Materiały źródłowe

• #1 Anorectal fistula: Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/anorectal-fistula-clinical-manifestations-diagnosis-and-management-principles

  Anorectal fistulas are sometimes also referred to as „fistula-in-ano.” An anorectal fistula is the chronic manifestation of the acute perirectal process that forms an anal abscess. When the abscess ruptures or is drained, an epithelialized track can form that connects the abscess in the anus or rectum with the perirectal skin. […] Over 90 percent of anorectal fistulas are cryptogenic. Cryptoglandular fistulas originate from an infected anal crypt gland. There are typically 8 to 10 anal crypt glands, arranged circumferentially within the anal canal at the level of the dentate line. The glands penetrate the internal sphincter and end in the intersphincteric plane. An anorectal fistula is the connection between two epithelial structures and connects the anal abscess from the infected anal crypt glands to the perirectal skin and occasionally to other pelvic organs.

• #2 Fistula-in-Ano – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557517/

  Fistula-in-ano is a tract connecting the anal canal to the perianal skin. […] A fistula-in-ano is an epithelial-lined tract connecting the anal canal to the perianal skin. Anal fistulas can have many causes but are most commonly the result of an anorectal abscess. […] Fistula-in-ano often occurs following anorectal abscess. An anorectal abscess occurs when an anal gland becomes obstructed, resulting in infection and abscess formation. […] Simple anal fistulas are thought to be due to glandular obstruction resulting in an anorectal abscess and, ultimately, a fistula. […] Complex fistulas include those that involve more than 30% of the external sphincter, fistulas with multiple tracts, recurrent fistulas, and those associated with other predisposing factors, including Crohn disease and radiation treatment.

• #3 Current concepts in the pathogenesis of cryptoglandular perianal fistula

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7894698/

  Cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery. The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts. Involvement of proctodeal glands in the inflammatory process could play a primary role in the formation of cryptoglandular perianal fistula. […] The most common theory of the formation of anorectal abscess and subsequent perianal fistula, stated by Parks in 1961, is the pathology of obstructed proctodeal glands and ducts. […] The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts.

• #4 Anal fistula pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Anal_fistula_pathophysiology

  Anal fistula develops from infection of anal crypts gland. The initial infection occurs in the ducts of the anal glands and the spread of infection results in the formation of the abscess. […] The crytoglandular theory states that obstruction of anal gland duct results in a infection. The presence of these glands deep in relation to the anal canal and sphincter, the infection follows the path of least resistance resulting in abscess formation at the termination of the gland. […] If the abscess is ruptured, a fistula is formed.

• #5 Fistula-in-Ano: Practice Essentials, Anatomy, Etiology

  https://emedicine.medscape.com/article/190234-overview

  Most fistulas are thought to arise as a result of cryptoglandular infection with resultant perirectal abscess. The abscess represents the acute inflammatory event, whereas the fistula is representative of the chronic process. […] The cryptoglandular hypothesis states that an infection begins in the anal canal glands and progresses into the muscular wall of the anal sphincters to cause an anorectal abscess. […] After surgical or spontaneous drainage in the perianal skin, a granulation tissue-lined tract is occasionally left behind, causing recurrent symptoms. Multiple series have shown that formation of a fistula tract after anorectal abscess occurs in 7-40% of cases. […] Other fistulas develop secondary to trauma (eg, rectal foreign bodies), Crohn disease, anal fissures, carcinoma, radiation therapy, actinomycoses, tuberculosis, and lymphogranuloma venereum secondary to chlamydial infection.

• #6 Current concepts in the pathogenesis of cryptoglandular perianal fistula

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7894698/

  An inflammatory process appears to play a crucial role. […] The aim of this narrative review was to investigate the current knowledge of the etiopathogenesis of cryptoglandular perianal fistula to characterize the role of pathological and inflammatory factors in the development of chronic inflammation. […] Recent findings further support the hypothesis that cytokines and immune cells contribute to the development and persistence of perianal fistulas. […] In a recent study, higher secretion of proinflammatory cytokines, such as IL-1beta and IL-8 were observed in perianal fistulous tracts compared with normal perianal tissue. […] The role of epithelial-to-mesenchymal transition (EMT) has been proven in normal and neoplastic processes related to wound healing. […] EMT may promote an increased migration of epithelial cells, which could contribute to fistula canal development.

• #7

  https://link.springer.com/article/10.1007/s10151-017-1645-5

  Anal fistulas continue to be a problem for patients and surgeons alike despite scientific advances. […] Their development and persistence likely involves a multifaceted interaction of histological, microbiological, and molecular factors. […] The presence of a perianal abscess that contains gut flora commonly leads to the development of anal fistula. […] Recent work has shown an increased expression of proinflammatory cytokines and epithelial to mesenchymal cell transition in both cryptoglandular and Crohns perianal fistulas. […] This suggests that molecular mechanisms may also play a role in both fistula development and persistence. […] The aim of this study was to examine the histological, microbiological, molecular, and host factors that contribute to the development and persistence of anal fistulas. […] Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohns disease. […] Pro-inflammatory cytokines in cryptoglandular anal fistulas. […] What role do bacteria play in persisting fistula formation in idiopathic and Crohns anal fistula?

• #8 The pathogenesis of cryptoglandular anal fistula: New insight into the immunological profile. | Sigma-Aldrich

  https://www.sigmaaldrich.com/KE/en/tech-docs/paper/1621718?srsltid=AfmBOor1557lHdnIRD-jB4r2ibzJQAMmkw-sGGgNJyArweBN-WDuP4qO

  The aetiology of cryptoglandular anal fistula (AF) is poorly understood. Evidence suggests that persistence and/or recurrence of the disease is more related to inflammatory than infectious factors. […] The aim of this study was to investigate the immune profile of cryptoglandular AF and to perform a histopathological characterization. […] Specific cytokine pathways differentiated AF from healthy tissue: pro-inflammatory cytokines interleukin (IL)-1β, IL-4, IL-8 and IL-17 and the anti-inflammatory cytokine IL-10 were overexpressed in AF compared with controls. […] Moreover, we showed that Tc17 cells characterize AF patients, thus confirming the enzyme-linked immunosorbent assay data. […] Furthermore, elevated infiltration of CD68+ myeloid cells and a reduction of the M1/M2 ratio characterize AF patients. […] For the first time an important prevalence of Tc17 cells and a reduction in the M1/M2 ratio was observed, thus suggesting new insights into the immunological characterization of AF patients.

• #9 Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula

  https://www.mdpi.com/1422-0067/25/3/1501

  The epithelial-to-mesenchymal transition (EMT) has been described in normal and neoplastic processes, including wound healing. […] The EMT, through stimulating chronic inflammation and the release of proinflammatory cytokines, could then lead to an increased migration of epithelial cells which could contribute to fistula formation. […] The gelatinases A (MMP-2) and B (MMP-9) are found among others in the gastrointestinal tract and have been shown to be highly upregulated in the large intestine during inflammatory processes. […] In accordance with the discussed papers, we noted that patients with complex perianal fistulas were characterized by higher expression of MMP-2. […] Multiple studies have indicated that the expression of MMP-9 is increased during episodes of acute inflammation in individuals with IBD.

• #10 Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula

  https://www.mdpi.com/1422-0067/25/3/1501

  The strong expression of Snail and the absence of E-cadherin may serve as markers for identifying the occurrence of EMT. […] We observed that indirect abnormalities in adipokine levels present substantial involvement in the inflammatory and metabolic pathways in the human organism and can affect the complexity, progression, and, therefore, treatment of cryptoglandular anal fistulas.

• #11 Exploring Perianal Fistulas: Insights into Biochemical, Genetic, and Epigenetic Influences—A Comprehensive Review

  https://www.mdpi.com/2036-7422/16/1/10

  Based on current knowledge, EMT and matrix remodeling enzymes appear to play a special role in the pathophysiology of fistulas associated with CD. The EMT process produces transitional cells (TCs). In this case, epithelial cells transform into mesenchymal cells (like myofibroblasts) while gaining the ability to migrate and penetrate adjacent tissues. A regulatory factor crucial to the development of EMT is TGF-β. […] A complete understanding of the pathophysiology of CD-associated fistulas has not yet been obtained. Two mechanisms seem to have a major role: EMT and matrix remodeling enzymes. […] The epithelial-to-mesenchymal transition (EMT) is mainly activated by TGF-β. The production of TGF-β may increase due to TNF-α; thus, it is also capable of inducing EMT via secondary messengers: Smad2, Smad3, and Smad4.

• #12 Current concepts in the pathogenesis of cryptoglandular perianal fistula

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7894698/

  Abnormal ECM integrity significantly impairs fistula healing. […] The latest studies describe a significant role of white adipose tissue (WAT), which apart from its ability to respond to afferent signals from the endocrine system and the central nervous system, is also involved in the expression and secretion of factors with important functions. […] These findings and similar cytokine profiles of cryptoglandular and CD perianal fistulas identified by Haddow et al. suggest that perianal fat tissue may play a crucial role in fistula treatment. […] The development of anal fistulas may depend on the presence of specific gut bacteria in anorectal abscesses. […] One study proposed that local bacterial replication might be an inflammatory factor in cryptoglandular perianal fistula development. […] Data confirming this thesis are insufficient; however, this shift in the etiology of anal fistula would have a strong impact on treatment; in particular, regarding the use of antibiotics.

• #13 The impact of adipose fat tissue on the pathogenesis o…

  https://ppch.pl/seo/article/01.3001.0054.4682/en

  Recent studies have highlighted the involvement of visceral adipose tissue (VAT) in colonic inflammation, linking its abnormal accumulation to a more severe disease phenotype and poorer prognosis in perianal patients. […] Patients with complex fistulas displayed a distinct cytokine and adipokine profile, characterized by elevated levels of IL-1β, IL-8, resistin, and leptin, and reduced levels of adiponectin. […] Our study revealed a higher expression of leptin in patients with complex perianal fistulas compared to those with simple fistulas. […] Our findings align with the observations of increased resistin expression in patients with complex cryptoglandular perianal fistulas compared to those with simple fistulas. […] We propose a potential mechanism for the impaired healing of fistulas, emphasizing the elevation of proinflammatory adipokines and the decrease of anti-inflammatory adiponectin and their relation to proinflammatory cytokines.

• #14 Preliminary study on the pathogenesis of anal fistula | medRxiv

  https://www.medrxiv.org/content/10.1101/2021.04.15.21254769.full

  Anal gland infection is one of the main pathogenic factors of anal fistula. The absence or diminished secretion of goblet cells could lead to the exposure of columnar epithelial cells to bacteria. In recent years, studies have found that most of the microorganisms in perianal abscess and anal fistula are intestinal bacteria. So, it can be considered that the occurrence and development of anal fistula is closely related to gut microbiota. However, the molecular mechanism of gut microbiota acting on the epithelial cells of anal gland leading to the occurrence and development of anal fistula has not been explored. […] The occurrence of anal fistula may be related to the abnormal permeability of mucus layer and the change of intestinal flora composition. The absence or diminished secretion of goblet cells may cause exception of the permeability of mucus layer which makes the columnar epithelial cells of anal gland exposed to the direct contact of peptidoglycan. The metabolite of pathogenic microorganisms could activate the signal pathway (i.g. NLR/NF-B) which leading to the overexpression of inflammatory factors and cause anal fistula.

• #15 Preliminary study on the pathogenesis of anal fistula | medRxiv

  https://www.medrxiv.org/content/10.1101/2021.04.15.21254769.full

  The abnormalities of goblet cells could cause the abnormal penetrability of mucus layer, and then the columnar epithelial cells are exposed to the direct contact of microorganisms. Finally, columnar epithelial cells release inflammatory factors excessively could cause anal fistula. […] Studies have found that NLR is ubiquitous in epithelial cells which suggest that PGN could up-regulate NLR/NF-B signaling pathway and promote the release of inflammatory factors in columnar epithelial cells of anal gland which may be an important pathogenic mechanism of anal fistula.

• #16 The potential roles of gut microbiome in anal fistula | AMB Express | Full Text

  https://amb-express.springeropen.com/articles/10.1186/s13568-023-01560-9

  Anal fistula is a common proctological disease, but the thorough mechanisms of the anal fistula formation are still unclear. […] The disruption of the balance of the gut microbiome can lead to the intestinal diseases like colorectal cancer and inflammatory bowel diseases. […] We hypothesize that the disruption of the balance of the gut microbiome plays an important role in the pathogenesis of anal fistula. […] Notably, there were significant differences in distribution of microbiota between the groups. […] The biodiversity of gut microbiome in the rectum revealed significant difference between anal fistula patients and healthy individuals. […] The phylum Synergistetes, a gram-negative anaerobe in the oral cavity, was related to periodontal and endodontic infections. […] We believe that the increase in the relative abundance of Synergistetes may cause persistent inflammation, which can lead to the anal fistula.

• #17 The potential roles of gut microbiome in anal fistula | AMB Express | Full Text

  https://amb-express.springeropen.com/articles/10.1186/s13568-023-01560-9

  We also found that at the genus level, Blautia, Faecalibacterium, Ruminococcus, Coprococcus, Bacteroides, Clostridium, Megamonas and Anaerotruncus were highly enriched in anal fistula patients, while the microbiome of healthy individuals was enriched with Peptoniphilus and Corynebacterium. […] The above results suggested that the diagnostic prediction model based on the microbiota of gut microbiome has high accuracy and may provide innovative biomarkers for anal fistula patients.

• #18 Discussion on the mechanism of intestinal flora participating in the pathogenesis of anal fistula by inducing EMT

  http://www.zhqkyx.net/en/article/doi/10.16766/j.cnki.issn.1674-4152.003346

  Anal fistula is a common and frequently-occurring disease in anorectal diseases, with perianal pus, pain, and itching as the main symptoms, and young men as the main patients. At present, the pathogenesis of anal fistula is still unclear, and the main treatment is surgery. […] Studies have shown that changes in the bacterial flora and disturbance of the intestinal microenvironment are involved in the occurrence of anal fistulas, which are specifically manifested in the increase in the abundance and diversity of bacterial flora and the infection of enterogenic bacteria. Epithelial-mesenchymal transition (EMT) is an important phenotypic change in diseases such as cancer. […] It is concluded that the formation of anal fistula may be due to changes in intestinal flora that affect the homeostasis of the intestinal mucosal barrier, thereby inducing the occurrence of EMT and participating in the development of inflammation-induced fibrosis and fistulas.

• #19 The Radiology Assistant : Perianal Fistulas

  https://radiologyassistant.nl/abdomen/rectum/perianal-fistulas

  Perianal fistula is a common disorder that often recurs because of infection that was missed at surgery. […] The causes of perianal fistulas: Primary: Obstruction of anal gland which leads to stasis and infection with absces and fistula formation (most common cause). […] Secondary: Inflammatory bowel diseases (Crohn’s disease more common than colitis ulcerosa). […] The most widely used classification is the Parks Classification which distinguishes four kinds of fistula: intersphincteric, transsphincteric, suprasphincteric and extrasphincteric. […] Treatment is focussed on the elimination of the primary and secondary tracts, prevention of recurrence and to retain continence.

• #20 Anal Fistulas and Fissures: Background, Pathophysiology and Etiology, Epidemiology

  https://emedicine.medscape.com/article/776150-overview

  An anal fistula is an inflammatory tract between the anal canal and the skin. The four categories of fistulas, based on the relationship of fistula to sphincter muscles, are intersphincteric, transsphincteric, suprasphincteric, and extrasphincteric. […] Most anal fistulas originate in anal crypts, which become infected, with ensuing abscess formation. When the abscess is opened or when it ruptures, a fistula is formed. An anal fistula can have multiple accessory tracts complicating its anatomy. […] Other causes of anal fistulas include opened perianal or ischiorectal abscesses, which drain spontaneously through these fistulous tracts. Fistulas are also found in patients with inflammatory bowel disease, particularly Crohn disease. […] Anal fistulas can also be associated with diverticulitis, foreign-body reactions, actinomycosis, chlamydia, lymphogranuloma venereum (LGV), syphilis, tuberculosis, radiation exposure, and HIV disease. Approximately 30% of patients with HIV disease develop anorectal abscesses and fistulas.

• #21 Perianal fistula | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/perianal-fistula?lang=us

  Perianal fistula (or fistula-in-ano) (plural: fistulae or fistulas) is the presence of a fistulous tract across/between/adjacent to the anal sphincters and is usually an inflammatory condition. […] The most commonly accepted pathophysiology is the cryptoglandular hypothesis, which suggests that obstruction of the deep submucosal glands results in infection and abscess formation in the intersphincteric space, which consequently drains inferiorly between the sphincters, opening onto the skin surface or, less commonly, erodes through both the internal and external sphincters into the ischiorectal space, then onto the skin surface. […] Transsphincteric fistulae are secondary to ischiorectal abscesses, with a resultant extension of the tract through the external sphincter. Intersphincteric fistulae are due to perianal abscesses. Suprasphincteric fistulae are due to supralevator abscesses.

• #22 Fistula-in-Ano – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557517/

  The treatment of an anal fistula depends on the location of the fistula as well as precipitating factors. Most fistulas are treated surgically, through a variety of different procedures depending on external and internal sphincter involvement. […] The ligation of intersphincteric fistula tract (LIFT) procedure can be used for the treatment of simple and complex fistulas with an average success rate of 71%. […] Fistula-in-ano is not a life-threatening condition but can have a significant impact on a patients quality of life. Treatment is focused on the destruction of the fistula tract with the preservation of the sphincter complex. […] The greatest risk of surgical treatment involves disruption of the external sphincter resulting in fecal incontinence. […] Recurrence of fistula-in-ano is higher in obese patients, smokers, and those with a history of anal surgery.

• #23 Anal fistula – Wikipedia

  https://en.wikipedia.org/wiki/Anal_fistula

  Treatment, in the form of surgery, is considered essential to allow drainage and prevent infection. Repair of the fistula itself is considered an elective procedure which many patients opt for due to the discomfort and inconvenience associated with an actively draining fistula. […] Definitive treatment of a fistula aims to stop it recurring. Treatment depends on where the fistula lies, and which parts of the internal and external anal sphincters it crosses. However, treatment is challenging as complete eradication of the anal sphincters may lead to continence impairment, but failure to excise the affected areas results in recurrence. Those already treated for recurring anal fistula are at higher risk to experience re-recurrence of the disease. […] The LIFT procedure is based on secure closure of the internal opening and removal of infected cryptoglandular tissue through the intersphincteric approach. Essential steps of the procedure include, incision at the intersphincteric groove, identification of the intersphincteric tract, ligation of intersphincteric tract close to the internal opening and removal of intersphincteric tract, scraping out all granulation tissue in the rest of the fistulous tract, and suturing of the defect at the external sphincter muscle.

• #24 Recurrent anal fistulas: When, why, and how to manage?

  https://www.wjgnet.com/2307-8960/full/v8/i9/1586.htm

  Anal fistula is a commonly encountered anal condition in the surgical practice. Despite being a benign condition, anal fistula remains to represent a surgical challenge, particularly the complex type of fistulas. One of the common complications of anal fistula surgery is the persistence or recurrence of the pathology, both defined as failure of surgery. Recurrent anal fistulas after previous surgery represent a unique challenge and usually warrant more experience with anal surgery to address the cause of recurrence and navigate through the disturbed anatomy after previous surgery. The majority of anal fistulas in the adult population are attributed to cryptoglandular infection which starts in the intersphincteric space and then spreads in various directions. Treatment of complex anal fistulas is challenging as these fistulas tend to entail a significant portion of the anal sphincters, rendering complete eradication of the fistula tract associated with a considerable risk of continence impairment. On the other hand, failure to excise the primary tract and its secondary extensions and to drain sepsis adequately may eventually result in persistence or recurrence of the anal fistula. Success of anal fistula surgery is generally defined as complete healing of the anal wound by epithelization without residual tract, external or internal openings, or perianal discharge. Various risk factors for failure of healing after anal fistula surgery have been identified. These risk factors can be broadly classified into preoperative, intraoperative, and postoperative factors. The preoperative predictors of recurrence are related to the fistula anatomy and patients comorbidities. The position of the primary tract can predict the onset of recurrence before surgery as high trans-sphincteric, suprasphincteric fistula, and extrasphincteric fistulas are typically more complex than simple intersphincteric fistulas and are more difficult to eradicate. A number of surgery-related factors can increase the risk of recurrence of anal fistula. Amongst these factors is the experience of the surgeons, selection of the procedure along with some technical considerations. Care of the anal wound after anal fistula surgery is crucial to achieve a successful outcome. Recurrent anal fistulas after previous surgery represent a unique challenge because they are associated with a high risk of re-recurrence and continence impairment. It has been estimated that previous fistula surgery increases the odds of recurrence after further surgery by two to three folds. The assessment plan entails detailed history taking, clinical examination, and investigations. The first and most important step in the treatment of recurrent anal fistulas is to identify and address the cause of recurrence. If the anal fistula is secondary to certain disease, then it would be reasonable to treat the primary disease firstly.

• #25 Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials | Stem Cell Research & Therapy | Full Text

  https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03331-6

  Stem cell therapy is an emerging treatment of perianal fistulas rooted the stem cells multipotential and self-renewal capacity. […] This new application accounted for the following aspects. Firstly, MSCs promote the regeneration and migration of vascularity. Admittedly, angiogenic action is a key point in any type of damage healing for blood-carrying nutrients or metabolic waste products. […] Therefore, MSCs are an alternative choice for complex perianal fistulas. […] Our study supports that MSCs transplantation could be a new therapeutic method for the treatment of complex perianal fistulas of two different origins with both short/long-term efficacy and sustained healing. The efficacy of MSCs of different cell types, cell sources and cell dosage is superior to the control. Besides, local MSCs therapy has shown more promising results of CD fistulas. Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future.

• #26 Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials | Stem Cell Research & Therapy | Full Text

  https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03331-6

  Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. […] MSCs are characterised by self-renewal and multi-differentiation ability. Furthermore, they can secrete cytokines through autocrine or paracrine modes in a morbid environment to promote re-epithelialisation and blood vessel regeneration. […] MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs efficacy.

• #27 New Techniques for Treating an Anal Fistula

  https://coloproctol.org/journal/view.php?number=1541

  This article aims to review the literature and to identify the new sphincter-preserving techniques, such as the anal fistula plug, the ligation of intersphincteric fistula tract (LIFT) procedure and the cell therapy, used in the management of anal fistulae. […] The anal fistula plug is expected to provide a collagen scaffold to promote tissue in growth and fistula healing. […] The technique of plug deployment is as follows: The tract is explored, probed, and irrigated gently with hydrogen peroxide. […] The LIFT procedure has been used in five case series with promising early results. […] The BioLIFT technique is a variation of the LIFT technique in which a bioprosthetic is placed in the intersphincteric plane to reinforce the closure of the fistula tract. […] An advantage of using stem cells to treat an anal fistula is that, because tract resection is not required, the treatment does not injure the anal sphincter. […] To the colorectal surgeon, the complex anal fistula remains a challenging condition to manage despite the best of technologic advances.

• #28 Discussion on the mechanism of intestinal flora participating in the pathogenesis of anal fistula by inducing EMT

  http://www.zhqkyx.net/en/article/doi/10.16766/j.cnki.issn.1674-4152.003346

  This mechanism suggests that in the future, we can participate in the prevention and treatment of anal fistula by regulating the intestinal flora of patients, reducing inflammation and intervening in the process of EMT, in order to provide a new way of non-surgical treatment for anal fistula and reduce the pain of diagnosis and treatment of patients.

• #29

  https://indigo.uic.edu/articles/journal_contribution/Pathogenesis_and_persistence_of_cryptoglandular_anal_fistula_a_systematic_review/10762574/1

  Anal fistulas continue to be a problem for patients and surgeons alike despite scientific advances. […] their development and persistence likely involves a multifaceted interaction of histological, microbiological, and molecular factors. Histological studies have shown that anal fistulas are variably epithelialized and are surrounded by dense collagen tissue with pockets of inflammatory cells. […] The presence of a perianal abscess that contains gut flora commonly leads to the development of anal fistula. […] Recent work has shown an increased expression of proinflammatory cytokines and epithelial to mesenchymal cell transition in both cryptoglandular and Crohn’s perianal fistulas. […] This suggests that molecular mechanisms may also play a role in both fistula development and persistence.

• #30 Exploring Perianal Fistulas: Insights into Biochemical, Genetic, and Epigenetic Influences—A Comprehensive Review

  https://www.mdpi.com/2036-7422/16/1/10

  The conducted analysis indicates a significant role of genetic factors, epigenetic factors, and proteins in the pathogenesis of perianal fistulas. Based on numerous studies, EMT and matrix remodeling enzymes are crucial in the development of fistulas associated with CD. Both EMT and matrix remodeling enzymes facilitate the transformation of epithelial cells into mesenchymal-like TCs, promoting invasion and tissue infiltration that contribute to fistula formation.

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