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Pancreas transplantation in Ireland
M. Downes P. Mohan D. Little D. Hickey
Department of Urology and Transplantation
Beaumont Hospital, Dublin 9, Ireland
Correspondence to: M. Downes, Department of Urology and Transplantation Beaumont Hospital, Beaumont Rd, Dublin 9, Ireland Email: mdownes@rcsi.ie
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Background:
We report on our experience of pancreatic transplants performed in Beaumont
Hospital from 1992 to January 2003. During this period, 63 pancreatic transplants were carried out.
Simultaneous pancreas and kidney transplantation is regarded as the treatment of choice for Type
1 diabetics with end stage renal failure (ESRF) by the American Diabetes
Association.1 Methods:
A
retrospective review of all the pancreas transplants between 1992 and January 2003 was carried out.
All of the patients had insulin-dependent diabetes mellitus (IDDM) and, in addition, 57 of the recipients
had concomitant end stage renal failure. For two of the patients, this was a second transplant, one
of them having had a previous renal graft which thrombosed. The second patient underwent a
simultaneous pancreas and kidney (SPK) transplant in 1998 with loss of the pancreatic graft shortly
afterwards. She subsequently received a pancreas only transplant in 2002. Results:
The follow-up
period ranges from one month to ten years and parameters used to assess graft function include Hb
A1c and serum creatnine (SPK only). There have been 22 graft losses (six kidneys, nine pancreases
and seven involving both the kidney and pancreas), to date. The one-year graft survival was 80.4%
(pancreas) and 92.7% (kidney), with a one-year patient survival of 94.8%, which compares favourably
with figures from other centres. At follow-up, the average Hb A1c at six months post-transplant
was 5.7% with a serum creatnine of 121micmol/L being recorded at one month. Conclusion:
Our
experience of pancreas transplants at Beaumont Hospital has been very encouraging with graft and
patient survival equivalent to other international centres
Keywords: Pancreas, transplant, survival Surgeon, 1 February 2005, 17-21
It is estimated that approximately 200,000 people have diabetes in Ireland with 50% of these being unaware that they have it. There is an average of seven years between onset of the disease and diagnosis, with many people presenting with one of the many diabetic complications. The American Diabetes Association estimates the annual amount spent on the management of diabetes at $44 billion.2 The pancreatic transplantation programme was initially set up in Beaumont Hospital in 1992. At this time a number of articles were reporting that SPK transplants had beneficial effects on the long-term complications encountered in Type 1 insulin-dependent diabetic mellitus (IDDM) eg. neuropathy, nephropathy and retinopathy.3-5 Mortality figures for IDDM patients on dialysis are high, 37% and 58% at one and two years, respectively and associated with this is the accelerated progression of micro and macrovascular disease.6 It was also at this time that SPK transplants were achieving graft and patient survival comparable with other solid organ transplants. Against this background, a pancreatic transplant programme was initiated with the first transplant being performed on the 31st December 1992. Pancreatic transplants are divided into SPK, PTA (pancreas transplant alone) and PAK (pancreas transplant in a patient with a previously functioning renal allograft). The majority of patients receive an SPK transplant as most units report a greater one-year graft and patient survival with this type of transplant.7
We retrospectively analysed our results of all the pancreas transplants performed at Beaumont between 1992 and January 2003. In total, there were 63 grafts transplanted in 62 patients. One patient had an SPK in July of 1998 and subsequently had an allograft pancreatectomy in August of that year for an anastamotic leak. She later received a PAK in January, 2002.
Fifty seven of the transplants were SPK with one PAK and five PTAs. All 62 of the patients suffered with IDDM and, in addition, 49 of the patients were also undergoing dialysis. The average age at transplantation was 39.9 years (range 25-54) with 34 males and 28 female recipients. The follow-up period ranged between one month to ten years and the parameters used to assess graft function being HBA1c (pancreas) and serum creatnine (kidney). Initial selection criteria demanded that recipients be <50 but this has been relaxed in later years with six patients >50 years having been transplanted. All patients had a coronary angiogram as part of their pre-transplant evaluation with the main exclusion criteria being coronary artery disease, which was not amenable to surgical correction.
The surgical technique used was that described by Sollinger et al (1998).8 Thirty three of the grafts were enterically drained with exocrine drainage into the bladder in 30 cases. Nine of these subsequently underwent enteric conversion. In the case of an SPK, the renal graft was transplanted contralaterally.
All patients who underwent SPK received quadruple immunosuppressive therapy consisting of Azathioprine, corticosteroids, antilymphocyte globulin (ATG; Fresenius, Bad Homburg, Germany) and a calcineurin inhibitor, the first 30 patients receiving Cyclosporin and the remainder receiving Tacrolimus and mycophenolic acid mofetil. The initial Cyclosporin levels were maintained between 300-400ng/ml, decreasing to 150-200ng/ml after six weeks (Homogenous Enzyme Immunoassay). Similarly, the Tacrolimus levels were originally kept at 20-30ng/ml and then reduced to 10-15ng/ml (Microparticle Enzyme Immunoassay by Abbot IMX; Fujisawa Healthcare Incorporated, Co. Kerry, Ireland).
The patients all received antiviral, antifungal and Pneumocystis prophylaxis in addition to their immunosuppressive regimens.
Patient survival was calculated from the date of the first transplant and the Kaplan Meier method was used to generate the survival curves.
The one-, three-, five- and eight-year patient, kidney and pancreas graft survival is shown in Table 1 and Figure 1 (not shown). The survivals are better in the bladder versus the enteric drained group (Figure 2 not shown). Pancreas survival figures are comparable with other centres. For example, a study of 500 SPKs in Wisconsin, USA showed a one, five and ten year survival of 96.4%, 88.6% and 76.3%, respectively.9
| TABLE 1. SURVIVAL (ONE TO EIGHT YEARS) OF PATIENTS AND GRAFTS FOLLOWING TRANSPLANTATION | |||
| Years post-surgery | Pancreas survival | Kidney survival | Patient survival |
| 1 | 80% | 92% | 95% |
| 3 | 77% | 92% | 95% |
| 5 | 75% | 76% | 91% |
| 8 | 67% | 53% | 82% |
In total there were six deaths. All the mortalities occurred in the SPK group. Cardiovascular causes accounted for two thirds of the deaths. One patient had a myocardial infarct in the perioperative period, three days after transplantation. A second at one month post-operatively, with another five and a half years post-transplant. One patient suffered a myocardial infarct three years after surgery, which was complicated by a stroke.The remaining two patients died, one at eight months after surgery from a subarachnoid haemorrhage and the other from septicaemia seven years later.
In total, 16 grafts were lost. Six of these were due to death as accounted for above. The remaining allograft losses were due to thrombosis of the graft in six cases, anastamotic leak in three patients and sepsis in one recipient.
Thirteen of the renal allografts were lost. Rejection accounted for seven cases and thrombosis of the graft in one case. The remaining allografts were lost due to death. There was only one case of delayed graft function amongst all the renal allografts.
Forty nine of the recipients were being dialysed prior to surgery with the majority undergoing haemodialysis. Eighteen patients were using chronic ambulatory peritoneal dialysis. Eight patients were transplanted pre-emptively, but all had a glomerular filtration rate of less than 60ml/min at the time of their transplant. Amongst the recipients, the average pre-transplant haemoglobin was 11.5g/dl (range 6.2-14.5) and thirty two patients were receiving Erythropoietin. The mean HBA1c was 8.42% prior to transplantion and 5.7% at six months. At one, three and five years it was 5.8%, 5.77% and 5.37%, respectively.
The average age of the donors was 26 years, with the youngest being nine and the oldest being 52 years of age. There were twice as many male as female donors.
Post-operative complications were variable, ranging from urinary tract infections, pulmonary emboli and haematuria to myocardial infarcts and pancreatectomy for graft thrombosis/anastamotic leak. Only one patient received a non-identical graft and as a result developed a haemolytic anaemia which resolved with blood transfusion.
Major complications included: Myocardial infarction (two cases), pulmonary embolism (one patient), one each of peritonitis, duodenal necrosis, intraperitoneal bleed, Gram- negative septicaemia and pancreatic abscess; one patient had an anastomotic leak and six had a thrombosed graft.
Insulin-dependent diabetes results in atherosclerosis, resulting in endothelial injury which will consequently lead to the appearance of macrophages and lipids in the vessel wall.10 The high blood glucose levels seen in diabetic patients produces advanced glycation end products which will also help the development of the atherosclerotic plaques.11 The DCCT trial published in 1993 showed the beneficial effects of tight glycaemic control with a lowering of blood glucose showing a 50%, 76% and 60% reduction in renal, retinal and neural complications, respectively.12 A successful kidney transplant will improve the survival rate of IDDM but it will not halt the progression of the disease, whereas a pancreatic transplant will eliminate abnormalities in insulin production, which subsequently will result in the control of hyperglycaemia.13 Recently published studies have shown a significant improvement in diabetic microangiopathy, neuropathy and nephropathy post-pancreatic transplantion.3,14,15 Besides these benefits, it has been shown that post SPK, graft recipients exhibit a less atherogenic profile with normal cholesterol and triglycerides and increased high density lipoprotein HDL.16 All of these changes reduce the development and progression of atherosclerotic plaques formation.
Currently, the graft and patient survival following SPK transplantation is equal to or better than other solid organ transplants.17 As a consequence it is becoming a more acceptable form of therapy. The International Transplant Registry reported in 1998 that, by the end of 1996, nine thousand pancreas transplants had been performed. For those between 1994 and 1996, the one- year pancreas survival rates were 81% for SPK, 71% for PAK and 64% for PTA.18
The reduction in long-term complications and improved survival means that an SPK transplant is now considered the treatment of choice for IDDM with end stage renal failure by the American Diabetic Association.1
In summary, our experience of pancreas transplants has been very encouraging with patient and graft survival comparable with the results from other centres. Most of our transplants have been SPKs but an increase in the number of PAKs may be seen if there is a reduction in the number of cadaveric renal donors. All of the successful recipients showed an improvement in their HBA1c post-surgery and a decrease in their serum creatnine in the case of the SPK transplant patients.
Copyright 20 December 2004
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