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. 2020 Aug 13;10:13720. doi: 10.1038/s41598-020-70641-7

Surgical procedures in the pilonidal sinus disease: a systematic review and network meta-analysis

Siwei Bi 1, Kaibo Sun 2, Shanshan Chen 2, Jun Gu 3,✉
PMCID: PMC7426950  PMID: 32792519

Abstract

The most appropriate surgical treatment for pilonidal sinus disease (PSD) is still in dispute. This study aims to comprehensively compare the outcomes of surgical interventions using network meta-analysis. Randomized controlled trial studies were searched systematically to identify all eligible studies in multiple databases and previous publications and Bayesian network meta-analysis was performed. Our primary outcome was the recurrence rate. Differences in the findings of the studies were explored in meta regressions and sensitivity analyses. The risk of bias of each study was assessed using the Cochrane risk of bias tool. Confidence in evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). A total of 39 studies and 5,061 patients were identified and the most common surgical intervention was the Limberg flap. In network meta-analysis, modified Limberg flap and off-midline closure were associated with the lowest recurrence rate. However, the Karydakis flap was associated with shorter operation time by several minutes compared with other interventions and few significant results were found in other outcomes. Modified Limberg flap and off-midline closure provided relatively low recurrence and complications rates. Therefore, they could be two promising surgical interventions for PSD patients.

Subject terms: Diseases, Outcomes research

Introduction

Pilonidal sinus disease (PSD) is a tract or cavity of the sacrococcygeal region characterized by repeated infection and chronic inflammation. PSD reportedly has an incidence rate of 26 per 100,000 people and predominately affects young males1. Risk factors include poor hygiene, obesity, and unhealthy behavior such as prolonged sitting2. Presenting symptoms vary from acute to chronic, with one or more non-inflamed pits in the natal cleft as the most common manifestation1,3. Although it is a benign disorder, it can be fairly painful and cause absence from work and school that greatly affects the quality of life. Moreover, it has a high risk of recurrence and brings many complications such as infection, chronic nonhealing wounds, and even squamous cell carcinoma within sinus tracts. Due to the constant exposure to pathogenic microbes, the recurrent abscesses can usually last for many years3–5. Therefore, the recurrence rate has become an important parameter for evaluating the treatments’ effects.

Clinicians nowadays are facing various surgical choices in treatments of PSD except excision and primary closure (PC), e.g., the off-midline approach including the Limberg flap (LF) and Karydakis flap (KF). LF is considered to be an effective treatment because of its low recurrence and complication rate in addition to a short healing time and hospital stay6. Meanwhile, KF is associated with significantly lower rates of complications and recurrence compared with excision only7. Some reports showed that the LF had a lower rate of postoperative complications and greater cosmetic satisfaction than KF8,9, while others reported that there are no significant differences between LF and KF10,11. Besides, minimally invasive techniques (MIT) such as phenol injection, unroofing and marsupialization, video-assisted ablation12 and endoscopic sinus treatment13 are also emerging as alternative procedures.

Network meta-analysis (NMA) facilitates the comparisons between collected interventions and analyzes the pooled data by connecting a network of evidence. It can also give a relative ranking of treatments included14. The obvious advantage is that all comparisons can be evaluated simultaneously because the indirect comparisons gaps can be filled. Additionally, with the combination of direct and indirect evidences, a greater statistical power and precision can be obtained15.

Literature search depicts, few previous pairwise meta-analysis comprehensively integrated all the surgical techniques and measured their effect in a wide range of outcomes. The aim of this study is to perform an NMA with randomized, controlled trials (RCTs) from present publications focusing on the comparisons of surgical interventions for PSD and to better inform clinical practice.

Results

Search results, study characteristics

The flowchart for the study selection process is shown (Fig. 1). A total of 295 studies was selected from the aforementioned databases for further screening. We excluded 177 duplicated articles, meta-analysis and systematic review (n = 16), and 137 other articles because of irrelevant topics (n = 67). However, Milone12,16 et al. published two papers reporting the same clinical trial in 2020 and 2016. We only included the one in 2020 to gain results from a longer follow-up duration. In the end, a total of 39 controlled studies with 5,061 participants were included for this meta-analysis7,9,16–52. The detailed classification and definition of treatments are documented in Supplementary Table S1. The transitivity of potential effect modifiers is illustrated. (Fig. 2) Notably, the majority population of the present study were adult males with an average follow-up duration of 24 months. The most frequent intervention used in surgical practice was LF. The number of studies published in the Mediterranean outnumbered the other regions (e.g., Pakistan, Switzerland, Netherlands, etc.) in 6 years. The LF interventions gained the most attention which was selected as an intervention for comparison in 20 studies. There are more studies that not specifying enrolled patients were primary or not than the ones that clarified. Only the study conducted by Bali53 et al. specifically included recurrent PSD patients. There were three outliers in male proportion and five in average follow-up duration. The detailed information was tabulated in Supplementary Table 2. The enhanced funnel plots were illustrated for potential publication bias detection and most of the comparisons in our study showed little bias (Supplementary Figs. S1–S7).

Figure 1.

Figure 1

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Flowchart for searching and identifying eligible studies.

Figure 2.

Figure 2

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The transitivity analysis of potential effect modifiers (A). The geography information (Mediterranean or other regions) for the included trials. (B) The frequency of each surgical intervention published in clinical trials. (C) The patient information (primary, recurrent or not specified) for each intervention. (D–F) The male proportion, median age, and average follow-up duration (month). KF Karydakis flap, PO primary open, PC primary closure, LF Limberg flap, MLF modified Limberg flap, OMC off-midline closure, MIT minimal invasive technique.

Study quality assessment and grading the evidence of the network meta-analysis using CINeMA

The summary risk of bias assessment of the 39 included studies was illustrated in Fig. 3. The authors showed the results of each quality item as percentages across studies. Most of the studies are with low risk of bias in all the items. Three studies showed a high risk of bias in allocation sequence concealment, blinding of participants and personnel and selective reporting. Two studies showed incomplete outcome data and other biases. Our judgments described below are based on the recommendations of the online documentation of CINeMA (https://cinema.ispm.ch/#doc). The results were summarized in Table 1 and showed the majority of comparisons were graded as moderate confidence. The most frequent downgrading reason is imprecision.

Figure 3.

Figure 3

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Summary of risk of bias of the included randomized controlled trials.

Table 1.

Summary meta-analysis results for recurrence and infection.

Outcome Comparison Sample size Number of studies Omited study Paiwise meta-analysis Network meta-analysis Node splitting (p-Value) Nature of evidence CINeMA level Downgraded reason
RR/SMD 95% CI I2 RR/SMD 95% CI
Recurrence PO vs. LF 142 2 – 1.28 0.49 3.32 75 – – – – – – –
PO vs. MIT 220 2 – 1.19 0.64 2.2 78 – – – – – – –
PC vs. KF 225 2 – 1.5 0.43 5.22 33 1.54 0.57 4.39 0.9988 Mixed Moderate Heterogeneity
PC vs. LF 957 8 – 5.39 2.84 10.23 30 1.83 0.87 3.84 0.0607 Mixed Low Heterogeneity, incoherence
PC vs. MLF 180 2 – 4 0.88 18.26 0 2.76 0.99 7.77 0.8402 Mixed Moderate Heterogeneity
PC vs. OMC 374 3 – 0.97 0.47 2.02 0 2.73 1.11 7.66 0.0129 Mixed Low Heterogeneity, incoherence
PC vs. MIT 208 3 – 5.36 0.7 41.23 0 1.35 0.35 4.76 0.99705 Mixed Moderate Heterogeneity
KF vs. LF 849 5 – 1.14 0.66 1.96 25 1.19 0.46 2.9 0.98485 Mixed Moderate Imprecision
KF vs. MLF 719 4 Sit, M 1.58 0.08 30.11 56 1.79 0.56 5.72 0.0147 Mixed Moderate Heterogeneity
KF vs. OMC 120 1 – – – – – 1.76 0.55 6.23 0.3072 Mixed Moderate Imprecision
KF vs. MIT – – – – – – – 0.89 0.17 3.89 – Indirect Low Imprecision,incoherence
LF vs. MLF 492 2 – 3.7 1.2 11.45 0 1.51 0.53 4.39 0.0179 Mixed Low Imprecision,incoherence
LF vs.OMC 203 2 – 0.98 0.15 6.46 0 1.49 0.55 4.5 0.51435 Mixed Moderate Imprecision
LF vs. MIT 140 1 – – – – 0.74 0.17 2.95 – Mixed Moderate Imprecision
MLF vs. OMC 409 3 – 2.19 0.78 6.12 0 0.99 0.36 3.07 0.0114 Mixed Low Imprecision,incoherence
MLF vs. MIT – – – – – – 0.49 0.1 2.14 – Indirect Low Imprecision,incoherence
OMC vs. MIT 191 2 – 0.88 0.49 1.55 0 0.5 0.12 1.62 0.9983 Mixed Moderate Imprecision
Infection PO vs. PC 40 1 – – – – 0.36 0.09 1.31 0.2863 Mixed Moderate Heterogeneity
PO vs. KF 321 1 – – – – 0.38 0.09 1.43 – Mixed Moderate Imprecision
PO vs. LF 246 4 – 0.69 0.31 1.52 19 0.51 0.14 1.56 – Mixed Moderate Imprecision
PO vs. MLF – – – – – – 0.54 0.12 2.15 – Indirect Moderate Imprecision
PO vs. OMC – – 0.58 0.24 1.4 0 0.59 0.14 2.6 – Indirect Moderate Imprecision
PC vs. KF 100 1 – – – – 1.04 0.39 2.66 0.679 Mixed Moderate Imprecision
PC vs. LF 853 8 – 2.94 1.59 5.44 0 1.4 0.69 2.73 0.6293 Mixed Low Heterogeneity, incoherence
PC vs. MLF 180 2 – 3.5 1.21 10.15 0 1.5 0.58 3.64 0.25695 Mixed Moderate Imprecision
PC vs. OMC 235 2 – 0.58 0.24 1.4 35 1.63 0.64 4.44 0.0415 Mixed Low Imprecision,incoherence
KF vs. LF 949 6 – 1.41 0.89 2.24 44 1.35 0.62 2.91 0.70835 Mixed Moderate Imprecision
KF vs. MLF 582 3 – 1.99 0.94 4.23 25 1.44 0.55 3.7 0.3267 Mixed Moderate Imprecision
KF vs. OMC – – – – – – – 1.57 0.54 5.1 – Indirect Moderate Imprecision
LF vs. MLF 492 2 – 1.94 0.79 4.79 82 1.07 0.45 2.54 0.13775 Mixed Moderate Imprecision
LF vs.OMC 203 2 – 0.68 0.31 1.53 47 1.16 0.48 3.22 0.52075 Mixed Moderate Imprecision
MLF vs. OMC 409 3 – 0.3 0.09 1.07 0 1.09 0.42 3.19 0.0033 Mixed Low Imprecision,incoherence
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The statistically significant results were shown in bold font.

KF Karydakis flap, PC primary closure, LF Limberg flap, MLF modified Limberg flap, OMC off-midline closure, PO primary open, MIT minimum invasive technique, RR risk ratio, SMD standardized mean difference, CI confidential interval, CINeMA Confidence in Network Meta-Analysis; Evidence were downgraded from high level of evidence by reasons including: imprecision, incoherence, heterogeneity, reporting bias, within-study bias, indirectness.

Results for recurrence rate

In the pairwise meta-analysis, PC versus LF and LF versus modified Limberg flap (MLF) showed significant results. (RR = 5.39, 95% CI 2.84, 10.23; RR = 3.7, 95% CI 1.2, 11.45, respectively, Table 1). Three heterogeneous comparisons and 3 single study comparisons were excluded before we performed the network meta-analysis. We chose the random model effect and included 3,661 patients, 27 studies and 6 interventions (Fig. 4). Four out of 12 comparisons (MLF versus KF, MLF versus LF, other midline closure (OMC) versus MLF, PC versus OMC) were statistically inconsistent (Table 1). There was a significant increase in the recurrence rate when comparing PC with OMC in network meta-analysis (RR = 2.73, 95% CI 1.11, 7.66, Fig. 4) but not in pairwise results. As shown in the SUCRA plot, the PC was the one with the lowest rankings with the highest recurrence. OMC and MLF presented similar results in the recurrence rate. The meta-regression results were illustrated in Fig. 5. OMC rose the recurrence rate with the increase of sample size, median age and average follow-up. (Fig. 5A,D,F) Interestingly, MLF showed decreased recurrence incidence as the prolongation of average follow-up time. (Fig. 5F) The recurrence rate decreased from the Mediterranean area to the other areas consistently with all interventions. (Fig. 5C).

Figure 4.

Figure 4

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Network analysis results for recurrence. (A) The league plot for surgical interventions. The number in each cell represents the comparison between the name of column versus the name of row. Results with statistically significant are annotated with an asterisk. (B) The network plot showing the interventions included in the network analysis. Size of nodes represents the sample size of each intervention; edges are the frequency of comparison. (C) The leverage plots showing the goodness of random and fixed effects. The model with fewer outliers would be preferred. Dres The posterior mean of the residual deviance. pD The effective number of parameters, calculated as the sum of the leverages. DIC deviance information criterion. (D) The surface under the cumulative ranking curve (SUCRA) plot. KF Karydakis flap, PC primary closure, LF Limberg flap, MLF modified Limberg flap, OMC off-midline closure, MIT minimal invasive technique.

Figure 5.

Figure 5

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Meta-regression results for recurrence rate adjusted by (A) sample size, (B) year, (C) region, (1 for the Mediterranean area and 2 for the other regions) (D) median age, (E) male proportion, (F) average follow-up. All regressions were plotted as effect relative to primary closure (PC) on the linear scale.

Results for infection

The pooled results of 8 studies showed a significant increase in the infection rate in PC compared with LF in pairwise meta-analysis. (RR = 2.94, 95% CI 1.59, 5.44, Table 1) The authors excluded one heterogeneous comparison and 5 single study comparisons. 26 studies with 6 interventions were selected for network meta-analysis with 3,383 patients. Node splitting results showed an overall consistency profile except OMC versus MLF and PC versus OMC (Table 1). The detailed results were presented in Fig. 6, primary open (PO) has ranked the best approach with the least infection rate followed by the off-midline closures. (LF, MLF, OMC and KF) The authors illustrated meta-regression results in Fig. 7. Notably, although PC was ranked the worst approach, with the increase of median age, the incidence of infection would converge for all the other approaches to a similar level of PC (Fig. 7D). The OMC also showed a significant increase when adjusted for average follow-up duration (Fig. 7F).

Figure 6.

Figure 6

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Network analysis results for infection. (A) The league plot for surgical interventions. The number in each cell represents the comparison between the name of column versus the name of row. Results with statistically significant are annotated with an asterisk. (B) The network plot showing the interventions included in the network analysis. Size of nodes represents the sample size of each intervention; edges are the frequency of comparison. (C) The leverage plots showing the goodness of random and fixed effects. The model with fewer outliers would be preferred. Dres The posterior mean of the residual deviance. pD The effective number of parameters, calculated as the sum of the leverages. DIC deviance information criterion. (D) The surface under the cumulative ranking curve (SUCRA) plot. KF Karydakis flap, PC primary closure, LF Limberg flap, MLF modified Limberg flap, OMC off-midline closure, PO primary open.

Figure 7.

Figure 7

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Meta-regression results for infection rate adjusted by (A) sample size, (B) year, (C) region, (1 for the Mediterranean area and 2 for the other regions) (D) median age, (E) male proportion, (F) average follow-up. All regressions were plotted as effect relative to primary closure (PC) on the linear scale.

Other results

For the other complications, KF versus MLF and KF versus LF showed a significant increase in wound dehiscence and seroma in pairwise-meta results, respectively. (RR = 3.36, 95% CI 1.6, 7.05 and RR = 2.31, 95% CI 1.21, 4.43) After the selection process, only seroma and wound dehiscence with 1,257 patients and 2,995 patients were included in network meta-analysis with 4 and 5 interventions respectively. There was little inconsistency in seroma but 3 comparisons needed to be concerned in wound dehiscence. (see Supplementary Figs. S8, S9) LF was associated with the highest wound dehiscence rate but a relatively low seroma rate. On the other hand, MLF could lower the occurrence of these two complications.

For other results, we chose the day as the unit for healing time, hospitalization period and minute for operation time. We used the pain after surgery assessment time point of day-1 post-surgery to achieve a consistent result. The time differences between the interventions were not clinically significant in pairwise meta-analysis. (see Supplementary Table S3) The network meta-analysis for these two outcomes had 1,087 and 925 sample sizes for hospitalization time and for operation time. KF outperformed the other three approaches by several minutes less in operation time (see Supplementary Figs. S10, S11). The detailed regression results were summarized in Supplementary Figs. S12–S15. Especially, when compared with PC, the operation time positively correlates with the year and sample size and negatively correlates with median age and average follow-up time.

Discussion

The recurrence rate of PSD has been a heated research topic that varies greatly in different factors including surgical interventions54 and geography55. Patients’ satisfaction and life quality after surgery have been seriously influenced by the re-emergence of PSD. Stauffer56 et al. conducted a thorough systematic review and meta-analysis with more than 80,000 PSD patients over the past 180 years. They concluded that the recurrence rate of PSD is highly dependent on follow-up time and the primary midline closure was associated with the highest rate of recurrence. These findings were consistent in our results. In another57 meta-analysis focusing on PSD children, the researchers asserted the results were generally worse than those reported in PSD adults. The lower recurrence rate of OMC and MIT showed in the current study was noticed in their results as well. Moreover, in the present study, the recurrence rate decreased from the Mediterranean area to the other areas such as Pakistan, Switzerland, Netherlands, etc. Combining the results together, the rate of recurrence could associate with age in a complicated manner which is worth investigating in the future. On the other hand, the follow-up duration could be a key factor to monitor the recurrence rate. As previous meta-analyses56 demonstrated, the long-term recurrence rate for primary midline closure reached 67.9% at 240 months, which soars from the 7% and 16.8% at 24 months and 60 months respectively. Regarding other approaches, the advancement flaps and rotational flaps have a smaller amount of increase in the recurrence rate: from 0.2 to 1.9% and 0.4 to 5.2% at 12 to 60 months separately. About 40% of patients who underwent phenolisation approach had recurrence at 60 months while only 1.9% at 12 months. It is important for future clinical trials to be designed with longer-term follow-up (i.e., 5–10 years), for a more reliable conclusion to be drawn.

In terms of infection and other complications, the results were agreed that PC and KF were associated with a higher occurrence rate comparatively. In previous meta-analysis1, the significant difference in infection rate between PO and PC was also illustrated. For midline primary closure58, surgical site infections occur in up to 24% of patients after surgical excision. A number of approaches were taken to decrease the infection rate and enhance the prognosis including phenolisation of the sinus tract59, antimicrobial irrigation60 and hydrocolloid dressings58. Based on our results, the OMC and MLF could be a promising intervention as they showed relatively lower rates of infection, wound dehiscence, and seroma incidence.

The off-midline approach was firstly published by George Karydakis as he proposed a simple lateral flap advancement technique later known as Karydakis flap61, which keeps the scar off the midline and flattens the natal cleft. In the following years, several off-midline approaches were categorized such as advancement flap (Karydakis flap, Bascom flap), local advancement flap (V–Y advancement flap), and rotational flap (Limberg flap, modified Limberg flap62, gluteus maximus myocutaneous flap). In the present study, we categorized the off-midline closures into KF, LF, MLF and OMC. As a result, the inevitable heterogeneity in OMC should be minded. Moreover, modification to the existing procedures was still a hot topic for researchers. In the present study, the MLF only showed a significant reduction in wound dehiscence and hospitalization time than LF. Recently, an eyedrop-shaped, modified Limberg transposition flap was designed and asserted to reduce wound tension and increase postoperative patient comfort.

A few limitations should be noted for our study. Firstly, the inclusion of both recurrent and primary PSD patients and the inconsistency of follow-up duration would add heterogeneity to the study. Secondly, the authors did not show the correlation between the time and recurrence or other complications in a cumulatively way. Additionally, a linear regression model was fitted to all the regressions analyzed which might not be the best way to analyze the correlation for the data. Nonetheless, to our knowledge, the present study is the first study using the network meta-analysis method to compare different surgical interventions with RCT studies. Moreover, we achieved good consistency in our study through strict screening studies for network meta-analysis. The potential relationship between each outcome and factors including region, publication year, median age, sample size, follow-up duration and male proportion were investigated using meta-regression analysis. There are several ongoing registered reviews focusing on different aspects of PSD, including the anesthesia method (PROSPERO 2020 CRD42020159358), dressings and topical agents (PROSPERO 2020 CRD42020168876) after surgery.

In summary, we have systematically reviewed all eligible RCTs relating to pilonidal sinus surgical interventions and performed a comprehensive network meta-analysis comparing different procedures with various outcomes. Although there were some significant results for the comparison between KF and LF, the superiority is still not determined. OMC and MLF provided relatively low recurrence and complications rates and therefore, could be two promising surgical interventions for PSD patients. MIT was associated with lower complications rates at the cost of a comparatively high recurrence rate. However, which is the best choice within OMC still needs more clinical trials with enough sample size and follow-up duration.

Materials and methods

Search strategy

The following English databases were searched systematically by two investigators (SWB, KBS): PubMed, Embase, Web of Science and Cochrane Library for clinical trials published from January 1, 2009, to December 12, 2019, using the following terms:(“pilonidal” OR “pilonidal disease” OR “pilonidal sinus” OR “pilonidal cyst” OR “sacrococcygeal disease” [Title/Abstract]) AND “randomized clinical trial”. To avoid the potential omission of studies, we also manually screened reference lists of previous systematic reviews and meta-analyses of pilonidal sinus. All of the titles and abstracts were screened out independently by the two reviewers (SWB, KBS) strictly following the inclusion criteria. Any differences were resolved through consensus, and if necessary, a senior reviewer (RQL) was consulted.

Study selection and exclusion

Studies were included if they satisfied the following criteria:

  1. Randomized controlled clinical trials to evaluate the outcomes for treating PSD patients using at least two modalities;

  2. Patients who were diagnosed as chronic PSD with both recurrent or primary. They were randomly divided into different treatment groups;

  3. The authors categorized all the treatments to fit a pre-defined classification (Supplementary files);

  4. Papers reporting recurrence rate and infection rate were included as primary outcomes. We also collected the other outcomes documented in the articles as secondary outcomes. The endpoint of each outcome varies based on the longest follow-up duration of each study.

Studies were excluded by the following exclusion criteria:

  1. Duplicated or abstracts without full texts or original data;

  2. Enrolled-patients were reported earlier with the same primary authors;

  3. Acute pilonidal sinus.

Data extraction and quality assessment

This process was conducted independently by two reviewers (SB, KS) using a standard collection form by the Cochrane Collaboration for Systematic Reviews guidelines63. All disputes were consulted with the senior researchers. Information in each study was extracted including first author, publication year, region, median age, number of participants, treatments, follow-up duration, outcomes, male proportion, gender ratio (Male/Female), and primary or recurrent PSD. All the missing data were calculated following the Cochrane Collaboration for Systematic Reviews guidelines63.

The methodological quality of each study was evaluated based on the assessment of the following items: random sequence generation, allocation sequence concealment, blinding of participants and personnel, blinding of the outcome assessment, incomplete outcome data, selective reporting, and other biases. For each study, every item was rated as “low risk of bias,” “high risk of bias,” or “unclear risk of bias”.

For each comparison in primary outcomes, the certainty of the evidence was evaluated using the CINeMA64 (Confidence in Network Meta-Analysis) web application which is an adaption of the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for network meta-analysis. It is based on a methodological framework that considers six domains: within-study bias, reporting bias, indirectness, imprecision, heterogeneity, and incoherence. It allows confidence in the results to be graded as high, moderate, low, and very low.

Statistical analysis

Firstly, the transitivity assumption was evaluated by comparing the distribution of potential effect modifiers (geographical factor, publication year, sample size, average follow-up duration, mean age, and percentage male) across studies. These modifiers were also selected for meta-regression analysis furtherly.

Secondly, the pair-wise meta-analysis was used to analyze the direct comparisons. The authors examined the heterogeneity between studies by I2 statistic65. A fixed-effect model was applied for comparisons with negligible heterogeneity (I2 < 50%)66. Otherwise, the random-effect model and influence diagnosis66 were conducted to identify the contributor of heterogeneity67,68 except for the comparisons with only two studies. Influence diagnosis is based on the Leave-One-Out-method, in which we recalculate the results of our meta-analysis K − 1 times, each time leaving out one study. (K equals the number of included studies) This way, studies that influence the overall estimate of meta-analysis the most would be detected. The authors identified and excluded the one with the most significant contribution to heterogeneity and calculated the adjusted results afterward. Publication bias was examined in contour-enhanced funnel plots69. Then, the results were reported as the mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes with corresponding 95% confidence intervals (CIs).

Moreover, before network meta-analysis, we selected the pair-wise comparisons of each outcome based on the following criteria:

  1. Insignificant heterogeneity (I2 < 50% and p > 0.05), with or without adjusted by sensitivity analysis;

  2. Two or more studies shared the same interventions.

For each outcome, the authors performed the analysis with fixed- and random-effect model. The goodness fit of each model was assessed through leverage plots that display the corresponding effective number of parameters, total residual deviance, and deviance information criterion (DIC). According to a visual examination of the leverage plots and comparison of the DIC values, the model with fewer outliers would be preferred. Then the network plots showed the entire network with nodes as interventions and the size of nodes representing the sample size. The edges represent the number of studies. The authors used the Markov Chain Monte Carlo algorithm for every eligible outcome and based on 100,000 simulation iterations and 20,000 adaptation iterations. A thinning interval of 10 was applied, which collected 1 sample every 10 iterations. We evaluated consistency statistically using node-splitting analysis70 that illustrates the inconsistency between indirect and direct comparisons. The residual heterogeneity and inconsistency were also explored by several meta-regressions based on modifiers mentioned earlier. The final results were shown in league plot and treatments were ranked using the surface under the curve cumulative ranking probabilities (SUCRA71). All the analyses and illustrations were done in R 3.6.2 using packages: “gemtc”72, “rjags”73, “dmetar”74, “ggplot2”75, “BUGSnet”76 and “netmeta”77.

Supplementary information

Supplementary information. (2MB, pdf)

Acknowledgements

The study was funded by the National Natural Science Foundation of China (Grant no. 81700410) and the Sichuan Science and Technology Program, China (Grant no. 2019YFS034).

Author contributions

J.G., S.B. designed the experiments. S.B., K.S. and S.C. carried out the data collection, analysis and interpretation. All authors drafted, write or revised the manuscript. The final manuscript was approved for submission by all authors.

Data availability

Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

is available for this paper at 10.1038/s41598-020-70641-7.

References

  • 1.McCallum IJ, King PM, Bruce J. Healing by primary closure versus open healing after surgery for pilonidal sinus: Systematic review and meta-analysis. BMJ. 2008;336:868–871. doi: 10.1136/bmj.39517.808160.BE. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Yildiz T, et al. Risk factors for pilonidal sinus disease in teenagers. Indian J. Pediatr. 2017;84:134–138. doi: 10.1007/s12098-016-2180-5. [DOI] [PubMed] [Google Scholar]
  • 3.Chintapatla S, et al. Sacrococcygeal pilonidal sinus: Historical review, pathological insight and surgical options. Tech. Coloproctol. 2003;7:3–8. doi: 10.1007/s101510300001. [DOI] [PubMed] [Google Scholar]
  • 4.Berry DP. Pilonidal sinus disease. J. Wound Care. 1992;1:29–32. doi: 10.12968/jowc.1992.1.3.29. [DOI] [PubMed] [Google Scholar]
  • 5.Sunkara A, Wagh D, Harode S. Intermammary pilonidal sinus. Int. J. Trichol. 2010;2:116–118. doi: 10.4103/0974-7753.77526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Bozkurt MK, Tezel E. Management of pilonidal sinus with the Limberg flap. Dis Colon Rectum. 1998;41:775–777. doi: 10.1007/BF02236268. [DOI] [PubMed] [Google Scholar]
  • 7.Keshvari A, et al. Karydakis flap versus excision-only technique in pilonidal disease. J. Surg. Res. 2015;198:260–266. doi: 10.1016/j.jss.2015.05.039. [DOI] [PubMed] [Google Scholar]
  • 8.Alvandipour M, et al. Comparison of Limberg flap and Karydakis flap surgery for the treatment of patients with pilonidal sinus disease: A single-blinded parallel randomized study. Ann. Coloproctol. 2019;35:313–318. doi: 10.3393/ac.2018.09.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Bali İ, et al. Effectiveness of Limberg and Karydakis flap in recurrent pilonidal sinus disease. Clinics (Sao Paulo). 2015;70:350–355. doi: 10.6061/clinics/2015(05)08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Gavriilidis P, Bota E. Limberg flap versus Karydakis flap for treating pilonidal sinus disease: A systematic review and meta-analysis. Can. J. Surg. 2019;62:131–138. doi: 10.1503/cjs.003018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Prassas D, et al. Karydakis flap reconstruction versus Limberg flap transposition for pilonidal sinus disease: A meta-analysis of randomized controlled trials. Langenbecks Arch Surg. 2018;403:547–554. doi: 10.1007/s00423-018-1697-7. [DOI] [PubMed] [Google Scholar]
  • 12.Milone M, et al. Safety and efficacy of minimally invasive video-assisted ablation of pilonidal sinus: A randomized clinical trial. JAMA Surg. 2016;151:547–553. doi: 10.1001/jamasurg.2015.5233. [DOI] [PubMed] [Google Scholar]
  • 13.Kalaiselvan R, et al. Minimally invasive techniques in the management of pilonidal disease. Int. J. Colorectal Dis. 2019;34:561–568. doi: 10.1007/s00384-019-03260-y. [DOI] [PubMed] [Google Scholar]
  • 14.Mills EJ, Thorlund K, Ioannidis JP. Demystifying trial networks and network meta-analysis. BMJ. 2013;346:f2914. doi: 10.1136/bmj.f2914. [DOI] [PubMed] [Google Scholar]
  • 15.Leucht S, et al. Network meta-analyses should be the highest level of evidence in treatment guidelines. Eur. Arch. Psychiatry Clin. Neurosci. 2016;266:477–480. doi: 10.1007/s00406-016-0715-4. [DOI] [PubMed] [Google Scholar]
  • 16.Milone M, et al. Long-term results of a randomized clinical trial comparing endoscopic versus conventional treatment of pilonidal sinus. Int. J. Surg. 2020;74:81–85. doi: 10.1016/j.ijsu.2019.12.033. [DOI] [PubMed] [Google Scholar]
  • 17.Galal Elshazly W, Said K. Clinical trial comparing excision and primary closure with modified Limberg flap in the treatment of uncomplicated sacrococcygeal pilonidal disease. Alexandr. J. Med. 2019;48:13–18. [Google Scholar]
  • 18.Caliskan M, et al. Comparison of common surgical procedures in non-complicated pilonidal sinus disease, a 7-year follow-up trial. World J. Surg. 2020;44:1091–1098. doi: 10.1007/s00268-019-05331-1. [DOI] [PubMed] [Google Scholar]
  • 19.Arnous M, et al. Excision with primary midline closure compared with Limberg flap in the treatment of sacrococcygeal pilonidal disease: A randomised clinical trial. Ann. R Coll. Surg. Engl. 2019;101:21–29. doi: 10.1308/rcsann.2018.0144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Jabbar MS, Bhutta MM, Puri N. Comparison between primary closure with Limberg Flap versus open procedure in treatment of pilonidal sinus, in terms of frequency of post-operative wound infection. Pak. J. Med. Sci. 2018;34:49–53. doi: 10.12669/pjms.341.13929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Abdelnaby M, et al. Rotational gluteal flap versus modified Limberg flap in treatment of sacrococcygeal pilonidal disease. J. Surg. Res. 2018;223:174–182. doi: 10.1016/j.jss.2017.11.017. [DOI] [PubMed] [Google Scholar]
  • 22.Milone M, et al. Video-assisted ablation of pilonidal sinus (VAAPS) versus sinusectomy for treatment of chronic pilonidal sinus disease: a comparative study. Updates Surg. 2019;71:179–183. doi: 10.1007/s13304-018-00611-2. [DOI] [PubMed] [Google Scholar]
  • 23.Calikoglu I, et al. Phenol injection versus excision with open healing in pilonidal disease: A prospective randomized trial. Dis Colon Rectum. 2017;60:161–169. doi: 10.1097/DCR.0000000000000717. [DOI] [PubMed] [Google Scholar]
  • 24.Ghasoup A, Sadieh O, Mansour A. Endoscopic pilonidal sinus treatment, a minimally invasive approach. Surg. Endosc. Other Interv. Tech. 2017;31:S84. [Google Scholar]
  • 25.Zorlu M, et al. Early results with the Mutaf technique: A novel off-midline approach in pilonidal sinus surgery. Ann. Surg. Treat. Res. 2016;90:265–271. doi: 10.4174/astr.2016.90.5.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Sevinc B, et al. Randomized prospective comparison of midline and off-midline closure techniques in pilonidal sinus surgery. Surgery. 2016;159:749–754. doi: 10.1016/j.surg.2015.09.024. [DOI] [PubMed] [Google Scholar]
  • 27.Tokac M, et al. Comparison of modified Limberg flap and Karydakis flap operations in pilonidal sinus surgery: prospective randomized study. Int.Surg. 2015;100:870–877. doi: 10.9738/INTSURG-D-14-00213.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Saydam M, et al. Comparison of modified Limberg flap transposition and lateral advancement flap transposition with Burow's triangle in the treatment of pilonidal sinus disease. Am. J. Surg. 2015;210:772–777. doi: 10.1016/j.amjsurg.2015.03.031. [DOI] [PubMed] [Google Scholar]
  • 29.Käser S, et al. Primary wound closure with a Limberg flap vs secondary wound healing after excision of a pilonidal sinus: A multicentre randomised controlled study. Int. J. Colorectal Dis. 2015;30:97–103. doi: 10.1007/s00384-014-2057-x. [DOI] [PubMed] [Google Scholar]
  • 30.Furnee EJ, et al. Pit excision with phenolisation of the sinus tract versus radical excision in sacrococcygeal pilonidal sinus disease: Study protocol for a single centre randomized controlled trial. Trials. 2015;16:92. doi: 10.1186/s13063-015-0613-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Shabbir F, et al. Modified Limberg's flap versus primary closure for treatment of pilonidal sinus disease: a comparative study. J. Pak. Med. Assoc. 2014;64:1270–1273. [PubMed] [Google Scholar]
  • 32.Rashidian N, et al. How to repair the surgical defect after excision of sacrococcygeal pilonidal sinus: a dilemma. J. Wound Care. 2014;23:630–633. doi: 10.12968/jowc.2014.23.12.630. [DOI] [PubMed] [Google Scholar]
  • 33.Enshaei A, Motearefi S. Comparison of two surgical methods, primary closure and rotational flap, in patients with chronic pilonidal sinus. Glob. J. Health Sci. 2014;6:18–22. doi: 10.5539/gjhs.v6n7p18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Emir S, et al. Sinotomy technique versus surgical excision with primary closure technique in pilonidal sinus disease. Bosn. J. Bas. Med. Sci. 2014;14:263–267. doi: 10.17305/bjbms.2014.4.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Arslan K, et al. Which flap method should be preferred for the treatment of pilonidal sinus? A prospective randomized study. Tech. Coloproctol. 2014;18:29–37. doi: 10.1007/s10151-013-0982-2. [DOI] [PubMed] [Google Scholar]
  • 36.Bessa SS. Comparison of short-term results between the modified Karydakis flap and the modified Limberg flap in the management of pilonidal sinus disease: A randomized controlled study. Dis Colon Rectum. 2013;56:491–498. doi: 10.1097/DCR.0b013e31828006f7. [DOI] [PubMed] [Google Scholar]
  • 37.Sit M, Aktas GL, Yilmaz EE. Comparison of the three surgical flap techniques in pilonidal sinus surgery. Am. Surg. 2013;79:1263–1268. [PubMed] [Google Scholar]
  • 38.Khan PS, Hayat H, Hayat G. Limberg flap versus primary closure in the treatment of primary sacrococcygeal pilonidal disease; a randomized clinical trial. Indian J. Surg. 2013;75:192–194. doi: 10.1007/s12262-012-0430-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Guner A, et al. Limberg flap versus Bascom cleft lift techniques for sacrococcygeal pilonidal sinus: prospective, randomized trial. World J. Surg. 2013;37:2074–2080. doi: 10.1007/s00268-013-2111-9. [DOI] [PubMed] [Google Scholar]
  • 40.Dass TA, et al. Elliptical excision with midline primary closure versus rhomboid excision with limberg flap reconstruction in sacrococcygeal pilonidal disease: A prospective, randomized study. Indian J. Surg. 2012;74:305–308. doi: 10.1007/s12262-011-0400-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Onder A, et al. Pilonidal sinus disease: Risk factors for postoperative complications and recurrence. Int. Surg. 2012;97:224–229. doi: 10.9738/CC86.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Okus A, et al. Comparison of Limberg flap and tension-free primary closure during pilonidal sinus surgery. World J. Surg. 2012;36:431–435. doi: 10.1007/s00268-011-1333-y. [DOI] [PubMed] [Google Scholar]
  • 43.Tavassoli A, Noorshafiee S, Nazarzadeh R. Comparison of excision with primary repair versus Limberg flap. Int. J. Surg. 2011;9:343–346. doi: 10.1016/j.ijsu.2011.02.009. [DOI] [PubMed] [Google Scholar]
  • 44.Lorant T, et al. Sinus excision and primary closure versus laying open in pilonidal disease: A prospective randomized trial. Dis. Colon Rectum. 2011;54:300–305. doi: 10.1007/DCR.0b013e31820246bf. [DOI] [PubMed] [Google Scholar]
  • 45.Ates M, et al. Short and long-term results of the Karydakis flap versus the Limberg flap for treating pilonidal sinus disease: A prospective randomized study. Am. J. Surg. 2011;202:68–73. doi: 10.1016/j.amjsurg.2010.10.021. [DOI] [PubMed] [Google Scholar]
  • 46.Nursal TZ, et al. Prospective randomized controlled trial comparing V-Y advancement flap with primary suture methods in pilonidal disease. Am. J. Surg. 2010;199:170–177. doi: 10.1016/j.amjsurg.2008.12.030. [DOI] [PubMed] [Google Scholar]
  • 47.Muzi MG, et al. Randomized comparison of Limberg flap versus modified primary closure for the treatment of pilonidal disease. Am. J. Surg. 2010;200:9–14. doi: 10.1016/j.amjsurg.2009.05.036. [DOI] [PubMed] [Google Scholar]
  • 48.Can MF, et al. Multicenter prospective randomized trial comparing modified Limberg flap transposition and Karydakis flap reconstruction in patients with sacrococcygeal pilonidal disease. Am. J. Surg. 2010;200:318–327. doi: 10.1016/j.amjsurg.2009.08.042. [DOI] [PubMed] [Google Scholar]
  • 49.Karakayali F, et al. Unroofing and marsupialization vs. rhomboid excision and Limberg flap in pilonidal disease: a prospective, randomized, clinical trial. Dis. Colon Rectum. 2009;52:496–502. doi: 10.1007/DCR.0b013e31819a3ec0. [DOI] [PubMed] [Google Scholar]
  • 50.Nordon IM, Senapati A, Cripps NP. A prospective randomized controlled trial of simple Bascom's technique versus Bascom's cleft closure for the treatment of chronic pilonidal disease. Am. J. Surg. 2009;197:189–192. doi: 10.1016/j.amjsurg.2008.01.020. [DOI] [PubMed] [Google Scholar]
  • 51.Jamal A, et al. Open excision with secondary healing versus rhomboid excision with Limberg transposition flap in the management of sacrococcygeal pilonidal disease. J. Pak. Med. Assoc. 2009;59:157–160. [PubMed] [Google Scholar]
  • 52.Ersoy E, et al. Comparison of the short-term results after Limberg and Karydakis procedures for pilonidal disease: Randomized prospective analysis of 100 patients. Colorectal Dis. 2009;11:705–710. doi: 10.1111/j.1463-1318.2008.01646.x. [DOI] [PubMed] [Google Scholar]
  • 53.Bali İ, et al. Effectiveness of Limberg and Karydakis flap in recurrent pilonidal sinus disease. Clinics. 2015;70:350–355. doi: 10.6061/clinics/2015(05)08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Mutus HM, et al. Long-term analysis of surgical treatment outcomes in chronic pilonidal sinus disease. J. Pediatr. Surg. 2018;53:293–294. doi: 10.1016/j.jpedsurg.2017.11.031. [DOI] [PubMed] [Google Scholar]
  • 55.Doll D, et al. Impact of geography and surgical approach on recurrence in global pilonidal sinus disease. Sci. Rep. 2019;9:15111. doi: 10.1038/s41598-019-51159-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Stauffer V, et al. Common surgical procedures in pilonidal sinus disease: A meta-analysis, merged data analysis, and comprehensive study on recurrence. Sci. Rep. 2018;8:3058. doi: 10.1038/s41598-018-20143-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Hardy EJO, et al. Surgical interventions for the treatment of sacrococcygeal pilonidal sinus disease in children: A systematic review and meta-analysis. J. Pediatr. Surg. 2019;54:2222–2233. doi: 10.1016/j.jpedsurg.2019.02.058. [DOI] [PubMed] [Google Scholar]
  • 58.Nguyen AL, et al. Local administration of gentamicin collagen sponge in surgical excision of sacrococcygeal pilonidal sinus disease: A systematic review and meta-analysis of the literature. Tech. Coloproctol. 2016;20:91–100. doi: 10.1007/s10151-015-1381-7. [DOI] [PubMed] [Google Scholar]
  • 59.Kayaalp C, Aydin C. Review of phenol treatment in sacrococcygeal pilonidal disease. Tech. Coloproctol. 2009;13:189–193. doi: 10.1007/s10151-009-0519-x. [DOI] [PubMed] [Google Scholar]
  • 60.Salih AM, et al. Nonoperative management of pilonidal sinus disease: One more step toward the ideal management therapy—a randomized controlled trial. Surgery. 2018;2:1. doi: 10.1016/j.surg.2017.12.014. [DOI] [PubMed] [Google Scholar]
  • 61.Karydakis GE. New approach to the problem of pilonidal sinus. Lancet. 1973;2:1414–1415. doi: 10.1016/s0140-6736(73)92803-1. [DOI] [PubMed] [Google Scholar]
  • 62.Mentes BB, et al. Modified Limberg transposition flap for sacrococcygeal pilonidal sinus. Surg Today. 2004;34:419–423. doi: 10.1007/s00595-003-2725-x. [DOI] [PubMed] [Google Scholar]
  • 63.Higgins, J. and G. Wells. Cochrane handbook for systematic reviews of interventions. (2011).
  • 64.Salanti G, et al. Evaluating the quality of evidence from a network meta-analysis. PLoS ONE. 2014;9:e99682. doi: 10.1371/journal.pone.0099682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Higgins JP, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560. doi: 10.1136/bmj.327.7414.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst. 1959;22:719–748. [PubMed] [Google Scholar]
  • 67.Viechtbauer W, Cheung MW. Outlier and influence diagnostics for meta-analysis. Res. Synth. Methods. 2010;1:112–125. doi: 10.1002/jrsm.11. [DOI] [PubMed] [Google Scholar]
  • 68.Baujat B, et al. A graphical method for exploring heterogeneity in meta-analyses: Application to a meta-analysis of 65 trials. Stat. Med. 2002;21:2641–2652. doi: 10.1002/sim.1221. [DOI] [PubMed] [Google Scholar]
  • 69.Peters JL, et al. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J. Clin. Epidemiol. 2008;61:991–996. doi: 10.1016/j.jclinepi.2007.11.010. [DOI] [PubMed] [Google Scholar]
  • 70.van Valkenhoef G, et al. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res. Synth. Methods. 2016;7:80–93. doi: 10.1002/jrsm.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Chaimani A, et al. Graphical tools for network meta-analysis in STATA. PLoS ONE. 2013;8:e76654. doi: 10.1371/journal.pone.0076654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.van Valkenhoef, G. and J. Kuiper. GeMTC: Network Meta-Analysis Using Bayesian Methods. R package version 0.7–1. (2014).
  • 73.Plummer, M., Rjags: Bayesian graphical models using MCMC. R package version. 4, (2016).
  • 74.Harrer, M., et al. Dmetar: companion R package for the guide “doing meta-analysis in R”. R package version 0.0. 9000. (2019).
  • 75.Wickham H. ggplot2: elegant graphics for data analysis. New York: Springer; 2009. [Google Scholar]
  • 76.Beliveau A, et al. BUGSnet: an R package to facilitate the conduct and reporting of Bayesian network Meta-analyses. BMC Med. Res. Methodol. 2019;19:196. doi: 10.1186/s12874-019-0829-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Rücker, G., et al. Netmeta: Network meta-analysis using frequentist methods. R package. Version 0.9–0. (2016).

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