SUMMARY Insulin sensitivity deteriorates with age, but mechanisms remain unclear. Age-related changes in the function of subcutaneous white adipose tissue (sWAT) are less characterized than those in visceral WAT. We hypothesized that metabolic alterations in sWAT, which in contrast to epididymal WAT, harbors a sub-population of energy dissipating UCP1+ brown adipocytes, promote age-dependent progression towards insulin resistance. Indeed, we show that a predominant consequence of aging in murine sWAT is loss of “browning.” sWAT from young mice is histologically similar to brown adipose tissue (multilocular, UCP1+), but becomes morphologically white by 12 months of age. Correspondingly, sWAT expression of ucp1 precipitously declines (~300-fold) between 3 and 12 months. Loss continues into old age (24 months), and is inversely correlated with the development of insulin resistance. Additional age- dependent changes in sWAT include lower expression of adbr3 and higher expression of maoa, suggesting reduced local adrenergic tone as a potential mechanism. Indeed, treatment with a ®3- adrenergic agonist to compensate for reduced tone rescues the aged sWAT phenotype. Age- related changes in sWAT are not explained by differences in body weight; mice subjected to 40% caloric restriction for 12 months are of similar body weight to 3 month-old ad lib fed mice, but display sWAT resembling that of age-matched ad lib fed mice (devoid of brown adipose-like morphology). Overall, findings identify loss of “browning” in sWAT as a new aging phenomenon, and provide insight into the pathogenesis of age-associated metabolic disease by revealing novel molecular changes tied to systemic metabolic dysfunction.
BackgroundWidespread concerns have been raised regarding the safety of power morcellation of uterine specimens because of the potential to disseminate occult malignancy. We sought to assess the safety and feasibility of contained manual uterine morcellation within a plastic specimen bag among women with uterine neoplasms.MethodsA retrospective single-institution descriptive cohort study was conducted from 2003 to 2014. Patients with leiomyoma and/or uterine malignancy who underwent minimally invasive surgery with contained uterine manual morcellation were identified from surgical logs. Demographic data, pathology results, operative details and adjuvant treatments were abstracted.ResultsEighty-eight patients were identified; 35 with leiomyoma and 53 with endometrial cancer. The mean age was 48 and 60, respectively. Uterine size/weight was greater in women with leiomyoma compared to those with cancer (15.1 weeks/448 g vs. 10.7 weeks/322 g). Mean operative time was 206 min (range 115–391) for leiomyoma cases and 238 min (range 131–399) for cancer cases. Median length of stay was 1 day (range 0–3 days). There were no cases of occult leiomyosarcoma and all specimens were successfully manually morcellated within a bag. There were no intraoperative complications. Thirty-day postoperative complications occurred in 7 patients, including one readmission for grade (G) 1 vaginal cuff separation after intercourse, G1 port-site hematoma (1), G2 port-site cellulitis (1), G2 vaginal cuff cellulitis (2), G2 bladder infection (2), G2 pulmonary edema (1), and G1 musculoskeletal injury (1).ConclusionsContained uterine hand morcellation is a feasible procedure with low peri-operative complication rates that allows for minimally invasive surgical procedures for women with large uterine neoplasms. Further evaluation is needed to assess survival outcomes for uterine malignancies.
As the average age that women have their first child increases and cancer therapies improve survival, obstetricians are more likely to care for pregnant women who have survived cancer. Managing these pregnancies can be challenging, as they may be associated with higher risks of maternal and neonatal morbidity and mortality. Different types of cancer require different types of intervention, including surgery, chemotherapy, radiation, or combinations of these. Prior cancer treatments therefore present different potential complications during pregnancy. Although for most women who survive cancer carrying a pregnancy does not seem to increase mortality rates, there are some associated neonatal morbidities. The most common perinatal complication associated with pregnancy after cancer is prematurity. Women who desire pregnancy after cancer survival should not be discouraged, but appropriate counseling and follow-up should be provided.
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