Clinical trial NCT01041105: Gastric Bypass After Previous Anti-reflux Surgery
Official title: Laparoscopic Revision Roux-en-Y Gastric Bypass Surgery After Previous Anti-rflux Surgery: Intermediate Results
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Clinically Severe Obesity
Gastroesophageal Reflux Disease
Keywords: Obesity
Gastroesophageal Reflux Disease
Nissen funduplication
Antireflux surgery
Revisional Gastric Bypass
Re-operative bariatric surgery
Bariatric surgery
Nissen
Conversion of Nissen to Gastric Bypass
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2009-12-31
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) after a previous functional or failed anti-reflux procedure and met National Institutes of Health criteria for bariatric surgery.

Brief summary: The goal of this study is to describe the clinical presentation, indications, and operative treatment as well as assess the morbidity, mortality, and overall performance of revisional Roux-en-Y gastric bypass (RYGB) after either failed or functional antireflux surgery "ARS" in obese patients. With such information, we hope to determine which features might assist us in advancing our knowledge about Gastro-Esophageal Reflux Disease "GERD", the best option for primary ARS, and mechanisms of failure in the obese population as well as in identifying predictors of outcome after revisional surgery in this population.

Detailed description: The epidemic of overweight and obesity in the United States of America along with its comorbidities continues to expand. Bariatric surgery has demonstrated to be the most effective and sustained method to control severe obesity and its comorbidities. For instance, type 2 diabetes mellitus was completely resolved in 76.8 percent, systemic arterial hypertension was resolved in 61.7 percent, dyslipidemia improved in 70 percent, and obstructive sleep apnea-hypopnea syndrome was resolved in 85.7 percent. Furthermore, bariatric surgery significantly increases life expectancy (89 percent) and decreases overall mortality (30-40 percent), particularly deaths from diabetes, heart disease, and cancer. Lastly, preliminary evidence about downstream savings associated with bariatric surgery offset the initial costs in 2 to 4 years.

Since 1998, there has been a substantially progressive increase in bariatric surgery. In 2005, the American Society of Metabolic and Bariatric Surgery "ASMBS" reported that 81 percent of bariatric procedures were approached laparoscopically. 205,000 people, in 2007, had bariatric surgery in the United States from which approximately 80 percent of these were Gastric Bypass. Moreover, there is a mismatch between eligibility and receipt of bariatric surgery with just less than 1 percent of the eligible population being treated for morbid obesity through bariatric surgery. Along with the increasing number of elective primary weight loss procedures, up to 20 percent of post RYGB patients cannot sustain their weight loss beyond 2 to 3 years after the primary bariatric procedure. Thus, revisional surgery for poor weight loss and re-operations for technical or mechanical complications will rise in a parallel manner.

Three systematic reviews and meta-analysis have examined the association between obesity (BMI \>30kg/m2) and several GERD-related disorders, including 1) GERD symptoms, 2) erosive esophagitis "EE", and 3) esophageal adenocarcinoma "EA". Obesity is associated with a 1.5-to-2-fold increased risk of GERD symptoms and EE and a 2- to 2.5-fold increased risk of EA. In two large case-control studies, abdominal diameter (waist-hip ratio), but not BMI, is an independent risk factor for another GERD-related disorder, Barrett´s esophagus "BE".

Current pathophysiological mechanisms of GERD in the obese encompass the following. 1) Mechanical: I) increased intra-gastric pressure: increased intra-peritoneal and abdominal wall fat mass increases the intra-abdominal and peri-gastric pressures with subsequent increased gastroesophageal pressure gradient "GEPE" with augmented esophageal acid exposure. Each BMI unit increase corresponds to a 10 percent increase in intra-gastric pressure. II) Hiatal Hernia: "HH" disrupts the integrity of the sphincter mechanisms and prolongs esophageal acid clearance. Thin, normal, overweight, and obese subjects have a 1.0, 1.9, 2.5, and 4.2 risk of having HH compared to thin subjects, respectively. 2) Motility: I) Increased Transient LES Relaxation "TLESR" are associated with acid reflux during the postprandial period, especially during inspiration. II) Low LES basal pressure: Increased prevalence of abnormally low LES basal pressure in the overweight and obese in comparison to the normoweight subject. III) Esophageal motility abnormality: Jaffin et al, with esophageal manometry, reported 61 percent of patients with altered esophageal motility from which 59 percent had altered visceral pain perception (asymptomatic). IV) Delayed gastric emptying: mostly associated with one of its major comorbidities, diabetes mellitus. 3) Esophageal sensitivity: Mercer et al., with a Bernstein test, found a significant difference between normoweight and obese subjects without clinical evidence of GERD (0 percent vs. 86 percent, respectively) for esophageal hypersensitivity. 4) Hormonal: mostly mediated by estrogen and adiponectin. 5) Environmental (Diet): high-fat, saturated fatty acids, high-cholesterol, and high caloric density diets have been associated with the highest likelihood of perceiving an acid reflux event; fat may confer its sensory effect by activating pain facilitatory pathways or by deactivating pain inhibitory pathways.

The most recent data is not conclusive on whether increased BMI affects acid-suppressive therapy for GERD. However, MacDougall et al. found that increased BMI was significantly associated with long-term acid suppression therapy. This can be explained based on either a higher prevalence of factors that predispose overweight and obese subjects to severe GERD, such as HH, greater GEPG, increased number of TLESR, or standard doses of PPI´s are suboptimal for patients with increased BMI and GERD.

Broad indications for antireflux surgery include: 1) Reflux of food associated with HH, 2) despite successful medical treatment or after poor or moderate symptom control on optimized PPI therapy, patient opts for surgery, and 3) Complicated GERD without including severe dysplasia.

Available traditional ARS are either 1) fundoplication, which is the most commonly performed procedure and can be partial -Toupet, Dor- or complete -Nissen-, or other procedures with limited use such as 2) Hill operation, 3) pyloroplasty, 4) vagotomy with antrectomy, and 5) duodenal switch.

Long-term control of typical symptoms after primary laparoscopic Nissen fundoplication "LNF", in properly selected patients and with an experienced surgical team, is attained in more than 90 percent of patients confirming that LNF is the gold standard for the treatment of severe GERD.

In a cohort study of 166 patients followed for 11 years, Smith et al found preoperative response to acid-reducing medication, typical symptoms, and BMI \< 35 Kg/m2 to predict successful outcome. However, HH size, normal 24-hour pH score, age \> 50 years, female gender, and prior abdominal surgery that previous studies found to be associated with poor outcomes were not corroborated by this study. Other risk factors for failure are short esophagus, HH greater than 3 cm, and diaphragmatic stressors such as retching, sports of weight lifting, and high-speed motor vehicle accident among others.

Another study found increased BMI to be a predictor of poor outcome. Perez et al, in a retrospective cohort analysis of 224 patients undergoing LNF and transthoracic ARS, found a significantly increased recurrence rate of GERD in obese and overweight compared to normoweight patients, regardless of procedure type.

In contrast, a cohort study of 257 consecutive patients undergoing LNF, D´Alessio et al analyzed outcomes based on BMI (\< 25, 25-30, and \>30 kg/m2); No significant differences in symptom scores and clinical success rates were found among the different subsets. However, mean BMI for obese patients was 33 kg/m2 (obesity class I) and only three patients were \>35 kg/m2.

Regardless of contradictory data about LNF efficacy in obesity, several studies have shown the effectiveness of RYGB for GERD in morbidly obese patients by symptoms, endoscopic findings, manometry and pH-metry results, and endoscopic biopsy-histopathology.

There are four retrospective cohort studies assessing mostly early outcomes after converting ARS to RYGB. First, Sarr et al analyzed 19 patients that underwent open conversion to RYGB. Next, Ikramuddin et al described the anatomic findings for fundoplication failure after the laparoscopic conversion to RYGB of 11 patients. Lastly, with seven patients each, Raftopoulos et al and Donnelly et al reported feasibility with a high morbidity rate as well.

In summary, there is little information about what is the best primary ARS and the best revisional strategy to address intractable or severe reflux after failed fundoplication in the obese population. Also, there is lack of data about the best revisional procedure to address obesity in the patient status post functional or competent ARS. With this pilot retrospective study, we will advance our knowledge and along with the existing literature, we will draw preliminary clinical recommendations.

Eligibility criteria: Inclusion Criteria:

* Status post, either open or laparoscopic, primary Nissen fundoplication with all the following requirements:

  * Met NIH criteria for bariatric surgery
  * With functional or failed antireflux surgery (Nissen fundoplication)
  * Laparoscopic approach for revisional surgery

Exclusion Criteria:

* Any other type of revisional bariatric procedure
* Nonstandard revisional RYGB surgery
* Open approach for revision surgery
* Missing records and/or unreachable patients with scant information for analysis

Primary outcomes:
measure: Morbidity and mortality
timeFrame: at discharge, 1 week, 3 weeks, 8 weeks, 3 months, 6 months, 1 year and annually thereafter for up to 4 years
measure: Remission or improvement of GERD-related symptoms
timeFrame: 6 months, 1 year and annually thereafter for up to 4 years
measure: Weight loss expressed as Body Mass Index and Percentage of excess weight loss
timeFrame: 6 months, 1 year, and annually thereafter for up to 4 years
Secondary outcomes:
measure: Remission or improvement of comorbidities
timeFrame: 6 months, 1 year, and annually thereafter for up to 4 years
measure: Length of operative time which is defined as the time duration of operation measured in minutes from the first skin incision to the final closure of the skin incision
timeFrame: It is measured in minutes from the first skin incision to the final closure of the skin incision at the time of revisional surgery under study. It is a transoperative measure of outcome of the surgery under study
measure: Length of Hospital Stay which is a measured of surgical recovery quantified and reported in days. It is a hospital pre-discharge traditional measure of outcome.
timeFrame: It is measured in days from the admission date to the discharge date for the hospitalization pertaining to revisional surgery under study
Other outcomes:
Locations:
city: Fresno
country: United States
facility: UCSF Fresno Center for Medical Education and Research
state: California
Study officials:
affiliation: Research Associate, University of California San Francisco
name: Francisco M Tercero, MD
role: STUDY_DIRECTOR
affiliation: Professor of Surgery, University of California San Francisco
name: Kelvin D Higa, MD
role: PRINCIPAL_INVESTIGATOR
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