Laparoscopic Gastric Plication for the Treatment of Severe Obesity Stacy A. Brethauer, MD Bariatric and Metabolic Institute Cleveland Clinic, Cleveland, OH Minimally Invasive Surgery Symposium February 25, 2011

Disclosures Ethicon Endo-Surgery Covidien Bard/Davol Consultant Scientific Advisory Board Speaker Covidien Bard/Davol Research Support

Objectives Preclinical studies Variations in Technique Clinical Outcomes Possibilities for the future

Concept of Gastric Plication Achieve gastric restriction No Staple Line Cost Safety No Prosthesis Serosa-to-serosa apposition Reversible/Revisable Given the low penetrance of bariatric surgery into the obese population worldwide, I think it is important to pursue new interventions that may offer a safer alternative to our current procedures or have a specific appeal to patients or referring physicians. The concept of gastric plication is relatively new and there is limited data available currently, but I think it does hold promise as a bariatric procedure. The potential advantages of this type of procedure is that it achieves gastric restriction immediately without a prosthetic device and without gastric resection. This has the advantage of a lower cost procedure that has a good safety profile and could be reversible. The major difference between this technique and some of the emerging endoluminal therapies is that we’re apposing serosa to serosa rather than mucosa to mucosa and are therefore creating a more durable plication. There are currently no endoluminal devices capable of achieving this degree of gastric infolding, but the data I’ll present here provides some proof of concept that may ultimatey have an endoluminal application. 4

Preclinical Studies

Evaluation of Gastric Greater Curvature Invagination for Weight Loss in Rats Fusco et al. Obesity Surgery 2006 16:172-177 Some initial animal work with this concept was published in 2006 by a group in Brazil and they divided 30 young Wistar rats into three groups of a sham anesthesia, a sham laparotomy, and a greater curvature gastric plication. The weight curves are shown here and the there was a significant decrease in weight gain in the greater curve rats at 21 days. 6

Comparison of Anterior Gastric Wall and Greater Gastric Curvature Invaginations for Weight Loss in Rats Fusco et al. Obesity Surgery 2007 17:1340-1345 They followed that study up with another rat study in which they compared 10 rats that underwent a greater curve plication to 10 rats that underwent an anterior plication without division of the greater curve vessels 7

Weight difference significant only at 21 days Comparison of Anterior Gastric Wall and Greater Gastric Curvature Invaginations for Weight Loss in Rats Fusco et al. Obesity Surgery 2007 17:1340-1345 Weight difference significant only at 21 days No difference in gastric volume measurement or epididymal fat pad wt at 28 days They did not find a significant difference at 28 days between the two groups in their weight gain or epididymal fat pat size 8

Gastric plication: a preclinical study of the durability of serosa-to-serosa apposition Menchaca et al. Surg Obes Relat Dis. 2011;7:8-14 Schematic of T-Tags (left) and buttressed T-Tags (right)

Serosa to Serosa Apposition 3 Weeks Post Op: Serosa to Serosa apposition has healed together through the creation of an adhesion 8 Weeks Post Op: Serosa to Serosa appostion zone has been replaced with fibrous connective tissue Figure 5 – Photomicrograph of distal pyloric region. The layers of the stomach wall (M = internal muscle tunic; m = external muscle tunic; muscle stains pink) are folded. The apposed serosal layers have healed together to form a 1-2 mm fibrous connective tissue bridge (S; collagen stains blue.) Spaces with sutures are shown (arrows.) Some sections of GVR sites with serosal abrasion were similar in appearance. Masson’s trichrome stain. confidential / for EES internal use

Preclinical Durability Studies Questions: Can serosa-to-serosa healing be achieve in a controlled manner? Is serosal treatment required? What type of fastener is needed? What type of pattern is needed? Is this procedure reversible or convertible? Acceleration plan increases cumm revenue from LGCP in year 2016 to 41.40MM from 29.80 and revenue in 2016 from 10.12 to 23.78 confidential / for EES internal use

Fastener Spacing and Number of Rows Braided Suture 3 Rows ~1cm spacing Braided Suture 1 Row ~2cm spacing Titanium Staple 3 Rows Interior Rows: ~2cm spacing Outer Row: ~1cm spacing confidential / for EES internal use

Titanium Clip vs. Suture Device Equivalence Methods: 10 dogs (5 Staple, 5 Suture), 8 weeks survival Mean procedure times for sutured and clip techniques were 53.5 and 25 minutes, respectively (p=0.028). Results: 100% of folds intact under endoscopic visualization; No significant difference observed between groups (p=0.317) Reversibility: All stapled animals were reversed and recovered normally; one sutured animal was reversed, but was not survived Results from the pre-clinical comparative study between suture and stapling. confidential / for EES internal use

Reversibility

2 weeks Post-reversal

Clinical Studies-Technique

Variations in Technique Laparoscopic Greater Curvature Plication Suture Type Suture Pattern Suture Spacing Depth of Fold Calibration Use of Endoscopy

Our Initial Technique for Greater Curvature Plication This video is not intended to be used as a surgical training guide.  Other surgeons may employ different techniques.  The steps demonstrated may not be the complete steps of the procedure.  Before using any medical device, including those demonstrated in this video, review all relevant package inserts, with particular attention to the indications, contraindications, warnings and precautions, and steps for use of the device. 21

Endostitch

Initial Suture Row

Intraoperative Endoscopy

Final Plication

Fastener Technique

Clinical Studies - Outcomes

Mean weight loss 26.4 +/- 8.7 kg (13-51 kg) Age 15-64 y BMI 31.64 - 45.09 kg/m2 Mean=37.47Kg/m2 Results at 1 year: Mean weight loss 26.4 +/- 8.7 kg (13-51 kg) Mean %EWL 69.6 +/- 7.44 (6.2 – 95.6) No reported complication or mortality 70% of patients below 40 BMI

Laparoscopic Greater Curve Plication Ramos et al Laparoscopic Greater Curve Plication Ramos et al. Obes Surg 2010 Jul;20(7):913-8 42 patients Mean BMI 41 kg/m2 Mean operative time 50 minutes Mean length of stay 36 hours No major complications Mean 62% EWL at 18 months

OUTCOME OF LAPAROSCOPIC TOTAL VERTICAL GASTRIC PLICATION IN MORBID OBESITY Talebpour M, Amoli B. J Laparo Adv Surg Tech 2007; 17:793-798 N=150, Mean BMI 47 61% 60% 57% 57% 72p 51p 55% 94p 23p 10p

OUTCOME OF LAPAROSCOPIC TOTAL VERTICAL GASTRIC PLICATION IN MORBID OBESITY Talebpour et al. Complications 1 liver hematoma Reoperation 2.6% 4 patients 1 leak from suture line 1 prepyloric perforation 1 liver abscess 1 persistent n/v due to adhesions kinking the stomach No Mortality

Laparoscopic Gastric Plication for the Treatment of Severe Obesity Brethauer et al. Surg Obes Relat Dis.2011;7:15-22 IRB approval obtained 15 patients (three male) Mean preop BMI 43.5 (36.9 – 49.0) 9 patients underwent anterior surface plication 6 patients underwent greater curvature plication

METHODS Progression of diet from liquid to solid over 4 week period postoperatively Endoscopy at 3, 6, and 12 months postop Weight loss Adverse events

Anterior Plication

Greater Curvature Plication

Results Volume reduction with intraluminal fold achieved in all patients based on endoscopic assessment in OR Mean procedure time AP 89 minutes GCP 72 minutes Mean LOS 37 hours First 2 Greater Curvature patients with severe nausea with LOS 77 hours

Results Endoscopy at 3 and 6 months Anterior Plications (n=6): One partially disrupted fold Greater Curve Plications (n=6): One plication disrupted distally with broken intraluminal suture Endoscopy 12 months Anterior Plications (n=5): Same as 6 mos Greater Curve Plications (n=6) Same as 6 mos

Anterior Plication 6 months 12 months

Greater Curvature Plication 12 months 6 months

Weight Loss Procedure Three Months Twelve Months N Δ BMI %EWL 9 Anterior 9 -4.8 +/- 1.4 23.0 +/- 6.4 7* - 4.3 +/- 4.5 19.8 +/- 19.3 ** Greater Curvature 6 -7.8 +/- 1.5 38.9 +/- 8.2 -10.9 +/- 5.5 53.9 +/- 22.3 * 2 patients lost to follow-up ** Data from 2 patients collected after scheduled 12 month visit

Complications No bleeding or infectious complications First GCP patient required reoperation and plication reduction on POD#2 due to gastric obstruction Mild to moderate nausea in all patients (2 severe). Resolved within two weeks. 1 Lap cholecystectomy 11 months after procedure

Comparison to Other Studies

Multicenter Trial Underway 3 centers 45 patients 3 year follow-up All sutured Greater Curve Plication Standardized technique Enrollment complete Preliminary Results Encouraging At 12 months (our site) Mean BMI decreased from 43.4 to 34.4

Laparoscopic Gastric Plication Summary Anterior Plication safe, but not effective Greater Curve Plication Technically feasible, reproducible Good short-term weight loss Low major complication rate Long-term safety and weight loss data needed Remains investigational

The Future?

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