Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Current practice of diagnosis and treatment for rectourethral fistula in male patients with anorectal malformation: a multicenter questionnaire survey in Japan.

PURPOSE: Surgical procedures for anorectoplasty for anorectal malformations (ARMs), particularly rectourethral fistula (RUF), depend on the institution. We investigated the diagnosis and treatment of RUF in male patients with ARMs in Japan using a questionnaire survey. METHODS: An online survey inquiring about the diagnosis and treatment (diagnostic modalities, surgical approaches, fistula dissection devices, and fistula closure techniques) of each type of ARM in male patients was conducted among institutional members of the Japanese Study Group of Anorectal Anomalies. Fisher's exact test was used to compare surgical methods between posterior sagittal anorectoplasty (PSARP) and laparoscopy-assisted anorectoplasty (LAARP). RESULTS: Sixty-one institutions (100%) completed the survey. LAARP was the preferred approach for high-type ARM (75.4%). PSARP was preferred for intermediate-type ARM (59.0%). Monopolar devices were most commonly used (72.1%) for RUF dissection. Blunt dissection was more frequent in the PSARP group (PSARP vs. LAARP: 55.6 vs. 20.0%, p < 0.005). Cystoscopy/urethroscopy to confirm the extent of dissection was used more frequently in the LAARP group (70.0% vs. 25.0%, p < 0.005). Clips and staplers were used more frequently in the LAARP group (p < 0.05). CONCLUSION: Distinct fistula management strategies for PSARP and LAARP were revealed. Further studies are needed to investigate the postoperative outcomes associated with these practices.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

BACKGROUND/AIMS: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. METHODS: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). RESULTS: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. CONCLUSION: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Perianal fistulizing Crohn's disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies.

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-ß) 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.

Efficacy of amoxicillin/clavulanic acid after surgical drainage of perianal abscess in the prevention of the development of anal fistula (PERIQxA study): study protocol for a multicenter randomized, double-blind clinical trial.

BACKGROUND: Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a fistula after incision and drainage of an anal abscess is seen in approximately 26-37%. Its treatment is a relevant topic, and the role of the use of antibiotic therapy in its prevention remains controversial, after the publication of several studies with contradictory results and several methodological limitations. Our hypothesis is that the combination of amoxicillin and clavulanic acid will reduce the incidence of anal fistula. METHOD: The aim of this study is to evaluate the efficacy of antibiotherapy after surgical drainage of perianal abscess in the development of perianal fistula. The PERIQxA study is a multicenter, randomized, double-blind controlled trial. The study has been designed to include 286 adult patients who will be randomly (1:1) assigned to either the experimental (amoxicillin/clavulanic acid 875/125 mg TDS for 7 days) or the control arm (placebo). The primary outcome measure is the percentage of patients that develop perianal fistula after surgery and during follow-up (6 months). DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of amoxicillin/clavulanic in the prevention of perianal fistula. The results of this study are expected to contribute to stablish the potential role of antibiotherapy in the therapeutics for anal abscess. TRIAL REGISTRATION: EudraCT Number: 2021-003376-14. Registered on November 26, 2021.

Adenocarcinoma arising from a chronic perianal fistula in a Crohn's disease patient: case report and review of the literature.

Crohn's disease patients frequently develop perianal fistulas during their life. They are also at higher risk to develop cancers. Rarely, those cancers appear within a prior chronic fistula. The main types are adenocarcinoma mostly mucinous and squamous cell carcinoma. They are generally discovered at an advanced stage with a poor prognosis because symptoms are generally the same as those of the fistula itself. Regular follow-up of chronic fistulas is then important for an early diagnosis as well as histological analysis of the fistula during surgery. There is no consensus on the ideal treatment but abdominoperineal resection is the corner stone with or without neo or adjuvant chemo-radiotherapy. This paper presents a rare case of mucinous adenocarcinoma in a chronic perianal fistula in a Crohn's disease female and provides a review of the literature.

European Society of Coloproctology: Guidelines for diagnosis and treatment of cryptoglandular anal fistula.

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.

Surface-enhanced Raman spectroscopy analysis reveals biochemical difference in urine of patients with perianal fistula.

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (PFCD) is different from the characteristics and outcomes of traditional non-inflammatory bowel disease (IBD) anal fistulas. The presence of perianal disease was a poor prognostic indicator for Crohn's disease (CD) patients and PFCD patients were more likely to bear an increased risk of recurrence. However, the effective and accurate diagnosis methods to early distinguish PFCD from simple perianal fistula were still scarce. The purpose of this study is to develop a non-invasive detecting approach to predict CD in patients with perianal fistulas. METHODS: Data on patients with anal fistulizing disease were collected from July 2020 to September 2020 in two IBD centers. Urine samples from PFCD and simple perianal fistula patients were investigated by surface-enhanced Raman spectroscopy (SERS). Principal component analysis (PCA)-support vector machine (SVM) was utilized to establish classification models to distinguish PFCD from simple perianal fistula. RESULTS: After a case-matched 1:1 selection by age and gender, 110 patients were included in the study. By analyzing the average SERS spectra of PFCD and simple perianal fistula patients, it revealed that there were significant differences in intensities at 11 Raman peaks. The established PCA-SVM model distinguished PFCD from simple perianal fistula with a sensitivity of 71.43%, specificity 80.00% and accuracy 75.71% in the leave-one-patient-out cross-validation. The accuracy of the model in validation cohort was 77.5%. CONCLUSIONS: Investigation of urine samples by SERS helps clinicians to predict Crohn's disease from perianal fistulas, which make patients achieve benefit from a more individualized treatment strategy.

Enhancing surgical precision: unveiling the impact of preoperative colonoscopy in anal fistula patients.

BACKGROUND: Anal fistula is a common benign anorectal disease that often requires surgical intervention for effective treatment. In recent years, preoperative colonoscopy as a diagnostic tool in patients with anal fistula has garnered increasing attention due to its potential clinical application value. By investigating underlying inflammatory bowel disease (IBD), polyps, and other abnormalities, preoperative colonoscopy can offer insights to refine surgical strategies and improve patient outcomes. METHODS: This retrospective study focused on 1796 patients with various benign anorectal diseases who underwent preoperative intestinal endoscopy and met surgical criteria within the preceding three years at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Among these patients, 949 diagnosed with anal fistula comprised group A, while 847 patients without anal fistula were assigned to group B for comparison. The investigation encompassed an analysis of general patient information, endoscopic findings, polyp histopathology, distribution of bowel inflammation sites, and results of inflammatory bowel disease assessments between the two patient cohorts. A subgroup analysis was also conducted on 2275 anal fistula patients with no surgical contraindications. This subgroup was categorized into Group A (949 patients who underwent preoperative intestinal endoscopy) and Group C (1326 patients who did not undergo preoperative colonoscopy). The study compared the rates of detecting endoscopic lesions and IBD-related findings between the two subgroups. RESULTS: The study initially confirmed the comparability of general patient information between groups A and B. Notably, the abnormal detection rate in group A was significantly higher than in group B (P < 0.01). In terms of endoscopic findings, the anal fistula group (group A) exhibited higher rates of detecting bowel inflammation, inflammatory bowel disease, and polyps compared to the non-anal fistula group (group B) (P < 0.05). The distribution of inflammation locations indicated higher detection rates in the terminal ileum, ileocecal region, and ascending colon for group A compared to group B (P < 0.05). Although the incidence of IBD in group A was higher than in group B, this difference did not reach statistical significance (P > 0.05). Subsequently, the analysis of the subgroup (groups A and C) revealed a significant disparity in intestinal endoscopic detection rates (P < 0.01) and statistically significant differences in detecting IBD (P < 0.05) and Crohn's disease (P < 0.05) between the two anal fistula subgroups. CONCLUSIONS: The findings of this study underscore the substantial clinical value of preoperative colonoscopy in the comprehensive evaluation of patients with anal fistula. Preoperative colonoscopy aids in ruling out localized perianal lesions caused by underlying inflammatory bowel disease, thereby mitigating the likelihood of missed diagnoses and enhancing treatment outcomes. This research highlights the importance of incorporating preoperative colonoscopy as a valuable diagnostic tool in managing anal fistula patients.

Perianal Fistulas Are Associated with Persistently Higher Direct Health Care Costs in Crohn's Disease: A Population-Based Study.

BACKGROUND: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era. AIM: To compare direct health care costs in persons with and without perianal fistulas. METHODS: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls. RESULTS: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater). CONCLUSION: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.

Study on the factors influencing the prognosis after perianal abscess surgery.

OBJECTIVE: To study the influence of clinical characteristics and diagnosis and treatment methods of perianal abscess on postoperative recurrence or formation of anal fistula to provide a basis for selecting appropriate surgical and inspection methods for clinical treatment of perianal abscess in the future. METHODS: The clinical data of 394 patients with perianal abscesses were collected, the influencing factors were investigated, and univariate analysis and multivariate logistic regression analysis were performed to further determine the risk factors affecting the prognosis of perianal abscess. RESULTS: The results showed that the rate of preoperative blood routine results in the uncured group was higher (51.16%) than in the cured group (35.61%); the rate of high abscess space in the uncured group (23.26%) was higher than in the cured group (9.11%); the proportion of patients in the uncured group who underwent magnetic resonance imaging (MRI) before surgery (27.90%) was lower than in the cured group (45.30%); the proportion of patients in the uncured group who underwent simple drainage (51.16%) was higher than in the cured group (28.49%). The two groups had significant differences in perineal MRI examination, surgical method, preoperative blood routine, and abscess space (p = 0.030, p = 0.002, p = 0.047 and p = 0.010, respectively). Based on the results of univariate analysis and multivariate logistic regression analysis, the extent of the abscess cavity (OR = 2.544, 95%CI = 1.087-5.954, p = 0.031) and the surgical method (OR = 2.180, 95%CI = 1.091-4.357, p = 0.027) were independent influencing factors for postoperative recurrence of perianal abscess or anal fistula. CONCLUSION: Preoperative assessment of the abscess range and precise intraoperative methods to resolve the infection of the abscess glands in the internal mouth can effectively improve the cure rate.

[Full-wall semi-circular mobilization of posterior wall of the lower ampullar rectum for complex recurrent anorectal fistula]. / Polnostennaya polutsirkulyarnaya mobilizatsiya zadnei stenki nizhneampulyarnogo otdela pryamoi kishki kak metod lecheniya slozhnykh retsidivnykh anorektal'nykh svishchei.

OBJECTIVE: To describe a new technique for closure of sphincter complex defects after excision of recurrent high rectal fistulas and compare with other traditional techniques. MATERIAL AND METHODS: We retrospectively analyzed patients operated on for recurrent posterior rectal fistula. All patients underwent fistulectomy and one of the methods for defect closure after excision of the fistula: sphincter suturing, muco-muscular flap or full-wall semicircular mobilization of the lower ampullar rectum. The last method implemented the principle of inter-sphincter resection in rectal cancer. We developed this method as an alternative to muco-muscular flap in patients with fibrosis of anal canal to form a full-thickness well-vascularized flap without tissue tension. RESULTS: Between 2019 and 2021, 6 patients underwent fistulectomy with sphincter suturing, 5 patients - closure with muco-muscular flap, 3 males underwent full-wall semicircular mobilization of the lower ampullar rectum. There was a tendency to better continence after a year (1 (0, 1.5), 1 (0, 1.5) and 3 (1, 3) points, respectively). Postoperative follow-up period was 12.5 (10, 15), 12 (9, 15) and 16 (12, 19) months, respectively. None patient had signs of recurrence throughout the follow-up period. CONCLUSION: Original technique can be considered as an alternative to standard approaches in patients with high recurrent posterior anorectal fistulas, when traditional displaced endorectal flap is ineffective or impossible due to excessive scarring and anatomical changes in the anal canal.

Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn's Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn's Disease (iCREST-CD).

BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD]. RESULTS: Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged <40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age <40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities. CLINICAL TRIALS REGISTRY: University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].

Fistula-Associated Anal Adenocarcinoma: A 20-Year Single-Center Experience.

BACKGROUND: Fistula-associated anal adenocarcinoma (FAAC) is a rare consequence in patients with long-standing perianal fistulas. A paucity of data are available for this patient collective, making clinical characterization and management of this disease difficult. OBJECTIVE: This study aimed to describe a single-center experience with FAAC patients, their clinical course, and histopathological and molecular pathological characterization. METHODS: All patients receiving surgery for an anal fistula in 1999-2019 at a tertiary university referral hospital were included in this retrospective analysis. Patients with FAAC were eligible for histopathological analysis, including immunohistochemistry and molecular profiling. RESULTS: This study included 1004 patients receiving surgical treatment for an anal fistula, of whom 242 had an underlying inflammatory bowel disease (IBD). Ten patients were diagnosed with a fistula-associated anal carcinoma (1.0%), and six of these patients had an FAAC (0.6%). The mean overall survival of FAAC patients was 24 ± 3 months. FAAC immunohistochemistry revealed positive staining for CK20, CDX2 and MUC2, while stainings for CK5/6 and CK7 were negative. All FAAC specimens revealed microsatellite stability. Molecular profiling detected mutations in 35 genes, with the most frequent mutations being TP53, NOTCH1, NOTCH3, ATM, PIK3R1 and SMAD4. CONCLUSION: FAAC is rare but associated with poor clinical outcome. Tissue acquisition is crucial for early diagnosis and therapy and should be performed in long-standing, non-healing, IBD-associated fistulas in particular. The immunophenotype of FAAC seems more similar to the rectal-type mucosa than the anal glands.

Safety and efficacy of injection of human placenta mesenchymal stem cells derived exosomes for treatment of complex perianal fistula in non-Crohn's cases: Clinical trial phase I.

BACKGROUND AND AIM: A perianal fistula is an abnormal tract that connects anal canal to skin. Current medical and surgical interventions have a high failure rate particularly in complex and refractory cases. MSC-derived exosomes have demonstrated immunomodulatory effects without the conventional complications; hence, in this study, we evaluated the safety of their application for complex perianal fistula. METHODS: Placenta-derived MSCs were cultured, and exosomes were isolated using ultracentrifugation. Exosome injections were administered in the operating room to 11 patients with complex perianal fistula (presence of fistulas for at least 1 year alongside medical and surgical treatment). The patients were followed for 6 months, and the patients were evaluated using physical examination, face-to-face interviews, and magnetic resonance imaging (MRI). RESULTS: Among 11 patients only one did not show any improvement upon physical examination. Five patients showed complete tract resolve. While the discharge was stopped in eight patients, two patients showed only reduction. None of the patients showed any acute or latent allergic reaction or injection related complications. CONCLUSION: Administration of exosomes isolated from MSCs demonstrates safety and a satisfactory therapeutic effect in treatment complex perianal fistulae; therefore, it can be a candidate for future studies and might play a significant role in treatment.

Darvadstrocel for Complex Perianal Fistulas in Japanese Adults with Crohn's Disease: A Phase 3 Study.

BACKGROUND AND AIMS: Previous studies conducted in Europe suggested that darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn's disease. METHODS: This is a phase 3, open-label, single-arm study conducted at nine sites in Japan. Adult patients with non-active or mildly active Crohn's disease and complex perianal fistulas received a single 24-mL intralesional injection of darvadstrocel [120 × 106 cells]. The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening, and absence of collections >2 cm, [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24. RESULTS: Between March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% confidence interval [CI], 38.5-79.6). The effect was maintained at Week 52, with 68.2% [95% CI, 48.7-87.6] of patients achieving combined remission. Treatment-related adverse events included: one [4.5%] patient with worsening of Crohn's disease and diarrhoea, and one [4.5%] patient with blood bilirubin increase. No new safety findings were identified in this study. CONCLUSIONS: The efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn's disease were similar to those observed in the previous European study. ClinicalTrials.gov number, NCT03706456.

Anorectal Malignancies Presenting as a Perianal Abscess or Fistula.

BACKGROUND: Acute anorectal abscess and fistula are common conditions that usually presents as a painful lump close to the anal margin. Tumors in the distal rectum and in the perianal region may mimic the symptoms and signs of anorectal sepsis, thereby leading to a delay in diagnosis and management. The purpose of this study was to describe patients presenting with acute perianal abscess or fistula who were subsequently diagnosed with anorectal cancer. METHODS: We performed a retrospective, review of all cases presenting with acute perianal abscess or fistula who were subsequently found to have anorectal carcinoma on biopsy in two tertiary centers. We analyzed the data focusing on the clinical features, laboratory values, clinical staging of the tumors, the subsequent management, the pathological staging, and the outcome of each patient. RESULTS: Overall, 3219 patients presenting with anorectal abscess or fistula were reviewed. Cancer was diagnosed in 16 (.5%) patients, 12 with adenocarcinoma of the rectum and 4 with squamous cell carcinoma of the anus. In 5 patients (31.2%), cancer was diagnosed in the setting of chronic perianal fistula, 4 of them had Crohn's disease. In 10 patients (62.5%), cancer was not diagnosed during the initial evaluation of the acute symptoms. CONCLUSIONS: A high index of suspicion is required to make the diagnosis of perianal tumors when assessing patients presenting with perianal sepsis, particularly those with Crohn's disease, a long history of persistent perianal disease, and an advanced age. In most cases, proper drainage followed by proximal diversion are the surgical treatment of choice in the acute setting.

Gluteal and Presacral Abscess Due to Crohn's Disease with Multiple Fistulas.

The abscess is a common complication of Crohn's disease (CD), with the perianal form more frequent than gluteal or presacral which is relatively rare. There are few case reports of gluteal abscess combined with presacral abscess caused by CD and the treatment has not been established. A 21-year-old male was admitted with right buttock and lower back pain with a duration of 3 months. He had a history of CD in the small intestine diagnosed 10 months previously. He had poor compliance and had not returned for follow-up care during the previous 6 months. Abdominopelvic CT indicated newly developed multiple abscess pockets in right gluteal region, including piriformis muscle and presacral space. Additionally, fistula tracts between small bowel loops and presacral space were observed. Patient's CD was moderate activity (273.12 on the Crohn's Disease Activity Index [CDAI]). Treatment was started with piperacillin/ tazobactam antibiotic but patient developed a fever and abscess extent was aggravated. Therefore, surgical incision and drainage was performed and 4 Penrose drains were inserted. Patient's pain and fever were resolved following surgery. Infliximab was then administered for the remaining fistulas. After the induction regimen, multiple fistula tracts improved and patient went into remission (CDAI was -0.12).

Predictors of Perianal Fistula Healing in Children With Newly Diagnosed Crohn Disease.

OBJECTIVES: Perianal fistulas are among the most severe complications of Crohn disease, but limited data regarding their outcomes are available in children. Our objective was to determine predictors of perianal fistula healing among pediatric patients newly diagnosed with Crohn disease. METHODS: This single-center retrospective study followed patients with perianal fistulas at Crohn disease diagnosis until fistula healing. Time to healing was analyzed using Cox proportional hazard regression models considering relevant covariates including patient demographics, disease characteristics, medical therapies [no anti-tumor necrosis factor (TNF)α therapy, anti-TNFα therapy ±therapeutic drug monitoring], and perianal surgical procedures including fistulotomy, fistulectomy, removal of perianal lesions, seton placement, and incision and drainage. RESULTS: Of 485 patients identified, 107 (22%) had a perianal fistula at Crohn disease diagnosis. Multivariate analysis identified that perianal fistulotomy, fistulectomy, and lesion removal [hazard ratio (HR) 0.46; P = 0.028], non-White race (HR 0.30, P < 0.01), and male sex (HR 0.42; P = 0.02) were associated with delayed fistula healing. Faster fistula healing was associated with treatment with anti-TNFα with therapeutic drug monitoring (HR 1.78, P = 0.009). There were no other differences in healing by treatment. CONCLUSIONS: Fistulotomy, fistulectomy, and perianal lesion removal as well as non-White race were associated with delayed fistula healing. Anti-TNFα therapy was associated with faster fistula healing when combined with therapeutic drug monitoring, compared to all other medical treatment groups, including anti-TNFα therapy without therapeutic drug monitoring.