,medicine.drug - Abstract
BACKGROUND The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch), and neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP). METHODS We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP in place of thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from eight different ECs were statistically compared using multivariate analysis. RESULTS The NEM consistently achieved higher islet yields from pancreatitis (P
- Published
- 2012
29. Ten-Year Outcome after Rapid Discontinuation of Prednisone in Adult Primary Kidney Transplantation
- Author
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Arthur J. Matas, Ty B. Dunn, David E.R. Sutherland, Timothy L. Pruett, William D. Payne, Richard Spong, Erik B. Finger, Raja Kandaswamy, John S. Najarian, Aleksandra Kukla, Michael Rizzari, Hassan N. Ibrahim, Thomas M. Suszynski, Srinath Chinnakotla, and Kristen J. Gillingham
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Epidemiology ,Minnesota ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Critical Care and Intensive Care Medicine ,Risk Assessment ,Living donor ,Drug Administration Schedule ,Risk Factors ,Prednisone ,Diabetes mellitus ,Living Donors ,medicine ,Humans ,Kidney transplantation ,Transplantation ,business.industry ,Incidence (epidemiology) ,Graft Survival ,Immunosuppression ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Discontinuation ,Surgery ,Treatment Outcome ,surgical procedures, operative ,Nephrology ,Female ,Graft survival ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein.Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied.Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year death-censored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups.Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.
- Published
- 2012
30. Pushing the envelope
- Author
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Angelika C. Gruessner, David M. Radosevich, Rainer W.G. Gruessner, Raja Kandaswamy, and David E.R. Sutherland
- Subjects
medicine.medical_specialty ,Waiting Lists ,medicine.medical_treatment ,Future application ,Pancreas transplantation ,Living donor ,Pancreatectomy ,Diabetes mellitus ,Cadaver ,Diabetes Mellitus ,Living Donors ,medicine ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,Dialysis ,Transplantation ,business.industry ,Mortality rate ,medicine.disease ,Kidney Transplantation ,Surgery ,Pancreas Transplantation ,business - Abstract
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.
- Published
- 2012
31. Long-term outcome after pancreas transplantation
- Author
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Angelika C. Gruessner, David E.R. Sutherland, and Rainer W.G. Gruessner
- Subjects
medicine.medical_specialty ,Time Factors ,Waiting Lists ,endocrine system diseases ,medicine.medical_treatment ,Decision Making ,Treatment outcome ,Pancreas transplantation ,Gastroenterology ,Renal Dialysis ,Diabetes mellitus ,Internal medicine ,Insulin Secretion ,Living Donors ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Immunology and Allergy ,Diabetic Nephropathies ,In patient ,Renal Insufficiency ,Insulin secretion ,Kidney transplantation ,Immunosuppression Therapy ,Transplantation ,business.industry ,Graft Survival ,nutritional and metabolic diseases ,medicine.disease ,Kidney Transplantation ,Diabetes Mellitus, Type 1 ,Logistic Models ,Treatment Outcome ,medicine.anatomical_structure ,Pancreas Transplantation ,business ,Pancreas - Abstract
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.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.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.
- Published
- 2012
32. Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases
- Author
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David E.R. Sutherland, R. Paul Robertson, Timothy L. Pruett, Stuart K. Amateau, Bernhard J. Hering, Mustafa A. Arain, Ty B. Dunn, Gregory J. Beilman, Sarah Jane Schwarzenberg, Marie Cook, David M. Radosevich, Martin L. Freeman, Srinath Chinnakotla, Joshua J. Wilhelm, J. Shawn Mallery, Louise Berry, Melena D. Bellin, and Alfred L. Clavel
- Subjects
Adult ,Male ,Narcotics ,medicine.medical_specialty ,Adolescent ,Total pancreatectomy ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Article ,Young Adult ,Pancreatectomy ,Risk Factors ,Pancreatitis, Chronic ,medicine ,Humans ,Pancreatitis, chronic ,Young adult ,Child ,Aged ,Retrospective Studies ,geography ,Pain, Postoperative ,geography.geographical_feature_category ,business.industry ,General surgery ,Graft Survival ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Islet ,Autotransplantation ,Surgery ,Treatment Outcome ,Child, Preschool ,Pancreatitis ,Female ,business - Abstract
Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT).Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly.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.In our patients, the duration (mean ± SD) of CP before their TP-IAT was 7.1 ± 0.3 years and narcotic usage of 3.3 ± 0.2 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 index30, 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.This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention.
- Published
- 2015
33. Insulin Degradation by Acinar Cell Proteases Creates a Dysfunctional Environment for Human Islets Before/After Transplantation: Benefits of α-1 Antitrypsin Treatment
- Author
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Klearchos K. Papas, Subbiah Pugazhenthi, Zhiguang Guo, Appakalai N. Balamurugan, Alexander C. Wiseman, Gopalakrishnan Loganathan, Sajjad M. Soltani, Ashok K. Saluja, Rajinder K. Dawra, Mark A. Sanders, Bernhard J. Hering, Kumaravel Velayutham, and David E.R. Sutherland
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Proteases ,Serine Proteinase Inhibitors ,endocrine system diseases ,medicine.medical_treatment ,Transplantation, Heterologous ,Islets of Langerhans Transplantation ,Mice, Nude ,Heterologous ,Acinar Cells ,Biology ,Article ,Streptozocin ,Diabetes Mellitus, Experimental ,Islets of Langerhans ,Mice ,Internal medicine ,Acinar cell ,medicine ,Animals ,Humans ,Insulin ,Protease inhibitor (pharmacology) ,Cells, Cultured ,Transplantation ,geography ,Islet cell transplantation ,geography.geographical_feature_category ,Graft Survival ,Islet ,Disease Models, Animal ,Treatment Outcome ,surgical procedures, operative ,Endocrinology ,alpha 1-Antitrypsin ,Cancer research ,Peptide Hydrolases - Abstract
Pancreatic acinar cells are commonly cotransplanted along with islets during auto- and allotransplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and improve function with supplementation of α-1 antitrypsin (A1AT).Acinar cell protease activity, insulin levels, and percent islet loss were measured after culture of pure and impure clinical islet preparations. The effect of proteases on ultrastructure of islets and β-cell insulin granules were examined by transmission electron microscopy. The number of insulin granules and insulin-labeled immunogold particles were counted. The in vivo effect of proteases on islet function was studied by transplanting acinar cells adjacent to islet grafts in diabetic mice. The effects of A1AT culture supplementation on protease activity, insulin levels, and islet function were assessed in pure and impure islets.Islet loss after culture was significantly higher in impure relative to pure preparations (30% vs. 14%, P0.04). Lower islet purity was associated with increased protease activity and decreased insulin levels in culture supernatants. Reduced β-cell insulin granules and insulin degradation by proteases were confirmed by transmission electron microscopy. Transplantations in mice showed delayed islet graft function when acinar cells were transplanted adjacent to the islets under the kidney capsule. Supplementation of A1AT to impure islet cultures maintained islet cell mass, restored insulin levels, and preserved islet functional integrity.Culture of impure human islet fractions in the presence of A1AT prevents insulin degradation and improves islet recovery.
- Published
- 2011
34. Quality of Life Improves for Pediatric Patients After Total Pancreatectomy and Islet Autotransplant for Chronic Pancreatitis
- Author
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David E.R. Sutherland, Antoinette Moran, Bernhard J. Hering, David M. Radosevich, Sarah Jane Schwarzenberg, Gregory J. Beilman, Appakalai N. Balamurugan, Melena D. Bellin, Srinath Chinnakotla, Martin L. Freeman, Selwyn M. Vickers, and Ty B. Dunn
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,SF-36 ,Minnesota ,medicine.medical_treatment ,Population ,Islets of Langerhans Transplantation ,Transplantation, Autologous ,Article ,Pancreatectomy ,Quality of life ,Pancreatitis, Chronic ,Internal medicine ,medicine ,Humans ,Pancreatitis, chronic ,Child ,education ,Academic Medical Centers ,education.field_of_study ,Hepatology ,business.industry ,Gastroenterology ,medicine.disease ,Surgery ,Clinical trial ,Transplantation ,Treatment Outcome ,Child, Preschool ,Quality of Life ,Pancreatitis ,Female ,business - Abstract
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.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.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).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.
- Published
- 2011
35. Deterioration of glycemic control after corticosteroid administration in islet autotransplant recipients: a cautionary tale
- Author
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Melena D. Bellin, David E.R. Sutherland, Anh Ngo, and Gregory J. Beilman
- Subjects
Adult ,Blood Glucose ,medicine.medical_specialty ,Urticaria ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Transplantation, Autologous ,Gastroenterology ,Article ,Young Adult ,Pancreatectomy ,Endocrinology ,Insulin resistance ,Adrenal Cortex Hormones ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Pain Management ,Aged ,Glycated Hemoglobin ,geography ,geography.geographical_feature_category ,business.industry ,Insulin ,General Medicine ,Middle Aged ,medicine.disease ,Islet ,Transplantation ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Sitagliptin ,Corticosteroid ,Female ,business ,medicine.drug - Abstract
Islet autotransplantation (IAT) is performed at the time of total pancreatectomy (TP) to prevent or minimize post-surgical diabetes. Corticosteroids induce insulin resistance and present a risk to islet autografts, through glucotoxicity and increased metabolic demand on a marginal islet mass. We present four IAT recipients treated with oral or injected corticosteroids after transplant for medical conditions unrelated to chronic pancreatitis or TPIAT. Hyperglycemia or insulin resistance was evident in all four patients, including reversion to long-term insulin therapy in two patients. One patient receiving corticosteroid injections had a transient increase in hemoglobin A1c (+0.6% above baseline), and one patient given a one time dose of oral dexamethasone exhibited hyperglycemia despite high insulin (>200 mU/L) and C-peptide (15.3 ng/mL) production on an oral glucose tolerance test. IAT recipients have insufficient islet mass to compensate for the insulin resistance induced by corticosteroids. Caution should be given to using these agents in IAT recipients. When corticosteroids are medically necessary, insulin therapy should be administered temporarily to compensate for the increased metabolic demand and minimize long-term risks on the islet graft.
- Published
- 2011
36. Development of diabetes mellitus in living pancreas donors and recipients
- Author
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David E.R. Sutherland, Stephan Gruessner, Helena Reijonen, Rainer W.G. Gruessner, Tun Jie, George W. Burke, Alberto Pugliese, and Chirag S. Desai
- Subjects
Risk ,medicine.medical_treatment ,Immunology ,Autoimmunity ,Pancreas transplantation ,medicine.disease_cause ,Pancreatectomy ,Postoperative Complications ,Insulin-Secreting Cells ,Diabetes mellitus ,Diabetes Mellitus ,Living Donors ,Secondary Prevention ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Obesity ,Immunosuppression Therapy ,Autoimmune disease ,Transplantation ,business.industry ,Autoantibody ,Immunosuppression ,medicine.disease ,medicine.anatomical_structure ,Hyperglycemia ,Pancreas Transplantation ,business ,Pancreas - Abstract
Previously, recurrence of insulin-dependent diabetes mellitus after pancreas transplants was only sporadically reported. Newer data, however, indicate recurrence rates as high as 5%. After identical-twin pancreas transplants, diabetes recurs in the absence of immunosuppressive therapy - strong evidence that it is an autoimmune disease. After deceased donor pancreas transplants, immunologic markers (autoantibodies, autoreactive T cells) herald recurrence. Selective destruction of β cells, still relatively uncommon, is not restricted to MHC compatibility. The development of diabetes in living pancreas donors is rare; it can be largely avoided by meticulous metabolic evaluation before donation and prevention of obesity after donation.
- Published
- 2011
37. Prediction of Pancreatic Tissue Densities by an Analytical Test Gradient System Before Purification Maximizes Human Islet Recovery for Islet Autotransplantation/Allotransplantation
- Author
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S. Matsumoto, Joshua J. Wilhelm, Bernhard J. Hering, Takayuki Anazawa, Gopalakrishnan Loganathan, Sajjad M. Soltani, Appakalai N. Balamurugan, Klearchos K. Papas, David E.R. Sutherland, and Yukihide Yonekawa
- Subjects
Adult ,Male ,endocrine system ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Density gradient ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Cell Separation ,Biology ,Transplantation, Autologous ,Andrology ,Islets of Langerhans ,Young Adult ,Pancreatitis, Chronic ,Internal medicine ,Centrifugation, Density Gradient ,medicine ,Humans ,Transplantation, Homologous ,Centrifugation ,Pancreatitis, chronic ,Pancreas ,Transplantation ,geography ,geography.geographical_feature_category ,Middle Aged ,medicine.disease ,Islet ,Autotransplantation ,Endocrinology ,medicine.anatomical_structure ,Female ,Allotransplantation - Abstract
Background Using standard density gradient (SDG) ranges for human islet purification frequently results in islet loss and transplantation of lower islet mass. Measuring the densities of islet and acinar tissue beforehand to customize the gradient range for the actual COBE 2991 cell processor (COBE) purification is likely to maximize the recovery of islets. We developed an analytical test gradient system (ATGS) for predicting pancreatic tissue densities before COBE purification to minimize islet loss during purification. Methods Human islets were isolated from deceased donor (n=30) and chronic pancreatitis pancreata (n=30). Pancreatic tissue densities were measured before purification by the ATGS, and the density gradient range for islet purification in a COBE was customized based on density profiles determined by the ATGS. The efficiency of custom density gradients (CDGs) to recover high islet yield was compared with predefined SDGs. Results Pancreatic tissue densities from autografts were significantly higher than in allograft preparations. In allograft purifications, a higher proportion of islets were recovered using ATGS-guided CDGs (85.9%±18.0%) compared with the SDG method (69.2%±27.0%; P=0.048). Acinar contamination at 60%, 70%, and 80% cumulative islet yield for allografts was significantly lower in the CDG group. In autograft purifications, more islets were recovered with CDGs (81.9%±28.0%) than SDGs (55.8%±22.8%; P=0.03). CDGs effectively reduced islet loss by minimizing islet sedimentation in the COBE bag. Conclusions Using ATGS-guided CDGs maximizes the islet recovery for successful transplantations by reducing acinar contamination in allograft preparations and by reducing sedimentation of islets in the COBE bag in autograft preparations.
- Published
- 2011
38. Chylous Ascites Requiring Surgical Intervention after Donor Nephrectomy: Case Series and Single Center Experience
- Author
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David E.R. Sutherland, Arthur J. Matas, Raja Kandaswamy, and Johan Aerts
- Subjects
Male ,medicine.medical_specialty ,Chyle ,medicine.medical_treatment ,Single Center ,Nephrectomy ,Article ,Postoperative Complications ,Renal Artery ,Chylous ascites ,Ascites ,Living Donors ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Chylous Ascites ,Kidney transplantation ,Transplantation ,business.industry ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Parenteral nutrition ,Tissue and Organ Harvesting ,Laparoscopy ,medicine.symptom ,business ,Complication - Abstract
Chylous ascites as a result of laparoscopic donor nephrectomy (LDN) is a rare complication which carries significant morbidity, including severe protein-calorie malnutrition and an associated immunocompromised state. We report a patient who underwent hand-assisted left LDN and subsequently developed chylous ascites. He failed conservative therapy including low-fat diet with medium-chain triglycerides (LFD/MCT) and oral protein supplementation as well as strict NPO status with intravenous (IV) total parenteral nutrition (TPN) and subcutaneous (SQ) somatostatin analogue administration. Laparoscopic re-exploration and intracorporeal suture ligation and clipping of leaking lymph channels successfully sealed the chyle leak. We review the literature to date including diagnosis, incidence, management options, psychosocial aspects and clinical outcomes of chylous ascites after LDN.
- Published
- 2010
39. Correlation of Pancreatic Histopathologic Findings and Islet Yield in Children With Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation
- Author
-
David E.R. Sutherland, Martin L. Freeman, Bernhard J. Hering, Antoinette Moran, J C Manivel, Takashi Kobayashi, Melena D. Bellin, and Annelisa M. Carlson
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Nesidioblastosis ,Gastroenterology ,Article ,Pancreatectomy ,Endocrinology ,Atrophy ,Pancreatitis, Chronic ,Internal medicine ,Outcome Assessment, Health Care ,Internal Medicine ,Acinar cell ,Humans ,Medicine ,Child ,Pancreas ,geography ,geography.geographical_feature_category ,Hepatology ,business.industry ,Age Factors ,medicine.disease ,Islet ,Fibrosis ,Autotransplantation ,medicine.anatomical_structure ,Child, Preschool ,Pancreatitis ,Female ,Beta cell ,business ,Follow-Up Studies - Abstract
OBJECTIVES: The probability of insulin independence after intraportal islet autotransplantation (IAT) for chronic pancreatitis (CP) treated by total pancreatectomy (TP) relates to the number of islets isolated from the excised pancreas. Our goal was to correlate the islet yield with the histopathologic findings and the clinical parameters in pediatric (age
- Published
- 2010
40. Predicting islet yield in pediatric patients undergoing pancreatectomy and autoislet transplantation for chronic pancreatitis
- Author
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Melena D. Bellin, Antoinette Moran, Ty B. Dunn, Appakalai N. Balamurugan, William Thomas, Gregory J. Beilman, David E.R. Sutherland, and Juan J. Blondet
- Subjects
Blood Glucose ,Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Cystic Fibrosis Transmembrane Conductance Regulator ,Gastroenterology ,chemistry.chemical_compound ,Insulin ,Medicine ,Trypsin ,Prospective Studies ,Child ,geography.geographical_feature_category ,C-Peptide ,Area under the curve ,Fasting ,Islet ,Pain, Intractable ,Treatment Outcome ,Trypsin Inhibitor, Kazal Pancreatic ,Child, Preschool ,Creatinine ,Pancreatectomy ,Female ,endocrine system ,medicine.medical_specialty ,Adolescent ,Transplantation, Autologous ,Article ,Islets of Langerhans ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Humans ,Hypoglycemic Agents ,Glycated Hemoglobin ,geography ,business.industry ,medicine.disease ,Transplantation ,Diabetes Mellitus, Type 1 ,Endocrinology ,chemistry ,Pediatrics, Perinatology and Child Health ,Pancreatitis ,Carrier Proteins ,business - Abstract
Bellin MD, Blondet JJ, Beilman GJ, Dunn TyB, Balamurugan AN, Thomas W, Sutherland DER, Moran A. Predicting islet yield in pediatric patients undergoing pancreatectomy and autoislet transplantation for chronic pancreatitis. Background/Objective: Chronic pancreatitis (CP) in children is associated with significant morbidity and can lead to narcotic dependence. Total pancreatectomy (TP) may be indicated in refractory CP to relieve pain; simultaneous islet autotransplant (IAT) may prevent postsurgical diabetes. About half of pediatric patients are insulin independent 1 yr after IAT. Insulin independence correlates best with the number of islets available for transplantation (islet yield). Currently there is no known method to predict islet yield in a given patient. We assessed the ability of preoperative metabolic tests to predict islet yields in 10 children undergoing TP/IAT. Design/Methods: Hemoglobin A1c (HbA1c) and mixed meal tolerance tests (MMTT) were obtained prior to surgery in 10 patients age ≤ 18 yr. Fasting glucose, C-peptide, and creatinine were used to calculate the C-peptide to glucose* creatinine ratio (CPGCR). C-peptide peak and area under the curve (AUC) were determined from 2 h MMTT. Linear regressions were performed to predict islet yield from baseline test results. Results: Islet yield ranged from 7000 to 434 000 islet equivalents (IE) (mean 222 452 ± 148 697 IE). Islet yield was well predicted from body weight and fasting plasma glucose (R 2 = 57%, adjusted for overfitting by bootstrap). Islet yield was positively associated with CPGCR, peak C-peptide, and AUC C-peptide and negatively associated with HbA1c. Conclusions: Pilot data from 10 pediatric patients suggest that simple preoperative measurement of fasting plasma glucose may give a useful prediction of islet yield. Islet yield correlates with HbA1c and C-peptide levels. This information allows individual candidates to weigh the specific risk of becoming diabetic against the benefit of pain relief should they undergo TP-IAT.
- Published
- 2009
41. Short‐ and long‐term outcome for living pancreas donors
- Author
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David E.R. Sutherland, Jason F. Reynoso, Christine Gruessner, and Rainer W.G. Gruessner
- Subjects
Blood Glucose ,medicine.medical_specialty ,Time Factors ,Pancreatic pseudocyst ,medicine.medical_treatment ,Pancreas transplantation ,Lower risk ,Pancreatectomy ,Postoperative Complications ,Metabolic Diseases ,Internal medicine ,Living Donors ,medicine ,Humans ,Pancreas ,Glycated Hemoglobin ,Hepatology ,business.industry ,Pancreatic Diseases ,Immunosuppression ,Prognosis ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Pancreatitis ,Pancreas Transplantation ,business ,Follow-Up Studies ,Pancreatic abscess - Abstract
The advantages of living donor pancreas transplants for the recipient include good HLA matching, lower immunologic risk, less immunosuppression, lower risk of infection and of posttransplant malignancies, and shorter pancreas graft preservation time. In 2008, a total of 155 segmental pancreas transplants using living donors were reported to the International Pancreas Transplant Registry from six countries. Pancreas living donors need to undergo a thorough pretransplant endocrinologic workup in order to minimize the risk of metabolic complications. The pretransplant workup has evolved over time, after initial reports showed that up to 25% of living donors had elevated hemoglobin A(1c) levels after donation. Avoiding obesity after donation diminishes the risk of long-term metabolic complications. The risk of surgical complications for the donor (such as pancreatitis, pancreatic leak or fistula, pancreatic abscess, and pancreatic pseudocyst) is less than 5%. If both the donor and recipient operations are technically successful, the long-term graft survival rate is significantly higher for living (versus deceased) donor pancreas transplant recipients. Future long-term studies of metabolic function in living donors are warranted to determine whether living donor pancreas transplants can safely be applied more widely and whether living donors can be used for islet transplants.
- Published
- 2009
42. Upregulating CD4+CD25+FOXP3+ Regulatory T Cells in Pancreatic Lymph Nodes in Diabetic NOD Mice by Adjuvant Immunotherapy
- Author
-
Jianqiang Hao, H Yi, Z. Guo, Bole Tian, L. Tian, Yu Zhang, Timothy O'Brien, David E.R. Sutherland, and Bernhard J. Hering
- Subjects
Blood Glucose ,CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Adoptive cell transfer ,Time Factors ,medicine.medical_treatment ,Freund's Adjuvant ,Autoimmunity ,Mice, SCID ,Nod ,T-Lymphocytes, Regulatory ,complex mixtures ,Transforming Growth Factor beta1 ,Mice ,Adjuvants, Immunologic ,Mice, Inbred NOD ,Insulin-Secreting Cells ,Diabetes mellitus ,Internal medicine ,Animals ,Hypoglycemic Agents ,Insulin ,Medicine ,IL-2 receptor ,Pancreas ,Cell Proliferation ,NOD mice ,Transplantation ,Type 1 diabetes ,Venoms ,business.industry ,Interleukin-2 Receptor alpha Subunit ,FOXP3 ,Forkhead Transcription Factors ,medicine.disease ,Adoptive Transfer ,Up-Regulation ,Disease Models, Animal ,Diabetes Mellitus, Type 1 ,Endocrinology ,Immunology ,Exenatide ,Drug Therapy, Combination ,Female ,Lymph Nodes ,Peptides ,business - Abstract
Background Immunotherapy with Complete Freund's adjuvant (CFA) is effective in ameliorating autoimmunity in diabetic nonobese diabetic (NOD) mice. We investigated whether CFA treatment up-regulates CD4+CD25+Foxp3+ regulatory T cells and increases transforming growth factor (TGF)-beta1 production in diabetic NOD mice. Methods New-onset diabetic NOD mice were treated with CFA and exendin-4, a potent analog of glucagon-like peptide-1. Reversal of diabetes was determined by monitoring blood glucose level. Ameliorating autoimmunity through immunoregulation was assessed by adoptive transfer. Regulatory T cells in the peripheral blood, spleen, thymus, and pancreatic nodes were measured. TGF-beta1 in plasma and the insulin content in the pancreas were also measured. Immunostainings for insulin and BrdU were performed. Results New-onset diabetes could be reversed in 38% of NOD mice treated with CFA alone and in 86% of NOD mice treated with both CFA and exendin-4. Diabetes adoptive transfer by splenocytes from CFA-treated NOD mice was delayed. The percentage of CD4+CD25+Foxp3+ regulatory T cells in the pancreatic lymph nodes of CFA-treated NOD mice was significantly increased at 1, 5, and 15 to 17 weeks after treatment. TGF-beta1 in the plasma of CFA-treated NOD mice was also significantly increased. Combining CFA with exendin-4 treatment significantly increased the insulin content and the numbers of insulin and BrdU double-labeled beta cells in the islets. Conclusions Our results demonstrated that CFA treatment ameliorates autoimmunity in diabetic NOD mice by up-regulating CD4=CD25+Foxp3+ regulatory T cells and increasing TGF-beta1 production. Exendin-4 enhanced the effect of CFA on reversing diabetes in NOD mice by stimulating beta-cell replication.
- Published
- 2009
43. 2202 Kidney Transplant Recipients with 10 Years of Graft Function: What Happens Next?
- Author
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William D. Payne, Raja Kandaswamy, Kristen J. Gillingham, Abhinav Humar, Arthur J. Matas, John S. Najarian, Ty B. Dunn, and David E.R. Sutherland
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Urinary system ,Population ,Malignancy ,Article ,Risk Factors ,Chronic allograft nephropathy ,Humans ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,Registries ,education ,Aged ,Transplantation ,education.field_of_study ,Kidney ,business.industry ,Graft Survival ,Cancer ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Cardiovascular Diseases ,Chronic Disease ,Female ,Kidney Diseases ,Skin cancer ,business - Abstract
The ultimate goal of clinical transplantation is for the recipients to achieve long-term survival, with continuing graft function, that is equivalent to that of the age-matched general population. We studied subsequent outcome in kidney transplant recipients with 10 years of graft function. In all, 2202 kidney transplant recipients survived with graft function10 years. For 10-year survivors, the actuarial 25-year patient survival rate for primary transplant living donor (LD) recipients was 57%; graft survival, 43%. For primary transplant deceased donor (DD) recipients, the actuarial 25-year patient survival rate was 39%; graft survival, 27%. The two major causes of late graft loss were death (with graft function) and chronic allograft nephropathy (tubular atrophy and interstitial fibrosis). The two major causes of death with function were cardiovascular disease (CVD) and malignancy. For nondiabetic recipients, the mean age at death with function from CVD was 54 +/- 13 years; for diabetic recipients, 53 +/- 7 years. By 20 years posttransplant, morbidity was common:40% recipients had skin cancer (mean age for nondiabetic recipients, 53 +/- 13 years; for diabetics, 49 +/- 8 years),10% had non-skin cancer (mean age for nondiabetic recipients, 53 +/- 16 years; for diabetics, 46 +/- 9 years), and30% had CVD (mean age for nondiabetic recipients, 53 +/- 15 years; for diabetics, 47 +/- 9 years). We conclude that long-term transplant recipients have a high rate of morbidity and early mortality. As short-term results have improved, more focus is needed on long-term outcome.
- Published
- 2008
44. What happens to the kidney in an SPK transplant when the pancreas fails due to a technical complication?
- Author
-
David E.R. Sutherland, Ty B. Dunn, Mark J. Hill, Raquel Garcia, Raja Kandaswamy, and Abhinav Humar
- Subjects
Transplantation ,medicine.medical_specialty ,Kidney ,business.industry ,Incidence (epidemiology) ,Urinary system ,medicine.disease ,Thrombosis ,Surgery ,surgical procedures, operative ,medicine.anatomical_structure ,medicine ,Pancreatitis ,Pancreas ,Complication ,business - Abstract
We examined a group of SPK recipients that had early (
- Published
- 2008
45. Pancreas Allotransplants in Patients with a Previous Total Pancreatectomy for Chronic Pancreatitis
- Author
-
David E.R. Sutherland, Mary Beth Drangstveit, Angelika C. Gruessner, Raja Kandaswamy, and Rainer W.G. Gruessner
- Subjects
Adult ,Male ,Reoperation ,medicine.medical_specialty ,Time Factors ,Pancreatic disease ,medicine.medical_treatment ,Gastroenterology ,Cohort Studies ,Diabetes Complications ,Pancreatectomy ,Pancreatitis, Chronic ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Exocrine pancreatic insufficiency ,Survival rate ,Retrospective Studies ,Immunosuppression Therapy ,business.industry ,Graft Survival ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Transplantation ,medicine.anatomical_structure ,Pancreatitis ,Female ,Pancreas Transplantation ,Pancreas ,business - Abstract
Background A total pancreatectomy is the last resort in the treatment of chronic pancreatitis because it results in complete endocrine and exocrine pancreatic insufficiency. More than 50% of total pancreatectomy patients experience severe glucose control problems, which cause up to 50% of late deaths. Study Design Between June 1, 1986, and May 15, 2007, we performed 26 pancreas allotransplants (18 primary, 8 retransplants) in 18 patients who had previously undergone a total pancreatectomy for chronic pancreatitis. All patients had a history of labile diabetes mellitus with hypoglycemic unawareness; secondary diabetic complications developed in 12. The median time interval from the total pancreatectomy to the pancreas allotransplant was 5 years (range 9 months to 22 years). Of the 26 transplants, 6 were performed in the cyclosporine (CSA) era, 15 in the tacrolimus (TAC) era, and 5 in the calcineurin inhibitor (CNI)-free era. Results Patient survival rates at 1 and 3 years in both the CSA and TAC eras were 100% and 100%; in the CNI-free era, at 1 year, the survival rate was 40%. Pancreas graft survival rates in the CSA era were 67% and 50% at 1 and 3 years, respectively; in the TAC era, 73% and 51%, respectively; and in the CNI-free era, at 1 year, 40% (p=0.13). The mean number of rejection episodes in the CSA era was 2.1; in the TAC era, 1.4; and in the CNI-free era, 0.6. Conclusions Our series of pancreas allotransplants in patients with a previous total pancreatectomy for chronic pancreatitis showed that pancreas graft survival rates of more than 70% can be achieved with TAC-based immunosuppression; pancreas transplants can successfully treat both endocrine and exocrine insufficiency; and sequential pancreas allotransplants should be considered a treatment option in patients with pancreatectomy-induced brittle diabetes mellitus or with progression of secondary complications of diabetes mellitus.
- Published
- 2008
46. Over 500 Solitary Pancreas Transplants in Nonuremic Patients with Brittle Diabetes Mellitus
- Author
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Angelika C. Gruessner, David E.R. Sutherland, Rainer W.G. Gruessner, and Raja Kandaswamy
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Tacrolimus ,chemistry.chemical_compound ,Renal Dialysis ,Risk Factors ,Diabetes mellitus ,medicine ,Humans ,Survival rate ,Retrospective Studies ,Immunosuppression Therapy ,Coma ,Transplantation ,Creatinine ,business.industry ,Graft Survival ,Immunosuppression ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Survival Rate ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,medicine.anatomical_structure ,chemistry ,Multivariate Analysis ,Cyclosporine ,Female ,Pancreas Transplantation ,medicine.symptom ,Pancreas ,business ,Immunosuppressive Agents - Abstract
Background. A pancreas transplant alone (PTA) in a nonuremic patient with brittle diabetes mellitus remains a rare procedure because the tradeoff for insulin independence is lifelong immunosuppression. Methods. Herein we report our results at the University of Minnesota of 513 PTAs from December 17, 1966, through December 31, 2006. Of these recipients, 87% had previously experienced hypoglycemic unawareness and 23% experienced coma and/or seizures. These transplants spanned four immunosuppressive eras: pre-cyclosporine A (pre-CsA) era (16%), CsA era (23%), tacrolimus (TAC) era (47%), and calcineurin-inhibitor (CNI)-free era (14%). Results. The overall patient survival rate at 1 year posttransplant was about 95%; at 5 years, it was 90%. The pancreas graft survival rate at 1 year increased significantly from the pre-CsA era (31%) to the TAC era (75%), thanks to a significant decline in immunologic and technical failures. The CNI-free protocol, because of its high infection and hematologic infection rate, did not further improve outcome. Risk factors for subsequent kidney failure (13% at 5 years posttransplant) were serum creatinine levels > 1.5 mg/dl at the time of the pancreas transplant and recipient age
- Published
- 2008
47. How Can the Care of Diabetic ESRD Patients Be Improved?
- Author
-
David E.R. Sutherland
- Subjects
medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,Intensive care medicine ,business - Published
- 2007
48. Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients
- Author
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Mark T. Reding, Milena Elimelakh, Angelika C. Gruessner, David E.R. Sutherland, Katharine S. Park, Ted Eastlund, Nigel S. Key, Jo Anne H. Van Burik, Timothy P. Singleton, Vanessa Dayton, Robert B. Howe, and Rainer W.G. Gruessner
- Subjects
Adult ,Male ,Hemolytic anemia ,Daclizumab ,Antibodies, Neoplasm ,T-Lymphocytes ,medicine.medical_treatment ,Pure red cell aplasia ,Pilot Projects ,Opportunistic Infections ,Antibodies, Monoclonal, Humanized ,Lymphocyte Activation ,Red-Cell Aplasia, Pure ,Mycophenolic acid ,Autoimmune Diseases ,Postoperative Complications ,Bone Marrow ,medicine ,Humans ,Aplastic anemia ,Alemtuzumab ,Retrospective Studies ,Purpura, Thrombocytopenic, Idiopathic ,business.industry ,Incidence ,Antibodies, Monoclonal ,Immunosuppression ,Hematology ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Immunoglobulin G ,Immunology ,Female ,Anemia, Hemolytic, Autoimmune ,Pancreas Transplantation ,Autoimmune hemolytic anemia ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Background and Objectives Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy. Design and Methods Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005. Results Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made. Interpretation and Conclusions We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.
- Published
- 2007
49. Pediatric Autologous Islet Transplantation
- Author
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David E.R. Sutherland, Sarah Jane Schwarzenberg, Marie Cook, Srinath Chinnakotla, and Melena D. Bellin
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Transplantation, Autologous ,Article ,Pancreatectomy ,Diabetes mellitus ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Child ,geography ,geography.geographical_feature_category ,business.industry ,Pancreatic islets ,General surgery ,Immunosuppression ,Islet ,medicine.disease ,Surgery ,Transplantation ,medicine.anatomical_structure ,Pancreatitis ,Quality of Life ,Pancreas ,business - Abstract
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.
- Published
- 2015
50. Transplantation in Diabetic Patients
- Author
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John S. Najarian and David E.R. Sutherland
- Subjects
Transplantation ,medicine.medical_specialty ,business.industry ,Medicine ,business ,Surgery - Published
- 2015
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