Skip Navigation


NDT Advance Access originally published online on November 11, 2005
Nephrology Dialysis Transplantation 2006 21(2):483-487; doi:10.1093/ndt/gfi252
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/2/483    most recent
gfi252v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Monroy-Cuadros, M.
Right arrow Articles by McLaughlin, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Monroy-Cuadros, M.
Right arrow Articles by McLaughlin, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Dialysis and Transplantation

Bladder vs enteric drainage in simultaneous pancreas–kidney transplantation

Mauricio Monroy-Cuadros1, Anastasio Salazar1, Serdar Yilmaz1 and Kevin McLaughlin2

1 Department of Surgery, Division of Transplantation, and 2 Department of Internal Medicine, Division of Nephrology, University of Calgary, Foothills Medical Centre, Calgary, UK

Correspondence and offprint requests to: Mauricio Monroy-Cuadros, MD, Foothills Medical Centre, Department of Surgery, Division of Transplantation. Email: Mauricio.monroy{at}calgaryhealthregion.ca



   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. As a valid therapeutic option for patients with type 1 diabetes mellitus (IDDM) and secondary diabetic nephropathy, simultaneous pancreas–kidney (SPK) transplantation remains more undeveloped than other solid organ transplantations due to restrictions of surgical techniques, especially modes of exocrine pancreatic secretion. Enteric drainage (ED) has recently been increasingly popular due to the long-term complications with bladder drainage (BD).

Objectives. Compare results of SPK transplants with enteric vs bladder exocrine drainage since the beginning of our experience with this type of transplantation.

Methods. From March 1998 to October 2004, 53 SPK transplants were performed, consisting of 30 with bladder drainage (BD) and 23 with enteric drainage (ED). Induction therapy included antilymphocyte globulin (ALG) or anti-CD25 monoclonal antibody. Maintenance regimen consisted of tacrolimus (TAC)/cyclosporine (CsA), mycophenolate mofetil (MMF) and steroids.

Results. Mean age of recipients was 39±7 in both groups. No anastomosis leakage occurred in either group. Surgical complications were not significantly different between the two groups. Incidence of acute rejection, major infections and cytomegalovirus disease were also similar. However, the BD group was characterized by a slight increase in number of urologic complications, metabolic acidosis and dehydration. The length of initial hospital stay was likewise comparable. All patients with a functional graft no longer required exogenous insulin. BD actuarial patient survival and graft three-year survival were 96 and 86%, respectively. For ED, the respective results were 97 and 91%, respectively.

Conclusion. Compared with BD, perioperative morbidity is not increased by ED, and ED is not associated with increased long-term pancreas graft failure. These data suggest that ED is superior to BD and should be considered as the preferred technique for simultaneous pancreas–kidney transplants.

Keywords: bladder drainage; enteric drainage; exocrine drainage; pancreas–kidney transplantation



   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
Since the first pancreatic allograft in 1966, numerous surgical teams throughout the world have performed pancreatic transplantations. Initial results were disappointing with a high percentage of technical failures and rejection. Over-optimistic enthusiasm for islet-cell allografts also retarded the development of pancreatic transplantation. Despite this slow start, the results of pancreatic transplantation from 1995 onwards have been very satisfactory and equivalent to, or even better than, the results of other solid organ transplants. This success has been due to better graft selection, improved surgical techniques and preservation solutions, and especially to improvements in immunosuppressive protocols. Simultaneous pancreas–kidney transplantation (SPK) is the procedure of choice in our programme to treat type I diabetic patients with end-stage renal disease when no potential living donor is available. Its value in type II diabetic patients continues to be carefully evaluated. Debate continues over the optimum technique for exocrine drainage. Bladder drainage (BD) via pancreaticoduodenocystostomy is the most widely used technique [1]. The major benefits of BD include the ability to monitor pancreatic allograft function via urinary amylase measurements and cystoscopically directed biopsy. These advantages are mitigated by the frequently observed urological complications that occur with BD, including metabolic acidosis and volume depletion secondary to sodium bicarbonate wasting, reflux pancreatitis, urinary tract infections (UTI) and haematuria [2,3]. Conversion surgery to the enteric route may be necessary in 20–25% of patients to eliminate a persistence or recurrence of these undesirable effects. Enteric drainage (ED) has recently been increasingly popular owing to the long-term complications of BD. Although this technique largely avoids the urological complications of BD, it does not lend itself to the conventionally used methods of monitoring pancreas allograft function. ED is associated with an increased incidence of technical failure and overall lower graft survival rates [1]. However, several studies have reported favourable results with ED compared with BD [4–6].

At our institution, 53 SPK transplants, with at least 6 months follow-up after transplantation, have been performed since 1998. Both BD and ED methods of pancreas allograft duct management have been used to manage exocrine pancreatic secretions. The purpose of this study was to compare the long-term consequences of BD and ED in terms of morbidity, patient and graft survival, and evaluate the complication rates associated with each procedure.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
A retrospective study across a six-year period, from March 1998 to October 2004, was performed and a total of 53 consecutive recipients of SPK transplant were identified. All patients included in the analysis were transplanted at the Foothills Medical Centre and have had at least 6 months follow-up after transplantation. From March 1998 until December 2001, all pancreas transplants were performed using BD. From January 2002, a new policy was implemented and ED was used exclusively. Overall, the primary pancreatic drainage technique was BD in 30 patients and ED in 23 patients, respectively. Exclusion criteria included patients who received a kidney transplant after pancreas transplantation.

Technical aspects
All SPK transplants were performed through a midline incision with both organs placed intraperitoneally. The kidney was placed in the left lower quadrant, with the renal vessels anastomosed to the external iliac vessels in an end-to-side fashion. The portal vein of the pancreas allograft was anastomosed to the recipient right external iliac vein in an end-to-side fashion. The superior mesenteric and splenic arteries were reconstructed using a donor iliac artery Y graft, which was anastomosed with the right external iliac artery of the recipient. In BD cases, the duodenal segment of the graft was anastomosed to the dome of the recipient bladder in a side-to-side manner, with manual anastomosis with an interrupted double layer of 4:0 PDS sewing. For primary ED, a segment of distal ileum, approximately 40 cm from the ileocaecal valve, was anastomosed to the donor duodenum in a side-to-side fashion, with manual anastomosis with an interrupted double layer of 4:0 PDS.

Immunosuppression
All patients received induction therapy with antibodies, which included anti-lymphocyte globulin (ALG) or anti-CD25 monoclonal antibody. Maintenance immunosuppressive regimen consisted of cyclosporine (CsA)/tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids. Cyclosporine was dosed to obtain maintenance target trough levels of 250–350 ng/ml for the first post-transplant year and 100–200 ng/ml thereafter. Tacrolimus was dosed to obtain maintenance target levels of 10–15 ng/ml for the first post-transplant year and 5–10 ng/ml thereafter. An i.v. injection of 500 mg of methylprednisolone was administered immediately before the surgery. Patients were then started on oral prednisone at 1 mg/kg per day rounded to the nearest 5 kg body weight and tapered every 3 days to a maintenance dose on day 22 (referred to as our prednisone taper protocol). Mycophenolate mofetil was started the day prior to surgery at a dose of 1 g twice a day.

Rejection monitoring and treatment
The diagnosis of acute rejection was made on the basis of clinical criteria in combination with positive findings on a kidney core biopsy. They included the simultaneous occurrence of an increase in serum creatinine concentration over the basal value associated with a stable immunosuppression trough blood level, and a renal ultrasound that excluded any other cause of allograft dysfunction (including urinary tract obstruction). All suspected cases of acute rejection were confirmed by percutaneuous renal transplant biopsy. The biopsies were graded for evidence of rejection according to the Banff 97 scheme. Pancreatic rejection in BD patients was diagnosed by monitoring for reduction in urinary amylase excretion (greater than 50% reduction from baseline on two consecutive days). Monitoring for acute pancreatic rejection in ED subjects was not specifically performed, and the rationale for rejection therapy was based entirely on the diagnosis of renal allograft rejection. The protocol regimen for first-line treatment of clinically suspected rejection episodes was pulse methylprednisolone therapy at 500 mg once daily for three days, and then 250 mg once daily on day four, followed by our prednisone taper protocol.

Perioperative management
The immediate post-transplant management was the same for both BD and ED-treated patients. All patients had a nasogastric tube placed, which was removed when GI motility was restored to baseline. Fungal prophylaxis was given with fluconazol for the first week. The diet was gradually progressed as tolerated. Foley catheter was removed on the sixth post-operative day.



   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Between March 1998 and October 2004, 53 pancreas grafts were transplanted into 53 patients at the Foothills Medical Centre. Thirty of these were completed using BD of the pancreatic exocrine secretions, and 23 were completed using ED of the exocrine secretions. The indication for transplantation for all 53 recipients was insulin-dependent diabetes mellitus. The demographic, relevant immunological background and transplant characteristics of the two groups are presented in Table 1. The two groups were well matched for age, sex, weight and pre-transplant duration of diabetes. The mean post-transplant follow-up has been significantly longer in the BD group (70±3.3 vs 35.7±3.9 months in the ED patients, p<0.005). Although the majority of recipients were Caucasians, the racial distribution between the two groups was comparable. At least two-thirds of all patients received pre-transplant dialysis. The distribution of dialysis modality and duration of dialytic therapy in each group was similar. Immunological factors including the degree of sensitization (prior transplants and panel-reactive antibody titers), HLA matching, length of cold ischaemia and donor variables were equivalent between the two groups. The time spent on the waiting list was similar for both groups. There were no significant differences in patients’ renal or pancreas allograft survival rates after mean follow-up of 18 months.


View this table:
[in this window]
[in a new window]
  		Table 1. Pre-transplant demographics and immunological characteristics of SPK transplant recipients

 
With an average follow-up period of 18 months, we found a complication rate of 53% in the BD group, and 41% in the ED group (P = 0.47). Results of complications are provided in Table 2. Within the cohort of patients who received pancreas transplant with BD, there were 8 patients who required readmission. Complications included metabolic acidosis (universal), dehydration (25 patients), urinary tract infection (18 patients), haematuria (4 patients), reflux pancreatitis (1 patient), intra-abdominal haemorrhage (2 patients), pancreatitis (1 patient) and leak (1 patient). In this group, three patients underwent conversion to ED.


View this table:
[in this window]
[in a new window]
  		Table 2. Complications

 
The complications developed in the ED group were more heterogeneous. These included calcineurin toxicity (1 patient), intra-abdominal abscess (1 patient), fascial dehiscence (2 patients) and GI tract bleeding from the enteric anastomosis (2 patients).

With regard to rejection, there were 12 patients (40%) with biopsy-proven kidney graft rejection in the BD group. All these episodes of rejection were treated successfully with steroid pulse therapy. Among the patients who underwent ED of their pancreas graft, 7 patients (30%) had episodes of rejection. Again, these were all treated successfully with pulses of steroids. The difference in rejection rates between the two groups (ED and BD) was not statistically significant (P>0.05). The incidence of CMV infection was similar in both cohorts of patients. The initial length of hospital stay in both groups was 13 days.



   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
Since the first SPK transplant in 1966, several techniques of pancreas transplantation have been studied [7]. According to the United Network for Organ Sharing Registry data, BD with a duodenal segment conduit is the preferred technique for managing exocrine secretion after vascularized pancreas transplantation [8]. From 1987 through 1995, this method was used in 94% of the pancreas transplantation performed in the United States. BD technique became popular because it is safe, sterile and convenient as it enables urinary monitoring of exocrine pancreatic secretions, affords access to cystoscopic biopsy and permits easy control for anastomotic problems with uretheral catheter drainage [7,9,10]. Prieto et al. [11] found that a decline in urinary amylase is a sensitive indicator of pancreas graft dysfunction, and that there exists a temporal relation between graft dysfunction and amylase decline. More specifically, they asserted that a urinary amylase decline of >50% from baseline was suggestive of pancreas graft rejection. However, the BD technique also creates a non-physiologic connection between the allografted pancreas with a duodenal conduit and the urinary bladder. This results in obligatory fluid and bicarbonate losses in the urine and alterations in the normally enzyme-free milieu of the lower genitourinary tract [7,11]. Although well tolerated in many pancreas transplant recipients, BD has been associated with unique metabolic and urologic complications resulting from an altered physiology [3,12–14]. When these complications become intractable, conversion from BD to ED may be therapeutic. Enteric conversion ranges from 10 to 20% in most large series [14–16].

In an effort to avoid these complications, some centers have returned to primary ED and are reporting improving results [6,9,16,18,19]. In the past, the disadvantages of ED included the inability to directly monitor the exocrine pancreatic secretions, the occurrence of septic complications (such as peritonitis, abscess and mycotic aneurysm) and difficulties with the healing process. The healing problems were related to the anastomosis of an ischaemic organ and an inadequately prepared bowel in the setting of high-dose immunosuppression with incomplete distal decompression [7].

Based on the favourable experience with enteric conversion [14–16] and recent improvements in organ retrieval and preservation, surgical techniques, immunosuppression, diagnostic technology and anti-microbial prophylaxis, the results of primary ED are similar to those with BD [9,17–24]. Centers at which primary ED is done generally employ the duodenal segment technique with either a direct side-to-side anastomosis to the small bowel or an anastomosis to a diverting Roux limb.

The results presented in this analysis demonstrate that the elimination of the BD-related urological complications by utilizing primary ED translates into significantly fewer hospitalizations, of shorter duration over the long term. Also the results show that ED is not associated with an increased risk of chronic pancreas allograft failure.

The historic reduction in graft survival seen with ED has been attributed to factors implicated in early graft loss, including increased technical failure and infection-related morbidity [17], as well as the inability to monitor pancreatic exocrine function via urinary amylase measurements. In this study, the two patient cohorts were closely matched on baseline characteristics and there was no difference in early pancreas survival within the first three months post-transplant.

As reported previously by other authors [11,13], urological complications were a major cause of chronic morbidity in the BD cohort of this study. The virtual elimination of this morbidity in enteric drainage patients translated into fewer hospitalizations with shorter annualized lengths of stay over the study interval. Although a cost analysis is beyond the purpose of this paper, the implications of fewer and shorter duration hospitalizations over the long term are obviously extremely important, and are desirable goals in the current health care climate.

From our results we believe that we provide substantial evidence, over the long term, that primary ED is a safe alternative to primary BD in the management of pancreas allograft exocrine drainage in simultaneous pancreas and kidney transplant. In particular, when compared with BD: (a) morbidity and technical failure are not increased in ED, (b) ED is associated with significantly fewer complications, hospitalizations and in-hospital days, and (c) ED is not associated with an increased risk of long-term pancreas graft failure, given the limitation in monitoring for pancreas rejection. This study opens the doors for future economical analysis of the two surgical techniques and the influence they have on patients’ quality of life.

Limitations of this study include that this was a retrospective, single centre study involving a small sample size of patients where no randomization was applied. The fact that no pancreas biopsies were performed, and rejection episodes were treated on the basis of kidney rejection, may have impacted our results.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. Sutherland DE, Gruessner A. Pancreas transplantation in the United States as reported to the United Network for Organ Sharing (UNOS) and analyzed by the International Pancreas Transplant Registry. Clin Transpl 1995; 47: 49
  2. Sutherland DE, Dunn DL, Goetz FC et al. A 10-year experience with 290 pancreas transplant at a single institution. Ann Surg 1989; 210: 274[Web of Science][Medline]
  3. Sollinger HW, Messing EM, Eckhoff DE et al. Urological complications in 210 consecutive simultaneous pancreas-kidney transplants with bladder drainage. Ann Surg 1993; 218: 561[Medline]
  4. Gaber AO, Shokouh-Amiri MH, Hathaway DK et al. Results of pancreas transplantation with portal venous and enteric drainage. Ann Surg 1995; 221: 613[Medline]
  5. 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 1996; 62: 1353[Medline]
  6. Kuo PC, Johhnson LB, Schweitzer EJ, Bartlett ST. Simultaneous pancreas/kidney transplantation: a comparison of enteric and bladder drainage of exocrine pancreatic secretions. Transplantation 1997; 63: 238[CrossRef][Medline]
  7. Stratta RJ, Taylor RJ, Gill IS. Pancreas transplantation: a managed cure approach to diabetes. Curr Prob Surgery 1996; 33: 709–816
  8. Gruessner AC, Sutherland DER. Analysis of the United States (US) and non-US pancreas transplant as reported to the International Pancreas Registry (ITPR) and to the United Network Organ Sharing (UNOS). In: Cecka JM, Terasaki PI (eds), Clinical Transplant 1998. Los Angeles: UCLA Tissue Typing Laboratory; 1999. p. 53–71
  9. Sollinger HW, Odorico JS, Knechtle SJ, D’Alessandro AM, Kaloyogou M, Pirsh JD. Experience with 500 simultaneous pancreas-kidney transplants. Ann Surg 1998; 228: 284–296[CrossRef][Medline]
  10. Sollinger HW, Pirsch JD, D’Alessandro AM, Kalayogou M, Belzer FO. Advantages of bladder drainage pancreas in pancreas transplantation: a personal view. Clin Transplant 1990; 4: 32–36
  11. Prieto M, Collins W, Scott MH et al. Method for home monitoring of urinary amylase after pancreas transplantation. Diabetes 1989; 38: 68
  12. Diem P, Abid M, Redmon JB, Sutherland DER, Robertson RP. Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in Type I diabetic recipients. Diabetes 1990; 39: 534–540[Abstract]
  13. Stratta RJ, Sindhi R, Sudan D, Jerius JT, Radio SJ. Duodenal segment complications in vascularized pancreas transplantation. J Gastrointest Surg 1997; 1: 534–544[Medline]
  14. Sindhi R, Stratta RJ, Lowell JA et al. Experience with enteric conversion after pancreatic transplantation with bladder drainage. J Am Coll Surg 1997; 184: 281–289[Medline]
  15. Sollinger HW, Sasaki TM, D’Alessandro AM et al. Indications for enteric conversion after pancreas transplantation with bladder drainage. Surgery 1992; 112: 842–846[Medline]
  16. West M, Gruessner AC, Metrakos P, Sutherland DER, Gruessner RWG. Conversion from bladder to enteric drainage after pancreaticoduodenal transplantation. Surgery 1998; 124: 883–893[Medline]
  17. Douzdijian B, Rajagopalan PR. Primary enteric drainage of the pancreas allograft revisited. J Am Coll Surg 1997; 185: 471–475[CrossRef][Medline]
  18. Corry RJ, Egidi MF, Shapiro R et al. Enteric drainage of pancreas transplants revisited. Transplant Proc 1995; 27: 3048–3049[Medline]
  19. Tyden G, Tibell A, Sandberg J, Brattstrom C, Groth CG. Improved results with a simplified technique for pancraticoduodenal transplantation with enteric exocrine drainage. Clin Transplant 1996; 10: 306–309[Medline]
  20. Pearson TC, Santa Maria PJ, Routenberg KL et al. Drainage of the exocrine pancreas in clinical transplantation: comparison of bladder versus enteric drainage in a consecutive series. Clin Transplant 1997; 11: 201–205[Web of Science][Medline]
  21. Busing M, Martin D, Schulz T et al. Pancreas-kidney transplantation with urinary bladder and enteric exocrine diversion: seventy cases without anastomotic complications. Transplant Proc 1998; 30: 434–437[Medline]
  22. Fernandez-Cruz L, Astudillo E, MacMillan N, Ricart MG, Sabater L. Should enteric drainage be used as a primary procedure instead of bladder drainage in clinical pancreas transplantation? Transplant Proc 1998; 30: 430–431[Medline]
  23. Tagral CF, Dawhara M, Benchaib M, Lefrancois N, Martin X, Dubernard JM. Effect of the surgical technique on long-term outcome of pancreas transplantation. Transpl Int 1998; 11: 295–300[Medline]
  24. Bloom RD, Olivares M, Rehman L, Raja RM, Yang S, Badosa F. Long-term pancreas allogaft outcome in simultaneous pancreas-kidney transplantation: a comparison of enteric and bladder drainage. Transplantation 1997; 64: 1689–1695[CrossRef][Medline]
Received for publication: 26. 9.05
Accepted in revised form: 11.10.05


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CJASNHome page
A. S. Weiss, G. Smits, and A. C. Wiseman
Twelve-Month Pancreas Graft Function Significantly Influences Survival Following Simultaneous Pancreas-Kidney Transplantation
Clin. J. Am. Soc. Nephrol., May 1, 2009; 4(5): 988 - 995.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/2/483    most recent
gfi252v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Monroy-Cuadros, M.
Right arrow Articles by McLaughlin, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Monroy-Cuadros, M.
Right arrow Articles by McLaughlin, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?