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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both Wnt and cyclooxygenase (COX-2) pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-delta, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E2 (PGE2) accelerates intestinal adenoma growth in Apc(Min) mice. Moreover, these effects are lost in Apc(Min) mice lacking PPARdelta. These findings implicate PPARdelta as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPARdelta agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPARdelta may provide a novel approach for prevention and treatment of colorectal cancer.
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PMID:WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. 1553 57

Untreated Cushing's disease and the resultant chronically elevated glucocorticoid levels lead to severe metabolic disturbances, including diabetes mellitus, obesity, hypertension, muscle wasting, and osteoporosis. Although transsphenoidal resection has become the standard of care for Cushing's disease with high initial success rates, little information is available on the long-term morbidity and mortality of patients in remission compared with patients with recurrent or persistent Cushing's disease after such treatment. We therefore conducted a retrospective study of 289 patients with Cushing's disease who underwent transsphenoidal microsurgery for an ACTH-secreting adenoma at a tertiary care center exclusively by one surgeon (C.B.W.). Postoperative remission was achieved in 82% (n = 236) of patients, with best initial remission rates observed in patients with grade I (86%) and II (83%) or stage 0 (88%), A (94%), and B (100%) tumors. Male gender, larger tumor size, and higher stage predicted poorer initial outcome. Long-term follow-up was obtained on 178 patients, with a median follow-up time of 11.1 yr (range, 0.6-24.1 yr). Thirteen of 150 (9%) of patients in initial remission developed recurrent disease, and 12 patients underwent additional treatment. At last follow-up, only two of these patients had active disease. However, of the 28 patients with initial persistent disease who had follow-up greater than 6 months, 10 patients continued to have active disease at last follow-up. Although overall survival rates in patients with initial remission did not differ significantly from expected compared with the general population based on age and sex distribution, patients with initial persistent disease had a significant increase in mortality compared with the expected mortality. Thus, successful treatment of Cushing's disease is associated with normal long-term survival. These results suggest that patients with persistent Cushing's disease require early and aggressive intervention to attempt to prevent this excess mortality.
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PMID:Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. 1557 2

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.
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PMID:Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma. 1575 38

Although both physical inactivity and obesity have been associated with an increased risk of colorectal adenomas, it is unclear whether physical activity modifies the relationship between obesity and colorectal adenomas or through what mechanism this might occur. The aim of this study is to evaluate whether physical activity modifies the relationship between body mass index (BMI) and colorectal adenomas and whether apoptosis is a plausible mechanism responsible for this effect modification. Study subjects were part of a large, cross-sectional study, the Diet and Health Study III. Consecutive patients underwent colonoscopy between August 1998 and March 2000. Apoptosis was measured by morphological evaluation of hematoxylin and eosin-stained sections obtained from rectal pinch biopsy samples. There were 226 patients with adenomas and 494 adenoma-free controls. When comparing overweight subjects with the referent group (high physical activity/normal BMI), the relative odds of having an adenoma decreased as physical activity increased: low (odds ratio, OR=1.6; 95% confidence interval, CI=0.7-3.4); moderate (OR=1.1; 95% CI=0.6-2.0); and high (OR=0.8; 95% CI=0.4-1.6). When comparing obese subjects with the referent group, relative odds of having an adenoma were increased regardless of physical activity level. Apoptosis was not associated with obesity or physical activity. Our results suggest that physical activity may modify the association between obesity and colorectal adenoma until a high level of obesity is achieved. Apoptosis does not appear to be associated with obesity or physical activity.
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PMID:Does physical activity modify the association between body mass index and colorectal adenomas? 1586 Apr 35

Clinically inapparent adrenal masses, or adrenal incidentalomas, are discovered inadvertently in the course of workup or treatment of unrelated disorders. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50% of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner, that is not fully restrained by pituitary feed-back, in 5 to 20% of cases depending on study protocols and diagnostic criteria. A number of different alterations in the endocrine tests aimed to assess the function of the hypothalamic-pituitary-adrenal axis has been demonstrated in such patients. This heterogeneous condition has been termed as subclinical Cushing's syndrome, a definition that is more accurate than preclinical Cushing's syndrome since the evolution towards clinically overt hypercortisolism does occur rarely, if ever. The criteria for qualifying subclinical cortisol excess are controversial and we presently do not have sufficient evidence to define a gold standard for the diagnosis of subclinical Cushing's syndrome. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipoproteinemia has been described in patients with subclinical Cushing's syndrome; however, there is not evidence-based demonstration of its long-term complications and, consequently, the management of this condition is largely empirical. Either adrenalectomy or careful observation associated with treatment of metabolic syndrome has been suggested as treatment options because data are insufficient to indicate the superiority of a surgical or nonsurgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas.
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PMID:Subclinical Cushing's syndrome. 1613

This review highlights areas of clinical research in gastroenterology and hepatology that were published during the last year and were summarized during the most recent American Gastroenterological Association Plenary Session. The topics include a comparison of the risk of recurrent bleeding in patients taking clopidogrel versus aspirin plus a proton pump inhibitor, the introduction of rifaximin for the treatment of traveler's diarrhea, and the results of an oral vaccine for cholera tested in a high endemic area where there is also a high prevalence of human immunodeficiency virus infection. In inflammatory bowel disease, the impact of a biomarker of inflammation, C-reactive protein, to the response to a new biologic therapy is identified as potentially important because it might facilitate the selection of patients for these treatments. Results of device, endoscopic, and surgical treatment of obesity are reviewed, including the evidence of significant impact of surgery-induced weight loss on comorbid diseases. In the field of cancer, colonoscopic screening results in more polyps detected, down-staging of cancers identified, and improved cancer survival. A new familial syndrome associated with a serrated adenoma/carcinoma phenotype and variability in microsatellite instability is described. A controlled study demonstrates that a urine-derived substance, ulinastatin, reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Hepatic stellate cells are involved in the fibrogenesis associated with nonalcoholic fatty liver disease. These areas of clinical research demonstrate the breadth of significant advances that will impact on the clinical practice of gastroenterology and hepatology.
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PMID:GIH clinical research update: 2004-2005. 1636 Oct 39

Silent corticotroph adenomas (SCA) are rare pituitary tumors with histologic hallmarks of corticotroph differentiation, including ACTH immunoreactivity, but lacking clinical evidence of Cushing's syndrome. We report on four female patients, aged 19-66 years, each presenting with a nonfunctional macroadenoma. Leading symptoms were headache in two cases and visual field deficits in one. One patient was incidentally diagnosed while undergoing cranial MRI for an unrelated condition. Three patients had marked obesity; none of them presented constitutional signs of Cushing's syndrome. Serum cortisol levels were moderately elevated in the two patients systematically tested in this respect. Marginal to moderate hyperprolactinemia was present in two cases. Two patients also were shown to be deficient in either gonadotroph or thyrotroph axis, while a third had a combined insufficiency of both gonadotroph and thyrotroph axis. MRI scans revealed intratumoral hemorrhage and/or cystic change in three cases, as well as tumor-related occlusive hydrocephalus in one. The latter patient was biopsied only, while the remaining underwent gross total resection. Histologically, all four lesions were diagnosed as SCA subtype I displaying intense immunoreactivity for ACTH. In three tumors, scattered cells coexpressed PRL as well. In addition, Crooke's hyaline change was noted in a significant number of tumor cells and in residual non-neoplastic corticotrophs in one case each. With MIB-1 labeling indices of 1-3%, none of the tumors qualified as atypical adenoma. We conclude that SCAs are more likely to be discovered as expansile tumors, whose advanced local space-occupying character at surgery rather than an inherently aggressive growth potential may negatively influence the clinical outcome. Subtle morphologic evidence of corticotroph suppression in residual pituitary adjacent to tumor lends further support to literature data indicating minimal or intermittent functional activity in this tumor type.
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PMID:Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: report of four cases and literature review. 1649 45

Obesity is a risk factor for colon cancer, possibly due to elevated levels of circulating cytokines derived from adipose tissue. Aspirin, which may affect the levels of these cytokines, has been shown in randomized controlled trials to decrease the risk of colorectal adenomas. We hypothesized that the chemopreventive effect of aspirin might be greater in individuals with higher body mass index (BMI). Data were available from the Aspirin/Folate Polyp Prevention Study, a randomized controlled trial of aspirin and folic acid to prevent recurrent colorectal adenomas. Obesity was defined as BMI > or = 30 (kg/m2), overweight as BMI of 25-29 (kg/m2) and normal weight as BMI <25 (kg/m2). For the analysis of the effect of aspirin on the recurrence of colorectal adenoma by BMI, we computed risk ratios for aspirin versus placebo within the three BMI strata using a modified Poisson model. Overall the risk reduction of adenomas with a daily dose of 325 mg aspirin was greater among subjects with higher BMI. Among obese subjects the risk ratio (RR) for advanced adenomas compared with placebo was 0.44 (95% CI 0.17-1.10), versus RR = 1.23 (95% CI 0.55-2.77) among those with normal weight. However, 81 mg aspirin daily did not interact with BMI to modify the risk of adenomas in such a fashion. The more pronounced effect of 325 mg aspirin in individuals with higher BMI suggests a possible protective role of anti-inflammatory aspirin against increased adipose-driven cytokines among obese subjects.
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PMID:Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States). 1711 Dec 62

A 49-year-old woman with hypertension, obesity and impaired glucose tolerance (IGT) was admitted for evaluation of pituitary incidentaloma. Although she presented no Cushingoid feature, endocrine examination of hypothalamo-pituitary-adrenal (HPA) axis showed elevated basal plasma ACTH and cortisol levels, their lack of circadian rhythm, non-suppressibility to low-dose (1 mg) dexamethasone, and responsiveness to CRH, suggesting autonomous ACTH secretion from a pituitary tumor. She underwent transsphenoidal surgery, and was diagnosed as chromophobe adenoma with positive ACTH immunoreactivity. Postoperatively, her abnormal HPA axis was resolved, along with improvement of hypertension, obesity and IGT. Thus, her metabolic comorbidities are likely due to subclinical Cushings disease.
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PMID:Subclinical Cushings disease with amelioration of metabolic comorbidities after removal of pituitary tumor. 1713 24

Peroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes. However, PPARdelta's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARdelta decreases intestinal adenoma growth in Apc(Min/+) mice and inhibits tumor-promoting effects of a PPARdelta agonist GW501516. More importantly, we found that activation of PPARdelta up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARdelta agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer.
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PMID:Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. 1714 4


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