Chronic Marginal Ulcers After Gastric Bypass
Condition: Marginal Ulcer; Chronic Ulcer Disease; Persistent Ulcer Disease; Recurrent Ulcer Disease; Late Morbidity After Gastric Bypass
MeSH terms: Peptic Ulcer; Ulcer
Study type: Observational

Summary: 
      The purpose of this study is to determine the feasibility, safety, and efficacy of revision
      gastroplasty along with other adjunct procedures in the treatment of intractable / chronic
      marginal ulcers after Roux-en-Y gastric bypass. A secondary aim is the identification of good
      and poor outcome predictors after revisional strategies for intractable or chronic marginal
      ulcer.
    

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%, systemic arterial hypertension was
      resolved in 61.7%, dyslipidemia improved in 70% and obstructive sleep apnea-hypopnea syndrome
      was resolved in 85.7%. Furthermore, bariatric surgery significantly increases life expectancy
      (89%) and decreases overall mortality (30-40%), 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 ASMBS reported that 81% of bariatric procedures were approached laparoscopically
      and in 2007, 205,000 people had bariatric surgery in the United States from which
      approximately 80% of these were Gastric Bypass. Moreover, there is a mismatch between
      eligibility and receipt of bariatric surgery with just less than 1% 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% 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.

      A common late complication after gastric bypass surgery is marginal ulceration, an ulcer at
      the margins of the gastrojejunostomy on the jejunal side. Its incidence after RYGB ranges
      from as low as 0.6 to as high as 16%. After 1,040 laparoscopic RYGB surgeries, the incidence
      rate, in our hands, is 1.4% and mainly related to NSAID´s use. In observational cohort
      studies, the presence of specific technical factors - staple-line dehiscence or
      gastro-gastric fistula, enlarged pouch, foreign material and local ischemia - and
      environmental factors - tobacco, NSAID´s, alcohol consumption, and H pylori infection among
      others - have been associated with marginal ulceration however the exact etiopathogenesis has
      not been completely elucidated.

      Similar to peptic ulcer disease (PUD), most marginal ulcers respond to medical therapy,
      specifically sucralfate and acid-lowering medication. In contrast, when perforation,
      obstruction, penetration, bleeding and/or intractability presents, complex or complicated
      ulcer disease, warrants surgical intervention.

      The intestinal mucosa is not typically exposed to gastric acid, which is neutralized by the
      alkaline biliopancreatic secretions. The jejunal mucosa has no natural barriers; when exposed
      to gastric acid, it ulcerates easily. Capella & Capella demonstrated that transecting the
      gastric segments significantly reduce staple-line dehiscence; this is the so-called divided
      gastric bypass. In the retrospective analysis of their consecutive series, the incidence for
      gastro-gastric fistula (GGF) formation after undivided gastric bypass (GBP) was 23%, after a
      partially divided GBP was 19%, after a completely divided GBP was 2% and after complete
      transection with interposition of the jejunal limb was 0% (p <0.001). MacLean et al confirmed
      that divided primary gastric bypass decreases GGF formation (29% vs. 3%). Also, patients who
      developed marginal ulcers had a lower pH as well as a greater time with a pH less than 2
      correlating 100% with the presence of GGF; closure of the GGF increased the pH in the pouch
      with subsequent healing of the marginal ulcer.

      An unusually large gastric pouch (such as horizontal pouches, retained fundus, long lesser
      curvature based pouches or enlarged after initially being sized adequately) contain more
      acid-producing parietal cells. Increased acid production in the pouch carries the risk of
      developing marginal ulcers. Acid secretion in the small pouch after RYGB is virtually absent.
      Smith et al measured basal and pentagastrin-stimulated gastric acid secretion from the pouch
      were significantly lower compared to age and sex-matched controls. Likewise, MacLean et al
      reported a significantly lower pH & greater time with pH <2 in the gastric pouches of
      marginal ulcers and/or GGF patients after RYGB compared to non-complicated RYGB controls.
      Thus, creating a esophagojejunostomy would solve the gastric acid factor for developing
      marginal ulcers however the high incidence of anastomotic failure and unknown weight loss
      results are prohibitive for this approach. Sapala et al created a micro-pouch or
      cardiojejunostomy to decrease at maximum the parietal cell mass with a low incidence of
      marginal ulcers (0.01% at 1 years of follow-up) as well as to limit the pouch dilation. By
      Histopathology with a semi-quantitative approach, Gustavsson et al reported less
      acid-producing parietal cells within smaller pouches. With his next study (n=12), Gustavsson
      et al, demonstrated a significantly higher time exposure to a pH<4 in patients with marginal
      ulcer after RYGB (4x3cm pouch) compared to controls (p< 0.01). Furthermore, after downsizing
      the pouch, repeated pH-metry showed the % of time with pH <4 declined from 100% prior to 6%
      after revisionary surgery.

      The anastomotic techniques influence the incidence of marginal ulcers. Capella & Capella
      reported a consecutive series with significant decrement from 5.1% to 1.5% (p< 0.001) after
      switching from a stapled to a hand-sewn anastomosis. Likewise, after changing from an inner
      layer of absorbable suture and an outer layer of nonabsorbable material to a double-layer of
      absorbable suture the incidence rate improved from 1.6% to 0%. Dr Schauer´s group confirmed a
      significant improvement in the incidence rate of MU from a 2.6% with the use of nonabsorbable
      suture for the outer layer to 1.3% after the change to absorbable suture for both layers (p <
      0.001).

      Local ischemia, in the immediate postoperative period, is probably secondary to technical
      reasons. Fundamental aspects for decreasing tension and local ischemia at the
      gastrojejunostomy are dissection of the tissues around the pouch without devascularizing the
      lesser curvature and complete mobilization of a well-perfused Roux limb.

      In epidemiological, clinical and experimental studies, NSAID´s have been identified as one of
      the three major risk factors for PUD. Wilson et al found NSAID´s consumption to significantly
      increase the risk for marginal ulcer following RYGB (adjusted OR 11.5, 95%CI 4.8-28).

      In epidemiological, clinical and experimental studies, Tobacco is another major risk factor
      for PUD. Smoking carries an overall relative risk of 2.2 (95%CI, 2.0-2.3).

      Helicobacter pylori (H pylori) infection carries an overall relative risk of 3.3 (95%CI,
      2.6-4.4) for developing PUD. A synergistic relationship exists between H pylori infection and
      NSAID´s consumption for developing PUD with an overall risk of 3.5 (95%CI, 1.26-9.96)
      compared to either H pylori or NSAID´s negative individuals. In Papasavas et al study,
      preoperative H. pylori testing with prophylactic eradication did not decrease the incidence
      of MU or erosive pouch gastritis.

      The pathophysiological mechanisms of damage to the gastric mucosa of ethanol and alcoholic
      beverages are poorly understood. There are no studies available about the effect of alcohol
      on marginal ulcer development after RYGB.

      Cocaine use is responsible for approximately 143,000 Emergency Department visits annually;
      19% of American, between 18 to 25 years old, have used cocaine: more than 1% of the Americans
      use cocaine at least once a week; and approximately 50% of all drug-related deaths were
      secondary to Cocaine. The temporal association between smoking cocaine (crack) and GI tract
      manifestations include ulceration, perforation, visceral infarction, and retroperitoneal
      fibrosis.

      Re-operative strategies for addressing chronic marginal ulcers after gastric bypass have been
      scarcely described and mostly are reports of a case or small series of cases. The revisional
      strategies described are I) ulcer excision with revision of the gastrojejunostomy and gastric
      transection if needed, II) ulcer excision with pouch downsizing and redo of
      gastrojejunostomy, III) ulcer excision with resection of the ischemic Roux limb segment, and
      IV) ulcer excision and reversal. The possible adjuvant procedures includes I) proximal
      remnant gastrectomy (partial gastrectomy), and II) vagotomy.

      In summary, there is scant information about late complications after gastric bypass
      especially after the widespread adoption of the laparoscopic approach and the modern
      anatomical construct of Roux-en-Y Gastric Bypass surgery.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients after Roux-en-Y gastric bypass for clinically severe obesity complicated with
        intractable or chronic marginal ulcer disease
      
Keywords: ulcer disease; marginal ulcer; morbidity of gastric bypass; late morbidity of gastric bypass; chronic abdominal pain; GI hemorrhage; Perforation; Penetration; Obstruction