Metastatic involvement of skeletal muscle from gastric adenocarcinoma.

Gastric cancer represents the fifth most common cancer diagnosis worldwide and the third leading cause of cancer-related mortality. In the USA, the overall 5-year survival rate is 31%, with distant disease nearing 5%. The most common sites of metastasis are the liver and peritoneum. Skeletal muscle involvement has been rarely reported. Since clinical and imaging findings overlap with primary sarcomas, a confirmatory biopsy is required for diagnosis. Prognosis remains poor with treatment options including palliative chemotherapy, radiotherapy and surgical resection. We report the case of a 57-year-old female presenting with extensive involvement of skeletal muscle 10 years after achieving remission. In addition to illustrating the refractoriness and poor outcomes associated with muscle involvement, this case and comprehensive review of the literature highlights important characteristics of disease biology and tumor genomics that warrant detailed discussion and exposition to a wider audience.

Effect of Lifestyle Intervention on the Hormonal Profile of Frail, Obese Older Men.

OBJECTIVE: Obesity-associated hypogonadism is hypothesized to be due to the suppressive effect of high estradiol (from an increase in aromatase activity present in the abundant adipose tissue) on the hypothalamic-pituitary-gonadal unit resulting in low testosterone production. Although weight loss has been found to be effective in reducing estradiol and raising testosterone levels in studies of younger men, its effect in frail, obese older men is understudied. Thus, the objective of this study was to determine the effect of lifestyle intervention on hormone levels in frail, obese older men. DESIGN: Randomized controlled trial of lifestyle intervention in frail, obese older men (≥65 yo) for 1 year. SETTING: University hospital. METHODS: Forty frail, obese elderly men were randomized, for a 52-week study, to any of the following treatment groups: (1) control group, (2) diet-induced weight loss group (diet group), (3) exercise training group (exercise group), and (4) diet-induced weight loss and exercise training group (diet-exercise group). The objective was to achieve a ~10 % weight loss at 6 months and maintain this weight for an additional 6 months. Physical function was assessed by the modified physical performance testing (modified PPT). Estradiol was measured by radioimmunoassay, testosterone by automated immunoassay, and sex hormone-binding globulin by enzyme-linked immunoassay. RESULTS: After 12 months of intervention, diet alone resulted in a weight loss of -10.1 ± 1.9 kg in the diet group and -9.1 ± 0.9 kg in the diet-exercise group. This resulted in a significant decrease (both p<0.05) in total estradiol compared to baseline among subjects in the diet (-2.5 ± 1.3 pg/ml) and diet-exercise group (-2.2 ± 4.0 pg/ml). Free estradiol index also significantly decreased (both p <0.05) in both the diet (-0.39 ± 0.14 pmol/nmol) and diet-exercise (-0.52 ± 0.12 pmol/nmol) group. Total testosterone significantly increased (p<0.05) in response to diet (71.0 ± 21.0 ng/dl) and diet-exercise (49.9 ± 15.5 pg/ml) resulting in values of 287.0 ± 28.1 ng/dl in the diet and 317.6 ± 33.1 ng/dl in the diet-exercise group. However, because there was a significant increase in sex hormone-binding globulin levels in both the diet and diet-exercise groups, free testosterone index and the changes in free testosterone index were not significant compared to baseline. Regardless of changes in hormonal levels, patients in the diet, exercise, and diet-exercise groups experienced significant improvements in the modified PPT from baseline. CONCLUSION: Weight loss from lifestyle intervention resulted in significant decreases in total and free estradiol levels in frail, obese older men, but this did not result in a clinically important increase in total testosterone nor a significant increase in free testosterone. Thus, alternative forms of treatment in addition to lifestyle intervention may be necessary to improve the hormonal profile among these patients. Nevertheless, whether further improvement in hormonal profile would result in better physical performance than what can be achieved by lifestyle alone in these subjects remains uncertain.

Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone.

AIM: Intramyocellular triglyceride (IMTG) correlates with insulin resistance, but there is no clear causal relationship. Insulin resistance and associated hyperinsulinaemia may increase IMTG, via the insulin-regulated transcription factor, sterol regulatory element-binding protein 1 (SREBP-1). PPAR agonists may also affect IMTG via changes in insulin sensitivity, SREBP-1 or other factors. METHODS: We examined skeletal muscle IMTG and SREBP-1 expression, and metabolic parameters in Zucker diabetic fatty rats (ZDF) after 25 weeks of PPAR-gamma or PPAR-alpha administration. RESULTS: Compared with Zucker lean rats (ZL), untreated ZDF had significantly higher weights, serum glucose, insulin, free fatty acids, total cholesterol and triglycerides. IMTG and SREBP-1c messenger RNA (mRNA) were also higher in untreated ZDF; both were decreased by fenofibrate (FF). Rosiglitazone (Rosi), despite marked improvement in glycaemia, hyperinsulinaemia and hyperlipidaemia, failed to affect SREBP-1 expression, and increased body weight and IMTG. Rosi/FF combination caused less weight gain and no IMTG increase, despite metabolic effects similar to Rosi alone. CONCLUSIONS: IMTG and SREBP-1c mRNA are high in the ZDF. FF and Rosi both improved insulin sensitivity but had opposite effects on IMTG. Thus, there was a clear discordance between insulin sensitivity and IMTG with PPAR agonists, indicating that IMTG and insulin sensitivity do not share a simple relationship.