Perforated esophageal intervention focus (PERF) study: a multi-center examination of contemporary treatment.

The treatment of esophageal perforation (EP) remains a significant clinical challenge. While a number of investigators have previously documented efficient approaches, these were mostly single-center experiences reported prior to the introduction of newer technologies: specifically endoluminal stents. This study was designed to document contemporary practice in the diagnosis and management of EP at multiple institutions around the world and includes early clinical outcomes. A five-year (2009-2013) multicenter retrospective review of management and outcomes for patients with thoracic or abdominal esophageal perforation was conducted. Demographics, etiology, diagnostic modalities, treatments, subsequent early outcomes as well as morbidity and mortality were captured and analyzed. During the study period, 199 patients from 10 centers in the United States, Canada, and Europe were identified. Mechanisms of perforation included Boerhaave syndrome (60, 30.1%), iatrogenic injury (65, 32.6%), and penetrating trauma (25, 12.6%). Perforation was isolated to the thoracic segment alone in 124 (62.3%), with 62 (31.2%) involving the thoracoabdominal esophagus. Mean perforation length was 2.5 cm. Observation was selected as initial management in 65 (32.7%), with only two failures. Direct operative intervention was initial management in 65 patients (32.6%), while 29 (14.6%) underwent esophageal stent coverage. Compared to operative intervention, esophageal stent patients were significantly more likely to be older (61.3 vs. 48.3 years old, P < 0.001) and have sustained iatrogenic mechanisms of esophageal perforation (48.3% vs.15.4%). Secondary intervention requirement for patients with perforation was 33.7% overall (66). Complications included sepsis (56, 28.1%), pneumonia (34, 17.1%) and multi-organ failure (23, 11.6%). Overall mortality was 15.1% (30). In contemporary practice, diagnostic and management approaches to esophageal perforation vary widely. Despite the introduction of endoluminal strategies, it continues to carry a high risk of mortality, morbidity, and need for secondary intervention. A concerted multi-institutional, prospectively collected database is ideal for further investigation.

Cerebrovascular adaptation in chronic hydrocephalus.

This study characterizes the regional changes in vascularity, which accompanies chronic progressive hydrocephalus. Fifteen dogs underwent surgical induction of hydrocephalus and were used for histologic studies. Animals were divided into 4 groups: surgical control, short term (< or = 5 weeks), intermediate term (8 weeks), and long term (10 to 12 weeks). Vessel diameter, density, and luminal area were calculated by imaging quantification after manual vessel identification in the cortical gray, white matter, and caudate nucleus. Capillary vessel diameter decreased 23.5% to 30.2% (P < 0.01) in the caudate, but then returned to normal at 12 weeks. Capillary vessel density decreased 53.5% (P < 0.05) in the cortical gray, but then increased to 234.8% (P < 0.01) over surgical controls at 12 weeks. There was no initial decrease in capillary density in the caudate; however, the long-term group capillary density was significantly greater (172.8% to 210.5%, P < 0.01) than surgical controls. Overall, there was a short-term decrease in lumen area, with recovery in the longer term. Glial fibrillary acidic protein (GFAP) immunohistochemistry demonstrated the pattern of GFAP staining and reactive astrocytes differed in the caudate compared with the occipital cortex. This data suggest that an increase in capillary density and diameter may be an adaptive process allowing maintenance of adequate cerebral perfusion and metabolic support in the hypoxic environment of chronic hydrocephalus.

Development and characterization of an adult model of obstructive hydrocephalus.

While hydrocephalus is common in adults its pathophysiology is not fully understood and its treatment remains problematic. Previous animal models have been acute, developmental, or involved non-specific blockage or inflammation and are not suitable for study of chronic adult-onset hydrocephalus. In this study, we describe the development of a canine model which allows basic physiological studies along with diagnostic and treatment procedures via surgical occlusion of the fourth ventricle with a bolus injection of cyanoacrylic gel glue. A total of 26 adult male canine mongrels were used for the induction of chronic hydrocephalus and were monitored for 1-12 weeks post-induction using magnetic resonance imaging (MRI), intracranial pressure measurements, and neurological fitness assessments. Of these, 81% (21/26) developed hydrocephalus that was mild (N = 6), moderate (N = 7), or severe (N = 8). Pressures were mild and transiently elevated, and brain compliance decreased. Clinical symptoms were also mild and transient. This model is unique in its focal obstruction without local compression or general inflammation and should facilitate the study of the pathophysiology and treatment of chronic adult-onset hydrocephalus.

Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.

Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.