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Cells Jul 2019Perianal fistulizing Crohn's disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two... (Review)
Review
Perianal fistulizing Crohn's disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.
Topics: Animals; Crohn Disease; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Quality of Life; Randomized Controlled Trials as Topic; Rectal Fistula; Wound Healing
PubMed: 31340546
DOI: 10.3390/cells8070764 -
European Radiology Sep 2020To develop imaging guidelines for patients with fistula-in-ano and other causes of anal sepsis.
OBJECTIVES
To develop imaging guidelines for patients with fistula-in-ano and other causes of anal sepsis.
METHODS
An expert group of 13 members of the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) used a modified Delphi process to vote on a series of consensus statements relating to the imaging of patients with potential anal sepsis. Participants first completed a questionnaire to gather practice information and to help frame the statements posed.
RESULTS
In the first round of voting, the expert group scored 51 statements of which 45 (88%) achieved immediate consensus. The remaining 6 statements were redrafted following input from the expert group and consensus achieved for all during a second round of voting, including an additional statement drafted. No statement was rejected due to a lack of consensus. After redrafting to improve clarity, 53 individual statements were presented.
CONCLUSION
These expert consensus statements can be used to guide appropriate indication, acquisition, interpretation and reporting of medical imaging for patients with potential fistula-in-ano and other causes of anal sepsis.
KEY POINTS
• Medical imaging, notably magnetic resonance imaging, is used widely for the diagnosis and monitoring of fistula-in-ano and other causes of anal and perianal sepsis. • While the indexed medical literature is clear that diagnostic accuracy is potentially excellent, this depends on competent image acquisition and interpretation. • In order to facilitate this, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) has produced expert consensus guidelines regarding the imaging of fistula-in-ano and related conditions.
Topics: Anal Canal; Anus Diseases; Humans; Magnetic Resonance Imaging; Radiography, Abdominal; Rectal Fistula; Sepsis
PubMed: 32307564
DOI: 10.1007/s00330-020-06826-5 -
Annals of Palliative Medicine Aug 2021Many hospitals favor magnetic resonance imaging (MRI) as the preferred diagnostic method to detect anal fistula, trans-fistula contrast-enhanced ultrasound (CEUS) for...
BACKGROUND
Many hospitals favor magnetic resonance imaging (MRI) as the preferred diagnostic method to detect anal fistula, trans-fistula contrast-enhanced ultrasound (CEUS) for the diagnosis of anal fistula have attracted the attention of investigators worldwide. This study aimed to investigate the efficacy of trans-fistula contrast-enhanced endoanal ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of anal fistula.
METHODS
Ninety-eight patients undergoing trans-fistula CEUS and MRI were retrospectively analyzed. The fistulous trend and positional relation between the fistula, levator ani muscle, and sphincter (Parks classification), as well as the numbers of fistulous branches, number and position of the fistula, and distance between internal opening and anal edge were recorded. These parameters were compared with the postoperative results.
RESULTS
There were no significant statistical differences (P>0.05) in the accuracy rates of trans-fistula CEUS and MRI, respectively, in terms of Parks classification (90.82%, 92.86%), branches (89.19%, 81.08%), internal openings (92.68%, 89.43%), and internal openings ≥3 cm from the anal edge (85.71%, 92.86%). However, we observed a significant difference in terms of internal openings <3 cm from the anal edge (96.30%, 87.65%) (P=0.043).
CONCLUSIONS
Although both methods exhibited a perfect accuracy rate in diagnosing anal fistula, trans-fistula CEUS displayed superior diagnostic value for internal openings <3 cm from the anal edge, and could provide reliable pre-operative evidence.
Topics: Anal Canal; Humans; Magnetic Resonance Imaging; Rectal Fistula; Retrospective Studies; Ultrasonography
PubMed: 34488402
DOI: 10.21037/apm-21-1624 -
Deutsches Arzteblatt International Oct 2011Cryptoglandular anal fistula arises in 2 per 10 000 persons per year and is most common in young men. Improper treatment can result in fecal incontinence and thus in...
BACKGROUND
Cryptoglandular anal fistula arises in 2 per 10 000 persons per year and is most common in young men. Improper treatment can result in fecal incontinence and thus in impaired quality of life.
METHOD
This S3 guideline is based on a systematic review of the pertinent literature.
RESULTS
The level of evidence for treatment is low, because relevant randomized trials are scarce. Anal fistulae are classified according to the relation of the fistula channel to the sphincter. The indication for treatment is established by the clinical history and physical examination. During surgery, the fistula should be probed and/or dyed. Endo-anal ultrasonography and magnetic resonance imaging are of roughly the same diagnostic value and may be useful as additional studies for complex fistulae. Surgical treatment is with one of the following operations: laying open, seton drainage, plastic surgical reconstruction with suturing of the sphincter, and occlusion with biomaterials. Only superficial fistulae should be laid open. The risk of postoperative incontinence is directly related to the thickness of sphincter muscle that is divided. All high anal fistulae should be treated with a sphincter-saving procedure. The various plastic surgical reconstructive procedures all yield roughly the same results. Occlusion with biomaterials yields a lower cure rate.
CONCLUSION
This is the first German S3 guideline for the treatment of cryptoglandular anal fistula. It includes recommendations for the diagnostic evaluation and treatment of this clinical entity.
Topics: Digestive System Surgical Procedures; Gastroenterology; Humans; Organ Sparing Treatments; Rectal Fistula; Surgery, Computer-Assisted
PubMed: 22114639
DOI: 10.3238/arztebl.2011.0707 -
World Journal of Gastroenterology Nov 2020One of the most challenging phenotypes of Crohn's disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other... (Review)
Review
One of the most challenging phenotypes of Crohn's disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn's disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.
Topics: Crohn Disease; Fecal Incontinence; Humans; Quality of Life; Rectal Fistula; Surgical Stomas
PubMed: 33268947
DOI: 10.3748/wjg.v26.i42.6572 -
World Journal of Gastroenterology Apr 2022Crohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main...
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 ( < 0.05). In the ideal model rabbit group, on the 7 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.
Topics: Animals; Colitis; Crohn Disease; Humans; Male; Proctitis; Rabbits; Rectal Fistula; Treatment Outcome
PubMed: 35582134
DOI: 10.3748/wjg.v28.i15.1536 -
BMC Medical Imaging Sep 2023Accurate preoperative fistula diagnostics in male anorectal malformations (ARM) after colostomy are of great significance. We reviewed our institutional experiences and... (Review)
Review
BACKGROUND
Accurate preoperative fistula diagnostics in male anorectal malformations (ARM) after colostomy are of great significance. We reviewed our institutional experiences and explored methods for improving the preoperative diagnostic accuracy of fistulas in males with ARMs after colostomy.
METHODS
A retrospective analysis was performed on males with ARMs after colostomy admitted to our hospital from January 2015 to June 2022. All patients underwent magnetic resonance imaging (MRI) and high-pressure colostogram (HPC) before anorectal reconstruction. Patients with no fistula as diagnosed by both modalities underwent a voiding cystourethrogram (VCUG). General information, imaging results and surgical results were recorded.
RESULTS
Sixty-nine males with ARMs after colostomy were included. Age at the time of examination was 52 ~ 213 days, and the median age was 89 days. The Krickenbeck classification according to surgical results included rectovesical fistula (n = 19), rectoprostatic fistula (n = 24), rectobulbar fistula (n = 19) and no fistula (n = 7). There was no significant difference in the diagnostic accuracy between MRI and HPC for different types of ARMs. For determining the location of the fistula, compared to surgery, HPC (76.8%, 53/69) performed significantly better than MRI (60.9%, 42/69) (p = 0.043). Sixteen patients diagnosed as having no fistula by MRI or HPC underwent a VCUG, and in 14 patients, the results were comfirmed. However, there were 2 cases of rectoprostatic fistula that were not correctly diagnosed.
CONCLUSION
High-pressure colostogram has greater accuracy than MRI in the diagnosis of fistula type in males with ARMs after colostomy. For patients diagnosed with no fistula by both methods, VCUG reduces the risk of false-negative exclusion, and rectoprostatic fistula should be considered during the operation.
Topics: Humans; Male; Infant; Anorectal Malformations; Retrospective Studies; Colostomy; Rectal Fistula; Magnetic Resonance Imaging
PubMed: 37749545
DOI: 10.1186/s12880-023-01105-3 -
International Journal of Surgery... Oct 2017Video-Assisted Anal Fistula Treatment (VAAFT) is a relatively new minimally invasive videoendoscopic procedure for treating fistula-in-ano. We reviewed and performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Video-Assisted Anal Fistula Treatment (VAAFT) is a relatively new minimally invasive videoendoscopic procedure for treating fistula-in-ano. We reviewed and performed metaanalysis to evaluate the efficacy of this procedure.
METHODS
Studies from the period 2010 to 2016 were searched in PubMed, Medline, Scopus, Embase, Ovid, SCI database, Cochrane Central Register of Controlled Trials (CENTRAL) & Google Scholar database. All studies which utilized VAAFT to treat fistula-in-ano were extracted. The studies in which the Cryptoglandular fistula were treated were included. Procedure's done in patients with Crohn's disease, pediatric patients and associated malignancy were excluded from the study. The primary outcome parameter was success rate in fistula healing and the secondary outcome parameters were operating time, hospital stay, return to work, incontinence rate and complication rate.
RESULTS
A total of 1378 studies were screened. Out of these, eight studies were finally included for meta-analysis. The analysis (n = 786) demonstrated a net Proportion Meta-analysis pooled rate of 76.01% (95% CI = 68.1 to 83.9) for success rate, 16.2% (95% CI = 12.1 to 20.2) for complications, 44.7 min (95% CI = 38.3 to 51.2) for operating time, 1-4.1 days for mean hospital stay and 1-11 days for return to work. None of the studies reported worsening of continence levels.
CONCLUSIONS
VAAFT is a safe videoendoscopic method to treat fistula-in-ano with an overall success rate of 76% (net Proportion Meta-analysis pooled rate). The main benefit of the procedure is minimal risk to incontinence, minimal hospital stay and early return to work.
Topics: Humans; Length of Stay; Operative Time; Rectal Fistula; Video-Assisted Surgery
PubMed: 28882770
DOI: 10.1016/j.ijsu.2017.08.582 -
Colorectal Disease : the Official... Dec 2022The aetiology of anal fistula has not been fully clarified. One of the causes of anal fistulas may be the markedly deep crypts that characterize the primary openings. We...
AIM
The aetiology of anal fistula has not been fully clarified. One of the causes of anal fistulas may be the markedly deep crypts that characterize the primary openings. We developed subcutaneous incision of the fistula tract and internal sphincterotomy (SIFT-IS) to eradicate these deep crypts. The aim of this study was to evaluate outcomes in patients with anal fistula treated with SIFT-IS.
METHOD
A retrospective study was performed over a 2-year period. Patients with transsphincteric anal fistula who underwent SIFT-IS were enrolled. The primary endpoint was the anal fistula healing rate at 16 weeks postoperatively. The secondary endpoints were healing time, postoperative complications and clinical continence status.
RESULTS
One hundred and fifty one patients were enrolled. Primary healing was accomplished in 129 patients (85%). There were 17 patients (11%) with a remnant fistula and five (3%) with a recurrence. The remnant fistulas healed spontaneously at more than 16 weeks postoperatively in seven patients. The median healing time was 6 (3-96) weeks. Surgical intervention was required in seven patients with a remnant fistula and four with recurrence. At the final follow-up, the wounds had healed in 148 patients (98%). No significant postoperative complications or incontinence were observed.
CONCLUSION
Subcutaneous incision of the fistula tract and internal sphincterotomy is a promising surgical option for transsphincteric anal fistulas, with a satisfactory healing rate.
Topics: Humans; Lateral Internal Sphincterotomy; Retrospective Studies; Treatment Outcome; Rectal Fistula; Postoperative Complications; Surgical Wound; Anal Canal
PubMed: 35946094
DOI: 10.1111/codi.16297 -
Cellular and Molecular Gastroenterology... 2023Perianal fistula represents one of the most disabling manifestations of Crohn's disease (CD) due to complete destruction of the affected mucosa, which is replaced by...
BACKGROUND AND AIMS
Perianal fistula represents one of the most disabling manifestations of Crohn's disease (CD) due to complete destruction of the affected mucosa, which is replaced by granulation tissue and associated with changes in tissue organization. To date, the molecular mechanisms underlying perianal fistula formation are not well defined. Here, we dissected the tissue changes in the fistula area and addressed whether a dysregulation of extracellular matrix (ECM) homeostasis can support fistula formation.
METHODS
Surgical specimens from perianal fistula tissue and the surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing. Genes significantly modulated were validated by real-time polymerase chain reaction, Western blot, and immunofluorescence assays. The effect of the protein product of TNF-stimulated gene-6 (TSG-6) on cell morphology, phenotype, and ECM organization was investigated with endogenous lentivirus-induced overexpression of TSG-6 in Caco-2 cells and with exogenous addition of recombinant human TSG-6 protein to primary fibroblasts from region surrounding fistula. Proliferative and migratory assays were performed.
RESULTS
A markedly different organization of ECM was found across fistula and surrounding fistula regions with an increased expression of integrins and matrix metalloproteinases and hyaluronan (HA) staining in the fistula, associated with increased newly synthesized collagen fibers and mechanosensitive proteins. Among dysregulated genes associated with ECM, TNFAI6 (gene encoding for TSG-6) was as significantly upregulated in the fistula compared with area surrounding fistula, where it promoted the pathological formation of complexes between heavy chains from inter-alpha-inhibitor and HA responsible for the formation of a crosslinked ECM. There was a positive correlation between TNFAI6 expression and expression of mechanosensitive genes in fistula tissue. The overexpression of TSG-6 in Caco-2 cells promoted migration, epithelial-mesenchymal transition, transcription factor SNAI1, and HA synthase (HAs) levels, while in fibroblasts, isolated from the area surrounding the fistula, it promoted an activated phenotype. Moreover, the enrichment of an HA scaffold with recombinant human TSG-6 protein promoted collagen release and increase of SNAI1, ITGA4, ITGA42B, and PTK2B genes, the latter being involved in the transduction of responses to mechanical stimuli.
CONCLUSIONS
By mediating changes in the ECM organization, TSG-6 triggers the epithelial-mesenchymal transition transcription factor SNAI1 through the activation of mechanosensitive proteins. These data point to regulators of ECM as new potential targets for the treatment of CD perianal fistula.
Topics: Humans; Crohn Disease; Caco-2 Cells; Epithelial-Mesenchymal Transition; Rectal Fistula; Transcription Factors; Extracellular Matrix
PubMed: 36521659
DOI: 10.1016/j.jcmgh.2022.12.006