Randomized Controlled Trial
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World J Diabetes. Dec 15, 2014; 5(6): 951-961
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.951
Pancreas transplantation: The Wake Forest experience in the new millennium
Jeffrey Rogers, Alan C Farney, Giuseppe Orlando, Samy S Iskandar, William Doares, Michael D Gautreaux, Scott Kaczmorski, Amber Reeves-Daniel, Amudha Palanisamy, Robert J Stratta
Jeffrey Rogers, Alan C Farney, Giuseppe Orlando, Michael D Gautreaux, Robert J Stratta, Department of General Surgery, Wake Forest Baptist Medical Center, Winston Salem, NC 27157, United States
Samy S Iskandar, Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, United States
William Doares, Scott Kaczmorski, Department of Pharmacy, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, United States
Amber Reeves-Daniel, Amudha Palanisamy, Department of Internal Medicine (Nephrology), Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, United States
Author contributions: Rogers J, Farney AC, Orlando G and Stratta RJ contributed equally to this work, including study design, data analysis and writing the manuscript; Iskandar SS, Doares W, Gautreaux MD, Kaczmorski S, Reeves-Daniel A and Palanisamy A provided critical review and revisions of the manuscript.
Correspondence to: Robert J Stratta, MD, Department of General Surgery, Wake Forest Baptist Medical Center, Medical Center Blvd., Winston Salem, NC 27157, United States. rstratta@wakehealth.edu
Telephone: +1-336-7160548 Fax: +1-336-7135055
Received: April 23, 2014
Revised: October 31, 2014
Accepted: November 7, 2014
Published online: December 15, 2014
Processing time: 234 Days and 15.7 Hours
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.

Keywords: Alemtuzumab; Mycophenolate mofetil; Pancreas transplantation; Portal-enteric; Rabbit anti-thymocyte globulin; Simultaneous kidney-pancreas transplantation; Solitary pancreas transplantation; Steroid elimination; Surveillance biopsy; Tacrolimus

Core tip: Vascularized pancreas transplantation is able to establish a chronic insulin-free state characterized by normoglycemia. In selected recipients with insulin-requiring diabetes, simultaneous kidney-pancreas transplantation has become acknowledged as a favored alternative to kidney alone transplantation because of more intense glucose control, enhanced quality of life and improved long-term survival. The evolution in surgical technique, current patient management strategies, and biopsy directed immunosuppression have resulted in excellent outcomes, even in populations previously considered high risk, such as African-American recipients, patients with a “type 2 diabetes” phenotype and solitary pancreas transplants recipients.