Impaired orthotopic glioma growth and vascularization in transgenic mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia among the aging population and is characterized pathologically by the progressive intracerebral accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The level of proangiogenic growth factors and inflammatory mediators with proangiogenic activity is known to be elevated in AD brains which has led to the supposition that the cerebrovasculature of AD patients is in a proangiogenic state. However, angiogenesis depends on the balance between proangiogenic and antiangiogenic factors and the brains of AD patients also show an accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic. To determine whether angiogenesis is compromised in the brains of two transgenic mouse models of AD overproducing Abeta peptides (Tg APPsw and Tg PS1/APPsw mice), we assessed the growth and vascularization of orthotopically implanted murine gliomas since they require a high degree of angiogenesis to sustain their growth. Our data reveal that intracranial tumor growth and angiogenesis is significantly reduced in Tg APPsw and Tg PS1/APPsw mice compared with their wild-type littermates. In addition, we show that Abeta inhibits the angiogenesis stimulated by glioma cells when cocultured with human brain microvascular cells on a Matrigel layer. Altogether our data suggest that the brain of transgenic mouse models of AD does not constitute a favorable environment to support neoangiogenesis and may explain why vascular insults synergistically precipitate the cognitive presentation of AD.

Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management.

Nelson syndrome (NS) is a rare clinical manifestation of an enlarging pituitary adenoma that can occur following bilateral adrenal gland removal performed for the treatment of Cushing disease. It is characterized by excess adreno-corticotropin secretion and hyperpigmentation of the skin and mucus membranes. The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS. Corticotroph adenomas in NS remain challenging tumors that can lead to significant rates of morbidity and mortality. A better understanding of the natural history of NS, advances in neurophysiology and neuroimaging, and growing experience with surgical intervention and radiation have expanded the repertoire of treatments. Currently available treatments include surgical, radiation, and medical therapy. Although the primary treatment for each tumor type may vary, it is important to consider all of the available options and select the one that is most appropriate for the individual case, particularly in cases of lesions resistant to intervention.

Who should be doing laparoscopic bariatric surgery?

BACKGROUND: The training and credentialing of surgeons for laparoscopic bariatric surgery is controversial. We sought to determine if there is an association between surgeons' practice and choice of open or laparoscopic bariatric surgery. METHODS: Members of the ASBS were surveyed via email. Associations were tested with Cochran-Mantel-Haenszel or Pearson's chi-square. RESULTS: 104/472 members responded; 65% were in private practice; 47% did 1-5 operations/week, 48% offered open procedures only, and 76% undertook gastric bypass. Respondents believe that laparoscopic procedures: should mimic open ones (77%), are safe (63%), should be evaluated by clinical trials (48%), and that expertise in bariatric surgery is more important than laparoscopic experience. 75% believe that courses and preceptorships are important. Regarding laparoscopic operations, surgeons doing only open procedures believe that: 1) the ASBS should be the main credentialing body; 2) surgeons should do > 25 open before laparoscopic ones; and 3) clinical trials are needed (P < 0.02, all). Surgeons with laparoscopic training or practices believe that laparoscopic surgery is safe and effective (P < 0.002). Both laparoscopic and open surgeons believe bariatric surgeons should be the only surgeons doing laparoscopic bariatric procedures (P < 0.008). CONCLUSIONS: There is consensus that laparoscopic bariatric surgery should be undertaken only by surgeons with strong interest in bariatric surgery. Laparoscopic bariatric surgeons should incorporate lessons learned from open surgery. Both laparoscopic and open bariatric surgeons should seek added expertise via courses and preceptorships. The skepticism of surgeons with 'open' practices could be addressed by clinical trials. The ASBS should maintain its leadership position and foster emerging technologies.

Gastric bypass is an effective treatment for obstructive sleep apnea in patients with clinically significant obesity.

BACKGROUND: We have demonstrated that obstructive sleep apnea (OSA) is prevalent in 60% of patients undergoing bariatric surgery. A study was conducted to determine whether weight loss following bariatric surgery ameliorates OSA. METHODS: All 100 consecutive patients with symptoms of OSA were prospectively evaluated by polysomnography before gastric bypass. Preoperative and postoperative scores of Epworth Sleepiness Scale (ESS), Respiratory Disturbance Index (RDI), and other parameters of sleep quality were compared using t-test. RESULTS: Preoperative RDI was 40 +/- 4 (normal 5 events/hour, n = 100). 13 patients had no OSA, 29 had mild OSA, while the remaining 58 patients were treated preoperatively for moderate-severe OSA. At a median of 6 months follow-up, BMI and ESS scores improved (38 +/- 1 vs 54 +/- 1 kg/m2, 6 +/- 1 vs 12 +/- 0.1, P < 0.001, postoperatively vs preoperatively). To date, 11 patients have completed postoperative polysomnography (3-21 months) after losing weight (BMI 40 +/- 2 vs 62 +/- 3 kg/m2, P < 0.001). There was significant improvement in ESS (3 +/- 1 vs 14 +/- 2), minimum O2 saturation (SpO2 86 +/- 2 vs 77 +/- 5), sleep efficiency (85 +/- 2% vs 65 +/- 5%), all P < 0.001, postop vs preop; and RDI (56 +/- 13 vs 23 +/- 7, P = 0.041). Regression analysis demonstrated no correlation between preoperative BMI, ESS score and the severity of OSA; and no correlation between % excess body weight loss and postoperative RDI. CONCLUSION: Weight loss following gastric bypass results in profound improvement in OSA. The severity of apnea cannot be reliably predicted by preoperative BMI and ESS; therefore, patients with symptoms of OSA should undergo polysomnography.

The impact of bariatric surgery on the Veterans Administration healthcare system: a cost analysis.

BACKGROUND: The economic burden of caring for veterans with clinically severe obesity and its comorbidities is straining the Veterans Administration (VA) healthcare system. The authors determined the cost of Roux-en-Y Gastric Bypass (RYGBP) in the VA's single-payor healthcare system. METHODS: The records of all 25 patients who underwent RYGBP from May 1999 to October 2001 were reviewed. All obesity-related health-care costs including hospitalizations as well as outpatient visits, medications and home health devices were calculated for 12 months before and after the RYGBP. RESULTS: Age was 52+/-2 yr and preoperative BMI was 52+/-2 kg/m(2); ASA score was III (21 patients) and II (4 patients). Mean follow-up was 18 months. Total cost of care for these patients preoperatively was $10,778+/-2,460/patient (outpatient visits=$5,476+/-682, hospital admissions=$12,221+/-6,062, and home health devices=$1,383+/-349). Postoperative length of stay was 8+/-0.5 days. Cost of the gastric bypass was $8,976+/-497/pt (OR fixed cost=$1,900/patient + ICU and ward=$7,076+/-497/patient). For the first postoperative year, 6 patients had 12 admissions, but routine outpatient visits were significantly reduced from 55+/-6 to 18+/-2 postoperatively (P<0.001). The cost of all care excluding peri-operative charges for 1 year after gastric bypass was $2,840+/-622/patient (P=0.005 vs preop). CONCLUSIONS: Operative treatment of clinically severe obesity reduces obesity-related expenditures and utilization of healthcare resources. The cost of undertaking RYGBP at the VA is offset by reduction of health-care costs within the first year after surgery. These data support allocation of resources to support existing bariatric surgery programs throughout the VA system.