The PAPYRUS Study: Permanent vs. Absorbable Sutures in PrimarY Repair of Umbilical HerniaS: A Multicentre, Single-blind, Non-inferiority, Randomized Controlled Trial

Umbilical hernias make up a notable proportion of abdominal wall hernia repairs annually. Up to 25% of the population have asymptomatic umbilical hernias when examined using ultrasound. Recent computed tomography studies have identified umbilical hernia in up to 62% of the population. In Canada in 2019, there were 66,234 hernia surgeries performed. Similarly, there are around 175,000 umbilical hernia repairs per year in the United States.

The European Hernia Society (EHS) guidelines classify umbilical hernias by size as small (0-1cm), medium (more than 1 cm up to 4cm), and large (over 4 cm) based on diameter. Although many hernias are asymptomatic, intra-abdominal contents, such as fat or bowel, can protrude through the defect and result in a surgical emergency. Up to 20% of patients with asymptomatic umbilical hernia will later require elective surgery, and another 4% will require emergency surgery.

The EHS guidelines recommend mesh for all hernia repairs to reduce rate of recurrence, but quality of evidence is limited for hernias less than 1cm in size and therefore suture repair can be considered in these situations. Despite EHS guidelines, in many cases, umbilical hernias up to 2 cm in size are repaired with suture based on intra-operative assessment, for example, to avoid enlarging the defect necessary to accommodate a pre-peritoneal mesh with an overlap of 3cm.

The Americas Hernia Society Quality Collaborative Database found that mesh repairs were used for 82% of umbilical hernias \>1cm in diameter and 33% of those ≤1cm in diameter. For the National Health Service in England, 50% of umbilical hernias were repaired with mesh. This has led to the controversial reclassification of small hernias to those \<2cm in size. Of small (\<2cm) umbilical hernias captured by Herniamed, a hernia registry in Germany, Austria, and Switzerland, suture repair was performed for 76.5% of all cases.

The double-blind multicentre randomized controlled trial by Kauffmann and colleagues. compared suture to mesh repair of primary umbilical hernias and found an 8% recurrence rate following suture repair of umbilical hernias 1-2cm in size.

Based on clinical experience, there does appear to be higher rates of granuloma formation, sinus tract formation, and wound complications following the use of non-absorbable sutures. A systematic review and meta-analysis of techniques for the closure of midline abdominal incisions compared absorbable and non-absorbable suture and identified increased pain and suture sinus formation with the use of non-absorbable suture. Another systematic review comparing slowly absorbable versus non-absorbable suture for laparotomy fascial closure found no difference in hernia rate, but a higher rate of suture sinus formation after using non-absorbable suture. Rat models have also demonstrated that slowly absorbable polydioxanone suture may be preferable to permanent polypropylene suture due to a favourable macrophage response. Two large Danish studies compared non-absorbable, slowly absorbable, and quickly absorbable sutures and found no significant difference in recurrence rates.

There is currently insufficient evidence to recommend a suture type or technique for the suture repair of small umbilical hernias. The PAPYRUS Trial will help guide surgical management and suture decisions for thousands of patients annually in North America.

Common umbilical hernia repair complications include wound infection, pain, or hematoma. Multiple terms exist to describe complications following hernia surgery, and the Ventral Hernia Working Group has endeavoured to standardize this nomenclature by defining surgical site occurrence (SSO) and surgical site occurrences requiring procedural intervention (SSOPI). The PAPYRUS Trial will utilize these metrics as outcome variables because SSO will capture suture complications.

Suture type may play a role in reducing risk of recurrence and post-operative complications following primary suture repair of umbilical hernia. There have been no recent systematic reviews or meta-analyses comparing suture types for umbilical hernia. In the systematic review comparing mesh versus suture for elective repair of umbilical hernia, the studies using slowly absorbable suture may favour suture repair, whereas those using permanent suture may favour mesh repair. The European Hernia Society Guidelines state that there is insufficient clinical literature to determine whether permanent or absorbable suture should be used for the primary open repair of small umbilical hernias. This trial is needed to guide the best practices on the use of suture type when performing suture repair of primary umbilical hernia.

The results of this trial will add to the limited evidence base of the surgical management of umbilical hernias ≤2 cm in size and inform treatment guidelines for suture selection in the management of suture repair for primary umbilical hernia. This trial will guide surgical decisions on preferred suture material for primary umbilical hernia repair based on differences or lack of differences in recurrence, SSO, SSOPI, and patient-reported QoL.

Thus, the research question for this trial is: Does slowly absorbable polydioxanone suture compared to permanent polypropylene suture for primary open repair of small \<2 cm umbilical hernias result in non-inferior recurrence, SSO, SSOPI, or QoL at 24 months following surgery?

The primary hypothesis is that slowly absorbable polydioxanone suture will be non-inferior (at a non-inferiority margin of 5%) to permanent polypropylene suture for primary repair of small (≤2cm) umbilical hernias for recurrence at 24 months.

Secondary hypotheses are:

1. Slowly absorbable polydioxanone suture is non-inferior to permanent polypropylene suture for primary repair of small (≤2cm) umbilical hernias for SSO and SSOPI at 24 months post-operatively.

Slowly absorbable polydioxanone suture is non-inferior to permanent polypropylene suture for primary repair of small (≤2cm) umbilical hernias in patient-reported QoL as measured by the HerQLes and the SF-12 surveys at 24 months.

All analyses will be conducted on the intention-to-treat (ITT) population. Continuous data will be expressed as means and standard deviations and analyzed using two-sample t-test. Categorical data will be expressed as contingency tables using counts and percentages and analyzed using Chi-squared test or Fisher's exact test.

Recurrence, SSO, and SSOPI will be analyzed as follows:

* Descriptive statistics using Chi-squared test at 30 days, 12 months and 2 years * Kaplan-Meier survival analysis at 30 days, 12 months and 2 years * Log-rank test to compare differences in survival distributions * Cox proportional hazards model to adjust for covariates and obtain estimates for hazard ratio and 95% confidence interval

HerQLes and SF-12 scores:

• Differences between preoperative and postoperative HerQLes and SF-12 scores at 30 days, 12 months, and 2 years will be first evaluated using repeated measures ANOVA. If significant overall event is detected, then pairwise comparisons using paired t-test at 30 days, 12 months, and 2 years with Bonferroni correction will be conducted.

Subgroup analyses will be conducted to evaluate differences in hernia risk factors and sites. All analyses will be conducted using R Statistical Software (v4.5.0; Vienna, Austria).

• SSO [Срок оценки: 30 days, 12 months, 24 months]
• SSOPI [Срок оценки: 30 days, 12 months, 24 months]
• Quality of Life - HerQLes [Срок оценки: 30 days, 12 months, 24 months]
• Quality of Life - SF-12 [Срок оценки: 30 days, 12 months, 24 months]
• Post-Operative Complications [Срок оценки: 30 days]