Surgery: Considerations and Research

Sayeed Ikramuddin, MD

First Annual Minnesota Pediatric Obesity Conference Practical Approaches for Managing and Preventing Pediatric Obesity

Aldolescent obesity

Disclosures

•Fellowship support: Ethicon, Covidien•Research grant support: Covidien•Proctorship: Ethicon•I will discuss off label use of the gastric band system

Pories, W.J., et al., Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg, 1995. 222(3): p. 339-50; discussion 350-2.

Bariatric surgery procedures

Laparoscopic Adjustable Gastric Banding (LAGB)40% of procedures in 2008

Biliopancriatic Diversion w/ Duodenal Switch (Switch) 3-5% of procedures in 2008

Laparoscopic Sleeve Gastrectomy (LSG)5-7% of procedures in 2008

Roux En Y Gastric Bypass (RNYGP)50% of procedures in 2008

Buchwald H. Estok R. Fahrbach K. Bantle D. Jensen MD. Pories WJ. Bantle JP. Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. American Journal of Medicine. 122(3):248-256.e5, 2009 Mar.

Diabetes resolved = discontinued treatment, Diabetes improved = reduced treatment.

7 |

Glycemia as an Endpoint

Year Author N Level Therapy Control Outcome

2008 Dixon J 60 ALAGB (BMI

30-40 kg/m2)Medical

management 72% Resolution of Type 2 DM

2007 Sjostrom L 4047 A

Surgery (GBP, GB,

VBG)Medical

management 24% reduction in mortality with surgery

2006 O’Brien PE 79 ALAGB (BMI 30-34 kg/m2)

Medical management

Reduction in metabolic syndrome 93%- surgery vs.

46%- medical management

2004 Buchwald H 22,094 BBariatric Surgery Meta Analysis 77% Resolution of Type 2 DM

2007 Adams TD 15,850 B RYGBPConventional

treatment 92% reduction in diabetes related death

2006 le Roux CW 39 BRYGBP/LAGB

Lean and obese patients

improved insulin, GLP-1 response after RYGBP

2008 Lee WJ 158 CRYGBP < 35

kg/m2RYGBP >35

kg/m276.5% success in BMI<35 kg/m2; 88.9%

success in BMI 35–45 kg/m2,

2006 Cohen R 37 CRYGBP < 35

kg/m2   97% Resolution of Type 2 DM

2005 Torquati A 107 C RYGBP   72% Resolution of Type 2 DM

2005Wickremesekera

K 31 C RYGBP   Insulin resistance decrease at 6 days post surgery maintained after 12 months;

In which remission is defined as: No antihyperglycemic meds AND either A1c<6% or Glu<100, except in the case of both labs being available, in which case BOTH conditions must be met.

When multiple lab values are available for one AV, the one closest to the midpoint (ie: 12, 24, 36 months, etc) is used.

%Weight Loss (%WL) = [ (Weight Preop – Weight Postop) / Weight Preop ] *100

-40%

-20%

0%

20%

40%

60%

80%

0 1 2 3 4 5

Annual Visit

Remission A1c<6% Glu<100 No meds %WL

Gastric bypass

Small divided gastric pouch (30 cc)Roux limb 75cm-150cm Biliopancreatic limb 20cm-100cmantecolic or retrocolic roux“Gold Standard”

Bypass considerations

Longest followupmoderate malabsorption (Iron, B12, Thiamine)hypoglycemiamarginal ulcersexcluded stomachinternal herniaHigher perioperative complications

adjustable band

Restrictive procecureLow volume high pressure bandPars Flaccida Approachadjust to produce wt loss of 0.5-1 kg/week

Band considerations

Not FDA approved for < 18very low short term morbidity and mortalitypoor results in the superobese explantation 10%long-term risk of slippagelong-term risk of erosionneed for adjustments

Procedures

• Band

• Sleeve• Gastric bypass• Duodenal switch

Sleeve considerationslittle long term datapotential for leak insurance coverage an issueIncreased incidence of GERDNo nutritional complicationsease of conversion to DS or to RNY

Duodenal switch

Malabsorbtive and restrictive proceduremost durable weight loss4% incidence of revision for nutritional problems42F sleeve (32-60)100 cm common channel (50-125)

Effectiveness of Weight Management Programs inChildren and Adolescents

http://www.ahrq.gov/downloads/pub/evidence/pdf/childweight/chweight.pdf

Effectiveness of Weight Management Programs inChildren and Adolescents

http://www.ahrq.gov/downloads/pub/evidence/pdf/childweight/chweight.pdf

Introduction Weight Loss Surgery in Adolescents

The treatment of the morbidly obese adolescent patient is controversial.No clear consensus on best treatment of the morbidly obese adolescent.Contention between bariatric surgeons and pediatricians.

Adolescent Obesity and DiabetesWhat is Known

A steep rise in the prevalence of T2DM parallels the rise in obesity .Young patients with T2DM have rapidly progressive disease.5 fold increase in the incidence of obesity since 1970’sProgressive retinopathy and ASHD noted within 5yrs of diagnosis of T2DM in young adults.Health-related QOL 5.5x more likely to be impaired compared to healthy kids. similar to those diagnosed as having cancer.

# Kohn M and Booth M. Adol Med 2003 *Schwimmer JB, Burwinkle TM, Varni JW. JAMA 2003

Adolescent ObesityWhat is Unknown

When is the best time in the course of development (physical and emotional) for surgical intervention?How is compliance in this patient population?What are the long-term nutritional sequelae?What are the multi-generational sequelae?What are the long-term outcomes and recidivism rates?

Author (year) N Procedure (n) Age range

Mean follow-

up

Mean %EWL

Compl.rate Deaths

Lawson MLet al. (3 centers;

2006)39 LRYGB (34)

ORYGB (5) 13 to 21 1 year(n=30) 63% 39%

(n=15)1

(9 mos.)

Sugerman, et al. (2003) 33

LRYGB (2)ORYGB (28)

Open gastroplasty (3)12 to 17 Up to

14 years 58% 40% (n=13) 2 (late)

Stanford et al.(2003) 4 LRYGB (4) 17 to 19 17 mos. 87% 0% 0

Strauss et al. (2001) 10 ORYGB (10) 15 to 17 > 1 year 55% 50% late

(n=5) 0

Rand et al.(1994) 34 ORYGB (30)

Open gastroplasty (4) 11 to 19 6 years 66% NR 0

Barnett et al.(2005) 15

Open gastroplasty (7)ORYGB (5)

JIB (3)13 to 17

6 years(>9 mos.)

(n=9)64% 33%

(n=5) 0

Bariatric surgery Outcomes

Author (year) N Procedure (n) Age range

Mean follow-

up

Mean %EWL

Compl.rate Deaths

Silberhumer(2006) 50 LAGB (50) 9 to 19 35 mos. 61% 2% 0

Dolan et al.(2003) 17 LAGB (17) 12 to 19 2 years 59% 12%

(n=2) 0

Agrisani (2005) 58 LAGB(58) 15-19 7 56% 10% band removal 0

Lap Band Outcomes

Current Management of the Morbidly Obese Adolescent at the University of Minnesota

Evaluation by multidisciplinary team(statewide).Pediatric gastroenterologist / weight loss specialistPediatric psychologistBariatric surgeon with > 50 cases adolescentDietician: minimum of 6 months

Intensive medical weight loss programOutpatient / inpatient treatment

Bariatric surgery candidateDemonstrated compliance with medical weight lossSerious medical comorbidities

Demographics: LRYGB (n=30)Laparoscopic Weight Loss Surgery in Adolescents

Mean age 17.0 (range 12-19)8 patients ≤ 15 years

Mean BMI 55 kg/m2 (range 35-100)Mean weight 156 kg (range 99-275 kg)All > 95th percentile for BMI

Two patients with BMI > 90 kg/m2 were hospitalized ≥ 1 month preoperatively for intensive medical management.

Comorbid DiseaseComorbid Diseases (Total 66) N

Musculoskeletal Painful joints (10) Low back pain (6) Arthritis (2)

18

Pulmonary Obstructive sleep apnea (5) Asthma (4) Bronchitis (1)

10

Depression / Anxiety 10

Cardiovascular Hypertension (4) Dyslipidemia (9)

13

GERD 5

Metabolic / Endocrine Type 2 diabetes mellitus (2) Polycystic ovary syndrome (3)

5

Genitourinary Urinary stress incontinence (2) Renal stones (1)

3

Pseudotumor cerebri 2

Follow-UpLaparoscopic Weight Loss Surgery in Adolescents

Range 0 to 45 months, mean 15.8 months.14 patients had ≥ 12 month follow-up.Poor overall compliance with follow-up.

28.1% (n=9) lost to follow-up.Letters sent, phone calls made.

Of those who didn't follow-up55.6% (n=5) lost within first year44.4% (n=4) lost after 18 months

Adolescent Outcomes

Results: LRYGB Weight LossWeight Loss Surgery in Adolescents

12 y/o Pseudotumor cerebri BMI 47

33 months post op BMI 25.5 = 90% EWL

Normal growth exceeding mid-parental height

Summary of Findings

Adolescent bariatric surgery appears to be similar to adult bariatric surgery in terms of weight loss and complications.surgery safe in short term followup across the age spectrumfollowup can be more difficult than the adult populationAbsolute commitment to post-operative follow-up schedules need to be made pre-operatively with adolescent patients and their parents.evidence for choice of operation mixed

Weight Loss Surgery in Adolescents

Band Lower BMI(30-40)• it is the amount of weight loss not the method that determines the remission of type 2

diabetes

Dixon et al JAMA January 23rd 2008

The Effects of Bariatric Surgery on Type 2 Diabetes

The Entero-insular Axis

• Glucagon-Like Peptide-1 or GLP-1 (“Enteroglucagon”)– Secreted by ileal “L-cells” in (rapid) response to a meal– Actions

• Potent stimulator of insulin / supresses glucagon• Slows gastric emptying• Reduces appetite• Increases beta cell mass• Increased after gastric bypass (??)

• Peptide YY (PYY)• Gastric Inhibitory Polypeptide (GIP)

Wynne K. J Clin Endo Met, 2004

The Effects of Bariatric Surgery on Type 2 Diabetes

The Entero-insular Axis• Enteral glucose ingestion yields a greater insulin release

than does parenteral glucose infusion *

• Secreted gut hormones effect insulin production, secretion and usage = “incretins” / “anti-incretins”

• Select “known” peptides with various effects

* Elrick H. J Clin Endocrinol Metab. 1964

The Effects of Bariatric Surgery on Type 2 Diabetes

The Entero-insular Axis

Rehfeld J, 2004

1967 – Gastric Bypass

Peptides in T2DM

• GLP-1 response to mixed meal is blunted compared to non diabetics

• GIP response is blunted• After weight loss GLP-1 response improves

Exaggerated GLP-1 and Blunted GIP Secretion are Associated with Gastric Bypass but not Gastric Banding

Korner J, Bessler M, Inabnet WB et al. Surg Obes Relat Dis. 2007 Oct 10; [Epub ahead of print] .

Insulin response with OGTT RNY

LaFerre et al JCEM 2008

Ghrelin

Cummings et al NEJM

| April 22, 2023 | Confidential38 |38 |

Bariatric Surgery: Effects on Weight Loss and Mortality

29%

Sjostrom, L, et.al.; N Engl J Med. 2007;357:741-52

Years

Band

VBG

Cha

nge

in W

eigh

t (%

)

Control

80 4 6 15102

-30

0

-20

Gastric Bypass

Years80 4 1612

p = 0.04Cum

ulat

ive

Mor

talit

y (%

)

14

0

2

4

6

8

10

12Control

Surgery

-10

Case Matched Mortality (Mean Follow up of 7.1 years; out to 18 years

All Subjects Matched Subjects

Surgery Group(N = 9949)

Control Group(N = 9628)

Surgery Group(N = 7925)

Control Group(N = 7925)

No ./10,000person-yr

No /10,000person-yr

No n/10,000person-yr

No /10,000person-yr

All causes of death 288 37.2 425 61.1 213 37.6 321 57.1

All deaths caused by disease 198 25.6 380 54.7 150 26.5 285 50.7

Cardiovascular disease 66 8.5 134 19.3 55 9.7 104 18.5

Coronary artery disease 17 2.2 46 6.6 15 2.6 33 5.9

Heart failure 2 0.3 7 1.0 2 0.4 6 1.1

Stroke 9 1.2 14 2.0 7 1.2 11 2.0

Other cardiovascular disease 38 4.9 67 9.6 31 5.5 54 9.6

Diabetes 2 0.3 24 3.5 2 0.4 19 3.4

Cancer 42 5.4 102 15.0 31 5.5 73 13.3

Other diseases 88 11.4 120 17.0 62 11.0 89 15.5

All nondisease causes 90 11.6 45 6.5 63 11.1 36 6.4

Accident unrelated to drugs 29 3.7 19 2.7 21 3.7 17 3.0

Poisoning of undetermined intent 15 1.9 4 0.6 9 1.6 4 0.7

Suicide 21 2.7 8 1.2 15 2.6 5 0.9

Other nondisease cause 25 3.2 14 2.0 18 3.2 10 1.8

Conclusion• Type 2 DM is a complex disease • It is most strongly associated with obesity• Patient and physicians struggle to meet therapeutic goals• Bariatric surgery is established as a treatment of obesity• The effect on diabetes is profound• Clinical trials will allow for treatment of lower BMI

individuals• Adolescents want to look like their peers but they also

want to eat like their peers