Mubin Syed, M.D. No relevant financial relationship reported

Transcription

1 by: Mubin I. Syed, MD, FACR, FSIR President, Dayton Interventional Radiology Clinical Associate Professor of the Radiological Sciences Wright State University School of Medicine *Financial Disclosure: Partial funding for above study provided by 2015 SIR Foundation Pilot Research Grant and 2016 RSNA Seed Research Grant. No other relevant financial relationships.

2 Mubin Syed, M.D. No relevant financial relationship reported

3 2008: 1.5 billion overweight; 500 million obese (1 in every 8) Major risk factor for diabetes, heart attacks, stroke, cancer, osteoarthritis - Increases risk of diabetes 18-fold Fifth leading risk for death globally Ex. 25 year old morbidly obese loses 12 years (on average)

4 The number of obese people in the world rose from 105 million in 1975 to 641 million in 2014, with obesity rates rising from 3 percent to 11 percent among men and from 6 percent to 15 percent among women, the study found. The researchers added that about one-fifth of adults could be obese by Over the same time, the proportion of underweight people fell from 14 percent to 9 percent of men and from 15 percent to 10 percent of women, according to the study HEALTH: Accessed April 14, 2016.

5 1 in 10 American adults has diabetes (if the trends continue, the number of people with diabetes is expected to double or even triple by Every 5 minutes, 2 people die from diabetes and 14 are newly diagnosed. 90% - 95% of all diabetes cases are type 2 86 million adults in the U.S. who had prediabetes in

6 Diet / exercise - Difficult to sustain Medications - Average wt. loss: 6-10lbs Surgery

7 Average weight loss: 88lbs (sustained) Diabetes: 77% resolved Hypertension: 62% resolved Sleep apnea: 86% Hypercholesterolemia: 87% improved Effects of obesity

8 Major Abdominal Surgery Mortality: 1-2% Wound complications: 7% Hernias: 9% Esp high risk: -Extreme obesity -Co-existing medical conditions Need an alternative for surgery!

9 Pioneered by Aravind Arepally, MD Concept: Interventional radiologist can decrease cells by limiting the blood supply Most ghrelin secreting cells in the fundus Interventional radiologist are experts at finding and targeting specific arteries.

10 What is it? How does it work (metabolism, site of action)? Where is it produced? What treatments are currently being developed to target Ghrelin? Vaccine (etc. refer to Monteiro talk) How would Bariatric embolization work

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12 40 year old procedure. First described in the early 1970 s. The left gastric artery is embolized typically with a gel-foam slurry and coils If necessary. The procedure is used for life-threatening hemorrhage from the gastric fundus and gastro esophageal hemorrhage not controllable by endoscopic intervention. Currently is the standard of care as an on call procedure for Interventional Radiology. Procedure takes 20 minutes. Safe and effective.

13 RSNA Press Release - Embolization Procedure Aids in Weight Loss In the retrospective study conducted at Massachusetts General Hospital in Boston, researchers reviewed the records of patients who underwent transarterial embolization for upper gastrointestinal (GI) bleeding. The study group included 14 patients who underwent embolization of the left gastric artery, which supplies blood to the part of the stomach where the hormone ghrelin is predominantly produced. "Ghrelin is the only hormone known to stimulate the appetite, so it is an intriguing potential target for combating obesity," said senior researcher Rahmi Oklu, M.D., Ph.D., assistant professor of radiology at Harvard Medical School. "Animal studies have shown that when this artery is blocked, blood levels of ghrelin decrease and weight loss occurs."

14 The study also included a review of the records of 18 age-matched control patients who were treated for upper GI bleeding with transarterial embolization of a different upper gastrointestinal artery. The study group included eight men and six women with a median age of 66.1 years; the control group included eight men and 10 women with a median age of 63.5 years. The researchers found that patients who underwent left gastric artery embolization lost an average of 7.9 percent of their body weight within three months of the procedure. Weight loss within the control group was 1.2 percent during the same time frame. "Embolizing the left gastric artery may be a potential bariatric treatment for weight loss and an alternative to other invasive procedures," Dr. Oklu said. "This is an important data point in the development of a new clinical tool for the treatment of obesity." Dr. Oklu pointed out that left gastric artery embolization performed by an interventional radiologist is low risk when compared to more invasive weight loss interventions, such as gastric bypass and laparoscopic approaches.

15 Kipshidze "It's a one day surgery. You can do the procedure on patients in the morning and send them home in the evening." The study included just five people. All were obese; the average body mass index (BMI) was 42.3 kg/m 2, with a range of 33.9 kg/m 2 to 52.8 kg/m 2. Researchers used an endoscope to examine each person's esophagus and stomach before and after the procedure, as well as one week later. No ulcers or other complications occurred. Three people had discomfort during the first few hours after the procedure, but the endoscopy did not show blockages or other complications.

16 One month after bariatric embolization, the average BMI dropped to 37.9 kg/m 2, with an average weight loss of 29.2 pounds. After three months, the average BMI was 36.7 kg/m 2 and the average total weight loss was 37 pounds. At six months, the average BMI was 35.3 kg/m 2 and average total weight loss was 45.1 pounds. Blood ghrelin levels also dropped. At one month, levels had fallen 29 percent from baseline (p<0.05). At three months, they were 36 percent below baseline (p<0.05). At six months, they were 18 percent below baseline (p>0.5).

17 Currently there are 3 active FDA supervised studies enrolling human patients in the USA GET LEAN (Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically), Dayton, Ohio, u Beadblock BEAT Obesity (Bariatric Embolization of the Arteries for the Treatment of Obesity), Baltimore, MD and NYC u Embospheres Albany Study, Albany NY u PVA

18 Beat Obesity (Bariatric Embolization of the Arteries for the Treatment of Obesity)-presented by Dr. Clifford Weiss, Johns Hopkins University SIR 2016 Weight loss at 1 mos Weight loss at 6 mos 10.3 lbs 21.0 lbs 7.1% EWL 13.4% EWL Weight loss at 3 mos N= lbs u Embospheres 10.1% EWL 17.5% Ghrelin drop EWL=(BL-post)/BL-IBW)*100 Devine formula for IBW (1974) Reprinted with permission from Clifford Weiss,MD

19 GET LEAN (Gastric Artery Embolization Trial for Lessening of Appetite Nonsurgically)- PI: Mubin Syed, Dayton Interventional Radiology Weight loss at 1 mos 13.5 lbs 5.3% 10.6% EWL Weight loss at 3 mos 16.8 lbs 7.0% 14.3 % EWL All patients subjectively reported appetite suppression Weight loss at 6 mos lbs 8.5 % 17.2% EWL EWL=(BL-post)/BL-IBW)*100 Devine formula for IBW (1974) N=4 ( u Beadblock)

20 Kipshidze University Hospital CV Center, Frankfurt, Germany DIR, Dayton, OH John Hopkins university St. Ekaterina Hospital, Odessa, Ukraine Center for Laser and Interv. Surg. Beirut, Lebannon Total Number Follow-up 24 mos 20 mos 6 mos 6 mos 2 mos 1-9 mos 2-24mos Total Weight Loss Mean Minor Adverse Events Major Adverse Events 16% 12% 8.5% 8% 9% 1-1.5kg/mos 10% ( 37.5%) Reprinted with permission from Nicholas Kipshidze, MD

21 Morbid obesity with a BMI 40 Age 22years Ability to lay supine on an angiographic table <400lbs due to table weight limits Appropriate anesthesia risk as determined by certified anesthesia provider evaluation pre procedure Subjects who have failed previous attempts at weight loss through diet, exercise, and behavior modification (as it is recommended that conservative options, such as supervised low-calorie diets combined with behavior therapy and exercise, should be attempted prior to enrolling in this study).

22 Major Surgery within the past eight weeks Previous gastric, pancreatic, hepatic, and/or splenic surgery Previous radiation therapy to L or R upper quadrant Previous gastric, hepatic, and/or splenic embolization Any history of portal venous hypertension Serum creatinine > 1.8 mg/dl History of kidney problems Pregnant or intend to become pregnant within 1 year History of Severe bleeding (platelet count less than 40,000) Enrolled in another study History of allergic reaction to iodinated contrast Abnormal baseline studies (gastric emptying, CTA, EGD, etc) Active substance abuse or alcoholism Hiatal Hernia Known aortic disease, such as dissection or aneurysm

23 Defined noncompliance with previous medical care Subjects with mesenteric atherosclerotic disease or abdominal angina should be excluded due to safety concerns. Comorbidity such as cancer, peripheral arterial disease or other cardiovascular disease Patients with any abnormality on their baseline EGD Patients taking anti-coagulants Patients taking or requiring chronic use of NSAID or steroid medications Patients with any history of peptic ulcer disease Certain psychiatric disorders such as schizophrenia, borderline personality disorder, and uncontrolled depression, and mental/cognitive impairment that limits the individual s ability to understand the proposed therapy PLEASE note that GET LEAN does not exclude diabetics and does not exclude patients with H. Pylori (50% of the population) and currently does not exclude anatomic variants

24 Femoral or radial artery access Pigtail catheter for flush aortogram Reverse curve catheter to access celiac artery followed by the left gastric artery Coaxial microcatheter for selective left gastric arteriogram past esophageal branch Particle embolization using BeadBlock micron to stasis (at least 5 cardiac pulsations) Closure device

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28 CH1190 THO6761 CRA1984 ADK1970

29 Baseline 6 months 10 0 CH1190 ThO6761 CRA1984 ADK1970

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31 CH1190 THO6761 CRA1984 ADK1970* Pre Week 803 1, Month Month Month mos % 39.1% 10.1% -9.5% -18.7% 1 Year

32 CH1190 THO6761 CRA1984 ADK1970* Pre Week Month Month Month % change % 75.28% % % All patients who lost weight dropped Leptin levels 1 Year 4.0

33 CH1190 THO6761 CRA1984 ADK1970* Pre Week Month Month Month % change -5.00% % % % 1 Year 47

34 Serum Ghrelin +8.68%+/ % at 1 month / % at 3 months QOL parameters trend toward improvement Hunger appetite scores markedly decreased at 2 weeks post BE and remain suppressed

35 GET LEAN study 3 patients with superficial ulcerations by 3 day endoscopy All healed by 30 day endoscopy BEAT OBESITY 3 minor adverse events Subclinical transient pancreatitis 2 patients with superficial ulcerations healed by 2 and 3 weeks respectively

36 Maybe: Still in Phase 1 pilot study Criteria Proper patient selection Inclusion/exclusion criteria Motivation is key Ability to exercise and be active post procedure BMI range Presently BMI >40 in future possibly >35 with comorbidities similar to bariatric surgery Exclusion criteria Exclude patients who are depressed or on antidepressants

37 48 lbs lost or 49% EBW equivalent to surgical outcome at one year

38 Radial artery access is feasible and may have huge potential

39 Bariatric embolization may have a possible role in morbidly obese diabetic patients Baseline 1 month 3 months 6 months 12 months Normal Hgb A1C-4.5 to 6.0 Prediabetic Hgb A1C- 5.7 to 6.4 Diabetic HgbA1C- >6.5 ADK1970

40 All 4 patients were performed in the GET LEAN study at a free standing center

41 Durability not known (possible upregulation in other parts of stomach and GI tract) Role of mental component (complexity of human emotional responses that effect food consumption) Anatomic variability (size and supply area) Side effect potential with ghrelin reduction Ulcer risk with potential for nonhealing (role of H. Pylori) Risk of potentially limiting future gastric sleeve surgery Ideal patient is not yet defined (BMI etc.)

42 Bariatric embolization, or gastric (stomach) artery embolization promising treatment for obesity Can be done outpatient Potential for major weight loss equal to surgery Diabetic patients may be candidates Wrist artery access Still too early for RCT Need to improve effectiveness without increasing risk (lower BMI, and smaller particles) Procedure is safe is short and intermediate term Appears to be effective in the short and intermediate term.

43 Continuation of the FDA trial with additional patients Including further experience with radial artery access and diabetic patients Possible use of alternative embolic agents (smaller size) Randomized control trial

44 Procedure still experimental Still in infancy and being done only context of clinical trials at this stage

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