Nine-year experience with 126 pancreas transplants with portal-enteric drainage

Nine-Year Experience With 126 Pancreas Transplants With Portal-Enteric Drainage R.J. Stratta, A.O. Gaber, M.H. Shokouh-Amiri, M.F. Egidi, H.P. Grewal, A.T. Kizilisik, R.R. Alloway, D.K. Hathaway, and L.W. Gaber

T

HE HISTORY OF clinical pancreas transplantation (PTX) largely revolves around the development and application of various surgical techniques. According to United Network for Organ Sharing (UNOS) Registry data, and most PTXs are performed with systemic venous delivery of insulin and either bladder or enteric drainage of the exocrine secretions.1 To further improve the physiology of PTX and to avoid the potential complications of systemic hyperinsulinemia (such as dyslipidemia and accelerated atherosclerosis), a new surgical technique was developed at our center, using portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric [P-E]).2 Herein we chronicle a 9-year single-center experience with 126 PTXs with P-E drainage. METHODS The University of Tennessee (UT), Memphis, PTX Program began in 1989.3 Between 4/89 and 9/90, 24 simultaneous kidney-PTXs (SKPTs) were performed with systemic-bladder (S-B) drainage. The first SKPT with P-E drainage was performed in October 1990, and this patient continues to enjoy excellent dual allograft function nearly 10 years later. Also in 1990, the first solitary PTXs were performed at our program, including both sequential pancreas after kidney transplant (PAKT) and PTX alone (PTA). From 10/90 to 12/94, we performed 42 SKPTs, including 26 with P-E and 16 with S-B drainage, and 18 solitary PTXs with S-B drainage. From 1/95 to 2/97, 46 PTXs (31 SKPT, 9 PAKT, 6 PTA) were performed exclusively with P-E drainage. From 3/97 to 3/98, 35 PTXs (25 SKPT, 3 PAKT, 7 PTA) were prospectively allocated to S-B (n ⫽ 18) versus P-E (n ⫽ 17) drainage.4 From 4/98 to 12/99, 66 PTXs were allocated to systemic-enteric (21 SKPT, 8 solitary PTX) or P-E (22 SKPT, 15 solitary PTX) drainage. Our overall experience accumulated over 10.5 years consists of 231 PTXs (163 SKPT, 39 PA, 29 PAKT) including 126 with P-E drainage (90 SKPT, 18 PTA, 18 PAKT). The surgical technique of P-E drainage has been previously described in detail. From October 1990 to June 1995, immunosuppression at our center consisted of quadruple therapy with OKT3 induction in combination with cyclosporine (Sandimmune), prednisone, and azathioprine (era 1).3 From 7/95 to 5/98, we switched to tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone without antibody induction (era 2).5 From 6/98 to 12/99, maintenance immunosuppression remained TAC, MMF, and prednisone but patients were randomized to receive either basiliximab or daclizumab induction therapy (era 3). © 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

RESULTS

The P-E group included 69 male and 57 female patients with a mean age of 39 years (Table 1). Thirty patients underwent SKPT in era 1 and were compared to 42 SKPTs performed in era 2 and 18 in era 3. We also compared 23 solitary PTXs (11 PAKT, 12 PTA) performed in era 2 with 13 (7 PAKT, 6 PTA) performed in era 3. One-year patient survival rates after SKPT were 77% in era 1, 93% in era 2, and 100% in era 3 (P ⫽ 0.06). The 1-year kidney graft survival rates were 77% in era 1, 93% in era 2, and 94% in era 3 (P ⫽ .06). The 1-year pancreas graft survival rates after SKPT were 60% in era 2, 83% in era 2, and 83% in era 3 (P ⫽ .02). The incidences of rejection, major infection, thrombosis, and relaparotomy were all decreased in eras 2 and 3 (Table 1). The 1-year patient survival rates after solitary PTX were both 100% in eras 2 and 3, while the corresponding pancreas graft survival rates were 61% and 69%, respectively. The incidences of acute rejection, major infection, thrombosis, and relaparotomy after solitary PTX were all slightly improved in era 3 compared to era 2 (Table 1). DISCUSSION

With an evolution in surgical techniques, an increasing number of PTXs are performed with enteric drainage (about 60% of cases in 1999). The proportion of cases with enteric exocrine drainage coupled with portal venous delivery of insulin has remained low and represents only 15% to 20% of enteric-drained PTXs.1 In the most recent Registry analysis including PTXs performed between 1996 and 1999, the 1-year pancreas graft survival rates were similar for P-E versus systemic-enteric drainage, 83% and 84%, respectively.1 We have previously reported our initial experience with P-E drainage, including both retrospective and prospective From the Departments of Surgery (R.J.S., A.O.G., M.H.S.-A., H.P.G., A.T.K., D.K.H.), Medicine (M.F.E.), Pharmacy (R.R.A.), and Pathology (L.W.G.), University of Tennessee-Memphis, Memphis, Tennessee. Address reprint requests to Dr R.J. Stratta, Department of Surgery, University of Tennessee-Memphis, 956 Court Avenue, Suite A202, Memphis, TN 38163. 0041-1345/01/$–see front matter PII S0041-1345(00)02641-5 1687

Transplantation Proceedings, 33, 1687–1688 (2001)

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STRATTA, GABER, SHOKOUH-AMIRI ET AL Table 1. Demographic and Transplant Characteristics and Results Group Characteristics (n ⫽ 126)

Age (years) Gender Female Male Race Caucasian African-American Years of diabetes Transplant type SKPT PAKT PTA Prior PTX HLA match: ABDR Pancreas cold ischemia (hours) Mean (range)

Era 1 (n ⫽ 30)

Era 2 (n ⫽ 42)

Era 3 (n ⫽ 18)

39 (19 –56) 57 (45%) 69 (55%) 111 (88%) 15 (12%) 24 (8 –50) 90 (72%) 18 (14%) 18 (14%) 13 (10%) 1.4 (0 –5) 13 (6 –23)

Results: SKPT 1-year survival Patient Kidney Pancreas Acute rejection Major infection Thrombosis Relaparotomy

23 (77%) 23 (77%) 18 (60%) 19 (63%) 18 (60%) 6 (20%) 14 (47%)

Results: Solitary PTX*** PAKT PA 1-year survival Patient Pancreas Acute rejection Major infection Thrombosis Relaparotomy

39 (93%) 39 (93%) 35 (83%) 14 (33%) 18 (43%) 3 (7%) 13 (31%)

18 (100%)* 17 (94%)* 15 (83%)** 7 (39%)** 8 (44%) 1 (6%)** 6 (33%)

n ⫽ 23 11 (48%) 12 (52%)

n ⫽ 13 7 (54%) 6 (46%)

23 (100%) 14 (61%) 13 (57%) 8 (35%) 5 (22%) 10 (43%)

13 (100%) 9 (69%) 5 (38%) 4 (31%) 2 (15%) 5 (38%)

*P ⬍ .06. **P ⫽ .05. ***P ⫽ NS.

comparisons to control groups of patients who underwent SKPT with S-B drainage.2– 4 The present study reports the chronology of our experience with P-E drainage spanning different immunosuppressive eras. This overall experience demonstrates that SKPT and solitary PTX with P-E drainage can be performed with improving outcomes. Increasing experience with the P-E technique coupled with advances in immunosuppression are associated with: (1) increasing patient, kidney, and pancreas graft survival rates; (2) less medical morbidity with a decreasing incidence of acute rejection and major infection; and (3) reduced surgical complications including decreasing rates of thrombosis and relaparotomy. The P-E technique does not appear to incur any additional or unique risks and can be performed with results comparable to the other standard techniques of PTX. We believe that this technique should be included in the repertoire of PTX,

because it offers potential physiologic, metabolic, and immunologic advantages over the other techniques currently available.

REFERENCES 1. Gruessner AC, Sutherland DER: in Cecka JM, Terasaki PI (eds): Clinical Transplants 1999. Los Angeles, Calif: UCLA Immunogenetics Center; 2000, p 51 2. Gaber AO, Shokouh-Amiri MH, Hathaway DK, et al: Ann Surg 221:613, 1995 3. Stratta RJ, Gaber AO, Shoukouh-Amiri MH, et al: in Cecka JM, Terasaki PI (eds): Clinical Transplants 1998. Los Angeles, Calif: UCLA Tissue Typing Laboratory; 1999, p 239 4. Stratta RJ, Gaber AO, Shokouh-Amiri MH, et al: Surgery 127:217, 2000 5. Stratta RJ, Gaber AO, Shokouh-Amiri MH, et al: Ann Surg 229:701, 1999