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Evaluating an experimental model consecutive to abdominal wall hernia repair outcome
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. (Clister)ORCID iD: 0000-0003-2538-2351
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2020. , p. 81
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2086
Keywords [en]
Hernia, mesh, luciferase, full thickness skin grafts, mice, IPOM, onlay, reinforcement materials, abdominal wall
Keywords [sv]
Bråck, nät, luciferas, fullhudstransplantat, FTSG, möss, IPOM, onlay, förstärkningsmaterial, bukvägg
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-170629ISBN: 978-91-7855-278-8 (print)ISBN: 978-91-7855-279-5 (electronic)OAI: oai:DiVA.org:umu-170629DiVA, id: diva2:1429852
Public defence
2020-06-05, Kirurgbiblioteket, korridor B91, målpunkt T, 9 tr, byggnad 1A, Norrlands Universitetssjukhus, Daniel Naezéns väg, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-05-15 Created: 2020-05-12 Last updated: 2020-05-13Bibliographically approved
List of papers
1. Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence
Open this publication in new window or tab >>Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence
2016 (English)In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 20, no 4, p. 509-516Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To compare recurrence and surgical complications following two dominating techniques: the use of suture and mesh in umbilical hernia repair.

METHODS: 379 consecutive umbilical hernia repair procedures performed between 1 January 2005 and 14 March 2014 in a university setting were included. Gathering was made using International Classification of Diseases codes for both procedure and diagnosis. Each patient record was scrutinized with respect to 45 variables, and the results entered in a database.

RESULTS: Exclusion <18 years-of-age (32), non-primary umbilical hernia (25), wrong diagnosis (7), concomitant major abdominal surgery (5), double registration (3) and pregnancy (1) left 306 patients eligible for analysis. Gender distribution was 97 women and 209 men. There was no difference between mesh and suture with regard to the primary outcome variable, cumulative recurrence rate, 8.4 %. Recurrence was both self-reported and found on clinical revisit and defined as recurrence when verified by a clinician and/or radiologist. Results presented as odds ratio (OR) with 95 % confidence interval (CI) show a significantly higher risk for recurrence in patients with a coexisting hernia OR 2.84, 95 % CI 1.24-6.48. Secondary outcome, postoperative surgical complication (n = 51 occurrences), included an array of postoperative surgical events commencing within 30 days after surgery. Complication rate was significantly higher in patients receiving mesh repair OR 6.63, 95 % CI 2.29-20.38.

CONCLUSIONS: Suture repair decreases the risk for surgical complications, especially infection without an increase in recurrence rate. The risk for recurrence is increased in patients with a history of another hernia.

Keywords
Hernia,  Umbilical,  Recurrence,  Surgical complication,  Suture,  Mesh
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-118320 (URN)10.1007/s10029-016-1466-x (DOI)000380119100003 ()26879081 (PubMedID)
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2020-05-12Bibliographically approved
2. Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position versus onlay position in mice
Open this publication in new window or tab >>Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position versus onlay position in mice
Show others...
2018 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 230, p. 155-163Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Importance: Hernia surgery requires reinforcement material with few side effects when used in the intraperitoneal position. Autologous skin grafting may meet this requirement, but animal experiments are obligatory before being applied in humans.

OBJECTIVE: To compare survival and effects of isogeneic full-thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice, with a control group using the onlay position. Primary end point was graft survival and secondary end point adhesion formation and inflammation through NF-κB activity.

METHODS: Design: Intervention study with 8-week follow-up in accordance with ARRIVE criteria, performed between 2015 and 2016.

SETTING: Animal laboratory.

PARTICIPANTS: Transgenic C57BL/6 mice with isogeneic background were used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were male or female mice >7 mo, with phenotype-positive for the luciferase gene (n = 20) or positive for NF-κB-luciferase gene (n = 4).

INTERVENTION: Full-thickness skin was grafted in the IPOM position and compared with grafts in the onlay position as controls. Survival was evaluated by regular longitudinal postoperative luminescence imaging over 8 wk. Adherence formation was evaluated macroscopically after sacrifice. Inflammation of full-thickness skin grafts in IPOM position of NF-κB mice was evaluated in four additional mice. Main outcome and measure: Survival of grafts, evaluated by luminescence.

RESULTS: Ten animals received grafts in the IPOM position, and 10 in the onlay position as controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale >2) were seen. Four animals with grafts in the IPOM position showed peak inflammation (NF-κB activity) 5 d after surgery subsiding toward the end of follow-up.

CONCLUSIONS: Full-thickness skin survives as well in the IPOM position as in the onlay control position, and few adherences develop. Further studies are required to fully characterize the tissue remodeling and repair processes associated with IPOM skin grafting. The result is relevant in the search for alternative reinforcement materials to be used in complex hernia surgery in humans.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Abdominal wall reinforcement, Acellular scaffold, Autologous full-thickness skin graft, Hernia repair, IPOM/onlay, Intraperitoneal, Isogeneic
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-151807 (URN)10.1016/j.jss.2018.04.041 (DOI)000441170900023 ()30100033 (PubMedID)2-s2.0-85047625025 (Scopus ID)
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2020-05-12Bibliographically approved
3. Full-thickness skin grafts for reinforcement of the abdominal wall – a cross-sectional histological study comparing intra- and extraperitoneal onlay positions in mice
Open this publication in new window or tab >>Full-thickness skin grafts for reinforcement of the abdominal wall – a cross-sectional histological study comparing intra- and extraperitoneal onlay positions in mice
(English)Manuscript (preprint) (Other academic)
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-170619 (URN)
Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-05-12
4. IPOM and onlay position of full thickness skin grafts comparable in collagen distribution – an experimental study in mice
Open this publication in new window or tab >>IPOM and onlay position of full thickness skin grafts comparable in collagen distribution – an experimental study in mice
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-170622 (URN)
Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-05-14

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