Dataset Information

Wnt-? Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter.

ABSTRACT: Wnt-? catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed. Anal canal was harvested and processed for histochemical studies (Masson trichrome stain), molecular markers of fibrosis (collagen and transforming growth factor-?) and immunostaining for ? catenin. Surgical myotomy of the EAS resulted in significant impairment in anal canal pressure and EAS muscle L-T function. Following myotomy, the EAS muscle was replaced with fibrous tissue. Immunostaining revealed ? catenin activation and molecular studies revealed 1.5-2 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the ? catenin activation and fibrosis. EAS muscle content and function was significantly improved following sFRP-2 treatment. Our studies suggest that upregulation of Wnt signaling is an important molecular mechanism of injury related EAS muscle fibrosis and sphincter dysfunction.

SUBMITTER: Rajasekaran MR

PROVIDER: S-EPMC5430485 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter.

Rajasekaran M Raj MR Kanoo Sadhana S Fu Johnny J Bhargava Valmik V Mittal Ravinder K RK

Scientific reports 20170419 1

Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animal ...[more]

PMID: 28424479

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Project description:Background & aimsThe anal sphincters and puborectalis are imaged routinely with an endoanal magnetic resonance imaging (MRI) coil, which does not assess co-aptation of the anal canal at rest. By using a MRI torso coil, we identified a patulous anal canal in some patients with anorectal disorders. We aimed to evaluate the relationship between anal sphincter and puborectalis injury, a patulous anal canal, and anal pressures.MethodsWe performed a retrospective analysis of data from 119 patients who underwent MRI and manometry analysis of anal anatomy and pressures, respectively, from February 2011 through March 2013 at the Mayo Clinic. Anal pressures were determined by high-resolution manometry, anal sphincter and puborectalis injury was determined by endoanal MRI, and anal canal integrity was determined by torso MRI. Associations between manometric and anatomic parameters were evaluated with univariate and multivariate analyses.ResultsFecal incontinence (55 patients; 46%) and constipation (36 patients; 30%) were the main indications for testing; 49 patients (41%) had a patulous anal canal, which was associated with injury to more than 1 muscle (all P ≤ .001), and internal sphincter (P < .01), but not puborectalis (P = .09) or external sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted anal resting pressure. A patulous anal canal was the only significant predictor (P < .01) of the anal squeeze pressure increment.ConclusionsPatients with anorectal disorders commonly have a patulous anal canal, which is associated with more severe anal injury and independently predicted anal resting pressure and squeeze pressure increment. It therefore is important to identify a patulous anal canal because it appears to be a marker of not only anal sphincter injury but disturbances beyond sphincter injury, such as damage to the anal cushions or anal denervation.

Project description:BackgroundIncidence of complications following obstetrical anal sphincter injury (OASI) during vaginal delivery are poorly defined. They are only studied in high level maternities, small cohorts, all stages of perineal tear or in low-income countries. The aim of our study was to describe complications after primary OASI repair following a vaginal delivery in all French maternity wards at short and midterm and to assess factors associated with complication occurrence.MethodsWe conducted a historical cohort study using the French nationwide claim database (PMSI) from January 2013 to December 2021. All women who sustained an OASI repair following a vaginal delivery were included and virtually followed-up for 2 years. Then, we searched for OASIS complications. Finally, we evaluated factors associated with OASIS complication repaired or not and OASIS complication repairs.ResultsAmong the 61,833 included women, 2015 (2.8%) had an OASI complication and 842 (1.16%) underwent an OASI complication repair. Women were mainly primiparous (71.6%) and 44.3% underwent an instrumental delivery. During a follow-up of 2 years, 0.6% (n = 463), 0.3% (n = 240), 0.2% (n = 176), 0.1% (n = 84), 0.06% (n = 43) and 0.01% (n = 5) of patients underwent second surgery for a perineal repair, a fistula repair, a sphincteroplasty, a perineal infection, a colostomy and a sacral nervous anal stimulation, respectively. Only one case of artificial anal sphincter was noticed. Instrumental deliveries (OR = 1.56 CI95%[1.29;1.9]), private for-profit hospitals (OR = 1.42 [1.11;1.82], reference group "public hospital"), obesity (OR = 1.36 [1;1.84]), stage IV OASIS (OR = 2.98 [2.4;3.72]), perineal wound breakdown (OR = 2.8 [1.4;5.48]), ages between 25 and 29 years old (OR = 1.59 [1.17;2.18], refence group "age between 13 and 24 years old") and 30 and 34 years old (OR = 1.57 [1.14; 2.16], refence group "age between 13 and 24 years old") were factors associated with OASIS complication repairs.ConclusionsMaternal age, stage IV OASIS, obesity, instrumental deliveries and private for-profit hospitals seemed to predict OASIS complications. Understanding factors associated with OASIS complications could be beneficial for the patient to inform them and to influence the patient's follow-up in order to prevent complications, repairs and maternal distress.

Dataset Information

Wnt-? Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter.

Publications

Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter.

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