Retroperitoneal pancreas transplantation with portal-enteric drainage

Retroperitoneal Pancreas Transplantation With Portal-Enteric Drainage U. Boggi, F. Vistoli, M. Del Chiaro, S. Signori, P. Marchetti, A. Coppelli, R. Giannarelli, G. Rizzo, and F. Mosca ABSTRACT Background. Portal-enteric drainage (PED) is the latest refinement in the surgical technique for pancreas transplantation (PTx). We herein describe the results of a modified technique for PED that places the pancreas in a totally retroperitoneal position. Methods. Between April 2001 and June 2003, 79 PTx were performed using a retroperitoneal PED technique. Results. No graft was lost due to surgical complications and the relaparotomy rate was 11.4%. Mean hospital stay averaged 25.9 days (⫾14.4 days) with a 30-day redamission rate of 12.7%. One graft was lost due to delayed (6 months) arterial thrombosis and three to acute rejection. The overall 1-year patient and graft survivals were 98.7% and 93.7%, respectively. Conclusions. Our data confirm that PED of pancreas grafts is associated with low morbidity and mortality rates. Whether retroperitoneal graft placement has actual advantages over the “classical” intraperitoneal position remains to be ascertained.

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ancreas transplantation is the most effective treatment option to routinely and consistently obtain tight glucose control and correct abnormal metabolism in diabetic patients who require a kidney transplantation or fail other avenues of intensive insulin therapy.1 Refinements in surgical technique2–5 and advances in immunosuppression as well as prophylaxis for either thromobosis or infection5–7 are the main reasons for the current success of pancreas transplantation. Although systemic venous bladder drainage of whole pancreaticoduodenal grafts is safe,2 the technique is clearly nonphysiological, being associated with metabolic and urologic complications8,9 and producing peripheral hyperinsulinemia.10 Primary enteric drainage of pancreatic secretions associated with systemic venous effluent (systemic-enteric) does not increase the surgical risk but avoids the metabolic and urologic complications.3,11 To improve the physiology of pancreas transplantation in 1992 Shokouh-Amiri et al described a new technique,12 further popularized by Gaber et al4 and Stratta et al,13 coupling primary enteric drainage with portal venous insulin delivery (portal-enteric drainage). The advantages of portal insulin delivery include avoidance of systemic hyperinsulinemia,14 improvement of lipoprotein composition,15 and, possibly, reduction of rejec© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 36, 571–574 (2004)

tion rates.16 –18 However, portal venous drainage is probably more technically demanding than systemic efflux, and enteric drainage necessarily precludes the use of urinary amylase concentration as a marker for pancreas rejection. We herein present our experience with PED of pancreas grafts. Different from all the other techniques described to date, the transplant procedure was performed via a transperitoneal approach with the pancreas placed into a fully retroperitoneal position. MATERIALS AND METHODS Between April 2001 and June 2003, the technique of PED was used to transplant 79 pancreata. In most instances the pancreas was transplanted simultaneously with a kidney procured from either the From the Divisione di Chirurgia Generale e Trapianti (U.B., F.V., M.D.C., S.S., F.M.) and Divisione di Diabetologia (P.M., A.C., R.G.), Universita` di Pisa, Pisa, Italy, and Unita´ Operativa Nefrologia e Trapianti (G.R.), Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. This work was supported by a grant from ARPA Foundation (www.fondazionearpa.it). Address reprint requests to Franco Mosca, MD, FACS, FRCSEd, Head, Divisione di Chirurgia Generale e Trapianti, Universita` di Pisa, Ospedale di Cisanello, via Paradisa 2, 56124, Pisa, Italy. 0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.02.033 571

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same cadaveric donor (n ⫽ 33; 41.8%) or a living donor (n ⫽ 17; 21.5%). Among the remaining 29 patients the pancreas was transplanted alone (n ⫽ 27; 34.2%) or after a successful kidney transplant (n ⫽ 2; 2.5%).

Donor Selection and Graft Procurement All cadaveric donors were aged less than 55 years, without a history of diabetes, pancreas trauma, or chronic pancreatic disease. ABO compatibility was mandatory while HLA matching was not regarded as a donor acceptance criterion, although the best HLA matching was considered at the time of graft allocation. The final decision to accept a pancreas was based on the gross appearance of the graft and the vessels and on the quality of visceral perfusion. The pancreata were procured en bloc with liver and kidneys and separated on the back table, as described previously.19

Transplant Technique Through a midline laparotomy, the right colon was fully mobilized and the superior mesenteric vein and its main tributary branches were dissected in the root of mesentery. The common iliac artery was encircled. The venous anastomosis was performed end-to-side between donor portal vein and recipent superior mesenteric vein. No venous extension graft was employed. Next, an arterial anastomosis was constructed end-to-side between the Y-graft and the recipient common iliac artery (Fig 1). Enteric drainage was accomplished through a Roux-en-Y jejunal limb brought to the right flank region through an opening in the right colon mesentery. The duodenojejunostomy was performed side-to-side by means of a hand-sewn, double-layered anastomosis. At the end of transplant procedure closed suction drains were placed around the pancreas. The colon was returned to its original position, thus completely covering the pancreas and making it a totally retroperitoneal organ.

Definition of Graft Function Primary endocrine pancreas nonfunction was defined as the absence of any metabolic improvement with constant insulin requirements. Delayed endocrine pancreas function was defined as a total insulin requirement of ⬎30 U between post-Tx days 5 and 10 and/or ⬎15 U between days 11 and 15, irrespective of the insulin dose administered during the first 5 days after Tx.20

Immunosuppression Immunosuppression consisted of a quadruple regimen including induction with either basiliximab (n ⫽ 76; 96.2%), namely 20 mg before graft reperfusion and on posttransplant day 4, or ATG (n ⫽ 3; 3.8%) namely 1 mg/kg for 7 to 10 days. The maintenance therapy included low-dose steroids, tacrolimus (n ⫽ 63; 79.7%) targeting trough levels 12 to 15 ng/mL in the first 2 posttransplant weeks or cyclosporine (n ⫽ 16; 20.3%) targeting trough levels of 200 to 250 ng/mL in the first 2 posttransplant weeks and mycophenolate mofetil (2 g/daily).

Graft Survival and Statistical Analysis Graft loss was determined when the patient required exogenous insulin to remain euglycemic or upon death. Survival estimates were calculated using the Kaplan-Meier method.

RESULTS

The study group included 38 men and 41 women of mean age 38.9 years (⫾7.9 years) and mean pretransplant diabe-

Fig 1. Retroperitoneal pancreas transplantation with portalenteric drainage.

tes duration of 24.0 years (⫾8.3 years). The mean pretransplant total insulin dose was 42.3 U/d. Two patients (2.5%) had undergone prior kidney transplantation (PAK) while 50 (63.3%) simultaneously received a pancreas and a kidney donated from either the same cadaveric donor (SPK) (n ⫽ 33; 41.8%) or from a cadaveric and a living donor, respectively (SPLK) (n ⫽ 17; 21.5%). The remaining 27 patients underwent pancreas transplantation alone (PTA) (34.2%), including 24 patients (48.0%) who were not yet on dialysis at the time of transplantation. The remaining 26 recipients (52.0%) (22 hemodialysis, four peritoneal dialysis) had a mean pretransplant dialysis duration of 17.5 months. Mean cold and warm ischemia times of the pancreas were 11.3 hours (⫾2.0 hours) and 36.4 minutes (⫾6.2 minutes), respectively. No primary pancreas nonfunction occurred but one patient (1.3%) developed delayed endocrine graft function. All ten patients (12.7%) diagnosed with peripancreatic fluid collections were successfully treated by watchful waiting (n ⫽ 6), percutaneous catheter drainage (n ⫽ 3), or a formal surgical approach (n ⫽ 1). Nine recipients required secondlook surgery, because of bleeding (n ⫽ 3), small bowel occlusion due to bezoar (n ⫽ 1), negative relaparotomy for

PORTAL-ENTERIC DRAINAGE

suspected visceral perforation (n ⫽ 1), and allograft pancreatectomy due to acute rejection (n ⫽ 3) or arterial thrombosis (n ⫽ 1). Overall, the relaparotomy rate was 11.4% (nine relaparotomies in nine recipients out of 79 transplants). Relaparotomy rate was 6.1% for SPKT, 17.6% for SPLK, 14.8% for PTA, and 0% for PAK. Overall, the hospital stay averaged 25.9 days (⫾14.4 days) with a 30-day readmission rate of 12.7%. Equivalent figures for each transplant category were 27.9 days (⫾15.6 days) and 6.1% for SPK, 30.2 days (⫾17.8 days) and 11.8% for SPLK, 21.1 days (⫾9.2 days) and 18.5% for PTA, and 23.5 days (⫾6.4 days) and 50.0% for PAK. Overall, the pancreas rejection rate was 6.3%. The five rejection episodes were diagnosed in recipients of solitary pancreas grafts (SPLK, PTA, and PAK) included 1 (1.3%) that was steroid-resistant. One patient died suddenly with a functioning pancreas and kidney. One pancreas was lost to arterial thrombosis, one to chronic rejection, and three to acute rejection. No graft was lost to portal thrombosis but three partial venous thromboses were rescued by intravenous heparin infusion. The overall 1-year patient and pancreas survival rates were 98.7% and 93.7%, respectively. Equivalent figures for each transplant category were: 97.0% and 97.0% for SPK, 100% and 94.1% for SPLK, 100% and 88.9% for PTA, and 100% and 100% for PAK. DISCUSSION

The history of pancreas transplantation has been marked by refinements in both surgical technique and immunosuppressive regimens. Bladder drainage of whole pancreaticoduodenal grafts is safe and sterile, permits graft monitoring through urinary amylase assay and cystoscopic biopsy, and facilitates resolution of anastomotic problems with catheter drainage.21 However, this technique, although well tolerated by the majority of patients, is clearly nonphysiological and is associated with unique metabolic and urologic complications.8,9 When complications of bladder drainage are severe, conversion from bladder to enteric drainage is the preferred therapeutic option.22 Because of this favorable experience, primary enteric drainage is currently performed at a growing number of transplant centers. Accordingly, 71% of SPK, 53% of PAK, and 38% of PTA performed in the United States between 1999 and 2001 were drained primarily into the gut.23 Portal-enteric drainage is the ultimate refinement of the pancreas transplantation technique. Although several techniques have been described between 1984 and 1992,24 –26 most centers currently adopt the technique popularized by Gaber and associates4 or one of its modifications.27 The new method neither increased the surgical risk nor jeopardized patient and graft survival when compared to either systemic-bladder drainage27–30 or systemic-enteric drainage.31 All these series, however, refer to intraperitoneal pancreas transplants with portal-enteric drainage.4,27–31 In our series, a transperitoneal approach was employed to gain

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simultaneous access to the superior mesenteric vein, right common iliac artery, and proximal jejunum with the graft left in the retroperitoneal space. Although the pancreas is not placed in an orthotopic position, it is made retroperitoneal by being placed behind the right colon. Since the pancreas is a retroperitoneal organ, this modification should further improve the physiologic behavior of the transplant. Without a control group we were not able to show any benefit of this method as compared with intraperitoneal graft placement. However, our results favorably compare with earlier series of portal-enteric drainage.4,13,27–31 Surgical complications, as witnessed by the rather low relaparotomy rate, were not increased by this approach. Only one graft was lost to late arterial thrombosis and no allograft pancreatectomy had to be performed due to venous thrombosis. Whether presentation of antigens to the host through the portal vein confers an immunologic advantage, surpassing that achieved with current immunosuppressive regimens, remains to be determined.13 However, in our experience, the rate of pancreas rejection episodes was exceptionally low with only three grafts lost to acute rejection. The meaning of this finding, at least in our view, is reinforced by the good results achieved with solitary and isolated pancreas transplantation. We conclude that beyond any metabolic or immunological consideration, portal-enteric drainage of pancreas grafts is safe and associated with good short-term results. Retroperitoneal graft placement, as described herein, further improves our ability to reproduce the physiology of the “normal” pancreas. Whether this approach carries actual advantages over intraperitoneal graft placement, however, remains to be determined.

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574 9. Sollinger HW, Messing EM, Eckhoff DE, et al: Urological complications in 210 consecutive simultaneous pancreas-kidney transplants with bladder drainage. Ann Surg 218:561, 1993 10. Matte J, Fery F, Lankoande C, et al: Insulin secretion and glucose tolerance evolution in kidney-pancreas graft. Transplant Proc 27:3073, 1995 11. Kuo PC, Johnson LB, Schweitzer EJ, et al: Simultaneous pancreas/kidney transplantation—a comparison of enteric and bladder drainage of exocrine pancreatic secretions. Transplantation 63:238, 1997 12. Shokouh-Amiri MH, Gaber AO, Gaber LW, et al: Pancreas transplantation with portal venous drainage and enteric exocrine diversion: a new technique. Transplant Proc 24:776, 1992 13. Stratta RJ, Gaber AO, Shokouh-Amiri MH, et al: Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction. Ann Surg 229:701, 1999 14. Gaber AO, Shokouh-Amiri H, Hathaway DK, et al: Pancreas transplantation with portal venous and enteric drainage eliminates hyperinsulinemia and reduces post-operative complications. Transplant Proc 25:1176, 1993 15. Hughes TA, Gaber AO, Amiri HS, et al: Kidney-pancreas transplantation. The effect of portal versus systemic venous drainage of the pancreas on the lipoprotein composition. Transplantation 60:1406, 1995 16. Lo A, Buell JF, Thistlehwaite JR, et al: Clinical experience with 114 portal-enteric drained simultaneous pancreas-kidney transplants. Acta Chir Austriaca 33:4, 2001 17. Troppmann C, Cecka M, McVicar J, et al: Does portal venous drainage of the pancreas graft in simultaneous pancreaskidney transplant confer an immunologic advantage? Acta Chir Austriaca 33:3, 2001 18. Philosophe B, Farney AC, Schweitzer EJ, et al: Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study. Ann Surg 234:689, 2001 19. Boggi U, Vistoli F, Del Chiaro M, et al: Pancreas procurement from cadaveric donors of multiple grafts: In Farinon A (ed): Advances in Abdominal Surgery. The Netherlands: Kluwer Academic Publisher; 2002, p. 359

BOGGI, VISTOLI, DEL CHIARO ET AL 20. Troppmann C, Gruessner AC, Papalios BE, et al: Delayed endocrine pancreas graft function after simultaneous pancreaskidney transplantation. Incidence, risk factors and impact on long term outcome. Transplantation 61:1323, 1996 21. Sollinger HW, Odorico JS, Knetchtle SJ, et al: Experience with 500 simultaneous pancreas-kidney transplants. Ann Surg 228:284, 1998 22. Sindhi R, Stratta RJ, Lowell JA, et al: Experience with enteric conversion after pancreas transplantation with bladder drainage. J Am Coll Surg 184:281, 1997 23. International Pancreas Transplant Registry Newsletter. August 31, 2000; Volume 12, Number 1 24. Calne RY: Paratopic segmental pancreas grafting: a technique with portal venous drainage. Lancet 1:595, 1984 25. Muhlbacher F, Gnant MF, Auinger M, et al: Pancreatic venous drainage to the portal vein: a new method in pancreas transplantation. Transplant Proc 22:636, 1990 26. Rosenlof LK, Earnhardt RC, Pruett TL, et al: Pancreas transplantation: a initial experience with systemic and portal drainage of pancreas allografts. Ann Surg 215:586, 1992 27. Newell KA, Bruce DS, Cronin DC, et al: Comparison of pancreas transplantation with portal venous and enteric exocrine drainage to the standard technique utilizing bladder drainage of exocrine secretions. Transplantation 62:1353, 1996 28. Gaber AO, Shokouh-Amiri MH, Hathaway DK, et al: Results of pancreas transplantation with portal venous and enteric drainage. Ann Surg 221:613, 1995 29. Stratta RJ, Gaber AO, Shokouh-Amiri MH, et al: A prospective comparison of systemic-bladder versus portal-enteric drainage in vascularized pancreas transplantation. Surgery 127:217, 2000 30. Cattral MS, Bigam DL, Hemming AW, et al: Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts. Clinical outcome of 40 consecutive transplant recipients. Ann Surg 232:688, 2000 31. Stratta RJ, Shokouh-Amiri MH, Egidi MF, et al: A prospective comparison of simultaneous kidney-pancreas transplantation with systemic-enteric versus portal-enteric drainage. Ann Surg 233:740, 2001