The Use of Biological Meshes in Diaphragmatic Defects – An Evidence-Based Review of the Literature

The widespread use of meshes for hiatal hernia repair has emerged in the era of laparoscopic surgery, although sporadic cases of mesh augmentation of traumatic diaphragmatic rupture have been reported. The indications for biologic meshes in diaphragmatic repair are ill defined. This systematic review aims to investigate the available evidence on the role of biologic meshes in diaphragmatic rupture and hiatal hernia repair. Limited data from sporadic case reports and case series have demonstrated that repair of traumatic diaphragmatic rupture with biologic mesh is safe technique in both the acute or chronic setting. High level evidence demonstrates short-term benefits of biologic mesh augmentation in hiatal hernia repair over primary repair, although adequate long-term data are not currently available. Long-term follow-up data suggest no benefit of hiatal hernia repair using porcine small intestine submucosa over suture repair. The effectiveness of different biologic mesh materials on hernia recurrence requires further investigation.


INTRODUCTION
Blunt or penetrating trauma of the abdomen and thorax may cause injury to the diaphragm (1). In the case of traumatic diaphragmatic rupture, abdominal organs such as the stomach, spleen, colon, or the liver may herniate into the thoracic cavity causing a wide range of symptoms, which may occur several years after the injury (2)(3)(4)(5). Chest X-ray is often diagnostic, whereas computed tomography and magnetic resonance imaging provide detailed information about the herniated structures and the size of the defect (6,7). There is no consensus on the absolute indications for surgery or the timing of surgical intervention. A traumatic rupture of the diaphragm is generally considered an indication for surgical repair, especially in the presence of symptoms.
Relevant literature evidence is limited, mainly due to the rarity of the condition. Primary suture repair or covering the defect with a synthetic mesh has been the standard of care during the past decades (8). Biologic meshes have been thought to be effective in closing the diaphragmatic defect, induce limited inflammatory response, and minimize adhesion formation.
In the presence of insufficient evidence, there is ongoing debate on the need of augmentation of the diaphragmatic hiatus during hernia repair (9). A number of randomized controlled trials (RCTs) and a meta-analysis have demonstrated lower recurrence rates after mesh repair; however, long-term data are not currently available (10). Several studies have reported complications, which has created skepticism with regard to the benefits of augmented hiatal hernia repair (11)(12)(13).Several biologic materials have been manufactured and are currently in use in surgical practice. Experimental data have shown biologic meshes to possess characteristics of an ideal mesh material, such as reduced adhesion formation, improved biocompatibility, decreased inflammatory response, and optimal neovascularization (14). Our objective was to review the evidence investigating the role of biologic meshes in traumatic repair of the diaphragm and in hiatal hernia repair.

Repair of Traumatic Diaphragmatic Defects
Electronic searches of the Medline database were conducted using the PubMed search engine. The following combination of terms and keywords was applied: (trauma OR traumatic OR posttraumatic OR rupture*) AND (diaphragm* OR phren*) AND (mesh OR implant). The search returned 141 reports. The last search was run in November 2014. Titles and abstracts were interrogated and clinical reports on the use of biologic material for closure of traumatic diaphragmatic defects were selected. The full texts of 17 articles were assessed for eligibility; three relevant reports were identified (15)(16)(17). The remaining 15 articles were excluded because they reported on the use of synthetic materials in diaphragmatic rupture repair or did not provide relevant outcomes. A summary of the study characteristics and outcomes is presented in Table 1.

Hiatal Hernia Repair with Mesh Augmentation
Similarly, Medline was searched to identify relevant clinical evidence using the PubMed interface up to November 2014. The keywords (hiat*) AND (hernia) AND (mesh OR implant) were used. Of a total of 309 records, 28 articles were selected for full text review based on relevant information from titles and abstracts. Twenty-two articles provided relevant outcome data on meshreinforced hiatal hernia repair with biologic meshes . The study characteristics and outcomes are listed in Table 2.

Repair of Traumatic Diaphragmatic Defects
Two case reports and one case series reported on the use of biologic meshes in traumatic diaphragmatic rupture. Four chronic traumatic defects and two acute ruptures were repaired laparoscopically, or with a laparotomy or a combined (thoracotomy and laparotomy) approach using human acellular cadaveric dermis (HACD) or porcine small intestine submucosa (SIS). Two of the repairs were performed in contaminated surgical fields, one due to inflammation of the herniated gallbladder and one due to pleural empyema. No septic complications requiring prolonged hospital stay or reintervention were reported. Chest X-ray in five of these cases did not reveal recurrence within a 6-to 24-month follow-up period.

Hiatal Hernia Repair with Mesh Augmentation
A plethora studies reporting use of biologic mesh augmentation of the esophageal hiatus have been published since 2003. Most of these are retrospective industry-sponsored cohort studies. Both    HACD and SIS meshes have been used, most commonly in a U-shape or a pantaloon fashion, placed in a retroesophageal position with the limbs of the mesh encircling the esophagus. The graft is anchored to the diaphragm and, in some cases, to the esophagus with non-absorbable sutures, tacks, or fibrin sealant, most commonly following suture repair of the crura or in a tension-free bridging fashion. A Collis gastroplasty has also been reported as a lengthening procedure in cases of a short esophagus (27,32). Although no adverse effects associated with allografts or xenografts have been reported, in a chart review of 51 pediatric patients, Sharp and colleagues found that fever occurred more frequently after mesh repair and this group of subjects presented with a higher mean temperature during their hospital stay (37). The best available evidence is provided by two well-designed RCTs (21)(22)(23)39). In an industry-sponsored trial, Oelschlager and colleagues assigned 108 patients with paraesophageal hernia to receive either U-shaped SIS or suture repair. The authors found a significant reduction in the incidence of hernia recurrence (24 vs. 9%) at 6 months (21); however, long-term follow-up data (median 58 months, range 40-78) demonstrated no such benefit (22). Although this outcome may be biased by significant attrition (exceeding 20%), the reported recurrence rate for the mesh group remains unacceptably high.
In a recent double blind RCT that was sponsored by a national authority, suture mesh repair was compared with SIS or collagencoated titanium mesh augmentation of the hiatus(39); similar recurrence rates at 6 months (7.9 vs. 5.9%, respectively) were found in the suture and biologic mesh repair groups, whereas no recurrence occurred in the synthetic mesh group. This finding, however, should be cautiously interpreted in the presence of wide confidence interval (95% confidence interval, 0.24-9.78). Longterm follow-up data of this trial are pending.
Most authors have focused their interest on potential beneficial effects of biologic grafts in paraesophageal hernia. In a cohort study, Schmidt and colleagues compared suture repair and mesh augmentation with HACD in small hernias (1-5 cm as assessed by barium upper gastrointestinal series or esophagogastroscopy) (36). A benefit of mesh repair was demonstrated, as indicated by a reduced recurrence rate (16 vs. 0%) at 1 year and improvement of symptoms of dysphagia.

DISCUSSION
Limited evidence exists investigating the role of biologic meshes in traumatic diaphragmatic repair. Low quality evidence (Level 4) suggests that this approach is feasible, at least in chronic cases. Biologic meshes have also been used in contaminated surgical fields with favorable results (Level 5). Because of the difficulties randomizing patients in the acute setting and the rarity of this condition, clinicians should be encouraged to publish their experience with biologic meshes in traumatic diaphragmatic rupture.
Level 1b data currently support lower recurrence rates for biologic mesh repair in the setting of paraesophageal hernia in the short term with conflicting evidence, whereas level 2b data support that this outcome benefit is lost in the long term. In a recent systematic review and meta-analysis of randomized and observational studies conducted by our research group, we found a beneficial short-term effect of mesh augmentation of the hiatus using biologic mesh (odds ratio 3.74, 95% confidence interval 0.92-8.98, p = 0.003) (40). However, no long-term outcome data were available for meta-analysis. Low quality data (level 4) suggest that patients with hiatal hernia measuring between 1 and 5 cm may benefit from biologic mesh augmentation. Nevertheless, costbenefit assessment is lacking and the available evidence favoring biologic over synthetic meshes is insufficient.
The impact of type of biologic graft on hernia recurrence remains to be investigated. Further experimental and clinical research is required to assess new biologic implants in hiatal hernia repair. Although current data have shown SIS implants to be associated with high recurrence rates, other biologic materials have not been adequately investigated. Considering the rarity of cases with traumatic diaphragmatic defects, the effectiveness of biologic implants in such situations may be extrapolated from evidence derived from hiatal hernia repair. Future RCTs are required to investigate the role of biologic meshes in both paraesophageal and small hiatal hernias and evaluate their comparative efficacy to synthetic meshes.

AUTHOR CONTRIBUTIONS
Conception and design: SA, FK. Acquisition and interpretation of data: SA, FG, RP. Drafting the work or revision for important intellectual content: SA, FG, RP, FK. Final approval: SA, FG, RP, FK. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: SA, FG, RP, FK.