1 / 51

Bariatric (Metabolic) Surgery for Life-Long Weight Control and Mortality Risk Reduction

Bariatric (Metabolic) Surgery for Life-Long Weight Control and Mortality Risk Reduction. First Canadian Summit on Surgery for T2DM May 6, 2010 Montreal, Canada. Ted Adams, Ph.D., MPH University of Utah School of Medicine, Salt Lake City, Utah.

iren
Download Presentation

Bariatric (Metabolic) Surgery for Life-Long Weight Control and Mortality Risk Reduction

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Bariatric (Metabolic) Surgery for Life-Long Weight Control and Mortality Risk Reduction First Canadian Summit on Surgery for T2DM May 6, 2010 Montreal, Canada Ted Adams, Ph.D., MPH University of Utah School of Medicine, Salt Lake City, Utah

  2. Editorial, NEJM 2007;357:818George A. Bray, M.D. “The Missing Link – Lose Weight, Live Longer”

  3. Editorial, NEJM 2007;357:818George A. Bray, M.D. “The Missing Link – Lose Weight, Live Longer??”

  4. Does Weight Loss = Improved Mortatity? • Observational studies reporting mortality of obese subjects who have lost weight without bariatric surgery are inconclusive, with studies reporting no change, increased, or reduced mortality. Solomon CG & Dluhy. NEJM 2004;351:2751 Hu FB, et al. NEJM 2004;351:2694 Yaari S & Goldbourt U. Am J Epidemiol 1998;148:546 Gregg EW, et al. Ann Intern Med 2003;138:383

  5. “The Missing Link – Have Bariatric Surgery, Lose Weight (?), Live Longer”

  6. “The Missing Link – Have Bariatric Surgery,Lose Weight,Keep Weight Off,Live Longer”

  7. 0 20 40 60 80 100 0 2 4 6 8 10 12 14 Long-term Effect of Gastric Bypass Surgery on Body Weight Weight Loss (% of Excess Weight) Years After Surgery BMI (kg/m2): 50 34 35 35 Pories et al. Ann Surg 1995;222:339.

  8. Change in BMI Over Time for Patients Followed for >10 Years BMI Figure 3, Christou et al. Ann Surg 2006;244:737.

  9. 13% GBP; 19% LAGB & LGB; 68% VBG Sjöström, L. NEJM 2004;351:2683-2693.

  10. Maintenance of weight loss after gastric bypass surgery % of Initial Body Weight

  11. “The Missing Link – Have Bariatric Surgery,Lose Weight,Keep Weight Off,Improve Health,Live Longer”

  12. Improvement in obesity associated diseases with bariatric surgery – McGill Data * * * p<0.001 * * * Christou et al Ann. Surg. 240:416-424, 2004

  13. Prevalence, Incidence andResolution of Diabetes (2 years) • Adams, T. et al. Obesity 2009;17:796-802

  14. “The Missing Link – Have Bariatric Surgery,Lose Weight,Keep Weight Off,Improve Health,Live Longer”

  15. Mortality FollowingBariatric Surgery • 11 published studies • Methods vary by: surgery type, follow-up time, control group selection, BMI • When severely obese control groups are included, all studies report improved mortality for bariatric surgery groups

  16. Bariatric Surgery & Reduced Mortality (%)

  17. Christou, et al. (2004) Christou, NV. Ann Surg;2004:416-424.

  18. Sjöström et al. SOS (2007) Sjöström, L. NEJM 2007;357:741-752.

  19. Adams et al. (2007) Adams, et al. NEJM 2007;357:753-761.

  20. Results: % Difference (based on mortality HR) Matched Groups Adams, et al. NEJM 2007;357:753-761.

  21. Results: % Difference (based on mortality HR) Matched Groups (cont.) Adams, et al. NEJM 2007;357:753-761.

  22. Christou, N. et al. Ann Surg 2006;244:734-740 • 272 post-gastric bypass patients followed (4.7 to 14.9 years) = 7 deaths • (1) suicide at 4.8 years • (1) suicide at 5.7 years • (1) liver failure at 6.6 years • (1) Unknown cause at 8 years • (1) Pulmonary embolus at 8.8 years • (1) Cardiac failure at 8.8 years • (1) Cardiovascular accident at 13 years

  23. Results: First Year Deathsby Matched Groups Adams, et al. NEJM 2007;357:753-761.

  24. An Unexpected Finding! • The SOS study on mortality revealed a strong effect from cancer (control group, 47 deaths; surgery group, 29 deaths) • The Utah study on mortality reported a 60% reduction in cancer deaths following bariatric surgery when compared to severely obese controls Sjöström, L. NEJM 2007;357:741-752 Adams et al. NEJM 2007;357:753

  25. Well Known Finding Increased BMI  Increased CA Risk

  26. Association Between BMI and Cancer RiskWorld Cancer Research Fund (WCRF) • Body fatness associated with increased cancer risk for: • Oesphageal adenocarcinoma • Pancreas • Colorectum • Postmenopausal breast • Endometrium • Kidney • And probable association for gallbladder WCRF. Food, Nutrition, Physical Activity, and Prevention of Cancer: A Global Perspective, 2nd ed. Washington, D.C.: American Institute for Cancer Research, 2007.

  27. Association Between BMI and Cancer RiskRenehah, et al. Lancet 2008;371:569 221 data sets analyzed 282,137 incident cases 5 kg/m2increase in BMI associated with the following cancers: Renehah, et al. Lancet 2008;371:569

  28. Association Between BMI and Cancer Risk Renehah, et al. Lancet 2008;371:569

  29. Possible ReasonsWhy Obesity Increases Cancer Risk 1.Chronic inflammation  adipocyte release of inflammatory promoters • Tumor nucrosis factor-alpha interleukin-6 (TNF-IN-6) • C-reactive protein • Leptin – shown to increase in inflammatory states Calle, et al. Obesity and Cancer. Oxford University Press, Oxford, pp. 196. Renehan, et al. Arch Physiol Biochem 2008;114(1):71. WCRF. Food, Nutrition, Physical Activity, and Prevention of Cancer: A Global Perspective, 2nd ed. Washington, D.C.: American Institute for Cancer Research, 2007.

  30. Possible ReasonsWhy Obesity Increases Cancer Risk (cont.) 2. Increased release of sex-steroid hormones • Estrogens • Androgens • Progesterone • Adipocyte  primary point for synthesis of estrogen for men and postmenopausal women • Increased body fat  increase in insulin-like growth factor 1 (IGF-1)  rise in estradiol in men and women and potential increase in testosterone in women Calle, et al. Obesity and Cancer. Oxford University Press, Oxford, pp. 196. Renehan, et al. Arch Physiol Biochem 2008;114(1):71. WCRF. Food, Nutrition, Physical Activity, and Prevention of Cancer: A Global Perspective, 2nd ed. Washington, D.C.: American Institute for Cancer Research, 2007.

  31. Possible ReasonsWhy Obesity Increases Cancer Risk (cont.) 3. Insulin related mechanisms • Increased body fatness (in particular, abdominal or central obesity)  increased insulin resistance • Subsequent increased insulin production by the pancreas • Hyperinsulinemia in the face of insulin resistance increases risk of colon and endometrial cancer with potential increased risk of pancreatic and kidney cancer Calle, et al. Obesity and Cancer. Oxford University Press, Oxford, pp. 196. Renehan, et al. Arch Physiol Biochem 2008;114(1):71. WCRF. Food, Nutrition, Physical Activity, and Prevention of Cancer: A Global Perspective, 2nd ed. Washington, D.C.: American Institute for Cancer Research, 2007.

  32. Important Question??? Increased BMI  Increased CA Risk but does Decreasing BMI  Decrease CA Risk??

  33. To Date – Four Cancer & Bariatric Surgery Studies • 1 Prospective • Sjöström, L. et al. Lancet Oncol 2009;10:653-62 • 3 Retrospective • Christou, N. et al. SurgObesRelatDis 2008;4:691-95 • McCawley, G. et al.JAm CollSurg 2009;208:1093-98 • Adams, T. et al. Obesity 2009;17:796-802

  34. Sjöström, L. et al. Lancet Oncol 2009;10:653-62 • Unique • First prospective, controlled intervention study • Weight loss follow-up  compare weight loss to cancer incidence • Medical and lifestyle history followed over time • 2010 bariatric surgery patients; 2037 well-matched controls • 1st time cancers: 117 surgery group;169 control group (HR 0.67, p=0.0009) • 1st CAs in women: 79 surgery group; 130 control group (HR 0.58, p=0.0001) • No effect in men: 38 surgery group; 39 control group (HR 0.97, p=0.90)

  35. Sjöström, L. et al. Lancet Oncol 2009;10:653-62 • Similar results after CAs in the first 3 years of study excluded • Sagittal trunk diameter  strong multiple CA predictor • Body weight, BMI and reduced energy intake were not CA incidence predictors

  36. The Canadian Bariatric Cohort Study • Restrospecitve, observational 2-cohort • 1035 post-bariatric surgery patients; 5746 severely obese controls (ICD-9 codes) without surgery • CA diagnosis within 6 months prior to study onset excluded • Physician/hospital visits for all CA-related diagnosis • Follow-up for a maximum of 5 years • Cancer-related visits: 2% (21 visits) surgery group; 8.5% (487 visits) control group (RR 0.22, p=0.0001) Christou, N. et al. SurgObesRelatDis 2008;4:691-95

  37. The Canadian Bariatric Cohort Study 78% Reduction in Overall Cancer Risk

  38. The Canadian BariatricCohort Study 83% 68% (p=0.001) (p=0.063)

  39. Adams, T. et al. Obesity 2009;17:796-802 • Retrospective, 2-cohort • Compared incidence, case-fatality, and mortality of total and stage-specific cancer • Surgical Group: From 9949 GBP patients all non-Utah residents excluded leaving 6709 patients (surgery 1984 through 2002) • Comparative Group: 9609 severely obese (Utah driver’s license applicants – 1984 through 2002) • In previous study, comparative group matched to represent the gender, age, and body mass index (BMI) distribution of the surgical patients

  40. Methods • Subjects linked to Utah Cancer Registry for years 1984 through 2007 (24 year follow-up; mean of 12.5 years) • Type of cancer (CA), stage of CA, date of diagnosis, vital status, and death date (SEER standards used) • SEER standards: 0 = in situ; 1 = localized; 2-5 = regional; 7 = distant; and unstaged • Prevalent CA (1.9% surgery group; 2.0% comparative group) was excluded • Adams, T. et al. Obesity 2009;17:796-802

  41. Incidence (Rates/1,000 PY) Adams, T. et al. Obesity 2009;17:796-802

  42. HR for Incident Cancer – Surgery versus Comparative Adams, T. et al. Obesity 2009;17:796-802

  43. Mean Time to Diagnosis by Cancer Stage, years Adams, T. et al. Obesity 2009;17:796-802

  44. Mortality (Rates/1,000 PY) Adams, T. et al. Obesity 2009;17:796-802

  45. Opportunity for Discovery!(Similar to diabetes remission following bariatric surgery) • What are the causes for reduced cancer incidence? • Weight loss (or not) • Change in central adiposity • Reduced energy intake • Other mechanisms?? • How rapid are the effects that influence cancer incidence reduction – what is the timeline? • Does cancer incidence vary in relation to bariatric surgical procedures (i.e., GBP vs. banding)? • Does bariatric surgery influence cancer remission (if yes, does this vary by surgery type)?

  46. Opportunity for Discovery (cont.) • Do protective cancer effects (physiological mechanisms) following bariatric surgery vary based upon gender? • Do protective cancer effects (physiological mechanisms) following bariatric surgery vary based upon cancer type? • If larger data sets representing male bariatric surgery data were available, would reduced cancer incidence appear? • Can robust animal models of obesity and cancer risk be explored and combined with human bariatric surgical outcomes?

  47. Final Perspective –Thought #1 It would appear that recent national guidelines recommending weight loss to reduce future cancer risk are supported by results from these bariatric surgery cancer-related studies.

  48. Final Perspective –Thought #2 “… to put this risk reduction (HR 0.58) into perspective, it might be helpful to compare it with statin treatment, where the HR for reduction in incidence of fatal plus non-fatal myocardial infarction (vs placebo) has been in the order of 0.80.” Sjöström, L. Lancet Oncol 2009;10:653-62

  49. Final Perspective –Thought #3 “As the obesity epidemic shows few signs of abating, incidences of obesity-related cancers may rise; however, the establishment that the development of these cancers is reversible brings about an encouraging new paradigm in cancer prevention.” Andrew G. Renehan Lancet Oncology 2009;10:640

  50. “The Missing Link – Have Bariatric Surgery,Lose Weight,Keep Weight Off,Improve Health,Live Longer”

More Related