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Rogers J, Jay CL, Farney AC, Orlando G, Jacobs ML, Harriman D, Gurram V, Sharda B, Gurung K, Reeves‐Daniel A, Doares W, Kaczmorski S, Mena‐Gutierrez A, Sakhovskaya N, Gautreaux MD, Stratta RJ. Simultaneous pancreas‐kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes? Clin Transplant 2022; 36:e14599. [PMID: 35044001 PMCID: PMC9285604 DOI: 10.1111/ctr.14599] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 01/11/2022] [Accepted: 01/12/2022] [Indexed: 11/30/2022]
Abstract
The influence of African American (AA) recipient race on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) is uncertain.
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Affiliation(s)
- Jeffrey Rogers
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Colleen L. Jay
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Alan C. Farney
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Giuseppe Orlando
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Marie L. Jacobs
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - David Harriman
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Venkat Gurram
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Berjesh Sharda
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Komal Gurung
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Amber Reeves‐Daniel
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - William Doares
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Scott Kaczmorski
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Alejandra Mena‐Gutierrez
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Natalia Sakhovskaya
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Michael D. Gautreaux
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
| | - Robert J. Stratta
- Department of Surgery Section of Transplantation Atrium Health Wake Forest Baptist Winston‐Salem NC United States
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Gurram V, Gurung K, Rogers J, Farney AC, Orlando G, Jay C, Reeves-Daniel A, Mena-Gutierrez A, Sakhovskaya N, Doares W, Kaczmorski S, Sharda B, Gautreaux MD, Stratta RJ. Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study. Clin Transplant 2021; 36:e14498. [PMID: 34599533 DOI: 10.1111/ctr.14498] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/17/2021] [Accepted: 09/27/2021] [Indexed: 11/27/2022]
Abstract
Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp- (level < 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p = .15), and pancreas graft survival (60% versus 86%, p = .03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p = .026) or rejection (17% Cp+ versus 6.5% Cp-, p = .2). Post-transplant weight gain > 5 kg occurred in 72% of Cp+ versus 26% of Cp- patients (p = .0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.
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Affiliation(s)
- Venkat Gurram
- Departments of General Surgery, (Section of Transplantation)
| | - Komal Gurung
- Departments of General Surgery, (Section of Transplantation)
| | - Jeffrey Rogers
- Departments of General Surgery, (Section of Transplantation)
| | - Alan C Farney
- Departments of General Surgery, (Section of Transplantation)
| | | | - Colleen Jay
- Departments of General Surgery, (Section of Transplantation)
| | | | | | | | | | | | - Berjesh Sharda
- Departments of General Surgery, (Section of Transplantation)
| | - Michael D Gautreaux
- Department of Pathology, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA
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Gurung K, Alejo J, Rogers J, Farney AC, Orlando G, Jay C, Reeves-Daniel A, Mena-Gutierrez A, Sakhovskaya N, Doares W, Kaczmorski S, Gautreaux MD, Stratta RJ. Recipient age and outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature. Clin Transplant 2021; 35:e14302. [PMID: 33783874 DOI: 10.1111/ctr.14302] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 12/30/2022]
Abstract
The influence of recipient age on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the modern era is uncertain. METHODS We retrospectively studied 255 patients undergoing SPKT from 11/01 to 8/20. Recipients were stratified according to age group: age <30 years (n = 16); age 30-39 years (n = 91); age 40-49 years (n = 86) and age ≥50 years (n = 62 [24.3%], including 9 patients ≥60 years of age). RESULTS Three-month and one-year outcomes were comparable. The eight-year patient survival rate was lowest in the oldest age group (47.6% vs 78% in the 3 younger groups combined, p < .001). However, eight-year kidney and pancreas graft survival rates were comparable in the youngest and oldest age groups combined (36.5% and 32.7%, respectively), but inferior to those in the middle 2 groups combined (62% and 50%, respectively, both p < .05). Death-censored kidney and pancreas graft survival rates increased from youngest to oldest recipient age category because of a higher incidence of death with functioning grafts (22.6% in oldest group compared to 8.3% in the 3 younger groups combined, p = .005). CONCLUSIONS Recipient age did not appear to significantly influence early outcomes following SPKT. Late outcomes are similar in younger and older recipients, but inferior to the middle 2 age groups.
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Affiliation(s)
- Komal Gurung
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Jennifer Alejo
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Jeffrey Rogers
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Alan C Farney
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Giuseppe Orlando
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Colleen Jay
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Amber Reeves-Daniel
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Alejandra Mena-Gutierrez
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Natalia Sakhovskaya
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - William Doares
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Scott Kaczmorski
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Michael D Gautreaux
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Robert J Stratta
- Department of Surgery, Section of Transplantation, Wake Forest Baptist Health, Winston-Salem, NC, USA
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Kumar N, Joisher H, Ganguly A. Polymeric Scaffolds for Pancreatic Tissue Engineering: A Review. Rev Diabet Stud 2018; 14:334-353. [PMID: 29590227 PMCID: PMC6230446 DOI: 10.1900/rds.2017.14.334] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 01/24/2018] [Accepted: 02/05/2018] [Indexed: 12/17/2022] Open
Abstract
In recent years, there has been an alarming increase in the incidence of diabetes, with one in every eleven individuals worldwide suffering from this debilitating disease. As the available treatment options fail to reduce disease progression, novel avenues such as the bioartificial pancreas are being given serious consideration. In the past decade, the research focus has shifted towards the field of tissue engineering, which helps to design biological substitutes for repair and replacement of non-functional or damaged organs. Scaffolds constitute an integral part of tissue engineering; they have been shown to mimic the native extracellular matrix, thereby supporting cell viability and proliferation. This review offers a novel compilation of the recent advances in polymeric scaffolds, which are used for pancreatic tissue engineering. Furthermore, in this article, the design strategies for bioartificial pancreatic constructs and their future applications in cell-based therapy are discussed.
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Affiliation(s)
| | | | - Anasuya Ganguly
- Department of Biological Sciences, BITS-Pilani, K.K Birla Goa Campus, Goa, India 403726
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Development and results of a novel pancreas transplant program in Spain: the surgeon's point of view. Cir Esp 2018; 96:205-212. [PMID: 29501238 DOI: 10.1016/j.ciresp.2017.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 10/13/2017] [Accepted: 12/31/2017] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months). RESULTS Out of the total of this series, two patients died: one patient because of cardiac arrest immediately after surgery; and another patient due to traffic accident, complicated by pneumonia. Among the 51 living patients, two grafts were lost: one due to chronic rejection four years after transplantation; and the other due to arterial thrombosis 20 days after transplantation (the only case requiring transplantectomy). In ten patients, one or more re-operations were necessary due to the following: graft pancreatitis (n=4), small intestinal obstruction (n=4), arterial thrombosis (n=1), fistula (n=1) and hemoperitoneum (n=1). Overall patient and graft survival rates after 1, 3 and 5 years were 98, 95 and 95% and 96, 93 and 89%, respectively. CONCLUSIONS This study has shown that the results of a new pancreas transplant program, which relies on the previous experience of other groups, do not demonstrate a learning curve. Adequate surgeon education and training, as well as the proper use of standardized techniques, should ensure optimal results.
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Praksch D, Sandor B, Nagy KK, Viola M, Toth A, Toth K, Szakaly P, Varga A. Acetylsalicylic Acid Resistance After Simultaneous Pancreas-Kidney Transplantation. Transplant Proc 2016; 48:2555-2557. [PMID: 27742347 DOI: 10.1016/j.transproceed.2016.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND The most common conditions leading to death after simultaneous pancreas-kidney transplantations (SPKs) are cardiovascular diseases. The aim of this study was to test the platelet aggregation inhibitor acetylsalicylic acid (ASA) resistance in patients after SPKs, including investigations into the triggering factors. METHODS Thirty-two patients (22 men, 10 women; overall age, 47.4 ± 8.6 years) were involved in our study and took 100 mg ASA per day. We used optical platelet aggregometry to detect resistance. RESULTS Resistance occurred in 40.6% of the study group. However, with the use of logistic regression analysis, the examined 24 factors did not show any significant correspondence with resistance. CONCLUSIONS The incidence of ASA resistance seems to be higher compared with other groups, but the triggering effect is still unproved. Clarifying this question should be important regarding the mortality- and morbidity-reducing capacity of antiplatelet drugs in the management of cardiovascular conditions.
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Affiliation(s)
- D Praksch
- First Department of Medicine, Medical School, University of Pecs, Pecs, Hungary
| | - B Sandor
- First Department of Medicine, Medical School, University of Pecs, Pecs, Hungary
| | - K K Nagy
- Department of Surgery, Medical School, University of Pecs, Pecs, Hungary
| | - M Viola
- Department of Surgery, Medical School, University of Pecs, Pecs, Hungary
| | - A Toth
- First Department of Medicine, Medical School, University of Pecs, Pecs, Hungary
| | - K Toth
- First Department of Medicine, Medical School, University of Pecs, Pecs, Hungary
| | - P Szakaly
- Department of Surgery, Medical School, University of Pecs, Pecs, Hungary
| | - A Varga
- Department of Surgery, Medical School, University of Pecs, Pecs, Hungary.
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7
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Vrakas G, Arantes RM, Gerlach U, Reddy S, Friend P, Vaidya A. Solitary pancreas transplantation: a review of the UK experience over a period of 10 yr. Clin Transplant 2015; 29:1195-202. [DOI: 10.1111/ctr.12650] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2015] [Indexed: 12/11/2022]
Affiliation(s)
| | | | | | | | - Peter Friend
- Oxford Transplant Centre; Churchill Hospital; Oxford UK
| | - Anil Vaidya
- Oxford Transplant Centre; Churchill Hospital; Oxford UK
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Becker LE, Hallscheidt P, Schaefer SM, Klein K, Grenacher L, Waldherr R, Macher-Goeppinger S, Schemmer P, Mehrabi A, Suesal C, Zeier M, Morath C. A Single-center Experience on the Value of Pancreas Graft Biopsies and HLA Antibody Monitoring After Simultaneous Pancreas-Kidney Transplantation. Transplant Proc 2015; 47:2504-2512. [PMID: 26518960 DOI: 10.1016/j.transproceed.2015.09.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 09/02/2015] [Indexed: 11/22/2022]
Abstract
BACKGROUND In simultaneous pancreas-kidney transplantation (SPKT), monitoring of the pancreas allograft is more complex than the kidney allograft due to difficulties in obtaining pancreas histology and weak clinical evidence supporting the role of donor-specific antibodies (DSA). METHODS We performed a single-center retrospective analysis of all 17 SPKT recipients who underwent a total of 22 pancreas allograft indication biopsies from October 2009 to September 2012. Fifteen patients had at least 2 DSA measurements: pretransplantation and at the time of biopsy. RESULTS All 7 patients (100%) with post-transplantation DSA-positivity (de novo: n = 6; persistent: n = 1) at biopsy had at least 1 rejection episode either of the pancreas (n = 4) or the kidney (n = 3), with 3 antibody-mediated rejections (AMR). In contrast, only 4 of 8 patients (50%) without post-transplantation DSA had evidence of rejection, with 1 AMR. Findings during pancreas allograft biopsy procedures led to a change of immunosuppressive therapy in 11 of 15 (73%) patients. Patient survival, graft survival, and function were not adversely affected by the presence of post-transplantation DSA. One major and 2 minor procedure-related complications occurred during the pancreas biopsies. CONCLUSIONS In this small retrospective analysis, pancreas allograft histology provided the most therapeutically relevant information, rather than the kidney histology or DSA monitoring.
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Affiliation(s)
- L E Becker
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany.
| | - P Hallscheidt
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - S M Schaefer
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany
| | - K Klein
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany
| | - L Grenacher
- Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
| | - R Waldherr
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | | | - P Schemmer
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - A Mehrabi
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - C Suesal
- Institute of Immunology, University of Heidelberg, Heidelberg, Germany
| | - M Zeier
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany
| | - C Morath
- Division of Nephrology, University of Heidelberg, Heidelberg, Germany
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Liu X, Li X, Zhang N, Wen X. Engineering β-cell islets or islet-like structures for type 1 diabetes treatment. Med Hypotheses 2015; 85:82-4. [PMID: 25892491 DOI: 10.1016/j.mehy.2015.04.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Revised: 03/31/2015] [Accepted: 04/05/2015] [Indexed: 01/28/2023]
Abstract
Type 1 diabetes mellitus is a disease characterized by the destruction of the β-cells in the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is insulin injections administered multiple times throughout the day. However, this treatment cannot provide sustained physiological release of insulin and the insulin amount is not finely tuned to the glycemia condition. Pancreatic transplantation or islet transplantation would be the preferred treatment strategy but the lack of donor tissue and immunoincompatibility has been shown to be a roadblock to their widespread use. Bioengineering strategies are poised to combat these challenges. Islet encapsulation is expected to offer both immunoisolation and immunomodulation effects by: (1) physically protecting islets from the attacks of immunoglobulins, complements, and host immune cells, and (2) delivering immune regulatory and immunomodulatory factors locally to the islets to protect those islets from immune rejection. Semi-permeable coatings using biocompatible biomaterials can be used for immunoisolating islets away from the host immune systems. Immunoisolation technology also provides an opportunity to use other cell sources for cell therapy to treat type 1 diabetes. Recently, some studies reported that co-transplantation of islets with mesenchymal stem cells (MSCs) can control graft inflammation. MSCs have immunomodulatory property. They are able to secrete anti-inflammatory factors and repress the activity of various immune cells. Growth factors like interleukin 10 (IL-10) and leukemia inhibitory factor (LIF) also have immune regulatory properties. Therefore immunoisolation and immunomodulation technologies can be integrated and applied to β-cell encapsulation for the treatment of type 1 diabetes. Through engineering β-cell islets or islet-like microtissues, the viability and function of transplanted β-cells may be improved. In the meantime, the survival of transplanted β-cells can be further improved by promoting vascular network formation surrounding the transplanted islets or microtissues.
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Affiliation(s)
| | - Xiaowei Li
- Translational Tissue Engineering Center, Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD 21231, USA
| | - Ning Zhang
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Xuejun Wen
- Institute for Engineering and Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA.
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Horneland R, Paulsen V, Lindahl JP, Grzyb K, Eide TJ, Lundin K, Aabakken L, Jenssen T, Aandahl EM, Foss A, Øyen O. Pancreas transplantation with enteroanastomosis to native duodenum poses technical challenges--but offers improved endoscopic access for scheduled biopsies and therapeutic interventions. Am J Transplant 2015; 15:242-50. [PMID: 25394773 DOI: 10.1111/ajt.12953] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 07/02/2014] [Accepted: 07/22/2014] [Indexed: 01/25/2023]
Abstract
To facilitate endoscopic access for rejection surveillance and stenting of the pancreas, we have abandoned the duodenojejunostomy (DJ) in favor of duodenoduodenostomy (DD) in pancreas transplantation (PTx). From September 2012 to September 2013 we performed 40 PTx with DD; 20 solitary-PTx (S-PTx) and 20 simultaneous pancreas and kidney transplantation (SPK). We compared the outcomes with results from 40 PTx-DJ (10 S-PTx and 30 SPK) from the preceding era. The DD-enteroanastomoses were performed successfully. Endoscopic pancreas biopsies (endoscopic ultrasound examination [EUS]) yielded representative material in half of the cases. One exocrine fistula was treated by endoscopic stenting. PTxs-DD were associated with a higher rate of thrombosis compared to PTx-DJ (23% vs. 5%) and reoperations (48% vs. 30%), as well as inferior graft survival (80% vs. 88%). Time on waiting list, HLA A + B mismatches and reoperations were associated with graft loss. Only recipient age remained an independent predictor of patient death in multivariate analysis. PTx-DD showed a higher rate of thrombosis and inferior results, but facilitated a protocol biopsy program by EUS that was feasible and safe. Given that technical difficulties can be solved, the improved endoscopic access might confer long-term benefits, yet this remains to be proven.
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Affiliation(s)
- R Horneland
- Clinic for Cancer, Surgery and Transplantation, Department of Transplantation Medicine, Section for Transplant Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Stratta RJ, Rogers J, Farney AC, Orlando G, El-Hennawy H, Gautreaux MD, Reeves-Daniel A, Palanisamy A, Iskandar SS, Bodner JK. Pancreas transplantation in C-peptide positive patients: does "type" of diabetes really matter? J Am Coll Surg 2014; 220:716-27. [PMID: 25667140 DOI: 10.1016/j.jamcollsurg.2014.12.020] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 12/15/2014] [Indexed: 01/01/2023]
Abstract
BACKGROUND In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT). STUDY DESIGN We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥ 2.0 ng/mL or < 2.0 ng/mL. RESULTS From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥ 2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥ 5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2). CONCLUSIONS Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be used exclusively to determine candidacy for SPKT.
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Affiliation(s)
- Robert J Stratta
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC.
| | - Jeffrey Rogers
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Alan C Farney
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Giuseppe Orlando
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Hany El-Hennawy
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael D Gautreaux
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC; Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Amber Reeves-Daniel
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Amudha Palanisamy
- Department of Internal Medicine (Section of Nephrology), Wake Forest School of Medicine, Winston-Salem, NC
| | - Samy S Iskandar
- Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jason K Bodner
- Department of General Surgery (Section of Transplantation), Wake Forest School of Medicine, Winston-Salem, NC
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12
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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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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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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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Stratta RJ, Farney AC, Orlando G, Farooq U, Al-Shraideh Y, Rogers J. Similar results with solitary pancreas transplantation compared with simultaneous pancreas-kidney transplantation in the new millennium. Transplant Proc 2014; 46:1924-7. [PMID: 25131072 DOI: 10.1016/j.transproceed.2014.05.079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION The purpose of this study was to analyze our single-center outcomes according to pancreas transplant (PT) category in the new millennium by using standardized management protocols. PATIENTS AND METHODS We retrospectively studied 202 consecutive PTs (179 with portal-enteric drainage) in 192 patients; all received either rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and tapered corticosteroids or early steroid withdrawal. Unlike simultaneous pancreas/kidney (SPK) transplant, solitary PT (SPT) recipients were managed with routine perioperative anticoagulation and surveillance pancreas biopsies. RESULTS From November 2001 to March 2013, we performed 162 SPK transplants, 35 pancreas after kidney transplants, and 5 pancreas-alone transplants (40 SPTs). Demographic characteristics were mostly comparable; however, the SPT group had younger donors, shorter waiting time, fewer HLA mismatches, and fewer African-American recipients but more retransplants (all, P < .05). With a mean follow-up of 5.5 versus 7.5 years, overall patient (86.4% SPK vs 86.8% SPT), kidney graft (74% SPK vs 80% SPT), and pancreas graft (both 65%) survival rates were comparable. Although mortality rates were similar, mortality patterns differed because no SPT recipients died early, whereas the 1-, 3-, and 5-year mortality rates after SPK transplant were 4%, 9% and 12%, respectively (P < .05). The most common causes of pancreas graft loss were death with functioning grafts in SPK recipients and acute/chronic rejection in SPT recipients. Rates of early thrombosis were 8.6% in SPK patients and 5% in SPT patients. Cumulative clinical acute rejection rates were similar between groups (SPK 29% vs SPT 27.5%; P = NS). CONCLUSIONS In the setting of depleting antibody induction and tacrolimus-based therapy, HLA matching, careful donor and recipient selection, portal-enteric drainage, selective perioperative anticoagulation, and surveillance SPT biopsy monitoring, similar medium-term outcomes can be achieved in SPK transplants and SPTs in the new millennium.
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Affiliation(s)
- R J Stratta
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.
| | - A C Farney
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - G Orlando
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - U Farooq
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Y Al-Shraideh
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - J Rogers
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina
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Otsuki K, Yoshikawa K, Kenmoshi T, Akutsu N, Maruyama M, Asano T, Saigo K, Hasegawa M, Aoyama H, Matsumoto I, Ito T, Uchino Y. Evaluation of insulin independence using 11C-methionine positron emission tomography after living-donor and brain-dead donor pancreas transplantation. Transplant Proc 2014; 46:1913-6. [PMID: 25131069 DOI: 10.1016/j.transproceed.2014.05.069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.
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Affiliation(s)
- K Otsuki
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan.
| | - K Yoshikawa
- National Institute of Radiological Sciences, Chiba, Japan
| | - T Kenmoshi
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - N Akutsu
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Maruyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Asano
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - K Saigo
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - M Hasegawa
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - H Aoyama
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - I Matsumoto
- Department of Surgery, National Chiba-East Hospital, Chiba, Japan
| | - T Ito
- Department of Transplantation Surgery, Fujita Health University, Nagoya, Japan
| | - Y Uchino
- Chiba Ryogo Center, PET Imaging Division, Chiba, Japan
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Montiel-Casado MC, Pérez-Daga JA, Aranda-Narváez JM, Fernández-Burgos I, Sánchez-Pérez B, León-Díaz FJ, Cabello-Díaz M, Rodríguez-Burgos D, Hernández-Marrero D, Santoyo-Santoyo J. Pancreas graft survival in simultaneous pancreas-kidney versus pancreas-after-kidney and pancreas alone transplantations: a single institution experience. Transplant Proc 2014; 45:3609-11. [PMID: 24314973 DOI: 10.1016/j.transproceed.2013.10.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Pancreas transplantation offers excellent outcomes today in patients who have type-1 diabetes mellitus (DM) with difficult control in terms of increasing patient and pancreatic graft survival. Different factors in donors, recipients, and the perioperative period have been associated with long-term graft survival. The aim of this study was to compare pancreatic graft survival in simultaneous pancreas-kidney transplantation (SPK) and the other two modalities, pancreas-alone and pancreas-after-kidney transplantation (non-SPK), at our institution. METHODS This retrospective cohort study included 63 pancreas transplantation patients from January 2007 to May 2012 at our institution. The patients were divided into two groups: SPK and non-SPK transplantations. We excluded those patients who had transplants with vascular graft loss. The primary endpoint was 1-year and overall graft survival with consideration of multiple relevant variables. Non-parametric tests were calculated with the statistical package SPSS 20 (SPSS INC, Chicago, IL). RESULTS The 1-year and overall graft survival in this period was 87.3% and 82.5%, respectively. The median follow-up was 963 days. The causes of graft loss were vascular (64%) and immunologic (34%). Finally, we included 56 pancreas transplantations, 46 (82%) were SPK and 10 (18%) non-SPK. The donor and recipient characteristics were similar in both groups, except for the duration of DM (SPK 22 years vs. non-SPK 29 years) and recipient body mass index (SPK 23 vs. non-SPK 28); P = .042 and P = .003, respectively. The cold ischemia time was 563 minutes (standard deviation, 145). Bivariate analysis showed that long-term graft loss was only influenced by matching for gender (P = .023). Using the Kaplan-Meier method, the pancreas graft survival was better in SPK than in non-SPK transplants (log rank .038). CONCLUSIONS Patients who receive pancreas-alone or pancreas-after-kidney grafts have shorter long-term graft survival. Multiple strategies should be applied to improve immunologic surveillance and obtain an early diagnosis of graft rejection.
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Affiliation(s)
- M C Montiel-Casado
- Department of Digestive Surgery and Transplantation, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
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Stratta R, Rogers J, Orlando G, Farooq U, Al-Shraideh Y, Farney A. 5-Year Results of a Prospective, Randomized, Single-Center Study of Alemtuzumab Compared With Rabbit Antithymocyte Globulin Induction in Simultaneous Kidney–Pancreas Transplantation. Transplant Proc 2014; 46:1928-31. [DOI: 10.1016/j.transproceed.2014.05.080] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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van der Meulen T, Huising MO. Maturation of stem cell-derived beta-cells guided by the expression of urocortin 3. Rev Diabet Stud 2014; 11:115-32. [PMID: 25148370 DOI: 10.1900/rds.2014.11.115] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Type 1 diabetes (T1D) is a devastating disease precipitated by an autoimmune response directed at the insulin-producing beta-cells of the pancreas for which no cure exists. Stem cell-derived beta-cells show great promise for a cure as they have the potential to supply unlimited numbers of cells that could be derived from a patient's own cells, thus eliminating the need for immunosuppression. Current in vitro protocols for the differentiation of stem cell-derived beta-cells can successfully generate pancreatic endoderm cells. In diabetic rodents, such cells can differentiate further along the beta-cell lineage until they are eventually capable of restoring normoglycemia. While these observations demonstrate that stem cell-derived pancreatic endoderm has the potential to differentiate into mature, glucose-responsive beta-cells, the signals that direct differentiation and maturation from pancreatic endoderm onwards remain poorly understood. In this review, we analyze the sequence of events that culminates in the formation of beta-cells during embryonic development. and summarize how current protocols to generate beta-cells have sought to capitalize on this ontogenic template. We place particular emphasis on the current challenges and opportunities which occur in the later stages of beta-cell differentiation and maturation of transplantable stem cell-derived beta-cells. Another focus is on the question how the use of recently identified maturation markers such as urocortin 3 can be instrumental in guiding these efforts.
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Affiliation(s)
- Talitha van der Meulen
- The Salk Institute for Biological Studies, Clayton Laboratories for Peptide Biology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
| | - Mark O Huising
- The Salk Institute for Biological Studies, Clayton Laboratories for Peptide Biology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
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Jain M, Gupta S, Kaur S, Ponnusamy MP, Batra SK. Emerging trends for radioimmunotherapy in solid tumors. Cancer Biother Radiopharm 2013; 28:639-50. [PMID: 23844555 DOI: 10.1089/cbr.2013.1523] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed.
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Affiliation(s)
- Maneesh Jain
- 1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center , Omaha, Nebraska
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Abstract
PURPOSE OF REVIEW Antibody-mediated rejection (AMR) is acknowledged and defined in kidney transplantation, but where do we stand as far as pancreas transplantation is concerned? Here we appraise the most recent findings in pancreatic AMR and give suggestions for future research in the field by addressing currently unresolved issues. RECENT FINDINGS Five main topics are discussed: chronological assessment of all literature on biopsy-proven pancreatic AMR; role of C4d and recent development in other markers; the use of sentinel organs, such as kidney biopsies and duodenal patch biopsies for diagnosis of pancreatic AMR; studies addressing islet pathology and its relevance in AMR; and protocol and follow-up pancreas biopsy practice in relation to pancreas transplant management and survival. SUMMARY Antibody-mediated processes play a role in pancreas transplantation. However, sensitive markers, pathophysiological understanding, and adequate interventions have not yet been established. Much data are still lacking and we believe that studying protocol and follow-up biopsies along with serial donor-specific antibody data may improve pancreas transplant patient management and outcomes.
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Distinctive morphological features of antibody-mediated and T-cell-mediated acute rejection in pancreas allograft biopsies. Curr Opin Organ Transplant 2012; 17:93-9. [DOI: 10.1097/mot.0b013e32834ee754] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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