Chad E. Hamner

Pheochromocytoma and Paraganglioma in Children: A Review of Medical and Surgical Management at a Tertiary Care Center

OBJECTIVE. The aim of this study was to review our institutional experience managing pheochromocytomas and paragangliomas in children. METHODS. A retrospective chart review of the Mayo Clinic database from 1975 to 2005 identified 30 patients <18 years of age with histologically confirmed pheochromocytoma or paraganglioma. RESULTS. There were 12 patients with pheochromocytomas and 18 with paragangliomas. The most common presenting symptoms were hypertension (64%), palpitation (53%), headache (47%), and mass-related effects (30%). Nine patients (30%) had a genetic mutation or documented family history of pheochromocytoma or paraganglioma. Fourteen patients (47%) had malignant disease, whereas 16 (53%) had benign disease. Logistic analysis showed that statistically significant risk factors for malignancy were (1) paraganglioma, (2) apparently sporadic, as opposed to familial, pheochromocytoma or paraganglioma, and (3) tumor size of >6 cm. Surgical resection was performed for 28 patients (93%), with perioperative mortality and major morbidity rates of 0% and 10%, respectively. Resection achieved symptomatic relief for 25 patients (83%). All patients with benign disease appeared cured after resection. For patients with malignant disease, the 5- and 10-year disease-specific survival rates were 78% and 31%, respectively, and the mean survival time was 157 ± 32 months. CONCLUSIONS. The incidence of malignant pheochromocytoma/paraganglioma was high in children (47%), particularly those with apparently sporadic disease, paraganglioma, and tumor diameters of >6 cm. Patients with a known genetic mutation or familial pheochromocytoma/paraganglioma were more likely to achieve resection with negative microscopic margins and had improved disease-specific mortality rates. Surgical resection remains the treatment of choice for pheochromocytoma and paraganglioma.

Nitric oxide and prostacyclin in ultrasonic vasodilatation of the canine internal mammary artery

BACKGROUND Investigators recently demonstrated increased free blood flow from radial artery free grafts harvested using ultrasonic technology. We investigated the mechanism underlying this phenomenon. METHODS Canine internal mammary artery segments (with and without intact endothelium) were precontracted with norepinephrine and sonicated 3 seconds in organ chambers with ultrasonic coagulating shears (Harmonic Scalpel; Ethicon Endo-Surgery, Cincinnati, OH) functioning at level 2. Vessel tension was continuously measured to examine vasoactivity in response to sonication alone (control) or with N(ù)-Nitro-l-arginine (l-NNA) and indomethacin added to the chamber medium individually or in combination. Tissue heating, acoustic pressure, and endothelial damage as detected by scanning electron micrography were also assessed. RESULTS In vitro sonication with the Harmonic Scalpel induced predominately endothelium-dependent internal mammary artery vasorelaxation but a small endothelium-independent contribution was also observed. Early vasorelaxation (1 minute after stimulus) was maximally inhibited by l-NNA alone and in combination with indomethacin. Relaxation during this period was insignificantly affected by indomethacin alone. Only the combination of l-NNA and indomethacin maximally inhibited late vasorelaxation (5 minutes after stimulus), whereas inhibitory effects of l-NNA diminished during this time period. Indomethacin inhibited relaxation substantially during this phase, although significantly less than did l-NNA alone. The Harmonic Scalpel minimally heated the tissue surface (0.3 +/- 0.03 degrees C) and did not disrupt endothelial cell integrity while operating at 50 mW/cm(2) intensity (acoustic pressure 40 kPa). CONCLUSIONS Sonication induces vasorelaxation almost completely by time-dependent endothelial nitric oxide and prostacyclin release, which appears unrelated to tissue heating or endothelial architectural disruption.

Gene transfer to coronary artery bypass conduits

BACKGROUND Gene therapy is a rational approach to prevention of stenosis in saphenous vein grafts used as conduits for coronary artery bypass grafting. To explore this possibility we developed methods for adenoviral-mediated gene transfer to canine saphenous veins. METHODS During a single procedure, autogenous canine saphenous vein segments were transduced ex vivo and used as coronary artery bypass grafts. The proximal end of each vein was ligated, adenovirus containing the Escherichia coli beta-galactosidase gene (Ad.CMVLacZ) was delivered at titers of 2.5 x 10(9) or 5 x 10(9) plaque-forming units (pfu)/mL to the lumen through a distal heparin lock, and the segment was immersed in the viral solution for 1 hour at 37 degrees C. Control segments were exposed to diluent alone in an identical manner. Aortocoronary anastomoses were made using cardiopulmonary bypass. Transgene expression was assessed qualitatively and quantitatively after 3 days. RESULTS Beta-galactosidase levels showed a dose-dependent increase: 0.00 +/- 0.00 ng/mg total protein for controls; 5.60 +/- 2.27 ng/mg total protein for a viral titer of 2.5 x 10(9) pfu/mL and 11.97 +/- 6.14 ng/mg for 5 x 10(9) pfu/mL. The two dosage groups differed significantly from each other (p = 0.035) and from controls (p = 0.003). X-gal staining demonstrated mostly endothelial and scattered adventitial transgene expression. CONCLUSIONS Transgene expression after ex vivo gene transfer into saphenous vein grafts in a canine coronary artery bypass model indicates that this method may be useful for delivery of therapeutic genes to prevent or retard vein graft arteriosclerosis.

Safety and biocompatibility of the myosplint system - A passive implantable device that alters ventricular geometry for the treatment of heart failure

A passive implantable device developed for the treatment of heart failure, the Myosplint® System, has demonstrated therapeutic efficacy in a canine model of pacing induced heart failure. The current study sought to demonstrate chronic device safety and biocompatibility, in vivo, in a normal porcine model.Two devices were implanted into each normal, beating heart of 6 juvenile and 15 adult pigs without cardiopulmonary bypass. Animals survived 90 (juvenile and adult) or 180 days (adult only). Serial hematologic and biochemical profiles were evaluated in each pig during the study period. A comprehensive necropsy study was performed in each pig to evaluate device stability, healing response, thromboembolism, hemorrhage, and intravascular hemolysis related to the Myosplint system.Six adult animals died from infectious disease (four) or perioperative (two) complications unrelated to device design or function and were excluded from the final analysis. No clinical, biochemical or pathologic evidence of significant, device related adverse events was observed in surviving animals. The chronic myocardial healing response appeared normal at term, and all devices maintained their structural integrity throughout the study.The Myosplint system was easily implanted in beating hearts and was rapidly incorporated into host tissues without clinically significant morbidity in this porcine model.