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Bariatric Embolization for the Treatment of Morbid Obesity Clifford R. Weiss, MD Associate Professor of Radiology, Surgery and Biomedical Engineering, Division of Vascular and Interventional Radiology Director, Interventional Radiology Research Medical Director, Johns Hopkins CBID The Johns Hopkins University School of Medicine

Bariatric Embolization for the Treatment of Morbid Obesity€¦ · Bariatric Embolization for the Treatment of Morbid Obesity Clifford R. Weiss, MD ... Gross and histopathologic evaluation

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Page 1: Bariatric Embolization for the Treatment of Morbid Obesity€¦ · Bariatric Embolization for the Treatment of Morbid Obesity Clifford R. Weiss, MD ... Gross and histopathologic evaluation

Bariatric Embolization for the Treatment of Morbid Obesity

Clifford R. Weiss, MD

Associate Professor of Radiology, Surgery and Biomedical Engineering, Division of Vascular and Interventional Radiology

Director, Interventional Radiology Research Medical Director, Johns Hopkins CBID

The Johns Hopkins University School of Medicine

Page 2: Bariatric Embolization for the Treatment of Morbid Obesity€¦ · Bariatric Embolization for the Treatment of Morbid Obesity Clifford R. Weiss, MD ... Gross and histopathologic evaluation

Bariatric Embolization of Arteries for the Treatment of Obesity (BEAT Obesity) Clinical Trial: 6 month Safety, Feasibility and Early Efficacy

C. R. Weiss,1 O. Akinwande,1 K. Paudel,1 L. Cheskin,2 B. Holly,1 K. Hong,1 A. M. Fischman,3 R. S. Patel,3 E. Shin,4 K. Steele,5 T. H. Moran,6

K. Kaiser,7 D. Shade,7 D. L. Kraitchman,1 A. Arepally8

1. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States; 3. Department of Interventional Radiology, Mount Sinai, New York, NY, United States; 4. Department of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 5. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 6. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; 8. Department of Radiology, Piedmont Healthcare, Atlanta, GA, United States.

Twitter: @DrCliffWeiss

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Obesity is an Epidemic

•  1960 - 46% of American adults are Overweight (32%), Obese (13%) or Morbidly Obese (<1%)

•  2010 - 75% of American adults are Overweight (33%), Obese (36%) or Morbidly Obese (7%)

•  Morbid obesity (BMI > 40 kg/m2) is increasing ~15 million individuals affected 1Centers for Disease Control and Prevention, 1960-2010

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Bariatric Surgery Options

Adjustable Gastric Banding

Sleeve Gastrectomy

Roux-en-Y Gastric Bypass

Biliopancreatic Diversion Duodenal Switch

EWL 19%

25- 30%

36-33%

34%+

Pros •  Low Complications •  Good Weight Loss

•  Continuous GI Tract •  Good Weight Loss

•  Better Weight Loss

•  Best Weight Loss

Cons •  Reoperations •  Implanted Device

•  Long Staple Line •  Nutritional

•  Anastomoses •  Nutritional

Deficit

•  Nutritional Deficit

•  Anastomoses % Cases 7% 45% 43% 5%

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Bariatric Surgery is Mostly Effective!

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“In this issue of JAMA Surgery, an analysis of claims paid by BlueCross BlueShield for bariatric surgery patients for as long as 6 postoperative years failed to demonstrate a cost benefit for weight loss surgery”

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Bariatric Embolization: Is There a Role in the Obese Patient?

0% 5% 10% 15% 20% 25% 30% 35%

Diet and Lifestyle Lap Band Gastric Bypass

Treatment Gap

Too risky for many people

Pharmacotherapy? Embolization?

For many patients

Other devices?

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Nat Med. 2012 May 4;18(5):668-9. doi: 10.1038/nm.2748

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Bar. Surg

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Bariatric Surgeries “Isolate” the Fundus and Prevent Ghrelin Production

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What is Bariatric Embolization ?

Minimally Invasive, Image-Guided Therapy Targeting the Function of the Stomach

Targeted Delivery of Embolics

Defunctionalize specific portions of the stomach

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LABORATORY INVESTIGATION

Histopathologic and Immunohistochemical Sequelaeof Bariatric Embolization in a Porcine Model

Ben E. Paxton, MD, Christopher L. Alley, MD, Jennifer H. Crow, MD,James Burchette, Clifford R. Weiss, MD, Dara L. Kraitchman, VMD, PhD,

Aravind Arepally, MD, and Charles Y. Kim, MD

ABSTRACT

Purpose: To evaluate the histopathologic sequelae of bariatric embolization on the gastric mucosa and to correlate withimmunohistochemical evaluation of the gastric fundus, antrum, and duodenum.

Materials and Methods: This study was performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12swine, 6 had previously undergone bariatric embolization of the gastric fundus, and the 6 control swine had undergone a shamprocedure with saline. Gross pathologic, histopathologic, and immunohistochemical examinations of the stomach andduodenum were performed. Specifically, mucosal integrity, fibrosis, ghrelin-expressing cells, and gastrin-expressing cells wereassessed.

Results: Gross and histopathologic evaluation of treatment animals showed healing or healed mucosal ulcers in 50% ofanimals, with gastritis in 100% of treatment animals and in five of six control animals. The ghrelin-immunoreactive mean celldensity was significantly lower in the gastric fundus in the treated animals compared with control animals (15.3 vs 22.0, P o .01)but similar in the gastric antrum (9.3 vs 14.3, P ¼ .08) and duodenum (8.5 vs 8.6, P ¼ .89). The gastrin-expressing cell densitywas significantly lower in the antrum of treated animals compared with control animals (82.2 vs 126.4, P ¼ .03). A trend towardincreased fibrosis was suggested in the gastric fundus of treated animals compared with controls (P ¼ .07).

Conclusions: Bariatric embolization resulted in a significant reduction in ghrelin-expressing cells in the gastric fundus withoutevidence of upregulation of ghrelin-expressing cells in the duodenum. Healing ulcerations in half of treated animals underscoresthe need for additional refinement of this procedure.

Ghrelin is the only hormone known to stimulate appetiteand is referred to as the “hunger hormone” (1–4). Bystimulating food intake, ghrelin induces positive energybalance, resulting in weight gain (5,6). Morbidly obesepatients have been shown to have a higher expression of

ghrelin-producing cells in the gastric mucosa (7). Theunique nature of this hormone and its effect on appetitehave led to attempts of multiple approaches to modulateghrelin production, but no feasible direct clinical tech-nique has yet been achieved (8–12).A catheter-based procedure, termed “bariatric embo-

lization,” has been introduced more recently; this tech-nique directly targets the gastric fundus, owing to thefact that it contains the highest concentration of ghrelin-secreting cells in the body (13–16). In the investigationsof this technique, calibrated spheres were delivered intothe arterial vasculature of the gastric fundus to inducelocalized ischemia. The investigations have shown thatbariatric embolization results in suppression of systemicghrelin levels and has a significant impact on weightgain. However, the histologic sequelae of bariatricembolization on the gastric mucosa have not yet beenreported. Also, ghrelin homeostasis is complex, and thepotential impact of bariatric embolization on ghrelin-expressing cell upregulation is difficult to predict. Thepurpose of the present study was to evaluate thehistopathologic sequelae of bariatric embolization on

& SIR, 2014

J Vasc Interv Radiol 2014; 25:455–461

http://dx.doi.org/10.1016/j.jvir.2013.09.016

From the SIR 2013 Annual Meeting.

This study was funded by the SIR foundation resident grant award to B.E.P.and an RSNA foundation resident grant award to B.E.P.

A.A. is a consultant and shareholder with Surefire Medical. None of the otherauthors have identified a conflict of interest.

From the Division of Vascular and Interventional Radiology (B.E.P., C.Y.K.) andDepartment of Pathology (C.L.A., J.H.C., J.B.), Duke University MedicalCenter, Box 3808, Durham, NC 27710; The Russell H. Morgan Departmentof Radiology and Radiologic Science (C.R.W., D.L.K.), Johns Hopkins Uni-versity School of Medicine, Baltimore, Maryland; and Department of Radi-ology (A.A.), Piedmont Healthcare, Atlanta, Georgia. Received June 3, 2013;final revision received September 24, 2013; accepted September 25, 2013.Address correspondence to B.E.P.; E-mail: [email protected]

Timeline of Bariatric Embolization From Initial Concept to Clinical Translation

WEIGHT LOSS, HORMONAL SHIFTS

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Physician Sponsored IDE single-arm prospective clinical trial for 20 morbidly obese patients

•  Study Device: 300-500μm Embosphere® microspheres (Merit Medical)

•  FDA approved: 2/11/2014

•  IRB approved: 6/2/2014

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Endpoints

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Inclusion Criteria

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Exclusion Criteria

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Workflow

(if needed)

Extensive Counseling, Preprocedure weight management “run in” PPI & Carafate

Gastric Motility

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Case Example

31 y.o. AAM Height: 6’3” Weight: 359 BMI: 44.9

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Celiac Angiogram

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Left Gastric Angiogram

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LGA angiogram - Post Embolization

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Initial Patient Demographics: Patient Age Sex Height (in) Weight (lbs) BMI

1 49 F 68 264.3 40.2

2 31 M 75 359.0 44.93 37 F 67 268.8 42.14 31 F 61 253.0 47.85 36 F 65 263.9 43.96 59 F 63 265.0 46.97 48 F 65 274.0 48.0

8 49 F 71 284.3 40.0Mean 41.6 ± 9.8 66.3 ± 4.2 278.3 ± 33.5 44.8 ± 2.7

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Safety Primary Endpoints Major Adverse Events None

Minor Adverse Events (n=4) 1 sub-clinical and transient pancreatitis *1 small superficial fundal ulcer @ lesser curve at 2 weeks, resolved at 3 wks. *1 small healed ulcer in lesser curvature at 2 weeks *Several clean-based ulcers were found along the lesser curvature *Anticipated event

5 anticipated admissions for 24-48 hours for nausea/vomiting/pain

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Efficacy Primary Endpoint

Weight loss (1M) Mean Change: -10.3 (6.1) [7] Mean % EWL: -7.1% (4.1) [7]

Weight loss (3M) Mean Change: -14.8 (7.3) [6] Mean % EWL: -10.1 (4.5) [6]

Weight loss (6M) in lbs

Mean Change: -21.0 (9.9) [2] Mean % EWL: -13.4% (4.0) [2]

EWL=(BL-post)/(BL-IBW)*100 Devine formula for IBW (1974)

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0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12 14

Score

Weeks

Hunger/Appe=teScoresAverage6Days

BeforeBreakfast BeforeLunch MidAJernoon PostDinner

-81%

-59%

-29%

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0

200

400

600

800

1000

1200

1400

1600

1800

2000

0 2 4 6 8 10 12 14

Calorie

s(kcal)

Week

MeanCaloricIntake(2Week)

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Hormonal Trends:

Ghrelin -17.5% (± 29.0)

GLP-1 106.6% (± 208.5)

PYY 17.8% (± 54.8)

Page 29: Bariatric Embolization for the Treatment of Morbid Obesity€¦ · Bariatric Embolization for the Treatment of Morbid Obesity Clifford R. Weiss, MD ... Gross and histopathologic evaluation

Conclusions? •  Bariatric Embolization with “larger particles” is

well-tolerated in the short and intermediate term in the severely obese patient

•  Appears to be effective in the short and intermediate term in the severely obese patient

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BEAT Obesity ROADMAP

BEAT 1A

BEAT 1B

BEAT 2*

15 PATIENTS

SAFETY/efficacy

SAFETY/EFFICACY

EFFICACY

5 PATIENTS

120 PATIENTS

M. ADVERSE EVENTS (0)

TBL+AE

TBL, AE, COST

*Planning funded by SIRF FSDG

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Obesity Behavioral

Psychological

Sociocultural

Environmental Genetic

Physiological

Metabolic

Hormonal