Bariatric Surgery for Morbid Obesity: Tehran Obesity Treatment Study (TOTS) Rationale and Study Design

Background Obesity is a major health concern in the Middle East and worldwide. It is among the leading causes of morbidity, mortality, health care utilization, and costs. With bariatric surgery proving to be a more effective treatment option for overweight and obesity, the need for systematic assessment of different procedures and their outcomes becomes necessary. These procedures have not yet been described in detail in our region. Objective We aim to undertake a prospective study evaluating and comparing several surgical bariatric procedures in an Iranian population of morbid obese patients presenting to a specialized bariatric center. Methods In order to facilitate and accelerate understanding of obesity and its complications, the Tehran Obesity Treatment Study (TOTS) was planned and developed. This study is a longitudinal prospective cohort study in consecutive patients undergoing bariatric surgery. TOTS investigators use standardized definitions, high-fidelity data collection system, and validated instruments to gather data preoperatively, at the time of surgery, postoperatively, and in longer-term follow-up. Results This study has recruited 1050 participants as of September 2015 and is ongoing. Conclusions This study will ensure creation of high-level evidence to enable clinicians to make meaningful evidence-based decisions for patient evaluation, selection for surgery, and follow-up care.


A. Surgical Procedures
A standard 5-port laparoscopic technique with the bed in the reverse Trendelenburg position is used. At the completion of the procedure, some patients have white silicone drains (SUPA, Iran) placed in the proximity of the gastrojejunostomy (GJ), which are removed at the first postoperative inpatient visit barring any complications. In the interim, patients are asked to record the nature and amount of the output daily. Postoperatively, patients start on oral fluids and are promoted to mobilize. After discharge, patients continue on a liquid diet for 2 weeks followed by a sloppy diet for 4 weeks, before resuming a normal diet. Patients will receive daily multivitamin and mineral supplementations for the first 12 months. All patients undergoing RYGB will receive vitamin B12, vitamin D, and calcium supplements. Iron supplements are given depending on the control blood tests. Acid suppression with a proton pump inhibitor is considered in cases with GI problems. Discontinuation or modification of medical therapy is considered in cases of blood pressure, lipids, or glucose normalization or improvement.. Surgical techniques are as follows:

I . Roux-en-Y Gastric Bypass (RYGB)
Includes an antecolic and antegastric RYGB with an alimentary limb of 100-150 cm and a biliopancreatic limb of 50 cm. A 20-30 cm 3 vertical gastric pouch is created using a 45 or 60-mm stapling device (Endo GIA Auto suture, Covidien, Mansfield, MA, USA). A side-to-side GJ is performed using linear stapler. A side-to-side jejuno-jejunostomy is created using a 60-mm diameter lineal stapler with white loads. Methylene blue or air test is performed to identify possible leaks.

I I . Laparoscopic Sleeve Gastrectomy (LSG)
For the sleeve gastrectomy procedure, 75%-80% of the body and fundus is excised. The gastric tube is created over a 36-F bougie using multiple firings of the stapler. The stapler line is reinforced and imbricated with 2.0 PDS running sutures. A methylene blue or air test is performed to check for leaks and a closed suction drain is placed based on surgeon's decision.

Mini-gastric bypass
Mini-gastric bypass is a modification of the standard RYGB procedure using a long gastric tube with an antecolic loop GJ. A long gastric tube is created using Endo GIA stapler from the incisura angularis to the angle of His over a 36-F bougie. A loop gastroenterostomy is performed 200 cm distal to the ligament of Trietz with an Endo-GIA stapler. The gastroenterostomy is then reinforced with continuous sutures. A methylene blue or air test is performed to check for leaks and one drain is left in the lesser sac before closure of the wound.

I I I . Laparoscopic Adjustable Gastric Banding (LAGB)
This technique is performed by using the adjustable gastric band with velocity injection port and applier (MIDBAND™, MID, Dardilly, France), applying the "pars flaccida" technique. 1 The band is not secured by fixation to the walls of the stomach and drainage is not routinely used.

IV. Gastric plication
Gastric plication (GP) is a recently introduced bariatric procedure. One of the first descriptions of this procedure came from Iran with the total vertical gastric plication (TVGP). 2 In this operation, the greater curvature of stomach is folded inwards in 3 parallel lines and sewed to reduce the gastric volume without removing any tissue. An intraluminal guide (No. 36) is used to assure the best site for suturing.

B. Anthropometric measurements
Anthropometrics include weight, height, neck, waist, wrist, and hip circumference, measured according to WHO guidelines. 3

C. Smoking Status
Smoking status was defined according to CDC definitions for smoking, as shown in Adults who have never smoked a cigarette or who smoked fewer than 100 cigarettes in their entire lifetime.

Former Smokers
Adults who have smoked at least 100 cigarettes in their lifetime, but say they currently do not smoke. Nonsmokers Adults who currently do not smoke cigarettes, including both former smokers and never smokers.

Current Smokers
Adults who have smoked 100 cigarettes in their lifetime and currently smoke cigarettes every day (daily) or some days (nondaily).
After a 12-14-hour overnight fast, blood samples are drawn in a sitting position between 7-9 a.m. in three aliquots to be stored in -80°C ultra-freezers for biochemical and future genetic/molecular assessments. Blood sample for DNA analysis is stored in an EDTA containing tube. Other samples are then centrifuged within 30 to 45 minutes of collection.
The derived serum is separated into at least four 1-ml aliquots; one is sent for all biochemical analyses on the same day, and three others are stored in -80°C ultra-freezers for future studies. Table 2 outlines the blood and urine assessments used in TOTS.

E. Genetics and biomarkers
DNA obtained from consenting participants will be part of an ongoing research effort to identify genes related to human obesity. Blood samples drawn from subjects before and after the surgery are stored for further studies. Buffy coats are separated from EDTA-anti coagulated samples and genomic DNA is extracted with the salting-out method 4