Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model

Benlice, Çiğdem; Yildiz, Merve; Bağhaki, Semih; Ergüner, İlknur; Olgun, Deniz Çebi; Batur, Şebnem; Erdamar, Sibel; Ambarcioglu, Pinar; Hamzaoğlu, İsmail; Karahasanoğlu, Tayfun; Baca, Bilgi

doi:10.1007/s00384-015-2374-8

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…Second, the longest period of seton insertion was 21 d, an ideal result. Although in other studies, fistula-related thread insertion times were longer than ours[ 28 ],the prolongation of the seton insertion time may lead to longer fistula removal. However, given that our study required continuous weekly bowel administration, extending the duration of the study increased the damage to the animals.…”

Section: Discussioncontrasting

confidence: 53%

“…For the canine model, considering the unpredictable onset time and the difficulty of inducing fistula, the applicability of the model is limited. A previous study developed another experimental model in 16 rabbits[ 28 ] by the surgical creation of a high transsphincteric fistula. Another study developed a pig anal fistula model[ 29 ] (6 pigs) to test a new biological plug, which was confirmed by histology.…”

Section: Discussionmentioning

confidence: 99%

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Establishing a rabbit model of perianal fistulizing Crohn’s disease

Lu¹,

Liu²,

Niu³

et al. 2022

WJG

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BACKGROUND Crohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main complication of CD and is a difficult problem to solve at present. The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data. Therefore, an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa. AIM To improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies. METHODS Twenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis. Group A was treated with an improved equal interval small dose increasing method. The dosage of group B was constant. Seven days later, the rabbits underwent surgical creation of a transsphincteric fistula. Then, three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula. The rabbits were examined by endoscopy every 7 days, and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis. The disease activity index (DAI), colonoscopy and histological scores were recorded. Perianal endoscopic ultrasonography (EUS) was used to evaluate the healing of fistulas. RESULTS Except for the DAI score, the colonoscopy and histological scores in group A were significantly higher than those in group B ( P < 0.05). In the ideal model rabbit group, on the 7 th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness high signals. Histological inspection of the fistula showed acute and chronic inflammation, fibrosis, epithelialization and peripheral proctitis of the adjoining rectum. CONCLUSION The improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model, which was confirmed by endoscopy and pathology.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Establishing a rabbit model of perianal fistulizing Crohn’s disease

Lu¹,

Liu²,

Niu³

et al. 2022

WJG

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“…These results confirm those of the initial published models [ 9 ]. Some other experimental models of FAPLs exist in different species, including rats, pigs, and rabbits [ 18 , 19 , 20 , 21 , 22 ]. However, none of these models mimic fistulizing perianal Crohn’s disease since they do not exhibit proctitis or peripheral inflammation of the fistula tract.…”

Section: Discussionmentioning

confidence: 99%

A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn’s Disease

Cazelles

Collard

Lalatonne

et al. 2022

IJMS

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Fistulizing anoperineal lesions are severe complications of Crohn’s disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn’s disease.

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“…Rat [17], dog [18], and pig models were also established even the complex FIA [19], but no mouse model was established up to now. Rabbits are a good animal model for fistula research, which has been used to establish a model of transsphincteric fistula [20], aortocavitary fistula [21], esophageal anastomotic fistula [22], urinary fistula [23], and perianal fistula [24]. Rabbits have suitable body size, are easy to obtain, and can establish a large number of FIA models at a time; using this model can improve the therapeutic schedule.…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Stem Cells Are an Efficient Treatment for Fistula-in-ano of Japanese Rabbit

Qin

Wang

Huang

et al. 2019

Stem Cells International

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Fistula-in-ano (FIA, anal fistula) treatment remains a surgical challenge for coloproctologists. Adipose tissue-derived stem cells (ADSCs) are a new frontier in the treatment of FIA. In this study, we established a FIA model of Japanese rabbit and evaluated the effect of four treatments on fistula healing: ADSC transplantation, acellular small intestinal submucosa (ASIS), noncutting seton, and PBS as negative control. High-throughput RNA sequencing was also performed to investigate the anal tissue (normal and ADSC treatment group) expression profile of mRNA. Our data showed that ADSC treatment had the shortest time to promote fistula healing compared to the other treatments, and fistula filled with new adipose tissue and muscle cells without scar. Gene Ontology (GO) analysis of RNA-seq data showed that the differential genes are enriched in system development and animal organ development. Taken together, our findings demonstrate that ADSCs rapidly promote fistula healing through differentiation, a promising stem cell therapy for FIA. The rabbit is an effective animal model for evaluating FIA therapeutic options.

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Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model

Abstract: According to MRI and histopathological results, fistula tract curettage and fistula orifice closure improved transsphincteric anal fistula healing. Additionally, in this study, plug treatment favoring autologous dermal graft resulted in better healing.

Cited by 8 publications

References 36 publications

Establishing a rabbit model of perianal fistulizing Crohn’s disease

Establishing a rabbit model of perianal fistulizing Crohn’s disease

A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn’s Disease

Adipose-Derived Stem Cells Are an Efficient Treatment for Fistula-in-ano of Japanese Rabbit

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