Gastric Artery Embolization for Weight Loss: Rationale

Transcription

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

2 Gary Siskin, M.D. Consultant/Advisory Board: Boston Scientific, Embomedics, Biocompatibles, Medtronic Research Grants: Boston Scientific, Embomedics, Biocompatibles, Medtronic

3 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.

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5 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:

6 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:

7 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

8 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

9 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:

10 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:

11 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain

12 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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:

13 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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 Arepally at that A, et time. al. Radiology 2008; 249:

14 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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:

15 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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:

16 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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:

17 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss Alginate Beads 50μ Weight Gain - 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:

18 Preclinical Data Paxton BE, et al. J Vasc Interv Radiol 2014; 25:

19 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss 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

20 Preclinical Data Author Year N Embolic Agent Outcome Arepally Morrhuate Sodium Weight Gain Arepally Morrhuate Sodium Weight Gain Bawudun Bleomycin; PVA μ Weight Loss Paxton Embozene 40μ Weight Gain Weiss 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. Weiss CR, et al. ESIR Annual Meeting 2014; Glasgow, UK

21 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.

22 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.

23 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.

24 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.

25 Conclusions It is important to remember There is significant anatomic variability to the gastric vasculature, which can lead to nontarget embolization.

26 Anton K, et al. AJR 2016; 206:

27 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.

28 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