The first successful simultaneous pancreas-kidney (SPK) transplantation was performed at the University of Minnesota Hospital in 1966 [
Despite numerous advances in surgical techniques, organ preservation, and immunosuppression over the past 25 years, SPK is still associated with significant morbidity and rate of transplant graft loss remains significant [
Our aim was to review the experience of SPK transplantation at the National Pancreas Transplant Unit (NPTU) in Australia over the last 10 years, focusing on the incidence of major postoperative complications and the reasons for graft loss. We also aimed to identify risk factors leading to graft loss within our cohort.
A retrospective study was conducted on 165 first-time SPK transplants performed at the NPTU between January 2001 and May 2010. This period was chosen because tacrolimus-based immunosuppression and enteric drainage of pancreas transplant graft became standard therapy in our unit in January 2001. Eligibility criteria for SPK transplantation included the following: T1DM, significant renal impairment, and age less than 50 years. Exclusion criteria included a body mass index (BMI) greater than 30, cigarette smoking, and significant untreated coronary artery disease.
Prior to being accepted onto the waiting list for transplantation, all patients were reviewed by a transplant physician and surgeon. Preoperative assessment included clinical evaluation, comprehensive biochemical studies, and cardiac stress tests.
With the exception of one donation after cardiac death (DCD), organs were recovered from heart-beating donors with certified brain death. The donor pancreas procurement procedure has been previously described [
In the recipient, iliac artery exposure was performed through bilateral Rutherford-Morrison incisions or a midline laparotomy. The kidney graft was anastomosed to the recipient’s left iliac vessels. An external ureteroneocystostomy was performed over a 7-French ureteric stent. The donor pancreas was positioned in the right iliac fossa in an intraperitoneal position. The pancreatic head was placed inferiorly, and the donor vessels were anastomosed to the recipient’s right iliac vessels.
Since 2001, enteric drainage has been the preferred route of exocrine drainage in our unit. To achieve this, the donor duodenum segment and recipient jejunum were anastomosed in a side-to-side configuration. In most cases, this was fashioned in two layers using a 3–0 monofilament absorbable suture although a small number were performed with linear cutting stapler [
Maintenance immunosuppression typically consisted of a tacrolimus, mycophenolate mofetil and prednisolone. Induction therapy with monoclonal anti-CD25 antibody was used routinely after 2006.
Recipients received broad-spectrum antibiotic prophylaxis for 3 days, antifungal prophylaxis for one week, and CMV prophylaxis for six months postoperatively. Subcutaneous heparin (5000 units three times daily) was administered during convalescence in hospital, and acetylsalicylic acid (100 mg daily) was commenced upon resumption of diet.
Pancreas graft failure was defined as the day upon which permanent insulin administration was commenced or patient death. Kidney graft failure was defined as the day upon which permanent dialysis was commenced or death.
Measured values are reported as percentages for categorical data, and medians +/− interquartile range (IQR; 25th to 75th quartile) for continuous data. Differences between groups were compared by the Chi-squared or Fisher’s exact tests for categoric variables, Student’s
Between January 2001 and May 2010, 165 patients underwent SPK transplantation. Patient demographics are presented in Table
Recipient and donor demographics.
| |
---|---|
Recipient | |
Median age, yr (range) | 39 (16–53) |
Males | 87 (53%) |
Median BMI (range) | 24.1 (17.3–37.3) |
Duration of diabetes, yr (range) | 26 (4–45) |
Duration of dialysis | |
Preemptive | 39 (24%) |
0-1 year | 30 (18%) |
1–3 years | 61 (37%) |
>3 years | 35 (21%) |
Prior renal transplant, failed | 2 (1.2%) |
Coronary artery disease | 18 (11%) |
Ex-smoker | 61 (37%) |
Donor | |
Median donor age (years, IQR) | 26 (20–36) |
Cause of death | |
Trauma | 111 (67%) |
Nontraumatic causes | 54 (33%) |
Organ | |
Median pancreas cold ischaemic time ± SD, hr (range) | 12.1 (10.2–14.2) |
Median pancreas anastomotic time, min (IQR) | 27 (24–31) |
Median kidney cold ischaemic time ± SD, hr (range) | 10.8 (9.2–13.2) |
Median kidney anastomotic time, min (IQR) | 30 (25–38.5) |
Organs were retrieved from around Australia, including 83 from New South Wales and the ACT, 23 from Queensland, 18 from Victoria, and 41 from Western Australia and South Australia combined. The longest pancreas cold ischaemia time (CIT) was 19.3 hours.
Eighty-five secondary operations were performed on 56 out of 165 recipients (34%; Table
Return to theatre.
Complication requiring surgery | Presentation to theatre with de novo condition | ||
---|---|---|---|
<30 days | 30–365 days | >365 days | |
Pancreatic Thrombosis | 11 | 1a | 1 |
Severe rejection with secondary pancreatic thrombosis | 2 | 2 | |
Pancreatic leak | 7 | 5 | 2 |
Haemorrhage | 4 | 1b | |
Abscess, lymphocoele | 4 | 4 | 1 |
Exploratory laparotomy (including for pancreatitis) | 3 | 1 | |
Ureteric | 3 | 1 | |
Small bowel obstruction | 2 | 3 | 3 |
Acute limb ischaemia | 1 | ||
Wound resuture | 2 | ||
Hernia | 2 | ||
| |||
Total | 37 | 19 | 10 |
bFollowing transplant renal biopsy.
Thirty-six patients (21.8%) returned to theatre within the first 30 days. Within this group, thrombosis was the most common reason for return to theatre (
After the first 30 days, pancreatic leak was the commonest cause of return to theatre (
In total, 15/165 patients (9.1%) had confirmed pancreatic leaks. One, which fistulated through the wound, was managed nonoperatively. Fourteen of the 15 patients with pancreatic leaks returned to theatre for a total of 26 re-operations (range 1–6); in eleven the exocrine drainage was revised, and in two (1.2%) the allograft was removed due to ongoing sepsis.
While 11/15 pancreatic leaks occurred within the first 30 days, in three cases the first manifestation of leak occurred more than six months postoperatively (at 7 months, 13 months, and 18 months). Despite extensive investigation at the time, no cause for the late leaks was established.
Leak occurred in 3/16 bladder-drained and 12/149 enterically drained pancreases (
There were fifteen deaths from 165 recipients during a median followup of 5.2 years. The most common confirmed cause of death was opportunistic infection (
At 1 and 5 years, patient survival was 98% and 94%, respectively. Kidney allograft survival at one and five years was 96% and 89%, while pancreas allograft survival was 86% and 77%, respectively (Figure
Patient and graft survival.
Forty of 165 pancreas grafts (24%) were lost over the 10-year period. The most common cause of pancreas graft loss was organ failure, including failure due to rejection (
Causes of pancreas loss.
<1 year | >1 year | Total | |
---|---|---|---|
Thrombosis | 11 | 1 | 12 (30%) |
Failure (including acute and chronic rejection and thrombosis secondary to rejection) | 7 | 6 | 13 (32.5%) |
Pancreatic leak | 2 | 0 | 2 (5%) |
Death with functioning graft | 2 | 10 | 12 (30%) |
Primary nonfunction | 1 | 0 | 1 (2.5%) |
| |||
Total | 23 | 17 | 40 (100%) |
Of the 40 pancreas grafts lost, 23 (58%) were lost in the first year, including two due to recipient death (Table
Risk factors for pancreas graft loss at one year.
Graft failure < 1 year |
Functioning graft at 1 year |
|
|
---|---|---|---|
Median donor age (years, IQR) | 33 (21–39) | 26 (20–36) | 0.17 |
Median donor BMI | 24.4 (22.6–26.6) | 24.5 (22.5–26.2) | 0.88 |
Median ratio of donor-to-recipient weight (IQR) | 1.10 (0.94–1.41) | 1.08 (0.93–1.29) | 0.87 |
Median recipient BMI (IQR) | 23.6 (22.5–26.9) | 24.2 (22.1–26.5) | 0.99 |
Nontraumatic donor death | 10 (43.5%) | 44 (31.0%) | 0.24 |
Prior dialysis > 1 year | 18 (78.3%) | 65 (45.8%) | 0.03 |
Median pancreas anastomotic time (min, IQR) | 27 (23–33) | 27 (24–31) | 0.89 |
Median pancreas cold ischaemia time (hours, IQR) | 11.5 (8.6–13.2) | 12.1 (10.5–14.3) | 0.06 |
CMV-positive donor | 15 (65.2%) | 94/138 (68.1%) | 0.78 |
Return to theatre within 1 year | 17 (74.0%) | 31 (21.8%) | <0.001 |
Duration of dialysis greater than one year before SPK transplantation was associated with pancreas graft loss at one year (
There was no significant difference in pancreas CIT between grafts that failed and grafts that were still functioning at one year (
Reoperation correlated with earlier graft loss (RR = 3.6, 95% CI = 1.8–6.8), including death-censored graft loss (
Whole-organ pancreas transplantation is an effective treatment for patients with Type I diabetes mellitus. It leads to improved quality of life, independence from exogenous insulin administration, normalisation of glucose homeostasis, and can ameliorate diabetes-mediated organ dysfunction [
A variety of techniques to manage pancreatic exocrine secretions have been described. These include enteric drainage, bladder drainage, duct occlusion, and open drainage into the peritoneal cavity. The practice in our unit is to use enteric drainage (ED) in preference to bladder drainage (BD). While BD avoids exposing the operative field to enteric flora and permits monitoring of amylase secretion, ED has been shown to be at least equivalent to bladder drainage with regard to patient and graft survival [
We also advocate the orientation of the head of the pancreas in a caudal direction towards the pelvis. This configuration facilitates ease of conversion to bladder drainage in the event of a pancreatic leak, rather than resorting to graft pancreatectomy.
Pancreatic leak, while infrequent, was the most common cause of return to theatre. Salvage operations were effective at preserving organ function; in only two of fifteen patients was the pancreas lost due to the consequences of a leak. Our rate of allograft loss due to pancreatic leak (1.2%) is comparable to those of large international centres. A 1.3% rate of pancreas loss secondary to leak in ED grafts was reported by UNOS [
While pancreatic leak is often amenable to re-intervention, pancreatic thrombosis remains the major challenge faced by transplant surgeons [
Both medical and surgical strategies are used to minimise the risk of graft thrombosis. While we routinely use a short venous extension to the donor portal vein, it has been postulated that this may increase the risk of thrombosis [
Our relaparotomy rates of 21.8% at one month and 34% overall are similar to those reported elsewhere [
The five-year patient, pancreas, and kidney survival after SPK transplantation in this series are 94%, 77%, and 89%, respectively. This compares favourably with United States data in which five-year patient and pancreas-graft survival rates were 87% and 71–73%, respectively, for patients who received a SPK transplant [
There is evidence that SPK transplantation before the commencement of dialysis results in improved renal allograft outcomes [
SPK transplantation has established benefits in improving quality of life and survival in Type 1 diabetic patients. Nevertheless it is an operation with well-defined morbidity, including that of pancreatic leak and thrombosis. In a country as large as Australia, our service faces the added logistical issues posed by recipients and donors being in distant locations. Despite this, we have demonstrated that SPK transplantation can be performed safely and successfully with functional and survival outcomes comparable to those achieved by large international centres.
The authors declared that there is no Conflict of interests.