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Bellotti R, Brugger M, Oberhuber R, Cardini B, Resch T, Maglione M, Margreiter C, Weißenbacher A, Brandacher G, Schneeberger S, Messner F. The impact of delayed graft function after pancreas transplantation on clinical outcomes and survival. Pancreatology 2025:S1424-3903(25)00084-5. [PMID: 40374459 DOI: 10.1016/j.pan.2025.04.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/15/2025] [Accepted: 04/29/2025] [Indexed: 05/17/2025]
Abstract
INTRODUCTION Delayed graft function after pancreas transplantation (pDGF) is still lacking of a homogenous definition. So, its incidence and clinical impact are poorly understood. METHODS 151 consecutive pancreas transplants (PTx) performed at the Medical University of Innsbruck between January 2011 and December 2021. 142 were finally evaluated analyzed after excluding those with early graft loss due to surgical or infectious problems. RESULTS pDGF was defined as a total mean insulin requirement of 2.5 UI or greater within postoperative day 10. Of the 142 recipients, 52 (36.6 %) developed pDGF. By multivariate analysis, pDGF was found to be associated with a donor age (odds ratio, 1.05; 95 % CI: 1.01-1.09; p = 0.010) and the continuous postoperative administration of unfractioned heparin (odds ratio, 2.52; 95 % CI: 1.12-5.64; p = 0.025). The occurrence of pDGF lead to longer hospital stay (23 vs 20 days, p = 0.049), intensive care unit stay (5 vs 3 days, p < 0.003) and impaired glycemia at day 10 postoperative (146.0 vs 126.4 mg/dl, p < 0.001). Also, pDGF was found to be associated with a greater risk of pancreas graft failure at 5 years (p = 0.047) in the univariable analysis, while in the multivariable this trend was not statistically significant (p = 0.076). Of note, in the multivariable analysis pDGF showed a strong trend towards worse graft survival without reaching statistical significance (HR:2.33, 95 % CI: 0.95-5.82; p = 0.069) CONCLUSION: pDGF represents a common condition, depending both from donor and recipient conditions. Its clinical impact concerns the early postoperative stay and the long-term graft survival as well.
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Affiliation(s)
- Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Brugger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria; Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Annemarie Weißenbacher
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Gerald Brandacher
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Franka Messner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
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Rendell M. Pharmacotherapy of type 1 diabetes - part 2 Today. Expert Opin Pharmacother 2025; 26:719-730. [PMID: 40082213 DOI: 10.1080/14656566.2025.2479598] [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: 12/07/2024] [Revised: 02/27/2025] [Accepted: 03/11/2025] [Indexed: 03/16/2025]
Abstract
INTRODUCTION In the 100 years since isolation and administration of animal insulin to sustain life in Type 1 diabetes, there has been increasing progress in the administration of exogenous insulin to lower glucose levels. AREAS COVERED We reviewed using standard search engines and PubMed present-day techniques of management of type 1 diabetes. EXPERT OPINION Long-acting insulin formulations have been developed to maintain basal glucose levels in the normal range, while rapid acting insulins have been synthesized to address the sharp rise in glucose levels after a meal. Insulin pumps administer insulin continuously subcutaneously guided by continuous glucose monitoring systems. These almost closed loop systems achieve near normal glucose levels other than at meal times where the rapid glucose rise and then fall pose a significant challenge due to the extended duration of subcutaneous insulin depots. Implanted insulin pumps with intraperitoneal delivery may eventually permit improved post meal glucose control. Type 1 diabetes has now been redefined as an autoimmune disease which may be diagnosed purely from the presence of anti-beta cell antibodies with no abnormality of glucose levels. The future will see an intensification of efforts to combat the immune process which destroys beta cells.
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Affiliation(s)
- Marc Rendell
- The Association of Diabetes Investigators, Omaha, NE, USA
- The Rose Salter Medica Research Foundation, Newport Coast, CA, USA
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Zheng M, Wu Y, Xiang J, Wang L, Li Z, Gao F. Impact of Preprocurement Cardiac Arrest in Brain-Dead Donors on the Outcome of Pancreas Transplantation. Transplant Proc 2024; 56:2255-2262. [PMID: 39609177 DOI: 10.1016/j.transproceed.2024.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/10/2024] [Accepted: 11/11/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND This study aimed to determine the risk factors and whether cardiac arrest (CA) in brain-death donors (DBD) could affect pancreas transplantation outcomes. METHODS We analyzed data from the Scientific Registry of Transplant Recipients (2000-2020). The study included 21,499 pancreas transplantations, divided into CA-DBD and noCA-DBD groups based on whether the DBD had a history of CA. RESULTS There were 1129 CA-DBD (5.3%) transplantations. The principal donor death cause for both groups was head trauma. Graft and patient survival rates were similar in both groups. CA time (CAT) was a risk factor for pancreatic graft survival in the univariate analysis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.03-1.08; P = .010) and multivariate Cox regression model (HR, 1.03; 95% CI, 1.02-1.04; P =.015). Pancreas graft survival in those with CAT ≥30 minutes was significantly lower than in those with CAT <30 minutes and the noCA-DBD group (log-rank P = .018 and P = .014, respectively), which were comparable (log-rank P = .711). No relationships were found among the various transplantation types. CONCLUSIONS CA in donors did not affect the pancreatic graft prognosis. However, pancreatic donors with CAT ≥30 minutes should be meticulously evaluated.
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Affiliation(s)
- Minyan Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yue Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Li Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Feng Gao
- Department of Urological Surgery, Weifang People's Hospital, Shandong, China.
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Santos da Silva T, da Silva-Júnior LN, Horvath-Pereira BDO, Valbão MCM, Garcia MHH, Lopes JB, Reis CHB, Barreto RDSN, Buchaim DV, Buchaim RL, Miglino MA. The Role of the Pancreatic Extracellular Matrix as a Tissue Engineering Support for the Bioartificial Pancreas. Biomimetics (Basel) 2024; 9:598. [PMID: 39451804 PMCID: PMC11505355 DOI: 10.3390/biomimetics9100598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/22/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024] Open
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate vascularization. The main limitations to clinical islet transplantation are the scarcity of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. Despite extensive research, T1DM remains a major global health issue. In 2015, diabetes affected approximately 415 million people, with projected expenditures of USD 1.7 trillion by 2030. Pancreas transplantation faces challenges due to limited organ availability and complex vascularization. T1DM is caused by the autoimmune destruction of insulin-producing pancreatic cells. Advances in biomaterials, particularly the extracellular matrix (ECM), show promise in tissue reconstruction and transplantation, offering structural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas's intricate architecture and maintaining cell viability and functionality. Emerging technologies, such as 3D printing and advanced biomaterials, have shown potential in constructing bioartificial organs. ECM components, including collagens and glycoproteins, play essential roles in cell adhesion, migration, and differentiation. Clinical applications focus on developing functional scaffolds for transplantation, with ongoing research addressing immunological responses and long-term efficacy. Pancreatic bioengineering represents a promising avenue for T1DM treatment, requiring further research to ensure successful implementation.
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Affiliation(s)
- Thamires Santos da Silva
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
| | - Leandro Norberto da Silva-Júnior
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
- Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil; (M.C.M.V.); (M.H.H.G.); (J.B.L.)
| | - Bianca de Oliveira Horvath-Pereira
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
| | - Maria Carolina Miglino Valbão
- Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil; (M.C.M.V.); (M.H.H.G.); (J.B.L.)
| | | | - Juliana Barbosa Lopes
- Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil; (M.C.M.V.); (M.H.H.G.); (J.B.L.)
| | - Carlos Henrique Bertoni Reis
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, Brazil;
- UNIMAR Beneficent Hospital (HBU), Medical School, University of Marilia (UNIMAR), Marilia 17525-160, Brazil
| | - Rodrigo da Silva Nunes Barreto
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
- Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinary Sciences, São Paulo State University, Jaboticabal 14884-900, Brazil
| | - Daniela Vieira Buchaim
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, Brazil;
- Medical School, University Center of Adamantina (UNIFAI), Adamantina 17800-000, Brazil
| | - Rogerio Leone Buchaim
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil; (T.S.d.S.); (L.N.d.S.-J.); (B.d.O.H.-P.); (R.d.S.N.B.); (D.V.B.); (R.L.B.)
- Department of Biological Sciences, Bauru School of Dentistry (FOB/USP), University of Sao Paulo, Bauru 17012-901, Brazil
| | - Maria Angelica Miglino
- Postgraduate Department, University of Marília (UNIMAR), Marília 17525-902, Brazil; (M.C.M.V.); (M.H.H.G.); (J.B.L.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, Brazil;
- Postgraduate Program in Animal Health, Production and Environment, University of Marilia (UNIMAR), Marilia 17525-902, Brazil
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Yang KH, Ryu JH, Shim JR, Lee TB, Lee HJ, Kim SR, Ju SH, Choi BH. The Pancreas After Kidney Transplant is a Competitive Option, Comparable to the Simultaneous Pancreas and Kidney Transplant. Transplant Proc 2024; 56:1347-1352. [PMID: 39079788 DOI: 10.1016/j.transproceed.2024.03.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Simultaneous pancreas and kidney transplant (SPK) is the most common type of pancreas transplant performed worldwide. In contrast, there are a few drawbacks to pancreas after kidney transplant (PAK), such as the requirement for an additional operation, the immunologic risk, etc. SPK is the best option, but because of a lack of deceased donors and a lengthy waiting period, it is not always possible to use it. METHODS From 2015 to 2022, we performed 23 SPKs and 21 PAKs at the Pusan National University Yangsan Hospital in Korea. We compared the findings of PAK and SPK conducted within the same time period. RESULTS The waiting time for pancreatic graft was significantly shorter in the PAK than SPK group (345 days vs 1350 days, P ≤ .001). Throughout the monitoring period, just 1 pancreatic graft was lost in patients who underwent PAK, and the 7-year graft survival was 95%, with no statistically significant difference compared to SPK (90.3%, P = .600). Moreover, the graft survival of SPK or PAK was superior to that of pancreatic transplant alone (63.7%, P = .016). Only 1 pancreatic graft loss was a case of mortality with a functioning graft. No additional kidney transplant loss was observed in PAK recipients. There was no variation in creatinine levels between the pretransplant and posttransplant periods. There were 2 incidents of pancreatic graft and kidney graft rejection, respectively, but the grafts entirely recovered following rejection treatment. CONCLUSION According to our experiences, PAK could be another best choice for individuals with diabetic end-stage renal disease, especially in cases where deceased donors were severely deficient but living donor kidney transplants were actively performed in countries like Korea.
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Affiliation(s)
- Kwang Ho Yang
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Jae Ryong Shim
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Tae Beom Lee
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Hyun Ji Lee
- Department of Laboratory Medicine, Pusan National University School of Medicine, Yangsan, South Korea
| | - Seo Rin Kim
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Su Hyun Ju
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Byung Hyun Choi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
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Moein M, Maloney B, Baio S, Bahreini A, Abedini M, Abedini M, Saidi RF. Pancreas after kidney transplantation, is it the time to overcome the stigma? World J Surg 2024; 48:1501-1508. [PMID: 38682645 DOI: 10.1002/wjs.12191] [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: 11/10/2023] [Accepted: 04/08/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Pancreas transplantation is the most effective treatment to improve quality of life and overcome complications in patients with end-stage renal disease and diabetes mellitus. One of the main approaches for concurrent renal disease and diabetes mellitus which has been underutilized during the past decade is a pancreas transplant after kidney transplantation. Our study aimed to quantify outcomes following pancreas after kidney transplants (PAKs) in the United States from 2001 to 2020 with an emphasis on graft and patient survival. METHODS AND MATERIALS A retrospective registry analysis was performed by accessing the OPTN/UNOS database for PAKs that were performed in the United States from January 2001 to April 2020. The study population was divided into two subgroups: patients receiving a pancreas transplant between 2001 and 2010 and those receiving a pancreas transplant between 2011 and 2020. RESULTS The study examined a total number of 3706 PAK recipients; patients who received a PAK from January 2001 through December 2010 (n = 2892) and those who received a PAK from January 2011 to April 2020 (n = 814). The selection process of transplant recipients did not drastically change throughout the 2001-2010 and 2011-2020 periods. Length of stay at the hospital after the transplantation improved significantly in the 2011-2020 group relative to the 2001-2010 group (8.48 vs. 10.08 days, mean, p < 0.01). Additionally, more transplantation with 4-6 human leukocyte antigen mismatch occurred in the 2011-2020 group than in the 2001-2010 group (80.6% vs. 71.4%, p < 0.01). The pancreas preservation time of 13.35 h in the 2001-2010 group decreased significantly to 11.17 h in the 2011-2020 group (p < 0.001). The mean donor's amylase and lipase also decreased significantly in the 2011-2020 cohort. Significant graft survival improvement was observed in the 2011-2020 group compared to the 2001-2010 group after a long-term follow-up (p < 0.001). The mean Calculated Pancreas Donor Risk Index was 1.08 for the 2001-2010 group and 0.99 for the 2011-2020 group with a significant difference (p < 0.001). CONCLUSION The beneficial results and improved outcomes observed in PAK patients demonstrate the effectiveness of the operation for individuals in need of a pancreas transplant. PAKs can prove to be a meaningful solution to overcome long waiting times, decrease the donor-recipient imbalance, expand the donor pool, and overcome the current underutilization in order to improve the short- and long-term quality of life in the groups of interest.
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Affiliation(s)
- Mahmoudreza Moein
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Brendan Maloney
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Stephen Baio
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Amin Bahreini
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Marjan Abedini
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Mahsa Abedini
- Department of Medical and Serological Sciences, University of Bologna, Bologna, Italy
| | - Reza F Saidi
- Division of Transplant Services, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA
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Alfaro Villanueva LA, Junior RM, Rangel ÉB, Modelli LG, Viana LA, Cristelli MP, Requião-Moura L, Foresto RD, Tedesco-Silva H, Pestana JM. Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model. Clin Transplant 2024; 38:e15298. [PMID: 38545918 DOI: 10.1111/ctr.15298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 02/28/2024] [Accepted: 03/11/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.
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Affiliation(s)
| | | | - Érika Bevilaqua Rangel
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luis Gustavo Modelli
- Division of Nephrology, Department of Internal Medicine, Universidade Estadual Paulista (UNESP), Botucatu, Brazil
| | | | | | - Lúcio Requião-Moura
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | | | - Helio Tedesco-Silva
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
| | - José Medina Pestana
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil
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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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9
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Vafadar A, Vosough P, Jahromi HK, Tajbakhsh A, Savardshtaki A, Butler AE, Sahebkar A. The role of efferocytosis and transplant rejection: Strategies in promoting transplantation tolerance using apoptotic cell therapy and/or synthetic particles. Cell Biochem Funct 2023; 41:959-977. [PMID: 37787641 DOI: 10.1002/cbf.3852] [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: 06/05/2023] [Revised: 07/26/2023] [Accepted: 08/24/2023] [Indexed: 10/04/2023]
Abstract
Recently, efforts have been made to recognize the precise reason(s) for transplant failure and the process of rejection utilizing the molecular signature. Most transplant recipients do not appreciate the unknown length of survival of allogeneic grafts with the existing standard of care. Two noteworthy immunological pathways occur during allogeneic transplant rejection. A nonspecific innate immune response predominates in the early stages of the immune reaction, and allogeneic antigens initiate a donor-specific adaptive reaction. Though the adaptive response is the major cause of allograft rejection, earlier pro-inflammatory responses that are part of the innate immune response are also regarded as significant in graft loss. The onset of the innate and adaptive immune response causes chronic and acute transplant rejection. Currently employed immunosuppressive medications have shown little or no influence on chronic rejection and, as a result, on overall long-term transplant survival. Furthermore, long-term pharmaceutical immunosuppression is associated with side effects, toxicity, and an increased risk of developing diseases, both infectious and metabolic. As a result, there is a need for the development of innovative donor-specific immunosuppressive medications to regulate the allorecognition pathways that induce graft loss and to reduce the side effects of immunosuppression. Efferocytosis is an immunomodulatory mechanism with fast and efficient clearance of apoptotic cells (ACs). As such, AC therapy strategies have been suggested to limit transplant-related sequelae. Efferocytosis-based medicines/treatments can also decrease the use of immunosuppressive drugs and have no detrimental side effects. Thus, this review aims to investigate the impact of efferocytosis on transplant rejection/tolerance and identify approaches using AC clearance to increase transplant viability.
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Affiliation(s)
- Asma Vafadar
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parisa Vosough
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Kargar Jahromi
- Research Center for Non-Communicable Disease, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Amir Tajbakhsh
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardshtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland - Bahrain, Adliya, Bahrain
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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10
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Fujisawa-Tanaka C, Hiratsuka I, Shibata M, Kurihara K, Aida N, Takayanagi T, Seino Y, Ito T, Kenmochi T, Suzuki A. Pancreas transplantation improves the quality of life of Japanese type 1 diabetes patients with diabetic kidney disease. FUJITA MEDICAL JOURNAL 2023; 9:194-199. [PMID: 37554935 PMCID: PMC10405895 DOI: 10.20407/fmj.2022-019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/12/2022] [Indexed: 08/10/2023]
Abstract
OBJECTIVES Type 1 diabetes mellitus (T1DM) patients with diabetic kidney disease-induced kidney failure have a significantly impaired quality of life (QOL), resulting in a high level of physical, mental, and social anxiety. In this study, we evaluated the QOL of T1DM patients on the list for pancreas transplantation (PTx) at their registration, and determined whether PTx improved their QOL. METHODS There were 58 patients (men/women, 22/36; mean age, 42.8±8.0 years) with T1DM and who were registered on the waiting list for PTx. Quantitative QOL assessment was performed using the Medical Health Survey Short Form (SF-36) version 2. Changes in the QOL before and after PTx were also examined in 24 of these patients. RESULTS The mean value of each endpoint and the summary score of the SF-36 physical (PCS), mental (MCS), and role (RCS) components were all below the national normal level at PTx registration. No significant difference in QOL scores was observed in the intergroup comparison of 35 patients on dialysis, 13 patients without dialysis, and ten patients after kidney transplantation. The 24 patients who underwent PTx showed improvement in PCS, MCS, and most SF-36 scores. CONCLUSION T1DM patients waiting for PTx had a decreased QOL, regardless of dialysis, and PTx improved their QOL.
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Affiliation(s)
- Chika Fujisawa-Tanaka
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Izumi Hiratsuka
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Megumi Shibata
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Kei Kurihara
- Department of Transplantation and Regenerative Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Naohiro Aida
- Department of Transplantation and Regenerative Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Takeshi Takayanagi
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Yusuke Seino
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Taihei Ito
- Department of Transplantation and Regenerative Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Takashi Kenmochi
- Department of Transplantation and Regenerative Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Atsushi Suzuki
- Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
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11
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Ho GC, Samuel SL, Haroon U, Drage M. Youngest pancreas transplantation alone in the UK for type 1 diabetes and severe subcutaneous insulin resistance. BMJ Case Rep 2023; 16:e255068. [PMID: 37353238 PMCID: PMC10314501 DOI: 10.1136/bcr-2023-255068] [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] [Indexed: 06/25/2023] Open
Abstract
A child diagnosed with type 1 diabetes mellitus during her middle childhood developed severe subcutaneous insulin resistance as her illness progressed. This resulted in recurrent episodes of diabetic ketoacidosis and hypoglycaemia, eventually leading to intravenous insulin dependence. Despite intensive investigations, an organic cause was not found.The patient was in her late adolescence when she eventually received her pancreas transplant alone, the youngest patient in the UK. This case highlights severe peripheral insulin resistance as an important indication for whole organ pancreas transplantation in the paediatric population, as well as early recognition in the failure of conventional medical therapy.
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Affiliation(s)
- Garm Chi Ho
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Sajanee Liz Samuel
- Department of Paediatrics, Princess Alexandra Hospital NHS Foundation Trust, Harlow, UK
| | - Usman Haroon
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Martin Drage
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
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12
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Giuliani T, Ibáñez JM, Montalvá-Orón E, Robledo AB, Chicote CM, Sanz AH, Ibañez CB, Mizrahi DC, Castelló IB, Torres JFM, Andújar RL. Simultaneous pancreas-kidney transplantation: which graft warns the most? Langenbecks Arch Surg 2023; 408:196. [PMID: 37191721 DOI: 10.1007/s00423-023-02876-7] [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: 07/26/2022] [Accepted: 03/31/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Simultaneous pancreas-kidney transplantation (SPK) is still characterized by high rates of postoperative complications. This study aims to offer an in-depth characterization of early, medium-term, and late complications following SPK to derive insights for postoperative management and follow-up. METHODS Consecutive SPK transplantations were analysed. Pancreatic graft (P-graft)- and kidney graft (K-graft)-related complications were analysed separately. The global postoperative course was assessed in three timeframes (early, medium-term, and late) using the comprehensive complication index (CCI). Predictors of complications and early graft loss were explored. RESULTS Complications occurred in 61.2% of patients, and the 90-day mortality was 3.9%. The overall burden of complications was significantly high during admission (CCI 22.4 ± 21.1) and decreased gradually afterwards. P-graft-related complications burdened the most in the early postoperative course (CCI 11.6 ± 13.8); postoperative ileus and perigraft fluid collection were the most frequent complications, and pseudoaneurysms, haemorrhages, and bowel leaks were the major concerns. K-related complications were milder but represented the largest proportion of the CCI in the late postoperative timeframe (CCI 7.6 ± 13.6). No predictors of P-graft- or K-graft-related complications were found. CONCLUSION Pancreas graft-related complications represent the largest part of the clinical burden in the early postoperative timeframe but are negligible after 3 months. Kidney grafts have a relevant impact in the long term. The multidisciplinary approach to SPK recipients should be driven based on all graft-specific complications and tailored on a time-dependent basis.
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Affiliation(s)
- Tommaso Giuliani
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
- Department of General and Pancreatic Surgery, Verona Hospital Trust, University of Verona, Verona, Italy
| | - Javier Maupoey Ibáñez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Eva Montalvá-Orón
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
- IIS La Fe, CIBERehd, Instituto de Salud San Carlos III, Madrid, Spain
| | - Andrea Boscà Robledo
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Martínez Chicote
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Ana Hernando Sanz
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Ballester Ibañez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - David Calatayud Mizrahi
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Isabel Beneyto Castelló
- Department of Nephrology and Kidney Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | | | - Rafael López Andújar
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain.
- IIS La Fe, CIBERehd, Instituto de Salud San Carlos III, Madrid, Spain.
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13
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Martin D, Alberti P, Demartines N, Phillips M, Casey J, Sutherland A. Whole-Organ Pancreas and Islets Transplantations in UK: An Overview and Future Directions. J Clin Med 2023; 12:3245. [PMID: 37176684 PMCID: PMC10179530 DOI: 10.3390/jcm12093245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/19/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023] Open
Abstract
Whole-organ pancreas and islets transplantations are two therapeutic options to treat type 1 diabetic patients resistant to optimised medical treatment in whom severe complications develop. Selection of the best option for β-cell replacement depends on several factors such as kidney function, patient comorbidities, and treatment goals. For a patient with end-stage kidney disease, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK). However, it remains a major surgical procedure in patients with multiple comorbidities and therefore it is important to select those who will benefit from it. Additionally, in view of the organ shortage, new strategies to improve outcomes and reduce immune reactions have been developed, including dynamic organ perfusion technologies, pancreas bioengineering, and stem cell therapies. The purpose of this article is to review the indications, surgical techniques, outcomes, and future directions of whole-organ pancreas and islets transplantations.
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Affiliation(s)
- David Martin
- Department of Visceral Surgery and Transplantation, University Hospital CHUV, University of Lausanne (UNIL), 1015 Lausanne, Switzerland;
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK (M.P.); (J.C.); (A.S.)
| | - Piero Alberti
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK (M.P.); (J.C.); (A.S.)
| | - Nicolas Demartines
- Department of Visceral Surgery and Transplantation, University Hospital CHUV, University of Lausanne (UNIL), 1015 Lausanne, Switzerland;
| | - Melanie Phillips
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK (M.P.); (J.C.); (A.S.)
| | - John Casey
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK (M.P.); (J.C.); (A.S.)
| | - Andrew Sutherland
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK (M.P.); (J.C.); (A.S.)
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14
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Kale A, Rogers NM. No Time to Die-How Islets Meet Their Demise in Transplantation. Cells 2023; 12:cells12050796. [PMID: 36899932 PMCID: PMC10000424 DOI: 10.3390/cells12050796] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/27/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Islet transplantation represents an effective treatment for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycaemia unawareness, capable of circumventing impaired counterregulatory pathways that no longer provide protection against low blood glucose levels. The additional beneficial effect of normalizing metabolic glycaemic control is the minimisation of further complications related to T1DM and insulin administration. However, patients require allogeneic islets from up to three donors, and the long-term insulin independence is inferior to that achieved with solid organ (whole pancreas) transplantation. This is likely due to the fragility of islets caused by the isolation process, innate immune responses following portal infusion, auto- and allo-immune-mediated destruction and β-cell exhaustion following transplantation. This review covers the specific challenges related to islet vulnerability and dysfunction that affect long-term cell survival following transplantation.
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Affiliation(s)
- Atharva Kale
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Natasha M. Rogers
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
- Renal and Transplant Unit, Westmead Hospital, Westmead, NSW 2145, Australia
- Correspondence:
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15
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Naqvi RA, Naqvi AR, Singh A, Priyadarshini M, Balamurugan AN, Layden BT. The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells? Front Endocrinol (Lausanne) 2023; 13:1001041. [PMID: 36686451 PMCID: PMC9849241 DOI: 10.3389/fendo.2022.1001041] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 12/07/2022] [Indexed: 01/06/2023] Open
Abstract
Replacement of β cells is only a curative approach for type 1 diabetes (T1D) patients to avoid the threat of iatrogenic hypoglycemia. In this pursuit, islet allotransplantation under Edmonton's protocol emerged as a medical miracle to attain hypoglycemia-free insulin independence in T1D. Shortage of allo-islet donors and post-transplantation (post-tx) islet loss are still unmet hurdles for the widespread application of this therapeutic regimen. The long-term survival and effective insulin independence in preclinical studies have strongly suggested pig islets to cure overt hyperglycemia. Importantly, CRISPR-Cas9 technology is pursuing to develop "humanized" pig islets that could overcome the lifelong immunosuppression drug regimen. Lately, induced pluripotent stem cell (iPSC)-derived β cell approaches are also gaining momentum and may hold promise to yield a significant supply of insulin-producing cells. Theoretically, personalized β cells derived from a patient's iPSCs is one exciting approach, but β cell-specific immunity in T1D recipients would still be a challenge. In this context, encapsulation studies on both pig islet as well as iPSC-β cells were found promising and rendered long-term survival in mice. Oxygen tension and blood vessel growth within the capsules are a few of the hurdles that need to be addressed. In conclusion, challenges associated with both procedures, xenotransplantation (of pig-derived islets) and stem cell transplantation, are required to be cautiously resolved before their clinical application.
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Affiliation(s)
- Raza Ali Naqvi
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, United States
| | - Afsar Raza Naqvi
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, United States
| | - Amar Singh
- Department of Surgery, University of Minnesota, Minneapolis, MN, United States
| | - Medha Priyadarshini
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Appakalai N. Balamurugan
- Center for Clinical and Translational Research, Nationwide Children’s Hospital, Columbus, OH, United States
- Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, United States
| | - Brian T. Layden
- Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
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16
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Giuliani T, Ibáñez JM, Orón EM, Robledo AB, Chicote CM, Hernando Sanz A, Ballester Ibáñez C, Mizrahi DC, Castelló IB, Merino Torres JF, López Andújar R. Appraising pancreatic fistula in pancreas transplantation: A comprehensive complication index based analysis of postoperative outcomes and predictors of graft survival. Pancreatology 2022; 22:1167-1174. [PMID: 36220755 DOI: 10.1016/j.pan.2022.09.238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/05/2022] [Accepted: 09/12/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND A definition of pancreatic fistula specifically addressing pancreas transplantation (PT) is lacking. This study sought to characterize pancreatic fistula in this setting and to define its clinical relevance on the postoperative course and long-term graft survival (GS). METHODS Consecutive simultaneous pancreas and kidney transplantations were analysed. The global postoperative course was assessed through the comprehensive complication index (CCI). PF was defined according to the original International Study Group for Pancreatic Surgery (ISGPS) definition. Predictors of poor postoperative course and GS were explored. RESULTS Seventy-eight patients were analysed. Surgical morbidity was 48.7%, with severe complications occurring in 39.7%. Ninety-day mortality was 2.6%. PF occurred in 56.6% of patients, although its average clinical burden was low and did not correlate with either early or long-term outcomes. Peri-graft fluid collections, postoperative day (POD) 1 drain fluid amylase (DFA) ≥ 2200 U/L, and POD 5 DFA/serum amylase ratio ≥7.0 independently correlated with poor postoperative course. Perigraft fluid collections were associated with reduced GS. CONCLUSION Conventionally defined pancreatic fistula is frequent following PT, although its clinical impact is negligible. To define clinically relevant PF, novel cut-offs for DFA might be pondered in a future series, while perigraft fluid collections should be strongly considered.
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Affiliation(s)
- Tommaso Giuliani
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain; Department of General and Pancreatic Surgery, Verona Hospital Trust, University of Verona, Verona, Italy
| | - Javier Maupoey Ibáñez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Eva Montalvá Orón
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Andrea Boscà Robledo
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Martínez Chicote
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Ana Hernando Sanz
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Cristina Ballester Ibáñez
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - David Calatayud Mizrahi
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | - Isabel Beneyto Castelló
- Department of Nephrology and Kidney Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain
| | | | - Rafael López Andújar
- Department of HPB Surgery and Transplantation, La Fe University Hospital and University of Valencia, Valencia, Spain.
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17
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Outcomes of Primary Simultaneous Pancreas-kidney Transplants by Induction Agent in the United States. Transplant Direct 2022; 8:e1412. [PMID: 36406900 PMCID: PMC9671748 DOI: 10.1097/txd.0000000000001412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 09/20/2022] [Indexed: 01/25/2023] Open
Abstract
UNLABELLED Long-term outcome data by induction type in simultaneous pancreas-kidney (SPK) is limited. METHODS Utilizing the Scientific Registry of Transplant Recipients, we examined all primary SPK transplants between 2000 and 2020, excluding crossmatch-positive recipients. We grouped recipients according to induction regimen into 3 groups: rabbit anti-thymocyte globulin (r-ATG) (n = 5678), alemtuzumab (n = 1199), and interleukin-2 receptor antagonist (IL-2RA; n = 1593). We analyzed the 10-y recipient and composite (kidney and pancreas) graft survival using the Kaplan-Meier survival function. Cox-proportion hazard models were generated to examine the association between induction type, the 10-y recipient, and graft survival. Models were adjusted for recipient age, sex, ethnicity, HLA-mismatch, diabetes type, dialysis dependency, cold-ischemia time, local versus imported organs, panel reactive antibody, steroid maintenance, and Pancreas Donor Risk Index. RESULTS r-ATG was associated with the lowest 1-y kidney and pancreas rejection rates compared with other agents (P < 0.001). In the univariable analysis, induction type was not associated with recipient (log-rank P = 0.11) or graft survival (log-rank P = 0.36). In the multivariable model for the composite graft survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared with r-ATG (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05-1.42), whereas IL-2RA use was not a predictor of graft survival. Induction type did not influence recipient survival in the adjusted model. CONCLUSIONS r-ATG use was associated with the lowest SPK rejection rates. Compared with r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK graft outcome. Our analysis supports the common use of r-ATG for induction in US primary SPK recipients.
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18
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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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19
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Calil IL, Tustumi F, Sousa JHBD, Tomazini BM, Cruz RJ, Saliba GN, Pécora RAA, D’Albuquerque LAC. What is the role of heat shock protein in abdominal organ transplantation? EINSTEIN-SAO PAULO 2022; 20:eRB6181. [PMID: 35293529 PMCID: PMC8909122 DOI: 10.31744/einstein_journal/2022rb6181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/13/2021] [Indexed: 01/02/2023] Open
Abstract
Ischemia-reperfusion injury is a pathophysiological event occuring after abdominal organ transplantation, and has a significant influence on prognosis and survival of the graft. It is involved in delaying the primary function or non-functioning of the graft. The objective of this study was to provide information on heat shock protein mechanisms in ischemia-reperfusion injuries in abdominal organ transplantations, and to indicate the possible factors involved that may influence the graft outcome. Several classes of heat shock proteins are part of the ischemia and reperfusion process, both as inflammatory agonists and in protecting the process. Studies involving heat shock proteins enhance knowledge on ischemia-reperfusion injury mitigation processes and the mechanisms involved in the survival of abdominal grafts, and open space to support therapeutic future clinical studies, minimizing ischemia and reperfusion injuries in abdominal organ transplantations. Expression of heat shock proteins is associated with inflammatory manifestations and ischemia-reperfusion injuries in abdominal organ transplantations and may influence graft outcomes.
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20
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Tzvetanov IG, Tulla KA, Di Cocco P, Spaggiari M, Benedetti E. Robotic Kidney Transplant: The Modern Era Technical Revolution. Transplantation 2022; 106:479-488. [PMID: 34288638 DOI: 10.1097/tp.0000000000003881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Since the mid 20th century, transplantation has been a fast-developing field of contemporary medicine. The technical aspects of transplant operations were developed in the 1950s, with little significant change for >50 y. Those techniques allowed completion of various organ transplants and successful patient outcomes, but they also carried the inherent disadvantages of open surgery, such as postoperative pain, wound complications and infections, and prolonged length of hospital stay. The introduction and adoption of minimally invasive surgical techniques in the early 1990s to various surgical specialties including general, gynecologic, and urologic surgery led to significant improvements in postoperative patient care and outcomes. Organ transplantation, with its precision demanding vascular anastomoses, initially had been considered infeasible to accomplish with conventional laparoscopic devices. The institution of robotic surgical technology in the late 1990s and its subsequent wide utilization in fields of surgery changed its accessibility and acceptance. With the steady camera, 3D views, and multidirectional wrist motions, surgical robotics opened new horizons for technically demanding surgeries such as transplantation to be completed in a minimally invasive fashion. Furthermore, the hope was this technique could find a niche to treat patients who otherwise are not deemed surgical candidates in many fields including transplantation. Here in, robotics in kidney transplantation and its ability to help provide equity through access to transplantation will be discussed.
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Affiliation(s)
- Ivo G Tzvetanov
- Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL
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Montagud-Marrahi E, Amor AJ, Molina-Andujar A, Cucchiari D, Revuelta I, Esforzado N, Cofan F, Oppenheimer F, Torregrosa V, Casals J, Ferrer J, Esmatjes E, Ramírez-Bajo MJ, Musquera M, Bayes B, Campistol JM, Diekmann F, Ventura-Aguiar P. Impact of insulin therapy before donation on graft outcomes in pancreas transplantation: An analysis of the OPTN/UNOS database. Diabetes Res Clin Pract 2021; 182:109120. [PMID: 34742782 DOI: 10.1016/j.diabres.2021.109120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/27/2021] [Accepted: 11/01/2021] [Indexed: 11/20/2022]
Abstract
AIMS Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. METHODS Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. RESULTS A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98-1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85-1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98-1.16], P = 0.15). CONCLUSIONS Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.
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Affiliation(s)
- Enrique Montagud-Marrahi
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | - Antonio J Amor
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic Barcelona, Spain
| | - Alicia Molina-Andujar
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | - David Cucchiari
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | - Ignacio Revuelta
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | - Nuria Esforzado
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Frederic Cofan
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Federic Oppenheimer
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Vicens Torregrosa
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Joaquim Casals
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Joana Ferrer
- Hepatobiliopancreatic and Liver Transplant Department, Hospital Clínic Barcelona, Spain
| | - Enric Esmatjes
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic Barcelona, Spain
| | - Maria José Ramírez-Bajo
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | | | - Beatriu Bayes
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain
| | - Josep M Campistol
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
| | - Pedro Ventura-Aguiar
- Nephrology and Kidney Transplant Department, Hospital Clínic Barcelona, Spain; Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica (FCRB), Barcelona, Spain.
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Wang H, Fu YX, Song WL, Mo CB, Feng G, Zhao J, Pei GH, Shi XF, Wang Z, Cao Y, Nian YQ, Shen ZY. Suture ligation for submucosal hemostasis during hand-sewn side-to-side duodeno-ileostomy in simultaneous pancreas and kidney transplantation. World J Gastrointest Surg 2021; 13:988-999. [PMID: 34621475 PMCID: PMC8462074 DOI: 10.4240/wjgs.v13.i9.988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/17/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Enteric anastomotic (EA) bleeding is a potentially life-threatening surgical complication associated with enteric anastomosis during simultaneous pancreas and kidney transplantation (SPKT).
AIM To investigate whether suture ligation (SL) for submucosal hemostasis during hand-sewn enteric anastomosis could decrease the morbidity of early EA bleeding in SPKT.
METHODS We compared the outcomes of 134 patients classified into SL (n = 44) and no SL (NSL) groups (n = 90). This study adheres to the declarations of Istanbul and Helsinki and all donors were neither paid nor coerced.
RESULTS During the first postoperative week, the EA bleeding rate in the SL group was lower than that in the NSL group (2.27% vs 15.56%; P = 0.021); no relationship was found between EA bleeding and donor age, mean pancreatic cold ischemia time, platelet count, prothrombin time international normalized rate, activated partial thromboplastin time, and thrombin time. Anastomotic leakage was observed in one case in the SL group at postoperative day (POD) 14 and in one case at POD 16 in the NSL group (P = 0.754). No significant difference was found between the two groups in the patient survival, pancreas graft survival, or kidney graft survival.
CONCLUSION SL for submucosal hemostasis during hand-sewn enteric anastomosis in SPKT can decrease the morbidity of early EA bleeding without increasing the anastomotic leakage rate.
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Affiliation(s)
- Hui Wang
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Ying-Xin Fu
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Wen-Li Song
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Chun-Bai Mo
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Gang Feng
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Jie Zhao
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Guang-Hui Pei
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Xiao-Feng Shi
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Zhen Wang
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Yu Cao
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Ye-Qi Nian
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Zhong-Yang Shen
- Department of Kidney and Pancreas Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
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23
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Shih MS, Shyr BU, Shyr BS, Chen SC, Shyr YM, Wang SE. Pancreas transplant with enteric drainage at a single institute in Asia. Asian J Surg 2021; 45:412-418. [PMID: 34364767 DOI: 10.1016/j.asjsur.2021.07.028] [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: 02/26/2021] [Revised: 05/03/2021] [Accepted: 07/02/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND/OBJECTIVE This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia. METHODS Patients undergoing pancreas transplant with enteric drainage were included. Clinical data and outcomes were evaluated and compared between each subgroup. RESULTS There were 165 cases of pancreas transplant, including 38 (23 %) simultaneous pancreas-kidney transplant (SPK), 24 (15 %) pancreas after kidney transplant (PAK), 75 (46 %) pancreas transplant alone (PTA), and 28 (17 %) pancreas before kidney transplant (PBK). The overall surgical complication rate was 46.1 %, with highest (62.5 %) in PAK and lowest (32.0 %) in PTA, P = 0.008. The late complications included 32.7 % infection and 3.6 % malignancy. Overall rejection of pancreas graft was 24.8 % including 18.2 % acute and 9.7 % chronic rejection. Rejection was highest in PTA group (36.0 %) and lowest in PBK (3.6 %). There were 56 cases (33.9 %) with graft loss in total, with highest graft loss rate in PTA (38.7 %). The 1-year, 5-year and 10-year pancreas graft survivals for total patients were 98.0 %, 87.7 % and 70.9 % respectively. CONCLUSIONS Enteric drainage in pancreas transplant could be applied safely not only in SPK but also in other subgroups. Enteric drainage itself would not compromise the immunological and graft survival outcomes.
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Affiliation(s)
- Mu-Shan Shih
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Bor-Uei Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Bor-Shiuan Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shih-Chin Chen
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shin-E Wang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
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24
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Kochar IS, Jain R. Pancreas transplant in type 1 diabetes mellitus: the emerging role of islet cell transplant. Ann Pediatr Endocrinol Metab 2021; 26:86-91. [PMID: 34218630 PMCID: PMC8255858 DOI: 10.6065/apem.2142012.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 05/12/2021] [Indexed: 11/28/2022] Open
Abstract
Pancreas transplant, both whole pancreas and islet cell, is a known therapeutic option for treatment of type 1 diabetes mellitus. Islet cell transplant began as an experimental therapy but is emerging to be quite beneficial due to less surgical risk and fewer complications. It is also considered a promising option in pediatric patients. In this review the authors discuss the indications, procedure, and benefits of islet cell transplant along with newer strategies for improving outcomes.
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Affiliation(s)
- Inderpal Singh Kochar
- Department of Pediatric and Adolescent Endocrinology, Indraprastha Apollo Hospital, New Delhi, India
| | - Rakhi Jain
- Department of Pediatric and Adolescent Endocrinology, Indraprastha Apollo Hospital, New Delhi, India,Address for correspondence: Rakhi Jain Department of Pediatric and Adolescent Endocrinology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi 110076, India
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25
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Encapsulation Strategies for Pancreatic Islet Transplantation without Immune Suppression. CURRENT STEM CELL REPORTS 2021. [DOI: 10.1007/s40778-021-00190-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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26
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Mei S, Huang Z, Dong Y, Chen Z, Xiang J, Zhou J, Li Z, Zheng S, Hu Z. Pancreas preservation time as a predictor of prolonged hospital stay after pancreas transplantation. J Int Med Res 2021; 49:300060520987059. [PMID: 33626941 PMCID: PMC7925952 DOI: 10.1177/0300060520987059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Objective Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation. Methods Patients receiving pancreas transplantation (1998.7–2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days). Results We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas–kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours. Conclusion Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.
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Affiliation(s)
- Shengmin Mei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Zhichao Huang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Yinlei Dong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Zheng Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | - Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang Province, China
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27
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Pomposelli T, Schuetz C, Wang P, Yamada K. A Strategy to Simultaneously Cure Type 1 Diabetes and Diabetic Nephropathy by Transplant of Composite Islet-Kidney Grafts. Front Endocrinol (Lausanne) 2021; 12:632605. [PMID: 34054721 PMCID: PMC8153710 DOI: 10.3389/fendo.2021.632605] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 04/16/2021] [Indexed: 11/13/2022] Open
Abstract
In recent years islet cell transplant has proven itself to be a viable clinical option for a select group of diabetic patients. Graft loss after transplant however continues to hinder the long-term success of the procedure. Transplanting the islets as a pre-vascularized composite islet-kidney graft has emerged as a relevant solution. Much groundbreaking research has been done utilizing this model in conjunction with strategies aimed towards islet cell survival and prolongation of function in the host. Transplanting the islet cells as a prevascularized graft under the capsule of the donor kidney as a composite islet-kidney graft has been shown to provide long term durable blood glucose control in large animal studies by limiting graft apoptosis as well as providing a physical barrier against the host immune response. While promising, this technique is limited by long term immunosuppression requirements of the host with its well-known adverse sequelae. Research into tolerance inducing strategies of the host to the allogeneic and xenogeneic islet-kidney graft has shown much promise in the avoidance of long-term immunosuppression. In addition, utilizing xenogeneic tissue grafts could provide a near-limitless supply of organs. The islet-kidney model could provide a durable and long-term cure for diabetes. Here we summarize the most recent data, as well as groundbreaking strategies to avoid long term immunosuppression and promote graft acceptance.
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Affiliation(s)
- Thomas Pomposelli
- Columbia Center for Translational Immunology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States
- Department of Surgery, Columbia University Irving Medical Center, New York, NY, United States
| | - Christian Schuetz
- Columbia Center for Translational Immunology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States
| | - Ping Wang
- Precision Health Program, Michigan State University, East Lansing, MI, United States
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, United States
| | - Kazuhiko Yamada
- Columbia Center for Translational Immunology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States
- Department of Surgery, Columbia University Irving Medical Center, New York, NY, United States
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Nagaya M, Hasegawa K, Uchikura A, Nakano K, Watanabe M, Umeyama K, Matsunari H, Osafune K, Kobayashi E, Nakauchi H, Nagashima H. Feasibility of large experimental animal models in testing novel therapeutic strategies for diabetes. World J Diabetes 2021; 12:306-330. [PMID: 33889282 PMCID: PMC8040081 DOI: 10.4239/wjd.v12.i4.306] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/30/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes is among the top 10 causes of death in adults and caused approximately four million deaths worldwide in 2017. The incidence and prevalence of diabetes is predicted to increase. To alleviate this potentially severe situation, safer and more effective therapeutics are urgently required. Mice have long been the mainstay as preclinical models for basic research on diabetes, although they are not ideally suited for translating basic knowledge into clinical applications. To validate and optimize novel therapeutics for safe application in humans, an appropriate large animal model is needed. Large animals, especially pigs, are well suited for biomedical research and share many similarities with humans, including body size, anatomical features, physiology, and pathophysiology. Moreover, pigs already play an important role in translational studies, including clinical trials for xenotransplantation. Progress in genetic engineering over the past few decades has facilitated the development of transgenic animals, including porcine models of diabetes. This article discusses features that attest to the attractiveness of genetically modified porcine models of diabetes for testing novel treatment strategies using recent technical advances.
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Affiliation(s)
- Masaki Nagaya
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Department of Immunology, St. Marianna University School of Medicine, Kawasaki 261-8511, Kanagawa, Japan
| | - Koki Hasegawa
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
| | - Ayuko Uchikura
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
| | - Kazuaki Nakano
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Research and Development, PorMedTec Co. Ltd, Kawasaki 214-0034, Kanagawa, Japan
| | - Masahito Watanabe
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Research and Development, PorMedTec Co. Ltd, Kawasaki 214-0034, Kanagawa, Japan
| | - Kazuhiro Umeyama
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Research and Development, PorMedTec Co. Ltd, Kawasaki 214-0034, Kanagawa, Japan
| | - Hitomi Matsunari
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
| | - Kenji Osafune
- Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Kyoto, Japan
| | - Eiji Kobayashi
- Department of Organ Fabrication, Keio University School of Medicine, Shinjuku 160-8582, Tokyo, Japan
| | - Hiromitsu Nakauchi
- Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, United States
- Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Minato 108-8639, Tokyo, Japan
| | - Hiroshi Nagashima
- Meiji University International Institute for Bio-Resource Research, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
- Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Kanagawa, Japan
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29
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Hau HM, Jahn N, Rademacher S, Sucher E, Babel J, Mehdorn M, Lederer A, Seehofer D, Scheuermann U, Sucher R. The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival. J Clin Med 2021; 10:1632. [PMID: 33921391 PMCID: PMC8070486 DOI: 10.3390/jcm10081632] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/02/2021] [Accepted: 04/07/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/OBJECTIVES The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. MATERIAL AND METHODS 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. RESULTS Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3-17.1, p = 0.026) and five years (HR 3.7, 2.1-23.4, p = 0.040). CONCLUSION Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.
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Affiliation(s)
- Hans-Michael Hau
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Nora Jahn
- Department of Anesthesiology and Intensive Medicine, University Hospital of Leipzig, 04103 Leipzig, Germany;
| | - Sebastian Rademacher
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Elisabeth Sucher
- Department of Gastroenterology, Section of Hepatology, University Hospital of Leipzig, 04103 Leipzig, Germany;
| | - Jonas Babel
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Matthias Mehdorn
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Andri Lederer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Daniel Seehofer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Uwe Scheuermann
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
| | - Robert Sucher
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (S.R.); (J.B.); (M.M.); (A.L.); (D.S.); (U.S.); (R.S.)
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Abstract
Type 1 diabetes mellitus is a common and highly morbid disease for which there is no cure. Treatment primarily involves exogenous insulin administration, and, under specific circumstances, islet or pancreas transplantation. However, insulin replacement alone fails to replicate the endocrine function of the pancreas and does not provide durable euglycemia. In addition, transplantation requires lifelong use of immunosuppressive medications, which has deleterious side effects, is expensive, and is inappropriate for use in adolescents. A bioartificial pancreas that provides total endocrine pancreatic function without immunosuppression is a potential therapy for treatment of type 1 diabetes. Numerous models are in development and take different approaches to cell source, encapsulation method, and device implantation location. We review current therapies for type 1 diabetes mellitus, the requirements for a bioartificial pancreas, and quantitatively compare device function.
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Affiliation(s)
- Sara J. Photiadis
- From the Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA
| | - Rebecca C. Gologorsky
- From the Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA
| | - Deepika Sarode
- From the Department of Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA
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Kjøsen G, Rydenfelt K, Horneland R, Aandahl EM, Line PD, Dorenberg E, Berstad AE, Brabrand K, Hagen G, Pischke SE, Bergmann GB, Nordheim E, Jenssen TG, Tønnessen TI, Haugaa H. Early detection of complications in pancreas transplants by microdialysis catheters, an observational feasibility study. PLoS One 2021; 16:e0247615. [PMID: 33705460 PMCID: PMC7951931 DOI: 10.1371/journal.pone.0247615] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 02/09/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur relatively frequently and are rarely detected before the transplant is irreversibly damaged. METHODS To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours. RESULTS Nine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas. CONCLUSIONS Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.
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Affiliation(s)
- Gisle Kjøsen
- Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kristina Rydenfelt
- Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Rune Horneland
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Einar Martin Aandahl
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Pål-Dag Line
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Eric Dorenberg
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Audun Elnæs Berstad
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Knut Brabrand
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Gaute Hagen
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Sören Erik Pischke
- Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
- Department of Immunology, Oslo University Hospital, Oslo, Norway
| | | | - Espen Nordheim
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Trond Geir Jenssen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Tor Inge Tønnessen
- Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Håkon Haugaa
- Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
- Lovisenberg Diaconal University College, Oslo, Norway
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32
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Impact of Simultaneous Pancreas-kidney Transplantation on Cardiovascular Risk in Patients With Diabetes. Transplantation 2021; 106:158-166. [PMID: 33660656 DOI: 10.1097/tp.0000000000003710] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND cardiovascular disease is the major cause of death in patients with type 1 Diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one which includes kidney function as a risk factor, which is a well described independent risk factor for cardiovascular disease. METHODS we explore how SPKT modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016. RESULTS 268 SPKT recipients with a mean age of 40 years old and a median follow-up of 10 years were included. Prior to transplantation, the expected incidence of Cardiovascular Events (CVE) at 5 and 10 years according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P < 0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th month glomerular filtration rate (at 5 and 10 years predicted CVE incidence was of 10.5% and 19.4%, respectively). Early pancreas graft failure (HR 3.00 [95% CI 1.14 - 7.88]; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside with kidney graft failure (HR 2.90 [95% CI 1.53 - 5.48]; P = 0.001), and diabetes duration (HR 1.04 [95% CI 1.00-1.09], P = 0.04). CONCLUSIONS SPKT decreases in more two-thirds the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.
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Tomihara K, Hisadome Y, Noguchi H, Kaku K, Okabe Y, Nakamura M. Serum pancreatic enzymes in the early postoperative period predict complications associated with pancreatic fluid after pancreas transplantation: A retrospective, single-center, observational cohort study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:365-375. [PMID: 33460515 DOI: 10.1002/jhbp.895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/23/2020] [Accepted: 01/07/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND Pancreas transplantation (PT) is a radical treatment for diabetes mellitus (DM). Although the results of PT have been improving, surgical complications remain. Few reports have focused on complications associated with pancreatic fluid (CAPF) after PT. We aimed to investigate the risk factors and predictors for CAPF after PT. METHODS Sixty-nine patients, who underwent deceased-donor PT for type 1 DM at our institution from August 2001 to May 2020, were retrospectively studied. We identified CAPF from those with Clavien-Dindo Classification ≥grade III and assessed risk factors by univariate and multivariate analyses using logistic regression. RESULTS Twenty-one (30.4%) patients had complications with Clavien-Dindo Classification ≥grade III. Eleven (16.0%) patients were diagnosed with CAPF. Median serum pancreatic amylase (P-AMY) levels with CAPF on postoperative day (POD)1 and POD2 were significantly higher than those without CAPF (P = .019 and P = .027, respectively). In multivariable analysis, serum P-AMY levels on POD1 were an independent predictive factor for CAPF (odds ratio 1.83, 95% confidence interval 1.07-3.14, P = .008). CONCLUSIONS Complications associated with pancreatic fluid after PT is associated with high serum P-AMY in the early postoperative period. Serum pancreatic enzymes in the first few postoperative days after PT may be a significant predictive factor for CAPF.
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Affiliation(s)
- Kazuki Tomihara
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yu Hisadome
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Noguchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keizo Kaku
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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34
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Bonsdorff A, Sallinen V, Räihä J, Ekstrand A, Nordin A, Lempinen M, Helanterä I. First-day plasma amylase detects patients at risk of complications after simultaneous pancreas-kidney transplantation. Clin Transplant 2021; 35:e14233. [PMID: 33506535 DOI: 10.1111/ctr.14233] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/28/2020] [Accepted: 01/19/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Simultaneous pancreas-kidney transplantation (SPK) carries a high risk of major postoperative complications, but knowledge on early warning signs and surrogate markers for postoperative complications is scarce. AIMS Our aim was to analyze the complication-predictive value of different laboratory tests in pancreas transplantation. MATERIALS & METHODS All SPKs in Finland between January 2010 and February 2020 were retrospectively analyzed. Levels of first three-day plasma amylase, drain fluid amylase, C-reactive protein, C-peptide, plasma trypsinogen, and white blood cell count were assessed for their performance predicting cumulative postoperative complications (assessed using the Comprehensive Complication Index) within 90 days from transplantation by using ROC analyses. RESULTS Of the 164 SPK patients included, 39 suffered at least one complication requiring laparotomy. First-day plasma amylase had the best value in predicting complications based on its high AUC value and easy clinical applicability, with an optimum cutoff of six times the upper normal limit. Negative predictive values (NPVs) and positive predictive values of this cutoff were 0.81 and 0.71 for any relaparotomy, and 0.91 and 0.71 for the Comprehensive Complication Index >47.7 (which equals the morbidity of two relaparotomies), respectively. CONCLUSION In conclusion, first-day plasma amylase could be able to detect patients at risk of complications after SPK.
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Affiliation(s)
- Akseli Bonsdorff
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Ville Sallinen
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Juulia Räihä
- Department of Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Agneta Ekstrand
- Department of Nephrology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Arno Nordin
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Marko Lempinen
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Ilkka Helanterä
- Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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35
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Nakamura T, Fujikura J, Inagaki N. Advancements in transplantation therapy for diabetes: Pancreas, islet and stem cell. J Diabetes Investig 2021; 12:143-145. [PMID: 32654418 PMCID: PMC7858099 DOI: 10.1111/jdi.13358] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/06/2020] [Accepted: 07/07/2020] [Indexed: 12/25/2022] Open
Abstract
Pancreas transplantation and islet transplantation are now established in the treatment of IDDM. Several trials of stem cell-derived cell transplantation therapy are underway and may offer an alternative to the limited supply of donor islets in the near future. This article summarizes recent developments in transplantation therapy for diabetes as well as research on the use of stem cells for complications of diabetes.
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Affiliation(s)
- Toshihiro Nakamura
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Junji Fujikura
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
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36
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Glieberman AL, Pope BD, Melton DA, Parker KK. Building Biomimetic Potency Tests for Islet Transplantation. Diabetes 2021; 70:347-363. [PMID: 33472944 PMCID: PMC7881865 DOI: 10.2337/db20-0297] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 11/12/2020] [Indexed: 12/12/2022]
Abstract
Diabetes is a disease of insulin insufficiency, requiring many to rely on exogenous insulin with constant monitoring to avoid a fatal outcome. Islet transplantation is a recent therapy that can provide insulin independence, but the procedure is still limited by both the availability of human islets and reliable tests to assess their function. While stem cell technologies are poised to fill the shortage of transplantable cells, better methods are still needed for predicting transplantation outcome. To ensure islet quality, we propose that the next generation of islet potency tests should be biomimetic systems that match glucose stimulation dynamics and cell microenvironmental preferences and rapidly assess conditional and continuous insulin secretion with minimal manual handing. Here, we review the current approaches for islet potency testing and outline technologies and methods that can be used to arrive at a more predictive potency test that tracks islet secretory capacity in a relevant context. With the development of potency tests that can report on islet secretion dynamics in a context relevant to their intended function, islet transplantation can expand into a more widely accessible and reliable treatment option for individuals with diabetes.
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Affiliation(s)
- Aaron L Glieberman
- Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA
| | - Benjamin D Pope
- Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA
| | - Douglas A Melton
- Harvard Department of Stem Cell and Regenerative Biology, Cambridge, MA
- Harvard Stem Cell Institute, Cambridge, MA
| | - Kevin Kit Parker
- Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA
- Harvard Stem Cell Institute, Cambridge, MA
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37
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Shahrestani S, Hitos K, Hort A, Spike E, Gibbons TJ, Lendzion R, Yuen L, Pleass HC, Hawthorne WJ. Successful Expectant Management of Nonocclusive Thrombosis in Simultaneous Pancreas-Kidney Transplantation. Transplant Proc 2021; 53:371-378. [PMID: 33419574 DOI: 10.1016/j.transproceed.2020.10.042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 10/16/2020] [Accepted: 10/30/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND Simultaneous pancreas-kidney (SPK) transplantation can be complicated by thrombosis in the early post-transplant period. METHODS We performed a single-center retrospective study examining risk factors, management, and outcomes of modern era SPK transplants. We reviewed 235 recipients over 10 years (January 1, 2008, to September 1, 2017). We used multivariate analysis to examine donor, recipient, and operative risk factors for thrombosis. RESULTS Forty-one patients (17%) had a thrombosis diagnosed on postoperative imaging, but 61% of these patients (n = 25/41) did not lose their graft secondary to the thrombosis. Nine patients (22%) were managed with watchful waiting and serial imaging, 12 (29%) were managed with therapeutic anticoagulation, and 4 (10%) required laparotomy and graft thrombectomy. Sixteen of 235 pancreas grafts (6.8%) required pancreatectomy, and 10 of these cases occurred in the first half of the study, before 2012. The risk of thrombosis leading to graft loss increased 11.2-fold in recipients with a body mass index (calculated as weight in kilograms divided by height in meters squared) > 25 compared with others (odds ratio, 11.2; 95% CI, 1.1-116.7; P = .043). CONCLUSIONS The majority of SPK transplants (61%) complicated by thrombosis of the pancreatic graft were salvaged by use of imaging, anticoagulation, and in select cases, laparotomy and graft thrombectomy.
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Affiliation(s)
| | - Kerry Hitos
- Sydney Medical School, University of Sydney, Sydney, Australia; Westmead Research Centre for Evaluation of Surgical Outcomes, Department of Surgery, Westmead Hospital, Westmead, Australia
| | - Amy Hort
- Department of Surgery, Westmead Hospital, Westmead, Australia
| | - Erin Spike
- Department of Surgery, Westmead Hospital, Westmead, Australia
| | | | | | - Lawrence Yuen
- Sydney Medical School, University of Sydney, Sydney, Australia; Department of Surgery, Westmead Hospital, Westmead, Australia
| | - Henry C Pleass
- Sydney Medical School, University of Sydney, Sydney, Australia; Department of Surgery, Westmead Hospital, Westmead, Australia
| | - Wayne J Hawthorne
- Sydney Medical School, University of Sydney, Sydney, Australia; Department of Surgery, Westmead Hospital, Westmead, Australia; Centre for Transplant & Renal Research, Westmead Institute for Medical Research, Westmead, Australia.
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38
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Awata T, Kenmochi T, Tomimaru Y, Eguchi H, Ito T, Shimoda M. Pancreas transplantation for type 1 diabetes in Japan: past, present and future prospects. Glob Health Med 2020; 2:360-366. [PMID: 33409415 DOI: 10.35772/ghm.2020.01069] [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: 08/06/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 11/08/2022]
Abstract
In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue. Thereafter, the "Organ Transplant Act", which enables brain-dead transplantation, was enacted in 1997, and then revised in 2010 so that donation after brain death became possible only with the consent of the family. Under the recipient selection and registration system developed after the enactment of the "Organ Transplant Act", more than 400 pancreas transplants have been carried out at facilities certified for brain-dead pancreas transplantation in Japan. Of the 410 total cadaveric pancreas transplants performed by the end of 2019, the patient survival and pancreatic and kidney graft survival rates were considered to be comparable to those in the United States and Europe despite the high frequency of marginal donors. Minimally invasive allogenic islet transplantation came to be covered by national health insurance in 2020 following good outcomes of a recent trial. Furthermore, to overcome the serious donor shortage in Japan, development of xenogeneic islet transplantation and regenerative medicine using stem cells is in progress, with xenotransplantation using porcine islets appearing particularly promising.
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Affiliation(s)
- Takuya Awata
- Center for University-wide Education, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan.,The Central Coordination Committee of the Pancreas Transplantation in Japan, Tokyo, Japan.,Islet Cell Transplantation Project, Diabetes Research Center, Research Institute of National Center for Global Health and Medicine, Tokyo, Japan
| | - Takashi Kenmochi
- The Central Coordination Committee of the Pancreas Transplantation in Japan, Tokyo, Japan.,Department of Transplantation and Regenerative Medicine, School of Medicine, Fujita Health University, Aichi, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Toshinori Ito
- Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan
| | - Masayuki Shimoda
- Islet Cell Transplantation Project, Diabetes Research Center, Research Institute of National Center for Global Health and Medicine, Tokyo, Japan
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39
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Byrne MHV, Battle J, Sewpaul A, Tingle S, Thompson E, Brookes M, Innes A, Turner P, White SA, Manas DM, Wilson CH. Early protocol computer tomography and endovascular interventions in pancreas transplantation. Clin Transplant 2020; 35:e14158. [PMID: 33222262 DOI: 10.1111/ctr.14158] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/19/2020] [Accepted: 11/02/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Early vascular complications following pancreatic transplantation are not uncommon (3%-8%). Typically, cross-sectional imaging is requested in response to clinical change. We instituted a change in protocol to request imaging pre-emptively to identify patients with thrombotic complications. METHODS In 2013, protocol computer tomography angiography (CTA) at days 3-5 and day 10 following pancreas transplantation was introduced. A retrospective analysis of all pancreas transplants performed at our institution from January 2001 to May 2019 was undertaken. RESULTS A total of 115 patients received pancreas transplants during this time period. A total of 78 received pancreas transplant without routine CTA and 37 patients with the new protocol. Following the change in protocol, we detected a high number of subclinical thromboses (41.7%). There was a significant decrease in invasive intervention for thrombosis (78.6% before vs 30.8% after, p = .02), and graft survival was significantly higher (61.5% before vs 86.1% after, p = .04). There was also a significant reduction in the number of graft failures (all-cause) where thrombosis was present (23.4% before vs 5.6% after, p = .02). Patient survival was unaffected (p = .48). CONCLUSIONS Implementation of early protocol CTA identifies a large number of patients with subclinical graft thromboses that are more amenable to conservative management and significantly reduces the requirement for invasive intervention.
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Affiliation(s)
| | - Joseph Battle
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Avinash Sewpaul
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Freeman Hospital, Newcastle upon Tyne, UK
| | - Samuel Tingle
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Emily Thompson
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Freeman Hospital, Newcastle upon Tyne, UK
| | - Marcus Brookes
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Ailsa Innes
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Paul Turner
- Department of Radiology, Freeman Hospital, Newcastle upon Tyne, UK
| | - Steven A White
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Freeman Hospital, Newcastle upon Tyne, UK
| | - Derek M Manas
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Freeman Hospital, Newcastle upon Tyne, UK
| | - Colin H Wilson
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.,NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Freeman Hospital, Newcastle upon Tyne, UK
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40
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Goussous N, St Michel DP, Mcdade H, Gaines S, Borth A, Dawany N, Al-Qaoud T, Bromberg JS, Barth RN, Scalea JR. Is Prophylactic Drainage After Pancreas Transplant Associated With Reduced Reoperation Rate? EXP CLIN TRANSPLANT 2020; 19:64-71. [PMID: 33272163 DOI: 10.6002/ect.2020.0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Advances in surgery and perioperative care have contributed to improved outcomes after pancreas transplant. However, the development of peripancreatic infections carries a poor prognosis. It is not clear whether abdominal drainage is helpful in collection prevention. MATERIALS AND METHODS A retrospective review of adult consecutive pancreas transplants at a single institution between January 2017 and December 2018 was undertaken. Postoperative outcomes were compared between patients in whom prophylactic intraoperative drains were placed and patients with no drains. RESULTS We identified 83 patients who underwent pancreas transplant with a median age of 45 years; 54.2% were males, and median body mass index was 25.8. Thirty patients had 1 or 2 drains placed (36.1%). There was no difference in the readmission rate (70.0% vs 60.4%; P = .48), reoperation (20.0% vs 30.2%; P = .44), or percutaneous drainage of peripancreatic infections (20.0% vs 15.1%; P = .56) between patients with drains and no drains, respectively. However, prophylactic drainage was associated with a lower rate of reoperation for peripancreatic infections compared with those who were not drained (0.0% vs 13.2%; P < .05). No graft loss occurred in the drain group. CONCLUSIONS Prophylactic drainage after pancreas transplant may be helpful for reduction in the infection rate after reoperation. The risks of drain placement should be weighed against those of drain avoidance.
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Affiliation(s)
- Naeem Goussous
- From the Division of Transplantation, Department of Surgery, University of Maryland School of Medicine Baltimore, Maryland, USA
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41
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Takaki T, Shimoda M. Pancreatic islet transplantation: toward definitive treatment for diabetes mellitus. Glob Health Med 2020; 2:200-211. [PMID: 33330809 DOI: 10.35772/ghm.2020.01057] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/31/2020] [Accepted: 08/03/2020] [Indexed: 12/27/2022]
Abstract
Since the late 20th century, advances in pancreatic islet transplantation have targeted improved glycemic control and fewer hypoglycemic events in patients with type 1 diabetes, and some important milestones have been reached. Following the Edmonton group's success in achieving insulin independence in all transplanted patients with type 1 diabetes, clinical islet transplantation is now performed worldwide. β cell replacement therapy for type 1 diabetes was established based on the favorable outcomes of a phase 3, prospective, open-label, single-arm, clinical study conducted at 8 centers in North America, in which 42 of 48 patients who underwent islet transplantation from 2008 to 2011 achieved HbA1c < 7.0% (53 mmol/mol) at day 365, which was maintained at 2 years in 34 patients. In Japan, a phase 2 multicenter clinical trial of islet transplantation for type 1 diabetes patients is currently ongoing and will end soon, but the interim results have already led to positive changes, with allogeneic islet transplantation being covered by the national health insurance system since April 2020. Current efforts are being made to solve the problem of donor shortage by studying alternative donor sources, such as porcine islets and pancreatic progenitor cells derived from pluripotent stem cells. The results of clinical trials in this area are eagerly awaited. It is hoped that they will contribute to establishing alternative sources for insulin-producing β cells in the near future.
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Affiliation(s)
- Tadashi Takaki
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan.,Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.,Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA), Fujisawa, Kanagawa, Japan
| | - Masayuki Shimoda
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
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Witkowski G, Matejak-Górska M, Durlik M. Endovascular Treatment of Pseudoaneurysm After Simultaneous Pancreas-Kidney Transplant: A Case Report. Transplant Proc 2020; 52:2536-2538. [PMID: 32307150 DOI: 10.1016/j.transproceed.2020.02.108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 02/05/2020] [Indexed: 01/18/2023]
Abstract
Pseudoaneurysm is a rare vascular complication in pancreas transplantation that can lead into life-threatening situations. A 44-year-old male patient after simultaneous pancreas-kidney transplant was admitted to the hospital for routine tests 3 months after surgery. A computed tomography scan and ultrasound examination were done, and a diagnosis of pseudoaneurysm was made. The patient was qualified for endovascular treatment. The pseudoaneurysm was closed using coils, and kidney and pancreas grafts stayed in proper condition. Endovascular interventions in patients after pancreas transplantation are safe and preferable in managing postoperative complications.
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Affiliation(s)
- Grzegorz Witkowski
- Department of General and Transplantation Surgery, Central Clinical Hospital, Ministry of the Interior, Warsaw, Poland; Centre of Postgraduate Medical Education, Warsaw, Poland.
| | - Marta Matejak-Górska
- Department of General and Transplantation Surgery, Central Clinical Hospital, Ministry of the Interior, Warsaw, Poland; Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Marek Durlik
- Department of General and Transplantation Surgery, Central Clinical Hospital, Ministry of the Interior, Warsaw, Poland; Centre of Postgraduate Medical Education, Warsaw, Poland
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Abeling T, Scheffner I, Karch A, Broecker V, Koch A, Haller H, Schwarz A, Gwinner W. Risk factors for death in kidney transplant patients: analysis from a large protocol biopsy registry. Nephrol Dial Transplant 2020; 34:1171-1181. [PMID: 29860340 DOI: 10.1093/ndt/gfy131] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Identification and quantification of the relevant factors for death can improve patients' individual risk assessment and decision-making. We used a well-documented patient cohort (n = 892) in a renal transplant programme with protocol biopsies to establish multivariable Cox models for risk assessment at 3 and 12 months post-transplantation. METHODS Patients transplanted between 2000 and 2007 were observed up to 11 years (total observation 5227 patient-years; median 5.9 years). Loss to follow-up was negligible (n = 15). A total of 2251 protocol biopsies and 1214 biopsies for cause were performed. All rejections and clinical borderline rejections in protocol biopsies were treated. RESULTS Overall 10-year patient survival was 78%, with inferior survival of patients with graft loss and superior survival of patients with living-donor transplantation. Eight factors were common in the models at 3 and 12 months, including age, pre-transplant heart failure and a score of cardiovascular disease and type 2 diabetes, post-transplant urinary tract infection, treatment of rejection, new-onset heart failure, coronary events and malignancies. Additional variables of the model at 3 months included deceased donor transplantation, transplant lymphocele, BK virus nephropathy and severe infections. Graft function and graft loss were significant factors of the model at 12 months. Internal validation and validation with a separate cohort of patients (n = 349) demonstrated good discrimination of the models. CONCLUSIONS The identified factors indicate the important areas that need special attention in the pre- and post-transplant care of renal transplant patients. On the basis of these models, we provide nomograms as a tool to weigh individual risks that may contribute to decreased survival.
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Affiliation(s)
- Tanja Abeling
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Irina Scheffner
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Annika Karch
- Institute for Biostatistics, Hannover Medical School, Hannover, Germany
| | - Verena Broecker
- Department of Clinical Pathology and Genetics, University of Gothenburg, Gothenburg, Sweden
| | - Armin Koch
- Institute for Biostatistics, Hannover Medical School, Hannover, Germany
| | - Hermann Haller
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Anke Schwarz
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Wilfried Gwinner
- Department of Nephrology, Hannover Medical School, Hannover, Germany
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Nakamura T, Fujikura J, Anazawa T, Ito R, Ogura M, Okajima H, Uemoto S, Inagaki N. Long-term outcome of islet transplantation on insulin-dependent diabetes mellitus: An observational cohort study. J Diabetes Investig 2020; 11:363-372. [PMID: 31390159 PMCID: PMC7078128 DOI: 10.1111/jdi.13128] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/17/2019] [Accepted: 07/29/2019] [Indexed: 12/13/2022] Open
Abstract
AIMS/INTRODUCTION To investigate the long-term efficacy and safety of islet transplantation (ITx) compared with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). MATERIALS AND METHODS Among 619 patients diagnosed as insulin-dependent diabetes mellitus or type 1 diabetes at Kyoto University, Kyoto, Japan, seven patients were selected as the ITx group and 26 age-matched patients with no endogenous insulin secretion were selected as the MDI/CSII group. Hemoglobin A1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine were assessed retrospectively at 1, 2, 5 and 10 years for both groups; serum C-peptide immunoreactivity was assessed for the ITx group. Major clinical events were also assessed. RESULTS Hemoglobin A1c improvement in ITx was significant at 1 year (8.4% [7.8-9.9%] at baseline to 7.1% [6.3-7.4%] in ITx vs 8.2% [7.4-9.8%] at baseline to 8.1% [7.3-9.5%] in MDI/CSII, P < 0.01 between groups), and was maintained at 2 years (7.4% [6.3-8.2%] vs 8.4% [7.4-9.6%], P = 0.11). The increase of stimulated C-peptide immunoreactivity was significant at 1 year (0.57 ng/mL [0.26-0.99 ng/mL], P < 0.05 from baseline) and 2 years (0.43 ng/mL [0.19-0.67 ng/mL], P < 0.05), although it became insignificant thereafter. There was no significant difference in AST/ALT or creatinine at 10 years, although a transient AST/ALT elevation was observed in ITx. In regard to clinical events, the occurrence of severe hypoglycemia was 14% vs 31% (relative risk 0.46, P = 0.64), that of infectious disease was 43% vs 12% (relative risk 3.71, P = 0.09) and digestive symptoms was 43% vs 7.7% (relative risk 5.57, P = 0.05) in ITx vs MDI/CSII, respectively. No patient died in either group. CONCLUSIONS The present findings showed that ITx was considered to contribute to the reduction of hypoglycemia and better glycemic control with tolerable, but attention-requiring, risks over a period of 10 years compared with MDI/CSII.
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Affiliation(s)
- Toshihiro Nakamura
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Junji Fujikura
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Takayuki Anazawa
- Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Ryo Ito
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Masahito Ogura
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Hideaki Okajima
- Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Shinji Uemoto
- Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationGraduate School of MedicineKyoto UniversityKyotoJapan
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and NutritionGraduate School of MedicineKyoto UniversityKyotoJapan
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Girman P, Lipár K, Kočík M, Voska L, Kožnarová R, Marada T, Lánská V, Saudek F. Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study. Am J Transplant 2020; 20:779-787. [PMID: 31561278 DOI: 10.1111/ajt.15622] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 09/15/2019] [Accepted: 09/20/2019] [Indexed: 01/25/2023]
Abstract
The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5 years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P > .05). Death-censored pancreas survival was better in the sirolimus group (P = .037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P = .11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P = .19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P > .05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P = .007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P = .019). ClinicalTrials No.: NCT03582878.
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Affiliation(s)
- Peter Girman
- Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Květoslav Lipár
- Transplantation Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Matěj Kočík
- Transplantation Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Luděk Voska
- Clinical and Transplant Pathology Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Radomíra Kožnarová
- Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Tomáš Marada
- Transplantation Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Věra Lánská
- Department for Data Analysis and Statistics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - František Saudek
- Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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Zhou J, Dong Y, Mei S, Gu Y, Li Z, Xiang J, Zheng H, Chen Z, Huang Z, Hu Z. Influence of duration of type 1 diabetes on long‐term pancreatic transplant outcomes. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:583-592. [PMID: 31566900 DOI: 10.1002/jhbp.677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Yinlei Dong
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Shengmin Mei
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Yangjun Gu
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Huilin Zheng
- Zhejiang Provincial Collaborative Innovation Center of Agricultural Biological Resource Biochemical Manufacturing School of Biological and Chemical Engineering Zhejiang University of Science and Technology Hangzhou Zhejiang China
| | - Zheng Chen
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Zhichao Huang
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
| | - Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China
- Division of Hepatobiliary and Pancreatic Surgery Department of Surgery Fourth Affiliated Hospital School of Medicine Zhejiang University Yiwu Zhejiang China
- Division of Hepatobiliary and Pancreatic Surgery Yiwu Central Hospital Yiwu Zhejiang China
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St Michel D, Donnelly T, Jackson T, Taylor B, Barth RN, Bromberg JS, Scalea JR. Assessing Pancreas Transplant Candidate Cardiac Disease: Preoperative Protocol Development at a Rapidly Growing Transplant Program. Methods Protoc 2019; 2:mps2040082. [PMID: 31627355 PMCID: PMC6960608 DOI: 10.3390/mps2040082] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/01/2019] [Accepted: 10/11/2019] [Indexed: 12/22/2022] Open
Abstract
Pancreas transplant rates, despite improving outcomes, have decreased over the past two decades. This is due, in part, to ageing, increasingly co-morbid pancreas transplant candidates. There is a paucity of published data regarding coronary artery disease (CAD) in this population. To inform peri-operative management strategies, we sought to understand the frequency of CAD among recipients of pancreas transplants at our center. Informed by these data, we sought to develop a standard protocol for evaluation. A retrospective review of pancreas transplants (solitary pancreas and simultaneous pancreas-kidney) was undertaken at the University of Maryland. Transplant outcomes and frequency of cardiac disease were analyzed. Current data were compared with historic controls. Over the study period, 59 patients underwent pancreas transplantation. Coronary architecture was assessed in 38 patients (64.4%). Discrete evidence of CAD was present in 28 of 39 patients (71.7%). All pancreas candidates (n = 21) who underwent left heart catheterization (LHC) demonstrated CAD (100%). No patients experienced myocardial infarction (MI) and no deaths resulted from cardiac disease in the early post-transplant period. Pancreas transplant candidates are at high risk for CAD. At a center in which pancreas transplant rates are increasing, a rigorous cardiac work up revealed that 71.7% of assessed recipients had CAD. Although asymptomatic, 6.8% required coronary artery bypass graft (CABG). Despite increasing age and co-morbid status, pancreas transplant recipients can enjoy excellent results if protocolized preoperative testing is used.
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Affiliation(s)
- David St Michel
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
| | - Tracy Donnelly
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
| | - Towanda Jackson
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
| | - Bradley Taylor
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
| | - Rolf N Barth
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
| | | | - Joseph R Scalea
- Department of Surgery, University of Maryland, Baltimore, MD 20742, USA.
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Messner F, Etra JW, Haugen CE, Bösmüller C, Maglione M, Hackl H, Riedmann M, Oberhuber R, Cardini B, Resch T, Scheidl S, Margreiter R, Öfner D, Schneeberger S, Margreiter C. Sex matching does not impact the outcome after simultaneous pancreas-kidney transplantation. Clin Transplant 2019; 33:e13717. [PMID: 31545525 PMCID: PMC6899671 DOI: 10.1111/ctr.13717] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 09/11/2019] [Accepted: 09/18/2019] [Indexed: 01/31/2023]
Abstract
Background Several studies in solid organ transplantation have shown a correlation between donor and recipient sex mismatch and risk of graft loss. In this study, we aimed to analyze the impact of donor and recipient sex matching on patient and pancreas graft survival in a large single‐center cohort. Methods We retrospectively analyzed all first simultaneous pancreas‐kidney transplants performed between 1979 and 2017 at the Medical University of Innsbruck. Results Of 452 patients, 54.6% (247) received a sex‐matched transplant. Patient survival (P = .86), death‐censored pancreas graft survival (dcPGS, P = .26), and death‐censored kidney graft survival (dcKGS, P = .24) were similar between the sex‐matched and sex‐mismatched groups. Patient survival and dcPGS at 1, 5, and 15 years were 95.9%, 90.0%, and 62.1% and 86.1%, 77.1%, and 56.7% in the sex‐matched group and 93.6%, 86.2%, and 62.4% and 83.1%, 73.3%, and 54.3% in the sex‐mismatched group. Sex matching led to a lower odds of severe postoperative complications (41.2% vs 49.0%; OR 0.57, 95%CI 0.33‐0.97; P = .038); however, no increased odds of other adverse postoperative outcomes was detected. Conclusion Our study demonstrates that sex matching reduced the odds of postoperative complications but did not impact other early and late outcome parameters in our cohort.
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Affiliation(s)
- Franka Messner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Joanna W Etra
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christine E Haugen
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Claudia Bösmüller
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Hubert Hackl
- Division of Bioinformatics, Medical University of Innsbruck, Biocenter, Innsbruck, Austria
| | - Marina Riedmann
- Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Scheidl
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Raimund Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
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Wallace DF, Bunnett J, Fryer E, Drage M, Horsfield C, Callaghan CJ. Early allograft pancreatectomy—Technical failure or acute pancreatic rejection? Clin Transplant 2019; 33:e13702. [DOI: 10.1111/ctr.13702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 08/06/2019] [Accepted: 08/23/2019] [Indexed: 11/28/2022]
Affiliation(s)
- David F Wallace
- Department of Health Services Research and Policy London School of Hygiene and Tropical Medicine London UK
- Department of Nephrology and Transplantation Guy's and St Thomas' NHS Foundation Trust London UK
| | - Joanna Bunnett
- Statistics and Clinical Studies NHS Blood and Transplant Bristol UK
| | - Eve Fryer
- Department of Cellular Pathology Oxford University Hospitals NHS Foundation Trust John Radcliffe Hospital Oxford UK
| | - Martin Drage
- Department of Nephrology and Transplantation Guy's and St Thomas' NHS Foundation Trust London UK
| | - Catherine Horsfield
- Department of Histopathology Guy's and St Thomas' NHS Foundation Trust London UK
| | - Chris J Callaghan
- Department of Nephrology and Transplantation Guy's and St Thomas' NHS Foundation Trust London UK
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Qi Y, Ma J, Li S, Liu W. Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes. Stem Cell Res Ther 2019; 10:274. [PMID: 31455405 PMCID: PMC6712852 DOI: 10.1186/s13287-019-1362-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) and impaired insulin secretion. The chronic inflammatory process contributed to IR and could also hamper pancreatic β cell function. However, currently applied treatment cannot reverse β cell damage or alleviate inflammation. Mesenchymal stem cells (MSCs), the cell-based therapy for their self-renewable, differentiation potential, and immunosuppressive properties, have been demonstrated in displaying therapeutic effects in T2DM. Adipose-derived MSCs (AD-MSCs) attracted more attention due to less harvested inconvenience and ethical issues commonly accompany with bone marrow-derived MSCs (BM-MSCs) and fetal annex-derived MSCs. Both AD-MSC therapy studies and mechanism explorations in T2DM animals presented that AD-MSCs could translate to clinical application. However, hyperglycemia, hyperinsulinemia, and metabolic disturbance in T2DM are crucial for impairment of AD-MSC function, which may limit the therapeutical effects of MSCs. This review focuses on the outcomes and the molecular mechanisms of MSC therapies in T2DM which light up the hope of AD-MSCs as an innovative strategy to cure T2DM.
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Affiliation(s)
- Yicheng Qi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Jing Ma
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Shengxian Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China
| | - Wei Liu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, 160# Pujian Road, Pudong, Shanghai, 200127, China.
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