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Surgery Apr 2024Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability...
BACKGROUND
Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease.
METHODS
Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12.
RESULTS
Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed.
CONCLUSION
Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months.
Topics: Female; Humans; Crohn Disease; Bone Marrow; Treatment Outcome; Rectal Fistula; Mesenchymal Stem Cells; Hematopoietic Stem Cell Transplantation
PubMed: 38097485
DOI: 10.1016/j.surg.2023.11.007 -
Colorectal Disease : the Official... Jan 2024The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the... (Meta-Analysis)
Meta-Analysis
AIM
The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology.
METHODS
Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG.
RESULTS
In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations.
CONCLUSION
This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.
Topics: Adult; Humans; Abscess; Systematic Reviews as Topic; Rectal Fistula; Anus Diseases; Wound Healing; Treatment Outcome
PubMed: 38050857
DOI: 10.1111/codi.16741 -
Diseases of the Colon and Rectum Apr 2024
Topics: Humans; Abscess; Anus Diseases; Drainage; Skin Diseases; Rectal Fistula; Treatment Outcome
PubMed: 38150305
DOI: 10.1097/DCR.0000000000002949 -
Colorectal Disease : the Official... Aug 2023The aim of this work was to evaluate the robustness of randomized controlled trials (RCTs) on anal fistula management using the news tools of Fragility Index (FI),... (Review)
Review
AIM
The aim of this work was to evaluate the robustness of randomized controlled trials (RCTs) on anal fistula management using the news tools of Fragility Index (FI), Reverse Fragility Index (RFI) and their corresponding fragility quotients.
METHOD
A systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines which utilized MEDLINE, EMBASE, Cochrane Library and Web of Science databases. Inclusion criteria included RCTs related to the management of anal fistula published from 2000 to 2022 with dichotomous outcomes measures and 1:1 allocation. Calculation of FI and RFI was performed by creating 2 × 2 contingency tables by successively changing one nonevent to an event for each outcome measure until the result was made nonsignificant or significant, respectively. The Fragility Quotients were calculated by dividing the FI or RFI by the total sample size. Fragile results were defined as those with a FI or RFI equal to or less than the number of patients lost to follow-up. Additionally, those with a FI or RFI less than 3 were also considered fragile. Studies were considered extremely fragile if FI was ≤1 or FQ was ≤0.01.
RESULTS
There were 36 RCTs that met our criteria, with 3223 patients. Among these, 19 (53%) were positive RCTs (p < 0.005) and 17 (47%) were negative RCTs (p > 0.05). The median FI was 2 (0-5). The analysis by categorical subgroup showed a strong correlation between FI and the p-value (p = 0.000) and the number of events (p = 0.011). The median RFI was 5 (3.5-9.5) and the subgroup analysis showed a strong correlation between RFI and the p-value (p = 0.000), sample size (0.021) and number needed to treat/number needed to harm (0.000). We considered 63.2% of positive RCTs to be fragile and 35.3% of negative RCTs.
CONCLUSIONS
In the present study we demonstrated the lack of robustness of study findings in published RCTs in the field of anal fistula.
Topics: Humans; Randomized Controlled Trials as Topic; Sample Size; Databases, Factual; Rectal Fistula
PubMed: 37400967
DOI: 10.1111/codi.16645 -
Techniques in Coloproctology Oct 2023Approximately 15-50% of patients with an anorectal abscess will develop an anal fistula, but the true incidence of this entity is currently unknown. The aim of the study... (Observational Study)
Observational Study
PURPOSE
Approximately 15-50% of patients with an anorectal abscess will develop an anal fistula, but the true incidence of this entity is currently unknown. The aim of the study was to determine the incidence of anorectal abscess and development of a fistula in a specific population area and to identify potential risk factors associated with demographic, socioeconomic and pre-existing disease (e.g. diabetes and inflammatory bowel disease).
METHODS
A longitudinal observational study was designed including a large cohort study in an area with 7,553,650 inhabitants in Spain 1st january 2014 to 31st december 2019. Adults who attended for the first time with an anorectal abscess and had a minimum of 1-year follow-up were included. The diagnosis was made using ICD-10 codes for anorectal abscess and anal fistula.
RESULTS
During the study period, we included 27,821 patients with anorectal abscess. There was a predominance of men (70%) and an overall incidence of 596 per million population. The overall incidence of anal fistula developing from abscesses was 20%, with predominance in men, and a lower incidence in the lowest income level. The cumulative incidence of fistula was higher in men and in younger patients (p < 0.0001). On multivariate analysis, patients aged 60-69 years (hazard ratio 2.0) and those with inflammatory bowel disease (hazard ratio 1.8-2.0) had a strong association with fistula development (hazard ratio 2.0).
CONCLUSIONS
One in five patients with an anorectal abscess will develop a fistula, with a higher likelihood in men. Fistula formation was strongly associated with inflammatory bowel disease.
Topics: Adult; Male; Humans; Female; Abscess; Cohort Studies; Follow-Up Studies; Anus Diseases; Rectal Fistula; Inflammatory Bowel Diseases
PubMed: 37548781
DOI: 10.1007/s10151-023-02840-z -
Frontiers in Cellular and Infection... 2024Anal fistula is a common perianal disease that typically develops from an abscess caused by in-flammation in the area. It has long been believed that intestinal microbes...
Anal fistula is a common perianal disease that typically develops from an abscess caused by in-flammation in the area. It has long been believed that intestinal microbes play a significant role in its development, considering its close relation to the intestinal environment. This work attempts to identify the microbiomic signatures of anal fistula, and putative sources of microbes by analyzing microbiomes of 7 anal fistula-associated sites in 12 patients. This study found that microbes in anal fistulas may originate from the skin surface in addition to the intestinal tract. This finding was further validated by NMDS analysis, which also indicated that the microbial communities in the inner and outer openings of the fistula were more similar to their surrounding environments. Using MaAslin2, the characteristics of the microbiome were examined, demonstrating a higher similarity between the abundant bacteria in the anal fistula samples and those found on the skin surface. Moreover, pin-to-pair analysis conducted on all subjects consistently showed a higher abundance of skin-sourced bacteria in anal fistulas. This study identifies the microbiomic signatures of anal fistula, and provides novel insights into the origin of microorganisms in anal fistulas.
Topics: Humans; Rectal Fistula; Skin; Microbiota; Treatment Outcome
PubMed: 38312743
DOI: 10.3389/fcimb.2024.1332490 -
Zhonghua Wei Chang Wai Ke Za Zhi =... Oct 2023Radiation-induced intestinal injury significantly impacts the quality of life and even prognosis of patients. Timely diagnosis and accurate assessment are crucial in...
Radiation-induced intestinal injury significantly impacts the quality of life and even prognosis of patients. Timely diagnosis and accurate assessment are crucial in clinical practice. Imaging examinations play a vital role in the diagnosis and evaluation of radiation-induced intestinal injury. CT offers fast scanning speed and wide coverage but has limited soft tissue resolution. On the other hand, MRI offers superior soft tissue resolution, along with the capability for multi-sequence and multi-parameter imaging, and the ability to assess the effect of tumor treatment. However, its scanning range is restricted. Endorectal ultrasound enables observation of rectal wall thickness, submucosal blood flow signals, and the development of micro-ulcers and fistulas. The key imaging features of radiation-induced intestinal injury include intestinal wall thickening, layered enhancement on contrast-enhanced scans, fistula formation, and abscess formation, and so on. Previous studies have established correlations between certain imaging features and the severity as well as prognosis of the disease. Nonetheless, these imaging features lack specificity, and require differentiation from tumors, ischemic changes, and other intestinal inflammatory lesions, considering the patient's radiotherapy history in conjunction with the imaging findings.
Topics: Humans; Quality of Life; Rectum; Magnetic Resonance Imaging; Ultrasonography
PubMed: 37849262
DOI: 10.3760/cma.j.cn441530-20230808-00039 -
Indian Journal of Gastroenterology :... Feb 2024Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe... (Review)
Review
Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.
Topics: Humans; Crohn Disease; Rectal Fistula; Quality of Life; Tumor Necrosis Factor-alpha; Cytokines; Treatment Outcome
PubMed: 38308773
DOI: 10.1007/s12664-024-01524-2 -
Surgical Case Reports Oct 2023Sacrococcygeal teratomas (SCTs) are known to cause urological complications, but urethrovaginal (UV) fistula as a complication of SCT is rare. We herein report a case of...
BACKGROUND
Sacrococcygeal teratomas (SCTs) are known to cause urological complications, but urethrovaginal (UV) fistula as a complication of SCT is rare. We herein report a case of SCT with UV fistula and hydrocolpos.
CASE PRESENTATION
A 1-day-old female neonate presented to our department with prominent swelling in the sacrococcygeal region. She was born at 37 gestational weeks via spontaneous vaginal delivery from a 39-year-old woman. The weight of the baby was 2965 g, and her Apgar scores were 4/10 (at 1 and 5 min). An MRI examination confirmed an 11 × 11 cm Altman classification typeII SCT associated with hydrocolpos, a dilated urinary bladder, and bilateral hydronephrosis. When she was 5 days, the SCT was excised totally and a coccygectomy was performed. After the operation, as her urinary output appeared unstable, a cystoscopic examination was performed on the third postoperative day. This revealed that the UV fistula was located approximately 1 cm from the urethral opening. In addition, the proximal urethra was unobstructed and connected to the bladder. The cystoscope allowed for the passage of a urinary catheter through the urethra. After 1 month of catheter placement, she was discharged from the hospital at 57 days of age. Follow-up was uneventful, with neither urinary infection nor retention.
CONCLUSIONS
SCTs are associated with not only trouble with rectal function and lower extremity movement but also urinary complications. The pathogenesis of this UV fistula is thought to be the rapid growth of the SCT that developed in the fetal period, resulting in obstruction of the urethra by the tumor and the pubic bone, which in turn caused urinary retention and the formation of a fistula as an escape route for the pressure. Because SCTs can cause a variety of complications depending on the course of the disease, careful examination and follow-up are necessary.
PubMed: 37903968
DOI: 10.1186/s40792-023-01772-y -
BMC Gastroenterology Oct 2023Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early...
BACKGROUND
Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period.
METHODS
Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated.
RESULTS
In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18-65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing.
CONCLUSIONS
We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.
Topics: Humans; Male; Adult; Middle Aged; Aged; Female; Retrospective Studies; Anal Canal; Wound Healing; Rectal Fistula; Magnetic Resonance Imaging; Treatment Outcome
PubMed: 37907854
DOI: 10.1186/s12876-023-02963-5