Esthesioneuroblastoma: endonasal endoscopic treatment.

Objectives: To illustrate endoscopic techniques used in the treatment of esthesioneuroblastoma and to advocate this method of management followed by radiation therapy in selected cases. Methods: A retrospective case series of 10 patients with esthesioneuroblastomas treated between 1999 and 2004 at a tertiary referral center using endonasal techniques. Results: Mean age of patients at presentation was 56.2 years (median 57 years). Seven patients were female and 3 patients were male. Kadish staging at presentation was: A - 3 patients, B - 5 patients, C - 2 patients. Dulguerov stage at presentation was: T1 - 4 patients, T2 - 4 patients, T3 - 2 patients. The period of follow-up ranged from 11 months to 74 months (mean 38.1 months, median 39 months). To date no recurrence has developed in any patient. Conclusions: Our experience suggests that endoscopic surgery can be an effective method of management. Strict attention to selection criteria, careful surgical techniques, and regular follow-up are key elements for success.     

Experimental fetal hydrocephalus. Ventriculo-amniotic shunt

When the original idea was conceived 8 years ago to develop a surgical technique for the treatment of fetal hydrocephalus, the pathway towards prenatal surgery for this affection was totally unexplored. The operation appeared to be feasible because of the possibility of a ventriculo-amniotic shunt. The most important steps in our experimental studies in the ewe were creation of a fetal hydrocephalus by injection of a suspension of kaolin powder into cisterna magna; the treatment of the hydrocephalus by a mini-ventriculo-amniotic shunt, by cutting the cardiac end of a low pressure Pudenz pediatric catheter. Lambs were delivered by Cesarean two weeks before end of gestation. Coronal sections of brains of control and treated lambs showed reduction in hydrocephalus in the latter. These findings were the basis for the application of the method to treatment of human fetal hydrocephalus.     

The evolution of morphologic and biomechanical changes in reversed and in-situ vein grafts.

A comparative study of experimental reversed (RV) and in-situ (INS) vein grafts with respect to the evolution of morphologic and compliance characteristics was done in a canine model. In addition, the compliance characteristics in a series of human INS vein grafts were recorded as a function of time after operation. At 6 months after implantation, all experimental grafts displayed well-developed intimal hyperplasia. There was no significant difference in either absolute intimal thickness (INS 0.133 +/- 0.09 mm vs. RV 0.085 +/- 0.06 mm; NS) nor in the percentage of the total wall thickness occupied by the intima when experimental INS grafts were compared with RV grafts after 6 months. Similarly, compliance values of INS and RV vein grafts were similar at all time intervals examined up to 6 months after operation. Thirty-three human INS vein grafts had a mean compliance value of 1.74 +/- 0.72 (percent radial changes per mmHg X 10(-2) at a median postoperative interval of 14 weeks. This value did not differ significantly from those measured in the INS vein grafts. Although all vein grafts examined retained their native viscoelastic properties, this study suggests that functioning human INS vein grafts are less compliant than previously suspected on the basis of prior ex-vivo and clinical studies of RV saphenous vein grafts. The purported clinical superiority of the INS vein graft cannot be explained on the basis of superior biomechanical performance or failure to develop intimal hyperplasia.     

Abnormal wall strain at distal end-to-side anastomoses

Cyclic stretch has been demonstrated to induce proliferative and secretory activities by cultured arterial endothelial and smooth muscle cells, cellular processes that contribute to the development of intimal hyperplasia. A model of an end-to-side anastomosis was developed to examine the hypothesis that regions of the artery at such anastomoses are subjected to facally increased cyclic stretch, which may stimulate the development of intimal hyperplasia. Polytetrafluoroethylene grafts were anastomosed end to side to latex rubber tubes that have elastic properties similar to those of the human femoral artery. Pulse waves with physiologic pressure, rate, and contour were applied, and systolic and diastolic diameters were measured in two planes at longitudinal intervals. Circumferential strain imposed on the latex artery was calculated at each interval. Strain imposed perpendicular to the suture line was also measured. Circumferential strain was consistently maximal at a distinct region of the artery along the proximal third of the anatomosis (6.0±1.1% vs. 3.3±0.5% at other regions of the artery). The maximal strain across the suture line was found at precisely the same region (3.9±0.3% vs. 2.0±0.4%). The anastomotic region of the recipient artery in a distal end-to-side anastomosis is subjected to cyclic circumferential strains two times greater than those experienced by the remainder of the artery. This corresponds to a common location of intimal hyperplasia. Such strains may be a stimulus for intimal hyperplasia.Presented at the Seventeenth Annual Meeting of the Peripheral Vascular Surgery Society, June 7, 1992, Chicago, Ill.     

All-trans-retinoic acid decreases vein graft intimal hyperplasia and matrix metalloproteinase activity in vivo

BACKGROUND: Development of vein graft intimal hyperplasia has been associated with increased activity of matrix metalloproteinases (MMPs). All-trans-retinoic acid (atRA) decreases expression and activity of MMPs in tissue culture and has decreased intimal hyperplasia following arterial balloon catheter injury. We examined the effect of oral administration of atRA on intimal hyperplasia and MMP expression in an animal model of vein bypass grafting. MATERIALS AND METHODS: Interposition jugular vein bypass grafts were placed in the carotid artery of New Zealand white rabbits. Animals received either atRA (10 mg/kg/day) or vehicle (corn oil) for a period of 2 weeks. Retinoic acid serum levels were determined by HPLC. Intimal and medial areas were measured using morphometric analysis of perfusion-fixed vein graft specimens, and intimal thickness was calculated using circumferential measurements. Expression of MMP-2, MMP-9, and TIMP-1 in vein grafts and unoperated control veins was determined using Northern analysis, and proteolytic activity was determined using substrate gel zymography. RESULTS: Animals treated with atRA had significantly elevated serum levels of this compound and its metabolites. A decrease in intimal to medial ratio was noted after 28 days in vein grafts from treated animals (0.63 vs 0.88, P < 0.01), and a decrease in calculated intimal thickness was noted at 7 and 28 days. Expression of MMP-2 was decreased in treated animals 7 days following surgery, and expression of both MMP-2 and MMP-9 was decreased at 28 days. A decrease in proteolytic activity was noted on zymography at 68 kDa, 7 and 28 days following surgery in vein grafts from animals treated with atRA, corresponding with a decrease in the active form of MMP-2. Increased expression of TIMP-1 was noted in vein grafts from both the treated and the control groups, 7 and 28 days following graft placement. CONCLUSIONS: Oral administration of all-trans-retinoic acid resulted in decreased intimal hyperplasia in an animal model of vein bypass grafting. This was associated with decreased expression and activity of MMP-2 in treated animals.     

Metalloproteinase levels are decreased in symptomatic carotid plaques

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.