Evaluating an experimental model consecutive to abdominal wall hernia repair outcome

Sammanfattning: Background: Abdominal wall hernia is a common surgically treated condition. Patients with primary umbilical hernia are operated with suture or mesh repair, but recurrence and complication rates have been debated.Larger abdominal wall hernias need implantation of reinforcing material for repair. Synthetic implants are dominating. In complex hernia cases neither synthetic nor biologic implants are optimal. A randomized controlled trial has revealed satisfactory results from autologous full thickness skin grafts (FTSGs) in onlay position. Further application intraperitoneally (IPOM) in laparoscopic surgery and for repair of parastomal hernia in humans, must be based on a translational concept including animal and morphologic studies since the IPOM position has not been evaluated systematically. This thesis aims to be a link in a translational chain, focused on establishing an experimental model for FTSG evaluation.Problem formulations: -          Does synthetic mesh decrease the probability of recurrence and/or complications in primary umbilical hernia?-          Can FTSG be evaluated for IPOM versus onlay position in a transgenic mouse model using luminescence from substrate activated by the enzyme luciferase expressed in donor tissue?-          How does the FTSG in IPOM position perform compared to FTSG in onlay position?Results:Recurrence rate at a median of 6.8 years follow-up was 9% for suture- and 8% for mesh repair, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.40-2.02, in 306 patients investigated patients. Surgical complications were in favor of suture repair, OR 6.6, 95% CI 2.29-20.38.In an experimental evaluation of FTSG, 20 mice received intervention with either onlay or IPOM graft. Survival of FTSG was revealed for 8 weeks by luminescence detection. All animals regained weight within 8 days in median. At sacrifice 8 weeks postoperatively, adhesions were evaluated by a modified Jenkins’ scale. No onlay mice displayed adhesions while two IPOM mice had firm and one dense adhesions. Inflammatory response evaluated in four animals expressing nuclear factor ĸB (NF-ĸB) showed a peak at day 2 and returned to stable low levels from day 5 until end of the 33-day follow up. FTSG in IPOM position showed similar morphology and immunohistochemistry stain patterns as controls in onlay position. There was a low expression of the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and myeloperoxidase. Vascular structures were visualized by von Willebrand factor-stain. In Picrosirius red stain, collagen bundles in dermis of FTSG in both IPOM and onlay position was thicker, compared to internal controls. FTSG extracellular matrix had metamorphosed mainly into thick collagen bundles, with partially degraded skin appendages. Matrix metalloproteinases (MMP)-stain from MMP-1, MMP-8 and MMP-9 were not co-distributed with their respective collagen substrates.Conclusions:Synthetic mesh does not decrease the probability of recurrence but significantly increase complications in repair of small umbilical hernia. FTSG can be evaluated in IPOM and onlay position in an experimental transgenic mouse model. The two positions were similar in terms of graft survival, few adhesions, micro-vessel formation, low grade inflammation, cyst formation and collagen distribution. FTSG implanted in IPOM position does not exhibit any systematic differences from onlay position, thus from this perspective no difference in biomechanical behavior can be anticipated.