Lightweight versus Heavyweight mesh for open repair of inguinal hernia
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to systematically analyse the RCTs to compare the effectiveness of LWM versus HWM in patients undergoing open inguinal hernia repair.
Background
Description of the condition
Laparoscopic and open inguinal hernia repair are among the commonest operative interventions for an estimated 16% of symptomatic groin hernias in general surgical patients (Sarosi 2011; Thompson 2008). Approximately 20 millions groin hernioplasties are performed each year worldwide, over 17000 operations in Sweden, over 12000 in Finland, over 80,000 in England and over 800,000 in the USA (Cheek 1998; Heikkinen 1998; Rutkow 2003; Swedish Hernia Register 2007). Tension‐free mesh repair of inguinal hernia, called the “Lichtenstein repair” has become the gold standard because of its lower recurrence rates compared to old‐style posterior wall darning or Shouldice repair (Kingsnorth 2000; Prior 1998; Scott 2001;Zieren 1998). Since the introduction of mesh in inguinal hernioplasty, the reported incidence of post‐operative chronic groin pain has increased and ranges from 10% to 54% of patients undergoing hernia surgery (Bay‐Nielsen 2001; Callesen 1999; Poobalan 2001; Staal 2008). The cause of post‐operative groin pain in hernia surgery is multifactorial. The aetiological factors leading to post‐operative chronic groin pain include inguinal nerve irritation by the sutures or mesh (Heise 1998), inflammatory reactions against the mesh (Di Vita 2000) or simply scarring in the inguinal region incorporating the inguinal nerves (Morris‐Stiff 1998; Nahabedian 1997; Stulz 1982). The association of post‐operative chronic groin pain with mesh repair of inguinal hernia is a complex mechanism that possibly entails an extensive foreign body type local tissue inflammatory reactions to mesh biomaterial, bio‐incompatibility and abdominal wall compliance reduction (Aasvang 2007; Klinge 1999). Another important and a valuable factor which has been reported to influence the development of chronic groin pain is the use of various mesh fixation techniques. Suture fixation, staple fixation, tacker fixation, synthetic glue fixation, autologous fibrin glue fixation and no‐fixation are reported to be associated with variable incidence of chronic groin pain (Abdelhamid 2011; Anadol 2011; Negro 2011; Novik 2011; Paajanen 2011; Wong 2011). In addition to surgical aspects, the patient related factors which may potentially contribute and influence the course of chronic groin pain are anxiety, depression, stress, environment, and the use of analgesics for other pain (Aasvang 2007; Kehlet 2011; Staal 2008). Modifications are being introduced quite regularly to tackle the all possible factors responsible in the development of chronic groin pain (Alfieri 2011; Kehlet 2011). Therefore, one of the causative factors is the use of heavyweight mesh in open inguinal hernia repair. The heavyweight polymers of the mesh induce severe local foreign body reaction and extensive fibrotic scar formation, consequently entrapment of regional nerves in scarred tissue results in the development of chronic groin pain (Hakeem 2011; Klosterhlafen 1998; Klosterhlafen 2005).
Description of the intervention
The most frequently used biomaterial in all forms of hernia repair is polypropylene which offers maximum mechanical stability at hernial defect resulting in stiff and non‐flexible greatest scar formation to ensure a resilient hernia repair once mesh biomaterial is incorporated in abdominal wall. However, it produces a segment of abdominal wall with excessive tensile strength that is not adapted to local tissue leading to stiffness and foreign body sensations. Polymers of biomaterial used to construct mesh are considered physically and chemically inert, non‐immunogenic and non‐toxic but they can still trigger locally an extensive inflammatory adverse reaction called foreign body reaction (Bhardwaj 1997; Klosterhlafen 2005). If this reaction is too strong and unremitting, could together with hazards of bio‐incompatibility and mis‐matched tensile strength of the mesh play a key role in the development of chronic groin pain (Poobalan 2001; Poobalan 2003). Additionally, mesh biomaterial is directly in contact with vas deferens and testicular vessels during laparoscopic inguinal hernia repair, widespread regional fibrosis could leads to dysfunction of these structures resulting in fertility problems and testicular pain (Ridgway 2002; Shin 2005). In view of the fact that inflammatory reaction to biomaterial of heavyweight mesh (HWM) correlates with the weight of mesh (amount of polymer expressed as gm/m2) and pore size of the material inserted, the concept of lightweight mesh (LWM) was developed to minimize the content of non‐absorbable foreign material with pore size of more than 1 mm (Klosterhlafen 1998). A LWM is either composite mesh, containing both absorbable and non‐absorbable synthetic material (sometimes coated with titanium), or a reduced weight of non‐absorbable components. A LWM is defined as a surgical mesh (Klinge 1999; Klosterhlafen 2005) with tensile strength of 16 N/cm, elasticity of 20% to 35% at a tensile of 16 N/cm, pore size more than 1 millimetre and woven by lightweight polymers of biomaterial usually less than 50 g/m2. A LWM is thought to reduce the incidence of chronic groin pain and foreign body sensation compared with conventional HWM due to its greater biocompatibility and its matching elasticity with the abdominal wall (Champault 2005; Gao 2010; Weyhe 2007). There are conflicting and equivocal results following the use of LWM in open inguinal hernia repair in terms of chronic groin pain and potentially higher risk of hernia recurrence.
How the intervention might work
The strategies to avoid long‐term complications of open inguinal hernia repair resulting from exaggerated foreign‐body reaction induced by HWM have been adequately implemented and reported with variable outcomes. One of the suggested solutions was to limit the amount of heavyweight component in HWM to use a low‐density Polypropylene mesh reinforced by an absorbable biomaterial. Absorbable component would provide initial strength along with non‐absorbable polymer but soon it is absorbed, hence, limiting local inflammation and foreign‐body reaction. The first mesh that is partially absorbable and it is commercialised consists of non‐absorbable Polypropylene and absorbable polyglactin 910 fibers, with a density of 83 g/m2 in total, with 32 g/m2 of Polypropylene and 51 g/m2 of Polyglactin (Di Vita 2010; Junge 2002; Krause 2006; Rosch 2003). Increased bio‐compatibility and reduced incidence of chronic groin pain has been reported after insertion of both old and new generations of LWM such as lightweight Polypropylene, Polypropylene‐Polyglactin, beta‐D‐glucan, titanium‐coated Polypropylene and Polypropylene –Poliglecapron (Akolekar 2008; Hollinsky 2008; Khan 2006;Scheidbach 2004; Schopf 2011).
Why it is important to do this review
By analysing the published randomised controlled trials (RCTs) comparing the effectiveness of LWM versus HWM according to the principles of meta‐analysis, authors will attempt to reach a conclusion and recommend the routine use of LWM in open inguinal hernia repair in order to avoid long‐term complications such as chronic groin pain, foreign body sensations and recurrence.
Objectives
The objective of this review is to systematically analyse the RCTs to compare the effectiveness of LWM versus HWM in patients undergoing open inguinal hernia repair.
Methods
Criteria for considering studies for this review
Types of studies
We will analyse the RCTs comparing the effectiveness of LWM versus HWM in open inguinal hernia repair.
Types of participants
We will include RCTs on patients of any age, any gender, on both elective and emergency open inguinal hernia repair whatever the indication is i.e. groin lump, groin pain, inguinoscrotal lump, unilateral, bilateral, recurrent hernia. We will consider inclusion of trials in any language of publication, regardless of number of patients and whether hernia is acute in origin or chronic.
Types of interventions
We intend to compare the short‐term outcomes and long‐term outcomes following the use of LWM versus HWM in patients undergoing open inguinal hernia repair.
Types of outcome measures
Primary outcomes
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Chronic groin pain defined as the presence of groin pain after 3‐6 months of open inguinal hernia repair with either LWM or HWM.
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Recurrence: Presence of recurrent hernia in groin confirmed clinically as well as radiologically.
Secondary outcomes
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Postoperative pain
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Operation time
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Testicular atrophy, infertility, and pain
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Foreign body sensations in groin
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Sensory impairment in groin
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Limitations of mobility due to groin stiffness
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Postoperaitve morbidity (we will record and analyse all adverse events such as wound haematoma formation, wound seroma formation, wound infection, urinary retention, urinary tract infections, respiratory tract infection and any other untoward complication
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Postoperative mortality
Search methods for identification of studies
Electronic searches
Will will search the following electronic databases:
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The Cochrane Colorectal Cancer Group (CCCG) Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (Appendix 1) on The Cochrane Library,
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MEDLINE ( Appendix 2),
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EMBASE (The Intelligent Gateway to Biomedical & Pharmacological Information (Appendix 3),
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A filter for identifying relevant studies recommended by The Cochrane Collaboration (Higgins 2008) will be used to filter out irrelevant studies in Medline and Embase
The titles and abstracts of all papers identified by the search strategy will be independently assessed for inclusion, using a study eligibility form developed for this purpose. Full text copies of all potentially relevant studies will be obtained and assessed for inclusion. Any disagreements will be resolved by mutual consensus.
Searching other resources
The references from the included studies will be searched to identify more trials. The 'related article' function of MEDLINE will also be searched thoroughly in order to identify additional studies. Websites responsible for the registration of the randomised controlled trials will be searched to find out if there is recent trial running or ready to publish on this subject. We will attempt to gather information on all published, unpublished and ongoing trails from all possible data sources. If necessary, a personal communication by authors will be made to author for correspondence in published trials for further information on data or clarification. In addition, colorectal and hernia experts, specialist surgeons and pharmaceutical companies involved in provision of necessary equipment may be contacted and asked to provide details of outstanding clinical trials or any relevant unpublished materials. The international societies of colorectal surgery and hernia surgery will also be contacted and asked to provide information on any unpublished studies.
Data collection and analysis
Data will be collected on the Excel spread sheet separately by three authors (MSS, CL, MKB) and it will be further confirmed by the fourth author (PS). The conflict will be resolved by mutual agreement among authors. We will conduct the systematic review according to this protocol and the recommendations by The Cochrane Reviewers' Handbook (Higgins 2008; Review Manager 2008). The statistical analysis will be performed by MSS and will be further confirmed by PS and MKB. The software package RevMan 5.1.1 (Review Manager 2008) provided by The Cochrane Collaboration will be used for analysis. The odds ratio (OR) with a 95 percent confidence interval (CI) will be calculated for binary data variables, and the mean difference (MD) with a 95 percent CI for continuous data variables will be calculated. If the mean values are not available for continuous outcomes, median values will be used for the purpose of meta‐analysis. If the standard deviation is not available, it will be calculated according to the guidelines of The Cochrane Collaboration (Higgins 2008). This will involve the assumptions that both groups had the same variance, which may not be true. The random‐effects model (DerSimonian 1986) and the fixed‐effect model (DeMets 1987) will be used to calculate the combined outcome in both binary and continuous variables. The Mantel‐Haenszel method will be used for the calculation of OR under the fixed effect model, and the DerSimonian/Laird method will be used for the calculation of OR under the random effect model (Egger 2006). In a sensitivity analysis, 0.5 will be added to each cell frequency for trials in which no event occurred in either the treatment or control group, according to the method recommended (Deeks 2001). The estimate of the difference between both techniques will be pooled, depending upon the affect weights in results determined by each trial estimate variance. The forest plot will be used for the graphical display of results from the meta‐analysis. The square around the estimate will stand for the accuracy of the estimation (sample size) and the horizontal line will represent the 95% CI extraction of data. We will record the inclusion and exclusion criteria in each trial that fulfils our criteria for inclusion.
Following details on methods will be extracted:
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Technique of open inguinal hernia repair
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Use of prophylactic antibiotics
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Type of meshes used
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Peri‐operative untoward events
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Post‐operative untoward events
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Measuring scales of different variables
The following data on randomisation and blinding procedure will be extracted:
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Number of randomised patients
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Number of patients not randomised and reasons for non‐randomisation
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Exclusion after randomisation
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Drop‐outs
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Blinding of patients and observers
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'Intention‐to‐treat' analysis
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Internal validity
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External validity
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Power calculations
Selection of studies
Studies will be selected according to predefined inclusion criteria. We will analyse the RCTs comparing the effectiveness of LWM versus HWM in open inguinal hernia repair.
Data extraction and management
We will extract, collect and manage data as described above.
Assessment of risk of bias in included studies
We will define the methodological quality as the confidence that the design and report restrict bias in the intervention comparison (Higgins 2008; Moher 1998) and four important parameters (randomisation technique, allocation concealment, blinding, intention to treat analysis) for a high quality randomised controlled trial are clearly described in the reported study. We will also look for power calculation and strength of the trial in order to score it precisely and accurately. Due to the risk of overestimation of intervention effects in randomised trials with inadequate methodological quality (Higgins 2008;Kjaergard 2001; Moher 1998; Schulz 1995), we will assess the influence of methodological quality as follows.
Generation of the allocation sequence
Low, if the allocation sequence was generated by a computer or random number table. Drawing of lots, tossing of a coin, shuffling of cards, or throwing dice will be considered as adequate if a person who was not otherwise involved in the recruitment of participants performed the procedure. Unclear, if the trial was described as randomised, but the method used for the allocation sequence generation was not described. Inadequate, if a system involving dates, names, or admittance numbers were used for the allocation of patients. These studies are known as quasi‐randomised and will be excluded from the present review when assessing beneficial effects.
Allocation concealment
Low, if the allocation of patients involved a central independent unit, on‐site locked computer, or sealed envelopes. Unclear, if the trial was described as randomised, but the method used to conceal the allocation was not described. High, if the allocation sequence was known to the investigators who assigned participants or if the study was quasi‐randomised.
Double/blinding or masking
Low, if the trial was described as double blind and the method of blinding was described. Unclear, if the trial was described as double blind, but the method of blinding was not described. Not performed, if there was no blinding at all.
Follow‐up/intention to treat analysis
Low, if the numbers and reasons for dropouts and withdrawals in all intervention groups were described or if it was specified that there were no dropouts or withdrawals. Unclear, if the report gave the impression that there had been no dropouts or withdrawals, but this was not specifically stated. High, if the number or reasons for dropouts and withdrawals were not described.
Trial quality scoring
We will score each study according to methods recommended by Cochrane Group (Higgins 2008) in order to define risk of bias, power of the study, presence or absence of blinding and calculations based on the intention to treat analysis. Each trial will be scored as follows: score A (adequate), score B (unclear), score C (not concealed) and score D (not done). Trials scoring A and B will be included and trials scoring C and D will be excluded.
Unit of analysis issues
Measures of treatment effect
The OR with a 95 percent confidence interval (CI) will be calculated for binary data variables, and the mean difference (MD) with a 95 percent CI for continuous data variables will be calculated. If the mean values are not available for continuous outcomes, median values will be used for the purpose of meta‐analysis. If the standard deviation is not available, it will be calculated according to the guidelines of The Cochrane Collaboration (Higgins 2008). This will involve the assumptions that both groups had the same variance, which may not be true.
Unit of analysis issues
We will try to describe any possible issues relating to the unit of randomisation/analysis – for example cluster randomised trials, crossover trials and repeated measures etc.
Dealing with missing data
We will contact the first author via personal communication in order to get missing data. If further information are required from any source we will contact every relevant person involved in running of the published trial. If missing data could not be achieved and that particular trial does not score according to our inclusion criteria we will exclude that trial and explain it in the table giving details about excluded trials.
Assessment of heterogeneity
In case of heterogeneity, only the results of the random‐effects model will be reported. Heterogeneity will be explored using the Chi2 test, with significance set at P < 0.05, and it will be quantified (Higgins 2002) using I2 statistic, with a maximum value of 30 percent identifying low heterogeneity (Higgins 2008).
Assessment of reporting biases
We will consider all measures to reduce the impact of reporting biases such as outcome selection bias and publication bias. Reviewers will also consider checking on trials registers encompassing outcomes of each trial, to detect any outcome reporting bias. We will attempt to use funnel plots to assess potential impact of publication bias. The potential impact of missing data by conducting sensitivity analyses, imputing ‘best‐case/worst‐case’ to see whether results are robust to inclusion/exclusion of missing data will be evaluated.
Data synthesis
Data of all primary and secondary outcomes will be synthesized on the Revman 5 (Review Manager 2008) in order to achieve a summative outcome
Subgroup analysis and investigation of heterogeneity
We will attempt to study if some difference exists between trials with short‐term follow up (3‐6 months) and long‐term follow up (more than a year). We will perform a sensitivity analysis in order to compare the intervention effect in trials with high methodological quality (i.e. trials with adequate generation of the allocation sequence, allocation concealment, and blinding) to that of trials with low methodological quality (i.e., trials not having one or more adequate component). We will attempt to analyse if some difference exists between various groups of patients having primary inguinal hernia, unilateral hernia, bilateral hernia and recurrent inguinal hernia. Furthermore, we will explore causes of heterogeneity (defined as the presence of statistical heterogeneity by Chi2 test with significance set at P value less than 0.10 and measure the quantities of heterogeneity by I2 statistic (Higgins 2002) by comparing different groups of trials stratified according to patient risk factors, level of experience of the surgeon, and other factors that may explain heterogeneity. Clinical and methodological causes of the heterogeneity will be searched in reported trials and it will be clearly documented in the review.
Sensitivity analysis
Sensitivity analysis will be attempted by using funnel plot in order to determine potential bias in the reported trial and isolate the outliers.
