Mesh Location in Open Ventral Hernia Repair: A Systematic Review and Network Meta-analysis

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1 DOI /s SCIENTIFIC REVIEW Mesh Location in Open Ventral Hernia Repair: A Systematic Review and Network Meta-analysis Julie L. Holihan 1 Duyen H. Nguyen 1 Mylan T. Nguyen 1 Jiandi Mo 1 Lillian S. Kao 1 Mike K. Liang 1 Société Internationale de Chirurgie 2015 Abstract There is no consensus on the ideal location for mesh placement in open ventral hernia repair (OVHR). We aim to identify the mesh location associated with the lowest rate of recurrence following OVHR using a systematic review and meta-analysis. A search was performed for studies comparing at least two of four locations for mesh placement during OVHR (onlay, inlay, sublay, and underlay). Outcomes assessed were hernia recurrence and surgical site infection (SSI). Pairwise meta-analysis was performed to compare all direct treatment of mesh locations. A multiple treatment meta-analysis was performed to compare all mesh locations in the Bayesian framework. Sensitivity analyses were planned for the following: studies with a low risk of bias, incisional hernias, by hernia size, and by mesh type (synthetic or biologic). Twenty-one studies were identified (n = 5,891). Sublay placement of mesh was associated with the lowest risk for recurrence [OR (95 % CI )] and was the best of the four treatment modalities assessed [Prob (best) = 94.2 %]. Sublay was also associated with the lowest risk for SSI [OR (95 % CI )] and was the best of the 4 treatment modalities assessed [Prob (best) = 77.3 %]. When only assessing studies at low risk of bias, of incisional hernias, and using synthetic mesh, the probability that sublay had the lowest rate of recurrence and SSI was high. Sublay mesh location has lower complication rates than other mesh locations. While additional randomized controlled trials are needed to validate these findings, this network meta-analysis suggests the probability of sublay being the best location for mesh placement is high. Introduction & Julie L. Holihan Julie.L.Holihan@uth.tmc.edu; holihanj@gmail.com Duyen H. Nguyen Dhnguyen.06@gmail.com Mylan T. Nguyen Mylan.thi.nguyen@gmail.com Jiandi Mo Mojiandi@gmail.com Lillian S. Kao Lillian.S.Kao@uth.tmc.edu Mike K. Liang Mike.Liang@uth.tmc.edu 1 Department of General Surgery, University of Texas Health Science Center, 6431 Fannin St, Houston, TX 77030, USA Repair of ventral hernias with mesh as opposed to suture has substantially improved long-term outcomes and is accepted as the standard of care [1 3]. However, many studies demonstrate an increased risk for wound complications with mesh placement including infections, seromas, and mesh erosions [3, 4]. The risks of these complications are affected by where the mesh is placed. For example, mesh exposed to intra-abdominal contents potentially increases the risks of adhesions, bowel obstruction, and fistula formation [5, 6]. While repair of ventral hernias with mesh is considered routine, there is no consensus on the best location to place the mesh. For laparoscopic ventral hernia repair, the mesh is routinely placed in the intra-peritoneal position. However, for

2 load-bearing tissue in-growth from two directions. Underlay repair or intra-peritoneal repair was popularized with the advent of laparoscopy. Placing mesh in this location can be technically cumbersome requiring sutures to be placed closely to prevent intra-abdominal contents from sliding between the mesh and anterior abdominal wall. However, while protected from superficial wound complications, the mesh is exposed to intra-peritoneal contents. Meshes placed in this location must have an anti-adhesive barrier or anti-adhesive properties on the peritoneal side [6, 8 13]. In this study, we conducted a systematic review and performed a multiple treatment meta-analysis to identify the best location for mesh placement with open ventral hernia repair. We hypothesized that in open ventral hernia repair, sublay mesh placement has the lowest recurrence rate as compared to inlay, onlay, or underlay placement. Fig. 1 Mesh location. a onlay repair, b inlay repair, c sublay repair, d underlay; Key blue mesh red muscle black fascia gray hernia sac open surgery, there are numerous options for mesh placement (Fig. 1). Onlay repair places the mesh on the anterior fascia, which typically involves dissection of flaps and primary closure of the fascia below the mesh. Inlay repair places the mesh in the hernia defect and secures the mesh circumferentially to the edges of the fascia. Sublay repair refers to retro-rectus or preperitoneal mesh placement. It is also commonly referred to as a Rives-Stoppa or retromuscular repair. Finally, underlay repair is when mesh is placed in the intra-peritoneal position and secured to the anterior abdominal wall. Each mesh location has its theoretical risks and benefits. With onlay repair, skin flaps must be created, which increases the risk of wound complications and mesh infection [7]. However, onlay repair is technically easy to perform. In addition, for large complex hernias, this space is often already dissected with excision of the hernia sac or with myo-fascial release (i.e., anterior component separation). Inlay repair is technically easy. However, not only is the mesh often exposed to the intra-peritoneal contents, it is also vulnerable to superficial wound complications. Lack of overlap precludes mesh-tissue integration and theoretically increases the risk of recurrence. Sublay repair is often considered more challenging and complex to perform. Dissection of this plane can risk damaging the muscle, blood supply, and nerves to the rectus abdominus. In addition, this mesh location may not be appropriate for offmidline defects. However, this space potentially protects the mesh from both superficial wound complications and intra-peritoneal contents. In addition, it also allows for Methods Search strategy This systematic review and meta-analysis was registered with PROSPERO, registration number CRD In accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA), a search of PubMed, Cochrane Central Register of Controlled Trials, and Embase was performed to identify the articles for this review [14]. Clinicaltrials.gov was also searched for ongoing trials. The search included publications from January 1990 through April The search strategies were (ventral or incisional) AND hernia AND (onlay OR inlay OR retrorectus OR retro-rectus OR retromuscular OR retro-muscular OR preperitoneal OR Rives Stoppa OR sublay OR underlay OR intraperitoneal OR intra-peritoneal OR IPOM). Reference lists of selected articles were reviewed for additional articles. Only the most recent report from overlapping data was included. Studies were included if they were human-related and comparative studies evaluating two or more mesh locations in open ventral hernia repair. Systematic reviews, meta-analyses, letters, pediatric studies, laparoscopic repairs, techniques manuscripts, and non-ventral hernia repairs (i.e., inguinal, hiatal, etc.) were excluded. Non-comparative studies and reports of less than 10 cases were also excluded. Evaluation of articles The methodological index of nonrandomized studies (MINORS) was used to evaluate methodological quality and potential bias of the articles selected for this review [15]. The first eight of the twelve items evaluated non-

3 comparative and comparative studies. The last four items applied only to comparative studies. Items were scored on a 3-point scale of 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). The global ideal score is 24 for comparative studies. Two independent reviewers scored the articles based on the criteria listed by the assessment. Any disagreement or discrepancies were resolved by consensus among the authors. Only studies with MINORS C10 were included in the final analysis [16]. Primary and secondary outcomes The primary outcome measure was recurrence rate of ventral hernia repairs. Secondary outcome was surgical site infection (SSI). Data extraction The selected articles were reviewed and the primary and secondary outcome data were extracted. Two reviewers independently extracted the data. Study designs, number of patients, patients age, patients BMI, percent of incisional hernias included, mesh location, mesh type, mesh overlap, mesh fixation method, and follow-up period were recorded. Outcome measures recorded were recurrence, SSI, mesh infection, and mesh explantation. Statistical analysis Pairwise meta-analysis was performed to compare all direct treatment of mesh locations using fixed-effects and random-effects models. A multiple treatment meta-analysis was adapted from the guidelines developed by the International Society for Pharmacoeconomics and outcomes research task force to compare the four different locations for mesh placement in open ventral hernia repair [17, 18]. Unlike a traditional meta-analysis which only considers studies with direct comparisons, a multiple treatment metaanalysis, or network meta-analysis, considers studies with multiple competing treatments and combines direct and indirect evidence to determine the most effective treatment [17]. A network of treatment was created to map the relationship between available studies. Heterogeneity was assessed using a Mantel Haenszel method that provided pooled odds ratios and associated confidence intervals for both fixed effect and random effect. It also produces test statistics for heterogeneity utilizing the Higgins I 2, and reports the results as a p value. For a p value \0.05 (I 2 [ 50 %) significant statistical heterogeneity exists and the results of the random-effects model reported; otherwise the results fixed-effects model was reported [17, 18]. A multiple treatment meta-analysis was performed using onlay as the reference treatment to compare all mesh locations by estimating the fixed-effects and random-effects models in the Bayesian framework. The Bayesian approach estimates the odds ratio and the 95 % credible interval and the probability that each location is the best using Markov chain Monte Carlo technique [18, 19]. The credible interval is the Bayesian probability interval that is similar in use to a frequentist confidence interval; however the credible interval also incorporates information from the prior distribution into the estimate while the confidence intervals are solely based on the data. Model fit was assessed by the deviance information criterion and was used to select whether to use the fixed-effects or randomeffects model within the Bayesian framework [20]. Inconsistency of the network, also known as incoherence, was assessed for each model and demonstrated that the indirect evidence was not inconsistent with the direct evidence on the same treatment comparisons beyond chance [17, 18]. Statistical analysis was performed within the statistical software R version [20]. Sensitivity analysis Sensitivity analysis were determined prior to analyses and utilized as a second assessment of heterogeneity. The following sensitivity analyses were planned: studies with a low likelihood of bias based upon MINORS score ([17), studies of incisional hernias only, based on size (large median defect size C 100 cm 2 or width C 10 cm; medium: median size between 36 and 100 cm 2 or width between 6 and 10 cm; and small: median defect size B 36 cm 2 or width B 6 cm), and studies reporting the use of only synthetic mesh and use of only biological mesh were evaluated separately [16, 21]. Results The search resulted in a total of 957 titles and abstracts (Fig. 2). After de-duplication, 472 titles and abstracts were reviewed. An additional 431 articles were excluded for reasons including pediatric only or non-human studies, reviews, meta-analyses, letters, non-ventral hernia related, studies not related to open ventral hernia repair, noncomparative, and case reports of fewer than 10 patients. After screening, 41 full-text articles were reviewed and 19 articles were excluded. A total of 21 articles were subjected to MINORS for assessment and included in the systematic review. The studies included randomized controlled trials (n = 3), retrospective chart reviews (n = 13), and prospective cohort studies (n = 5) (Tables 1, 2).

4 Fig. 2 Search flow-chart Quality of and heterogeneity between the studies The median (range) MINORS score was 15 (10 21). The studies suffered the greatest weakness in criteria: (5) unbiased assessment of study endpoint, (8) calculation of sample size, (7) loss to follow-up of less than 5 %, (6) follow-up period appropriate to the aim of the study, (11) baseline equivalence of groups, and (12) adequate statistical analysis. The three randomized studies had the highest minor scores (Table 2) [22 24]. Of the remaining studies, there were 13 retrospective chart reviews and 5 prospective observational studies of variable quality. While the studies evaluated patients of similar age and BMI and treated patients with similar amounts of mesh overlap and mesh fixation, there was heterogeneity in the type of hernia included (incisional vs. primary), the type of mesh used (synthetic vs. biologic), as well as hernia defect size (Table 1). Recurrence reporting was based upon clinical exam in most studies. Follow-up duration ranged from mean 5 60 months (Table 1). There was sufficient clinical homogeneity between studies to perform a quantitative synthesis of results. Pooled results and analysis Twenty-one studies reported on recurrence rates for ventral hernia repair (Fig. 3). The pooled recurrence rate (range n) was 16.5 % (0 36 %, 1267) for onlay, 30.2 % ( %, 159) for inlay, 7.0 % ( %, 1719) for sublay, and 14.7 % ( %, 2746) for underlay. Ten studies reported on SSI. The pooled SSI rate (range n) was 16.9 % ( %, 302) for onlay, 31.3 % ( %, 112) for inlay, 3.7 % ( %, 702) for sublay, and 16.7 % ( %, 402) for underlay. Onlay mesh placement Seventeen of 21 studies included onlay mesh placement. In pairwise meta-analysis, onlay was associated with higher odds for recurrence and SSI compared to sublay and

5 Table 1 Characteristics of mesh repairs Author Year Age BMI (kg/m 2 ) F/U a (months) Size of defect Incisional, n (%) Mesh type Mesh overlap Mesh fixation Afifi et al Onlay: 52.8 ± ± (median) [10 cm diameter 41 (100) Synthetic C4 cm Onlay: suture underlay: suture, staplers Weber et al [5 cm 2 - synthetic C5 cm sutures Venclauskas et al Onlay: 56.9 ± 11.5 Sublay: 53 ± 11.6 Onlay: 30.5 Sublay: Onlay: ± 90.9 Sublay: 110 ± (100) synthetic 5 cm sutures Helgstrand et al (49 69 IQR) - 21 (10 35) (median, IQR) 7 cm (median) 593 (18) - 5 cm sutures, tacks, glue, clips Hope et al (24 89) [mean (range)] (84) Synthetic, biological - - Kumar et al Li et al Onlay: 57.6 ± 1.1 Onlay: 77(1 143) Onlay: 56.4 ± 9.4 cm 2 92 (69) ± 1.2 Rosen et al Sublay: 58.6 ± ± 13.4 Onlay: 32.3 ± ± 0.72 Sublay: 30.8 ± ± (2 140) (median, range) 50.3 ± 12.9 cm 2 12 Sublay: ± cm ± 125 cm 2 49 (100) Biological 3 5 cm Sutures Forte et al (34 84 range) (100) Synthetic C5 cm Sutures Prasad et al Sublay: 51.1 ± 11.1 Scheuerlein et al ± Onlay & Sublay: Sublay: 30.2 ± ± 2.6 Sublay: 22.7 ± ± 11.9 Sublay: 30.8 ± 24.4 cm ± 22.0 cm 2-20 [4 35] (median, range) Onlay & sublay: 57 (3 314) cm2 37 (3 158) cm (70) Synthetic, biological 29 (100) Synthetic Onlay & sublay: C 3cm C5 cm Suture, tacks Onlay & sublay: sutures sutures? clips Diaz et al (15.2) [17 87] 30.7 (9.6 SD) cm (100) Biological 3 5 cm - Lin et al. C 3cm (23 84) C25 cm (100) Biological - - Abdollahi et al (2 85) - 98 (48 174) (100) Synthetic - - Berrevoet et al Sublay: 54.8 Sublay: 28.2 Sublay: 48.8[42 56] Sublay: 2.6 cm 2 0 Synthetic Sublay: sutures [24 42] [median, range] 2.3 cm 2 C 2.5 cm Gleysteen et al Onlay: 57 (mean) Sublay: 55 Onlay: 66[1 204] Sublay: 62[3-116] [median, range] Onlay: 10 (3-30) cm Sublay: 9(3-20) cm Onlay: 29 (39) Sublay: 15 (30) Synthetic Sutures

6 Table 1 continued Mesh type Mesh overlap Mesh fixation Author Year Age BMI (kg/m 2 ) F/U a (months) Size of defect Incisional, n (%) (100) Synthetic Demetrashvili et al. sutures? staplers Israelsson et al (22 94) 29 [3 cm diameter 296 (100) Lomanto et al (30 83) Sublay: 21.9 Synthetic 3 5 cm Sublay: sutures 19.6 Sublay: cm cm 2 Sublay: 32 (64) 36 (72) [10 cm diameter 53 (100) Synthetic C2 cm Onlay: staples Inlay: sutures suture (28 94) Onlay: 19.4 Inlay: de Vries Reilingh et al (33 79) 6 72 (range) [5 cm diameter 50 (100) Synthetic 6 8 cm Sutures Kingsnorth et al. reported as mean unless otherwise stated a underlay but lower odds compared to inlay (Table 3). On multiple treatment meta-analysis, onlay was one of the worst mesh placement options with a very low probability (\0.001) of being the best treatment (Table 4). Inlay mesh placement Of the 21 studies, six reported on inlay. In pairwise metaanalysis, inlay was associated with higher odds for recurrence and SSI than onlay, sublay, and underlay (Table 3). On multiple treatment meta-analysis, inlay had higher odds for recurrence compared to onlay [3.946 ( )] (Table 4). Inlay also had a higher odds for SSI compared to onlay [1.113 ( )] (Table 3). Inlay was one of the worst mesh placement options with a very low probability (\0.001) of being the best treatment (Table 4). Sublay mesh placement Fourteen of the 21 studies reported on sublay. In pairwise meta-analysis, sublay was associated with lower risk of recurrence and SSI compared to onlay, inlay, and underlay (Table 3). On multiple treatment meta-analysis, sublay had a lower risk for recurrence [0.218 ( )] and SSI [0.449 ( )] compared to onlay (Table 4). Sublay was ranked the best mesh placement option with a high probability of being the best treatment. Sublay had a 94.2 % probability of having the lowest odds of recurrence and 77.3 % probability of having the lowest odds for SSI. Underlay mesh placement Fifteen of the 21 studies included underlay. In pairwise meta-analysis, underlay was associated with lower risk for recurrence and SSI than onlay and inlay but had higher risk compared to sublay (Table 3). On multiple treatment metaanalysis, underlay had a lower risk for recurrence [0.59 ( )] and SSI [0.878 ( )] compared to onlay (Table 4). While underlay had the second highest probability of being the best treatment, it remained a distant second. The probability of underlay having the lowest odds of recurrence was only 5.8 % and for SSI was 11.4 %. Sensitivity analysis Sensitivity analysis was performed for studies at low risk of bias (MINORS \ 17), studies of only incisional hernias, and studies using only synthetic mesh. For all of these, the probability that sublay repair was associated with the lowest risk of recurrence and SSI remained high (Table 5). Onlay, inlay, and underlay remained very unlikely to have the best outcomes. It was not feasible to perform a sensitivity analysis of ventral hernia repairs stratified by hernia

7 Table 2 Study characteristics and outcomes Author Year Study type MINORS N Mesh locations Recurrence N (%) SSI N (%) Mesh infection N (%) Mesh explantation N (%) Afifi et al PRCT Onlay (22) Onlay: 6 (27.3) Onlay: 1 (4.5) Onlay: 1 (4.5) Underlay (19) 0 1 (5.3) 0 Weber et al PRCT Onlay (181) Onlay: 22 (12.2) Sublay (369) Sublay: 53 (14.4) Venclauskas et al PRCT Onlay (57) Onlay: 6 (10.5) Sublay (50) Sublay: 1 (2.0) Helgstrand et al Prospective Onlay (454) Onlay: 73 (16.1) Sublay (323) Sublay: 39 (12.1) Underlay (2021) 328 (16.2) Hope et al Retrospective Onlay (39) Onlay: 14 (35.9) Inlay (10) Inlay: 8 (80.0) Underlay (9) 5 (55.6) Kumar et al Prospective Onlay (45) Onlay: 4 (8.9) Onlay: 6 (13.3) Underlay (18) 1 (5.6) 2 (11.1) Li et al Retrospective Onlay (67) Onlay: 12 (17.9) Onlay: 20 (29.9) Onlay: 5 (7.5) Underlay (67) 7 (10.4) 23 (34.3) 3 (4.5) Rosen et al Prospective Sublay (23) Sublay: 2 (8.7) Sublay: 5 (21.7) Underlay (26) 7 (26.9) 8 (30.8) Forte et al Retrospective Onlay (9) Onlay: 3 (33.3) Onlay: 3 (33.3) Onlay: 2 (22.2) Sublay (207) Sublay: 1 (0.48) Sublay: 9 (4.3) Sublay:2 (0.9) Underlay (30) Prasad et al Retrospective Sublay (68) Sublay: 2 (2.9) Sublay: 0 Underlay (211) 7 (3.3) 0 Scheuerlein et al Retrospective Onlay (10) Onlay: 7 (70.0) Onlay: 0 Onlay: 0 Sublay (4) Sublay: 0 Sublay: 0 Sublay: 0 Underlay (15) 1 (6.7) 0 0 Diaz et al Retrospective Onlay (28) Onlay: 4 (14.3) Onlay: 8 (28.6) Inlay (89) Inlay: 18 (20.2) Inlay: 33 (37.1) Underlay (91) 17 (18.7) 31 (34.1) Lin et al Retrospective Onlay (3) Onlay: 0 Inlay (34) Inlay: 12 (35.3) Underlay (103) 24 (23.3) Abdollahi et al Retrospective Onlay (33) Onlay: 2 (6.1) Onlay: 1 (3.0) Onlay: 1 (3.0) Sublay (312) Sublay: 2 (0.6) Sublay: 7 (2.2) Sublay: 1 (0.3) Underlay (9) Berrevoet et al Prospective Sublay (56) Sublay: 2 (3.6) Sublay: 0 Underlay (60) 5 (8.3) 0

8 Table 2 continued Author Year Study type MINORS N Mesh locations Recurrence N (%) SSI N (%) Mesh infection N (%) Mesh explantation N (%) Gleysteen et al Retrospective Onlay (75) Onlay: 15 (20.0) Onlay: 9 (12.0) Sublay (50) Sublay: 2 (4.0) Sublay: 2 (4.0) Demetrashvili et al Retrospective Onlay (44) Onlay: 3 (6.8) Sublay (51) Sublay: 1 (2.0) Israelsson et al Retrospective Onlay (171) Onlay: 33 (19.3) Inlay (2) Inlay: 0 Sublay () Sublay: 9 (7.3) Lomanto et al Prospective Sublay (50) Sublay: 5 (10.0) Sublay: 5 (10.0) Sublay: 2 (4.0) Underlay (50) 1 (2.0) 1 (2.0) 0) de Vries Reilingh et al Retrospective Onlay (13) Onlay: 3 (23.1) Onlay: 3 (23.1) Inlay (23) Inlay: 10 (43.5) Inlay: 2 (8.7) Underlay (17) 2 (11.8) 0 Kingsnorth et al Retrospective Onlay (16) Onlay: 2 (12.5) Inlay (1) Inlay: 0 Sublay (33) Sublay: 1 (3.0) Fig. 3 Network analysis of studies included in multiple treatments meta-analysis. Width of line represents number of studies. Size of node represents sample size Table 3 Summary of all pairwise meta-analysis Recurrence size or hernias repair only with biologic mesh only due to a low number of direct comparisons. Discussion OR 95 % CI P value Heterogeneity P value* Onlay (reference) vs. Inlay \ Sublay \0.001 Underlay Inlay (reference) vs. Sublay Underlay Sublay (reference) vs. Underlay \ SSI Onlay (reference) vs. Inlay \ Sublay Underlay Inlay (reference) vs. Sublay \0.001 Underlay Sublay (reference) vs. Underlay * Random-effects model reported for pairwise analysis with heterogeneity P value \ 0.05 In this network meta-analysis, sublay repair had the highest probability of having the lowest rate of hernia recurrence and SSI. Underlay repair had the second highest probability

9 Table 4 Multiple treatments meta-analysis OR 95 % credible interval Probability of being the best among four treatments Rank Recurrence a Onlay (reference) \ , 4 Inlay \ , 4 Sublay Underlay SSI b Onlay (Reference) \ Inlay Sublay Underlay a DIC b DIC 59.6 Table 5 Sensitivity analysis Probability of being the best among four treatments All trials Low risk of bias Synthetic mesh only Incisional hernias only Recurrence Onlay (reference) \ \0.001 Inlay \0.001 \ \0.001 Sublay Underlay SSI Onlay (reference) \ \ Inlay \0.001 \ Sublay Underlay \ of having the lowest rate of hernia recurrence and SSI while onlay and inlay had poor results. While there were few high-quality studies, the results when only evaluating studies at low risk for bias did not change. Furthermore, these results are in line with other systematic reviews addressing mesh location [5, 25, 26]. When considering the best location for mesh placement, a number of features are important to consider. First, meshtissue integration may reduce long-term recurrence, with theoretically improved rates with greater mesh-tissue overlap [27]. Second, wound complications increase the risk of recurrence. Thus, techniques that avoid of the development of devascularizing flaps may be preferred [15]. Third, the ideal mesh placement should have tissue coverage to minimize exposure to superficial SSIs as well as intra-peritoneal contents. Last, technical ease may affect surgeon choice of procedure as well as risks for postoperative complications. Sublay repair allows for tissue integration from two load-bearing tissues from both sides: posterior rectus sheath and the anterior myo-fascial complex. In addition, sublay mesh placement protects the mesh from exposure from superficial wound complications, intra-abdominal adhesions, and contamination. Creation of devascularizing skin flaps is avoided. Alternatively, inlay repair does not allow for any tissue integration, any wound complication can potentially expose the mesh, and the mesh is exposed to intra-abdominal contents. While onlay allows for tissue ingrowth from two directions, the skin flaps are not loadbearing. Mesh placed in the onlay location is vulnerable forcing the surgeon to create devascularizing skin flaps and leaving the mesh susceptible to superficial wound complications. Underlay has the advantages of protecting the mesh from superficial wound complications and avoiding development of skin flaps. However, this position requires mesh to be placed intra-abdominally which leaves the mesh

10 susceptible to organ/space infections. In addition, the mesh must grow into peritoneum, the body s natural anti-adhesion barrier. This may explain why the recurrence rates with this repair are higher despite the potential for increased mesh overlap. Sublay repair is not without its own set of challenges. The surgical approach can be perceived as more technically challenging than other techniques, particularly in patients who have had prior abdominal surgeries. Patients with previous stomas, gynecologic procedures, or ventral hernia repairs may have a damaged posterior sheath or damaged rectus muscle. This may leave this space difficult to develop, limited in size, or non-existent in rare circumstances. In addition, risks of damaging the blood supply, muscle, or lateral penetrating nerves pose technical concerns. Furthermore, the semilunar lines limit the lateral extent of the sublay repair and potentially limiting the amount of mesh overlap. Off-midline incisions may not be ideal hernias to approach with this technique. While those new to sublay repair may find it technically daunting, anecdotal experience has demonstrated ease in learning and adopting this approach; however studies to evaluate the learning curve are needed. Given the limited data available but the enormous clinical experience available, most surgeons no longer consider the inlay repair appropriate for ventral hernia repair. All studies demonstrate that inlay repair has the highest recurrence and SSI rates. Increasingly, onlay repair is losing favor with sublay and underlay repairs growing in popularity. Most studies with low risk of bias indicated that the recurrence rate of onlay repair is inferior to sublay and underlay. Between the two studies that examined the SSI rate of onlay repair, both studies demonstrate that onlay repair yield inferior results compared to sublay and underlay. This network analysis suggests that sublay repair may have the best results with underlay repair as a distant second best. A randomized controlled trial to compare sublay and underlay would require a sample size (given a = 0.05, b = 0.20) of 562 to show a difference in recurrence (7.0 vs %) and 198 to show a difference in SSI (3.7 vs %). Network meta-analyses allow for utilization of a larger amount of evidence, estimation of the relative effectiveness among multiple interventions, and rank ordering of the interventions [28]. In contrast to pairwise meta-analysis, network meta-analysis can provide estimates of relative efficacy between all interventions. For many comparisons, the network meta-analysis may yield more reliable and definitive results. However, there are a number of potential limitations. Inadequate reporting of findings and inadequate evaluation of the required assumptions may impede confidence in the findings and conclusions. We followed the grading of recommendations assessment, development, and evaluation (GRADE) Working Group guidelines to allow readers to determine confidence in the results from this network meta-analysis [20, 29]. This network meta-analysis is limited due to the quality of literature that is available. The majority of literature pertaining to mesh placement is of poor methodological quality. In particular, we noted that blinded outcomes assessment and improved follow-up is needed. However, using sensitivity analysis and only assessing studies with a low risk of bias, the results did not change. Furthermore, there was some heterogeneity in follow-up duration between studies, with many studies reporting follow-up as little as 1 month. Outcomes from studies with great differences in follow-up may not be comparable; however, the majority of the studies had a mean follow-up of at least 1 year. Hernia size could also affect outcomes, and a sensitivity analysis by hernia size was planned. However, this analysis was unable to be performed due to a low number of direct comparisons between studies with similar sizes. In addition, other differences in repair technique may have accounted for some of the differences in outcomes, including mesh type and method for mesh fixation. Future studies should compare mesh location in hernias of similar sizes with similar repair techniques to validate these results. Conclusion Sublay placement of mesh demonstrates improved outcomes compared to onlay, inlay, and underlay repairs; however the quality and level of data remains poor. Randomized controlled trials with longer follow-up may be warranted to validate the results of this network metaanalysis; however, this network meta-analysis demonstrates a high probability that sublay repair is associated with the fewest SSIs and hernia recurrences. Disclosures Mike K. Liang this work was supported by the Center for Clinical and Translational Sciences, which is funded by National Institutes of Health Clinical and Translational Award UL1 TR and KL2 TR from the National Center for Advancing Translational Sciences. The National Center for Research Resources or the National Institutes of Health was not responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. References 1. Luijendijk RW et al (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343(6):

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