Gastric Artery Embolization for Weight Loss: Artery Embolization for Weight Loss: Rationale Gary Siskin, MD FSIR Professor and Chairman Department of Radiology Albany Medical Center

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  • Gastric Artery Embolization for

    Weight Loss: Rationale

    Gary Siskin, MD FSIR

    Professor and Chairman

    Department of Radiology

    Albany Medical Center

    Albany, New York

  • Gary Siskin, M.D.

    Consultant/Advisory Board: Boston Scientific, Embomedics, Biocompatibles,

    Medtronic

    Research Grants: Boston Scientific, Embomedics, Biocompatibles, Medtronic

  • Gastric Embolization

    GI-tract hormones regulate appetite

    Interrupting the arterial supply to the GI tract can alter hormone production.

    Altering hormone production can reduce appetite.

    A reduced appetite can lead to weight loss.

  • Gastric Embolization

    Rationale

    There are several

    hormones produced in

    the GI tract that are

    involved in digestion and

    in the regulation of

    appetite and satiety.

    Murphy KG, Bloom SR. Nature 2006; 444:854-859

  • Gastric Embolization

    Hormone Site Appetite Mechanism of Action

    Ghrelin Gastric

    Fundus;

    Duodenum;

    Pituitary Gland

    Motility; Insulin Secretion

    GLP-1 Ileum; Colon Gastric Emptying; Insulin

    Secretion; Glucagon Secretion;

    Gastric Acid Secretion

    PYY Ileum; Colon Gastric Emptying; Gastric Acid

    Secretion

    CCK Proximal Small

    Bowel

    Gastric Emptying; Gallbladder

    Contraction; Pancreatic Enzymes;

    Vagus Nerve

    Leptin Adipocytes Intake; Energy Expenditure

    Weiss CR, et al. J Vasc Interv Radiol 2015; 26:613-624

  • Gastric Embolization

    Rationale

    Ghrelin

    Sites of Production

    Stomach (75%): The ghrelin producing cells in the stomach are

    concentrated in the fundus; expression of ghrelin decreases from the

    fundus to the antrum of the stomach.

    Duodenum

    Pancreas

    Ovaries

    Adrenal Cortex

    Pituitary Gland

    Wren AM, Bloom SR. Gastroenterology 2007; 132:2116

  • Gastric Embolization

    Rationale

    Ghrelin

    Plasma ghrelin levels increase significantly before meals and

    decrease after meals; prolonged food restriction causes an

    increase in circulating ghrelin levels.

    Actions

    Hunger/Appetite

    GI Motility

    Growth Hormone

    Insulin Production

    Cummings DE, Overduin J. J Clin Invest 2007; 117:13

  • Gastric Embolization

    Rationale

    Ghrelin

    Activatied by gastric O-acyl transferase enzyme

    Transported across BBB where it binds to receptors in the

    pituitary gland, hypothalamus, hippocampus, and ventral

    tegmental region.

    Within the arcuate nucleus, it stimulates neuropeptide Y and

    agouti-related peptide.

    This inhibits the release of alpha-melanocyte-stimulating

    hormone.

    Alpha-MSH typically reduces appetite and food intake so its

    inhibition increases appetite and food intake.

    Anton K, et al. AJR 2016; 206:202-210

  • Gastric Embolization

    Rationale

    Ghrelin

    Decreases in ghrelin production has the potential to increase

    the levels of Alpha-MSH, which may subsequently reduce

    appetite and food intake.

    Anton K, et al. AJR 2016; 206:202-210

  • Gastric Embolization

    Rationale

    Preclinical Data

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - 6 animals treated with variable doses of morrhuate sodium; 2 sham

    controls.

    - The highest dose of morrhuate sodium led to a ruptured gastric ulcer.

    - Pathologic evaluation showed decreased tissue ghrelin, preserved tissue

    architecture, and microulcers at the GE junction.Arepally A, et al. Radiology 2007; 244:138-143

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - 5 animals treated with 125 micrograms of morrhuate sodium; 5 sham

    controls.

    - There was a significant decrease in plasma ghrelin levels in the treated

    animals.

    - Plasma ghrelin levels increased to baseline by week 4; follow-up

    angiography showed restored patency at that time.Arepally A, et al. Radiology 2008; 249:127-133

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - 5 animals received bleomycin + lipiodol; 5 animals received PVA; 5 sham

    controls.

    - Ghrelin levels increased in the treated patients (more with PVA) and

    increased in the control animals.

    - The treated animals had decreases in weight and subcutaneous fat.Bawudun D, et al. Cardiovasc Intervent Radiol 2012; 35:1460-1466

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - Nontarget embolization to liver was found in 3 patients in bleomycin group.

    - Pathologic evaluation showed no evidence of gastric ulceration.

    Bawudun D, et al. Cardiovasc Intervent Radiol 2012; 35:1460-1466

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - 6 animals treated with 40 embozene microspheres; 6 sham controls.

    - Treated animals had a significant decrease in serum ghrelin levels and

    gained less weight than the control animals.

    Paxton BE, et al. Radiology 2013; 266:471-479

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    - Pathologic evaluation demonstrated that 3/6 of the animals treated had

    evidence of healed ulcers in the body of the stomach.

    - The number of ghrelin-producing cells was lower in the treated group.

    - The number of acid-producing cells in the antrum was lower as well.

    Paxton BE, et al. J Vasc Interv Radiol 2014; 25:455-461

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

  • Gastric Embolization

    Rationale

    Preclinical Data

    Paxton BE, et al. J Vasc Interv Radiol 2014; 25:455-461

  • Gastric Embolization

    Rationale

    Preclinical Data

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

    - 6 animals treated with 50 barium-impregnated alginate beads; 4 sham

    controls.

    - Cone-beam CT used to evaluate fundal arterial supply and the risk of

    nontarget embolization; anti-reflux catheters were used for embolization.

    Weiss CR, et al. ESIR Annual Meeting 2014; Glasgow, UK

  • Gastric Embolization

    Rationale

    Preclinical Data

    Weiss CR, et al. ESIR Annual Meeting 2014; Glasgow, UK

    Author Year N Embolic Agent Outcome

    Arepally 2007 8 Morrhuate Sodium Weight Gain

    Arepally 2008 10 Morrhuate Sodium Weight Gain

    Bawudun 2012 15 Bleomycin;

    PVA 500-700

    Weight Loss

    Paxton 2013 12 Embozene 40 Weight Gain

    Weiss 2015 10 Alginate Beads 50 Weight Gain

    - Treated animals had a significant decrease in serum ghrelin levels, a

    significant increase in GLP-1 levels, and gained less weight than the

    control animals.

    - 3/6 animals treated had superficial fundal ulcers; all treated animals had

    evidence of delayed gastric emptying.

  • Gastric Embolization

    Rationale

    It should be clear that the preclinical

    work done in this area has given us a

    signal that the concept of bariatric

    embolization initiated by Arepally has

    promise.

  • Gastric Embolization

    Rationale

    It should be clear that the preclinical

    work done in this area has given us a

    signal that the concept of bariatric