journal of surgical research xxx (2012) e1ee8 Available online at www.sciencedirect.com journal homepage: www.JournalofSurgicalResearch.com Eradication of Helicobacter pylori for prevention of ulcer recurrence after simple closure of perforated peptic ulcer: a meta-analysis of randomized controlled trials Chung-Shun Wong, MD, MS,a,b Chee-Fah Chia, MD, MS,c Hung-Chia Lee, MD,d Po-Li Wei, MD, PhD,a,d Hon-Ping Ma, MD, MS,a,b Shin-Han Tsai, MD, PhD,a,b Chih-Hsiung Wu, MD, PhD,a,c and Ka-Wai Tam, MD, MSa,d,e,* a Department of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan b Department of Emergency Medicine, Taipei Medical UniversityeShuang Ho Hospital, Taipei, Taiwan c Division of General Surgery, Department of Surgery, Taipei Medical UniversityeShuang Ho Hospital, Taipei, Taiwan d Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan e Center for Evidence-based Medicine, Taipei Medical University, Taipei, Taiwan article info abstract Article history: Background: Eradication of Helicobacter pylori has become part of the standard therapy for Received 1 July 2012 peptic ulcer. However, the role of H pylori eradication in perforation of peptic ulcers Received in revised form remains controversial. It is unclear whether eradication of the bacterium confers pro- 10 October 2012 longed ulcer remission after simple repair of perforated peptic ulcer. Accepted 23 October 2012 Methods: A systematic reviewand meta-analysis of randomized controlledtrials was performed Available online xxx to evaluate the effects of H pylori eradication on prevention of ulcer recurrence after simple closure of perforated peptic ulcers. The primary outcome to evaluate these effects was the Keywords: incidence of postoperative ulcers; the secondary outcome was the rate of H pylori elimination. Helicobacter pylori eradication Results: The meta-analysis included five randomized controlled trials and 401 patients. Perforated peptic ulcer A high prevalence of H pylori infection occurred in patients with perforated peptic ulcers. Meta-analysis Eradication of H pylori significantly reduced the incidence of ulcer recurrence at 8 wk (risk ratio 2.97; 95% confidence interval: 1.06e8.29) and 1 y (risk ratio 1.49; 95% confidence interval: 1.10e2.03) postoperation. The rate of H pylori eradication was significantly higher in the treatment group than in the nontreatment group. Conclusions: Eradication therapy should be provided to patients with H pylori infection after simple closure of perforated gastroduodenal ulcers. ª 2012 Elsevier Inc. All rights reserved. 1. Introduction usually involves a definite ulcer procedure or simple closure of the perforation hole. Perforation is a serious and potentially fatal complication of Immediate acid-reduction procedures in addition to repair peptic ulcer disease. Depending on the patient’s clinical effectively reduced recurrence. However, these can be difficult condition, traditional treatment of perforated peptic ulcers to apply in an emergency setting, especially in critically ill Chung-Shun Wong and Chee-Fah Chia contributed equally to this work. * Corresponding author. Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, No. 252 Wu-Hsing Street, Taipei 11031, Taiwan. Tel.: þ886 2 2737 2181x3918; fax: þ886 2 2738 9524. E-mail address: [email protected] (K.-W. Tam). 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2012.10.046 e2 journal of surgical research xxx (2012) e1ee8 patients, and are associated with long-term side effects [1]. eradication on prevention of ulcer recurrence in patients Advances in research on the pathophysiology of peptic ulcer with perforated peptic ulcer following simple closure; they disease have led to changes in surgical treatment of perfo- clearly documented the inclusion and exclusion criteria rated peptic ulcer disease. With the evolution of the proton used for patient selection; they adequately documented the pump inhibitor, a simple closure procedure for peptic ulcer administration of postoperative antibiotics and proton disease has gained wide acceptance and can be performed pump inhibitors; and they precisely documented the defi- laparoscopically [2,3]. However, it is associated with a high nition and evaluation of H pylori infection. Studies were ulcer recurrence rate and complications such as reperforation, excluded from the analysis if one or both of the following bleeding, or stenosis [4]. conditions applied: patients enrolled in the trials were Previous research has identified Helicobacter pylori (H pylori) undergoing other concomitant surgical procedures and as an opportunistic pathogen attracted by changes in the receiving H pylori eradication therapy preoperatively; an gastric mucosa caused by inflammation and ulcer. It plays overlap occurred between patient cohorts evaluated in two a critical role in the pathogenesis of peptic ulcer disease [5]. or more studies. Appropriate antibiotic treatment combined with proton pump inhibitors or histamine (H2) blockers eradicates H pylori 2.3. Data extraction and quality assessment infection in more than 90% of cases [6]. In the uncomplicated patient, eradication of H pylori is effective in prevention Two independent reviewers (C.S.W. and K.W.T.) extracted of ulcer recurrence. In cases of bleeding peptic ulcers, trial details pertaining to the participants, inclusion and eradication of H pylori is as efficacious as maintenance acid- exclusion criteria, administration of experimental drugs, reduction medication at preventing recurrent ulcer hemor- prevalence and assessment of H pylori infection, complica- rhage [7]. tions, and postoperative recovery. Discrepancies were Previous studies have extensively investigated the associ- resolved through discussion; any disagreements were ation between H pylori and perforated peptic ulcer, providing resolved by a third reviewer (C.F.C.). The authors of the conflicting results. In patient with perforated peptic ulcer, the studies were contacted for additional information when prevalence of H pylori infection varied from 47%, as deter- necessary. mined using serologic testing [8], to more than 80% in biopsy- The risk of bias in the included trials was assessed in based studies [9]. The effectiveness of H pylori eradication individual domains, reporting the following aspects: adequacy for prevention of ulcer recurrence after simple closure of of the randomization, allocation concealment, masking, perforated peptic ulcer remains unclear. The present study, duration of follow-up, numbers of drop-outs, and perfor- therefore, consists of a systematic literature review and meta- mance of intention-to-treat (ITT) analysis. analysis of randomized controlled trials (RCTs), which are conducted to evaluate the role of H pylori eradication in the 2.4. Outcome assessment prevention of ulcer recurrence following simple repair of peptic ulcer perforation. The ulcer healing rate and the H pylori eradication rate were the outcomes used to evaluate the efficacy of eradication of H pylori for perforated peptic ulcers following simple closure. 2. Methods The occurrence of residual and recurrent ulcers was identified using endoscopy. The occurrence of H pylori infection was 2.1. Data sources determined using assessments of histology, culture, rapid urease tests, breath tests, or serum levels of antieH pylori Literature searches were performed using four electronic immunoglobulin G using enzyme-linked immunosorbent databases (MEDLINE, EMBASE, SCOPUS, and Cochrane data- assay, at presentation with a perforated ulcer and at 6 wk, bases). The searches were unlimited by time up to October 8 wk, 16 wk, or 1 y after perforation closure. Patients with 2012 without language restriction. The following medical complete ulcer healing on the scheduled endoscopy were then search headings (MeSH) terms, words, and combinations of invited for a follow-up endoscopy at 1 y for ulcer surveillance words were used in constructing the systematic search: gastric and determination of H pylori status. or duodenal or peptic, ulcer, perforated or perforation, Helicobacter pylori, eradication. All included studies were also entered into 2.5. Data analysis the PubMed “related articles” function and the science citation index. In addition, we attempted to identify other studies by Analysis was performed using the statistical package Review hand-searching the reference sections of these papers and by Manager, version 5.1 (Cochrane Collaboration, Oxford, contacting known experts in the field. Finally, unpublished England). Meta-analysis was performed according to recom- trials were retrieved from the ClinicalTrials.gov registry mendations in the PRISMA guidelines [10,11]. (http://clinicaltrials.gov/). The dichotomous outcomes were statistically analyzed using risk ratios (RR) as the summary statistic. The results 2.2. Study selection were reported with 95% confidence intervals (CIs). A pooled estimate of the RR was calculated using the DerSimonian and To be included in the analysis, studies were required to Laird random effect model [12]. This provides a more appro- meet the following criteria: they were randomized priate estimate of the average treatment effect when trials are controlled trials that evaluated the efficacy of Hpylori statistically heterogeneous, and usually yields wider CIs, journal of surgical research xxx (2012) e1ee8 e3 Search for potentially relevant citations commonly applied modality for