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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ Weight Gain
Gastric Embolization
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
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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ Weight Gain
- 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
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 500-700μ
Weight Loss
Paxton 2013 12 Embozene 40μ Weight Gain
Weiss 2015 10 Alginate Beads 50μ 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
embolization initiated by Arepally has
promise.
The question then arises as to
whether or not this preclinical work
should be translated into human
study.
Gastric Embolization
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.
Gastric 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.
Gastric Embolization
Conclusions
It is important to remember …
There is significant anatomic variability to the gastric
vasculature, which can lead to nontarget embolization.
Gastric Embolization
Anton K, et al. AJR 2016; 206:202-210
Gastric Embolization
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.
Gastric 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.
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