Michelle L. Goble

The case for pancreas after kidney transplantation

Abstract:  Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti‐thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One‐yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus‐based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

Immediate Retransplantation for Pancreas Allograft Thrombosis

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1–16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin‐induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76–1137 days (mean 572 days). One‐year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first‐time pancreas transplantation.

Early reexploration for suspected thrombosis after pancreas transplantation

Background. Graft thrombosis is the most common cause of early graft loss after pancreas transplantation. Early reexploration may permit salvage or timely removal of the thrombosed graft. Methods. This was a retrospective review of 345 pancreas transplants performed at a single center between January 2003 and December 2009. Early reexploration was defined as within 1 week of pancreas transplantation. Results. Of the 345 transplants, there were 35 early reexplorations. The graft was compromised in 20 cases (57%): 10 venous thromboses, 3 arterial thromboses, 2 combined arterial and venous thrombosis, 2 thromboses secondary to allograft pancreatitis, and 3 cases of positional ischemia without thrombosis. Of these allografts, three reperfused once repositioned and six were successfully thrombectomized for a graft salvage rate of 45%. One of the thrombectomized grafts remained perfused but never functioned and was removed at retransplantation. The 10 remaining compromised grafts that were deemed unsalvageable and required allograft pancreatectomy. Nine of these recipients were retransplanted (eight within 2 weeks) and one was not a retransplantation candidate. Conclusions. Reexploration for suspected graft thrombosis after pancreas transplantation resulted in a negative laparotomy rate of 43%, but permitted graft salvage in 45% of compromised grafts.

No Difference in Transplant Outcomes for Local and Import Pancreas Allografts

Background. In the United States, pancreas allograft allocation is strictly regulated. Local centers have the first option to accept an organ, followed by regional and national allocation for those not accepted locally. For a pancreas to be imported, many centers must have previously rejected the organ for transplantation. This study reviews the outcomes of all pancreas allografts transplanted at a single center between January 2003 and November 2007. Early graft function and graft survival were stratified by geographic source of the donor pancreas. Methods. The records of 247 pancreas recipients and the donors of 11 imported and discarded pancreas allografts were reviewed. Pancreas allograft survival is represented using a Kaplan-Meier survival curve comparing (1) locally procured and imported pancreas grafts and (2) grafts procured by a team from our own center with the grafts procured by another team. Results. Of the 247 grafts, 184 (74%) were local and 63 (26%) were imported. There were no differences between the two geographic groups in 1-year graft survival (local 91%, import 90%, P=0.76). Similarly, graft survival was similar regardless of whether the organ was procured by our own team or by another center (local team 91%, another team 90%, P=0.96). Conclusions. Pancreas allografts refused by a large number of centers may still be imported and successfully transplanted without affecting survival results.

Impact of recipient age on whole organ pancreas transplantation

The goal of this study was to assess the impact of recipient age on post‐transplant outcome.

Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center.

Fridell JA, Johnson MS, Goggins WC, Beduschi T, Mujtaba MA, Goble ML, Powelson JA. Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center. 
Clin Transplant 2012: 26: 164–172. 
© 2011 John Wiley & Sons A/S.

Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation

Fridell JA, Mangus RS, Taber TE, Goble ML, Milgrom ML, Good J, Vetor R, Powelson JA. Growth of a nation part II: impact of recipient obesity on whole‐organ pancreas transplantation.
Clin Transplant 2011: 25: E366–E374.

Growth of a nation part I: impact of organ donor obesity on whole-organ pancreas transplantation

Fridell JA, Mangus RS, Taber TE, Goble ML, Milgrom ML, Good J, Vetor R, Powelson JA. Growth of a nation part I: impact of organ donor obesity on whole‐organ pancreas transplantation.
Clin Transplant 2011: 25: E225–E232.

Allograft Pancreatectomy: Indications and Outcomes.

This study evaluated the indications, surgical techniques, and outcomes of allograft pancreatectomy based on a single center experience. Between 2003 and 2013, 47 patients developed pancreas allograft failure, excluding mortality with a functioning pancreas allograft. Early graft loss (within 14 days) occurred in 16, and late graft loss in 31. All patients with early graft loss eventually required allograft pancreatectomy. Nineteen of 31 patients (61%) with late graft loss underwent allograft pancreatectomy. The main indication for early allograft pancreatectomy included vascular thrombosis with or without severe pancreatitis, whereas one recipient required urgent allograft pancreatectomy for gastrointestinal hemorrhage secondary to an arterioenteric fistula. In cases of late allograft pancreatectomy, graft failure with clinical symptoms such as abdominal discomfort, pain, and nausea were the main indications (13/19 [68%]), simultaneous retransplantation without clinical symptoms in 3 (16%), and vascular catastrophes including pseudoaneurysm and enteric arterial fistula in 3 (16%). Postoperative morbidity included one case each of pulmonary embolism leading to mortality, formation of pseudoaneurysm requiring placement of covered stent, and postoperative bleeding requiring relaparotomy eventually leading to femoro‐femoral bypass surgery 2 years after allograftectomy. Allograft pancreatectomy can be performed safely, does not preclude subsequent retransplantation, and may be lifesaving in certain instances.

Conversion From Tacrolimus to Belatacept to Prevent the Progression of Chronic Kidney Disease in Pancreas Transplantation: Case Report of Two Patients

Belatacept is a novel immunosuppressive agent that may be used as an alternative to calcineurin inhibitors (CNI) in immunosuppression (IS) regimens. We report two cases of pancreas transplant that were switched from tacrolimus (TAC) to belatacept. Case 1: 38‐year‐old female with pancreas transplant alone maintained on TAC‐based IS regimen whose serum creatinine (SCr) slowly deteriorated from 0.6 mg/dL at baseline to 2.2 mg/dL, 16 months posttransplant. A native kidney biopsy performed showed CNI toxicity. The patient was started on belatacept and TAC was eliminated. Case 2: 49‐year‐old female with simultaneous pancreas–kidney transplant, maintained on TAC‐based regimen where the SCr worsened over an initial 3‐month period from a baseline of 1.0 to 3.0 mg/dL. Belatacept was started and TAC was lowered. Due to persistent graft dysfunction and kidney transplant biopsy still showing changes consistent with CNI toxicity, the TAC was then discontinued. At >1 year postbelatacept and off TAC follow‐up, kidney function as measured by SCr remains stable at 1.0 ± 0.2 mg/dL in both recipients. Neither patient developed rejection following the switch, and pancreas allograft function remains stable in both recipients.