Long-Term Metabolic Control and Pancreatic Graft Survival According to Surgical Technique L.C.F. Tajra, J.M. Dubernard, M. Dawhara, N. Lefrancois, L. Badet, and X. Martin
HE PANCREAS transplantation programme at the Hopital Edouart Herriot was initiated in October 1976 and three different surgical techniques have been used: segmental graft with duct obstruction by neoprene injection (DO), described by our group in 1976,1 bladder drainage (BD), and enteric drainage (ED). To evaluate the long-term advantages of one technique over the others, we have retrospectively studied patients with a pancreas transplant functioning for 3 years or more. PATIENTS AND METHODS Of the 307 pancreatic transplantations realized between October 1976 and September 1998 in our center, 250 were performed before August 1994. A good pancreatic graft function for more than 3 years was observed in 102 patients (56 men and 46 women). Twenty-four grafts were lost more than 3 years after transplantation. Outcome of the remaining 78 patients (36 men and 42 women) was retrospectively studied regarding patient and graft survival, and endocrine function. Mean age of patients was 38 years (range 22 to 53). Mean duration of diabetes was 24 years (range 11 to 48). Duct obstruction was used in 42 patients, whereas 25 patients received a pancreaticoduodenal graft with bladder drainage and 11 had pancreaticoduodenal graft with enteric drainage. Protocols of immunosuppression utilized in our center have been described in detail elsewhere.2 Data between groups were compared with one-way analysis of variance (ANOVA test).
RESULTS Graft Survival
At 5 years, pancreatic graft survival was 40% for DO, 60% for BD, and 65% for ED (P ⬍ .05). Out of the 102 pancreatic grafts functioning more than 3 years, 24 lost their grafts at long term (8 at 4 years, 5 at 5 years, 2 at 6 years, 2 at 7 years, 3 at 8 years, 1 at 9 years, and 1 at 14 years). The cause of graft loss was death in 4 patients (myocardial infarction in three patients and cerebral hemorrhage in one) and arterial thrombosis in 4 patients. Sixteen were attributed to immunologic causes (rejection). Before 1987, 3-year pancreas graft survival was 50%. Since 1987, with quadruple therapy, it increased to 70%. Metabolic Evaluation
No difference was observed in fasting blood glucose and OGTT between BD and ED grafts. When total grafts were
compared to segmental grafts, significantly higher glucose levels and lower insulin and C-peptide levels were observed in DO pancreas. These differences were progressive with time and reached their higher levels at 5 years (P ⬎ .05 at 3 years, P ⬎ .0001 at 5 years). No difference was observed, up to 9 years, in glycosylated hemoglobin between total and segmental grafts. Insulin and C-peptide secretion were significantly higher with total than in segmental graft recipients during fasting and oral tolerance tests. One patient with DO graft maintained normal blood sugar and glycosylated hemoglobin 14 years after transplantation.
Although many efforts have been made to optimize insulin therapy, only pancreaticorenal transplantation can restore diabetic patients in a condition of normoglycemia compatible with a normal life at present.3 Pancreas graft survival continues to improve with new protocols of immunosuppression. Survival rates of pancreatic grafts are now comparable to those observed in transplantation of other organs. Several studies have shown that glucose control remains normal or near normal as long as patients have a functioning graft.4,5 However, even during the first year after transplantation, segmental grafts already show a significantly less physiologic response to glucose stimulation.6 In our study, these abnormalities increased during follow-up and achieved higher levels at 5 years. The differences observed in oral glucose tolerance tests at 5 years could be due to the smaller mass of endocrine tissue transplanted with a segmental graft. Later, a stabilization in endocrine function was observed, independently of the technique used. Total duodenopancreas grafts seem to offer an optimal mass of tissue and enteric drainage is more physiologic than bladder drainage. Segmental pancreas transplantation is technically simpler, but metabolic control after
From the Department of Urology and Transplantation Surgery, Hopital Edouard Herriot, Lyon, France. Address reprint requests to Luis Carlos Feitosa Tajra, Hopital Edouard Herriot, Service d’Urologie et Transplantation, Place d’Arsonval 69437, Lyon, France.
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Transplantation Proceedings, 31, 3192–3193 (1999)
LONG-TERM METABOLIC CONTROL
stimulation is less satisfactory. Glycosylated hemoglobin was more elevated in the enteric drainage group during the first two years but later the three groups showed similar ranges. In conclusion, we believe that total duodenopancreas graft with enteric drainage is presently the best technique leading at long term to the best graft survival and to an excellent metabolic control. Although the best glucose control is achieved with pancreatico-duodenal grafts, we have observed that segmental grafts also are able to maintain normal blood sugar and glycosylated hemoglobin in patients up to 14 years.
REFERENCES 1. Dubernard JM, Trager J, Neyra P, et al: Surgery 84:633, 1978 2. Dawahra M, Cloix P, Martin X, et al: Transplant Proc 25:827, 1993 3. Sutherland DER, Dunn DL, Goetz FC, et al: Ann Surg 210:274, 1989 4. Brattstrom C, Tibell A, Tyden G, et al: Transplant Proc 26:414, 1994 5. Sutherland DER, Gruessner A: Transplant Proc 27:2977, 1995 6. Souza Castelo A, Lefrancois N, Martin X: Transplant Proc 24:839, 1992