EHS Rapid Guideline: Evidence-Informed European Recommendations on Parastomal Hernia Prevention—With ESCP and EAES Participation

Introduction

The incidence of parastomal hernia exceeds 50% in the long term, with substantial implications on patients’ quality of life [1, 2]. Reinforcement of the stoma with a mesh has been suggested to be associated with lower incidence of parastomal hernia [3].

A previous guideline of the European Hernia Society (EHS) issued a strong recommendation for the use of a synthetic permanent prophylactic mesh in the construction of an end colostomy [1]. This recommendation was primarily based upon evidence synthesis of randomized trials, suggesting a lower risk of parastomal hernia with the use of a prophylactic mesh without increasing perioperative and longer-term stoma-related complications [4–6].

The surgical literature has since seen a growing body of evidence on the use of synthetic permanent, absorbable, and biologic mesh for parastomal hernia prevention. In view of this new evidence and evolving methods in the field of clinical practice guidelines development, of an update of the guideline on parastomal hernias focused on prevention, and based upon an update systematic review, rigorous evidence appraisal, and a structured evidence-todecision framework informed by an international and interdisciplinary panel, including patient representatives. The objective is to inform clinical and patient decision making, and healthcare policy, to optimize the outcomes of stoma construction, and improve patients' quality of life.

Methods

This rapid guideline follows AGREE-S, GRADE, Institute of Medicine, Guidelines International Network (GIN) and Cochrane Rapid Reviews Methods Group development and reporting standards [7–11]. It was registered at the International Practice Guideline Registry Platform (registration number IPGRP-2022CN216). An AGREE-S reporting checklist is provided in Supplementary File S2. We consulted GRADE official guidance published in a series of articles in the Journal of Clinical Epidemiology for up-to-date evidence appraisal and guideline development methodology. The development of this guideline was informed by the GRADE methodology to appraise the certainty of the evidence and the GRADE evidence-to-decision framework [12–15].

Steering Group

The steering group consisted of 2 general and colorectal surgeons with specific interest in hernia surgery, members of the EHS Scientific Advisory Board (FM, CS), and a general surgeon, certified guideline methodologist and INGUIDE guideline certification credentialling instructor (SAA, INGUIDE certificate number 2021-L2-V1-00001). The guideline methodologist and a member of the steering group (FM) were coordinators of the previous EHS guideline on prevention and treatment of parastomal hernias [1]. The third member of the steering group (CS) acted as content coordinator of this project and disclosed no direct nor indirect conflict [16]. We therefore consider that a potential indirect conflict of the coordinators of the original guideline has not affected the content of this guideline.

Guideline Panel

The guideline panel consisted of 3 colorectal surgeons (SB, NJS, MA), 2 general surgeons with specific interest in hernia surgery (KKJ, UB), 2 stoma care nurses (MK, CT), and 2 patient representatives (SC, SD). One of the patient representatives had an abdominoperineal resection 12 years ago for stage III colorectal cancer, and an end colostomy without prophylactic mesh. She developed a parastomal hernia months after surgery, and an incisional hernia at the site of an abdominal drain; she had not had any hernia repair. The other patient representative had an end colostomy construction without mesh for severe neurogenic bowel, slow transit constipation and passive fecal incontinence secondary to a spinal cord arteriovenous malformation. She had a revision surgery for a prolapse and possibly a small parastomal hernia with biological mesh reinforcement. At the time of the consensus meeting, she had no evident recurrence, apart from a subcutaneous prolapse. Both patient representatives were recruited through communication on Twitter.

The composition of panel members aimed to be representative of different parts of Europe and different age groups. Panel members disclosed no direct nor indirect conflicts [16]. We invited authors of randomized trials and evidence syntheses on the topic of interest as external advisors. These members were not involved in the decisions on the strength, the direction or the wording of the recommendations, but they were consulted in the development of the evidence-to-decision framework, as per GRADE and GIN guidance. The composition of the guideline development group and members’ roles are available in the online appendix [16].

Health Question

Should prophylactic mesh versus no prophylactic mesh be used in patients who undergo construction of a permanent end colostomy?

This guideline refers to patients scheduled to undergo surgery that includes construction of a permanent end colostomy in the elective or emergency setting.

Protocol

A protocol was developed a priori by the steering group [17]. The protocol draft was made publicly available through the social media, and the public was invited to comment on the content. The guideline question and outcomes of interest were refined in collaboration with the panel members. Amendments to the protocol with justifications are provided below.

Rating the Importance of Outcomes

The importance of outcomes was rated by panel members using the GRADE scale [18]. The classification of outcomes into each of the three categories (not important, important, critical) was made by the steering group under consideration of panel members’ ratings available online (scale from 1 to 9, from the least to the highest importance) [16]. The final rating was the median of panel members’ ratings, since there was no substantial deviation from the median.

We considered the importance of outcomes as follows:

1. Clinical diagnosis of parastomal hernia: critical - 7

2. 30 days or in-hospital complications Clavien-Dindo ≥3: critical - 8

3. Surgery for parastomal hernia: critical - 8

4. Quality of life: critical - 9

The following outcomes were additionally prioritized by the panel: pain, size of bulge, spillage, time off work, and computed tomography-classified diagnosis. The steering group considered that the outcomes pain, size of bulge, time off work, and spillage are overlapping with the outcomes: clinical diagnosis, 30 days or in-hospital complications, and quality of life. Computed tomography-classified diagnosis was not prioritized, because it was considered a non-patient-important outcome. An external advisor suggested that imaging findings of a parastomal hernia not evident on clinical examination may predict the development of a clinical parastomal hernia. Relevant evidence was, therefore, taken into account, albeit not in summary analyses.

Furthermore, the panel was informed that the outcomes clinical diagnosis of parastomal hernia, surgery for parastomal hernia, and quality of life may overlap to a substantial extent; they were, therefore, advised to exercise caution in their judgments on overall benefit/harm in the context of the evidence-to-decision framework.

Definitions

We considered clinical diagnosis of parastomal hernia negatively affecting patient experience as the outcome of interest of this guideline. The studies providing the evidence base of this work provided different definitions of clinically evident (but not necessarily clinically relevant) parastomal hernia, but we did not consider justified to downgrade for indirectness (different definition of the outcome in the source studies versus the definition used in this guideline). The definitions of parastomal hernia, clinical and/or radiological, used by each author group are provided in the online appendix [16]. Furthermore, we considered the pooled comparative effect estimates of clinical and clinical/radiological diagnosis of parastomal hernia, because sensitivity analyses suggested similar comparative effect estimates between clinical versus clinical/radiological diagnosis of parastomal hernia (see statistical analyses in the online appendix [16]).

Setting Minimal Important Differences

The evidence-to-decision framework was set within a fully contextualized approach [19]. This approach considers all relevant outcomes for clinical decision making and entails setting a decision threshold for clinically meaningful effect for each outcome. An anonymous web-based survey of panel members was performed to define decision thresholds (minimal important differences). The results of the survey are available online [16]. The final rating was the median of panel members’ ratings, since no substantial deviations from the median were observed.

Under consideration of panel’s responses, the following minimal important differences were set:

1. Clinical diagnosis of parastomal hernia: 50 per 1,000 patients

2. 30-day or in-hospital complications Clavien-Dindo ≥3: 50 per 1,000 patients

3. Surgery for parastomal hernia: 50 per 1,000 patients

4. Quality of life: 25 out of 100 points, or 0.2/0.5 standard deviation units (small/moderate difference)

The outcome quality of life was reported under different scales (EORTC QLQ-C30, Short Form 36, Stoma QoL questionnaire); we therefore calculated standardized mean differences. Although no universal cutoff can be applied [20], we considered the above differences in standard deviation units as important for small/moderate difference, based on expert guidance (INGUIDE McMaster guideline methodologist certification program).

Systematic Review and Evidence Synthesis

The full systematic review with details on the search strategy, study selection, data extraction, risk of bias assessment, statistical analyses (including sensitivity analyses), and assessment of the certainty of the evidence is published separately in this issue [21].

In brief, we updated a previous systematic review with de novo evidence search of PubMed. Study selection, data extraction, and risk of bias assessment were performed by an ad hoc evidence research team (AT, LR), and statistical analyses were performed independently by a statisticians’ team. We considered randomized controlled trials only, comparing the use of prophylactic mesh versus no mesh in the construction of an end colostomy. Overarching inclusion criteria were adult patients undergoing surgery with construction of an end colostomy for either benign or malignant disease, in an elective or emergency setting. An external advisor (HTB) provided long-term data of the PREVENT trial, which were unpublished by the time of development of the evidence tables, but were published recently [22]. Therefore, we do not consider that the risk of including these data was high. Another two external advisors indicated that longer-term data of their trials have been collected, but they were not available for third-party use.

We performed de novo risk of bias assessments using RoB-2 [23]. For the purposes of outcome-specific risk of bias assessment, outcomes were grouped as follows: 30 days complications Clavien-Dindo ≥3; parastomal hernia and surgery for parastomal hernia; and quality of life. We considered longest-term follow-up data for all outcomes, with a minimum follow-up of 12 months, except for perioperative complications. The panel considered 5-year follow-up as sufficient in the context of this guideline (median of votes).

We conducted random and fixed effect(s) meta-analyses to synthesize evidence. We used the DerSimonian & Laird estimator for the between study-variance. For the continuous outcome, we extracted the mean, the sample size and the standard deviation, and we estimated the study-specific standardized mean differences along with the corresponding 95% confidence interval for each group. For what we could not calculate the standard deviation, we used the maximum standard deviation among studies. We explored heterogeneity via the I² statistic and by computing the Q-statistic and the 95% predictive intervals. We performed sensitivity analyses of studies with a minimum follow-up duration of 5 years and compared the effect estimates with studies with shorter follow-up duration. We also performed subgroup analyses based on the anatomical position of the mesh (retrorectus/intraperitoneal/anterectus). We did not observe subgroup differences; we therefore considered the overall effect estimate.

Assessment of the Certainty of Evidence

We constructed GRADE evidence profiles of certainty for each pairwise comparison separately and for each outcome using GRADEpro GDT [24]. The certainty of evidence is determined by the risk of bias across studies, incoherence, indirectness, imprecision, publication bias and other parameters [25]. To inform calculations of absolute effect differences, we performed proportion meta-analyses of frequencies of baseline risks/effects provided by the source studies; these are available in the online appendix [16]. One study only provided data to allow time-to-event analyses [26], therefore time-to-event data meta-analysis could not be performed.

Evidence-to-Decision Framework and Development of Recommendations

We provided the evidence tables to the guideline panel for review in advance of an in-person consensus meeting. In the consensus meeting, the guideline development methodology was detailed, and panel members provided their judgements on:

• the magnitude of benefit of the intervention compared to the control

• the magnitude of harm of the intervention compared to the control

• the certainty of the evidence on benefits and harms

• any variability in patients’ values and preferences

• costs or savings related to the intervention compared to the control

• effect of the intervention on equity compared to the control

• acceptability of the intervention compared to the control

• feasibility of the intervention compared to the control

Panel members then participated in an online Delphi process to formulate the recommendation. A draft of the recommendation was developed by the steering group, and panel members were invited to anonymously propose modifications.

Amendments to the Protocol

For logistical reasons, we included 2 general surgeons with specific interest in hernia surgery, instead of 3. We searched PubMed, instead of MEDLINE via the Healthcare Databases Advanced Search interface, because the latter was not available since March 2022. OpenGrey was neither operational by the time of the update search.

Results

We identified 19 reports on 12 unique randomized trials [3, 22, 26–42] (PRISMA 2020 flow chart available in the online appendix [16]). Ten trials reported on elective surgery, 11 trials reported primarily on patients with malignancy as background pathology that necessitated construction of a stoma, and all trials reported on the use of synthetic non-absorbable or partially absorbable mesh. Detailed study characteristics are provided in the data extraction sheet available in the online appendix [16]. Detailed statistical analyses are available in the online appendix [16].

The evidence profile is provided in Table 1 and in Table 2 as summary of findings. Table 3 details the evidence-to-decision considerations.

TABLE 1. Evidence summary on the use of mesh for parastomal hernia prevention.

TABLE 2. Summary of findings table on the use of mesh for parastomal hernia prevention.

TABLE 3. Evidence-to-decision framework on the use of mesh for parastomal hernia prevention.

There was unanimous consensus on the direction, the strength, and the wording of the recommendations within the first Delphi round [16].

Recommendations

 • We suggest the use of a synthetic non-absorbable prophylactic mesh for the construction of an end colostomy.

Conditional recommendation

 • We recommend the use of a synthetic non-absorbable prophylactic mesh for the construction of an end colostomy in patients at high risk for parastomal hernia (patients with a history of an abdominal wall hernia, connective tissue disorder, obesity, likely to undergo chemotherapy) and life expectancy over 2 years.

Strong recommendation.

Discussion

Implications for Policy Makers

Policymakers are called to facilitate a parastomal hernia prevention strategy for most patients. This includes availability of synthetic mesh and additional operating room time. Training of surgeons to perform stoma construction with a prophylactic mesh may be necessary in some settings.

Implications for Healthcare Professionals

General and colorectal surgeons are called to discuss management options with their patients, providing detailed relative probabilities of the occurrence of key outcomes (see GRADE evidence table and Supplementary File S1, S2). When informed appropriately, the majority of patients is expected to opt for a parastomal hernia prevention with a synthetic non-absorbable mesh.

The clinical diagnosis of parastomal hernia, which was a core outcome in this guideline, may not always be important for patients (for example, small clinically detectable hernias, or hernias not causing symptoms and not affecting quality of life), and important variability may be expected in this regard.

The users of this guideline must be aware that the evidence informing these recommendations derives primarily, but not exclusively, from trials on elective surgery. Most trial reports did not provide subgroup data on emergency and elective surgery or clean and contaminated surgery, that would inform recommendations on these patient subgroups in the best possible way.

Furthermore, other factors, such as smoking and radiotherapy, might also be risk factors for the development of a parastomal hernia, whereas some of the listed factors might have a lesser effect. Findings from the CIPHER study are anticipated to provide more precise estimates on the effect of various factors on the risk of parastomal hernia, and users are advised to stay informed by the most recent evidence (see also Author Disclaimer).

Implications for Patients

Patients can be informed that the risks of perioperative complications, surgery for parastomal hernia and quality of life may be similar between prophylactic mesh versus no mesh. However, mesh prophylaxis likely reduces the risk of parastomal hernia by more than 50% (from 45% without mesh to 22% with mesh). There are no known frequent adverse events related to the mesh.

Of note, recent pooled long-term data from 3 randomized trials suggests that prophylactic mesh delays the occurrence of a parastomal hernia by about 5 years, rather than prevents it overall [45]. This hypothesis could not be tested across studies in the present analysis, because none had provided Kaplan-Meier plots nor hazard ratios, that would allow for time-to-event meta-analyses.

Implications for Researchers

The following research gaps were identified.

Randomized trials:

 - Long-term quality of life (low certainty)

 - Perioperative morbidity; ideally classified using the Clavien-Dindo classification (low certainty)

 - Surgery for parastomal hernia (low certainty)

 - Subgroup data on emergency/elective surgery, and contaminated/clean-contaminated surgery

 - Reporting both clinical and radiological recurrence. Significant clinical recurrence may be important to patients, however, radiological recurrence may predict future clinical recurrence.

Observational studies:

 - Long-term morbidity

Survey or qualitative studies:

 - Patients’, surgeons’ and stoma care nurses’ values and preferences related to the main outcomes

 - Patients’, surgeons’ and stoma care nurses’ thresholds for small, moderate and large effects with regards to key outcomes

 - Core outcome set of patient-important outcomes for studies reporting on stomas

Barriers and Facilitators

Implementing the intervention might be the most important challenge for surgeons who have not relevant experience. The majority of published information is derived from studies where a retromuscular mesh reinforcement was applied, and this practice may be particularly challenging to surgeons who are not familiar with abdominal wall reconstruction. We advise clinical visits or fellowships if the surgeon is not confident in using a prophylactic mesh. Professional organizations might want to consider offering training courses on cadaveric or animal models.

Organizational culture and resistance to change might be a substantial barrier. This document and the associated systematic review and meta-analysis [21] should serve as an independent, reliable source of information, that provides solid evidence on the balance between benefits and harms, in favor of benefits, especially from the patients’ perspective. Open, evidence-informed discussions and review of the evidence contained herein may inform organizational policy in the best possible way.

Monitoring

Use of the guideline by EHS members will be monitored through an online survey 2 years after publication. Feedback from target users in the form of email communications, letters to the editor, and comments in social media will be documented to be addressed in future versions of this guideline.

We suggest auditing of outcomes of stoma construction with a mesh and comparison to international standards, with observed risk intervals (based upon proportion meta-analysis of risks and 95% confidence intervals in the source studies; see online appendix [16]):

 • Parastomal hernia: 21.1% (13.8%–31.0%)

 • Major complications (Clavien-Dindo ≥3): 20.2% (7.2%–45.3%)

Validity Period

A scoping search of clinicaltrials.gov in March 2023 using the syntax (stoma OR ostomy OR colostomy) AND mesh with no limitations identified 47 records. Only one trial was identified as ongoing (NCT03799939), with estimated completion date in 2026. An average of 1.2 reports of randomized trials were published per year between 2012 and 2021. Substantial change in intervention effects and/or additional data on underreported outcomes (quality of life, surgery for parastomal hernia) is not expected earlier than 6 years since the last search. These recommendations are valid until December 2028.

Update

This guideline is planned to be updated in 2028, unless substantial new evidence will be identified.

Conclusion

A European interdisciplinary panel including patient representatives suggests the use of a synthetic non-absorbable mesh when constructing an end colostomy and recommends the routine use of a synthetic non-absorbable mesh in high-risk patients.

Data Availability Statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://osf.io/k4sh8/.

Author Contributions

AT and LR contributed to the systematic review. CS, FM, MA, UB, H-TB, SB, ML, SC, SD, KJ, MK, NS, CO, and CT contributed to the design of the study and revised it critically for intellectual content. OK and DM performed the statistical analyses and revised the work critically for intellectual content. SA coordinated the project, designed the study and revised it critically for intellectual content. All authors provided final approval of the version to be published.

Funding

This project was funded by the European Hernia Society.

Author Disclaimer

This clinical practice guideline has been developed under the auspice of the European Hernia Society (EHS). It is intended to be used primarily by health professionals (e.g., surgeons, anaesthetists, physicians) and to assist in making informed clinical decisions on diagnostic measures and therapeutic management. It is also intended to inform individual practice of allied health professionals (e.g., surgical nurses, dieticians, physical rehabilitation therapists, psychologists); to inform strategic planning and resource management by healthcare authorities (e.g., regional and national authorities, healthcare institutions, hospital administration authorities); and to inform patients wishing to obtain an overview of the condition of interest and its management. The use of recommendations contained herein must be informed by supporting evidence accompanying each recommendation and by research evidence that might not have been published by the time of writing the present document. Users must thus base their actions informed by newly published evidence at any given point in time. The information in the guideline should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time the guideline is developed and when it is published or read. The guideline is not continually updated and may not reflect the most recent evidence. The guideline addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This guideline does not mandate any particular course of medical care. Further, the guideline is not intended to substitute the independent professional judgment of the treating provider, as the guideline does not necessarily account for individual variation among patients. Even if evidence on a topic suggests a specific diagnostic and/or treatment action, users and especially health professionals may need to decide against the suggested or recommended action in view of circumstances related to patient values, preferences, co-morbidities and disease characteristics; available human, monetary and material resources; and healthcare infrastructures. EHS provides this guideline on an “as is” basis, and makes no warranty, express or implied, regarding the guideline.

Conflict of Interest

FM declared consultancy fees from Medtronic, Dynamesh, BD, and Gore. NS declared speakers fees on parastomal hernia prevention with mesh prophylaxis from Medtronic, WL Gore. All other panel members declared no financial conflict of interest. SA and FM were part of the guideline development group of the EHS Guidelines on Parastomal Hernias. ML, H-TB, and CO are authors of randomized trials and meta-analyses related to the content of this topic. Conflicts of interest were documented and managed as per Guidelines International Network Standards. Detailed conflict of interest statements of all contributors can be found in https://osf.io/k4sh8/.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontierspartnerships.org/articles/10.3389/jaws.2023.11549/full#supplementary-material

References