DOI: 10.1097/TP.0b013e3181722fde
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PMID: 18551078
Issn Print: 0041-1337
Publication Date: 2008/06/15
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Excerpt
A 19-year-old man with a CF (mutation R553X and 244–245Δ) had severe pancreatic insufficiency and insulin dependent diabetes since the age of 5 years. Plasma C peptide level was not detectable. Under external insulin pump with 98 IU/day insulin requirements, diabetes control was poor with an HbA1c of 9.8% and hypoglycaemic events. The patient had also chronic respiratory failure, with a FEV1 at 1070 mL (27%) and a FVC at 1500 mL (35%). He was dependent on intravenous antibiotic therapy and used nocturnal parenteral nutrition for severe denutrition (body mass index 17.6 kg/m2).
He was placed on waiting list for combined lung-islet transplantation on July 9, 2007 because of brittle diabetes and end-stage lung disease. On October 29, 2007, the patient received a double lung graft. At the same time, islets were purified from the pancreas of the same donor. One week after lung transplantation, 149,000 islets were maintained in culture in presence of human AB serum. Under local anesthesia, 3310 islets/kg body weight were injected by a percutaneous transhepatic approach which allowed the portal vein to be catheterized under ultrasound guidance. Immunosuppression consisted of corticosteroids (1 mg/kg for 1 week then rapidly tapered to 0.2 mg/kg), cyclosporin (trough level around 300 μg/L), and azathioprine (2 mg/kg). His postoperative course was satisfactory and he was extubated 3 days after lung transplantation. Four weeks latter, his FEV1 was 2680 mL (65%) and FVC 2730 mL (58%). One day after transplantation, grafted islets were functional with a plasma C peptide level of 1.4 μg/L for a glycemia of 6.6 mmol/L. One month after islet transplantation, insulin requirements decreased from 98 to 30 IU/day with disappearance of hypoglycemic events and an improvement in glucose stability (Fig. 1).
More and more centers worldwide perform islet allotransplantation in patients with type 1 diabetes as it is a simpler and safer method than whole organ pancreas transplantation (3). Ten years ago, Tschopp et al. (4) reported a case of simultaneous islet and lung transplantation in a patient with CF-related diabetes. At the same time and under general anesthesia, purified islets were injected into the transverse colic vein by a surgical approach. Recently, three cases of simultaneous lung and pancreas transplantations have been reported in CF patients with diabetes. Despite several complications among them a partial venous thrombosis of the donor pancreas portal vein, both metabolic and pulmonary functions were satisfactory (5). In our patient, islet transplantation was performed under local anesthesia and by a percutaneous transhepatic puncture avoiding morbidity of abdominal surgery. After lung transplantation, the islets were maintained in culture for 1 week without loss of cellular viability to wait the optimal clinical conditions for the islet transplantation.
During the early posttransplant period in patients with CF, there is a high risk of severe complications including acute rejection, infection, and renal failure. A careful management is warranted especially in patients with diabetes. By restoring glucose stability, islet transplantation may improve the management of lung grafted CF patient in intensive care unit and decrease complications in early postsurgical period. In our patient, the need to continue insulin therapy at low dose can be explained by the use of diabetogenic immunosuppressive agents together with the relatively low number of grafted islets.
