Mesh reinforcement for the prevention of incisional hernia formation: a systematic review and meta-analysis of randomized controlled trials

Accepted Manuscript Mesh Reinforcement for the Prevention of Incisional Hernia Formation: A Systematic Review and Meta-analysis of Randomized Controlled Trials Xi-Chen Wang, M.M., Dan Zhang, M.M., Zeng-Xi Yang, M.M., Jian-Xin Gan, M.M., Lan-Ning Yin, M.M. Ph.D. PII:

S0022-4804(16)30431-0

DOI:

10.1016/j.jss.2016.09.055

Reference:

YJSRE 14016

To appear in:

Journal of Surgical Research

Received Date: 6 July 2016 Revised Date:

4 September 2016

Accepted Date: 27 September 2016

Please cite this article as: Wang X-C, Zhang D, Yang Z-X, Gan J-X, Yin L-N, Mesh Reinforcement for the Prevention of Incisional Hernia Formation: A Systematic Review and Meta-analysis of Randomized Controlled Trials, Journal of Surgical Research (2016), doi: 10.1016/j.jss.2016.09.055. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Mesh Reinforcement for the Prevention of Incisional Hernia Formation: A Systematic Review and Meta-analysis of Randomized Controlled Trials Xi-Chen Wang, M.M.1,2; Dan Zhang, M.M.1,2; Zeng-Xi Yang, M.M.1,2; Jian-Xin Gan,

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M.M.1,2; Lan-Ning Yin, M.M. Ph.D.1,2,*

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou,

730030, Gansu Province, China 2

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Short Title: Prophylactic mesh for Incisional Hernia

Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730030,

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Gansu Province, China

The Chief Editor: Xi-Chen Wang Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu Province, China Tel:

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+8613919881448; E-mail address: [email protected]

*The Corresponding Author: Lan-Ning Yin

Department of General Surgery,

Lanzhou University Second Hospital, Lanzhou, 730030, Gansu Province, China Tel: +8613909465749; E-mail address:[email protected]

Authors’ Contributions Study design: Xi-Chen Wang; Lan-Ning Yin 1

ACCEPTED MANUSCRIPT Literature search: Xi-Chen Wang; Dan Zhang; Zeng-Xi Yang; Jian-Xin Gan; Lan-Ning Yin Selection of Studies: Xi-Chen Wang; Dan Zhang; Zeng-Xi Yang; Jian-Xin Gan;

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Lan-Ning Yin Data analysis: Xi-Chen Wang; Dan Zhang; Zeng-Xi Yang; Jian-Xin Gan; Lan-Ning Yin

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Data interpretation: Xi-Chen Wang; Dan Zhang; Zeng-Xi Yang; Jian-Xin Gan;

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Lan-Ning Yin

Writing of manuscript and critical revision: Xi-Chen Wang; Lan-Ning Yin

All the authors were thoroughly familiar with the data and have read and

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approved the complete manuscript.

Conflict of Interest: None

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Funding/Support: None

ACCEPTED MANUSCRIPT ABSTACT Background: European Hernia Society guidelines suggested that the evidence of mesh augmentation for the prevention of incisional hernia (IH) was weak.

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Additionally, previous systematic reviews seldom focused on quality of life and cost-effectiveness related to mesh placement. Therefore, an updated meta-analysis was performed to clarify quality of life, cost-effectiveness, the safety, and

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effectiveness of mesh reinforcement in preventing the incidence of IH.

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Methods: Embase, Pubmed and the Cochrane library were searched from the inception to May 2016 without language limitation for randomized controlled trials (RCTs) which explored mesh reinforcement for the prevention of IH in patients undergoing abdominal surgeries.

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Results: Twelve RCTs totaling 1661 patients (958 in Mesh, 703 in Non-mesh) were included in our study. Compared with non-mesh, mesh reinforcement can effectively decrease the incidence of IH (relative risk (RR): 0.19; 95% CI: 0.09 -0.42). Besides,

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mesh placement was associated with improved quality of life, a higher rate of seroma

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(RR: 1.64; 95% CI: 1.13- 2.37) and longer operating time (mean difference (MD): 17.62; 95% CI: 1.44-33.80). No difference can be found between both groups in postoperative overall morbidity, systemic postoperative morbidity, wound-related morbidity, surgical site infection, haematoma, wound disruption, postoperative mortality, and length of hospital stay. Conclusions: Prophylactic mesh reinforcement may be effective and safe to prevent the formation of IH after abdominal surgery, without impairing quality of life. Thus,

ACCEPTED MANUSCRIPT preventive mesh should be routinely recommended in high-risk patients.

Key Words: Surgical Mesh; Incisional Hernia; Meta-Analysis; Randomized

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Controlled Trials

ACCEPTED MANUSCRIPT INTRODUCTION Nearly 14.5 percent incisional hernia (IH) happened in patients who undergoing abdominal operation 1 year postoperatively[1,2], especially in open bariatric surgery

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and abdominal aortic aneurysm surgery[3,4], which was usually associated with increased readmission rate and hospital cost[5], diminished quality of life[6], and extended economic burden[7]. If the rate of IH can be decrease to 5% after abdominal

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surgery in France, a total of 4 million Euros have been saved in 2011[7]. Generally,

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complicated and multifactorial risk factors can promote the formation of IH after abdominal surgery, which involving midline incision, BMI ≥ 25 kg/m2, advanced age, COPD, and incisional surgical-site infection, and so on[8,9]. Sequentially, patients with these perioperative high-risk factors were associated with increased incidence of

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IH.

Mesh reinforcement as the golden standard of hernia repair, can significantly reduce the recurrence of abdominal hernia, involving inguinal hernia[10], parastomal

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hernia[11], and incisional hernia[12,6]. Moreover, recent clinical trials also indicated

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that prophylactic mesh reinforcement significantly decreased the occurrence of parastomal hernia in patients undergoing colostomy [13,14]. Understandably, mesh reinforcement seemed to be a promising method to prevent the formation of IH after laparotomy, which was verified by previous systematic reviews and meta-analyses [15-17]. However, these studies included low-quality clinical trials with small sample size and potential selection bias and confounding bias, which may be difficult to reach enough credible conclusions. Hence, European Hernia Society guidelines suggested

ACCEPTED MANUSCRIPT that the quality of evidence of mesh augmentation for the prevention of IH was weak and further high-quality evidence was essential [18]. Chronic incision pain was a hardly-neglected symptom after abdominal surgery and

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weakened quality of life. Interestingly, published studies suggested that along with a lower recurrence rate, mesh repair for incisional hernia was associated with reduced chronic pain and improved quality of life[19,20]. However, whether prophylactic

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mesh reinforcement also had similar influence on chronic incision pain and quality of

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life after abdominal operation was ill-defined. More importantly, published systematic reviews seldom evaluated these easily-neglected, but vitally important aspects. Therefore, an updated meta-analysis of randomized controlled trials (RCTs) was undertaken to systematically assess the safety and effectiveness of mesh

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reinforcement in preventing the incidence of IH, particularly including relevant data on chronic incision pain, quality of life, and cost-effectiveness. METHODS

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The current study was consistently performed according to the Cochrane Handbook

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for Systematic Reviews of Interventions and PRISMA guidelines [21,22]. Three reviewers separately conducted literature retrieval, date extraction, quality assessment, and statistical analysis, with controversy and inconsistence resolved by discussion and consensus.

Search Strategy and Inclusion Criteria PubMed, Embase, and the Cochrane library were systematically searched from the inception to May 2016 without language limitation. We merely included RCTs

ACCEPTED MANUSCRIPT focused on mesh reinforcement for the prevention of IH in patients undergoing abdominal surgery. We eliminated studies which explored the effectiveness of mesh reinforcement in patients undergoing primary abdominal hernia repair. The primary

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outcomes were the incidence of IH, chronic incision pain, quality of life, and cost-effectiveness, with operating time, length of hospital stay, morbidity related to wound, and mortality making up the secondary outcomes. In the current study, the

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incidence of IH was defined as a protrusion in the abdominal wound postoperatively

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with the longest duration whether it was detected by physical examination or imageological examination. Actually, it was difficult to distinguish IH from parastomal hernia, which usually appeared near stoma. Accordingly, we also excluded patients undergoing mesh reinforcement in stoma sites. Detailed inclusion and

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exclusion criteria were present in Table 1.

In order to retrieve as more studies meeting pre-defined inclusion criteria as possible, we generated enlarged search strategy, that is, ‘hernia*[Title/Abstract] AND

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"Mesh"[Title/Abstract] AND random*[Title/Abstract]’. In addition, the references of

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relevant reviews, published meta-analyses, and included studies were carefully checked for any possible inclusion. Data Extraction and Quality Assessment Data was extracted in the form of PICOS and all the relevant information was entered into a pre-designed extraction table. Detailed PICOS was as follows. Patients (P): Country and clinical setting, number of randomization, demographic characteristics, BMI (kg/m2), concomitant diseases, type of surgery and incision, and

ACCEPTED MANUSCRIPT so on. Intervention (I): Type, size, and location of mesh, surgical process of mesh location, and so on.

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Compare (C): The surgical process of conventional abdominal wound closure and so on.

Outcomes (O): The definition of outcomes of interest, diagnosis of IH, outcomes data

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of interest, and so on.

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Study design (S): The detail of randomization, blinding, allocation concealment, intention to treat analysis, and so on.

We used the Cochrane Collaboration’s tools to assessing the quality of included studies, that is, random sequence generation; allocation concealment; blinding of

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patients, personnel, outcome assessors; incomplete outcome data; selective reporting[23]. Individual trial with six elements of low risk of bias was regarded as low risk of bias, if not, unclear or high risk of bias.

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Statistical Analysis

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Data were analyzed on the basis of an ‘intention-to-treat’ principle. RRs (relative risks) and mean differences (MDs) with 95% confidence intervals (CIs) were employed to estimate overall pooled effect. More conservatively, random effects model was used to calculate overall effect size when considering the inherent difference among the include studies. The statistic heterogeneity across the included studies was evaluated by I2 statistic and I2 < 50% was deemed as accepted heterogeneity[24]. If I2 > 50%, we would perform post hoc subgroup analyses to investigate the potential source of

ACCEPTED MANUSCRIPT heterogeneity, according to sample size (<100 vs. >100), risk of bias (Low vs. Unclear or High), mean age (<60 vs. >60), mean BMI (<40 vs. >40), location of mesh (Intraperitoneal vs. Preperitoneal vs. Above the aponeurosis), and follow-up (<24

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vs. >24 months). Test of interaction (P < 0.05) in subgroup analyses was thought to provide evidence of an intervention effect statistically. Meantime, we undertook sensitive analysis to assess the influence of individual study on the overall pooled

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effect through omitting one study every time. A two-sided P-values <0.05 was

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considered to be statistically significant. Publication bias was estimated by funnel plots and the Begg and Egger test[25,26]. Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) and Stata 12.0 (Stata Corporation LP, College Station, TX) were used to perform all the statistic analyses.

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RESULTS

We acquired 2339 records from three databases (Pubmed 767, Embase 970, the Cochrane library 602) through our expanded search. After removing reduplicative and

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irrelevant literatures, 66 remaining items were screened for possible inclusion through

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full-text checking. Finally, 14 publications were left, of which two[27,28] reported the same RCT at different follow-up point and another two[29,30] involved the same RCT with different outcomes of interest. Eventually, 12 RCTs totaling 1661 patients (958

in

Mesh,

703

in

Non-mesh)

were

included

in

the

current

study[4,31,32,30,33-36,3,37,28,38]. Figure 1 showed the whole flow of literature selection. Characteristics of Included Studies

ACCEPTED MANUSCRIPT Baseline characteristics of included studies were present in Table 2. The sample size ranged from 64 to 480, and the follow-up duration from 1 to 49 months. Except for one study involving laparoscopic cholecystectomy[33], all the included studies

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encompassed patients who undergoing open midline laparotomy, of which 4 studies[4,31,35,38] were related to open abdominal aortic aneurysm repair and 3 studies [34,3,28] open bariatric surgery. In addition, the type, size, and location of

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mesh were varied from each other. Figure 2 showed each risk of bias item for

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individual included study. On the whole, seven[4,31,32,30,33,35,3] studies were regarded as low risk of bias, five[34,36,37,28] [38]unclear risk of bias, and no one high risk of bias.

Wound Pain, Quality of Life, and Cost-Effectiveness

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Chronic wound pain was reported in three studies[4,36,37] and the pooled result suggested that there was no difference between mesh and non-mesh group in patients who suffered from this long-term uncomfortable symptom (RR: 2.92; 95% CI: 0.55,

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15.36; Figure 3). Besides, acute wound pain was basically similar in both groups at 24

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hours postoperatively (3 in non-mesh and 2 in mesh), which was quantified using the visual analogue scale in only one study[33]. Three studies reported pain-related quality of life[4,37,29]. The study by Gutierrez et al. reported that only two patients in the mesh group suffered occasional wound pain at 3 years postoperatively, but the discomfortableness did not disturb their normal life[37]. Also, another study by Muysoms et al. showed analogous results[4]. Only 2% patients in mesh group underwent chronic wound pain and none of them were

ACCEPTED MANUSCRIPT hindered to enjoy a normal life. In particular, Caro-Tarragó and colleagues reported supportive conclusions that preventive mesh as compared with no-mesh can significantly improve quality of life, which was evaluated using ST-36 generic health

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questionnaire after midline laparotomy[29]. None of included studies reported relevant data on the cost-effectiveness associated with prophylactic mesh placement. The Incidence of IH

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Pooled analysis for 11 studies[4,32,30,33-36,3,37,28,38] suggested that mesh as

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compared with non-mesh was associated with a lower incidence of IH formation after laparotomy (RR: 0.19; 95% CI: 0.09-0.42; P< 0.0001; Figure 3), with foreseeable statistical heterogeneity (I2= 71%). To investigate the possible source of heterogeneity, we further performed post hoc subgroup analyses, which were showed in Table 3. The

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results of subgroup analyses were basically consistent with the overall pooled effect, although none of subgroup difference was statistically significant. Moreover, we conducted sensitive analysis to verify whether the pooled estimate was enough robust

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and credible. RR fluctuated from (0.16; 95% CI: 0.06-0.42; P= 0.0001) to (0.23; 95%

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CI: 0.11-0.49; P= 0.0001) after omitting one study each run. But it was noteworthy that I2 had a sharp reduction from 71% to 18% when the study by Pans et al. [28]was removed.

Wound-Related Morbidity, Mortality, Hospital stay, and Operating Time Pooled results indicated that there was no significant difference between mesh and non-mesh group in wound-related morbidity (12RCTs; RR: 1.10; 95% CI: 0.79 - 1.52; P = 0.57; Figure 3), postoperative overall morbidity (12RCTs; RR: 1.19; 95% CI:

ACCEPTED MANUSCRIPT 0.95-1.50; P = 0.13; Figure 3), systemic postoperative morbidity (5RCTs; RR: 1.36; 95% CI: 0.91-2.04; P = 0.14; Figure 3), surgical site infection (10RCTs; RR: 0.87; 95% CI: 0.63-1.20; P = 0.39; Figure 3), haematoma (4RCTs; RR: 1.84; 95% CI: 0.52-

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6.50; P = 0.35; Figure 3), wound disruption(6RCTs; RR: 0.92; 95% CI: 0.37-2.28; P = 0.86; Figure 3), postoperative mortality(5RCTs; RR: 0.94; 95% CI: 0.45-1.99; P = 0.87; Figure 3), and length of hospital stay(5RCTs; MD: -0.14; 95% CI: -0.75 - 0.48;

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P = 0.66; Figure 3). Particularly, mesh as compared with non-mesh group was

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associated with longer operating time (6RCTs; MD: 17.62; 95% CI: 1.44–33.80; P = 0.03; Figure 3) and a higher rate of seroma (11RCTs; RR: 1.64; 95% CI: 1.13-2.37; P = 0.009; Figure 3). Publication Bias

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Funnel plot seemed to be visually asymmetric, but no publication bias can be identified through statistical test for the primary outcome (11RCTs; Begg: P=0.533; Egger: P=0.491; Figure 4).

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Key Findings

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DISCUSSION

Compared with non-mesh, prophylactic mesh reinforcement was associated with improved quality of life, decreased IH formation, and a slight increase in wound seroma and operating time after laparotomy. Besides, no significant difference can be found between both groups in wound-related morbidity, postoperative overall morbidity, postoperative mortality, and length of hospital stay. There was no included studies reported relevant data on the cost-effectiveness.

ACCEPTED MANUSCRIPT Novelty of the Current Study Table 4 had a clear description of the difference between previous and the current study. Three previous systematic reviews [17,39,40] assessed the effectiveness of

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mesh placement for the prevention of IH, with the sample size ranging from 346 to 1224. Notably, two studies[39,40] included observational clinical trials with possible selection bias and confounding bias, which may overestimate the authentic

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intervention effect. Our study suggested that mesh reinforcement can effectively

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reduce the incidence of IH postoperatively, which was consistent with previous reviews. However, the current study included more trials (12RCTs) with bigger sample size (1661 patients) and subsequent subgroup analysis and sensitive analysis further confirmed this superiority of prophylactic mesh, which made the result more

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credible and robust. Also, our study indicated that mesh placement can induce a slight higher occurrence of seroma and no difference between both groups can be identified in length of hospital stay, which was incompatible with published reviews. Obviously,

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pooled analysis of high-quality RCTs with bigger sample size made our results more

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reliable. Finally, our study evaluated more integrated outcomes, especially including quality of life, wound disruption, and postoperative mortality. All in all, we believed that the current study should be the most high-quality systematic review with the most comprehensive and credible evidence until now. European Hernia Society guidelines based on previous systematic reviews announced that mesh reinforcement can effectively prevent IH formation following laparotomy, but the quality of evidence was weak. Maybe, the current meta-analysis can provide a powerful weighted

ACCEPTED MANUSCRIPT reference for updated guidelines. Application for Clinical Practice The current available evidence suggested that mesh reinforcement can be effectively

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and safely used to decrease the incidence of IH in patients undergoing laparotomy. Additionally, together with patients after open surgery, this advantage also remained evident in patients undergoing laparoscopic surgery, although only one study was

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included in the current meta-analysis[33]. Moreover, a recent retrospective study held

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the similar opinion that prophylactic synthetic mesh can significantly reduce the risk of IH formation without increasing postoperative morbidity, even after emergency midline laparotomy[41]. Actually, no all the patients undergoing abdominal operation ended up with developing IH when considering that the occurrence of IH usually from

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factors.

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perfect

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preoperative risk model can accurately estimate the possibility of IH formation and provide evidence-based recommendation on prophylactic mesh placement for

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‘special’ high-risk patients, which may largely save health system costs and resources.

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Accordingly, the current available risk stratification score from the HERNIA Project was calculated to predict the risk of IH formation, which merely quantified four independent factors, that is, open laparotomy, hand-assisted laparoscopy, COPD, and BMI ≥ 25 kg/m2[9]. However, inconsistent results were reported on preoperative risk factors associated with IH development in recent studies. Yamada and colleagues concluded that subcutaneous fat area, advanced age, and open surgery were the most important risk factors after colorectal cancer surgery[42]. Another study by Ooms at

ACCEPTED MANUSCRIPT el. suggested that the independent risk factors for IH were consisted of obesity (BMI >30), female sex, history of smoking, and concurrent abdominal wall hernias after kidney transplantation[43]. Therefore, considering the pluralism and complexity

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of risk factors, future study should focus on producing more comprehensive and precise risk estimation models to guide clinical decision of mesh placement in selective high-risk patients.

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Our study indicated that mesh reinforcement did not seem to have negative effect on

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chronic wound pain and normal life in the long-term follow up. Indeed, one included study did confirm the enhanced effect of mesh placement on quality of life[29]. Virtually, this positive influence on chronic pain and quality of life was supported in mesh repair for incisonal hernia. A recent comparative study suggested

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that laparoscopic and open ventral hernia mesh repair was associated with improved quality of life and decreased chronic pain and physical impairment[20]. There were no included studies focused on the cost-effectiveness of mesh reinforcement. However, a

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retrospective comparative study stated that an approximate average cost of $1,732 has

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been saved every year if primary suture closure can be superseded by prophylactic mesh augmentation after elective laparotomy [44]. Regardless of limited data on quality of life and cost-effectiveness, the long-term outcomes of the study by Timmermans and colleagues[31] and ongoing studies (https://clinicaltrials.gov. NCT02208557, NCT01203553) were in prospect. Limitations Our study had many limitations. Firstly, we included a variety of abdominal operation

ACCEPTED MANUSCRIPT with different baseline characteristics, so the substantial heterogeneity (I2=71%) was understandable and foreseeable. However, I2 had a sharp drop from 71% to 18% when the study by Pans and colleagues was omitted; maybe, this study was the potential

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source of statistical heterogeneity. After carefully checking its full text, we found that the prophylactic mesh was placed above the omentum and the rate of IH formation was the highest (23%) among all the included studies. Also, subgroup analysis in

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Table 3 also indicated that intraperitoneal mesh did not have obvious superiority over

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non-mesh to reduce the occurrence of IH (RR: 0.37; 95% CI: 0.06-2.26; P = 0.28). So, the location of mesh placement was likely to be the most weighted source of clinical heterogeneity. Moreover, regardless of considerable difference across included studies, subgroup analysis and sensitive analysis further confirmed the robustness and

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creditability of the pooled intervention effect. Secondly, limited information was available in quality of life and cost-effectiveness associated with preventive mesh after abdominal operation. Further studies should focus on these easily-neglected, but

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extremely important aspects to patients. Finally, statistical test for the primary

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outcome did not detect publication bias, but the funnel plot (Figure 4) was visually asymmetrical. Thus, underlying publication bias derived from low-quality studies with small sample size was hardly excluded, although we performed an enlarged literature search. Conclusions Irrespective of aforementioned limitations, the current available evidence indicated that mesh reinforcement may be effective and safe to prevent the formation of IH after

ACCEPTED MANUSCRIPT abdominal operation, without impairing quality of life. Further studies should focus on the cost-effectiveness of mesh placement.

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Compliance with ethical standards

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All the authors had no conflicts of interest or financial ties to disclose.

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research ed) 339:b2535

23. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 343:d5928 24. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557-560 25. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test

ACCEPTED MANUSCRIPT for publication bias. Biometrics 50:1088-1101 26. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315:629-634

prevention of incisional hernias. Acta Chir Belg 95:265-268

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27. Pans A, Desaive C (1995) Use of an absorbable polyglactin mesh for the

28. Pans A, Elen P, Dewe W, Desaive C (1998) Long-term results of polyglactin mesh

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for the prevention of incisional hernias in obese patients. World J Surg 22:479-482;

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discussion 482-473

29. Caro-Tarrago A, Olona-Casas C, Olona-Cabases M, Guillen VV (2014) Retracted: Impact on quality of life of using an onlay mesh to prevent incisional hernia in midline laparotomy: a randomized clinical trial. J Am Coll Surg 219:470-479

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30. Caro-Tarrago A, Olona Casas C, Jimenez Salido A, Duque Guilera E, Moreno Fernandez F, Vicente Guillen V (2014) Prevention of incisional hernia in midline

38:2223-2230

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laparotomy with an onlay mesh: a randomized clinical trial. World J Surg

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31. Timmermans L, Eker HH, Steyerberg EW, Jairam A, de Jong D, Pierik EG, Lases SS, van der Ham AC, Dawson I, Charbon J, Schuhmacher C, Izbicki JR, Neuhaus P, Knebel P, Fortelny R, Kleinrensink GJ, Jeekel J, Lange JF (2015) Short-term results of a randomized controlled trial comparing primary suture with primary glued mesh augmentation to prevent incisional hernia. Ann Surg 261:276-281 32. Garcia-Urena MA, Lopez-Monclus J, Hernando LA, Montes DM, Valle de Lersundi AR, Pavon CC, Ceinos CJ, Quindos PL (2015) Randomized controlled trial

ACCEPTED MANUSCRIPT of the use of a large-pore polypropylene mesh to prevent incisional hernia in colorectal surgery. Ann Surg 261:876-881 33. Armananzas L, Ruiz-Tovar J, Arroyo A, Garcia-Peche P, Armananzas E, Diez M,

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Galindo I, Calpena R (2014) Prophylactic mesh vs suture in the closure of the umbilical trocar site after laparoscopic cholecystectomy in high-risk patients for incisional hernia. A randomized clinical trial. J Am Coll Surg 218:960-968

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34. Abo-Ryia MH, El-Khadrawy OH, Abd-Allah HS (2013) Prophylactic

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preperitoneal mesh placement in open bariatric surgery: a guard against incisional hernia development. Obes Surg 23:1571-1574

35. Bevis PM, Windhaber RA, Lear PA, Poskitt KR, Earnshaw JJ, Mitchell DC (2010) Randomized clinical trial of mesh versus sutured wound closure after open abdominal

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aortic aneurysm surgery. Br J Surg 97:1497-1502

36. El-Khadrawy OH, Moussa G, Mansour O, Hashish MS (2009) Prophylactic

13:267-274

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prosthetic reinforcement of midline abdominal incisions in high-risk patients. Hernia

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37. Gutierrez de la Pena C, Medina Achirica C, Dominguez-Adame E, Medina Diez J (2003) Primary closure of laparotomies with high risk of incisional hernia using prosthetic material: analysis of usefulness. Hernia 7:134-136 38. Bali C, Papakostas J, Georgiou G, Kouvelos G, Avgos S, Arnaoutoglou E, Papadopoulos G, Matsagkas M (2015) A comparative study of sutured versus bovine pericardium mesh abdominal closure after open abdominal aortic aneurysm repair. Hernia 19:267-271

ACCEPTED MANUSCRIPT 39. Nachiappan S, Markar S, Karthikesalingam A, Karthikesaligam A, Ziprin P, Faiz O (2013) Prophylactic mesh placement in high-risk patients undergoing elective laparotomy: a systematic review. World journal of surgery 37:1861-1871

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40. Bhangu A, Fitzgerald JE, Singh P, Battersby N, Marriott P, Pinkney T (2013) Systematic review and meta-analysis of prophylactic mesh placement for prevention of incisional hernia following midline laparotomy. Hernia 17:445-455

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41. Argudo N, Pereira JA, Sancho JJ, Membrilla E, Pons MJ, Grande L (2014)

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Prophylactic synthetic mesh can be safely used to close emergency laparotomies, even in peritonitis. Surgery 156:1238-1244

42. Yamada T, Okabayashi K, Hasegawa H, Tsuruta M, Abe Y, Ishida T, Matsui S, Kitagawa Y (2016) Age, Preoperative Subcutaneous Fat Area, and Open Laparotomy

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are Risk Factors for Incisional Hernia following Colorectal Cancer Surgery. Annals of surgical oncology 23 Suppl 2:S236-241

43. Ooms LS, Verhelst J, Jeekel J, Ijzermans JN, Lange JF, Terkivatan T (2016)

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Incidence, risk factors, and treatment of incisional hernia after kidney transplantation:

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An analysis of 1,564 consecutive patients. Surgery 159:1407-1411 44. Fischer JP, Basta MN, Wink JD, Krishnan NM, Kovach SJ (2015) Cost-utility analysis of the use of prophylactic mesh augmentation compared with primary fascial suture repair in patients at high risk for incisional hernia. Surgery 158:700-711

ACCEPTED MANUSCRIPT Figure Legends

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Figure 1: PRISMA flow diagram of literature selection.

Figure 2: Risk of bias summary of individual included studies. Green = low risk of

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bias, Yellow = unclear risk of bias, Red = high risk of bias.

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Figure 3: Forest plot summary of outcomes comparing mesh with non-mesh after abdominal operation. CI = confidence interval, RR = relative risk, IH=incisional hernia, IV= inverse variance, MD= mean difference, MH=mantel haenszel.

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Figure 4: Funnel plots comparing mesh with non-mesh for the prevention of IH

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formation after abdominal operation. SE= Standard error

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Table 1: Detailed Inclusion and Exclusion Criteria of This Meta-Analysis Intervention

Control

Outcomes • Primary outcome:The incidence of incisional

hernia and underwent

• Intraoperative

any abdominal

mesh

surgery, including

reinforcement in

open and

surgical incisions

laparoscopic

• Conventional

hernia, Chronic pain, Quality

abdominal

of life, and cost-effectiveness

• Randomized

closure without

• Secondary outcomes:

controlled

mesh

Operating time, Length of

trials(RCTs)

reinforcement

hospital stay, Morbidity

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have primary ventral

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Inclusion Criteria

• Patients who did not

• Patients with primary incisional hernia

abdominal wall reinforcement • Mesh reinforcement in stoma sites

• Abdominal

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inguinal hernia

• Other non-mesh

• Studies which did not report

closure with mesh

primary and secondary

reinforcement

outcomes

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of ventral hernia and

Language

Follow-up

Any

Any

Any

No

No

No

Mortality

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Exclusion Criteria

underwent the repair

Sample Size

related to wound, and

operation • Patients who

Study Design

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Patients

• Study protocols, reviews articles, observational studies, descriptive studies,conference abstracts, and letters

ACCEPTED MANUSCRIPT Table 2: Baseline Characteristics of Included Studies NO. of randomization, Male(%), Diabetes Type of Surgery and Type,Size, and Location of Mesh Mellitus(%) Incision

Mesh

No Mesh

144; 20.8%; 36.4 ± 0.9; 43.7± 0.6

Pans 1998[28]

Belgium

144; 28.4%; 36.6 ± 0.9; 43.8 ± 0.5

Gutiérrez 2003[37]

Spain

50 (Mesh) and 50 (non-mesh); Age: 64.3 (42–83); Male(67%)

Poland

37; 66.7%; 39.4 ± 12.3; 46.2 ± 7.1

40; 60.5%; 38.9 ±11.8; 46.8 ± 7.6

Egypt

20; 40%; 47.86 ± 13.82; 45%(Obese)

20; 50%; 47.61 ± 14.11; 40%(Obese)

Bevis 2010[35]

Abo-ryia 2013[34]

Armañanzas 2014[33]

Caro-tarrago 2014[30]

Bail 2015[38]

NA

Laparotomy with A premilene Mesh; which extended past The incidece of IH, wound Abdominal medial and the incision by 3 cm in all directions; complications,chronic 36 months palpation and CT paramedial incision Placed on the aponeurosis pain,and quality of life

21%

A polypropylene mesh; 8 cm wide and 2 The incidece of IH, wound Open Roux-en-Y cm longer than the incision; Inserted complications,and systemic gastric bypass with Utrasonography 38 months between the rectus muscle and its complications,and hospital midline incision posterior sheath stay

20%

Abdominal A non-absorbable mesh;Adjusted mesh operations through size placed in the available preperitoneal midline incisions space

The incidece of IH, wound complications,and systemic Ultrasonography 36.7 months complications,and chronic pain

11.70%

Open abdominal A 15 × 15cm polypropylene mesh which aortic aneurysm was cut in half and trimmed to shape; repair with midline placed in the preperitoneal plane incision

Clinical examination or ultrasound imaging

The incidece of IH, wound 36 months complications

NA

Open bariatric surgery with midline incision

A prophylactic sheet of polypropylene mesh;4–5 cm longer than the wound length and 10–12 cm width; Fixed in the preperitoneal space

Clinical examination or ultrasound imaging

The incidece of IH, wound 49 months complications

Laparoscopic cholecystectomy

A bilaminar VPATCH (Atrium) polypropylene mesh coated with Clinical bioabsorbable omega-3 oil; Standard size examination or (6.4 cm); Fixed in the intraperitoneal CT compartment

The incidece of IH, wound complications, hospital 12 months stay,operating time, and chronic pain

The incidece of IH, wound complications,and systemic 29.8 months complications

40; 85%; Age:74 (59–84)

45; 95.5% Age:72 (59–89)

Egypt

32; 18.7%; 38.5 ± 10.8; 52.2 ± 9.1

32; 21.8%; 36.9 ± 11.3; 51.4 ± 10.5

Spain

53;24.4%; 60.3 ± 16.2; 30.5 ± 6.1

53;19.1; 61.9 ± 15.3; 30.6 19.50% ± 5.3

Spain

80;55%; 64.32 ± 14.27; BMI>30(26.3%), BMI<30(73.3%)

80;57.5%; 67.32 ± 11.11; 16.80% BMI>30(30.1%), BMI<30(69.9%)

A polypropylene monofilament mesh; The size of the mesh depended on the Midline laparotomy length of the laparotomy;Fixed on the aponeuroses

20; 90%; 75; 24.4

Open abdominal aortic aneurysm repair with midline incision

A biological mesh derived from processed Clinical bovine pericardium;The mesh completely examination or cover the sutured fascia line for at least 4 CT cm wide;placed in the preperitoneal plane

The incidece of IH, wound complications,and operating 36 months time,and hospital stay

Open colorectal procedure with midline incision

A large-pore, very low-weight polypropylene mesh; 15 × 10cm; placed on the overlay position

The incidece of IH, wound complications,and systemic 24 months complications,and hospital stay

Greece

20; 90%; 75; 25.4

25.00%

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53;58.5%; 54;61%; 65.6 ± 13.3; 61.46±15.6; 25.20% BMI>25(45.2%) BMI>25(40.7%)

Onlay Mesh: 188; 61.7%; Netherlands, 64.2 ± 12.3; Germany,and 30.8 ± 5.9 Austria (Multi-center) Sublay Mesh:

107; 63.5%; 65.2 ± 10.5; 29.8 ± 4.4

19.60%

185; 58.47%; 64.4 ± 10.4; 30.8 ± 5.2

Muysoms 2016[4]

Absorbable vicryl mesh; 21.5 × 26.5 cm; Physical Placed above the omentum examination

North Bristol(UK)

García-Ureña 2015[32] Spain

Timmermans 2015[31]

Follow-up

12.50%

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El-khadrawy 2009[36]

Outcomes of Interest

Open bariatric surgery with midline incision

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Strzelczyk 2006[3]

Diagnosis of Incisional Hernia

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Age(years), BMI(kg/m2 )

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Country

56;96%; Belgian 72 ± 7.4; (Multi-center) 25 ± 3.6

58;88%; 72 ± 8.5; 26 ± 3.7

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References

17.40%

Clinical examination or CT

Clinical examination or CT

Onlay Mesh: A polypropylene lightweight mesh;Cut to fit the dissected space; Placed on the anterior rectus fascia with an overlap of 3 cm at each side

Open abdominal aortic aneurysm NA repair with midline incision Sublay Mesh: A polypropylene lightweight mesh;Cut to fit the dissected space; Placed on the posterior plane with an overlap of 3 cm at each side Open abdominal aortic aneurysm repair with midline incision

A large pore, partially absorbable and lightweight polypropylene mesh; Width 7.5 cm and cut to appropriate dimensions ; placed in a retromuscular position

Clinical examination or ultrasound imaging or CT

The incidece of IH, wound 14.8 months complications

Wound complications and hospital stay

1 months

The incidece of IH, wound complications,and systemic 24 months complications,operating time,and hospital stay

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Table 3:Subgroup Analyses of Mesh Reinforcement for the Prevention of Incisional Hernia No. trials

No. patients

RR,95%CI

P-value for overall effect

Total

11

1181

0.19 (0.09, 0.42)

<0.0001

Sample size 0.24 (0.12, 0.50)

0.0001

6

875

0.19 (0.06, 0.58)

0.004

649 532 469 712

3 3

260 429

2 4 5 2 9

394 229 558

0.29 (0.07, 1.15) 0.17 (0.08, 0.35) 0.09 (0.03, 0.30) 0.24 (0.04, 1.61)

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4 7

0.17 (0.08, 0.38) 0.26 (0.07, 0.92)

RR:relative risk; CI, confidence interval

266 915

<0.0001 0.04

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6 5

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306

0.37 (0.06, 2.26) 0.27 (0.13, 0.56) 0.11 (0.04, 0.37)

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>100 Risk of bias Low Unclear or high Mean age(years) <60 >60 Mean BMI <40 >40 Location of mesh Intraperitoneal Preperitoneal Above the aponeurosis Follow-up(months) <24 >24

5

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<100

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Subgroup

0.09 (0.03, 0.25) 0.26 (0.12, 0.55)

0.08 <0.00001 <0.0001 0.14

I2(%) Test of interaction, P 71

Not applicable 0.7

0 82 0.58 48 71 0.51 62 38 0.4 0 73 0.41

0.28 0.0005 0.0003

84 0 50 0.11

<0.00001 0.0005

0 62

ACCEPTED MANUSCRIPT Table 4:The Difference Between the Current Study and Previous Meta-analyses Nachiappan et al.[16](2013)

Bhangu et al.[15](2013)

Our study (2016)

Included studies

5 RCTs

5 RCTs+4 Non-RCTs

4 RCTs+3Non-RCTs

12RCTs

Sample size

346

575(RCT)+649(Non-RCT)

299(RCT)+289(Non-RCT)

1661

The source of included studies

MEDLINE, Embase, Web of Science and the Cochrane library

MEDLINE, Embase, Web of Science and the Cochrane library

MEDLINE, Embase, the Cochrane library, ClinicalTrials.gov, and Google Scholar

Embase, Pubmed and the Cochrane library

The duration of the search

January 1990 and October 2012

January 1950 to May 2012

1980 to October 2012

The inception to May 2016

Quality of life

NR

NR

NR

Improved quality of life (Mesh group)

The incidence of IH

5RCTs; SZ:346; RR: 0.25 (0.12, 0.52)

5RCTs; SZ:575; OR: 0.32 (0.12, 0.83) 7CCTs; SZ:543; OR: 0.16 (0.08, 0.33) 4Non-RCTs; SZ:649; OR: 0.11 (0.04, 0.33)

Postoperative overall morbidity

NR

NR

Systemic postoperative morbidity

NR

NR

Wound-related morbidity

NR

NR

Outcomes of interest

5RCTs; SZ:346; RR: 1.22 (0.64, 2.33)

Chronic pain

2RCTs; SZ:128; RR:5.95 (0.74, 48.03)

Haematoma

NR

Wound disruption

NR

NR

NR

Operating time

NR

Subgroup analysis

Sensitive analysis

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Length of hospital stay

NR

NR

NR

5RCTs; SZ:1069; RR: 1.36(0.91, 2.04)

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12RCTs; SZ:1661; RR: 1.19(0.95, 1.50)

12RCTs; SZ:1661; RR: 1.10(0.79, 1.52)

5CCTs; SZ:409; OR: 0.97 (0.36, 2.59)

10RCTs; SZ:1544; RR: 0.87(0.63, 1.20)

6CCTs; SZ:463; OR: 1.86 (0.70, 4.97)

11RCTs; SZ:1373; RR: 1.64(1.13, 2.37)

2CCTs; SZ:128; OR: 6.57 (0.76, 56.69)

3RCTs; SZ:229; RR: 2.92(0.55, 15.36)

NR

2CCTs; SZ:183; OR: 1.08 (0.22, 5.33)

4RCTs; SZ:854; RR: 1.84(0.52, 6.50)

NR

NR

6RCTs; SZ:911; RR: 0.92(0.37, 2.28)

NR

NR

5RCTs; SZ:826; RR: 0.94(0.45, 1.99)

NR

2CCTs; SZ:169; MD: -1.02 (-1.37, -0.67)

NR

2CCTs; SZ:180; MD: 14.9 (12.1, 17.7)

NR

NR

NR

Sensitivity analysis were conducted in RCTs only, CCTs with high quality, and obesity-related surgery only and the incidence of IH was basically similar to overall pooled effect.

4RCTs; SZ:513; OR: 0.94 (0.38, 2.31) 3Non-RCTs; SZ:261; OR: 3.74 (0.29, 47.84) 4RCTs; SZ:302; OR: 1.18 (0.47, 2.99) 2Non-RCTs; SZ:194; OR: 2.71 (0.33, 21.95) NR

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Postoperative mortality

NR

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Seroma

11RCTs; SZ:1181; RR: 0.19 (0.09, 0.42)

NR

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Surgical site infection

5RCTs; SZ:346; RR: 0.86 (0.39, 1.91)

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Timmermans et al.[17](2013)

5RCTs; SZ:465; MD: -0.14(-0.75, 0.48) 6RCTs; SZ:612; MD: 17.62(1.44, 33.80) The incidence of IH was basically similar in pre-defined subgroup analysis, sensitive analysis, and influence analysis, which further confirmed the robustness of overall pooled effect estimate.

IH: incisional hernia; SZ: sample size; RCT: randomized clinical trial; CCT: clinical controlled trial; NR: not reported; MD: mean difference; OR: odds ratio; RR: relative risk; CI: confidence interval

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