[A new treatment option for complex perianal fistulas in Crohn's disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan].

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Management of anal fistulas in Crohn's disease after failure of Infliximab.

INTRODUCTION: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. AIM: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. METHODS: A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. CONCLUSION: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.

A case-control study of the risk factors for fistula-in-ano in infants and toddlers.

BACKGROUND: Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives. OBJECTIVES: The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies. DESIGN AND SETTINGS: A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021. INDEPENDENT VARIABLES: (a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors. RESULTS: Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089). CONCLUSION: Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.

Efficacy of surgical treatment of perianal infection in patients with hematological malignancy.

The efficacy of surgical intervention for perianal infection in patients with hematologic malignancies is not well established. Therefore, our study aimed to investigate the clinical efficacy and complications of surgical treatment of perianal infection in patients with hematologic malignancies. This retrospective study included patients with hematological malignancies who were diagnosed with perianal infections and treated at the China Aerospace Science & Industry Corporation 731 Hospital between 2018 and 2022. Patient characteristics, hematological data, surgical intervention, and complications, including recurrence and mortality, were analyzed. This study included 156 patients with leukemia aged 2 months to 71 years who were treated surgically for perianal infection, comprising 94 males and 62 females. Perianal infection included 36 cases of abscesses, 91 anal fistulas, and 29 anal fissures accompanied by infection. A total of 36 patients developed severe complications postoperatively, including 4 patients who died, 6 patients with severe incision bleeding, 18 patients with severe pain, 6 patients with sepsis, 12 patients who needed reoperation, 15 patients with hospitalization for more than 2 weeks, and 3 patients with anal stenosis; none of the patients developed anal incontinence. Additionally, risk factors for postoperative complications of perianal infection in patients with hematologic malignancies include leukopenia, agranulocytosis, thrombocytopenia, depth of abscess and not undergone an MRI. Surgical intervention may improve the prognosis of patients with perianal abscess formation, particularly in patients who show no improvement with medical therapy and those who develop perianal sepsis. Granulocytopenia and thrombocytopenia should be improved before surgery, which can significantly reduce postoperative complications. Although these findings are from a case series without a comparator, they may be of value to physicians because to the best of our knowledge, no randomized or prospective studies have been conducted on the management of perianal infections in patients with hematological malignancies.

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

BACKGROUND: Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2). OBJECTIVE: Presenting real-world effectiveness data for darvadstrocel in a Spanish population. DESIGN: Observational retrospective cohort study with prospective data gathering. SETTINGS: The study was conducted at 14 institutions in Spain. PATIENTS: From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery. INTERVENTIONS: Darvadstrocel treatment. MAIN OUTCOME MEASURES: Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment. RESULTS: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported. LIMITATIONS: Retrospective nature of the study. CONCLUSIONS: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract . USO DE DARVADSTROCEL TERAPIA CON CLULAS MADRE ALOGNICAS PARA FSTULA EN ENFERMEDAD DE CROHN EN LA PRCTICA CLNICA REAL EL PROYECTO NACIONAL PARA IMPLEMENTAR DE CLULAS MADRE MESENQUIMALES PARA EL TRATAMIENTO DE LA FSTULA DE CROHN PERIANAL EL ESTUDIO PRIME: ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

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.

Dynamic contrast-enhanced MR imaging in identifying active anal fistula after surgery.

BACKGROUND: It is challenging to identify residual or recurrent fistulas from the surgical region, while MR imaging is feasible. The aim was to use dynamic contrast-enhanced MR imaging (DCE-MRI) technology to distinguish between active anal fistula and postoperative healing (granulation) tissue. METHODS: Thirty-six patients following idiopathic anal fistula underwent DCE-MRI. Subjects were divided into Group I (active fistula) and Group IV (postoperative healing tissue), with the latter divided into Group II (≤ 75 days) and Group III (> 75 days) according to the 75-day interval from surgery to postoperative MRI reexamination. MRI classification and quantitative analysis were performed. Correlation between postoperative time intervals and parameters was analyzed. The difference of parameters between the four groups was analyzed, and diagnostic efficiency was tested by receiver operating characteristic curve. RESULTS: Wash-in rate (WI) and peak enhancement intensity (PEI) were significantly higher in Group I than in Group II (p = 0.003, p = 0.040), while wash-out rate (WO), time to peak (TTP), and normalized signal intensity (NSI) were opposite (p = 0.031, p = 0.007, p = 0.010). Area under curves for discriminating active fistula from healing tissue within 75 days were 0.810 in WI, 0.708 in PEI, 0.719 in WO, 0.783 in TTP, 0.779 in NSI. All MRI parameters were significantly different between Group I and Group IV, but not between Group II and Group III, and not related to time intervals. CONCLUSION: In early postoperative period, DCE-MRI can be used to identify active anal fistula in the surgical area. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033072.

Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients.

BACKGROUND: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.

Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn's Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial.

BACKGROUND AND AIMS: There is an unmet need in the treatment of perianal fistulising Crohn's disease [PFCD]. This study evaluated the efficacy and safety of the Janus kinase 1 preferential inhibitor, filgotinib, for the treatment of PFCD. METHODS: This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomised [2:2:1] to receive filgotinib 200 mg, filgotinib 100 mg, or placebo, once daily orally for up to 24 weeks. The primary endpoint was combined fistula response (reduction from baseline of at least one draining external opening determined by physical assessment, and no fluid collections >1 cm on pelvic magnetic resonance imaging [MRI]) at Week 24. RESULTS: Between April 2017 and July 2020, 106 individuals were screened and 57 were randomised. Discontinuations were lowest in the filgotinib 200 mg group (3/17 [17.6%] versus 13/25 [52.0%] for filgotinib 100 mg and 9/15 [60.0%] for placebo). The proportion of participants who achieved a combined fistula response at Week 24 was 47.1% (8/17; 90% confidence interval [CI] 26.0, 68.9%) in the filgotinib 200 mg group, 29.2% [7/24; 90% CI 14.6, 47.9%] in the filgotinib 100 mg group, and 25.0% [3/12; 90% CI 7.2, 52.7%] in the placebo group. Serious adverse events occurred more frequently with filgotinib 200 mg (5/17 [29.4%]) than with placebo (1/15 [6.7%]). There were no treatment-related serious adverse events or deaths. CONCLUSIONS: Filgotinib 200 mg was associated with numerical reductions in the number of draining perianal fistulas based on combined clinical and MRI findings compared with placebo, and was generally well tolerated [NCT03077412].

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.

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

Extrapulmonary tuberculosis as a cause of complex perianal fistula disease.

Extrapulmonary tuberculosis (TB) in the gastrointestinal tract is a rare, but yet an essential differential diagnosis to patients with complex fistula disease, since the initiation of immunosuppressive therapy for presumed Crohn's disease can lead to a fulminant course of TB. This case report presents a young Danish woman with a progressive complex fistula disease, where cause and treatment were uncovered by interprofessional collaboration between pulmonologists, gastroenterologists and surgeons including a screening test for TB as well as multiple biopsies from the anal fistula tissue.

Posterior Urethral Reconstruction at the Time of Rectourethral Fistula Repair: Technique and Outcomes.

OBJECTIVE: To assess the impact of posterior urethral stenosis or defect on outcomes following rectourethral fistula (RUF) repair, we present a cohort of 23 men who underwent posterior urethroplasty concurrent with RUF repair. METHODS: We identified 130 men who underwent RUF repair at our institution between 2003 and 2021. Of these, 23 (18%) underwent simultaneous posterior urethroplasty. Fifteen men received prior radiation for prostate cancer. Of the 8 men who were not radiated, 4 had a history of radical prostatectomy, 2 pelvic trauma, and 3 inflammatory bowel disease. All 23 men underwent fecal diversion prior to surgery (median, 6 months preoperatively), and 20 men suprapubic catheter placement (median, 5.5 months preoperatively). RESULTS: RUF repair was performed via perineal approach in 22 cases (96%) and prone Kraske position in 1 (4%). Intraoperatively, 20 men (87%) had urethral stenosis, and 3 (13%) had significant urethral defects due to cavitation and tissue loss. There was stenosis/stricture involving the prostatomembranous urethra in 18 cases (78%) and vesicourethral anastomosis in 5 (22%). Urethroplasty was performed with anastomotic repair in 18 patients (78%) and using a buccal mucosal graft in 5 (22%). Gracilis flap interposition was performed in 21 cases (91%). At a median follow-up of 55.7 months (interquartile range (IQR), 23-82 months), 20 men (87%) had successful RUF closure, with 3 patients experiencing RUF recurrence requiring further surgery. Fourteen men (61%) reported postoperative urinary incontinence, with 7 (30%) ultimately undergoing artificial urinary sphincter placement. There were no isolated stricture recurrences requiring instrumentation. CONCLUSION: Posterior urethral stenosis associated with RUF complicates an already challenging problem. However, most of these patients can be successfully treated concurrent with RUF repair. This series demonstrates that patients with RUF should not be ruled out for restorative reconstructive surgery based on the presence of posterior urethral stenosis or defect.

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.

[Clinical characteristics and prognosis of children with perianal fistulizing Crohn's disease]. / å„¿ç«¥è‚›å‘¨ç˜˜ç®¡åž‹å ‹ç½—æ©ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD). METHODS: A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis. RESULTS: The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05). CONCLUSIONS: There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.