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Tamburrini R, Yang CY, Philip JL, Neidlinger NA, Kaufman DB, Odorico JS. Simultaneous en bloc kidney and pancreas transplantation from pediatric donors: Selection, surgical strategy, management, and outcomes. Am J Transplant 2025; 25:567-573. [PMID: 39566660 DOI: 10.1016/j.ajt.2024.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024]
Abstract
Pediatric donors are underutilized for simultaneous pancreas-kidney transplantation due to concerns about technical complications and inadequate islet and/or renal mass. We analyzed our experience with simultaneous en bloc kidney and pancreas transplantation using pediatric donors on 8 consecutive adult patients from 1997-2018. En bloc kidney transplants were implanted intraperitoneally and contralaterally to right-sided pancreas grafts. All patients became insulin-independent immediately; with 1 case of delayed kidney function and 1 case of insulin resistance; there were no graft thromboses. Donor age averaged 5.0 ± 1.7 years and weight 19.8 ± 4.8 kg; recipient age averaged 46.6 ± 12.8 years and body mass index 25.2 ± 3.8 kg/m2. Postoperative creatinine, glucose, and C-peptide reflected good graft function. Simultaneous en bloc kidney and pancreas transplantation is a safe technique providing excellent long-term glycemic control and kidney function to adult recipients.
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Affiliation(s)
- Riccardo Tamburrini
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Ching-Yao Yang
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Department of Surgery, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan
| | - Jennifer L Philip
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; UWHealth Transplant Center, Madison, Wisconsin, USA
| | - Nikole A Neidlinger
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; UWHealth Transplant Center, Madison, Wisconsin, USA
| | - Dixon B Kaufman
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; UWHealth Transplant Center, Madison, Wisconsin, USA
| | - Jon S Odorico
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; UWHealth Transplant Center, Madison, Wisconsin, USA.
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Martinez EJ, Pham PH, Wang JF, Stalter LN, Welch BM, Leverson G, Marka N, Al-Qaoud T, Mandelbrot D, Parajuli S, Sollinger HW, Kaufman DB, Redfield RR, Odorico JS. Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation. Transpl Int 2024; 37:13087. [PMID: 39364120 PMCID: PMC11446817 DOI: 10.3389/ti.2024.13087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/10/2024] [Indexed: 10/05/2024]
Abstract
Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.
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Affiliation(s)
- Eric J. Martinez
- Anette C and Harold C Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Phuoc H. Pham
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
- Department of Medicine, School of Medicine, Creighton University, Omaha, NE, United States
| | - Jesse F. Wang
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Lily N. Stalter
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Bridget M. Welch
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Glen Leverson
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Nicholas Marka
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Talal Al-Qaoud
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Hans W. Sollinger
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Dixon B. Kaufman
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Robert R. Redfield
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Jon Scott Odorico
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
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Owen RV, Carr HJ, Counter C, Tingle SJ, Thompson ER, Manas DM, Shaw JA, Wilson CH, White SA. Multi-Centre UK Analysis of Simultaneous Pancreas and Kidney (SPK) Transplant in Recipients With Type 2 Diabetes Mellitus. Transpl Int 2024; 36:11792. [PMID: 38370534 PMCID: PMC10869449 DOI: 10.3389/ti.2023.11792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 10/27/2023] [Indexed: 02/20/2024]
Abstract
90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry (n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30 kg/m2. After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM (n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1 year (p = 0.120), 3 years (p = 0.237), and 10 years (p = 0.196) and kidney GS at 1 year (p = 0.438), 3 years (p = 0.548), and 10 years (p = 0.947). PS was comparable at 1 year (p = 0.886) and 3 years (p = 0.237) and at 10 years (p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS (p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS(p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation.
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Affiliation(s)
- Ruth V. Owen
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | | | - Claire Counter
- Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
| | - Samuel J. Tingle
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
- Blood and Transplant Unit, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Emily R. Thompson
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - Derek M. Manas
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - James A. Shaw
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
- Blood and Transplant Unit, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Colin H. Wilson
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
- Blood and Transplant Unit, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Steve A. White
- Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
- Blood and Transplant Unit, Newcastle University, Newcastle Upon Tyne, United Kingdom
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Parajuli S, Mandelbrot D, Aufhauser D, Kaufman D, Odorico J. Higher Fasting Pretransplant C-peptide Levels in Type 2 Diabetics Undergoing Simultaneous Pancreas-kidney Transplantation Are Associated With Posttransplant Pancreatic Graft Dysfunction. Transplantation 2023; 107:e109-e121. [PMID: 36706060 DOI: 10.1097/tp.0000000000004489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Among selected patients with type 2 diabetes mellitus (T2DM), simultaneous pancreas and kidney (SPK) transplants can be an effective option. However, data are limited about outcomes in T2DM SPK recipients based on the pretransplant C-peptide levels. METHODS In this study, we reviewed all T2DM SPK recipients and categorized them based on the pretransplant fasting C-peptide levels into 3 groups: low (≤2 ng/mL), medium (>2-8 ng/mL), and high (>8 ng/mL). Several measures of graft failures (GFs), graft dysfunction, and composite outcomes were of interest. RESULTS There were a total of 76 SPK recipients (low, n = 14; medium, n = 47; high, n = 15). At the last follow-up, the low group did not reach any outcome; in contrast, 11 (23%) in the medium group and 5 (33%) in the high group reached the uncensored composite outcome; 6 (13%) in the medium group and 2 (13%) in the high group had GF; and 8 (17%) in the medium group and 4 (26.7%) in the high group reached the death-censored composite outcomes. In a fully adjusted model, each pretransplant C-peptide unit was not associated with an increased risk of the composite outcome, GF, or death-censored composite outcomes. However, in multivariate analysis with limited adjustment, pretransplant C-peptide was associated with the composite outcome (hazard ratio: 1.18, 95% confidence interval, 1.01-1.38; P = 0.03) and death-censored composite outcome (hazard ratio: 1.20; 95% confidence interval, 1.01-1.42; P = 0.03). CONCLUSIONS Although limited by the small sample size, we found excellent outcomes among T2DM SPK recipients overall. However, higher levels of pretransplant C-peptide may be associated with inferior posttransplant outcomes that include graft dysfunction.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - David Aufhauser
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Dixon Kaufman
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jon Odorico
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
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Tissue engineering of decellularized pancreas scaffolds for regenerative medicine in diabetes. Acta Biomater 2023; 157:49-66. [PMID: 36427686 DOI: 10.1016/j.actbio.2022.11.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 11/27/2022]
Abstract
Diabetes mellitus is a global disease requiring long-term treatment and monitoring. At present, pancreas or islet transplantation is the only reliable treatment for achieving stable euglycemia in Type I diabetes patients. However, the shortage of viable pancreata for transplantation limits the use of this therapy for the majority of patients. Organ decellularization and recellularization is emerging as a promising solution to overcome the shortage of viable organs for transplantation by providing a potential alternative source of donor organs. Several studies on decellularization and recellularization of rodent, porcine, and human pancreata have been performed, and show promise for generating usable decellularized pancreas scaffolds for subsequent recellularization and transplantation. In this state-of-the-art review, we provide an overview of the latest advances in pancreas decellularization, recellularization, and revascularization. We also discuss clinical considerations such as potential transplantation sites, donor source, and immune considerations. We conclude with an outlook on the remaining work that needs to be done in order to realize the goal of using this technology to create bioengineered pancreata for transplantation in diabetes patients. STATEMENT OF SIGNIFICANCE: Pancreas or islet transplantation is a means of providing insulin-independence in diabetes patients. However, due to the shortage of viable pancreata, whole-organ decellularization and recellularization is emerging as a promising solution to overcome organ shortage for transplantation. Several studies on decellularization and recellularization of rodent, porcine, and human pancreata have shown promise for generating usable decellularized pancreas scaffolds for subsequent recellularization and transplantation. In this state-of-the-art review, we highlight the latest advances in pancreas decellularization, recellularization, and revascularization. We also discuss clinical considerations such as potential transplantation sites, donor source, and immune considerations. We conclude with future work that needs to be done in order to realize clinical translation of bioengineered pancreata for transplantation in diabetes patients.
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Pancreas Transplantation in Minorities including Patients with a Type 2 Diabetes Phenotype. URO 2022. [DOI: 10.3390/uro2040026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background: Prior to year 2000, the majority of pancreas transplants (PTx) were performed as simultaneous pancreas-kidney transplants (SPKTs) in Caucasian adults with end stage renal failure secondary to type 1 diabetes mellitus (T1DM) who were middle-aged. In the new millennium, improving outcomes have led to expanded recipient selection that includes patients with a type 2 diabetes mellitus (T2DM) phenotype, which excessively affects minority populations. Methods: Using PubMed® to identify appropriate citations, we performed a literature review of PTx in minorities and in patients with a T2DM phenotype. Results: Mid-term outcomes with SPKT in patients with uremia and circulating C-peptide levels (T2DMphenotype) are comparable to those patients with T1DM although there may exist a selection bias in the former group. Excellent outcomes with SPKT suggests that the pathophysiology of T2DM is heterogeneous with elements consisting of both insulin deficiency and resistance related to beta-cell failure. As a result, increasing endogenous insulin (Cp) production following PTx may lead to freedom checking blood sugars or taking insulin, better metabolic counter-regulation, and improvements in quality of life and life expectancy compared to other available treatment options. Experience with solitary PTx for T2DM or in minorities is limited but largely mirrors the trends reported in SPKT. Conclusions: PTx is a viable treatment option in patients with pancreas endocrine failure who are selected appropriately regardless of diabetes type or recipient race. This review will summarize data that unconventional patient populations with insulin-requiring diabetes may gain value from PTx with an emphasis on contemporary experiences and appropriate selection in minorities in the new millennium.
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Habeeb MA, Vishwakarma SK, Habeeb S, Khan AA. Current progress and emerging technologies for generating extrapancreatic functional insulin-producing cells. World J Transl Med 2022; 10:1-13. [DOI: 10.5528/wjtm.v10.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/05/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Affiliation(s)
- Md Aejaz Habeeb
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India
| | - Sandeep Kumar Vishwakarma
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India
| | - Safwaan Habeeb
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India
| | - Aleem Ahmed Khan
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India
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Gopal JP, McLean A, Crane J, Herbert P, Papalois V, Dor FJMF, Muthusamy AR. Pancreas Transplantation in Black, Asian and Minority Ethnic Patients-Single Centre Experience in the UK. Transpl Int 2022; 35:10490. [PMID: 35781938 PMCID: PMC9240992 DOI: 10.3389/ti.2022.10490] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022]
Abstract
Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients (n = 171; Caucasians = 118/Black Asian Ethnic Minorities, BAME = 53) from 2006 to 2020 was done. The median follow-up was 80 months. Patient & pancreas graft survival, rejection rate, steroid free maintenance rate, HbA1c, weight gain, and the incidence of secondary diabetic complications post-transplant were compared between the groups. p < 0.003 was considered significant (corrected for multiple hypothesis testing). Immunosuppression consisted of alemtuzumab induction and steroid free maintenance with tacrolimus and mycophenolate mofetil. Pancreas graft & patient survival were equivalent in both the groups. BAME recipients had a higher prevalence of type-2 diabetes mellitus pre-transplant (BAME = 30.19% vs. Caucasians = 0.85%, p < 0.0001), and waited for a similar time to transplantation once waitlisted, although pre-emptive SPK transplantation rate was higher for Caucasian recipients (Caucasians = 78.5% vs. BAME = 0.85%, p < 0.0001). Despite equivalent rejections & steroid usage, BAME recipients gained more weight (BAME = 7.7% vs. Caucasians = 1.8%, p = 0.001), but had similar HbA1c (functioning grafts) at 3-,12-, 36-, and 60-months post-transplant.
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Affiliation(s)
- Jeevan Prakash Gopal
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Adam McLean
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Jeremy Crane
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Paul Herbert
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Vassilios Papalois
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Frank J. M. F. Dor
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Anand Rathnasamy Muthusamy
- Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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Doherty D, Khambalia H, Summers A, Moinuddin Z, Yiannoullou P, Krishnan A, Augustine T, Naish J, van Dellen D. Future imaging modalities for the assessment of pancreas allografts a scan of the horizon. Transplant Rev (Orlando) 2022; 36:100692. [DOI: 10.1016/j.trre.2022.100692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 10/18/2022]
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Gurram V, Gurung K, Rogers J, Farney AC, Orlando G, Jay C, Reeves-Daniel A, Mena-Gutierrez A, Sakhovskaya N, Doares W, Kaczmorski S, Sharda B, Gautreaux MD, Stratta RJ. Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study. Clin Transplant 2021; 36:e14498. [PMID: 34599533 DOI: 10.1111/ctr.14498] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/17/2021] [Accepted: 09/27/2021] [Indexed: 11/27/2022]
Abstract
Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp- (level < 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p = .15), and pancreas graft survival (60% versus 86%, p = .03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p = .026) or rejection (17% Cp+ versus 6.5% Cp-, p = .2). Post-transplant weight gain > 5 kg occurred in 72% of Cp+ versus 26% of Cp- patients (p = .0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.
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Affiliation(s)
- Venkat Gurram
- Departments of General Surgery, (Section of Transplantation)
| | - Komal Gurung
- Departments of General Surgery, (Section of Transplantation)
| | - Jeffrey Rogers
- Departments of General Surgery, (Section of Transplantation)
| | - Alan C Farney
- Departments of General Surgery, (Section of Transplantation)
| | | | - Colleen Jay
- Departments of General Surgery, (Section of Transplantation)
| | | | | | | | | | | | - Berjesh Sharda
- Departments of General Surgery, (Section of Transplantation)
| | - Michael D Gautreaux
- Department of Pathology, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA
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Parsons RF, Matar A, Lentine KL, Woodside KJ, Singh N, Alhamad T, Basu A, Cabeza Rivera FH, Cheungpasitporn W, Romeo G, Rao S, Kensinger CD, Parajuli S, Sultan S, Tantisattamo E, Pavlakis M, Cooper M. Pancreas transplantation perceptions and practice: Results from a national US survey. Clin Transplant 2021; 35:e14432. [PMID: 34291503 DOI: 10.1111/ctr.14432] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/28/2021] [Accepted: 07/14/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Due to a substantial decline in pancreas transplantation (PT) across the United States over the past 15 years, we sought to understand the perceptions and practices of US PT programs. METHODS Surveys were sent to members of the American Society of Transplantation Surgeons and the American Society of Transplantation by email and professional society postings between August 2019 and November 2019. RESULTS One hundred twenty three responses were recorded from 56 unique programs. Program characteristics were obtained from the Scientific Registry of Transplant Recipients. Respondents were transplant surgeons (71%), transplant nephrologists (17%), trainees (9%), and allied professionals (3%). Programs were defined according to annual volume as: low (<5 PT/year), intermediate (6-20), or high (>20). High-volume programs reported that these factors were most important for increased PT: expansion of recipient selection, more aggressive donor utilization, and hiring of PT program-specific personnel. At both the program and national level, the vast majority (82% and 79%, respectively) felt the number of PTs currently performed are not in balance with patients' needs. CONCLUSIONS Overall, programs reported that the option of PT is not offered adequately to diabetic patients and that strategies to maintain higher PT volume are most evident at intermediate, and especially, high-volume programs.
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Affiliation(s)
| | - Abraham Matar
- Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Krista L Lentine
- Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA
| | | | - Neeraj Singh
- Willis Knighton Health System, John C. McDonald Regional Transplant Center, Shreveport, Louisiana, USA
| | - Tarek Alhamad
- John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Arpita Basu
- Department of Medicine, Emory University, Atlanta, Georgia, USA
| | | | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Mayo Clinic, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Giulio Romeo
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
- Joslin Diabetes Center, Boston, Massachusetts, USA
| | - Swati Rao
- Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Clark D Kensinger
- Piedmont Healthcare, Piedmont Transplant Institute, Atlanta, Georgia, USA
| | - Sandesh Parajuli
- Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
| | - Samuel Sultan
- Division of Transplantation Surgery, Weill Cornell Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Ekamol Tantisattamo
- Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Orange, California, USA
| | - Martha Pavlakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Matthew Cooper
- Department of Surgery, Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, District of Columbia, USA
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Shyr BS, Shyr BU, Chen SC, Loong CC, Shyr YM, Wang SE. A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus. Hepatobiliary Surg Nutr 2021; 10:443-453. [PMID: 34430523 DOI: 10.21037/hbsn-19-422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 09/19/2019] [Indexed: 11/06/2022]
Abstract
Background Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged. Methods In total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups. Results Majority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups. Conclusions T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.
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Affiliation(s)
- Bor-Shiuan Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Bor-Uei Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei.,Division of Transplant Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Shih-Chin Chen
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Che-Chuan Loong
- Division of Transplant Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
| | - Shin-E Wang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei
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13
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Pham PH, Stalter LN, Martinez EJ, Wang JF, Welch BM, Leverson G, Marka N, Al-Qaoud T, Mandelbrot D, Parajuli S, Sollinger HW, Kaufman D, Redfield RR, Odorico JS. Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes. Am J Transplant 2021; 21:2810-2823. [PMID: 33350048 PMCID: PMC8217396 DOI: 10.1111/ajt.16462] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 11/25/2020] [Accepted: 12/15/2020] [Indexed: 01/25/2023]
Abstract
Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.
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Affiliation(s)
- Phuoc H Pham
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Lily N Stalter
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Eric J Martinez
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- Anette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas
| | - Jesse F Wang
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Bridget M Welch
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Glen Leverson
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Nicholas Marka
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Talal Al-Qaoud
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Hans W Sollinger
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Dixon Kaufman
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Robert R Redfield
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Jon S Odorico
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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Cao Y, Liu X, Lan X, Ni K, Li L, Fu Y. Simultaneous pancreas and kidney transplantation for end-stage kidney disease patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Langenbecks Arch Surg 2021; 407:909-925. [PMID: 34279713 PMCID: PMC9151548 DOI: 10.1007/s00423-021-02249-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/13/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE The indications for patients with type 2 diabetes mellitus (T2DM) combined with end-stage kidney disease (ESKD) undertaking simultaneous pancreas and kidney transplantation (SPK) remain an unresolved issue. This study aimed to systematically review the survival outcomes of SPK among T2DM-ESKD patients. METHODS Online databases including PubMed, MEDLINE, EMBASE, and the CENTRAL Library, CNKI, Chinese Biomedical Literature Database, and Wan-Fang database were used to locate the studies of ESKD patients with T2DM undertaking SPK up to May 2021. A third reviewer was consulted if there were disagreements. Data were analyzed with STATA (15.0). RESULTS Nine cohort studies were identified. The pooled 1-year, 3-year, and 5-year patient survival rates of patients with T2DM and ESKD after SPK were 98%, 95%, and 91% respectively. Comparing the treatment effect of SPK between type 1 diabetes mellitus (T1DM) and T2DM, the survival estimates were comparable. For T2DM patients, SPK had a survival advantage compared with KTA. CONCLUSIONS The synthesized clinical outcomes of T2DM patients with ESKD after SPK were relatively better than KTA, but a subset of T2DM-ESKD patients who would benefit the most from SPK was to be defined. PROSPERO registration number CRD42019118321. Date of registration: 14 Jan 2019 (retrospectively registered).
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Affiliation(s)
- Yu Cao
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Xiaoli Liu
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Xiangyu Lan
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Kaiwen Ni
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Lin Li
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Yingxin Fu
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China.
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15
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Fu Y, Cao Y, Wang H, Zhao J, Wang Z, Mo C, Shi X, Feng G, Song W. Metabolic outcomes and renal function after simultaneous kidney/pancreas transplantation compared with kidney transplantation alone for type 2 diabetes mellitus patients. Transpl Int 2021; 34:1198-1211. [PMID: 33896062 PMCID: PMC8362174 DOI: 10.1111/tri.13892] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 01/01/2023]
Abstract
In this study, we aimed to compare the metabolic outcomes, renal function, and survival outcomes of simultaneous pancreas and kidney transplantation (SPK) and kidney transplantation alone (KTA) among end‐stage kidney disease (ESKD) patients with type II diabetes mellitus (T2DM). Patients with ESKD and T2DM who underwent KTA (n = 85) or SPK (n = 71) in a transplant center were retrospectively reviewed. Metabolic profiles, renal function, and survival outcomes were assessed repeatedly at different follow‐up time points. Propensity score procedures were applied to enhance between‐group comparability. The levels of renal and metabolic outcomes between SPK and KTA over time were examined and analyzed using mixed‐model repeated‐measures approaches. The median follow‐up period was 1.8 years. Compared with KTA, SPK resulted in superior metabolic outcomes and renal function, with lower levels of glycated hemoglobin (HbA1c; P = 0.0055), fasting blood glucose (P < 0.001), triglyceride (P = 0.015), cholesterol (P = 0.0134), low‐density lipoprotein (P = 0.0161), and higher estimated glomerular filtration rate (eGFR; P < 0.001). SPK provided better metabolic outcomes and renal function. The survival outcomes of the recipients and grafts were comparable between the two groups.
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Affiliation(s)
- Yingxin Fu
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Yu Cao
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Hui Wang
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Jie Zhao
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Zhen Wang
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Chunbai Mo
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Xiaofeng Shi
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Gang Feng
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Wenli Song
- Department of Kidney and Pancreas Transplantation, Tianjin First Central Hospital, Tianjin, China
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16
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Gurung K, Alejo J, Rogers J, Farney AC, Orlando G, Jay C, Reeves-Daniel A, Mena-Gutierrez A, Sakhovskaya N, Doares W, Kaczmorski S, Gautreaux MD, Stratta RJ. Recipient age and outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature. Clin Transplant 2021; 35:e14302. [PMID: 33783874 DOI: 10.1111/ctr.14302] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 12/30/2022]
Abstract
The influence of recipient age on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the modern era is uncertain. METHODS We retrospectively studied 255 patients undergoing SPKT from 11/01 to 8/20. Recipients were stratified according to age group: age <30 years (n = 16); age 30-39 years (n = 91); age 40-49 years (n = 86) and age ≥50 years (n = 62 [24.3%], including 9 patients ≥60 years of age). RESULTS Three-month and one-year outcomes were comparable. The eight-year patient survival rate was lowest in the oldest age group (47.6% vs 78% in the 3 younger groups combined, p < .001). However, eight-year kidney and pancreas graft survival rates were comparable in the youngest and oldest age groups combined (36.5% and 32.7%, respectively), but inferior to those in the middle 2 groups combined (62% and 50%, respectively, both p < .05). Death-censored kidney and pancreas graft survival rates increased from youngest to oldest recipient age category because of a higher incidence of death with functioning grafts (22.6% in oldest group compared to 8.3% in the 3 younger groups combined, p = .005). CONCLUSIONS Recipient age did not appear to significantly influence early outcomes following SPKT. Late outcomes are similar in younger and older recipients, but inferior to the middle 2 age groups.
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Affiliation(s)
- Komal Gurung
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Jennifer Alejo
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Jeffrey Rogers
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Alan C Farney
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Giuseppe Orlando
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Colleen Jay
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Amber Reeves-Daniel
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Alejandra Mena-Gutierrez
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Natalia Sakhovskaya
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - William Doares
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Scott Kaczmorski
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Michael D Gautreaux
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Robert J Stratta
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
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17
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Pham PH, Stalter LN, Martinez EJ, Wang JF, Welch BM, Leverson G, Marka N, Al-Qaoud T, Mandelbrot D, Parajuli S, Sollinger HW, Kaufman D, Redfield RR, Odorico JS. Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes. Am J Transplant 2020. [PMID: 33350048 DOI: 10.1111/ajt.16462.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p = .10, .43, respectively) or T2D (p = .12, .63) patients in the cohort; or with graft failure (T1D: p = .40, .09; T2D: p = .71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.
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Affiliation(s)
- Phuoc H Pham
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Lily N Stalter
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Eric J Martinez
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.,Anette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas
| | - Jesse F Wang
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Bridget M Welch
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Glen Leverson
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Nicholas Marka
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Talal Al-Qaoud
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Hans W Sollinger
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Dixon Kaufman
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Robert R Redfield
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Jon S Odorico
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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18
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Skrzypek P, Śmigielska K, Ziemiański P, Kosieradzki M, Lisik W. Retrospective Analysis of Pancreas Transplants in Poland in Years 1998-2015. Transplant Proc 2020; 52:2074-2080. [PMID: 32713819 DOI: 10.1016/j.transproceed.2020.02.116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 02/13/2020] [Indexed: 11/27/2022]
Abstract
Transplantation of the pancreas is an established method for the treatment of complicated diabetes mellitus. As the numbers of diabetic patients increase so does the need for efficient treatment methods. Despite significant perioperative risk and complications related to immunosuppression, pancreas transplant remains the best therapeutic option for selected patients. METHODS The analysis was based on the comparison of characteristics of all organ donors and recipients in years 1998 to 2015. The collected data were divided into 2 periods to facilitate identification of populational changes. RESULTS The total number of pancreas transplants in Poland was 139 in years 1998 to 2006 and 268 in years 2007 to 2015. The largest differences revealed by the comparison of donor-related variables in both periods were those related to the doses of pressor amines, duration of circulatory arrest, and duration of stay at the intensive care unit. The critical finding consisted in the improvement of short-term survival of recipients and organs being observed in contrast to the surprising lack of improvement in long-term survival. Reduced likelihood of transplantation success was observed already in overweight patients (body mass index 25-29.99 kg/m2). CONCLUSIONS No significant changes were observed with regard to pancreas transplant outcomes over the period of many years. Transplantation success is determined by 1-year survival of the organ, and the therapeutic success is measured by long-term disease-free survival of the patient. In the era of rapid advances in numerous areas of medicine, the lack of significant extension of patient survival times warrants a closer look of our knowledge on pancreas transplants.
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Affiliation(s)
- Paweł Skrzypek
- Department of General and Transplantation Surgery, Medical University of Warsaw, Poland
| | - Kaja Śmigielska
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, Poland
| | - Paweł Ziemiański
- Department of General and Transplantation Surgery, Medical University of Warsaw, Poland.
| | - Maciej Kosieradzki
- Department of General and Transplantation Surgery, Medical University of Warsaw, Poland
| | - Wojciech Lisik
- Department of General and Transplantation Surgery, Medical University of Warsaw, Poland
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19
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Buchwald H, Buchwald JN. The benefits of metabolic/bariatric surgery on diabetes mellitus. TRANSPLANTATION, BIOENGINEERING, AND REGENERATION OF THE ENDOCRINE PANCREAS 2020:229-240. [DOI: 10.1016/b978-0-12-814831-0.00016-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Spaggiari M, Tulla KA, Okoye O, Di Bella C, Di Cocco P, Almario J, Ugwu-Dike P, Tzvetanov IG, Benedetti E. The utility of robotic assisted pancreas transplants - a single center retrospective study. Transpl Int 2019; 32:1173-1181. [PMID: 31250486 DOI: 10.1111/tri.13477] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 07/31/2018] [Accepted: 06/25/2019] [Indexed: 11/26/2022]
Abstract
The prevalence of obesity within the diabetic population is on the rise. This development poses unique challenges for pancreas transplantation candidates as obese individuals are often denied access to transplant. The introduction of robotic approach to transplant has been shown to improve outcomes in obese patients. A single center retrospective review of pancreas transplant cases over a 4-year period ending December 2018 was performed. Patients undergoing robotic surgery were compared to their counterparts undergoing open transplant. 49 patients (10 robot, 39 open) received pancreas transplants over the study period. Mean age was 43.1 ± 7.5 vs. 42.8 ± 9.7 years. There were no significant differences in demographics except body mass index (33.7 ± 5.2 vs. 27.1 ± 6.6, P = 0.005). Operative duration (7.6 ± 1.6 vs. 5.3 ± 1.4, P < 0.001), and warm ischemia times [45.5 (IQR: 13.7) vs. 33 (7), P < 0.001] were longer in the robotic arm. There were no wound complications in the robotic approach patients. Graft (100% vs. 88%, P = 0.37) and patient survival (100% vs. 100%, P = 0.72) after 1 year were similar. Our findings suggest that robotic pancreas is both safe and effective in obese diabetic patients, without added risk of wound complications. Wide adoption of the technique is encouraged while long term follow-up of our recipients is awaited.
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Affiliation(s)
- Mario Spaggiari
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Kiara A Tulla
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Obi Okoye
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Caterina Di Bella
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Pierpaolo Di Cocco
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Jorge Almario
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Pearl Ugwu-Dike
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Ivo G Tzvetanov
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
| | - Enrico Benedetti
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA
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21
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Liu L, Xiong Y, Zhang T, Fang J, Zhang L, Li G, Xu L, Lai X, Chen R, Guo Y, Pan G, Ma J, Chen Z. Effect of simultaneous pancreas-kidney transplantation on blood glucose level for patients with end-stage renal disease with type 1 and type 2 diabetes. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:631. [PMID: 31930032 DOI: 10.21037/atm.2019.10.106] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND Simultaneous pancreas-kidney (SPK) transplants for patients with type 1 diabetes mellitus (T1DM) remains disproportionately higher than that for type 2 diabetes mellitus (T2DM) patients. However, understanding the surgical outcomes for these patients is not well described. Therefore, the results of DM patients with end-stage renal disease and their transplantations were reported. METHODS Between September 2016 and June 2019, 63 SPK transplants were performed in our organ transplantation center. χ2 and t-test compared the variables between the groups and the record review verified the patient survival. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of SPK on patient and graft survivals. RESULTS Sixty-three SPK transplantation was performed, 18 (29%) were T1DM, and 45 (71%) T2DM. T2DM recipients had older age, duration of diabetes, and pretransplant dialysis time. No differences were found in human leukocyte antigen (HLA) mismatch, body mass index (BMI), and other variables. Patient survivals for T1DM was 98.2% and 94.8% at 1 and 2 years vs. 100% and 94.1% for T2DM recipients (P=0.87). There was no increased risk between kidney disease, pancreas failure, or death when comparing T2DM and T1DM. CONCLUSIONS In our single-center cohort of SPK transplants, we concluded that SPK recipients with T2DM diagnosis were not at increased risk for death, kidney failure, or pancreas failure when compared with recipients with T1DM.
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Affiliation(s)
- Luhao Liu
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Yunyi Xiong
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Tao Zhang
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Jiali Fang
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Lei Zhang
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Guanghui Li
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Lu Xu
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Xingqiang Lai
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Rongxin Chen
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Yuhe Guo
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Guanghui Pan
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Junjie Ma
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Zheng Chen
- Department of Organ Transplantation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
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Andacoglu OM, Himmler A, Geng X, Ahn J, Ghasemian S, Cooper M, Abrams P. Comparison of glycemic control after pancreas transplantation for Type 1 and Type 2 diabetic recipients at a high volume center. Clin Transplant 2019; 33:e13656. [PMID: 31251417 DOI: 10.1111/ctr.13656] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 06/07/2019] [Accepted: 06/12/2019] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The number of pancreas transplants (PTX) in patients with Type 2 diabetes (T2DM) has increased in response to excellent outcomes in appropriately selected patients. Not all pancreas transplant centers share an enthusiasm for performing PTX for T2DM out of concern for increased complication rates. This study aims to clarify the characteristics of T2DM recipients with successful outcomes to clarify which candidates are more suitable for PTX as means of maximizing access to this highly effective therapy for Type 2 patients. METHODS & RESULTS At MedStar Georgetown Transplant Institute, 50 patients underwent pancreas transplant between 2013 and 2016. Based on patient characteristics, 38 (78%) were categorized as T1DM, and 11 (22%) were considered T2DM. One case was excluded due to early graft loss. The estimated age of diabetes onset was significantly different between T1DM and T2DM cohorts (13 years vs. 29 years, P < .001). T2DM patients had significantly higher preoperative C-peptide levels (4.11 vs. 0.05, P < .001). Preoperative HbA1c, preoperative Body Mass Index (BMI), number of diabetic complications, and hemodialysis status were similar between both groups. At 2-year follow-up, there was no statistical difference in glycemic control between the two groups (T1DM vs. T2DM). Infectious complications and readmission rates were similar. Other trends that did not meet statistical significance included T1DM group with a slightly higher mortality and re-intervention rate. The T2DM group demonstrated higher BMI, higher rejection rates, and higher short-term postoperative insulin requirements. Graft survival was 95% and 82% for T1 and T2DM at 2 years post-transplant, respectively. CONCLUSION Successful PTX in T1DM and T2DM recipient groups resulted in comparable glycemic control at 2-year post-transplant follow-up. T2DM group had a trend toward higher BMI as well as higher rates of rejection, temporary insulin requirement and graft failure, although none of these trends reached statistical significance. These results suggest that strict classification of T1 and T2DM by itself may not be relevant to achieving excellent outcomes in pancreas transplantation and, therefore, patient selection for PTX should not be based primarily on this classification.
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Affiliation(s)
- Oya M Andacoglu
- Medstar Georgetown Transplant Institute, Washington, District of Columbia
| | - Amber Himmler
- Georgetown University School of Medicine, Washington, District of Columbia
| | - Xue Geng
- Georgetown University Department of Biostatistics, Bioinformatics & Biomathematics, Washington, District of Columbia
| | - Jaeil Ahn
- Georgetown University Department of Biostatistics, Bioinformatics & Biomathematics, Washington, District of Columbia
| | - Seyed Ghasemian
- Medstar Georgetown Transplant Institute, Washington, District of Columbia
| | - Matthew Cooper
- Medstar Georgetown Transplant Institute, Washington, District of Columbia
| | - Peter Abrams
- Medstar Georgetown Transplant Institute, Washington, District of Columbia
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Abstract
PURPOSE OF REVIEW Pancreas transplantation in type 2 diabetes mellitus (T2DM) candidates remains disproportionately lower than in type 1 diabetes mellitus (T1DM); however, outcomes in carefully selected patients mirrors that of T1DM. Despite the 2014 United Network for Organ Sharing (UNOS) eligibility criteria for simultaneous pancreas/kidney transplant (SPK) transplantation in T2DM patients, an expected increase in the number of transplants was not observed. RECENT FINDINGS In an updated International Pancreas and Transplant Registry (IPTR) analysis, 1514 primary deceased donor pancreas transplants were performed in T2DM recipients [1995-2015, SPK 88%, pancreas after kidney (PAK) 9%, pancreas transplant alone (PTA) 3%]. In contrast to the declining number of SPK transplants for T1DM, the number of primary SPK transplants in T2DM patients is increasing over time in the USA. Improvement over time was noted for T2DM SPK patient and graft survival, and the rate of technical failures decreased, paralleling similar overall trends for pancreas transplants in general. Long-term follow-up data of pancreas outcomes in C-peptide positive vs. negative demonstrate noninferior outcomes. BMI does not appear to impact outcomes in carefully selected T2DM candidates. SUMMARY The current UNOS regulations that currently limit access of T2DM to pancreas transplantation based on strict BMI criteria and C-peptide levels need to be liberated.
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Buchwald H, Buchwald JN. Metabolic (Bariatric and Nonbariatric) Surgery for Type 2 Diabetes: A Personal Perspective Review. Diabetes Care 2019; 42:331-340. [PMID: 30665965 DOI: 10.2337/dc17-2654] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 07/17/2018] [Indexed: 02/03/2023]
Abstract
: Metabolic surgery can cause amelioration, resolution, and possible cure of type 2 diabetes. Bariatric surgery is metabolic surgery. In the future, there will be metabolic surgery operations to treat type 2 diabetes that are not focused on weight loss. These procedures will rely on neurohormonal modulation related to the gut as well as outside the peritoneal cavity. Metabolic procedures are and will always be in flux as surgeons seek the safest and most effective operative modality; there is no enduring gold standard operation. Metabolic bariatric surgery for type 2 diabetes is more than part of the clinical armamentarium, it is an invitation to perform basic research and to achieve fundamental scientific knowledge.
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Affiliation(s)
- Henry Buchwald
- Department of Surgery, University of Minnesota, Minneapolis, MN .,Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN
| | - Jane N Buchwald
- Division of Scientific Research Writing, Medwrite Medical Communications, Maiden Rock, WI
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Peloso A, Citro A, Zoro T, Cobianchi L, Kahler-Quesada A, Bianchi CM, Andres A, Berishvili E, Piemonti L, Berney T, Toso C, Oldani G. Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology. Front Endocrinol (Lausanne) 2018; 9:445. [PMID: 30233489 PMCID: PMC6127205 DOI: 10.3389/fendo.2018.00445] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 07/18/2018] [Indexed: 12/20/2022] Open
Abstract
According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25 million people in the United States (US) have type 1 diabetes, which makes them dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly doubled in the past 20 years resulting in more than 29 million American adults with diabetes and another 86 million in a pre-diabetic state. The International Diabetes Ferderation (IDF) has estimated that there will be almost 650 million adult diabetic patients worldwide at the end of the next 20 years (excluding patients over the age of 80). At this time, pancreas transplantation is the only available cure for selected patients, but it is offered only to a small percentage of them due to organ shortage and the risks linked to immunosuppressive regimes. Currently, exogenous insulin therapy is still considered to be the gold standard when managing diabetes, though stem cell biology is recognized as one of the most promising strategies for restoring endocrine pancreatic function. However, many issues remain to be solved, and there are currently no recognized treatments for diabetes based on stem cells. In addition to stem cell resesarch, several β-cell substitutive therapies have been explored in the recent era, including the use of acellular extracellular matrix scaffolding as a template for cellular seeding, thus providing an empty template to be repopulated with β-cells. Although this bioengineering approach still has to overcome important hurdles in regards to clinical application (including the origin of insulin producing cells as well as immune-related limitations), it could theoretically provide an inexhaustible source of bio-engineered pancreases.
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Affiliation(s)
- Andrea Peloso
- Division of Abdominal Surgery, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- HepatoPancreato-Biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Antonio Citro
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Tamara Zoro
- Department of General Surgery, IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Lorenzo Cobianchi
- Department of General Surgery, IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Arianna Kahler-Quesada
- Division of Abdominal Surgery, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Carlo M. Bianchi
- Department of General Surgery, IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Axel Andres
- Division of Abdominal Surgery, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- HepatoPancreato-Biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Ekaterine Berishvili
- Cell Isolation and Transplantation Center, University of Geneva, Geneva, Switzerland
- Institute of Medical Research, Ilia State University, Tbilisi, Georgia
| | - Lorenzo Piemonti
- San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Thierry Berney
- Cell Isolation and Transplantation Center, University of Geneva, Geneva, Switzerland
| | - Christian Toso
- Division of Abdominal Surgery, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- HepatoPancreato-Biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Graziano Oldani
- Division of Abdominal Surgery, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- HepatoPancreato-Biliary Centre, Geneva University Hospitals, Geneva, Switzerland
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Hashemi J, Pasalar P, Soleimani M, Arefian E, Khorramirouz R, Akbarzadeh A, Ghorbani F, Enderami S, Kajbafzadeh A. Decellularized Pancreas Matrix Scaffolds for Tissue Engineering Using Ductal or Arterial Catheterization. Cells Tissues Organs 2018; 205:72-84. [DOI: 10.1159/000487230] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 01/29/2018] [Indexed: 12/21/2022] Open
Abstract
Introduction: Diabetes is known as a worldwide disease with a great burden on society. Since therapeutic options cover a limited number of target points, new therapeutic strategies in the field of regenerative medicine are considered. Bioscaffolds along with islet cells would provide bioengineered tissue as a substitute for β-cells. The perfusion-decellularization technique is considered to create such scaffolds since they mimic the compositional, architectural, and biomechanical nature of a native organ. In this study, we investigated 2 decellularization methods preserving tissue microarchitecture. Methods: Procured pancreas from Sprague-Dawley rats was exposed to different percentages of detergent for 2, 4, and 6 h after cannulation via the common bile duct or aorta. Results: High concentrations of sodium dodecyl sulfate (SDS), i.e., > 0.05%, resulted in tissue disruption or incomplete cell removal depending on the duration of exposure. In both methods, 6-h exposure to 0.05% SDS created a bioscaffold with intact extracellular matrices and proper biomechanical characteristics. Tissue-specific stainings revealed that elastic, reticular, and collagen fiber concentrations were well preserved. Quantitative findings showed that glycosaminoglycan content was slightly different, but hydroxyproline was in the range of native pancreas tissue. Dye infusion through ductal and vascular cannulation proved that the vascular network was intact, and scanning electron microscopy indicated a homogeneous porous structure. Conclusions: Using the detergent-based method, an effective and time-efficient procedure, a whole pancreas extracellular matrix bioscaffold can be developed that can be used as a 3D structure for pancreas tissue engineering-based studies and regenerative medicine applications.
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Pancreas Transplantation at a Single Latin-American Center; Overall Results with Type 1 and Type 2 Diabetes Mellitus. Transplant Proc 2018; 50:1475-1481. [PMID: 29880374 DOI: 10.1016/j.transproceed.2018.03.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 03/06/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Simultaneous pancreas-kidney transplantation (SPK) has become the treatment of choice for type 1 diabetes mellitus (T1DM) patients with chronic renal failure. Type 2 diabetes mellitus (T2DM), was once considered to be a contraindication for pancreas transplantation; however, it has been accepted as a new indication, under strict criteria. Although favorable results have increase the indication for T2DM in developed countries, there have been no reports of long-term results for this indication from Latin American centers. METHODS From April 2008 to March 2016, patients receiving SPK or pancreas transplant alone (PTA) for T2DM were included and compared with T1DM recipients. Variables were compared between groups with the use of χ2 and t tests; Kaplan-Meier with log rank was used for patient and graft survivals; P < .05 was considered to be significant. RESULTS A total of 45 SPK and 1 PTA were performed, 35 (76.1%) for T1DM and 11 (24.5%) for T2DM. Mean pre-transplantation C-peptide was significantly higher in the T2DM group (P = .01); HbA1c was higher in the T1DM group (P = .03). No differences were found in weight, body mass index, and pre-transplantation glycemia. Patient survivals for T1DM recipients were 88.2% and 84.8% at 1 and 5 years, respetively, versus 100% and 74.1% for T2DM recipients (P = .87). CONCLUSIONS Our initial prospective experience in a single Latin American center showed that medium- and long-term outcomes for T1DM and T2DM individuals receiving pancreas transplants are similar, under strict selection criteria.
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Proceedings of the signature series event of the international society for cellular therapy: "Advancements in cellular therapies and regenerative medicine in digestive diseases," London, United Kingdom, May 3, 2017. Cytotherapy 2018; 20:461-476. [PMID: 29398624 DOI: 10.1016/j.jcyt.2017.12.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 12/01/2017] [Indexed: 12/18/2022]
Abstract
A summary of the First Signature Series Event, "Advancements in Cellular Therapies and Regenerative Medicine for Digestive Diseases," held on May 3, 2017, in London, United Kingdom, is presented. Twelve speakers from three continents covered major topics in the areas of cellular therapy and regenerative medicine applied to liver and gastrointestinal medicine as well as to diabetes mellitus. Highlights from their presentations, together with an overview of the global impact of digestive diseases and a proposal for a shared online collection and data-monitoring platform tool, are included in this proceedings. Although growing evidence demonstrate the feasibility and safety of exploiting cell-based technologies for the treatment of digestive diseases, regulatory and methodological obstacles will need to be overcome before the successful implementation in the clinic of these novel attractive therapeutic strategies.
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Elebring E, Kuna VK, Kvarnström N, Sumitran-Holgersson S. Cold-perfusion decellularization of whole-organ porcine pancreas supports human fetal pancreatic cell attachment and expression of endocrine and exocrine markers. J Tissue Eng 2017; 8:2041731417738145. [PMID: 29118967 PMCID: PMC5669317 DOI: 10.1177/2041731417738145] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Accepted: 09/29/2017] [Indexed: 12/23/2022] Open
Abstract
Despite progress in the field of decellularization and recellularization, the outcome for pancreas has not been adequate. This might be due to the challenging dual nature of pancreas with both endocrine and exocrine tissues. We aimed to develop a novel and efficient cold-perfusion method for decellularization of porcine pancreas and recellularize acellular scaffolds with human fetal pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular material, while preserving the extracellular matrix structure. Furthermore, recellularization of acellular pieces with human fetal pancreatic stem cells for 14 days showed attached and proliferating cells. Both endocrine (C-peptide and PDX1) and exocrine (glucagon and α-amylase) markers were expressed in recellularized tissues. Thus, cold-perfusion can successfully decellularize porcine pancreas, which when recellularized with human fetal pancreatic stem cells shows relevant endocrine and exocrine phenotypes. Decellularized pancreas is a promising biomaterial and might translate to clinical relevance for treatment of diabetes.
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Affiliation(s)
- Erik Elebring
- Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Vijay K Kuna
- Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Niclas Kvarnström
- The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Suchitra Sumitran-Holgersson
- Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Long-term Metabolic Outcomes of Functioning Pancreas Transplants in Type 2 Diabetic Recipients. Transplantation 2017; 101:1254-1260. [PMID: 27336397 DOI: 10.1097/tp.0000000000001269] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Limited data are available regarding the long-term metabolic outcomes of functioning pancreas transplants in patients with type 2 diabetes mellitus (T2DM). METHODS To compare the long-term effects of pancreas transplantation in terms of insulin resistance and β cell function, comparison of metabolic variables was performed between type 1 diabetes mellitus (T1DM) and T2DM patients from 1-month posttransplant to 5 years using generalized, linear-mixed models for repeated measures. RESULTS Among 217 consecutive patients who underwent pancreas transplantation at our center between August 2004 and January 2015, 193 patients (151 T1DM and 42 T2DM) were included in this study. Throughout the follow-up period, postoperative hemoglobin A1c did not differ significantly between T1DM and T2DM patients, and the levels were constantly below 6% (42 mmol/mol) until 5 years posttransplant, whereas C-peptide was significantly higher in T2DM (P = 0.014). There was no difference in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, HOMA β cell, or the insulinogenic index between the groups. Furthermore, fasting insulin and HOMA-insulin resistance steadily decreased in both groups during the follow-up period. CONCLUSIONS There was no significant difference in the insulin resistance or β-cell function after pancreas transplantation between T1DM and T2DM patients. We demonstrated that pancreas transplantation is capable of sustaining favorable endocrine functions for more than 5 years in T2DM recipients.
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Gruessner AC, Laftavi MR, Pankewycz O, Gruessner RWG. Simultaneous Pancreas and Kidney Transplantation-Is It a Treatment Option for Patients With Type 2 Diabetes Mellitus? An Analysis of the International Pancreas Transplant Registry. Curr Diab Rep 2017; 17:44. [PMID: 28478590 DOI: 10.1007/s11892-017-0864-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Pancreas transplantation remains the best long-term treatment option to achieve euglycemia and freedom from insulin in patients with labile diabetes mellitus. It is an approved procedure for type 1 (T1DM), but it is still considered controversial for type 2 diabetes mellitus (T2DM). RECENT FINDINGS This study analyzed all primary deceased donor pancreas transplants in patients with T2DM reported to IPTR/UNOS between 1995 and 2015. Characteristics, outcomes, and risk factors over time were determined using univariate and multivariate methods. The focus was on simultaneous pancreas/kidney (SPK) transplants, the most common pancreas transplant category. Patient, pancreas, and kidney graft survival rates increased significantly over time and reached 95.8, 83.3, and 91.1%, respectively, at 3 years posttransplant for transplants performed between 2009 and 2015. SPK is a safe procedure with excellent pancreas and kidney graft outcome in patients with T2DM. The procedure restores euglycemia and freedom from insulin and dialysis. Based on our results, SPK should be offered to more uremic patients with labile T2DM.
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Affiliation(s)
- Angelika C Gruessner
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA.
| | - Mark R Laftavi
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA
| | - Oleh Pankewycz
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Rainer W G Gruessner
- Department of Surgery, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY, 13210, USA
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Arous C, Wehrle-Haller B. Role and impact of the extracellular matrix on integrin-mediated pancreatic β-cell functions. Biol Cell 2017; 109:223-237. [PMID: 28266044 DOI: 10.1111/boc.201600076] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 03/01/2017] [Accepted: 03/02/2017] [Indexed: 12/17/2022]
Abstract
Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β-cells, and to recognise and revert the physiopathology of diabetes. Indeed, integrin-mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β-cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin-mediated cell-matrix adhesions and how they are affected during diabetes. To treat diabetes, a promising approach consists in replacing β-cells by transplantation. However, efficiency is low, because β-cells suffer of anoikis, due to enzymatic digestion of the pancreatic ECM, which affects the survival of insulin-secreting β-cells. The strategy of adding ECM components during transplantation, to reproduce the pancreatic microenvironment, is a challenging task, as many of the regulatory mechanisms that control ECM deposition and turnover are not sufficiently understood. A better comprehension of the impact of the ECM on the adhesion and integrin-dependent signalling in β-cells is primordial to improve the healthy state of islets to prevent the onset of diabetes as well as for enhancing the efficiency of the islet transplantation therapy.
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Affiliation(s)
- Caroline Arous
- Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland
| | - Bernhard Wehrle-Haller
- Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland
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Peloso A, Urbani L, Cravedi P, Katari R, Maghsoudlou P, Alvarez Fallas ME, Sordi V, Citro A, Purroy C, Niu G, McQuilling JP, Sittadjody S, Farney AC, Iskandar SS, Rogers J, Stratta RJ, Opara EC, Piemonti L, Furdui C, Soker S, De Coppi P, Orlando G. The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas. Ann Surg 2016; 264:169-79. [PMID: 26649588 PMCID: PMC4882269 DOI: 10.1097/sla.0000000000001364] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.
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Affiliation(s)
- Andrea Peloso
- Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Luca Urbani
- Surgery Unit, Stem Cells and Regenerative Section, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
| | - Paolo Cravedi
- Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Ravi Katari
- Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Panagiotis Maghsoudlou
- Surgery Unit, Stem Cells and Regenerative Section, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
| | - Mario Enrique Alvarez Fallas
- Surgery Unit, Stem Cells and Regenerative Section, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
- Stem Cells and Regenerative Medicine Lab, Fondazione Instituto di Ricerca Pediatrica Città della Speranza, Padova, Italy
| | - Valeria Sordi
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Antonio Citro
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carolina Purroy
- Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Guoguang Niu
- Wake Forest School of Medicine, Winston Salem, NC, USA
| | | | | | - Alan C Farney
- Wake Forest School of Medicine, Winston Salem, NC, USA
| | | | | | | | | | - Lorenzo Piemonti
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Shay Soker
- Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Paolo De Coppi
- Surgery Unit, Stem Cells and Regenerative Section, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK
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Katsuki Y, Yagi H, Okitsu T, Kitago M, Tajima K, Kadota Y, Hibi T, Abe Y, Shinoda M, Itano O, Takeuchi S, Kitagawa Y. Endocrine pancreas engineered using porcine islets and partial pancreatic scaffolds. Pancreatology 2016; 16:922-30. [PMID: 27350058 DOI: 10.1016/j.pan.2016.06.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 05/12/2016] [Accepted: 06/16/2016] [Indexed: 02/09/2023]
Abstract
OBJECTIVES Because therapeutic options for severe diabetes are currently limited, there is a continuing need for new therapeutic strategies, especially in the field of regenerative medicine. Collaborative efforts across the fields of tissue engineering technology and islet biology may be able to create functionally engineered islets capable of restoring endocrine function in patients with insulin-dependent diabetes. METHODS This engineered scaffold was seeded with isolated primary porcine islets via the pancreatic duct using a multi-step infusion technique. Endocrine function of perfusion-cultured islets in the native scaffold was analyzed by immunohistochemical staining of insulin and glucagon as well as by the insulin stimulation test. RESULTS The pancreas in this large animal could be uniformly decellularized by perfusion with trypsin and TritonX-100 via the pancreatic duct, as shown by positive staining of extracellular matrix (ECM) components. These scaffolds derived from porcine pancreas were able to maintain the cellular integrity of islets that had repopulated the parenchymal space, which is fundamental for the restoration of endocrine function. Insulin release up to four days after islet infusion was maintained. CONCLUSIONS This scaffold from a large animal maintained islet survival and function in the short-term, retaining the cells as a solid organ in the parenchymal space after infusion through the pancreatic duct. These results suggest that this scaffold is suitable for further fabrication of fully functional bioengineered endocrine pancreases when implanted in vivo. Therefore, it may represent a key improvement in the field of beta-cell replacement therapy. Nonetheless, the facilitation of longer-term islet survival and studies of implantation in vivo is required for successful clinical translation.
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Affiliation(s)
- Yusuke Katsuki
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Teru Okitsu
- Center for International Research on Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Meguro, Tokyo 153-8505, Japan.
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Kazuki Tajima
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Yoshie Kadota
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Taizo Hibi
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Osamu Itano
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
| | - Shoji Takeuchi
- Center for International Research on Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Meguro, Tokyo 153-8505, Japan.
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
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Redfield RR, Rickels MR, Naji A, Odorico JS. Pancreas Transplantation in the Modern Era. Gastroenterol Clin North Am 2016; 45:145-66. [PMID: 26895686 DOI: 10.1016/j.gtc.2015.10.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The field of pancreas transplantation has evolved from an experimental procedure in the 1980s to become a routine transplant in the modern era. With short- and long-term outcomes continuing to improve and the significant mortality, quality-of-life, and end-organ disease benefits, pancreas transplantation should be offered to more patients. In this article, we review current indications, patient selection, surgical considerations, complications, and outcomes in the modern era of pancreas transplantation.
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Affiliation(s)
- Robert R Redfield
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Clinical Science Cntr-H4/772, Madison, WI 53792, USA.
| | - Michael R Rickels
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 2-134 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Ali Naji
- Division of Transplantation, Department of Surgery, University of Pennsylvania Perelman School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA
| | - Jon S Odorico
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Clinical Science Cntr-H4/772, Madison, WI 53792, USA
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3D Culture of MIN-6 Cells on Decellularized Pancreatic Scaffold: In Vitro and In Vivo Study. BIOMED RESEARCH INTERNATIONAL 2015; 2015:432645. [PMID: 26688810 PMCID: PMC4672115 DOI: 10.1155/2015/432645] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 08/28/2015] [Accepted: 09/01/2015] [Indexed: 12/11/2022]
Abstract
Type 1 diabetes is an autoimmune disease which is due to the lack of β cells. The ideal therapy to cure the disease is pancreas transplantation, but its application is confined to a limited number of people due to the shortage of organ and the need for life-long immunosuppression. Regenerative medicine methods such as a tissue engineered pancreas seem to provide a useful method. In order to construct a microenvironment similar to the native pancreas that is suitable for not only cell growth but also cellular function exertion, a decellularized mouse pancreas was used as a natural 3D scaffold in this experiment. MIN-6 β cells were planted in the bioscaffold. The cell engraftment was verified by HE staining and SEM. Immunostaining procedures were performed to confirm the normal function of the engrafted cells. qRT-PCR demonstrated that insulin gene expression of the recellularized pancreas was upregulated compared with conventional plate-cultured cells. In vivo experiment was also accomplished to further evaluate the function of the recellularized bioscaffold and the result was inspiring. And beyond doubt this will bring new hope for type 1 diabetic patients.
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Bottino R, Trucco M. Clinical implementation of islet transplantation: A current assessment. Pediatr Diabetes 2015; 16:393-401. [PMID: 26084669 DOI: 10.1111/pedi.12287] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 04/24/2015] [Accepted: 05/01/2015] [Indexed: 01/03/2023] Open
Abstract
Beta-cell replacement is the only physiologically relevant alternative to insulin injections in patients with type 1 diabetes (T1D). Pancreas and islet transplantation from deceased organ donors can provide a new beta-cell pool to produce insulin, help blood glucose management, and delay secondary diabetes complications. For children and adolescents with T1D, whole pancreas transplantation is not a viable option because of surgical complications, whereas islet transplantation, even if it is procedurally simpler, must still overcome the burden of immunosuppression to become a routine therapy for children in the future.
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Affiliation(s)
- Rita Bottino
- Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, USA
| | - Massimo Trucco
- Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, USA
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Uva PD, Villavicencio Fornaciari S, Giunippero AE, Cabrera IC, Casadei DH. Case report: pancreas graft with a duodenal complication rescued using total duodenectomy. Transplant Proc 2015; 46:3068-71. [PMID: 25420824 DOI: 10.1016/j.transproceed.2014.07.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Simultaneous pancreas-kidney (SPK) transplantation is the treatment of choice for type 1 diabetics with end-stage renal disease. Recently patients with type 2 diabetes have been considered for transplantation. Despite that the patient and graft survival rates have improved over the past years, it continues to be a procedure with high surgical complication rates. We herein report a case of a pancreatic graft with a duodenal complication rescued using a total duodenectomy, a procedure that is seldom used. A 57-year-old type 2 diabetic underwent a SPK transplantation with systemic-enteric drainage. He was converted to a Roux en Y at day 7 for a small duodenal fistula without peritonitis. At day 13, with good graft function, he presented with gastrointestinal and abdominal bleeding. At laparotomy he had a congestive duodenum with intraluminal bleeding and an anastomotic fistula. We performed a total duodenectomy with enteric drainage. The patient was discharged home on day 39 with a pancreatic fistula on intramuscular Octretotide that lasted for 3 months. He was never readmitted and has good pancreas and kidney function at 16 months of follow-up. We think this is an option to rescue a pancreas graft with duodenal complications in selected cases.
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Affiliation(s)
- P D Uva
- Departamento de Trasplante Renopancreático, Instituto de Nefrología de Buenos Aires - Nephrology, Cabello 3889 (1425), Buenos Aires, Argentina.
| | - S Villavicencio Fornaciari
- Departamento de Trasplante Renopancreático, Instituto de Nefrología de Buenos Aires - Nephrology, Cabello 3889 (1425), Buenos Aires, Argentina
| | - A E Giunippero
- Departamento de Trasplante Renopancreático, Instituto de Nefrología de Buenos Aires - Nephrology, Cabello 3889 (1425), Buenos Aires, Argentina
| | - I C Cabrera
- Departamento de Trasplante Renopancreático, Instituto de Nefrología de Buenos Aires - Nephrology, Cabello 3889 (1425), Buenos Aires, Argentina
| | - D H Casadei
- Departamento de Trasplante Renopancreático, Instituto de Nefrología de Buenos Aires - Nephrology, Cabello 3889 (1425), Buenos Aires, Argentina
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The current challenges for pancreas transplantation for diabetes mellitus. Pharmacol Res 2015; 98:45-51. [DOI: 10.1016/j.phrs.2015.01.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Revised: 01/26/2015] [Accepted: 01/27/2015] [Indexed: 12/27/2022]
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Salvadori M, Bertoni E. What's new in clinical solid organ transplantation by 2013. World J Transplant 2014; 4:243-266. [PMID: 25540734 PMCID: PMC4274595 DOI: 10.5500/wjt.v4.i4.243] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 07/11/2014] [Accepted: 07/27/2014] [Indexed: 02/05/2023] Open
Abstract
Innovative and exciting advances in the clinical science in solid organ transplantation continuously realize as the results of studies, clinical trials, international conferences, consensus conferences, new technologies and discoveries. This review will address to the full spectrum of news in transplantation, that verified by 2013. The key areas covered are the transplantation activity, with particular regards to the donors, the news for solid organs such as kidney, pancreas, liver, heart and lung, the news in immunosuppressive therapies, the news in the field of tolerance and some of the main complications following transplantation as infections and cancers. The period of time covered by the study starts from the international meetings held in 2012, whose results were published in 2013, up to the 2013 meetings, conferences and consensus published in the first months of 2014. In particular for every organ, the trends in numbers and survival have been reviewed as well as the most relevant problems such as organ preservation, ischemia reperfusion injuries, and rejections with particular regards to the antibody mediated rejection that involves all solid organs. The new drugs and strategies applied in organ transplantation have been divided into new way of using old drugs or strategies and drugs new not yet on the market, but on phase Ito III of clinical studies and trials.
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Weems P, Cooper M. Pancreas transplantation in type II diabetes mellitus. World J Transplant 2014; 4:216-221. [PMID: 25540731 PMCID: PMC4274592 DOI: 10.5500/wjt.v4.i4.216] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Revised: 06/04/2014] [Accepted: 07/15/2014] [Indexed: 02/05/2023] Open
Abstract
Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.
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Stratta RJ, Rogers J, Farney AC, Orlando G, El-Hennawy H, Gautreaux MD, Reeves-Daniel A, Palanisamy A, Iskandar SS, Bodner JK. Pancreas transplantation in C-peptide positive patients: does "type" of diabetes really matter? J Am Coll Surg 2014; 220:716-27. [PMID: 25667140 DOI: 10.1016/j.jamcollsurg.2014.12.020] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 12/15/2014] [Indexed: 01/01/2023]
Abstract
BACKGROUND In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT). STUDY DESIGN We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥ 2.0 ng/mL or < 2.0 ng/mL. RESULTS From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥ 2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥ 5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2). CONCLUSIONS Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be used exclusively to determine candidacy for SPKT.
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Affiliation(s)
- Robert J Stratta
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC.
| | - Jeffrey Rogers
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Alan C Farney
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Giuseppe Orlando
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Hany El-Hennawy
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael D Gautreaux
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC; Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Amber Reeves-Daniel
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Amudha Palanisamy
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Samy S Iskandar
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jason K Bodner
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
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Rogers J, Farney AC, Orlando G, Iskandar SS, Doares W, Gautreaux MD, Kaczmorski S, Reeves-Daniel A, Palanisamy A, Stratta RJ. Pancreas transplantation: The Wake Forest experience in the new millennium. World J Diabetes 2014; 5:951-961. [PMID: 25512802 PMCID: PMC4265886 DOI: 10.4239/wjd.v5.i6.951] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 07/09/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression.
METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide.
RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.
CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.
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Abstract
Pancreatic transplantation, performed alone or in conjunction with kidney transplantation, is an effective treatment for advanced type I diabetes mellitus and select patients with type II diabetes mellitus. Following advancements in surgical technique, postoperative management, and immunosuppression, pancreatic transplantation has significantly improved the length and quality of life for patients suffering from pancreatic dysfunction. While computed tomography (CT) and magnetic resonance imaging (MRI) have more limited utility, ultrasound is the preferred initial imaging modality to evaluate the transplanted pancreas; gray-scale assesses the parenchyma and fluid collections, while Doppler interrogation assesses vascular flow and viability. Ultrasound is also useful to guide percutaneous interventions for the transplanted pancreas. With knowledge of the surgical anatomy and common complications, the abdominal radiologist plays a central role in the perioperative and postoperative evaluation of the transplanted pancreas.
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Affiliation(s)
- Matthew T Heller
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Puneet Bhargava
- Department of Radiology, University of Washington Harborview Medical Center, Seattle, Washington, USA
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Stratta RJ, Rogers J, Orlando G, Farooq U, Al-Shraideh Y, Doares W, Kaczmorski S, Farney AC. Depleting antibody induction in simultaneous pancreas-kidney transplantation: a prospective single-center comparison of alemtuzumab versus rabbit anti-thymocyte globulin. Expert Opin Biol Ther 2014; 14:1723-30. [DOI: 10.1517/14712598.2014.953049] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Otsuki K, Yoshikawa K, Kenmoshi T, Akutsu N, Maruyama M, Asano T, Saigo K, Hasegawa M, Aoyama H, Matsumoto I, Ito T, Uchino Y. Evaluation of insulin independence using 11C-methionine positron emission tomography after living-donor and brain-dead donor pancreas transplantation. Transplant Proc 2014; 46:1913-6. [PMID: 25131069 DOI: 10.1016/j.transproceed.2014.05.069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.
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Affiliation(s)
- K Otsuki
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan.
| | - K Yoshikawa
- National Institute of Radiological Sciences, Chiba, Japan
| | - T Kenmoshi
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - N Akutsu
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Maruyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Asano
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - K Saigo
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Hasegawa
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - H Aoyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - I Matsumoto
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Ito
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - Y Uchino
- Chiba Ryogo Center, PET Imaging Division, Chiba, Japan
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Fourtounas C. Transplant options for patients with type 2 diabetes and chronic kidney disease. World J Transplant 2014; 4:102-110. [PMID: 25032099 PMCID: PMC4094945 DOI: 10.5500/wjt.v4.i2.102] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 03/20/2014] [Accepted: 05/14/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic kidney disease (CKD) has become a real epidemic around the world, mainly due to ageing and diabetic nephropathy. Although diabetic nephropathy due to type 1 diabetes mellitus (T1DM) has been studied more extensively, the vast majority of the diabetic CKD patients suffer from type 2 diabetes mellitus (T2DM). Renal transplantation has been established as a first line treatment for diabetic nephropathy unless there are major contraindications and provides not only a better quality of life, but also a significant survival advantage over dialysis. However, T2DM patients are less likely to be referred for renal transplantation as they are usually older, obese and present significant comorbidities. As pre-emptive renal transplantation presents a clear survival advantage over dialysis, all T2DM patients with CKD should be referred for early evaluation by a transplant center. The transplant center should have enough time in order to examine their eligibility focusing on special issues related with diabetic nephropathy and explore the best options for each patient. Living donor kidney transplantation should always be considered as the first line treatment. Otherwise, the patient should be listed for deceased donor kidney transplantation. Recent progress in transplantation medicine has improved the "transplant menu" for T2DM patients with diabetic nephropathy and there is an ongoing discussion about the place of simultaneous pancreas kidney (SPK) transplantation in well selected patients. The initial hesitations about the different pathophysiology of T2DM have been forgotten due to the almost similar short- and long-term results with T1DM patients. However, there is still a long way and a lot of ethical and logistical issues before establishing SPK transplantation as an ordinary treatment for T2DM patients. In addition recent advances in bariatric surgery may offer new options for severely obese T2DM patients with CKD. Nevertheless, the existing data for T2DM patients with advanced CKD are rather scarce and bariatric surgery should not be considered as a cure for diabetic nephropathy, but only as a bridge for renal transplantation.
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