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Masset C, Mesnard B, Rousseau O, Walencik A, Chelghaf I, Giral M, Houzet A, Blancho G, Dantal J, Branchereau J, Garandeau C, Cantarovich D. Anti-TNFα as an Adjunctive Therapy in Pancreas and Kidney Transplantation. Transpl Int 2025; 38:14026. [PMID: 40170787 PMCID: PMC11957988 DOI: 10.3389/ti.2025.14026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 03/06/2025] [Indexed: 04/03/2025]
Abstract
The rate of early pancreas allograft failure remains high due to thrombosis but also to severity of rejection episodes. We investigated if adjunct anti-TNFα therapy was safe and could improve outcomes after pancreas transplantation. We investigated all pancreas transplants performed in our institution between 2010 and 2022. Etanercept, an anti TNFα therapy, was added to our standard immunosuppressive regimen since 2017 after approval from our institutional human ethics committee. Pancreas survival, rejection episodes, as well as infectious complications were analyzed. A total of 236 pancreas transplants were included, among whom 87 received Etanercept for induction. In multivariable analysis, after adjustment on confounding variables, pancreas survival did not differ between groups (HR = 0.92, CI 95% = 0.48; 1.73, p = 0.79). However, patients receiving Etanercept presented a significantly lower occurrence of pancreas rejection in multivariate analysis (HR = 0.36, CI 95% = 0.14; 0.95, p = 0.04). Patients receiving Etanercept did not experienced a higher risk of bacterial, fungal, CMV nor BK virus infections compared to the non-treated group. The use of anti-TNFα after pancreas transplantation was safe and did not increase infectious complications. Despite a similar rate of thrombosis, anti-TNFα significantly reduced pancreatic rejection, thus supporting its use among pancreas transplant recipients.
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Affiliation(s)
- Christophe Masset
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Benoit Mesnard
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Olivia Rousseau
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Alexandre Walencik
- Laboratoire Human Leucocyte Antigen (HLA), Etablissement Français du Sang, Nantes, France
| | - Ismaël Chelghaf
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
| | - Magali Giral
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Aurélie Houzet
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
| | - Gilles Blancho
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Jacques Dantal
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Julien Branchereau
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Claire Garandeau
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
| | - Diego Cantarovich
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
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Budhiraja P, Heilman RL, Butterfield R, Reddy KS, Khamash HA, Abu Jawdeh BG, Jadlowiec CC, Katariya N, Smith M, Jaramillo A, Alajous S, Mathur A, Hacke K, Chakkera HA. Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant. Clin Transplant 2024; 38:e15467. [PMID: 39324885 DOI: 10.1111/ctr.15467] [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: 04/12/2024] [Revised: 08/30/2024] [Accepted: 09/09/2024] [Indexed: 09/27/2024]
Abstract
This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.
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Affiliation(s)
- Pooja Budhiraja
- Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | | | | | - Kunam S Reddy
- Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Hassan A Khamash
- Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | | | | | - Nitin Katariya
- Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Maxwell Smith
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Andres Jaramillo
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Salah Alajous
- Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Amit Mathur
- Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Katrin Hacke
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA
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Bassaganyas C, Darnell A, Soler-Perromat A, Rafart G, Ventura-Aguiar P, Cuatrecasas M, Ferrer-Fàbrega J, Ayuso C, García-Criado Á. Accessibility of Percutaneous Biopsy in Retrocolic-Placed Pancreatic Grafts With a Duodeno-Duodenostomy. Transpl Int 2024; 37:12682. [PMID: 39165279 PMCID: PMC11333234 DOI: 10.3389/ti.2024.12682] [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: 01/11/2024] [Accepted: 07/24/2024] [Indexed: 08/22/2024]
Abstract
Duodeno-duodenostomy (DD) has been proposed as a more physiological alternative to conventional duodeno-jejunostomy (DJ) for pancreas transplantation. Accessibility of percutaneous biopsies in these grafts has not yet been assessed. We conducted a retrospective study including all pancreatic percutaneous graft biopsies requested between November 2009 and July 2021. Whenever possible, biopsies were performed under ultrasound (US) guidance or computed tomography (CT) guidance when the US approach failed. Patients were classified into two groups according to surgical technique (DJ and DD). Accessibility, success for histological diagnosis and complications were compared. Biopsy was performed in 93/136 (68.4%) patients in the DJ group and 116/132 (87.9%) of the DD group (p = 0.0001). The graft was not accessible for biopsy mainly due to intestinal loop interposition (n = 29 DJ, n = 10 DD). Adequate sample for histological diagnosis was obtained in 86/93 (92.5%) of the DJ group and 102/116 (87.9%) of the DD group (p = 0.2777). One minor complication was noted in the DD group. The retrocolic position of the DD pancreatic graft does not limit access to percutaneous biopsy. This is a safe technique with a high histological diagnostic success rate.
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Affiliation(s)
- Clara Bassaganyas
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Anna Darnell
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Alexandre Soler-Perromat
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Gerard Rafart
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Pedro Ventura-Aguiar
- Nephrology and Kidney Transplant Department, Institut Clínic de Nefrologia i Urologia (ICNU), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- Hepatobiliopancreatic Surgery and Liver & Pancreas Transplant Department, Institut Clínic de Malalties Digestives i Metabòliques (ICMDM), Hospital Clinic de Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
- Agust Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Ángeles García-Criado
- Radiology Department, Centre Diagnòstic per la Imatge (CDI), Hospital Clinic de Barcelona, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
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Srinivas Rao S, Pandey A, Mroueh N, Elias N, Katabathina VS, Kambadakone A. Comprehensive review of imaging in pancreas transplantation: a primer for radiologists. Abdom Radiol (NY) 2024; 49:2428-2448. [PMID: 38900315 DOI: 10.1007/s00261-024-04383-9] [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: 03/31/2024] [Revised: 05/06/2024] [Accepted: 05/10/2024] [Indexed: 06/21/2024]
Abstract
Pancreas transplantation is a complex surgical procedure performed to restore normoglycemia in patients with type 1 diabetes and includes whole/segmental organ transplant and islet cell transplantation (ICT). In the United States, simultaneous pancreas-kidney transplant (SPK) is most commonly performed due to the higher occurrence of end-stage renal disease in diabetic patients. Understanding the surgical technique and postoperative anatomy is imperative for effective and accurate surveillance following transplantation. Imaging plays an essential role in patients with pancreatic transplants and is often used to evaluate viability, vascular and parenchymal anatomy, and identify potential complications. Imaging techniques such as ultrasound, color and spectral Doppler, computed tomography (CT), magnetic resonance imaging (MRI), and angiography have a complementary role in the postoperative evaluation following a pancreas transplant. The common complications after a whole organ pancreas transplant include vascular thrombosis, graft rejection, pancreatitis, and infections. Complications can be classified into vascular (partial or complete venous thrombosis, arterial thrombosis, stenosis or pseudoaneurysm), parenchymal (pancreatitis, graft rejection), and bowel-related or miscellaneous causes (bowel obstruction, anastomotic leak, and peripancreatic fluid collections). Islet cell transplantation is an innovative therapy for patients with type 1 diabetes. It involves isolating insulin-producing islet cells from donor pancreas and transplanting into recipients, to provide long-term insulin independence or significantly reduce insulin requirements. In recent years, isolation techniques, immunosuppressive regimens, and post-transplant monitoring advancements have propelled ICT as a viable therapeutic option. This comprehensive review aims to provide insights into the current state-of-the-art imaging techniques discussing both normal and abnormal features following pancreas transplantation.
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Affiliation(s)
- Shravya Srinivas Rao
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114-2696, USA
| | - Ankur Pandey
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114-2696, USA
| | - Nayla Mroueh
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114-2696, USA
- Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| | - Nahel Elias
- Department of Surgery, Transplantation Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114-2696, USA
| | - Venkata S Katabathina
- Department of Radiology, University of Texas Health at San Antonio, Floyd Curl Drive, 7703, San Antonio, TX, 78229, USA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White 270, Boston, MA, 02114-2696, USA.
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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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Aziz F, Parajuli S, Kaufman D, Odorico J, Mandelbrot D. Induction in Pancreas Transplantation: T-cell Depletion Versus IL-2 Receptor Blockade. Transplant Direct 2022; 8:e1402. [PMID: 36505900 PMCID: PMC9722744 DOI: 10.1097/txd.0000000000001402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/07/2022] [Indexed: 12/15/2022] Open
Abstract
UNLABELLED There is limited data exist on relative outcomes with T-depletion versus IL-2 receptor (IL2R) blockade induction in pancreas transplantation. METHODS We analyzed all patients who underwent simultaneous pancreas-kidney or pancreas transplant alone at our institution between January 1, 2011, and December 31, 2019. RESULTS Of 417 pancreas transplant recipients, 291 received induction with a T-depleting agent and 126 received induction with an IL2R blocker. No difference was detected in pancreas allograft death-censored (P = 0.7) or uncensored (P = 0.5) survival. Although pancreas rejection was more common overall (P = 0.03), this difference was no longer present in recipients at low immunologic risk (P = 0.08). Cytomegalovirus and bacterial infections were significantly more common in the patients who received T-cell depleting agents for induction (21% versus 11%, P = 0.03; 34% versus 23%, P = 0.04, respectively). On multivariate analysis, history of pancreas rejection (Hazard ratio (HR) = 4.7, P = 0.0001; 95% Confidence interval (CI), 2.16-10.12) and higher calculated panel reactive antibodies (HR = 1.01, P = 0.04; 95% CI, 1.0002-1.02) were associated with increased risk of pancreas allograft failure, but choice of induction was not (HR = 0.64, P = 0.3; 95% CI, 0.27-1.51). Further, on multivariate analysis, Cytomegalovirus infection was associated with increased risk of pancreas allograft rejection (HR = 1.78, P = 0.01; 95% CI, 1.11-2.87), but choice of induction was not (HR = 0.84, P = 0.46; 95% CI, 0.54-1.32). Similarly, bacterial infection was associated with increased risk of patient death (HR = 2.94, P = 0.04; 95% CI, 1.03-8.32). CONCLUSION Our data suggest that IL-2 receptor blockade may be a reasonable choice of induction for pancreas transplant recipients at low immunologic risk.
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Affiliation(s)
- Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Dixon Kaufman
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jon Odorico
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
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Ibáñez JM, Robledo AB, López-Andujar R. Late complications of pancreas transplant. World J Transplant 2020; 10:404-414. [PMID: 33437673 PMCID: PMC7769730 DOI: 10.5500/wjt.v10.i12.404] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/18/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023] Open
Abstract
To summarize the long-term complications after pancreas transplantation that affect graft function, a literature search was carried out on the long-term complications of pancreatic transplantation, namely, complications from postoperative 3rd mo onwards, in terms of loss of graft function, late infection and vascular complications as pseudoaneurysms. The most relevant reviews and studies were selected to obtain the current evidence on these topics. The definition of graft failure varies among different studies, so it is difficult to evaluate, a standardized definition is of utmost importance to know the magnitude of the problem in all worldwide series. Chronic rejection is the main cause of long-term graft failure, occurring in 10% of patients. From the 3rd mo of transplantation onwards, the main risk factor for late infections is immunosuppression, and patients have opportunistic infections like: Cytomegalovirus, hepatitis B and C viruses, Epstein-Barr virus and varicella-zoster virus; opportunistic bacteria, reactivation of latent infections as tuberculosis or fungal infections. Complete preoperative studies and serological tests should be made in all recipients to avoid these infections, adding perioperative prophylactic treatments when indicated. Pseudoaneurysm are uncommon, but one of the main causes of late bleeding, which can be fatal. The treatment should be performed with radiological endovascular approaches or open surgery in case of failure. Despite all therapeutic options for the complications mentioned above, transplantectomy is a necessary option in approximately 50% of relaparotomies, especially in life-threatening complications. Late complications in pancreatic transplantation threatens long-term graft function. An exhaustive follow-up as well as a correct immunosuppression protocol are necessary for prevention.
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Affiliation(s)
- Javier Maupoey Ibáñez
- Hepato-Pancreatico-Biliary Surgery and Transplant Unit, La Fe University Hospital, Valencia 46026, Spain
| | - Andrea Boscà Robledo
- Hepato-Pancreatico-Biliary Surgery and Transplant Unit, La Fe University Hospital, Valencia 46026, Spain
| | - Rafael López-Andujar
- Hepato-Pancreatico-Biliary Surgery and Transplant Unit, La Fe University Hospital, Valencia 46026, Spain
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Aziz F, Mandelbrot D, Parajuli S, Al-Qaoud T, Redfield R, Kaufman D, Odorico JS. Alloimmunity in pancreas transplantation. Curr Opin Organ Transplant 2020; 25:322-328. [PMID: 32692039 DOI: 10.1097/mot.0000000000000776] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
PURPOSE OF REVIEW Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related to the impact of pretransplant and de-novo DSA (dnDSA) in pancreas transplant recipients, and the diagnosis and treatment of T-cell-medicated rejection (TCMR) and antibody-mediated rejection (ABMR) in this complex group of patients. RECENT FINDINGS Recent data suggest that pretransplant DSA and the emergence of dnDSA in pancreas transplant recipients are both associated with increased risk of ABMR. The pancreas allograft biopsy is essential for the specific diagnosis of TCMR and/or ABMR, distinguish rejection from other causes of graft dysfunction, and to guide-targeted therapy. This distinction is important especially in the setting of solitary pancreas transplants but also in simultaneous pancreas-kidney transplants where solid evidence has now emerged demonstrating discordant biopsy findings. Treatment of rejection in a functioning pancreas can prolong allograft survival. SUMMARY The accurate and timely diagnosis of active alloimmune destruction in pancreas transplant recipients is paramount to preserving graft function in the long term. This review will discuss new, rapidly evolving information that is valuable for the physician caring for these patients to achieve optimal immunological outcomes.
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Affiliation(s)
- Fahad Aziz
- Department of Medicine, Division of Nephrology
| | | | | | - Talal Al-Qaoud
- Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, the University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA
| | - Robert Redfield
- Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, the University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA
| | - Dixon Kaufman
- Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, the University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA
| | - Jon S Odorico
- Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, the University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA
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Pancreatic transplantation with duodenoduodenostomy drainage: technique, normal radiological appearance and complications. Abdom Radiol (NY) 2020; 45:479-490. [PMID: 31616962 DOI: 10.1007/s00261-019-02267-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pancreas transplantation is considered the curative treatment for severe type 1 diabetes mellitus in selected cases. Since the first procedure in 1966, surgical techniques have been improved. The current trend among most medical centers, as well as at our Institution, is enteric drainage and systemic venous or portal anastomosis. The aim of this pictorial essay is to describe the main imaging features of pancreatic transplantation with duodenoduodenostomy drainage.
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10
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Wan J, Fang J, Li G, Xu L, Yin W, Xiong Y, Liu L, Zhang T, Wu J, Guo Y, Ma J, Chen Z. Pancreas allograft biopsies procedure in the management of pancreas transplant recipients. Gland Surg 2019; 8:794-798. [PMID: 32042688 DOI: 10.21037/gs.2019.12.01] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pancreas transplantation is an effective therapy for diabetic patients, which can significantly improve the survival rate and quality of life of diabetic patients. According to the international registration of pancreas transplantation center, the global total pancreas transplantation has reached more than 80,000 cases by 2017, including pure pancreas transplantation and simultaneous pancreas-kidney transplantation (SPK). With the development and application of a new type of immunosuppressant, with the gradual maturity of organ preservation technology and surgical technology, the pancreas transplantation has rapidly on a global scale. However, pancreas transplantation still has more problems than limit its development compared with other organ transplantation. For example, the early diagnosis and treatment of pancreatic rejection are of considerable significance to the prognosis of pancreas transplantation. Some surveillance methods of diagnosis have been used increasingly, among which the histopathological diagnosis is particularly important. The first Banff schema for the histological diagnosis of pancreas rejection has been published, which primarily dealt with the diagnosis of acute T-cell-mediated rejection (ACMR). In recent years, antibody-mediated rejection (AMR) has been more emphasized as the primary cause of graft failure. The Banff pancreas allograft rejection grading schema was updated in 2011 by a broad-based multidisciplinary panel, presenting comprehensive guidelines for the diagnosis of AMR.
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Affiliation(s)
- Jiao Wan
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Jiali Fang
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Guanghui Li
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Lu Xu
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Wei Yin
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Yunyi Xiong
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Luhao Liu
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Tao Zhang
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Jialin Wu
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Yuhe Guo
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Junjie Ma
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
| | - Zheng Chen
- Organ Transplant Center, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China
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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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12
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Aziz F, Parajuli S, Uddin S, Harrold K, Djamali A, Astor B, Odorico J, Mandelbrot D. How Should Pancreas Transplant Rejection Be Treated? Transplantation 2019; 103:1928-1934. [PMID: 31233481 DOI: 10.1097/tp.0000000000002694] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Limited published data exist to guide the treatment of pancreas transplant rejection. METHODS We reviewed the treatment and outcomes of 158 first episodes of biopsy-proven pancreas rejection between 1 January 1997 and 31 December 2016. Within each Banff grade of rejection, we compared response rates and long-term outcomes with steroids alone versus steroids plus antithymocyte globulin (ATG). RESULTS Of 158 pancreas recipients with rejection, 65 were treated with steroids alone. Eighty-three percent of patients with grade I, 60% with grade II, and 33.33% with grade III rejection responded to treatment with steroids alone. Ninety-three patients were treated with steroids plus ATG. The response rates were 69% in grade I, 76% in grade II, and 73% in grade III. Response rates and graft survival were not different with grade I rejection treated with steroids alone versus steroids plus ATG. However, response rates and graft survival were significantly better with grade III rejection treated with the addition of ATG, and graft survival rates were significantly better with grade II rejection treated with the addition of ATG. CONCLUSIONS Grade I pancreas rejection can usually be successfully treated with steroids alone, whereas grade II and III rejection should usually be treated with steroids plus ATG, as the addition of ATG improves both response rates and graft survival.
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Affiliation(s)
- Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Salah Uddin
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Kylie Harrold
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Brad Astor
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Jon Odorico
- Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
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13
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Jadlowiec CC, Morgan PE, Nehra AK, Hathcock MA, Kremers WK, Heimbach JK, Wiesner RH, Taner T. Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection. Liver Transpl 2019; 25:425-435. [PMID: 30615251 DOI: 10.1002/lt.25411] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 12/19/2018] [Indexed: 12/13/2022]
Abstract
T cell-mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate-to-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.
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Affiliation(s)
| | - Paige E Morgan
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Avinash K Nehra
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Matthew A Hathcock
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Walter K Kremers
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Julie K Heimbach
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Russell H Wiesner
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
| | - Timucin Taner
- William J. von Liebig Center for Transplantation, Mayo Clinic, Rochester, MN
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14
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Hu ZH, Gu YJ, Qiu WQ, Xiang J, Li ZW, Zhou J, Zheng SS. Pancreas grafts for transplantation from donors with hypertension: an analysis of the scientific registry of transplant recipients database. BMC Gastroenterol 2018; 18:141. [PMID: 30231859 PMCID: PMC6146664 DOI: 10.1186/s12876-018-0865-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 08/24/2018] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND With the rising demands for pancreas transplantation, surgeons are trying to extend the donors pool and set up a more appropriate assessment system. We aim to evaluate the effect of donor hypertension on recipient overall and graft survival rates. METHODS Twenty-four thousand one hundred ninety-two pancreas transplantation patients from the Scientific Registry of Transplant Recipients database were subdivided into hypertension group (HTN, n = 1531) and non-hypertension group (non-HTN, n = 22,661) according to the hypertension status of donors. Recipient overall and graft survival were analyzed and compared by log rank test, and hazard ratios of predictors were estimated using Cox proportional hazard models. RESULTS Patient overall and graft survival of non-HTN group were higher than that of the HTN group (both p < 0.001). The duration of hypertension negatively influenced both overall and graft survival rates (both p < 0.001). Multivariate analyses demonstrated that hypertension was an independent factor for reduced survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.01-1.18; p < 0.001). Other independent factors included recipient body mass index (HR, 1.02; 95% CI, 1.01-1.05; p < 0.001) and transplant type (pancreas after kidney transplants / pancreas transplant alone vs. simultaneous pancreas-kidney transplants; HR, 1.41; 95% CI, 134-1.55; p < 0.001). CONCLUSIONS Donor hypertension is an independent factor for recipient survival after pancreas transplantation and could be considered in donor selection as well as post-transplant surveillance in clinical practice.
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Affiliation(s)
- Zhen-Hua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yang-Jun Gu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wen-Qi Qiu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhi-Wei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China.,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Shu-Sen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79N, Qingchun RD, Hangzhou, China. .,Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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15
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Li J, Guo QJ, Cai JZ, Pan C, Shen ZY, Jiang WT. Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus. World J Gastroenterol 2017; 23:8104-8108. [PMID: 29259387 PMCID: PMC5725306 DOI: 10.3748/wjg.v23.i45.8104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 08/27/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
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Affiliation(s)
- Jiang Li
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Qing-Jun Guo
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Jin-Zhen Cai
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Cheng Pan
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Zhong-Yang Shen
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
| | - Wen-Tao Jiang
- Department of Liver Transplant, Tianjin First Central Hospital, Tianjin 300192, China
- Department of Transplant Surgery, Tianjin First Central Hospital, Tianjin 300192, China
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16
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Dholakia S, Mittal S, Quiroga I, Gilbert J, Sharples EJ, Ploeg RJ, Friend PJ. Pancreas Transplantation: Past, Present, Future. Am J Med 2016; 129:667-73. [PMID: 26965300 DOI: 10.1016/j.amjmed.2016.02.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 02/16/2016] [Accepted: 02/16/2016] [Indexed: 01/07/2023]
Abstract
Diabetes is the pandemic disease of the modern era, with 10% of these patients having type 1 diabetes mellitus. Despite the prevalence, morbidities, and associated financial burden, treatment options have not changed since the introduction of injectable insulin. To date, over 40,000 pancreas transplants have been performed globally. It remains the only known method for restoring glycemic control and thus curing type 1 diabetes mellitus. The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel, and support when encountering them within their own specialty. This study was a narrative review conducted in October 2015, with OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to October 2015. Articles were assessed for clinical relevance and most up-to-date content, with articles written in English as the only inclusion criterion. Other sources used included conference proceedings/presentations and unpublished data from our institution (Oxford Transplant Centre). Pancreatic transplantation is growing and has quickly become the gold standard of care for patients with type 1 diabetes mellitus and renal failure. Significant improvements in quality of life and life expectancy make pancreatic transplant a viable and economically feasible intervention. It remains the most effective method of establishing and maintaining euglycemia, halting and potentially reversing complications associated with diabetes.
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Affiliation(s)
- Shamik Dholakia
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK.
| | - Shruti Mittal
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
| | - Isabel Quiroga
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
| | - James Gilbert
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
| | - Edward J Sharples
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
| | - Rutger J Ploeg
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
| | - Peter J Friend
- Nuffield Department of Surgical Sciences and Oxford Transplant Centre, University of Oxford and Oxford University Hospitals NHS Trust, UK
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17
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Rogers J, Farney AC, Orlando G, Iskandar SS, Doares W, Gautreaux MD, Kaczmorski S, Reeves-Daniel A, Palanisamy A, Stratta RJ. Pancreas transplantation: The Wake Forest experience in the new millennium. World J Diabetes 2014; 5:951-961. [PMID: 25512802 PMCID: PMC4265886 DOI: 10.4239/wjd.v5.i6.951] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 07/09/2014] [Accepted: 11/10/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression.
METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide.
RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a “type 2 diabetes” phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels.
CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.
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18
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Stratta RJ, Farney AC, Rogers J, Orlando G. Immunosuppression for pancreas transplantation with an emphasis on antibody induction strategies: review and perspective. Expert Rev Clin Immunol 2014; 10:117-32. [PMID: 24236648 DOI: 10.1586/1744666x.2014.853616] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
A review of recent literature was performed to identify trends and evaluate outcomes with respect to immunosuppression in pancreas transplantation (PTX). In the past decade, the majority of PTXs were performed with depleting antibody induction, particularly in the setting of either calcineurin inhibitor minimization, corticosteroid withdrawal or both. Maintenance immunosuppression consisted of predominantly tacrolimus (TAC)/mycophenolatemofetil, TAC/mycophenolic acid or TAC/sirolimus with or without corticosteroids. Depending on PTX category, donor and recipient risk factors, case mix and immunosuppressive regimen, the 1-year incidence of acute rejection has decreased to 5-20%. Current 1-year rates of immunological pancreas graft loss range between 1.8 and 6%. Depleting antibody induction and either TAC/mycophenolatemofetil or TAC/sirolimus maintenance therapy with early steroid withdrawal have become the mainstay of immunosuppression in PTX. However, the development of non-nephrotoxic, nondiabetogenic, and nongastrointestinal toxic regimens is highly desirable to improve quality of life in all solid organ transplant recipients.
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Affiliation(s)
- Robert J Stratta
- Department of General Surgery, Section of Transplantation, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC27157, USA
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19
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Stratta RJ, Rogers J, Orlando G, Farooq U, Al-Shraideh Y, Doares W, Kaczmorski S, Farney AC. Depleting antibody induction in simultaneous pancreas-kidney transplantation: a prospective single-center comparison of alemtuzumab versus rabbit anti-thymocyte globulin. Expert Opin Biol Ther 2014; 14:1723-30. [DOI: 10.1517/14712598.2014.953049] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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20
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Risk Factors of Pancreatic Graft Loss and Death of Receptor After Simultaneous Pancreas/Kidney Transplantation. Transplant Proc 2014; 46:1827-35. [DOI: 10.1016/j.transproceed.2014.05.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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21
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Zachariah M, Gregg A, Schold J, Magliocca J, Kayler LK. Alemtuzumab induction in simultaneous pancreas and kidney transplantation. Clin Transplant 2013; 27:693-700. [PMID: 23924066 DOI: 10.1111/ctr.12199] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2013] [Indexed: 12/01/2022]
Abstract
BACKGROUND Alemtuzumab (AZ) is a monoclonal anti-CD52 antibody used as an induction agent in organ transplantation. Few studies have analyzed this agent in the context of simultaneous kidney-pancreas transplantation (SPKT). METHODS We examined US registry data of SPKT recipient outcomes from January 2002 to October 2009 stratified by induction agent including AZ, other T-cell-depleting agents combined (T cell), IL2 receptor blockade (IL-2RAb), and no induction (none). RESULTS Of 6860 SPKT recipients, induction therapy was AZ in 10%, T cell in 49%, IL-2RAb in 18%, and none in 22%. On multivariate analysis, there were no significant differences in overall patient survival, pancreas or renal allograft survival, or delayed renal graft function for the three induction groups compared with no induction. Rehospitalization within six months of transplantation occurred more often with AZ (51%) T cell (52%), and IL-2RAB (45%) compared with none (41%; p < 0.0001). On multivariate analysis, there was a significant higher odds of six-month rehospitalization with AZ (aOR 1.40, 95%CI 1.14-1.71), IL-2RAb (aOR 1.20, 95%CI 1.01-1.42-1.20), and other T-cell-depleting agents (aOR 1.50, 95%CI 1.31-1.73) compared with none. Median length of stay was significantly shorter in the AZ (8 d) compared with the IL-2RAb (9 d), T cell (10 d), and none (10 d) groups (p < 0.0001). CONCLUSIONS There are no differences in patient, pancreas or renal allograft survival using AZ induction. AZ may confer an advantage in the perioperative period as evidenced by a decreased hospital length of stay. However, this benefit may be lost due to more frequent rehospitalizations.
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Affiliation(s)
- Mareena Zachariah
- Department of Medicine, State University New York at Buffalo, Buffalo, NY, USA
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22
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Dong M, Parsaik AK, Kremers W, Sun A, Dean P, Prieto M, Cosio FG, Gandhi MJ, Zhang L, Smyrk TC, Stegall MD, Kudva YC. Acute pancreas allograft rejection is associated with increased risk of graft failure in pancreas transplantation. Am J Transplant 2013; 13:1019-1025. [PMID: 23432918 DOI: 10.1111/ajt.12167] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2012] [Revised: 12/18/2012] [Accepted: 12/26/2012] [Indexed: 01/25/2023]
Abstract
The effect of acute allograft rejection (AR) on long-term pancreas allograft function is unclear. We retrospectively studied 227 consecutive pancreas transplants performed at our institution between January 1, 998 and December 31, 2009 including: 56 simultaneous pancreas and kidney (SPK), 69 pancreas transplantation alone (PTA); and 102 pancreas after kidney (PAK) transplants. With a median follow-up of 6.1 (IQR 3-9) years, 57 patients developed 79 episodes of AR, and 19 experienced more than one episode. The cumulative incidence for AR was 14.7%, 19.7%, 26.6% and 29.1% at 1, 2, 5 and 10 years. PTA transplant (hazards ratio [HR]=2.28, p=0.001) and donor age (per 10 years) (HR=1.34, p=0.006) were associated with higher risk for AR. The first AR episode after 3 months post PT was associated with increased risk for complete loss (CL) (HR 3.79, p<0.001), and the first AR episode occurring during 3- to 12-month and 12- to 24-month periods after PT were associated with significantly increased risk for at least partial loss (PL) (HR 2.84, p=0.014; and HR 6.25, p<0.001, respectively). We conclude that AR is associated with increased risk for CL and at least PL. The time that the first AR is observed may influence subsequent graft failure.
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Affiliation(s)
- M Dong
- Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, MN.,Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China
| | - A K Parsaik
- Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - W Kremers
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN
| | - A Sun
- Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, MN.,Department of Endocrinology and Metabolism, Zibo First People's Hospital, Zibo, Shandong, P. R. China
| | - P Dean
- Division of Transplantation Surgery, Department of Surgery
| | - M Prieto
- Division of Transplantation Surgery, Department of Surgery
| | - F G Cosio
- Division of Nephrology and Hypertension, Department of Internal Medicine
| | - M J Gandhi
- Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology
| | - L Zhang
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - T C Smyrk
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - M D Stegall
- Division of Transplantation Surgery, Department of Surgery
| | - Y C Kudva
- Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, MN
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23
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24
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Mujtaba MA, Fridell JA, Higgins N, Sharfuddin AA, Yaqub MS, Kandula P, Chen J, Mishler DP, Lobashevsky A, Book B, Powelson J, Taber TE. Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience. Clin Transplant 2012; 26:E492-9. [DOI: 10.1111/ctr.12005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2012] [Indexed: 11/30/2022]
Affiliation(s)
- Muhammad A. Mujtaba
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Jonathan A. Fridell
- Division of Transplant; Department of Surgery; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Nancy Higgins
- Transplant Immunology lab; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Asif A. Sharfuddin
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Muhammad S. Yaqub
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Praveen Kandula
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Jeanne Chen
- Division of Transplant; Department of Surgery; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Dennis P. Mishler
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Andrew Lobashevsky
- Transplant Immunology lab; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Benita Book
- Division of Transplant; Department of Surgery; Indiana University School of Medicine; Indianapolis; IN; USA
| | - John Powelson
- Division of Transplant; Department of Surgery; Indiana University School of Medicine; Indianapolis; IN; USA
| | - Tim E. Taber
- Division of Nephrology; Department of Medicine; Indiana University School of Medicine; Indianapolis; IN; USA
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Augustine T. SIMULTANEOUS PANCREAS AND KIDNEY TRANSPLANTATION IN DIABETES WITH RENAL FAILURE: THE GOLD STANDARD? J Ren Care 2012; 38 Suppl 1:115-24. [DOI: 10.1111/j.1755-6686.2012.00269.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome. Transplantation 2011; 92:1039-43. [DOI: 10.1097/tp.0b013e3182313e4f] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Effects of octreotide on activated pancreatic stellate cell-induced pancreas graft fibrosis in rats. J Surg Res 2011; 176:248-59. [PMID: 21816420 DOI: 10.1016/j.jss.2011.06.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2011] [Revised: 05/10/2011] [Accepted: 06/03/2011] [Indexed: 01/08/2023]
Abstract
BACKGROUND Of solid organ transplantations, pancreas transplantation is associated with the highest incidence of pancreatic fibrosis in the early post-transplantation period. Activated pancreatic stellate cells (PSCs) are the main source of pancreatic fibrosis. Octreotide is widely used as a prophylactic for postoperative complications in pancreas transplant recipients. Recent studies have shown that it can inhibit liver fibrosis. This study investigated the effect of octreotide in pancreas graft fibrosis in rats. MATERIALS AND METHODS Isolated PSCs from Sprague Dawley rats were co-cultured with different doses of octreotide (1.25, 2.5, 5, 10, 20, and 40 ng/mL). PSC proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide at 48, 72, and 96 h. The α-smooth muscle actin (α-SMA) and collagen I expressions of PSCs were detected by immunohistochemistry and reverse-transcriptase polymerase chain reaction. Rat heterotopic pancreaticoduodenal transplantation was performed with and without octreotide treatment (0.01 mg/kg). Pancreas grafts were harvested at postoperative d 1, 3, 5, and 7. Hematoxylin-eosin staining, Masson's trichrome staining, and immunohistochemical staining for α-SMA, collagen I, and tumor growth factor-β1 (TGF-β1) were performed. RESULTS Octreotide at a concentration of >20 ng/mL significantly inhibited PSC activation and proliferation in vitro. Inflammatory infiltration was reduced in the octreotide group in vivo, and the expression levels of α-SMA, collagen I, and TGF-β1 were also lower, with statistic significant difference or not. Masson's trichrome staining showed a decrease in collagen deposition with octreotide treatment. CONCLUSIONS Octreotide effectively inhibits PSC activation and proliferation in vitro, but has a limited inhibitory effect on the development of pancreas graft fibrosis.
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Zhang SH, Wu HY, Zhu L. Current status of pancreas transplantation. Shijie Huaren Xiaohua Zazhi 2011; 19:1651-1658. [DOI: 10.11569/wcjd.v19.i16.1651] [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] [Indexed: 02/06/2023] Open
Abstract
Pancreas transplantation has emerged as the treatment of choice for patients with end-stage diabetes mellitus. Over the last four decades, many improvements have been made in the surgical techniques and immunosuppressive regimens, which contributed to increased number of indications and improved allograft survival. Pancreas transplantation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure with a relatively higher complication rate, and lifelong immunosuppression. Therefore, efforts to develop more minimally invasive techniques for endocrine replacement therapy such as islet transplantation have been in progress. This article summarizes the current understanding of pancreas transplantation-associated indications, donor selection, surgical techniques, immunosuppression, and rejection.
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Rogers J, Farney AC, Al-Geizawi S, Iskandar SS, Doares W, Gautreaux MD, Hart L, Kaczmorski S, Reeves-Daniel A, Winfrey S, Ghanta M, Adams PL, Stratta RJ. Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center. Rev Diabet Stud 2011; 8:17-27. [PMID: 21720669 DOI: 10.1900/rds.2011.8.17] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.
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Affiliation(s)
- Jeffrey Rogers
- Department of General Surgery, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
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Yamamoto S, Tufveson G, Wahlberg J, Berne C, Wadström J, Biglarnia AR. Factors influencing outcome of simultaneous kidney and pancreas transplantation: a 23-year single-center clinical experience. Transplant Proc 2011; 42:4197-201. [PMID: 21168663 DOI: 10.1016/j.transproceed.2010.09.076] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2010] [Accepted: 09/20/2010] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Simultaneous kidney and pancreas transplantation (SKPT) has become an effective treatment for patients who have diabetes mellitus type I with advanced nephropathy. This study assesses the progress of the SKPT program at Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft survival. MATERIALS AND METHODS Between February 1986 and September 2009, we performed 113 SKPT. The immunosuppression protocols changed over time and are defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S); era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA, mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4, tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF, steroids and basiliximab induction (T/M/S/B). We analyzed donor/recipient/operative and postoperative variables to assess their influence on pancreas graft and patient survivals. RESULTS The overall 1-, 5-, and 10-year patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10-year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-, and 10-year pancreas graft survivals in SKPT patients transplanted between October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%, 72.7%, and 63.1%, respectively, which was significantly better than those of patients transplanted between February 1986 and September 1997 (era, 1 through 3) (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF (eras 4 and 5) decreased the incidence of acute rejection episodes compared with eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate analysis revealed that donor age (younger than 40 years), immunosuppressive regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes independently affected pancreas graft survival. CONCLUSIONS We demonstrate a superiority of the quadruple protocol with T/M/S/B for graft and patient survival with a decreased incidence of CMV infection after SKPT.
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Affiliation(s)
- S Yamamoto
- Division of Transplantation and Liver Surgery, Department of Surgery, Uppsala University Hospital, Uppsala, Sweden.
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Rangel ÉB, Malheiros DMAC, De Castro MCR, Antunes I, Torres MA, Crescentini F, Genzini T, Perosa M. Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation. Transpl Int 2009; 23:602-610. [DOI: 10.1111/j.1432-2277.2009.01026.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have been in progress, yet this surgical procedure still remains the treatment of choice for diabetic patients with end-stage renal failure. Many improvements have been made in the surgical techniques and immunosuppressive regimens, both of which have contributed to an increasing number of indications for pancreas transplantation. This operation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure and lifelong immunosuppression. The various indications, categories, and outcomes of patients having a pancreas transplant are discussed, particularly with reference to the effect on long-term diabetic complications.
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Affiliation(s)
- Steve A White
- Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK.
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Abstract
Gene expression profiling has emerged as a powerful strategy to define transcriptional mechanism activated in organ transplantation. We performed a pilot feasibility study of mRNA-based pancreas transplant biopsy stratification. The mRNAs expression of 32 genes, observed in renal transplant dysfunction, and 10 pancreas-specific genes were evaluated in 26 pancreas transplant biopsy specimens by quantitative real-time polymerase chain reaction using TaqMan Low Density Array technology. Unsupervised 2D hierarchical clustering segregated the biopsies in two main cluster branches, A and B. Six of seven patients (85.7%) in cluster A and 6 of 19 (31.6%) in cluster B retained functioning pancreas allograft. CD20/MS4A1 mRNA and protein, in addition to CD 3 protein, were detected in four specimens in cluster B. Three of those four pancreas transplants were subsequently lost. Our study demonstrates the potential association of gene expression with clinical outcome of pancreas transplants and justifies further studies in an independent cohort.
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Pancreas transplant alone as an independent risk factor for the development of renal failure: a retrospective study. Transplantation 2009; 86:1789-94. [PMID: 19104423 DOI: 10.1097/tp.0b013e3181913fbf] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Pancreas transplant alone (PTA) is a controversial procedure. Without clearly demonstrated patient survival, recipients report improved quality of life. Nephrotoxic immunosuppression (IS) may exacerbate diabetic renal injury post-PTA. METHODS A single institution retrospective review of patients receiving PTA over a 14-year period was completed. Patient and donor demographics, surgical outcomes, rejection, and patient or graft survival were analyzed. Pre- and Postoperative estimated glomerular filtration rates (eGFR) were calculated based on the modification of diet and renal disease. Multivariate analysis was performed. RESULTS One hundred twenty-three patients undergoing 131 PTAs had an average age of 40.0 years. Seven patients were retransplanted and one received a third pancreas. Mean graft survival was 3.26 years (0-11.3 years) with 21 patients (17%) lost to follow-up. One- and 5-year patient survivals were 96.6% and 91.5%, respectively (mean, 7.15 year). Seventeen patients had an eGFR less than 50 mL/min/1.73 m preoperatively, whereas 64 patients did so post-PTA and 24 had an eGFR less than 30 mL/min. Mean eGFR pretransplantation was 88.9 vs. 55.6 posttransplantation (P<0.0001) with mean follow-up of 3.68 years. All but 16 (12%) patients showed a decrease in eGFR. Mean decrement was 32.1 mg/min/1.73 m. Thirteen developed end-stage renal disease chronic kidney disease (CKD 5) requiring kidney transplantation (KT) at a mean of 4.36 years. Eighty-three patients had an episode of rejection. In post-PTA RF, graft survival was 3.2 vs. 2.4 years (P=0.13). In those requiring KT, graft survival was 7.9 vs. 2.9 years (P<0.0001). Cold ischemia times, donor age, and preoperative eGFR for those with and without RF-requiring KT were not significant. Body mass index was statistically significant. Leukocyte-depleting agents was evaluated, but was not significant. All patients received calcineurin inhibitor IS. CONCLUSIONS Patients who undergo PTA may be at increased risk for RF. After comparing patient and donor demographics, IS, and human leukocyte antigen mismatch, it seems that PTA is an independent risk factor for the development of renal failure. Patients with more successful pancreatic grafts demonstrated lower eGFR. Patients should be made aware of the risks of long-term IS. Only the most appropriate patients should be chosen for PTA.
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Drachenberg CB, Odorico J, Demetris AJ, Arend L, Bajema IM, Bruijn JA, Cantarovich D, Cathro HP, Chapman J, Dimosthenous K, Fyfe-Kirschner B, Gaber L, Gaber O, Goldberg J, Honsová E, Iskandar SS, Klassen DK, Nankivell B, Papadimitriou JC, Racusen LC, Randhawa P, Reinholt FP, Renaudin K, Revelo PP, Ruiz P, Torrealba JR, Vazquez-Martul E, Voska L, Stratta R, Bartlett ST, Sutherland DER. Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel. Am J Transplant 2008; 8:1237-49. [PMID: 18444939 DOI: 10.1111/j.1600-6143.2008.02212.x] [Citation(s) in RCA: 135] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.
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Affiliation(s)
- C B Drachenberg
- Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
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Nguyen TH, Melancon K, Lake J, Payne W, Humar A. Do graft type or donor source affect acute rejection rates after liver transplant: a multivariate analysis. Clin Transplant 2008; 22:624-9. [DOI: 10.1111/j.1399-0012.2008.00834.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Sá JRD, Gonzalez AM, Melaragno CS, Saitovich D, Franco DR, Rangel EB, Noronha IL, Pestana JOM, Bertoluci MC, Linhares M, Miranda MPD, Monteagudo P, Genzini T, Eliaschewitz FG. Transplante de pâncreas e ilhotas em portadores de diabetes melito. ACTA ACUST UNITED AC 2008; 52:355-66. [DOI: 10.1590/s0004-27302008000200024] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2008] [Accepted: 01/08/2008] [Indexed: 02/12/2023]
Abstract
O transplante simultâneo de pâncreas/rim tem indicações específicas, riscos e benefícios. O procedimento, cada vez mais realizado, traz vantagens se comparado ao paciente em diálise, em relação à qualidade de vida, anos de vida ganhos e evolução das complicações crônicas. Se o paciente tiver a opção de realizar o transplante de rim com doador vivo, que apresenta sobrevida semelhante do enxerto e do paciente aos dez anos, o procedimento deverá ser considerado. O transplante de pâncreas após rim, quando efetivo, pode melhorar a evolução das complicações cardiovasculares, mas em contrapartida provoca maior mortalidade nos primeiros meses após a cirurgia. O transplante isolado de pâncreas também ocasiona a maior mortalidade pós-operatória, resultado da complexidade do procedimento e da imunossupressão. O transplante de ilhotas tem sua indicação para um seleto grupo de diabéticos com instabilidade glicêmica.
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Szakály P, Kalmár Nagy K, Wittmann I. The first case of single pancreas transplantation in Hungary. Orv Hetil 2008; 149:387-91. [DOI: 10.1556/oh.2008.28254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Az 1-es típusú inzulindependens cukorbetegség veseelégtelenséggel szövődött esetében a kombinált hasnyálmirigy- és veseátültetés az egyetlen olyan rutineljárás, mely inzulin nélkül normoglycaemiássá teszi a beteget jó vesefunkció mellett. A cukorbetegek egy részénél megtartott vesefunkció mellett is kialakulhat számos szövődmény. Ilyen esetben lehet választandó eljárás a hasnyálmirigy önmagában történő átültetése. 6 évvel hasnyálmirigy-transzplantációs programunk elindítását követően elvégeztük az első szóló hasnyálmirigy-átültetést. A beteg egy 40 éves férfi volt. Enterális drenázst alkalmaztunk portális vénás drenázs mellett. Időben kiterjesztett indukciós kezelésre IL-2-receptor-gátlót használtunk. A műtétből eredő technikai és immunológiai nehézségek ellenére szövődményünk nem volt, illetőleg kilökődést nem észleltünk. 3 évvel a műtét után betegünk életminősége jó, vesefunkciója megtartott, és nem szorul inzulinkezelésre. Összefoglalva megállapíthatjuk, hogy a szoliter hasnyálmirigy-átültetés rutinszerűen jó eredményekkel használható terápiás lehetőség az I-es típusú cukorbetegség veseelégtelenséggel nem komplikált eseteiben.
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Affiliation(s)
- Péter Szakály
- 1 Pécsi Tudományegyetem, Orvostudományi és Egészségtudományi Koordinációs Központ, Általános Orvostudományi Kar Sebészeti Klinika Pécs Ifjúság u. 13. 7624
| | - Károly Kalmár Nagy
- 1 Pécsi Tudományegyetem, Orvostudományi és Egészségtudományi Koordinációs Központ, Általános Orvostudományi Kar Sebészeti Klinika Pécs Ifjúság u. 13. 7624
| | - István Wittmann
- 2 Pécsi Tudományegyetem, Orvostudományi és Egészségtudományi Koordinációs Központ, Általános Orvostudományi Kar II. Belgyógyászati Klinika Pécs
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Wang SN, Sturdevant M, Kandaswamy R, Gruessner RGW, Sutherland DER, Humar A. Technical failure of the pancreas after SPK transplant: are these patients good candidates for later pancreas retransplant? Clin Transplant 2008; 22:50-4. [PMID: 18217905 DOI: 10.1111/j.1399-0012.2007.00743.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Technical failure of the pancreas graft after a simultaneous pancreas-kidney (SPK) transplant is not uncommon, affecting roughly 10% of SPK recipients. These patients often recover with good kidney function, but have persistent issues related to their diabetes. The aim of this study was to determine if these patients were good candidates for a later pancreas retransplant. Outcomes were compared between 21 PASPK (pancreas after SPK) recipients and 361 recipients of a primary pancreas after kidney (PAK) transplant. Except for kidney graft source, there was no significant difference in the demographic characteristics between these two groups. In general, early surgical complications were more common in PASPK than PAK recipients (47.6% vs. 35.5%, p = 0.15), although the difference was not statistically significant. The incidence of acute rejection was no different between these two groups (28% vs. 33%, p = NS). At three yr post-transplant, patient and pancreas graft survival rates were also no different between the two groups (p = NS). The most common cause for graft loss in both groups was acute or chronic rejection. In conclusion, pancreas retransplant is a viable option for SPK recipients experiencing early technical failure of the pancreas graft. These recipients are not at higher immunologic risk vs. primary PAK recipients.
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Affiliation(s)
- Shen-Nien Wang
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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40
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Dean PG, Kudva YC, Larson TS, Kremers WK, Stegall MD. Posttransplant diabetes mellitus after pancreas transplantation. Am J Transplant 2008; 8:175-82. [PMID: 17973965 DOI: 10.1111/j.1600-6143.2007.02018.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Some patients do not achieve normoglycemia after an otherwise successful pancreas transplant. The aim of this study was to define the incidence and risk factors for the development of persistent diabetes mellitus after pancreas transplantation. We studied the outcomes of 144 pancreas transplants performed at our institution between January 2001 and December 2005. Diabetes mellitus was defined as the persistent need for pharmacologic treatment of diabetes mellitus despite evidence of allograft function. Data are expressed as median (25-75% inter-quartile range). Median follow-up was 39 months (IQR 26-55 months). During the follow-up period, 28 patients (19%) developed diabetes mellitus with a functioning allograft. Factors predicting hyperglycemia included: pretransplant insulin dose, BMI and acute rejection episodes (p < 0.0001, p = 0.0002 and p < 0.02, respectively). The median pretransplant hemoglobin A1c for patients developing diabetes was 8.3% (IQR 7.0-9.4%) compared to 6.2% (IQR 5.8-7.4%) at 2 years after transplant (p = 0.0069). In conclusion, persistent diabetes mellitus can occur despite the presence of a functioning pancreas allograft and is due to increased pretransplant BMI, high pretransplant insulin requirements and episodes of acute rejection.
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Affiliation(s)
- P G Dean
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
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41
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Drachenberg CB, Papadimitriou JC. Spectrum of Histopathological Changes in Pancreas Allograft Biopsies and Relationship to Graft Loss. Transplant Proc 2007; 39:2326-8. [PMID: 17889178 DOI: 10.1016/j.transproceed.2007.06.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Histological evaluation of pancreas allografts through the use of needle biopsies is of paramount importance for the determination of the etiology of graft dysfunction. In addition, pathological assessment of the overall status of the exocrine, endocrine, and vascular components provides invaluable information with regards to the prognosis of the graft. Pancreas allograft failure results from a variety of causes, highly dependent on the time posttransplantation, but after the first 6 months' posttransplantation the most common cause of graft loss is chronic rejection. The main histological manifestations of chronic rejection are progressive graft sclerosis (increasing fibrosis and proportional atrophy of the glandular components), secondarily leading to endocrine failure. Evaluation of serial biopsies in patients with graft failure has shown that the most important histological predictors of chronic rejection/graft sclerosis are diffuse acinar inflammation and acute and chronic vascular injury in the form of intimal arteritis and proliferative transplant arteriopathy, respectively.
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Affiliation(s)
- C B Drachenberg
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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42
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Gaber LW. Pancreas allograft biopsies in the management of pancreas transplant recipients: histopathologic review and clinical correlations. Arch Pathol Lab Med 2007; 131:1192-9. [PMID: 17683181 DOI: 10.5858/2007-131-1192-pabitm] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2007] [Indexed: 11/06/2022]
Abstract
CONTEXT Pancreas transplantation has become a therapeutic option for patients with type 1 diabetes mellitus who are in end-stage renal failure. It also is indicated for a subset of nonuremic, insulin-dependent diabetics who experience extreme difficulties in maintaining proper glucose homeostasis by insulin therapy that compromises their productivity and safety. OBJECTIVE To provide a review of the literature and expert experiences for understanding the histologic findings in pancreas transplantation. DATA SOURCES The published literature between 1990 and 2005 was reviewed for this report. Additionally, personal files of the author were used, along with biopsy slides that were used for figures. CONCLUSIONS Pancreas transplantation reestablishes the physiologic state of insulin secretion, and pancreas transplant recipients are able to maintain a state of long-term euglycemia and are less likely to be exposed to hyperglycemia and its systemic complications. Key to the success of transplantation is the scrupulous management and close monitoring of the pancreas transplant recipients. To that end, histologic evaluation of pancreas allografts assumed a pivotal role in management of pancreas allograft dysfunction episodes, and in some centers surveillance biopsies are used to monitor immunologically high-risk situations.
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Affiliation(s)
- Lillian W Gaber
- Department of Pathology, University of Tennessee Health Science Center, Memphis, Tenn, USA.
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Takahashi H, Delacruz V, Sarwar S, Selvaggi G, Moon J, Nishida S, Weppler D, Levi D, Kato T, Tzakis A, Ruiz P. Contemporaneous chronic rejection of multiple allografts with principal pancreatic involvement in modified multivisceral transplantation. Pediatr Transplant 2007; 11:448-52. [PMID: 17493229 DOI: 10.1111/j.1399-3046.2007.00703.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The patient was a 10 yr-old-male with short gut syndrome secondary to Hirschsprung's disease, who underwent a modified (no liver) multivisceral transplant (stomach, pancreas, small and large intestine). The patient experienced malabsorption early in the post-operative course and had been dependent on a combination of enteral and intravenous nutrition. He developed symptoms of bowel obstruction and was suspected to have chronic rejection by an exploratory laparotomy four yr after transplant. Re-transplantation of a multivisceral transplant (stomach, pancreas, liver, small and large intestine) was performed. Microscopic examinations of the explanted allograft organ block revealed varying degrees of chronic rejection in many of the organs but with the pancreatic allograft being affected most severely. The malabsorption symptom following the first transplant may have been caused by the early onset of chronic pancreatic allograft dysfunction. Our case indicates varying severity of chronic rejection among multiple allografts where the pancreatic allograft appeared most susceptible to chronic rejection.
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Abstract
Diabetes mellitus (DM) is a major health problem worldwide, which affects 18.2 million individuals (6.3% of the population) in the United States. Currently, the prevalence of Type 1 DM in the United States is estimated to be 1,000,000 individuals, and 30,000 new cases are diagnosed each year. In addition to end-stage renal disease (ESRD), DM is associated with blindness, accelerated atherosclerosis, dyslipidemia, cardio- and cerebrovascular disease, amputation, poor quality of life, and overall lifespan reduction. It accounts for more than 160,000 deaths per year in the United States alone. In 2002, the annual national direct and indirect costs of Types 1 and 2 DM exceeded $130 billion, which included hospital and physician care, laboratory tests, pharmaceutical products, and patient workdays lost because of disability or premature death. Hyperglycemia alone or in concert with hypertension is the primary factor influencing the development of major diabetic complications. From 1990 to 2001, the number of existing ESRD cases to DM increased by more than 300%, while the rate per million populations increased from 167% to 491%. The number is expected to grow 10-fold by 2030 to 1.3 million accounting for 60% of ESRD population. To date, DM is the leading indication for transplantation and is the cause of ESRD in more than 40% of all transplant recipients each year.
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Affiliation(s)
- Martin L Mai
- Department of Transplantation, Mayo Clinic, Jacksonville, FL 32216, USA
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Stratta RJ, Alloway RR, Lo A, Hodge EE. Risk Factors and Outcomes Analyses at 36 Months of a Prospective, Randomized, Multicenter, Trial of Daclizumab Induction in Simultaneous Kidney–Pancreas Transplant Recipients. Transplant Proc 2005; 37:3527-30. [PMID: 16298650 DOI: 10.1016/j.transproceed.2005.09.061] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
UNLABELLED The purpose of this study was to analyze risk factors for acute rejection (AR) and long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) patients enrolled in a prospective, multicenter study of daclizumab (DAC) versus no antibody induction. METHODS A total of 298 SKPT patients were randomized into three groups and categorized based on an intent to treat analysis, and factors associated with AR and survival were identified using logistic regression and Cox proportional hazards models. RESULTS There were no differences in patient or allograft survival or rejection rates among the three groups at 36 months follow-up. Delayed (kidney) graft function (DGF) was a risk factor for subsequent kidney AR (odds ratio = 2.79, P = .002). The presence of kidney AR was also a risk factor (hazard ratio [HR] = 3.1, P = .003) for kidney graft loss, whereas risk factors for pancreas graft loss (censored for graft loss within 30 days or death with functioning graft) included pancreas AR (HR = 1.97, P = .012), kidney AR (HR = 1.61, P = .042), CMV serostatus donor +/recipient - (HR = 1.62, P = .026), and HLA-B mismatch (HR = 1.58, P = .01). Kidney graft loss (HR = 5.5, P = .02) was the only predictor of mortality. CONCLUSIONS At 36 months, no significant differences in outcomes were noted in the three study groups. DGF was the major risk factor for kidney AR, kidney AR was the major risk factor for kidney graft loss, and kidney graft loss was the major determinant of mortality. Prevention of kidney DGF and AR in SKPT recipients may play a pivotal role in optimizing long-term outcomes.
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Affiliation(s)
- R J Stratta
- Dept. of General Surgery, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1095, USA.
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Casey ET, Smyrk TC, Burgart LJ, Stegall MD, Larson TS. Outcome of untreated grade II rejection on solitary pancreas allograft biopsy specimens. Transplantation 2005; 79:1717-22. [PMID: 15973174 DOI: 10.1097/01.tp.0000159148.13431.d0] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The most widely used grading scheme for acute pancreas allograft rejection grades biopsy specimens from 0 (normal) to V (severe rejection). Although the more advanced grades correlate strongly with immunologic graft loss, it is unclear how lesser grades impact graft outcome. The authors therefore report the outcomes of untreated grade II (minimal) rejection of solitary pancreas biopsy specimens. METHODS The authors retrospectively analyzed all solitary pancreas transplants performed at the Mayo Clinic between January 2001 and November 2002. The authors selected all patients who were found with grade II findings on biopsy. Whether patients underwent follow-up biopsies, what the results were, and graft survival at the end of the study period were then determined. RESULTS A total of 88 pancreas transplants were performed; 20 pancreas transplant recipients (23%) developed grade II (minimal) rejection and were followed for a mean of 22.8+/-8.7 months. Eighteen patients underwent biopsy for protocol purposes and two patients underwent clinically indicated biopsies. Of the patients who underwent biopsy as per protocol, 15 of the patients had a total of 25 follow-up biopsies: 10 were grade 0; 3 were grade I; and 10 were unchanged (grade II). Rejection in one patient progressed to grade III and in another patient to grade IV. The three patients who did not undergo repeat biopsy had a functioning allograft pancreas at the end of the study period. Of the two patients with grade II biopsy specimens obtained for clinical reasons, one had resolution of all inflammation noted on three follow-up biopsies, and the other patient did not undergo follow-up biopsy and died with a functioning graft. CONCLUSIONS Grade II (minimal) rejection of solitary pancreas allograft rarely progresses to more severe degrees of inflammation. Morphologic findings in this category may not have unfavorable prognoses over a period of 2 years when untreated.
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Affiliation(s)
- Edward T Casey
- Division of Nephrology and Department of Internal Medicine, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA
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Nath DS, Gruessner A, Kandaswamy R, Gruessner RW, Sutherland DE, Humar A. Late anastomotic leaks in pancreas transplant recipients - clinical characteristics and predisposing factors. Clin Transplant 2005; 19:220-4. [PMID: 15740558 DOI: 10.1111/j.1399-0012.2005.00322.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Anastomotic leaks after pancreas transplants usually occur early in the postoperative course, but may also be seen late post-transplant. We studied such leaks to determine predisposing factors, methods of management, and outcomes. RESULTS Between January 1, 1994 and December 31, 2002, a total of 25 pancreas transplant recipients at our institution experienced a late leak (defined as one occurring more than 3 months post-transplant). We excluded recipients with an early leak or with a leak seen immediately after an enteric conversion. The mean recipient age was 40.3 yr; mean donor age, 31.3 yr. The category of transplant was as follows: simultaneous pancreas-kidney (n = 5, 20%), pancreas after kidney (n = 10, 40%), and pancreas transplant alone (n = 10, 40%). At the time of their leak, most recipients (n = 23, 92%) had bladder-drained pancreas grafts; only two recipients (8%) had enteric-drained grafts. The mean time from transplant to the late leak was 20.5 months (range = 3.5-74 months). A direct predisposing event or risk factor occurring in the 6 wk preceding leak diagnosis was identified in 10 (40%) of the recipients. Such events or risk factors included a biopsy-proven episode of acute rejection (n = 4, 16%), a history of blunt abdominal trauma (n = 3, 12%), a recent episode of cytomegalovirus infection (n = 2, 8%), and obstructive uropathy from acute prostatitis (n = 1, 4%). Non-operative or conservative care (Foley catheter placement with or without percutaneous abdominal drains) was the initial treatment in 14 (56%) of the recipients. Such care was successful in nine (64%) of the 14 recipients; the other five (36%) required surgical repair after failure of conservative care at a mean of 10 d after Foley catheter placement. Of the 25 recipients, 11 underwent surgery as their initial leak treatment: repair in nine and pancreatectomy because of severe peritonitis in two. After appropriate management (conservative or operative) of the initial leak, five (20%) of the 25 recipients had a recurrent leak; the mean length of time from initial leak to recurrent leak was 5.6 months. All five recipients with a recurrent leak ultimately required surgery. CONCLUSIONS Late anastomotic leaks are not uncommon; they may be more common with bladder-drained grafts. One-third of the recipients with a late leak had experienced some obvious preceding event that predisposed to the leak. For two-thirds of our stable recipients with bladder-drained grafts, non-operative treatment of the leak was successful.
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Affiliation(s)
- Dilip S Nath
- Department of Surgery, University of Minnesota, Minneapolis, MN, USA
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Cantarovich D, Karam G, Hourmant M, Dantal J, Blancho G, Giral M, Soulillou JP. Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation. Am J Transplant 2005; 5:1332-8. [PMID: 15888038 DOI: 10.1111/j.1600-6143.2005.00816.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Two steroid-sparing immunosuppressive regimens were prospectively compared in recipients of simultaneous pancreas-kidney transplants, one did not include steroids at all and the other included steroids for the first 3 months following transplantation. All patients received rabbit anti-thymocyte globulin, mycophenolate mofetil (MMF) and cyclosporine. Fifty patients were randomised in an open-label, single center and prospective study. The incidence of biopsy-proven acute rejection during the first 12 months after transplantation was the primary endpoint of the study. The incidence of biopsy-proven acute rejection was 4% in both groups. No statistically significant difference in patient (96 and 100%), kidney (96 and 100%) or pancreas (84 and 92%) survival was observed 1 year after transplantation in the steroid avoidance and steroid withdrawal groups, respectively. The total number of adverse events (including severe ones), length of hospitalization and infectious episodes did not differ between groups. Blood glucose and insulin levels, lipid profile and hemoglobin A1C levels did not differ statistically between the two groups. However, the 1-year serum creatinine level was significantly higher in the steroid avoidance group (132 vs. 114 micromol/L; p = 0.02). Steroid avoidance and steroid withdrawal 3 months after transplantation are safe and effective regimens for diabetic patients with pancreas-kidney transplants.
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Affiliation(s)
- Diego Cantarovich
- Institut de Transplantation et de Recherche en Transplantation (ITERT), Centre Hospitalier et Universitaire de Nantes, France.
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Abstract
Transplantation of the pancreas or islet cells constitutes surgical treatment for patients with type 1 diabetes mellitus. Pancreas transplantation is now an established procedure for the surgical treatment of diabetes mellitus. Islet cell transplantation has the potential to be the procedure of choice once it becomes more routine because of the minimal surgery involved. Included in this chapter are the pathophysiology of diabetes, rationale for transplantation, and the surgical procedure itself.
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Affiliation(s)
- Karla Larson-Wadd
- Department of Anesthesiology, University of Minnesota Medical Center, Minneapolis, MN 55455, USA
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50
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Abstract
Pancreas transplantation continues to evolve as a strategy in the management of diabetes mellitus. The first combined pancreas-kidney transplant was reported in 1967, but pancreas transplant now represents a number of procedures, each with different indications, risks, benefits, and outcomes. This review will summarize these procedures, including their risks and outcomes in comparison to kidney transplantation alone, and how or if they affect the consequences of diabetes: hyperglycemia, hypoglycemia, and microvascular and macrovascular complications. In addition, the new risks introduced by immunosuppression will be reviewed, including infections, cancer, osteoporosis, reproductive function, and the impact of immunosuppression medications on blood pressure, lipids, and glucose tolerance. It is imperative that an endocrinologist remain involved in the care of the pancreas transplant recipient, even when glucose is normal, because of the myriad of issues encountered post transplant, including ongoing management of diabetic complications, prevention of bone loss, and screening for failure of the pancreas graft with reinstitution of treatment when indicated. Although long-term patient and graft survival have improved greatly after pancreas transplant, a multidisciplinary team is needed to maximize long-term quality, as well as quantity, of life for the pancreas transplant recipient.
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Affiliation(s)
- Jennifer L Larsen
- Section of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, 983020 Nebraska Medical Center, Omaha, Nebraska 69198-3020, USA.
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