Robert J. Stratta, M.D., M. Hosein Shokouh-Amiri, M.D., Hani P. Grewal, M.D., A. Osama Gaber, M.D.
Department of Surgery (Division of Transplantation)
University of Tennessee Memphis
ALI: Anti-lymphocyte Induction
ATN: Acute Tubular Necrosis
ESRD: End Stage Renal Disease
HIV: Human Immunodeficiency Virus
HLA: Human Leukocyte Antigen
IPTR: International Pancreas Transplant Registry
KTA: Kidney Transplant Alone
MMF: Mycophenolate Mofetil
PA: Pancreas Alone
PAKT: Pancreas After Kidney Transplant
PRA: Panel Reactive Antibody
PTX: Pancreas Transplant
SKPT: Simultaneous Kidney-Pancreas Transplant
UNOS: United Network for Organ Sharing
UT: University of Tennessee
We gratefully acknowledge the expertise of Joyce Lariviere in preparation of the manuscript.
Vascularized pancreas transplantation (PTX) was first developed as a means to reestablish endogenous insulin secretion responsive to normal feedback controls. From 1966 through July 2000, over 14 000 PTXs were performed worldwide and reported to the International Pancreas Transplant Registry (IPTR).1 According to IPTR data, most PTXs are performed with systemic venous delivery of insulin and either bladder (systemic-bladder [S-B] or systemic-enteric [S-E]) drainage of the exocrine secretions.2 From 1988 through 1995, more than 90% of PTX procedures were performed by the standard technique of S-B drainage using a duodenal segment conduit. Although well tolerated in most PTX recipients, S-B drainage was associated with a finite and troublesome rate of unique metabolic and urologic complications resulting from altered physiology. When these complications became persistent or refractory, conversion from bladder to enteric drainage (enteric conversion) was often necessary and successful.3 Because of a favorable experience with enteric conversion, coupled with advances in preservation, donor selection, and immunosuppression that placed the duodenal segment at a lower risk for ischemic or immunologic injury, a resurgence of interest occurred in primary enteric drainage in an effort to avoid the complications of bladder drainage.
Since 1995, the number of PTX procedures performed with primary enteric drainage has steadily increased, accounting for 60% of cases in 1999.1 In the last few years, the results of simultaneous kidney-PTX (SKPT) with enteric drainage have improved and are now comparable to SKPT with bladder drainage.2 Despite an evolution in surgical techniques, the majority of PTXs with enteric drainage are performed with systemic venous delivery of insulin, resulting in peripheral hyperinsulinemia. In the non-transplant setting, chronic hyperinsulinemia has been associated with insulin resistance, dyslipidemia, accelerated atherosclerosis, and macroangiopathy. To improve the physiology of PTX, a new surgical technique was developed, combining portal venous delivery of insulin with enteric drainage of the exocrine secretions (portal-enteric [P-E]).4-6 In a recent survey of surgical techniques among PTX centers, seven reported experience with the P-E technique, of which five used a diverting Roux limb.7 Table 1 provides a list of centers that have reported experience in PTX with P-E drainage. Many of these centers have adopted the P-E technique as their preferred method of PTX. However, the proportion of cases with P-E drainage has remained low and represents only 15-20% of enteric-drained PTXs.1,2 In the most recent IPTR analysis including PTXs performed between 1996-1999, the one-year pancreas graft survival rates were similar for SKPT with either P-E or S-E drainage, 83% and 84%, respectively.
The history of clinical PTX largely revolves around the development and application of various surgical techniques. Experience in PTX with portal venous delivery of insulin dates back to the mid-1980s. Initial attempts employed segmental PTX with either gastric (Calne 1984),8 pyelic (Gil-Vernet 1985),9 or jejunal (Tyden 1985,10 Sutherland 1987)11 drainage. Whole organ PTX using the P-E technique was first described clinically by our group in 19924 and was based on experimental work by Shokouh-Amiri et al. in a porcine model.12-14 This new technique employed a tributary of the superior mesenteric vein to reestablish portal venous drainage and differed substantially from other initial reports of whole organ PTX with portal venous drainage. In 1990, Muhlbacher et al. described a whole organ technique involving an end-to-side anastomosis between the distal splenic vein of the donor and the recipient’s portal vein in combination with bladder drainage.15 In 1992, Rosenlof et al. applied Calne’s original technique to whole organ PTX using an end-to-side anastomosis between the donor portal vein and the recipient’s splenic vein coupled with enteric drainage.16 In each of these other series, however, the procedure was not widely applied because of technical problems associated with the vascular reconstruction.
In 1993, our group reported that P-E PTX with Roux limb diversion not only achieves acceptable metabolic control and eliminates hyperinsulinemia but was also associated with reduced post-operative complications.6 In 1995, we compared 19 patients undergoing SKPT with the P-E technique versus a concurrent and historical control group of 28 patients receiving SKPT with the conventional S-B technique.18 Actuarial patient and graft survival rates at one and three years were no different in the two groups. Metabolic and urologic complications and urinary tract infections were more common in the S-B group. Metabolic control was comparable between groups, and peripheral hyperinsulinemia did not occur in patients with P-E drainage. In 1995, Newell et al. from the University of Chicago reported their initial experience with a similar P-E technique in 12 SKPT recipients compared to a retrospective control group of 12 SKPT patients with S-B drainage.19 Six-month patient and graft survival rates were comparable, and the P-E group had less acidosis, dehydration, hematuria, rejection, and need for enteric conversion. There were no differences in technical complications, and renal and pancreas allograft functions were similar. In 1996, Newell et al. presented 12-month follow-up on the same two groups with similar findings.20 In addition, the initial length of stay and total hospital days in the first year after SKPT were slightly lower in the P-E group. There were no significant differences in costs, no delay in the diagnosis of rejection, and the authors concluded that their initial results confirmed the safety and efficacy of this new technique.
In 1997, Nymann et al. from our group reported improving outcomes with increased experience with the P-E technique.21 Two groups were compared: 23 SKPTs with P-E drainage performed from 1991 to 1994 versus 23 P-E PTXs (17 SKPT, 3 PAKT, 3 PA) performed in 1995-96. The latter group received tacrolimus (TAC)-based immunosuppression, while the former group was managed with cyclosporine (CyA). Cold ischemia time and peri-operative blood transfusions were significantly lower in the latter group. In addition, the incidence of technical graft loss was reduced from 26% to 9%. Consequently, one-year patient and pancreas graft survival rates were improved in the later era. In 1998, Nymann et al. analyzed 47 SKPTs with graft function at one month, including 30 with S-B and 17 with P-E drainage.22 All patients had received CyA-based therapy. Although the authors noted comparable patient and graft survival and surgical complication rates, the incidences of rejection, graft loss due to rejection, and the density of rejection were all lower in patients with P-E drainage. Also in 1998, Eubanks et al. from our group compared 12 solitary PTXs with S-B drainage performed from 1991-95 with 16 solitary PTXs with P-E drainage performed between July 1995 and March 1997.23 The former group was managed with CyA and the latter group with TAC-based immunosuppression. One patient in each group experienced graft loss as a result of thrombosis. In the remaining patients, the incidence and density of rejection were lower in the more recent era, leading to an improvement in the one-year pancreas graft survival rate to 80%. In each of these studies, the authors concluded that the results of PTX with the P-E technique are now comparable to the other reported techniques.
In 1998, Bruce et al. from the University of Chicago reported their updated experience with 70 consecutive SKPTs with P-E drainage performed between January 1992 and August 1997.24 They compared this group to a “historical” control group of 70 SKPTs with S-B drainage performed between January 1987 and December 1994. One-year patient, kidney, and pancreas graft survival rates were comparable between groups. There were no significant differences in technical or immunologic graft failure rates (no enteric or anastomotic leaks were reported). Renal and pancreas allograft functions at one year were similar. However, the total number of hospital days and operative complications in the first year were significantly higher in the S-B group, with the difference in these results almost entirely accounted for by a 21% rate of enteric conversion in patients with S-B drainage. In addition, the authors noted a possible “learning curve” effect, with improved results in the latter 35 versus the former 35 SKPTs with P-E drainage. In 1998, Busing et al. reported on 70 consecutive SKPTs without anastomotic complications, including 2 with P-E drainage.25 Busing later updated his experience to 10 SKPTs with P-E drainage, including none using a Roux limb.26 Kidney and pancreas survival rates were both 90%, with one graft lost due to thrombosis. Buell et al. likewise updated the University of Chicago experience, including 16 SKPTs with P-E drainage without a Roux limb.27 This group also reported good initial results with the P-E technique in the absence of a diverting Roux limb.
In 1999, Reddy et al. reported a reduction in the surgical complication rate after PTX with P-E drainage that was attributed to increased experience with the technique.28 Also in 1999, Stratta et al. reported that the incidence of allograft pancreatectomy was not influenced by the surgical technique of implantation.29 In 1999, Philosophe et al. from the University of Maryland reported their initial experience with 66 PTXs with P-E drainage compared to 183 PTXs with S-E drainage.30 Graft survival rates for SKPT, sequential pancreas after kidney transplant (PAKT), and PTX alone (PA) recipients were similar according to technique. However, when stratified for human leukocyte antigen (HLA)-matching, the incidence of rejection was lower in patients with P-E drainage. In a follow-up report in 2000, Philosophe et al. compared 117 solitary PTXs with P-E drainage versus 70 with S-E drainage.31 The authors noted not only an improvement in the pancreas graft survival rate, but also a decrease in the incidence and severity of rejection in patients with P-E drainage. The authors concluded that P-E drainage may be associated with an immunologic advantage.
In 2000, the Lyon group reported a prospective study of 34 SKPT recipients randomized to either S-E or P-E drainage with a Roux limb.32 Patient and graft survival rates and morbidity were similar between groups. Also in 2000, Cattral et al. prospectively studied 20 SKPTs with S-B drainage followed by a sequential cohort of 20 consecutive SKPTs with P-E drainage.33 One-year patient and graft survival rates were similar between groups. However, medical morbidity, CMV infections, and acute rejection were more common in the S-B group. Zibari et al. reported their initial experience with 17 SKPTs with P-E drainage and a Roux-en-y venting jejunostomy to monitor for rejection and prevent anastomotic leak.34 Patient, kidney, and pancreas graft survival rates were 100%, 100% and 94%, respectively, after a mean follow-up of 16 months. In each of these studies, the authors concluded that SKPT with P-E drainage can be performed with excellent short-term outcomes and minimal morbidity. Herein we report the chronology of our nine-year single center experience with 126 PTXs with P-E drainage spanning different immunosuppressive eras.
The University of Tennessee (UT) Memphis PTX program began in 1989 (Figure 1).35 Between April 1989 and September 1990, 24 consecutive SKPTs were performed with S-B drainage (Figure 2). The first SKPT with P-E drainage was performed in October 1990, and this patient continues to enjoy excellent dual allograft function over ten years later. Also in 1990, the first solitary PTXs were performed at our program including both sequential PAKT and PA (Figure 1).
From October 1990 through December 1994, we performed 42 SKPTs, including 26 with P-E and 16 with S-B drainage (Figure 2). During the same interval, a total of 18 solitary PTXs were performed with S-B drainage, including 13 PA and 5 PAKT. In 1995 and 1996, 42 consecutive PTXs (29 SKPT, 9 PAKT, 4 PA) were performed exclusively with P-E drainage. From February 1997 through March 1998, we compared 32 consecutive PTXs performed with either S-B or P-E drainage.36 From April 1998 through May 2000, 54 consecutive SKPT recipients were entered into a prospective study of S-E versus P-E drainage at our center. From 1989 through 2000, we performed a total of 276 PTXs, including 153 with P-E, 76 with S-B, and 47 with S-E drainage (Figure 3). This overall experience accumulated over a decade includes 196 SKPTs, 43 PA, and 37 PAKTs (Figure 4). The UT Memphis PTX program is currently one of the seven largest centers in the United States and recently became the thirteenth center worldwide to perform 250 PTXs. Through 1999, we have one of the largest single center experiences with the P-E technique, including 126 PTXs (90 SKPT, 18 PAKT, 18 PA) with P-E drainage (Figure 5). This report represents a case series and our collective experience with the P-E technique.
Prior to transplantation, the pancreas was reconstructed on the back table with a donor iliac artery bifurcation Y-graft to the splenic and superior mesenteric arteries.37 The P-E procedure requires that the arterial bifurcation graft be constructed intentionally long for subsequent arterialization. The donor portal vein was mobilized and dissected back to the splenic and superior mesenteric venous confluence without the need for a venous extension graft. The proximal duodenal staple line (just distal to the pylorus) was inverted with suture, and the distal duodenal closure incorporated the third and a variable length of the fourth portion of the duodenum, as previously described.35 The closure of the mesenteric root was reinforced with a running suture. The spleen was left attached to the tail of the pancreas to be used as a handle, but in some cases, the splenic hilar structures were ligated in continuity before revascularization. The kidney was likewise prepared using standard techniques. The pancreaticoduodenal graft was repackaged separately and in sterile fashion in cold UW solution prior to implantation. After preparation of the organs, the recipient operation was performed through a midline intraperitoneal approach. The surgical technique of P-E drainage has been previously described in detail by our group (Figure 6).4-6,18,35 The portal vein of the pancreas graft was anastomosed end-to-side to a major tributary of the superior mesenteric vein. The donor iliac bifurcation graft was brought through a window made in the distal ileal mesentery and anastomosed end-to-side to the right common iliac artery. The transplant duodenum was anastomosed to a diverting Roux-en-y limb of recipient jejunum. Splenectomy was performed after revascularization, and an attempt was made to anchor the tail of the pancreas to the anterior abdominal wall with interrupted sutures. These anchoring sutures permitted subsequent percutaneous, ultrasound-guided pancreas allograft biopsies to be performed as needed.
Most PTX centers use quadruple drug immunosuppression with anti-lymphocyte induction (ALI) because of a high incidence of rejection and the general impression that the pancreas is a highly immunogenic organ. The evolution of surgical techniques has been, in large part, facilitated by the rapid changes in immunosuppressive therapy. With the recent commercial availability of potent immunosuppressive agents such as tacrolimus (TAC) and mycophenolate mofetil (MMF), the need for routine ALI therapy after PTX has been questioned.
From October 1990 through June 1995 (Era 1), 30 SKPTs with P-E drainage were performed at our center with quadruple therapy consisting of OKT3 induction in combination with CYA-Sandimmune, Prednisone, and Azathioprine (Figure 7).18 CYA dosing was titrated to achieve a target 12-hour trough level of greater than 300 ng/ml for the first three months after transplant and greater than 200 ng/ml thereafter. Azathioprine dosing was 1-2 mg/kg/day. Prednisone was tapered to achieve a dose of 10 mg/day by one year and 5 mg/day by two years after transplant. From July 1995 through May 1998 (Era 2), 42 SKPTs and 23 solitary PTXs (11 PAKT, 12 PA) with P-E drainage received TAC, Prednisone, and MMF triple therapy without antibody induction.23,39,40 TAC dosing was titrated to a 12-hour trough level of 15-25 ng/ml by IMX assay for the first three months after transplant. After three months, TAC blood levels were maintained at 10-15 ng/ml in the absence of rejection. Oral MMF was begun immediately after transplant at 2-3 gm/day in 2-4 divided doses. The MMF dose was reduced in patients with gastrointestinal intolerance (nausea, vomiting, diarrhea) or when the total white blood cell count was less than 3000/mm.3 MMF was discontinued temporarily in patients with active CMV infection or septicemia, or when the total white blood cell count was less than 2000/mm;3 it was restarted later at a reduced dose. Prednisone was gradually tapered to achieve a dose of 5 mg/day at one year.
From June 1998 through December 1999 (Era 3), 18 SKPTs and 13 solitary PTXs (7 PAKT, 6 PA) with P-E drainage received TAC, MMF, and Prednisone immunosuppression with or without either Simulect (Basiliximab) or Zenapax (Daclizumab) antibody induction41 (Figure 8). Half of the SKPT and all of the solitary PTX recipients received either Basiliximab (20mg intravenous on day 0 and 4) or Daclizumab (1mg/kg on day 0 and then at two week intervals for a total of five doses) as induction therapy.
Data are reported as mean and range. Renal allograft loss was defined as death with function, transplant nephrectomy, return to dialysis or to the pre-transplant serum creatinine level. Pancreas graft loss was defined as death with function, transplant pancreatectomy, or the need for daily scheduled insulin therapy.
With preliminary data demonstrating the equivalence of both procedures, we designed a prospective evaluation of PTX with S-B versus P-E drainage.36 During an 11-month period extending from February 1997 to January 1998, 32 consecutive PTXs were performed at our center and patients were alternately assigned to either S-B or P-E drainage. The total of 16 patients were allocated to each technique. The S-B group included 11 SKPT, 1 PAKT, and 4 PA recipients while the P-E group included 12 SKPT, 2 PAKT, and 2 PA recipients. The two groups were well matched for donor and recipient demographic, immunologic, and transplant characteristics (Table 2). All SKPT and PAKT recipients received primary immunosuppression with TAC, MMF, and steroids without ALI. PA recipients in both groups received OKT-3 induction in addition to the above triple maintenance therapy. Patient, kidney, and pancreas graft survival rates were 88% S-B versus 94% P-E, 92% S-B versus 93% P-E, and 81% S-B versus 88% P-E, respectively, with a mean follow-up of eight months (minimum of three months) (Table 3). All kidney grafts had immediate function and the incidence of early technical problems related to the pancreas allograft (pancreatitis, thrombosis) was similar in the two groups. There were no graft losses either to immunologic or infectious complications in either group, but the incidence of acute rejection was slightly higher in the S-B group (44% S-B versus 31% P-E, P=NS). Length of stay and hospital charges for the initial hospitalization were similar between groups (Table 3). For all patients, the mean length of initial hospital stay was 13 days and initial hospital charges approximated $100 000.
The incidence of urologic complications was doubled in the S-B group (25% S-B versus 12% P-E, P=NS). The S-B group was also characterized by a higher incidence of urinary tract infections (50% S-B versus 19% P-E, P=0.12). Metabolic acidosis with oral bicarbonate supplementation was universal in the S-B group, but rarely occurred with P-E drainage. Dehydration with the need for intravenous fluid supplementation and placement of long-term indwelling central venous catheters occurred in all patients with S-B drainage but in only 44% with P-E drainage.
The incidence of operative complications was similar, but the relaparotomy rate was higher in the P-E group (two patients in this group required a second reoperation, while no patients in the S-B group received multiple laparotomies). In the P-E group, one patient (6%) had an enteric leak with intra-abdominal infection. Two patients underwent enteric conversion in the S-B group. The incidences of major infections and CMV infection were similar between groups. We believe that this study represented the first prospective analysis comparing PTX performed by a standardized technique of P-E drainage versus the conventional technique of S-B drainage with similar immunosuppression.36 These preliminary results suggested that whole organ PTX with P-E drainage could be performed with results comparable to the conventional technique of S-B drainage.
As the number of PTXs with enteric drainage has steadily increased, we decided to compare SKPT with S-E versus P-E drainage in a prospective fashion with standardized immunosuppression. During a 26-month period from April 1998 through May 2000, 54 consecutive SKPT recipients were entered into a prospective study of S-E (N=27) versus P-E (N= 27) drainage. The technique to be performed was chosen before the transplant with selection determined by an alternating methodology. The two groups were well matched for most donor and recipient demographic, immunologic, and transplant characteristics (Table 4). The racial distribution differed slightly, with African-American patients representing 15% of the S-E and 33% of the P-E group. With regard to immunosuppression, 63% of S-E and 44% of P-E patients were managed with no antibody induction. The remaining S-E patients received either Daclizumab or Basiliximab induction, while the P-E patients received Daclizumab, Basiliximab, or Thymoglobulin in two patients with acute tubular necrosis (ATN). Maintenance immunosuppression in both groups consisted of TAC, MMF, and steroids.
Results are depicted in Table 5. Patient survival rates were 93% S-E versus 96% P-E, while kidney graft survival rates were 93% in both groups. PTX survival (complete insulin independence) rates were 74% after S-E versus 85% after P-E drainage, with a mean follow-up of 17 months. All but three of the 54 transplanted renal allografts had immediate function. ATN, defined as the need for dialysis in the first week after transplant, occurred in one patient after S-E and two patients after P-E drainage. All three of these kidneys eventually functioned. All 54 transplanted pancreas allografts had initial function, although three were subsequently lost to thrombosis in the first week after transplant. The incidence of allograft pancreatitis, early leaks, or other technical problems related to the pancreas allograft were similar between groups.
The mean length of initial hospital stay was 12.4 days in the S-E and 12.8 days in the P-E groups, respectively. Mean initial hospital charges were comparable between groups. The S-E group was characterized by a slight increase in the number of readmissions (mean 2.8 S-E versus 2.2 P-E, P=NS) and total hospital days (mean 33 days S-E versus 24 days P-E, P=NS). The incidence of acute rejection was similar (33%) in both groups, with immunologic pancreas graft loss occurring in 3 S-E patients versus 1 P-E patient. The incidence of major infection was 52% in both groups, with 1 CMV infection (4%) in each group. The incidence of intra-abdominal infection was slightly higher in the S-E group (26% S-E versus 11% P-E, P=NS). However, the early relaparotomy rate was similar between groups (30% S-E versus 26% P-E). The composite endpoint of no rejection, graft loss, or death was attained by 56% of S-E and 59% of P-E patients (Table 5). These results suggested that SKPT with S-E or P-E drainage could be performed with comparable short-term outcomes.
From October 1990 through December 1999, we performed 126 PTXs with P-E drainage (Figure 5), including 90 SKPTs and 36 solitary PTXs (18 PAKT, 18 PA). The P-E group included 69 male and 57 female patients with a mean age of 39 years (Table 6). The mean duration of pre-transplant diabetes was 24 years (range 8-50). The majority of recipients were Caucasian, although 15 (12%) were African-American recipients. A total of 13 patients (10%) underwent pancreas re-transplantation with the P-E technique. The majority of patients had poor HLA matching (mean 1.4, range 0-5), and the mean pancreas cold ischemia was 13 hours (range 6-23). Minimum follow-up was 11 months (mean 4.6 years).
Thirty patients underwent SKPT with P-E drainage in Era 1 and were compared to 42 SKPTs performed in Era 2 and 18 in Era 3 (Figure 7). The patients in Era 1 were managed with CYA while those in Eras 2 and 3 received TAC/MMF. We also compared 23 solitary PTXs (11 PAKT, 12 PA) performed in Era 2 with 13 (7 PAKT, 6 PA) performed in Era 3. One-year patient survival rates after SKPT (Figure 9) were 77% in Era 1, 93% in Era 2, and 100% in Era 3 (P=0.03). The one-year kidney graft survival rates were 77% in Era 1, 93% in Era 2, and 94% in Era 3 (P=0.08). The one-year pancreas graft survival rates after SKPT (Figure 9) were 60% in Era 1, and 83% both in Eras 2 and 3 (P=0.06). The most common causes of kidney graft loss were death with function and chronic rejection (Table 7). The overall incidence of kidney graft loss decreased from 56% in Era 1 to 23% in Era 2 to 11% in Era 3. The most common causes of pancreas graft loss were thrombosis, death with function, chronic rejection, and infection (Table 7). The overall incidence of pancreas graft loss decreased from 60% in Era 1 to 31% in Era 2 to 22% in Era 3.
The incidences of rejection (63% versus 33% versus 39%, and major infection (60% versus 43% versus 44%, P=NS) after SKPT were decreased in each successive era (Figure 10). The rates of thrombosis (20% versus 7% versus 6%, ) and early relaparotomy (47% versus 31% versus 33%, P=NS) after SKPT were also decreased in each consecutive era (Figure 11).
The one-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 (Table 8). The most common causes of graft loss after solitary PTX were thrombosis and chronic rejection. The overall incidence of pancreas graft loss after solitary PTX decreased from 70% in Era 2 to 31% in Era 3 (P=0.02). The rates of acute rejection (57% versus 38%), major infection (35% versus 31%), thrombosis (22% versus 15%), and relaparotomy (43% versus 38%) after solitary PTX were all slightly improved in Era 3 compared to Era 2 (P=NS). 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.
The UT Memphis group has made a number of important contributions to the field of PTX, including development of a novel whole organ technique of PTX with portal venous drainage of insulin and primary enteric drainage of the exocrine secretions. The P-E technique has the potential to become the standard of care in the near future because it is more physiologic, normalizes carbohydrate and lipid metabolism, and minimizes complications attributed to the transplant procedure. In addition, we have been actively involved in studying new immunosuppressive regimens in order to improve and simplify the care of the PTX recipient. We believe that PTX will remain an important treatment option for insulin-treated diabetic patients with complications until other strategies are developed that can provide equal glycemic control with less or no immunosuppression and less overall morbidity.