title: Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life.
abstract: OBJECTIVE
  The study objectives were to determine baseline endometrial histology in morbidly obese women undergoing bariatric surgery and to assess the surgical intervention's impact on serum metabolic parameters, quality of life (QOL), and weight.
  
  
  METHODS
  Women undergoing bariatric surgery were enrolled. Demographic and clinicopathologic data, serum, and endometrium (if no prior hysterectomy) were collected preoperatively and serum collected postoperatively. Serum global biochemical data were assessed pre/postoperatively. Welch's two sample t-tests and paired t-tests were used to identify significant differences.
  
  
  RESULTS
  Mean age of the 71 women enrolled was 44.2 years, mean body mass index (BMI) was 50.9 kg/m(2), and mean weight loss was 45.7 kg. Endometrial biopsy results: proliferative (13/30; 43%), insufficient (8/30; 27%), secretory (6/30; 20%) and hyperplasia (3/30; 10%-1 complex atypical, 2 simple). QOL data showed significant improvement in physical component scores (PCS means 33.9 vs. 47.2 before/after surgery; p<0.001). Twenty women underwent metabolic analysis which demonstrated significantly improved glucose homeostasis, improved insulin responsiveness, and free fatty acid levels. Significant perturbations in tryptophan, phenylalanine and heme metabolism suggested decreased inflammation and alterations in the intestinal microbiome. Most steroid hormones were not significantly impacted with the exception of decreased DHEAS and 4-androsten metabolites.
  
  
  CONCLUSIONS
  Bariatric surgery is accompanied by an improved physical quality of life as well as beneficial changes in glucose homeostasis, insulin responsiveness, and inflammation to a greater extent than the hormonal milieu. The potential cancer protective effects of bariatric surgery may be due to other mechanisms other than simply hormonal changes.
authors.affiliation: Gynecologic Oncology Division, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Modesitt
authors.affiliation: Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hallowell
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Jill K
authors.initials: JK
authors.lastname: Slack-Davis
authors.affiliation: Metabolon, Inc., Durham, NC, United States.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Michalek
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Atkins
authors.affiliation: College of Arts and Sciences, University of Virginia, Charlottesville, VA, United States.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kelley
authors.affiliation: Gynecologic Oncology Division, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Sanja
authors.initials: S
authors.lastname: Arapovic
authors.affiliation: Endocrinology Division, University of Virginia School of Medicine, Charlottesville, VA, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shupnik
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, United States; School of BABS, University of New South Wales, Sydney, Australia.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hoehn
mesh_terms: D000328:Adult; D000368:Aged; D050110:Bariatric Surgery; D001835:Body Weight; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D004714:Endometrial Hyperplasia / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D011788:Quality of Life; D055815:Young Adult
chemical_list: D005947:Glucose
keywords: Bariatric surgery; Endometrial hyperplasia; Metabolomics; Morbid obesity; QOL