Update on Bariatrics Nothing to Disclose

Jonathan Carter, MD Jonathan Carter, MD Associate Professor of Surgery Associate Professor of Surgery

6/20/2018 6/20/2018

Case Presentation: Patty

33 year-old woman with morbid . 5’5” 262 lbs BMI 44

Morbidly obese since childhood. She has tried Weight Watchers, Curves, South Beach , Low Carb Diet, Atkins Diet, Slim-Fast, Nutrisystem and the UCSF Medically Managed Program. Although she has been able to lose some weight from diets and , over time the weight has always returned, and she has remained morbidly obese Patty

Past Medical History 262 lbs Migraine mellitus (HBA1C 6.7%) Asthma Intertrigo Urinary stress incontinence Polycystic ovarian syndrome

1 What can we offer Patty? What can we offer Patty?

1. There are more and more patients like Patty and the 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight. obesity epidemic continues without a plateau in sight.

2. We have new insights about why diets fail in the long 2. We have new insights about why diets fail in the long run. run.

3. No effective and durable drug therapy for severe 3. No effective and durable drug therapy for severe obesity exists. obesity exists.

4. has evolved rapidly 4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, • Safety now better than cholecystectomy, hysterectomy. hysterectomy. • Durability of weight loss now firmly established. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus. • Metabolic surgery is now the focus.

1990 1995

https://stateofobesity.org/adult-obesity/

2 2000 2003

2004 2005

3 2006 2007

2008 2009

4 2010 2011

2012 2013

5 2014 2015

2016 Why is obesity unhealthy? CARDIOVASCULAR RESPIRATORY Hypertension obstructive Congestive Heart Failure Pickwickian syndrome Cor pulmonale asthma Varicose veins GASTROINTESTINAL Pulmonary embolism GERD Coronary artery disease / NASH ENDOCRINE Hernia Colon GENITOURINARY Dyslipidemia Urinary stress incontinence Polycystic ovary syndrome Obesity-related glomerulonephropathy Amenorrhea, infertility, menstrual disorders Hypogonadism MUSCULOSKELETAL Breast and uterine cancer Gout Pregnancy complications NEUROLOGIC Lower back pain Stroke Carpal tunnel syndrome Idiopathic intracranial hypertension SKIN Meralgia paresthetica dermatoliposclerosis Dementia lymphedema PSYCHOLOGIC cellulitis Depression intertrigo Low self-esteem hidradenitis suppurativa Body image disturbance Social stigmatization

Mechanick et al. SOARD 2008

6 Obesity reduces life expectancy What can we offer Patty? Years of lost life expectancy in women 1. There are more and more patients like Patty and the 10 obesity epidemic continues without a plateau in sight.

8 2. We have new insights about why diets fail in the long 6 run. 4 3. No effective and durable drug therapy for severe obesity exists.

4. Bariatric surgery has evolved rapidly 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, hysterectomy. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus.

Randomly assigned 811 patients to 4 groups: low fat, low protein high fat, high protein low fat, high protein high fat, low protein Intensive group/individual instructional sessions Intensive follow-up to 2 years

7 “They [study patients] were offered 59 group and 13 individual training sessions over the course of two years…

[But] even these highly motivated, intelligent participants, who were coached by expert professionals, could not achieve the weight losses needed to reverse the obesity epidemic.”

- Katan, NEJM 2009

14 participants of “The Biggest Loser” competition

Participants were studied 1. prior to participation in the show 2. at the end of the 30 week competition 3. 6 years later

30 weeks: VLCD exercise

8 Outcome variables Methodology Measured resting metabolic • Indirect calorimetry rate (RMR) • Fast for 12 hours, then lay supine • Breath into metabolic cart for 15 min • Measure O2 intake and CO2 emission • Calculate Resting Metabolic Rate (RMR)

Body composition • By dual-energy x-ray absorptiometry • Measures Fat Mass (FM) and Fat-Free Mass (FFM) Predicted RMR

Indirect calorimetry to measure resting metabolic rate Fast for 12 hours Breathe into

18 2 Total energy expenditure • Clearance of O H2O and H H2O over 2 weeks • CO2 generation calculated, used to calculate TEE

Metabolic Adaptation

= RMR (measured) – RMR (predicted)

= the difference between what you are actually burning versus what you should be burning based upon your body composition, age, and sex.

Reflects the body’s ability to slow metabolic rate in order to preserve fat mass

In lay terms, is the body’s “ mode”

9 What happened at 6 years?

Body weight change Fat-free mass change Fat mass change in kilograms in kilograms in kilograms

What happened at 6 years?

Metabolic adaptation foils long-term attempts at

Obesity is not a disease of gluttons and sloths.

The body acts to preserve the fat mass set point.

Diet and exercise do not change the set point.

10 The Good... Phentermine About 5% loss in total body weight What can we offer Patty? beyond placebo

FDA approved (schedule IV controlled) 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight. The Bad... Side effects: 2. We have new insights about why diets fail in the long dry mouth insomnia run. dizzyness hypertension Mechanism: 3. No effective and durable drug therapy for obesity tachycardia exists. abuse potential stimulant similar to amphetamine 4. Bariatric surgery has evolved rapidly About 50% drop out of therapy from • Band out, Sleeve in, Bypass still the gold standard side effects. • Safety now better than chole or • The weight stays off for most – rigorous durability Only indicated for SHORT TERM use • Metabolic surgery more and more accepted The Ugly... Phen-Fen still fresh in everyone’s mind (induced severe pulmonary HTN and/or cardiac valve disease)

The Good... The Good... Orlistat (Xenical) Over one year, good for about 4-8 Rimonabant pounds over placebo About 5% weight loss beyond placebo

FDA approved for LONG term use May also help with smoking cessation

Reduces DM, HTN The Bad...

The Bad... Side effects: Side effects: nausea Mechanism: oily spotting Mechanism: depression staining with flatus diarrhea pancreatic lipase inhibitor in the GI tract fecal urgency antagonist of cannibinoid receptor CB1 steatorrhea NOT FDA approved Decreases LDL cholesterol The Ugly... Requires daily vitamin ADEK dosing Europe approved, then later withdrew because of suicides (2x risk of psychiatric disorder and 10% The Ugly... depression, 1% suicidal ideation 3x risk of acute kidney injury

FDA label: risk of severe liver injury

11 The Good... The Good... (Belviq) Qsymia About 10% weight loss beyond placebo Lorcaserin About 4-8 pounds additional weight loss at 12 weeks beyond placebo FDA approved in 2012 FDA approved in 2012 – Schedule IV Lowers BP. Benefit in sleep apnea. Not a lot of side effects! The Bad... The Bad... Side effects: Side effects: Mechanism: dry mouth Mechanism: hallucinations phentermine: stimulant tingling fingers selective serotonergic agonist 5HT2c topiramate: anticonvulsant constipation Initially declined by FDA over concerns BIRTH DEFECTS about safety. FDA reversed decision in 2012. DEA lists as Schedule IV Initially declined by FDA over concerns narcotic. about suicidal thoughts, palpitations, memory lapses, and cleft lip/palatte The Ugly... The Ugly... Heart valve damage? Need to wait for Requires monthly urine pregnancy tests! post marketing studies....

Patty We performed an intervention…… 262 lbs

12 Patty

252 lbs 2 months after 208 lbs Day of intervention

6 months

4 months after

180 lbs

13 6 months after 8 months after

161 lbs 149 lbs

10 months after 12 months after

146 lbs 143 lbs

14 18 months after 2 years after

142 lbs 138 lbs

…first half-marathon!

2 year check-up:

Weight: 138 pounds BMI 21.6

Hypertension: resolved. Off all meds. What was the intervention? Diabetes: complete resolution. HBA1C 5.6% PCOS: just stopped OCPs, trying to get pregnant Migraines: none in last year Asthma: resolved Stress incontinence: resolved

15 What can we offer Patty?

Gastric bypass anatomy 1. There are more and more patients like Patty and the obesity epidemic continues without a plateau in sight.

2. We have new insights about why diets fail in the long run.

3. No effective and durable drug therapy for severe obesity exists.

4. Bariatric surgery has evolved rapidly • Band out, Sleeve in, Bypass still the gold standard • Safety now better than cholecystectomy, hysterectomy. • Durability of weight loss now firmly established. • Metabolic surgery is now the focus.

Bariatric surgery has a durable effect on weight

obese controls

bypass band

bypass

number of patients

JAMA Surgery, 2017

16 GHRELIN

418 409 379 387

NEJM 2017 Cummings, NEJM 2002

The only durable way to change the set point is bariatric surgery Surgical options to treat obesity.

Gastric Bypass Sleeve gastrectomy LapBand

NEJM 2007

17 Surgical options to treat obesity. Gastric Bypass Sleeve gastrectomy LapBand Safety: Early Complications

NEJM 2007

Sleeve (n=101) Bypass (n=104)

JAMA 2018

18 bypass Safety:

sleeve Late Complications

Bypass Sleeve Nutritional Deficiencies after Gastric Bypass Surgery leak (1-2%) staple line leak (0.5-%) Risk of deficiency Diagnosis Treatment treatment: reoperation or drainage procedure with feeding tube treatment: reoperation, stent placement, feeding tube Nutrient placement placement, drain placement, or some combination thereof Protein <5% Hypoalbuminemia Prophy: dietary training >60g Dietary diary <60g Rx: Protein shakes stricture of gastrojejunostomy (2-3%) sleeve stricture (1-4%) Calcium / vitamin D 0.9% hypocalcemia Serum calcium Prophy: Ca 500mg + vit D 200IU TID treatment: dilation during endoscopy treatment: reoperation, conversion to gastric bypass Serum PTH Rx: vit D 100,000 IU IM weekly until 30% secondary HPTH Vitamin D level 25-OHD levels normalize marginal ulceration (3-5%) gallstone disease (2% with prevention) Essential fatty acids Rare Dry scaly skin, hairloss Prophy: soy protein treatment: antacids, surgery in rare cases prevention: ursodiol for 6 months Triene:tetraene ratio >0.2 Rx: soy protein, safflower oil treatment: remove gallbladder Vits ADEK Rare A -Night blindness Rx: ADEK tablet daily gallstone disease (2% with prevention) gastroesophageal reflux (20-50%) E - Eczematous rash vitamin A 4,000 IU prevention: ursodiol for 6 months treatment: acid blocking medications. K - Coagulopathy vitamin D 400 IU D - Osteomalacia vitamin E 150 IU treatment: remove gallbladder (conversion to gastric bypass in extreme cases) vitamin K 0.15mg internal hernias / obstruction (1-5%) dumping syndrome (0-10%) (also contains folate, thiamine, B vits) treatment: surgery in most cases treatment: limit simple sugars, high protein diet, complex Iron Up to 50% of women Anemia Prophy:FeSO4 325mg daily + vitC carbs, high fiber, smaller more frequent meals without supplements Rx: mild: FeSO4 TID severe: Iron dextran IV dumping syndrome (0-10%) treatment: limit simple sugars, high protein diet, complex Vitamin B12 Up to 33% if only Anemia Prophy: vit B12 500ug SL daily carbs, high fiber, smaller more frequent meals taking multivitamin Neuropathy Rx: 1000uG IM monthly until normal Folate Rare if taking MVI Hyperhomocysteinemia Prophy: MVI Anemia Rx: folate acid supplementation Neural tube defects of preg Thiamine (vit B1) Rare, unless severe Wernicke-Korsakoff Prophy: MVI LATE REOPERATION (5%) LATE REOPERATION (3% - 10%) nausea and vomiting Peripheral neuropathy Rx: thiamine 100mg/day IV Beriberi

19 Metabolic benefits of bariatric surgery

courtesy of ASMBS

20