Perforated Marginal Ulcer After Gastric Bypass
Condition: Ulcer Disease After Gastric Bypass; Marginal Ulcer; Perforated Marginal Ulcer; Acutely Perforated Marginal Ulcer
MeSH terms: Peptic Ulcer; Ulcer
Study type: Observational

Summary: 
      A common late complication after gastric bypass surgery is marginal ulceration that is
      defined as ulcers at the margins of the gastrojejunostomy, mostly on the jejunal side. Most
      marginal ulcers respond to medical therapy and complicated or complex ulcer disease warrants
      operative intervention; specifically, perforated, penetrated, obstructing, bleeding and
      intractable marginal ulcers require surgical intervention.

      Diverse operative strategies for addressing perforated marginal ulcers after gastric bypass
      have been described including I) Omental (Graham) patch repair, II) Revision of
      gastrojejunostomy, III) Irrigation and drainage, IV) any previous procedure with truncal
      vagotomy, V) Esophagojejunostomy, and VI) Reversal. We formally analyze our experience with
      the laparoscopic resection and repair of acutely perforated marginal ulcers after Roux-en-Y
      gastric bypass (RYGB), with or without concomitant resolution of technical risk factors for
      marginal ulceration.
    

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 2000, there has been a substantially progressive increase in bariatric surgery. In
      2007, the ASMBS reported that 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 that is
      defined as ulcers at the margins of the gastrojejunostomy, mostly 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, most marginal ulcers respond to medical therapy and
      complicated or complex ulcer disease warrants operative intervention. Specifically,
      perforated, penetrated, obstructing, bleeding and intractable marginal ulcers require
      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. 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).

      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.

      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%.

      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.

      NSAID´s inhibit prostaglandin synthesis 1) decreasing blood flow to the mucosa (mainly by PG
      subgroups E and I, which promotes vasodilatation), 2) increased adherence of neutrophils, 3)
      topical irritant effect, 4) impair of the repair/healing process, and 5) gastric-acid-related
      effects. In a retrospective cohort study, Wilson et al found NSAID´s consumption to correlate
      with the marginal ulcer development after RYGB. Numerous studies have identified NSAID´s use
      as a main risk factor for PUD; however, the precise relevance of NSAID´s as a factor in
      marginal ulcer development after RYGB is largely unknown.

      In epidemiological, clinical and experimental studies, Tobacco has been identified as a major
      risk factor for peptic ulcer disease (PUD). Smoking carries an overall relative risk of 2.2
      for developing PUD. A synergistic relationship for developing PUD exists between H pylori
      infection and smoking (2.3 vs. 6.1). Biological evidence suggests that smoking compromises
      the gastric mucosa barrier, decreases gastric emptying and increases gastric secretion. For
      marginal ulcer after RYGB, there are three cohort studies that showed positive correlation
      between smoking with developing anastomotic ulcer.

      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. Furthermore, a 61.1 (95%CI,
      9.98-373) overall risk exist when compared to H pylori negative individuals not taking
      NSAID´s. For marginal ulcers after RYGB, three cohort studies have showed that H. pylori
      infection is not associated with the development of marginal ulcers. 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 scant retrospective epidemiological studies that
      determine if a relationship between alcohol consumption and PUD exists. Although alcohol is
      not associated with an increased risk of PUD, patients with PUD are advised to avoid
      alcoholic drinks. Basic science studies have showed that instillation of pure ethanol at
      lower concentrations (4-40% v/v) causes hemorrhagic gastritis in a dose-dependant fashion.
      Also a synergistic relationship exists between ethanol and NSAID´s, since both cause mucosal
      injury. On the other hand, 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. Most ulcer perforations are juxtapyloric or duodenal (D1) however jejunal location
      has been reported. The physiopathologic hypothesis includes the following mechanisms 1)
      cocaine blocks the re-uptake of norepinephrine leading to intense vasoconstriction
      (alpha-adrenergic receptors), mesenteric ischemia, focal tissue ischemia, coagulative
      necrosis and perforation; and 2) cocaine causes thrombus formation and platelet aggregation
      mediated by endogenous Thromboxane B2. A few retrospective cohort studies suggest that
      primary patch repair is the recommended therapeutic option for this type of ulcers. However,
      Shuster et al reported a high recurrence rate (42%) after omental patch repair compared to a
      definitive anti-ulcer procedure (0%). Little information exists about the association between
      crack and gastroduodenal ulcer perforations other than the temporal association reported in
      small retrospective cohort studies. In a communication, Dr Mason recalls two patients with
      perforated "stomach ulcers" associated with cocaine use.

      The following Critically-Ill patients have a significant increased risk of stress-related
      mucosal disease (SRMD): 1) mechanical ventilation > 48hrs conveys a 16-fold risk (p < 0.001),
      2) coagulopathy has a 4-fold risk (p < 0.001), 3) shock carries a 3.7-fold risk (p= 0.08), 4)
      drop of intramural pH (from 8 to 6, 5), 5) increase of the number of risk factors (from 0 to
      4), 6) recent major surgery, 7) major trauma, 8) severe burns, 9) head trauma, 10) hepatic or
      renal disease at admission, and 11) sepsis. SRMD encompasses stress-related injury (SRI),
      which is primarily erosion in the GI tract, and stress ulcer, which is a focal deep mucosal
      damage. The pathogenesis of SRMD has not being unraveled completely but there is strong
      evidence that hypoperfusion and reperfusion of the upper GI tract is the major cause. There
      is no literature available about marginal ulcer after RYGB associated to ICU or critically
      ill patients.

      Diverse operative strategies for addressing perforated marginal ulcers after gastric bypass
      have been described including I) Omental (Graham) patch repair, II) Revision of
      gastrojejunostomy, III) Irrigation and drainage, IV) any previous procedure with truncal
      vagotomy, V) Esophagojejunostomy, and VI) Reversal.

      Summarizing, 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 who underwent laparoscopic repair of perforated marginal ulcer after Roux-en-Y
        gastric bypass (RYGB) for weight loss.
      
Keywords: obesity; ulcer disease; marginal ulcer; perforation; abdominal pain; bariatric surgery; weight loss surgery