Recurrent Inguinal Hernia Repair: What is the Evidence of Case Series? A Meta-Analysis and Metaregression Analysis Georgia Dedemadi, MD, PhD, FACS,* Ioannis Kalaitzopoulos, MD, PhD,* Christos Loumpias, MD,* Aggeliki Papapanagiotou, MD, PhD,w Charilaos Karaliotas, MD,z Stavroula Lyra, MD,z Athanasios Papatheodorou, MD,z and George Sgourakis, MD, PhD, FACSz Abstract: To examine, if case series considered together with observational studies tend to produce similar results as random- ized-controlled trials (RCTs), on recurrent hernia repair. A sys- tematic literature review and meta-analysis between 1990 and 2013 revealed 46 nonrandomized studies (NRCTs) and 5 RCTs includ- ing 25,730 patients. A direct comparison of the summary estimates between RCTs and NRCTs is presented. Outcomes, within or across studies, were compared. Comparisons of all outcomes in NRCTs and RCTs failed to show statistical significance. Pro- spective/retrospective cohort studies, case series, and RCTs did not differ significantly in their estimates. Adjusted testing for metare- gression disclosed that rerecurrence among NRCTs was inde- pendent of the study design. The number of included patients and study setting were independent predictors of outcome. Our pro- posed methodology for a systematic review could potentially give answers where level I evidence is missing or could be a tool for optimization of a RCT design. Key Words: TAPP, TEP, laparoscopic, Lichtenstein, meta-analysis, metaregression, recurrent inguinal hernia (Surg Laparosc Endosc Percutan Tech 2014;24:306–317) R andomized-controlled trials (RCTs) have been largely established as providing the highest grade of evidence in the taxonomy of research designs. 1 Observational studies have a number of benefits over RCTs, comprising lower cost, greater suitability, and a wide-ranging of patients. 2 Evaluations in the literature imply that observational studies may incorrectly mis- calculate treatment benefits, reaching to deceptive con- clusions. 3 Lately, this question has reemerged. Observa- tional studies compared with RCT yielded similar 4 or opposing results 5 in a number of diverse research topics. Observational studies and case series are largely used to find risk and prognostic factors and in circumstances in which RCTs would be unfeasible or unethical. Worries about inherent bias in these studies, however, has limited their use. 6 Selection bias, limits statements on the founda- tion of correlations observed. Until now, outcomes of retrospective and prospective case series have not been compared with those of RCTs in the context of a systematic methodology. Moreover, the resulting evidence of the combination of observational and case series studies has not been questioned under a sys- tematic statistical manner. This systematic and comprehensive search of a great number of dissimilar studies on recurrent inguinal hernia repair surgery inquires about resolving the following query: do case series studies considered with observational studies tend to produce the same results as RCTs? METHODS All articles concerning recurrent inguinal hernia repair were identified. The electronic databases MEDLINE, Embase, Pubmed, and the Cochrane Library were used to search for relevant articles published in European languages from 1990 until 2013 using the following terms and/or combinations in their titles, abstracts, or keyword lists: recurrent inguinal hernia, open tension-free, totally extraperitoneal, transabdominal preperitoneal, and Lich- tenstein procedure. The above-mentioned terms were used in “[MESH]” (Pubmed and the Cochrane Library), where applicable, otherwise they were combined with “AND/OR” and asterisks. The following exclusion criteria were initially applied to all articles identified: publication of abstracts only, case reports, letters, comments, reviews, mean or median follow- up of <6 months. After the initial screening, additional criteria for exclusion were imposed as follows: pediatric population, papers analyzing femoral and inguinal hernias collectively, papers evaluating >1 method of repair jointly, and studies focusing on incarcerated or massive scrotal hernias. Studies reporting recurrence after initial repair were not included. The 2 authors (G.D. and G.S.) independently selected studies for inclusion and exclusion and reached a consensus when they did not agree on the initial assignment. A full- text copy of each article was obtained for review. Refer- ences within the selected articles were checked manually to supplement the electronic search for additional relevant articles. Selected studies could be of any design. When different articles reporting on overlapping populations were identified, the most recent article with the largest study population was selected for review. The following variables concerning studies addressing patients with recurrent her- nia repair were recorded: authors, journal and year of publication, country of origin, trial duration, participant demographics, and data concerning complications and follow-up evaluation. Received for publication September 11, 2013; accepted March 7, 2014. From the *Surgical Department of “A. Fleming” General Hospital; wDepartment of Biological Chemistry, University of Athens Med- ical School; and z2nd Surgical Department and Surgical Oncology Unit of “Korgialenio-Benakio,” Red Cross Hospital, Athens, Greece. The authors declare no conflicts of interest. Reprints: Georgia Dedemadi, MD, PhD, FACS, 7 Agias Lauras str., Pallini, Athens 15351, Greece (e-mail: gdedemadi@yahoo.gr). Copyright r 2014 by Lippincott Williams & Wilkins REVIEW ARTICLE 306 | www.surgical-laparoscopy.com Surg Laparosc Endosc Percutan Tech  Volume 24, Number 4, August 2014