Analysis of large versus small pheochromocytomas: operative approaches and patient outcomes.

BACKGROUND: Laparoscopic adrenalectomy for small pheochromocytomas, although challenging, is widely accepted. However, its application to pheochromocytomas larger than 6 cm is questioned due to concerns of malignancy and case complexity. Our aim was to examine the impact of pheochromocytoma tumor size (>/=6 cm vs <6 cm) on operative approach and postoperative patient outcomes. METHODS: A retrospective review of adrenalectomies performed at 3 university hospitals over 1 decade was analyzed. All pheochromocytomas were identified and then divided based on size into large (>/=6 cm) and small (<6 cm) groups. We examined patient and tumor demographics, pathologic diagnosis, operative approach (laparoscopic vs open), postoperative complications, and biochemical cure rates. Data were analyzed using the Student t test and Fisher exact test with a P value <.05 considered significant. RESULTS: From 1995 to 2005, 65 pheochromocytomas were resected. Of the total, 38% (n = 25) tumors were >/=6 cm and 62% (n = 40) were <6 cm. For the large tumors, 1 out of 25 (4%) was malignant, whereas no small tumors were malignant. There was no statistically significant increased risk of malignancy in tumors >/=6 cm in size (P = .31). Initial operative approach was based on surgeon preference. Of the adrenalectomies performed, 88% were laparoscopic, with 3 of 25 (12%) large tumors requiring conversion from laparoscopic to open for intraoperative bleeding. None of the small tumors required conversion. No major postoperative complications (eg, stroke or myocardial infarction) occurred in either group. Minor complications (eg, wound infections and hematomas) were noted in 16% of large tumors and 12.5% of small tumors (P = .45). A total of 96% (24 of 25) patients with large tumors and 100% with small tumors showed postoperative biochemical cure. Tumor recurrence was noted in 1 patient with a tumor <6 cm. CONCLUSIONS: Pheochromocytomas >/=6 cm pose a challenge for laparoscopic resection, and concerns have been raised about the validity of this operative approach. This study demonstrates that there is no significant difference in the rate of malignancy for pheochromocytomas >/=6 cm versus <6 cm. There also were no significant differences identified in complication rates, postoperative biochemical cures, or tumor recurrence rates between these groups. Laparoscopic resection of pheochromocytomas can be safely accomplished regardless of size in centers with surgeons experienced in these procedures.

A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans.

AIMS/HYPOTHESIS: Successful gene transfer to pancreatic islets might be a powerful tool for dissecting the biological pathways involved in the functional impairment and destruction of beta cells in type 1 diabetes. In the long run, such an approach may also prove useful for promoting islet graft survival after transplantation in diabetic patients. However, efficient genetic modification of primary insulin-producing cells is limited by the specific compact structure of the pancreatic islet. We present here a whole-pancreas perfusion-based transduction procedure for genetic modification of intact pancreatic islets. MATERIALS AND METHODS: We used flow cytometry analysis and confocal microscopy to evaluate the efficiency of in vitro and perfusion-based transduction protocols that use adenoviral and lentiviral vectors expressing green fluorescent protein. Islet cell viability was assessed by fluorescence microscopy and beta cell function was determined via glucose-stimulated insulin secretion. RESULTS: In intact rat and human pancreatic islets, adenoviral and lentiviral vectors mediated gene transfer to about 30% of cells, but they did not reach the inner cellular mass within the islet core. Using the whole-pancreas perfusion protocol, we demonstrate that at least in rodent models the centrally located insulin-producing cells can be transduced with high efficiency, while preserving the structural integrity of the islet. Moreover, islet cell viability and function are not impaired by this procedure. CONCLUSIONS/INTERPRETATION: These results support the view that perfusion-based transduction protocols may significantly improve the yield of successfully engineered primary insulin-producing cells for diabetes research.

Novel experimental strategies to prevent the development of type 1 diabetes mellitus.

Type 1 diabetes is an autoimmune disease leading to extensive destruction of the pancreatic beta-cells. Our research focusses on the role of beta-cells during the course of the disease, aiming at finding novel strategies to enhance beta-cell resistance against the cytotoxic damage inflicted by the immune system. Special attention has been paid to the possibility that cytokines released by the immune cells infiltrating the pancreatic islets can directly suppress and kill beta-cells. Certain cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma) either alone or in combination, are able to activate signal transduction pathways in beta-cells leading to transcription factor activation and de novo gene expression. In this context, it has been found that induction of inducible nitric oxide synthase mediates an elevated production of nitric oxide, which impairs mitochondrial function and causes DNA damage eventually leading to apoptosis and necrosis. However, other induced proteins SUCH AS heat shock protein 70 and superoxide dismutase may reflect a defense reaction elicited in the beta-cells by the cytokines. Our strategy is to further seek for proteins involved in both destruction and protection of beta-cells. Based on this knowledge, we plan to apply gene therapeutic approaches to increase expression of protective genes in beta-cells. If this is feasible we will then evaluate the function and survival of such modified beta-cells in animal models of type 1 diabetes such as the NOD mouse. The long-term goal for this research line is to find novel approaches to influence beta-cell resistance in humans at risk of developing type 1 diabetes.

A clinical, epidemiological and laboratory study on avoiding the risk of transmitting viral hepatitis during vaccinations with the Dermojet protected by an anticontaminant disposable device.

Jet injectors may transmit blood-borne infections, such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). To evaluate the safety of an anticontaminant disposable device which protects the jet injector apparatus, 22,714 healthy subjects were intradermally inoculated (38,162 inoculations) with a variety of vaccines. All the subjects were systematically followed-up clinically and epidemiologically for 6-18 months after inoculation; blood samples from 1619 subjects, before and 60-75 days after inoculation, were examined by enzyme-linked immunosorbent assay (ELISA) for HBV, hepatitis C virus (HCV) and HIV. Before vaccination 212 (13.09%) subjects were positive: 204 positive for HBV markers and eight for the HCV marker. None of the subjects were positive for the anti-HIV marker. During the clinico-epidemiological surveillance and the laboratory investigations mentioned above no clinical viral hepatitis B or C case and no seroconversion to positivity for HBV or HCV markers among the susceptible persons in the group were reported. Considering that in similar situations there is a theoretical risk of transmission as high as 1 per 388 to 1 per 3367 injections and that in our case 38,162 inoculations were performed in 22,714 subjects with the same Dermojet protected by the same type of anticontaminant disposable device, no contamination risk being reported, the conclusion can be reached that jet injectors can be safely used in the medical practice if they are protected by the sterile anticontaminant disposable device.