Sleeve Gastrectomy The Metabolic Choice Shahzeer Karmali MD, FRCSC Assistant Professor Surgery Centre for the Advancement of Minimally Invasive Surgery, University Of Alberta, Edmonton, Alberta, Canada

Why Sleeve Gastrectomy? “We need a bariatric procedure that does not cause as much morbidity and does not need as much follow up as the current ones” E.E. Mason Presidential Address 2007 ASMBS

Mechanism of action Restriction Natural Band Formation Hormonal

1. Restriction LSG reduces the size of the gastric reservoir to 60-100 ml permitting intake of only small amounts of food and imparting a feeling of satiety earlier during a meal

2. Natural Band The pylorus functions as a natural band in this procedure facilitating further restriction

3. Ghrelin hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger Ghrelin levels increase before meals and decrease after meals. the counterpart of the hormone leptin, produced by adipose tissue, which induces satiation when present at higher levels

3. Ghrelin By resecting the fundus in a LSG, the majority of ghrelin producing cells are removed reducing plasma ghrelin levels and subsequently hunger.

Current Weight loss Evidence 35 Studies between 1/03 and 1/09 2,570 patients Pre-op BMI 35 – 69 kg/m2 (mean 50) Post-op BMI 26 – 53 kg/m2 ( mean 37) Follow-up 3 months to 5 years 33 – 83% EWL (mean 55%) Complication rate 0 – 24% 0 – 15% in 11 studies with n> 100 5 postoperative mortalities (0.19%)

Sleeve Gastrectomy Good Excess Weight loss Technically feasible Safe

Sleeve Gastrectomy and Diabetic Control

Resolution, Remission or Cure It is generally accepted that effective medical or surgical diabetes therapy results in remission of the disease and not cure This generally means that the patient is off all hypoglycemic medications and/or insulin and that they have normal fasting plasma glucose, normal post prandial glucose excursions and normal HbA1c

Bariatric Surgery Efficacy Procedure % EWL T2DM (Remission) Gastric Banding 47% (n=1848) 48% Gastric Bypass 62% (n=4204) 84% BPD 70% (n=2480) 98% Buchwald H. JAMA, 2004

Bariatric Surgery is Effective, But Not Equal-Where does sleeve fit in? Benefit 100% Switch Roux-en-Y Excess Weight Loss Diabetes Resolution Rate 50% Banding 10% 0.001 0.01 0.1 1 10 Risk 30 Day Mortality Adapted from Buckwald H, et al, Bariatric surgery, a systematic review and meta-analysis, JAMA. 2004;292:1724-1737 and Maggard M, et al, Meta-Analysis: Surgical Treatment of Obesity, Ann Intern Med. 2005;142:547-559.

Diabetes Surgical Interventions (DSI) High Efficacy Medium Low Low Medium High Technical Complexity

How does a Sleeve Gastrectomy impart its Diabetic Remission?

1. Hormonal Changes 2. Hindgut theory

1. Hormonal Changes-Ghrelin Effect Marked Reduction of fasting ghrelin levels post-operatively Karamkos et al. 2008 Ghrelin is a hormone produced primarily by the gastric fundus Ghrelin : suppress the insulin sensitizing hormone adiponectin Blocks hepatic insulin signaling Inhibits insulin secretion By gastric fundus removal, the reduced circulating ghrelin level and its insulinostatic effect will increase the maximal captacity of glucose induced insulin release and enable the islet to secrete more insulin Abbatini et al. 2009

2. The Hindgut Theory The more rapid delivery of undigested nutrients to the distal bowel upregulates the production of L-cell derivatives like GLP-1, Peptide YY Mason E. Obes Surg 2005 15, 459-461 Rubino et.al, Ann Surg, 2006

The But we are not making any new anastamosis like a BPD or a RNYGB so how does this happen with a SG??? Melissas et al. Obes Surg 2007 gastric emptying half-time (T1/2) accelerated (47.6 +/- 23.2 vs 94.3 +/- 15.4, P<0.01) post-operatively. The percentage of the meal emptied from the stomach 90 min after consumption increased significantly after SG (75.4 +/- 14.9% vs 49.2 +/- 8.7%, P<0.01). study indicates that following SG, the stomach empties its contents rapidly into the small intestine Thus despite preservation of the pylorus, the stomach emptying of solid foods into the small intestine is increased

Hindgut theory: Peptide YY Secreted from entire GI tract – “L” cells Mainly distal (ileum, colon and rectum) Food intake stimulates its release – fasting reduces it Effects May ameliorate insulin resistance (in mice) Delays pancreatic/gastric secretions/gastric emptying/intestinal transit Bloom SR. et.al. Nature 2006

Hindgut theory-Glucagon Like Peptide– 1 GLP-1 “Enteroglucagon” Secreted by ileal “L-cells” in (rapid) response to a meal Animal study Li et al. demonstrated an increased in GLP 1 levels in SG group Actions Potent stimulator of insulin / supresses glucagon Slows gastric emptying Reduces appetite Increases beta cell mass Wynne K. J Clin Endo Met, 2004

The Evidence-Diabetes Remission post LSG

Systematic Review Remission of Diabetes post Sleeve Gastrectomy Karmali S, Shi X, Sharma A.M., Birch D.W.

Methodology Search strategy: Medline, Pubmed, Embase, Scopus, Dare, Cochrane library, Clinical evidence, TRIP, HTA database; meanwhile, conference abstracts, registered clinical trials were also searched. Google was also used for grey or other literature, such as clinical practice guidelines, government documents. Search terms: sleeve gastrectomy, or vertical gastrectomy, or bariatric surgery, or metabolic surgery and diabetes, or T2DM, or DM or comorbidities. All human studies, not limited to English language, reported from 2000 to April 2010 were included in our searching.

3,621 Citations Identified for Screening 261 Rejected (Did Not Meet Inclusion Criteria 230 Wrong Publication Type (case report, <5 patients, technique only, no outcomes measured, experts opinions, animal models) 5 Wrong Population (not adult) 20 Wrong Intervention (sleeve gastrectomy combined with other procedures) 6 Kin Relationship (substudies, duplicate patients) 3,332 Rejected (Met Exclusion Criteria) 289 Abstracts Reviewed 28 Primary Studies Included 4 Nonrandomized Prospective Controlled Trials 3 Retrospective Controlled Trials 15 Prospective Case Series 6 Retrospective Case Series

Year Nation study pt# 2010 Netherlands prospective 20 India 53 retrospective 23 UK 34 Brazil non-R CT 32 New Zealand 25 2009 USA 30 retrospective CT Italy France 33 Isreal 18   Chile 14 39 7 2008 Spain Taiwan(rct) 13 Australia Czech 17 Japan 6 2007 21 2006 75 2005 Korea 8

Results-Demographics Total number of patients: 705 Mean BMI: 46.3 +/- 7.9 (31-53.5) Mean Age: 47.3 +/- 3.8 (42-53) Mean Follow-up: 13.0 +/- 8.1 months (3-36) %EWL: 47.3 +/-19.1 (6.3-74.6) Post-surgical BMI: 35.9 +/-6.6 (24.6-44.7)

Type 2 Diabetes Mellitus Resolution: 66.5 +/- 24.5 Improvement 29.9 +/- 25.1 Stable 13.1 +/- 13.45

Glucose Levels 181.1 to 119.2

HbA1C change 7.9 to 6.2

Bariatric Surgery Efficacy Procedure % EWL T2DM (Remission) Gastric Banding 47% (n=1848) 48% Sleeve Gastrectomy 47.3% (n=705) 66.5% Gastric Bypass 62% (n=4204) 84% BPD 70% (n=2480) 98% Buchwald H. JAMA, 2004

Diabetes Surgical Interventions (DSI) High Efficacy Medium Low Low Medium High Technical Complexity

So Why choose Sleeve?

Sleeve vs. LAGB %EWL, Diabetes remission better with sleeve No need for adjustments. No needles !!! Removes Ghrelin Cell mass. Loss of appetite Creates restriction more than obstruction less follow up ?

SLEEVE VS. RYGB and BPD-DS %EWL and T2DM remission may not be as strong BUT.. LSG is much technically less complex-wider applicability to general surgeons No risk of Internal Hernias No/Less malabsorption – No/Less micronutrient deficiency ? Maintains oral access to GI and Biliary tract Completely removes Ghrelin cell mass No dumping Does not interfere with immunosuppressant Can always be upgraded to RYGBP or BPD-DS

SLEEVE WINS!!!!

Questions? Questions?