Chronic Marginal Ulcers After Gastric Bypass

Marginal Ulcer Clinical Trial

— ChronicMU  

Official title:

Laparoscopic Revision Gastric Bypass Surgery for Chronic Marginal Ulcers: a 10 Year Experience

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01041079
• Other study ID #: CMC IRB No. 2008078
• Secondary ID: U1111-1112-9755
• Status: Completed
• Phase: N/A
• First received: December 25, 2009
• Last updated: December 31, 2009
• Start date: December 2008
• Est. completion date: December 2009

Study information

• Verified date: December 2009
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Chronic/Intractable, either recurrent or persistent, marginal ulcers after Roux-en-Y gastric bypass surgery for clinically severe obesity

Exclusion Criteria:

• Chronic or Intractable marginal ulcer after other bariatric procedures

• Revision or re-operation by open approach

• missing records and/or unreachable patients with scant information for analysis

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Chronic Ulcer Disease
• Late Morbidity After Gastric Bypass
• Marginal Ulcer
• Peptic Ulcer
• Persistent Ulcer Disease
• Recurrent Ulcer Disease
• Ulcer

Locations

Country	Name	City	State
United States	University of California San Francisco, Department of Surgery/Fresno Medical Education Program	Fresno	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (40)

Abstracts of the 2008 Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Philadelphia, Pennsylvania, USA, 9-12 April 2008. Surg Endosc. 2008 Apr;22 Suppl 1:144-301. doi: 10.1007/s00464-008-9821-3. — View Citation

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Capella JF, Capella RF. Staple Disruption and Marginal Ulceration in Gastric Bypass Procedures for Weight Reduction. Obes Surg. 1996 Feb;6(1):44-49. — View Citation

Chin EH, Hazzan D, Sarpel U, Herron DM. Multimedia article. Laparoscopic repair of a perforated marginal ulcer 2 years after gastric bypass. Surg Endosc. 2007 Nov;21(11):2110. Epub 2007 Aug 18. — View Citation

Christou NV, Sampalis JS, Liberman M, Look D, Auger S, McLean AP, MacLean LD. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg. 2004 Sep;240(3):416-23; discussion 423-4. — View Citation

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Flum DR, Khan TV, Dellinger EP. Toward the rational and equitable use of bariatric surgery. JAMA. 2007 Sep 26;298(12):1442-4. — View Citation

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Higa KD, Boone KB, Ho T. Complications of the laparoscopic Roux-en-Y gastric bypass: 1,040 patients--what have we learned? Obes Surg. 2000 Dec;10(6):509-13. — View Citation

Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet. 2002 Jan 5;359(9300):14-22. — View Citation

Jordan JH, Hocking MP, Rout WR, Woodward ER. Marginal ulcer following gastric bypass for morbid obesity. Am Surg. 1991 May;57(5):286-8. — View Citation

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Lublin M, McCoy M, Waldrep DJ. Perforating marginal ulcers after laparoscopic gastric bypass. Surg Endosc. 2006 Jan;20(1):51-4. Epub 2005 Dec 7. — View Citation

Madan AK, DeArmond G, Ternovits CA, Beech DJ, Tichansky DS. Laparoscopic revision of the gastrojejunostomy for recurrent bleeding ulcers after past open revision gastric bypass. Obes Surg. 2006 Dec;16(12):1662-8. — View Citation

Mason EE. Warning patients about cocaine and aspirin. Obes Surg. 1998 Jun;8(3):312-3. — View Citation

McTigue KM, Harris R, Hemphill B, Lux L, Sutton S, Bunton AJ, Lohr KN. Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003 Dec 2;139(11):933-49. — View Citation

Meguid MM, Glade MJ, Middleton FA. Weight regain after Roux-en-Y: a significant 20% complication related to PYY. Nutrition. 2008 Sep;24(9):832-42. doi: 10.1016/j.nut.2008.06.027. Review. — View Citation

Nguyen NT, Hinojosa MW, Gray J, Fayad C. Reoperation for marginal ulceration. Surg Endosc. 2007 Nov;21(11):1919-21. Epub 2007 Aug 19. Review. — View Citation

Nguyen NT. Reoperations and revisions in bariatric surgery. Surg Endosc. 2007 Nov;21(11):1907-8. Epub 2007 Sep 8. — View Citation

Papasavas PK, Gagné DJ, Donnelly PE, Salgado J, Urbandt JE, Burton KK, Caushaj PF. Prevalence of Helicobacter pylori infection and value of preoperative testing and treatment in patients undergoing laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2008 May-Jun;4(3):383-8. Epub 2007 Nov 5. — View Citation

Patel RA, Brolin RE, Gandhi A. Revisional operations for marginal ulcer after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2009 May-Jun;5(3):317-22. doi: 10.1016/j.soard.2008.10.011. Epub 2008 Nov 6. — View Citation

Ramaswamy A, Lin E, Ramshaw BJ, Smith CD. Early effects of Helicobacter pylori infection in patients undergoing bariatric surgery. Arch Surg. 2004 Oct;139(10):1094-6. — View Citation

Rasmussen JJ, Fuller W, Ali MR. Marginal ulceration after laparoscopic gastric bypass: an analysis of predisposing factors in 260 patients. Surg Endosc. 2007 Jul;21(7):1090-4. Epub 2007 May 19. — View Citation

Sacks BC, Mattar SG, Qureshi FG, Eid GM, Collins JL, Barinas-Mitchell EJ, Schauer PR, Ramanathan RC. Incidence of marginal ulcers and the use of absorbable anastomotic sutures in laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2006 Jan-Feb;2(1):11-6. — View Citation

Santry HP, Gillen DL, Lauderdale DS. Trends in bariatric surgical procedures. JAMA. 2005 Oct 19;294(15):1909-17. — View Citation

Sanyal AJ, Sugerman HJ, Kellum JM, Engle KM, Wolfe L. Stomal complications of gastric bypass: incidence and outcome of therapy. Am J Gastroenterol. 1992 Sep;87(9):1165-9. — View Citation

Sapala JA, Wood MH, Sapala MA, Flake TM Jr. Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients. Obes Surg. 1998 Oct;8(5):505-16. — View Citation

Schuster KM, Feuer WJ, Barquist ES. Outcomes of cocaine-induced gastric perforations repaired with an omental patch. J Gastrointest Surg. 2007 Nov;11(11):1560-3. Epub 2007 Aug 15. — View Citation

Sharma R, Organ CH Jr, Hirvela ER, Henderson VJ. Clinical observation of the temporal association between crack cocaine and duodenal ulcer perforation. Am J Surg. 1997 Dec;174(6):629-32; discussion 632-3. — View Citation

Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lönroth H, Näslund I, Olbers T, Stenlöf K, Torgerson J, Agren G, Carlsson LM; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug 23;357(8):741-52. — View Citation

St Jean MR, Dunkle-Blatter SE, Petrick AT. Laparoscopic management of perforated marginal ulcer after laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2006 Nov-Dec;2(6):668. — View Citation

Stenström B, Løseth K, Bevanger L, Sturegård E, Wadström T, Chen D. Gastric bypass surgery does not increase susceptibility to Helicobacter pylori infection in the stomach of rat or mouse. Inflammopharmacology. 2005;13(1-3):229-34. — View Citation

Teyssen S, Singer MV. Alcohol-related diseases of the oesophagus and stomach. Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):557-73. Review. — View Citation

Yang CS, Lee WJ, Wang HH, Huang SP, Lin JT, Wu MS. The influence of Helicobacter pylori infection on the development of gastric ulcer in symptomatic patients after bariatric surgery. Obes Surg. 2006 Jun;16(6):735-9. — View Citation

* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morbidity and mortality		at discharge, 1 week, 3 weeks, 8 weeks, 3 months, 6 months, 1 year and annually thereafter for up to 4 years	Yes
Primary	Weight loss expressed as Body Mass Index and Percentage excess weight loss		at 6 months, 1 year and annually thereafter for up to 4 years	No
Primary	Remission or improvement of marginal ulcer-related symptoms		at 6 months, 1 year and annually thereafter for up to 4 years	No
Primary	Remission or improvement of comorbidities		at 6 months, 1 year and annually thereafter for up to 4 years	No
Secondary	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		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	No
Secondary	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.		It is measured in days from the admission date to the discharge date for the hospitalization pertaining to revisional surgery under study.	No

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