552731

research-article2014
SRIXXX10.1177/1553350614552731Surgical InnovationBurcharth et al

In Context: Review
Surgical Innovation

Patient-Related Risk Factors for

2015, Vol. 22(3) 303317
The Author(s) 2014
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Recurrence After Inguinal Hernia sagepub.com/journalsPermissions.nav
DOI: 10.1177/1553350614552731

Repair: A Systematic Review and sri.sagepub.com

Meta-Analysis of Observational Studies

Jakob Burcharth, MD, PhD1, Hans-Christian Pommergaard, MD, PhD1,

Thue Bisgaard, MD, DMSc2, and Jacob Rosenberg, MD, DMSc1

Abstract
Background. Several factors influence the risk of recurrence after inguinal hernia surgery; however, a systematic
review and meta-analysis of patient-related risk factors for recurrence after inguinal hernia surgery has not been
performed earlier. Methods. MEDLINE, Embase, and Cochrane databases were searched in June 2013 for studies
evaluating patient-related risk factors for recurrence after inguinal hernia operation. Observational studies evaluating
nontechnical patient-related risk factors for recurrence after inguinal hernia surgery were included. Outcome variables
were grouped under patient demographics, hernia characteristics, connective tissue composition and degradation, habits and
social relations, and conditions related to inguinal hernia recurrence. Results. From a total of 5061 records screened, we
included 40 observational studies enrolling 720651 inguinal hernia procedures in 714917 patients in the systematic
review. Of the 40 studies, 14 studies were included in 8 meta-analyses evaluating sex, hernia type, hernia size, re-
recurrence, bilaterality, mode of admission, age, and smoking as risk factors for recurrence after inguinal hernia surgery in
a total of 378824 procedures in 375620 patients. Conclusions. We found that female sex, direct inguinal hernias at the
primary procedure, operation for a recurrent inguinal hernia, and smoking were significant risk factors for recurrence
after inguinal hernia surgery. This knowledge of patient-related risk factors for recurrence after inguinal hernia surgery
could be implemented in clinical practice.

Keywords
inguinal hernia, recurrence, reoperation, risk factors, systematic review, meta-analysis

Background
Recurrence after inguinal hernia repair remains a clinical
problem with 13% of all groin hernia repairs being per-
formed for recurrent hernias.1 The definitive reason for
recurrence remains unclear; however, risk factors include
technical factors such as surgical technical methods,2,3
methods of anesthesia,4 mesh-fixation techniques,5 sur-
geon experience, and hospital volume.6-8 A wide range of
nontechnical patient-related risk factors such as the her-
nia type,9-11 mode of admission,12 family disposition,13
connective tissue composition and degradation,14,15 and
habits such as smoking16 and convalescence17 affect the
risk of recurrence to varying degrees.
Knowledge of patient-related risk factors combined
with knowledge of the controllable technical risk factors
could reduce the recurrence rate. The purpose of this
study was to provide a systematic overview of nontechni-
cal patient-related risk factors for recurrence after ingui-
nal hernia surgery.
Methods
This systematic review was planned, conducted, and
reported according to the PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) and
MOOSE (Meta-analysis of Observational Studies in
Epidemiology) guidelines whenever appropriate.18-20
Prior to data extraction and data analysis, a detailed
protocol for the review was registered at the PROSPERO
trial registration site (Registration Number: CRD42013
004790).21
1
Herlev Hospital, University of Copenhagen, Herlev, Denmark
2
Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
Corresponding Author:
Jakob Burcharth, Department of Surgery, Herlev Hospital, Herlev
Ringvej 75, Herlev DK-2730, Denmark.
Email: jakobburcharth@gmail.com
304 Surgical Innovation 22(3)
Table 1.PICO(S).
Participants (P) of interest:
Human adults (minimum of 18 years of age) with inguinal
hernias eligible for operation.
Intervention (I) of interest:
Inguinal hernia surgery (acute or elective).
Comparison (C) of interest:
Patients with risk factors versus patients without risk
factors leading to higher or lower risk of recurrence.
Outcome (O) of interest:
Clinical recurrence or reoperation due to recurrence
after inguinal hernia surgery.
Study types (S) of interest:
Comparative or non-comparative observational studies.
The research question that drove this systematic
review was the following: Which nontechnical patient-
related risk factors affect the risk of recurrence after
inguinal hernia surgery?
Study Eligibility
Study Characteristics. This study was performed accord-
ing to PICO(S) (Table 1). We excluded the following
study types based on design: meeting abstracts, editorials,
letters-to-editors, case reports, and randomized studies.
Furthermore, we excluded studies performed in children
(younger than 18 years of age) and studies focusing on
other hernias than inguinal hernias. This review focused
on risk factors, and therefore, we chose only to include
observational exploratory studies and not to include ran-
domized controlled trials (RCTs) in this review since
they are designed to evaluate the effect of treatments and
not to identify patient-related risk factors. Furthermore, it
is not possible to randomize patients according to their
nontechnical patient-related risk factors.
Study Reports Characteristics. No restrictions were made
regarding time of publication. We included only studies
in English and only published records with available data
(no submitted or in press publications). Only full-text
articles were eligible for inclusion (electronic access or
by contacting the responsible corresponding author).
Search Strategy, Study Identification, and
Study Selection Process
A detailed and systematic literature search was conducted
on June 7, 2013, in the MEDLINE, Embase, and Cochrane
databases (Figure 1). The literature search strategy was
developed by the first author along with a professional
medical research librarian and was deliberately made
wide in order not to overlook potentially relevant studies.
We supplemented the literature search from the reference
lists of the included studies as described.22
The potentially eligible records were imported into an
Excel sheet (Office 2011, Microsoft) where duplicates and
non-English records were removed. We commenced with
a screening assessment of the title and abstracts of the
records according to the above-mentioned criteria. For
records deemed not eligible for exclusion, the full-text
articles were obtained and evaluated in detail for inclusion
in the review and meta-analyses. Two reviewers (JB and
HCP) performed each step of the above-mentioned pro-
cess, and any differences were settled by discussion.
Data Collection, Extraction, and Data Items
All the included studies were initially screened to identify
all reported patient-related risk factors for recurrence
after inguinal hernia surgery (ie, variables). After this ini-
tial screening to identify reported variables, all studies
were evaluated again and data were extracted with regard
to whether the studies reported the outcome for each vari-
able. Two reviewers (JB and HCP) performed this
independently.
The collected study data were the following: study
design, statistical methods, number of participants, and
number of inguinal hernia procedures. The type of hernia
at recurrence did not have to be an inguinal hernia and
could also be another type of groin hernia, since focus
was on the risk of recurrence instead of the type of hernia
at recurrence. The extracted outcome variables (patient-
related risk factors for recurrence after inguinal hernia
surgery) were the following:
Patient demographics (age, sex, weight/body mass
index [BMI], positive family history of inguinal
hernia occurrence/operation)
Local hernia characteristics (inguinal hernia sub-
type, inguinal hernia size, inguinal hernia side
[right/left], operation/occurrence of bilaterality vs
unilaterality of inguinal hernia, mode of admission
[acute/elective], operation for a recurrence vs
operation for primary inguinal hernia)
Patient habits and employment (smoking, use of
specific medications, employment, physical activ-
ity, and heavy lifts)
Conditions and diseases hypothesized to relate to
recurrence after inguinal hernia surgery (chronic
obstructive pulmonary disease, varices, appendec-
tomy, obstipation)
Connective tissue composition and degradation in
relation to recurrence after inguinal hernia sur-
gery (collagen I/III ratio, pro-collagen I/III, matrix
metalloproteinase [MMP] levels, tissue inhibitor
of metalloproteinase [TIMP] levels)
Burcharth et al 305
Figure 1. Detailed literature search strategy.
The comprehensive literature search as performed in MEDLINE. The literature search in Embase and Cochrane databases were adapted from
this literature search.
It was not a condition that the outcome variables cho-
sen for this systematic review figured as the primary out-
come variables in the included studies.
We extracted the relative effects (hazard ratio [HR],
relative risk [RR], odds ratio [OR]) of the outcome vari-
ables to be able to compare the results across the studies.
Multivariate adjusted values were preferred when pro-
vided; however, in cases where univariate relative effects
were provided or calculable from raw data they were
included.
Data Synthesis and Variation Between Studies
All outcomes were narratively summarized and quantita-
tive meta-synthesis of each outcome variable was planned
where possible. The review manager (Revman version
5.1, Cochrane Collaboration, 2011) was used for data
synthesis. For typing in data, the generic inverse variance
method was used. The random effects model was chosen
on all outcome variables not assumed to be identically
defined or collected between the studies.23 This was con-
sidered to be the case for all outcome variables.
We expected some variation between the results from
the included studies due to chance alone. Variability in
excess of that was defined as heterogeneity and was con-
sidered to arise from clinical diversity (relating to partici-
pants, interventions, and outcomes) as well as from
methodological diversity (relating to risk of bias). The
between-study heterogeneity was quantified by perform-
ing inconsistency I2 statistics, which reflects the percent-
age of the variability across the included studies that is
due to heterogeneity rather than random chance. We clas-
sified heterogeneity as low, moderate, or high on the basis
of the I2 statistics value of 25%, 50%, or 75%, respec-
tively.24 Meta-analysis of an outcome would only be con-
sidered appropriate if variation of the results was not
considerable (I2 < 75%) and if the amount of information
was sufficient (size and number of trials). If I2 > 75% for
an outcome variable, the pooled effect estimate would not
be presented; however, the graphical depiction of the esti-
mate (Forest plot) would still be presented in order to pro-
vide an overview of the data. In outcome variables with
any heterogeneity (I2 > 0%) and where a small-study
effect was suspected, we tested the pooled effect estimate
using both the random-effects model and the fixed-effects
model. If estimates were equal, the effects from the
smaller studies had little impact on the outcome, whereas
higher effect estimates in the random-effects model would
point toward a small-study effect.
To detect possible publication bias, the relative effect
of the outcome variable was plotted by its inverse stan-
dard error (SE) as a funnel plot. The symmetry of this
funnel plot would be assessed visually to detect possible
publication bias (ie, toward the possibility of smaller
studies with negative results not being published),
acknowledging that other factors such as difference in
trial quality can produce funnel plot skewness.
Assessment of Methodological Risk of Bias
and Outcome Quality
For detecting study-level bias, we used the Newcastle-
Ottawa scale (NOS) developed for evaluating bias in non-
randomized studies25 as recommended by the Cochrane
collaboration.26 The NOS is a star-based assessment
system (range = 0-9) where higher scores indicate lower
risk of bias in the study and lower scores indicate higher
risk of bias. The NOS is adapted to either casecontrol
studies or cohort studies and evaluates 3 topics: selection
of participants (maximum of 4 stars), comparability of
study groups (maximum of 2 stars), and outcome assess-
ment (maximum of 3 stars). The NOS was compiled at
each study to assess the methodological aim of this review
(patient-related risk factors predicting recurrence after
inguinal hernia operation). To simplify the interpretation
of the NOS assessment scores, we defined an NOS score
of 1 to 3 as high risk of bias, 4 to 6 as moderate risk of
bias, and 7 to 9 as low risk of bias. The NOS assessment
was performed unblinded by 2 reviewers (JB and HCP),
and discrepancies were settled by discussion. The com-
piled NOS score is presented as median and range.
Evaluating the general quality of each of the outcome
variables, we used the GRADE (Grading of Recom
mendations Assessment, Development and Evaluation)
306 Surgical Innovation 22(3)
Figure 2. Flow chart of study selection process.
profiler assessment tool (GRADEpro version 3.2). The
GRADE tool uses downgrading and upgrading factors on
the quality of the outcome measurements. The downgrad-
ing factors are risk of bias (compiled NOS score < 7),
inconsistency (heterogeneity measured by the I2 statis-
tics), indirectness, imprecision of the effect estimate, and
publication bias (visualized from the funnel plot). The
upgrading factors are large effect estimates (RR > 2),
confounding changes of the effect estimate that lowers
the effect estimate, and occurrence of a doseresponse
gradient. The GRADE tool then assesses each outcome
variable to be a very low, low, moderate, or high quality
outcome. Observational studies by definition produce
low-quality outcomes measured by GRADE due to the
risk of bias and confounders, in contrast to RCTs that
automatically produce high-quality outcomes.
Results
The literature search yielded 5061 potentially relevant
studies following removal of duplicates and non-English
studies, and a total of 2457 potentially relevant records
were screened (Figure 2). From these, a total of 112 studies
were retrieved in full-text and 40 studies were included in
the systematic review covering a total of 719901 proce-
dures in 714167 patients. A total of 14 studies9-14,16,27-33
were eligible for inclusion in 8 different meta-analyses
evaluating sex, age, hernia type, hernia size, re-recurrence,
Burcharth et al 307

Table 2. Overview of Included Studies and Risk of Bias Assessment Measured by Newcastle-Ottawa Score.

Included in Number of Patients/ Newcastle-Ottawa

Study Study Design Meta-Analysis Number of Procedures Score
El-Dhuwaib et al40 (2012) Cohort 125342/125342 9
Van der Linden et al11 (2011) Cohort + 123917/123917 9
Sevonius et al9 (2011) Cohort + 13165/13165 8
Smigielski et al15 (2011) Case control 150/150 3
Brandt-Kerkhof et al41 (2011) Cohort 191/213 5
Rosemar et al46 (2010) Cohort 49094/49094 9
Choi et al48 (2010) Cohort 944/1065 4
Stylianidis et al28 (2010) Cohort + 90567/90567 9
Jansen et al35 (2009) Cohort 75/75 4
Sevonius et al34 (2009) Cohort 4544/4544 9
Smigielski et al59 (2009) Case control 90/90 5
Matthews et al46 (2007) Cohort 1696/1696 9
Lamb et al50 (2006) Cohort 1283/1682 6
Junge et al13 (2006) Cohort + 229/293 4
Bay-Nielsen et al27 (2006) Cohort + 3696/3696 7
Koch et al12 (2005) Cohort + 6895/6895 8
Lau42 (2004) Case control 100/100 3
Nordin et al10 (2004) Cohort + 59823/59823 9
Junge et al14 (2004) Case control + 78/78 5
Bittner et al33 (2002) Cohort + 6479/8050 4
Zheng et al58 (2002) Case control 5/5 4
Sorensen et al16 (2002) Case control + 544/544 7
Hawasli et al37 (2002) Cohort 708/989 4
Kald et al30 (2002) Cohort + 36390/36390 9
Haapaniemi et al32 (2001) Cohort + 17985/17985 9
Kald et al43 (1998) Cohort 1505/1565 7
Nilsson et al29 (1997) Cohort + 4474/4879 8
Schaap et al38 (1992) Cohort 112/112 6
Ijzermans et al39 (1991) Cohort 170/207 6
Thomas et al48 (1990) Cohort 616/616 7
Sparso et al51 (1983) Cohort 297/297 6
Cahlin et al44 (1980) Cohort 274/285 7
Ross52 (1975) Cohort 260/289 6
Read53 (1975) Cohort 1186/1420 7
Borgstrom45 (1951) Cohort 744/744 5
Nilsson et al31 (1998) Database + 11378/12542 9
Magnusson et al56 (2010) Database 142578/142578 9
Bay-Nielsen et al17 (2004) Cohort 1059/1059 5
Schmedt et al57 (2002) Cohort 5524/6860 6

bilaterality, mode of admission, and smoking as risk factors
for recurrence after inguinal hernia surgery. The studies
included in the meta-analyses covered a total of 378824
procedures in 375620 patients. Eight studies9,32,34-39
reported data exclusively from 37177 recurrent inguinal
hernia procedures in 36859 patients, and the remaining 35
studies focused on primary inguinal hernias.
The designs of the included studies varied from database
studies (n = 15), cohort studies (n = 19), and casecontrol
studies (n = 6). The median number of procedures per
included study was 1123 (range = 5142578). The most
commonly reported outcome variable was the hernia type
(n = 21 studies) followed by operation for a recurrent her-
nia (n = 19 studies). The overall NOS score for all included
studies was 7 (range = 3-9), whereas the overall NOS score
for studies in the meta-analyses was 8 (range = 4-9;
Table 2). In general, the NOS score was lowered since
many studies did not adjusted for possible confounders.
308 Surgical Innovation 22(3)

Figure 3. Meta-analysis of sex as a risk factor for recurrence.

Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. Female sex
was found to be a risk factor for recurrence with a pooled RR of 1.38 (95% CI = 1.28-1.48, P < .001, I2 = 0%).

Figure 4. Meta-analysis of age as a risk factor for recurrence.

Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. Age was
not found to be a risk factor for recurrence in this analysis with an RR of 0.99 (95% CI = 0.84-1.17, P = .9, I2 = 64%).

Patient Demographic Factors as Risk Factor
for Recurrence After Inguinal Hernia Surgery
Sex. A total of 12 studies covering 448065 procedures in
447968 persons10-13,16,27,28,40-44 evaluated sex as a risk fac-
tor for recurrence after inguinal hernia surgery. Of those,
5 studies were eligible for meta-analysis covering 284898
procedures in 284898 persons.10-12,27,28 The overall NOS
score for the studies evaluating sex was 8 (range = 3-9)
and 9 (range = 7-9) for studies in the meta-analysis.
The meta-analysis found female sex to be a risk factor
for recurrence after inguinal hernia surgery with an RR of
1.38 (95% CI = 1.28-1.48, P < .001, I2 = 0%; Figure 3).
No evidence of publication bias was seen in the funnel
plot. The GRADE quality assessment found the level of
quality low, due to the observational design of the studies
and the lack of upgrading factors.
Of the remaining studies not included in the meta-
analysis studying sex as risk factor for recurrence, a total
of 6 studies found no impact of sex on risk of recur-
rence.13,16,41-44 One study found male sex to be a risk fac-
tor for recurrence after open repair (P < .001); however,
that was not case for laparoscopic repair.40 A hypothesis
for the higher recurrence rate in females could be that
femoral hernias were missed at the primary procedure.27
In conclusion, the meta-analysis found female sex to be
a risk factor for recurrence after inguinal hernia surgery.
Age. A total of 15 studies covering 422824 procedures in
422322 persons9-11,13,16,27-29,39-45 evaluated age as a risk fac-
tor for recurrence after inguinal hernia surgery. A total of 4
studies evaluated age above 60 years as a risk factor for
recurrence9,10,29,43 covering 79432 procedures in 78967
persons. The overall NOS score was 8 (range = 3-9) and 8
(range = 7-9) for the studies in the meta-analysis.
The meta-analysis showed no significant impact of
age on the risk of recurrence after inguinal hernia surgery
with a pooled risk estimate of RR of 0.99 (95% CI = 0.84-
1.17, P = .9, I2 = 64%; Figure 4). The heterogeneity was
high, most likely due to clinical diversity of the included
studies. The visualization of the funnel plot did not indi-
cate publication bias.
The remaining studies that evaluated age as a risk fac-
tor for recurrence could likewise not provide a clear con-
clusion regarding age as a risk factor for recurrence. One
study found that persons in the age-group 50 to 70 years
Burcharth et al 309

Figure 5. Meta-analysis of type of inguinal hernia as a risk factor for recurrence.

Abbreviations: DIH, direct inguinal hernia; IIH, indirect inguinal hernia.
Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. A direct
inguinal hernia was found to be a risk factor for recurrence with a pooled RR of 1.91 (95% CI = 1.62-2.26, P < .001, I2 = 10%).

had a significantly lower risk of reoperation compared
with persons younger than 50 years (P < .05).39 Twelve
studies found that age had no impact on the risk of recur-
rence.10,11,16,27-29,40-45 In contrast, a single study found that
age >50 years correlated significantly to increased risk of
recurrence with an OR of 12.88 (95% CI = 1.15-138.94).13
Stratified to open and laparoscopic procedures, it was
shown that high age was a risk factor for recurrence after
laparoscopic hernia surgery, but not after open hernia sur-
gery (P < .01).40
In conclusion, the meta-analysis did not find age to be
a risk factor for recurrence after inguinal hernia surgery.
Weight/Body Mass Index (BMI). A total of 6 studies cover-
ing 52728 procedures in 52653 persons evaluated the
risk of recurrence in relation to weight/BMI.13,44-48 None
of the studies were eligible to include in a meta-analysis
due to measurement differences. The overall NOS score
of the included studies was 7 (range = 4-9).
Three studies found that BMI did not have any impact
on the risk of recurrence.13,44,45 One study found that a
BMI > 25 significantly lowered the risk of recurrence
after inguinal hernia surgery,47 while another study
showed the same tendency, but not significantly.48 The
largest of the included studies, covering more than 49000
patients, found that a BMI of 25 to 30 increased the risk
of recurrence with an RR of 1.19 (95% CI = 1.0-1.40)
compared with a BMI of 20 to 25.46
In conclusion, the included studies pointed at increas-
ing BMI up to 30 to be a risk factor for recurrence after
inguinal hernia surgery.
Positive Family History of Inguinal Hernia.Two studies
including 368 procedures in 304 persons investigated
the effect of a positive family history on the risk of
recurrence after inguinal hernia surgery.13,35 A positive
family history was in the studies defined as more than 2
first-degree family members either operated for or
diagnosed with an inguinal hernia. The studies had a
moderate risk of bias, with both scoring NOS 4. One
study found that recurrence occurred at an earlier age in
patients with a positive family history (P = .04),35 while
another study found that the overall recurrence rate was
not significantly affected with an OR of 8.43
(0.91-78.4).13
In conclusion, no final conclusions could be made
regarding the risk of recurrence in relation to positive
family history of inguinal hernia.
Local Hernia Characteristics as Risk Factor for
Recurrence After Inguinal Hernia Surgery
Inguinal Hernia Subtype.A total of 21 studies covering
228756 procedures in 227041 persons evaluated the risk
of recurrence in relation to the inguinal hernia sub-
type9-13,16,29,31,32,37,39,41-44,47,49-53 Of those, 4 studies evalu-
ating primary inguinal hernias were included in a
meta-analysis evaluating the risk of recurrence of direct
inguinal hernias (DIH) compared with indirect inguinal
hernias (IIH), covering 36971 procedures in 35342 per-
sons.29,31,32,43 The reasons for not including more studies
into the meta-analysis was not reporting relative risk esti-
mates or analyzing re-recurrence after operations for
recurrent inguinal hernias instead of primary inguinal
hernias. The overall NOS score was 7 (range = 3-9), and
9 (range = 7-9) for the studies in the meta-analysis.
The meta-analysis showed that surgery for a primary
DIH was a significant risk factor for recurrence com-
pared with surgery for a primary IIH with a pooled RR
of 1.91 (95% CI = 1.62-2.26, P < .001, I2 = 10%; Figure
5). Limited variability between the included studies was
observed and no evidence of publication bias visualized
by the funnel plot. The pooled effect estimate merely
changed to RR 1.89 (95% CI = 1.62-2.21) when ana-
lyzed by the fixed-effects model, which indicated a lim-
ited small-study effect. The overall GRADE quality
310 Surgical Innovation 22(3)

Figure 6. Meta-analysis of size of hernia as a risk factor for recurrence.

Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. The size of
the hernia was not found to a risk factor for recurrence with a pooled RR of 1.09 (95% CI = 0.92-1.30, P = .33, I2 = 0%).

assessment was low due to the observational design of
the included studies.
Of the 14 remaining studies not included in the meta-
analysis, 7 studies found that the risk of recurrence was
significantly higher after primary operation of a DIH
compared with an IIH.9-12,16,36,47 Stratification by sex
showed that both males12,36 and females12 had higher risk
of recurrence after being operated for a DIH compared
with an IIH. One study examined recurrent inguinal her-
nias and found higher risk of re-reoperation after a DIH
recurrence compared with IIH recurrences.34 The remain-
ing studies found the same tendency that primary opera-
tion for DIH resulted in higher risk of reoperation, but not
significantly.13,37,39,41,44,49-53 No studies found indications
that IIH resulted in higher risk of recurrence than DIH.
In conclusion, the meta-analysis found that operation
for a DIH led to higher risk of recurrence compared with
IIH in both primary and recurrent inguinal hernias.
Inguinal Hernia Defect Size. A total of 4 studies covering
104769 procedures in 104705 persons evaluated the size
of the inguinal hernia defect (as assessed by surgery and
not by clinical evaluation) in relation to the risk of recur-
rence.9,13,28,45 Of those 4 studies, 2 studies were eligible
for inclusion in a meta-analysis, which covered 103732
procedures in 103732 persons9,28 (Figure 6). The overall
NOS score was 7 (range = 4-9) and 8 and 9 for the studies
in the meta-analysis.
The meta-analysis found that the size of the inguinal
hernia defect (<3 cm/>3 cm) did not influence the risk of
recurrence with a pooled RR of 1.09 (95% CI= 0.92-1.30,
P = .33, I2 = 0%; Figure 6). The GRADE quality assess-
ment of this outcome was low, due to the observational
design of the included studies. Of the remaining 2 studies
not included in the meta-analysis, none found a signifi-
cant correlation between inguinal hernia size defect and
the risk of recurrence.13,45
In conclusion, the meta-analysis found that the size of
the inguinal hernia defect did not affect the risk of
recurrence.
Re-Recurrence.A total of 19 studies covering 389447
procedures in 385850 persons evaluated operation for a
recurrent inguinal hernia compared with operation for a
primary inguinal hernia as a risk of recur-
rence.10,12,13,16,29,32-34,39-41,43,44,47,51-54 Of the 19 studies, 7
studies were included in the meta-analysis, which cov-
ered 111739 procedures in 108539 persons.10,12,32,33,43,54,55
The overall NOS score was 7 (range = 4-9), and 8
(range = 4-9) for the studies in the meta-analysis.
The meta-analysis found a pooled RR of 2.2 (95% CI =
2.0-2.42, P < .001, I2 = 6%), which indicated that operation
for a recurrent inguinal hernia increased the risk of recur-
rence (Figure 7). This pooled effect estimate did not change
when testing the outcome variable with the fixed-effects
model, indicating that no small-study effect was present. A
low heterogeneity was found. The GRADE quality assess-
ment found that the quality of this outcome was high, since
a strong association (RR > 2.0) and a doseresponse gra-
dient of recurrent inguinal hernias could be observed. This
was due to the fact that the risk of recurrence increased
cumulatively with the number of recurrences.34
Of the remaining studies not included in the meta-
analysis, 5 studies found significantly higher recurrence
rates after operation for recurrent inguinal hernias com-
pared with recurrence rates after operation for primary
inguinal hernias,13,16,34,47,56 which in one study was the
case for both laparoscopy and open approach.47 Three
studies found no differences in the risk of recurrence,40,41,44
whereas 4 studies found tendencies toward higher recur-
rence rates after operation for recurrent inguinal hernias
(not significantly).39,51-53 One study found that operation
for recurrence was a significant risk factor for earlier
recurrence with an RR of 1.52 (95% CI = 1.36-1.70).56
In conclusion, the meta-analysis found that the risk of
recurrence was significantly increased when being oper-
ated for a recurrent inguinal hernia compared with a pri-
mary inguinal hernia.
Bilaterality. A total of 6 studies covering 176832 proce-
dures in 173925 persons investigated whether bilateral
Burcharth et al 311

Figure 7. Meta-analysis of size of operation for a recurrent inguinal hernia as a risk factor for re-recurrence.
Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. We found
that operation for a recurrent inguinal hernia was a risk factor for re-recurrence with a pooled RR of 2.20 (95% CI = 2.00-2.42, P < .001, I2 = 6%).

Figure 8. Meta-analysis of bilateral inguinal hernia occurrence as a risk factor for recurrence.
Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. Arrows
indicates that the 95% CI extends beyond the depicted range. The size of the hernia was not found to be a risk factor for recurrence with a
pooled RR of 1.08 (95% CI = 0.84-1.37, P = .56, I2 = 3%).

occurrence of inguinal hernia was a risk factor for devel-
oping recurrence compared with unilateral occurrence of
inguinal hernia.13,30,33,38,40,57 A total of 3 studies were
included in the meta-analysis covering 44518 procedures
in 42947 persons.13,30,33 The overall NOS score was 6
(range = 4-9), and 5 (range = 4-7) for the studies included
in the meta-analysis.
The meta-analysis showed that bilateral occurrence of
inguinal hernia was not a risk factor for recurrence with a
pooled OR of 1.08 (95% CI = 0.84-1.37, P = .5, I2 = 3%;
Figure 8). The pooled effect estimate did not change
when the model was changed to fixed-effects, which indi-
cated that no small-study effect was present. The overall
GRADE quality assessment was low due to the observa-
tional design of the included studies.
One study found bilateral occurrence of inguinal her-
nia to be a risk factor for unilateral recurrence,38 while the
remaining 2 studies not included in the meta-analysis did
not find this association.40,57
In conclusion, the meta-analysis did not find bilateral-
ity of inguinal hernia to be a risk factor for recurrence.
Hernia Side.A total of 4 studies covering 3246 proce-
dures in 2667 patients evaluated if the side (right vs left)
of the primary inguinal hernia had influence on overall
the risk of recurrence.13,16,37,53 No studies were eligible
for meta-analysis. All 4 studies showed tendency toward
right-sided inguinal hernias leading to a higher risk of
recurrence; however, none of the studies found this rela-
tion to be significant.13,16,37,53 The overall median NOS
score was 6 (range = 4-7).
In conclusion, no final conclusion could be made
regarding hernia side and risk of recurrence.
Mode of Admission (Acute Versus Elective). A total of 4 stud-
ies covering 73162 procedures in 72697 persons inves-
tigated the relation between risk of recurrence and the
mode of admission (acute vs elective).10,12,29,43 Three
studies were eligible for inclusion in the meta-analysis,
which covered 66267 procedures in 65802 persons.10,29,43
The overall median NOS score was 8 (range = 7-9), and 8
(range = 7-8) for the studies in the meta-analysis.
The meta-analysis did not find that acute admission
compared with elective admission affected the risk of
recurrence with a pooled RR of 1.28 (95% CI = 0.97-
1.70, P = .08, I2 = 24%; Figure 9). This estimate changed
to a pooled RR of 1.21 (95% CI = 1.00-1.46, P = .05, I2 =
24%) when analyzed by a fixed-effects model, which
312 Surgical Innovation 22(3)

Figure 9. Meta-analysis of mode of admission as a risk factor for recurrence.

Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
RR (extended horizontal lines). The pooled RR estimate and 95% CI calculated by the random-effects model are shown by diamonds. Emergency
admission was found just barely not to be a risk factor for recurrence with a pooled RR of 1.28 (95% CI = 0.97-1.70, P = .08, I2 = 24%).

Figure 10. Meta-analysis of smoking as a risk factor for recurrence.

Each study is shown by point estimate of each study (square proportional to the weight given for each study in the analysis) and 95% CI for the
OR (extended horizontal lines). The pooled OR estimate and 95% CI calculated by the random-effects model are shown by diamonds. Arrows
indicates that the 95% CI extends beyond the depicted range. Smoking was found to be a risk factor for recurrence with a pooled OR of 2.53
(95% CI = 1.43-4.47, P = .001, I2 = 0%).

indicated that a minor small-study effect was present. The
overall quality of the outcome measure was by the
GRADE approach evaluated to be of low quality due to
the observational design of the included studies.
In conclusion, the meta-analysis did not find the type
of admission as a risk factor for recurrence.
Patients Social Relations and Habits as Risk
Factors for Recurrence
Smoking.Three studies covering 837 procedures in 773
persons examined the effect of smoking on the recurrence
rate.13,16,38 Two studies were eligible for inclusion in a
meta-analysis13,16 (Figure 10), which found that smoking
was a substantial risk factor for recurrence with a pooled
OR of 2.53 (95% CI = 1.43-4.47, P = .001, I2 = 0%). The
remaining study did not find any relation between smoking
and the risk of recurrence after inguinal hernia surgery.38
The median overall NOS score was 6 (range = 4-7), and 4
and 7 for the studies included in the meta-analysis.
The overall quality assessment of the outcome by the
GRADE approach found the quality level as low. This
emerged by a downgrading because of the moderate risk
of bias in the included studies and an upgrade by a large
effect estimate (OR > 2).
In conclusion, the meta-analysis found that smoking
significantly increased the risk of recurrence after ingui-
nal hernia surgery.
Return to Work and Physical Activity.A total of 5 studies
covering 3995 procedures in 3929 persons examined the
effect of lifting or postoperative convalescence on the
risk of inguinal hernia recurrence.17,39,45,47,52 None of
these studies were eligible for a meta-analysis. Two stud-
ies found that extended hospital admission time and lon-
ger postoperative relaxing did not influence the recurrence
rate.39,52 One study found that instruction in early return
to daily normal activity and hence a short convalescence
after inguinal hernia surgery did not increased the recur-
rence rate.17
Regarding physically demanding jobs, a single study
documented that persons working with manual labor
jobs (blue collar) had statistically lower recurrence rates
than persons working with nonmanual labor jobs (white
collar),45 whereas the last study found that an overall
active daily life was a risk factor for recurrence after
inguinal hernia repair.47 The median NOS score was 6
(range = 5-9).
In conclusion, the available literature could not pro-
vide conclusions on the impact of return to work and
Burcharth et al 313
physical activity on the risk of recurrence, and given the
moderate risk of bias of the included studies the quality of
the conclusion was not optimal.
Other Nontechnical Risk Factors for Recurrence.A single
study showed that unemployment did not lead to higher
recurrence rates after inguinal hernia surgery compared
with employed persons.16 The absence of a caregiver has
in a single study been correlated to a higher risk of recur-
rence.47 Medications, such as steroids and ACE inhibi-
tors, have not been found to influence the risk of
recurrence after inguinal hernia surgery.13 A moderate
intake of alcohol (1-7 drinks per week) was found to be
protective against risk of recurrence with an OR of 0.30
(95% CI = 0.10-0.93) compared with alcohol absti-
nence.16 Last, a higher American Society of Anesthesiol-
ogist class predicted a higher risk of recurrence after
inguinal hernia surgery in one study.47
In conclusion, none of the studies investigating other
nontechnical risk factors for recurrence were appropriate
for meta-analysis, and broad conclusions could therefore
not be made regarding these nontechnical risk factors
impact on the risk of recurrence. Each variable was exam-
ined by a limited number of studies, so the conclusions
should be seen as hypothetical rather than final.
Conditions and Diseases Hypothesized to
Relate to Recurrence After Inguinal Hernia
Surgery
A total of 4 studies covering 1162 procedures in 1076
patients investigated other conditions and diseases in
relation to the risk of recurrence after inguinal hernia sur-
gery.13,16,38,41 No studies were eligible for meta-analysis.
The median overall NOS score was 5 (range = 4-7). The
diseases that were investigated included constipation,
chronic obstructive pulmonary disease, varices, appen-
dectomy, and incisional herniation. None of the diseases
was found to correlate to the risk of recurrence.
In conclusion, due to the moderate risk of bias in the
included studies and the lack of meta-analyses final con-
clusions could not be made.
Connective Tissue Composition and
Degradation
A total of 4 studies covering 323 procedures in 323
patients evaluated the connective tissue composition and
degradation in relation to risk of recurrence.14,15,58,59 None
of the studies were eligible for meta-analysis due to non-
comparable study designs.
One study found a lowered collagen type-I/III ratio in
removed meshes from patients with recurrent inguinal
hernias compared with mesh removal due to chronic pain
(P < .001) and postoperative infections (P = .014).14
Furthermore, a lowered collagen type-I/III ratio was
found in the meshes from the recurrent inguinal hernia
group compared with patients with primary hernias (P =
.003).14 A lowered pro-collagen type-I/III ratio was found
in skin fibroblast in patients with recurrent inguinal her-
nias compared with a control group (P < .01),58 and the
same study found that the level of matrix metalloprotein-
ase-1 and 13 (MMP-1, MMP-13) was higher in the recur-
rent inguinal hernia group compared to control groups
(P < .01).58 The level of MMP-2 has been investigated
and found higher in recurrent inguinal hernias compared
with primary inguinal hernias (P < .01).15,59 Last, the tis-
sue inhibitor of matrix metalloproteinase-2 (TIMP-2)
was found at higher concentrations in the serum of
patients with inguinal hernia recurrences compared with
primary inguinal hernias and control groups.15
In conclusion, due to the methodology and heteroge-
neity of the included studies no final conclusions could be
made on this subject.
Discussion
Through meta-analyses, we found that operation for a
DIH, operation for a recurrent inguinal hernia, and smok-
ing were risk factors for recurrence after inguinal hernia
surgery. Furthermore, the narrative summation of data
identified age below 65 years, a positive family history of
inguinal hernia, right-sided primary operations for ingui-
nal hernia, emergency procedures, and connective tissue
degradation as possible risk factors for recurrence.
Recurrence after inguinal hernia surgery most likely
holds a multifactorial etiology with a combination of
patient-related and non-patient-related risk factors. We
found that female sex was a significant risk factor for
recurrence. The reason for this is unknown; however, it
has been hypothesized to be the result of a high percent-
age of femoral hernia recurrences after primary inguinal
hernia surgery, which could indicate overlooked femoral
hernias during the primary procedure.27,60-62 This problem
is most likely to occur in open surgery in contrast to lapa-
roscopic surgery, where the overview of the groin area
includes all possible hernia orifices. As a consequence of
this, it could be recommended that females primarily
should be operated laparoscopically.7,63,64 Some state that
the higher risk of recurrence after a DIH operation is due
to the lack of mesh overlap medially over the pubic tuber-
cle,65,66 while other indicative factors lie in the more fre-
quent and distinct connective tissue changes in patients
with DIH compared with patients with other inguinal her-
nia types.67-71
We found solid evidence of a high recurrence risk after
operation for a recurrent inguinal hernia compared with a
314 Surgical Innovation 22(3)
primary inguinal hernia (Figure 7). This could be caused
by the fact that the majority of recurrent inguinal hernias
are direct inguinal hernias.10,72 Furthermore, a single
study documented that the re-recurrences developed
faster than recurrences after primary procedures,56 while
another study found that the cumulative re-recurrence
rate increased with each recurrence up to the fourth
recurrence.34
Recurrence in relation to smoking has been hypothe-
sized to occur due to a compromised collagen production
in smokers,73,74 due to temporary tissue hypoxia,75 or due
to excessive proteolysis, which has been found to impair
wound healing.76 This is in contrast to primary inguinal
hernia development, where 2 epidemiologic studies
showed that active cigarette smoking decreased the risk of
inguinal hernia development.77,78 This could indicate that
different pathophysiology is involved in primary and
recurrent inguinal hernia development. In a clinical set-
ting with regard of reducing the risk of postoperative com-
plications in general,79,80 it seems reasonable to advise
patients to quit smoking prior to and after surgery.
Several limitations of this study should be recognized.
Being a literature review, the data presented are limited to
the literature search and the extraction of outcome vari-
ables. That said, the data material for this review were
substantial mainly due to the inclusion of the Danish and
Swedish hernia registers. Our literature search was lim-
ited to the English language studies and therefore subject
to possible language bias, despite the fact that including
solely English language studies has been shown to have
limited impact on final conclusions.81 Furthermore, anal-
yses from observational studies should always be read
with attentiveness due to the possibility of unadjusted
confounding factors. Regarding bilaterality of inguinal
hernia, we defined recurrence as any recurrence (not side-
specific), which is a limitation since the risk of recurrence
thereby is higher. Furthermore, we could not correct for
this in the review.
This study represents the largest and most method-
ological and rigorously performed review on this topic.
The extensive search strategy limited the risk of over-
looking potentially relevant studies that could have been
overlooked. A methodological strength was the combined
use of risk of bias assessment (NOS) and quality assess-
ment (GRADE approach). Due to the number of included
studies and the number of included patients, our findings
are assumedly representative of the true effects.
Several technical controllable risk factors for recurrence
after inguinal hernia surgery are known. Suturing an ingui-
nal hernia instead of mesh-repairing the hernia is a major
risk factor for recurrence.82,83 Using short-term absorbable
mesh fixation rather than long-term absorbable or nonab-
sorbable sutures produces higher recurrence rates.5
Laparoscopic hernia surgery carries a significantly higher
risk of recurrence compared with open hernia surgery,84 and
local anesthesia carries a higher risk of recurrence com-
pared with general anesthesia for primary hernia surgery.10
Conclusion
Though recurrence after inguinal hernia surgery remains
a clinical problem, a systematic and comprehensive over-
view of the nontechnical, patient-related risk factors for
recurrence has not been published earlier. In conclusion,
we found that female sex, operation for a direct inguinal
hernia, operation for a recurrent hernia, and smoking sub-
stantially increased the risk of recurrence after inguinal
hernia surgery.
Author Contributions
Jakob Burcharth: Initiated the study, designed the study, wrote
and registered the protocol, performed literature search, screen-
ing, bias assessment and data extraction. Wrote initial draft,
coordinated revisions, and accepted final edition.
Hans-Christian Pommergaard: Designed the study, per-
formed literature screening, bias assessment and data extrac-
tion. Performed critical revision and accepted final edition.
Thue Bisgaard: Designed the study. Performed critical revi-
sion and accepted final edition.
Jacob Rosenberg: Initiated the study and designed the study.
Performed critical revision and accepted final edition.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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