As a consequence of its large volume, a microencapsulated islet graft can be implanted only into the peritoneal cavity. The graft volume can be reduced by using small capsules. However, reduction of the diameter of the capsules holds a certain risk, because with smaller capsules, more islets may be found to protrude from the capsules. We have developed a lectin binding assay which, after encapsulation, specifically labels islets or parts of islets that are insufficiently immunoprotected as a consequence of inadequate, and particularly incomplete, encapsulation. With this assay, we found that a reduction of the capsule diameter from 800 micrometers to 500 micrometers was associated with an increase in the percentage of inadequately encapsulated islets from 6.3+/-1.2% to 24.2+/-1.5%. The in vivo significance of this finding was investigated by performing allotransplantations with large diameter (700-800 micrometers) and small diameter (400-500 micrometers) capsules. With large-capsule islet grafts, all recipients (n=5) became normoglycemic for 7-16 weeks, whereas with small-capsule islet grafts, only one of seven recipients became normoglycemic. The in vivo significance of inadequate encapsulation was further substantiated by our finding that most large capsules were floating freely in the peritoneal cavity without any cell adhesion, whereas the vast majority of small capsules was found to be adherent to the surface of intra-abdominal organs and infiltrated by immune cell elements characteristic of both an allograft reaction and a foreign body reaction. We conclude that successful use of capsules with small diameters requires further study to determine which factors in the encapsulation procedure should be modified to reduce the number of inadequate small capsules.

Several factors stand in the way of successful clinical transplantation of alginate-polylysine-alginate microencapsulated pancreatic islets. These obstacles can be classified into three categories. The first regards the technical aspects of the production process. Limiting factors are the insufficient ability to produce small capsules with an adequate production rate, and insufficient insight into the factors determining the optimal chemical and mechanical properties of the capsules. The second category regards the functional aspects of the microencapsulated islets, such as the limitations of the transplantation site and the absence of a physiologic insulin response of the encapsulated islets to elevated blood glucose levels. The third category regards the fact that survival times of encapsulated islet grafts are still limited to several weeks or months, which is mainly explained by a pericapsular fibrotic overgrowth reaction as a consequence of the bioincom-patibility of the capsule membrane. This study describes these obstacles, and thereby summarizes the requirements needed for successful clinical application of encapsulated islet transplantation.

Several aspects of false aneurysm development after prosthetic resconstruction for aortoiliac obstructive disease were studied. For this purpose the long-term results (up to 20 years of follow-up) of 518 patients with implanted arterial prostheses in the aortoiliofemoral tract were retrospectively evaluated. Completeness of follow-up data was 83.2% 15 years after operation. A total of 101 false aneurysms (21 aortic, 53 iliac, and 27 femoral) were detected in 69 patients and verified by operation. The incidence per patient was 69 of 518 patients (13.3%). The incidences per anastomosis were: aortic, 21 of 438 anastomoses (4.8%); iliac, 53 of 835 anastomoses (6.3%); and femoral, 27 of 198 anastomoses (13.6%). Almost one half (47.5%) of all the false aneurysms were asymptomatic and were detected by angiography or ultrasonography. Chances for late survivors to develop a false aneurysm during follow-up were calculated by the life-table method. The chance to be free of a false aneurysm at any site was 77.2% 15 years after operation. These chances were 92.3%, 84.5%, and 76.2% for aortic, iliac, and femoral anastomoses, respectively. Analyses of subgroups showed that the development of a false aneurysm was significantly correlated with the presence of hypertension, multilevel disease, the type of suture material, and the type of anastomosis. These results indicate unexpectedly high chances for the development of false aneurysms in long-term survivors after aortoiliac or aortofemoral prosthetic reconstructions. We advocate the use of a life-long follow-up schedule with periodic angiography and ultrasonography for these patients.

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