Download pdf - 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

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.


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


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


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


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


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


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


Rationale

Preclinical Data

Author Year N Embolic Agent Outcome

Arepally 2007 8 Morrhuate Sodium Weight Gain


Bawudun 2012 15 Bleomycin;

PVA 500-700μ

Weight Loss

Paxton 2013 12 Embozene 40μ Weight Gain

Weiss 2015 10 Alginate Beads 50μ Weight Gain


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





PVA 500-700μ

Weight Loss




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





PVA 500-700μ

Weight Loss




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





PVA 500-700μ

Weight Loss




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





PVA 500-700μ

Weight Loss




Rationale

Preclinical Data

- 6 animals treated with 40μ 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





PVA 500-700μ

Weight Loss




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





PVA 500-700μ

Weight Loss




Rationale

Preclinical Data

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


Rationale

Preclinical Data





PVA 500-700μ

Weight Loss



- 6 animals treated with 50μ 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


Rationale

Preclinical Data

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





PVA 500-700μ

Weight Loss



- 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.


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.


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.

The question then arises as to

whether or not this preclinical work

should be translated into human

study.


Rationale

This procedure should be

within the skill-set of IR.

Most of us have

significant experience

with left gastric

embolization in the

treatment of GI bleeding.

This experience can be

translated to bariatric

embolization.


Conclusions

The preclinical work and early feasibility studies in

humans (to be discussed) have shown that embolization

has promise as a minimally invasive treatment for obesity.


Conclusions

It is important to remember …

There is significant anatomic variability to the gastric

vasculature, which can lead to nontarget embolization.


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


Conclusions

It is important to remember …

There is significant anatomic variability to the gastric

vasculature, which can lead to nontarget embolization.

There is a significant risk of gastric ulceration, as seen in all

studies utilizing small embolic microspheres (with or without the

use of anti-reflux catheters).

Only one preclinical study showed actual weight loss

(performed with nonspherical PVA particles).

Weight gain/loss is clearly a multifactorial problem and much

work lies ahead in determining where embolization can fit into

the overall management of obesity.


Conclusions

The preclinical work and early feasibility studies in

humans (to be discussed) have shown that embolization

has promise as a minimally invasive treatment for obesity.

Be Patient

This procedure MUST only be done in a clinical research

setting.

There is no role for gastric embolization in the routine treatment

of obesity at this time