Hiatal Hernia and the Risk of Barrett's Esophagus

Juliana Andrici; Martin Tio; Michael R Cox; Guy D Eslick

Disclosures

J Gastroenterol Hepatol. 2013;28(3):415-431. 

In This Article

Methods

Literature Search Strategy

We followed the PRISMA Statement for Systematic Reviews and Meta-Analyses in performing our systematic review.[24] A systematic search was performed by two reviewers (J.A. and M.T.) through four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) to 4 April 2012, for observational studies of Barrett's esophagus patients, to identify relevant articles. The search used the terms "Barrett's Esophagus" OR "Barrett's Esophagus" AND "hiatal hernia" OR "hiatus hernia", which were searched as text word and as exploded medical subject headings where possible. The reference lists of relevant articles were also searched for appropriate studies. No language restrictions were used in either the search or study selection. A search for unpublished literature was not performed and authors were not contacted for missing data.

Inclusion and Exclusion Criteria

We included studies that met the following inclusion criteria: (i) BE was recognized on endoscopy and confirmed histologically as specialized intestinal metaplasia (SIM). Where studies reported on multiple subgroups, such as endoscopically suspected non-SIM BE cases and SIM BE cases, only the SIM BE cases were included in our analyses; (ii) the risk point estimate was reported as an odds ratio (OR), or the data were presented such that an OR could be calculated; (iii) the 95% confidence interval (CI) was reported, or the data were presented such that the CI could be calculated; (iv) an internal control group was used when calculating the risk estimate; (v) the total sample size of the study exceeded 50 patients. We excluded studies that did not meet the inclusion criteria. Studies were included or excluded following consensus between three authors (J.A., M.T. and G.E.).

Data Extraction

We performed the data extraction via a standardized data extraction form, collecting information on the publication year, study design, number of cases, number of controls, total sample size, temporal direction of the study (prospective or retrospective), control groups used, population type, country, continent, economic development, case control matching, mean age, number of adjusted variables, the risk estimates or data used to calculate the risk estimates, and CIs or data used to calculate CIs, the type of BE investigated (SSBE or LSBE), and size of hernia. We selected only subjects with SIM to serve as the BE cases in our analysis. Where BE length was not stated, the study was included in the any length BE analysis. Adjusted ratios were extracted in preference to non-adjusted ratios; however, where ratios were not provided, unadjusted ORs and CIs were calculated. Where more than one adjusted ratio was reported, we chose the ratio with the highest number of adjusted variables. Where multiple risk estimates were available in the same study, for example, when studies reported on the risk estimates of different lengths of BE, or when risk estimates were reported for different control groups, they were included as separate risk estimates.

Statistical Analysis

Pooled OR and 95% CIs were calculated for the effect of hiatal hernia on the risk BE using a random effects model.[25] This was performed for the association between hiatal hernia and any length BE. Where a study reported risk estimates for different control groups (for example, a GERD control group, a non-GERD control group, and a combined control group comprising both GERD non-GERD controls), we included the risk estimate for the combined control group where possible, with the separate control groups included in a subgroup analysis. Subgroup analyses by length of BE, adjustment of ORs, study type, and continent were also performed. In particular, we performed subgroup analyses by studies that adjusted for body mass index (BMI) and reflux, both independent risk factors for BE. Where a single study reported multiple ORs for different sized hernias (that is, different risk estimates associated with different sized hernias), we computed a pooled OR from the multiple ORs and used that figure as the OR for that study. We quantified the degree of heterogeneity using the I2 statistic, which represents the percentage of the total variability across studies, which is due to heterogeneity. I2 values of 25%, 50% and 75% corresponded to low, moderate and high degrees of heterogeneity, respectively.[26] We performed sensitivity analyses, with individual studies excluded one at a time, when statistically significantly heterogeneity was detected. Publication bias was quantified using the Egger's regression model,[27] and if statistically significant publication bias was detected, the effect of bias was assessed using the fail-safe number method and the trim-and-fill method. The fail-safe number represents the number of studies that we would need to have missed for our observed result to be nullified to statistical non-significance at the P < 0.05 level. Publication bias is generally regarded as a concern if the fail-safe number is less than 5n + 10, with n being the number of studies included in the meta-analysis.[28] The trim-and-fill method adjusts for potential unpublished studies in the meta-analysis by augmenting the observed data to create a more symmetric funnel plot. New pooled ORs are then calculated and compared to the original pooled OR, and similarity between the two decreases the likelihood that publication bias significantly affected the meta-analysis results. Results were regarded as statistically significant if P < 0.05. All analyses were performed with Comprehensive Meta-analysis (version 2.0).

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