Citations

Abstract Purpose: Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma. Experimental Design: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 μg twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated. Results: Dose escalation to 1,750 μg twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively. Conclusions: Inhalation of GM-CSF at doses from 250 to 1,750 μg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen. Clin Cancer Res; 16(15); 4024–30. ©2010 AACR.

Abstract The natural history of postirradiation extracranial cerebrovascular disease is uncertain. Previous reported cases spanning 20 years of carotid surgery are difficult to evaluate, because patients may sometimes have unspecified symptoms, physical examinations, postoperative results, and follow-up. Also, the evolution of carotid surgery over the past two decades makes it impossible to compare earlier operative technique with the state-of-the-art technique of today. Our series of 7 patients underwent 9 carotid endarterectomies with an average follow-up period of 46 months. The number of patients is small, and although technically this is a more difficult operation, we feel the results are favorable and may be comparable with endarterectomy procedures in nonirradiated patients. These patients should be approached as if radiation changes are not a major factor when they are considered for reconstructive arterial surgery.

Abstract Twenty surgically verified pituitary adenomas were imaged in a systematic comparative fashion with high field strength magnetic resonance imaging (MRI) and computed tomography (CT) before operation. The study group included 11 microadenomas, 4 macroadenomas, 2 recurrent microadenomas, and 3 recurrent macroadenomas. The MRI and CT examinations were evaluated for lesion detection, pituitary stalk displacement, cavernous sinus displacement or invasion, hemorrhage, cystic degeneration within the adenoma, bony erosion, detection of suprasellar extension, and displacement of suprasellar structures. T1 and T2 relaxation characteristics of the adenomas were evaluated on MRI examinations, and contrast enhancement characteristics were evaluated on CT examinations. MRI was superior to CT for detecting the extrasellar extent of tumor. Within the sella turcica, MRI and CT were equivalent with regard to lesion detection, except for 1 patient in whom CT was able to detect a surgically confirmed 3-mm microadenoma that was not visualized on the MRI examination. (Neurosurgery 22:380-385, 1988)

Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26–83 years). The median duration of pain before GKS was 10 years (range 1.3–40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I–IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

The high prevalence of no-shows in residents’ primary care clinic acts as a barrier to continuity of care, results in loss of outpatient learning opportunities, and may result in more emergency department (ED) visits. The authors seek to identify if high rates of no-shows correlate with more ED visits. In a selected primary care internal medicine (PCIM) continuity clinic, 650 patients were randomly selected, with 325 patients each from the faculty and resident practices. The number of ED visits between January 1, 2006, and December 30, 2008, was recorded. Demographic characteristics of the population were obtained, and comparisons between the faculty and resident groups were performed using Student t test. Linear multiple regression analysis was performed to compare frequency of ED visits between the faculty and the resident groups, controlling for age, interpreter requirement, number of ED visits, proportion of no-shows, and insurance type. A P value <.05 was considered statistically significant. During 2006-2008, the average number of ED visits per patient in the faculty’s practice was 2.1 compared with 4.1 in the resident’s practice ( P < .001). A multiple linear regression model showed that patients who had more ED visits were likely to be younger ( P = .004), had shorter duration of care in the PCIM clinic ( P < .001), and had a higher proportion of no-shows to the PCIM clinic ( P < .001). There was no statistical difference between faculty and resident practice after adjusting for the above-mentioned variables. Shorter duration in the PCIM clinic and higher proportion of missed appointments were associated with more ED visits, but the use of interpreters and Medicaid insurance did not result in more ED visits. Future interventions are necessary to reduce the no-show rate in the clinic as this may result in a reduction of ED visits.

Stiff skin syndrome, an autosomal dominant congenital form of scleroderma, is caused by mutations in the domain of fibrillin-1 that mediates integrin binding.