Perianal Fistula After Ileoanal Pouch in Patients With Ulcerative Colitis: A Review of 475 Patients Operated on at a Major IBD Center.

BACKGROUND: Ileoanal pouch anastomosis is the surgical treatment of choice for patients with intractable ulcerative colitis. Perianal disease is a feature that is often present in Crohn's disease and infrequently in ulcerative colitis. OBJECTIVE: The aim of this study is to identify the incidence and factors associated with the development of postoperative perianal fistula in patients undergoing ileoanal pouch anastomosis for ulcerative colitis. DESIGN: A prospectively collected database at the time of surgery with subsequent follow-up was utilized. SETTING: The study was conducted at a high-volume single institution. PATIENTS: We studied a series of 475 consecutive patients with preoperative diagnosis of ulcerative colitis who underwent ileoanal pouch anastomosis. MAIN OUTCOME MEASURES: The incidence of postoperative perianal fistula and the factors correlating with its development were primary outcome measures of the study. RESULTS: The overall number of patients developing perianal fistulas was 44 of 475 (9%). Eleven patients with perianal fistula (25%) required return to ileostomy, of which 7 had pouch excision. Patients who developed a postoperative perianal fistula had a younger age at the onset of disease, had a lower age at index surgery, and were more likely to be subsequently classified as indeterminate colitis or Crohn's disease. Patients developing perianal fistulas were also more likely to develop partial dehiscence or stricture of the ileoanal anastomosis. LIMITATIONS: This study spans nearly 40 years during which the surgical procedure evolved. CONCLUSIONS: Young age at the onset of disease, lower age at surgery, and postoperative diagnosis of Crohn's disease and indeterminate colitis were the factors correlating with perianal fistulas. Delayed healing of the ileoanal anastomosis with partial separation and/or stricture also correlated with the onset of perianal fistulas. The severity of rectal inflammation at the time of surgery or the presence of stapled versus handsewn anastomosis did not correlate with the development of perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B705. FSTULA PERIANAL POSTERIOR A RESERVORIO ILEOANAL EN PACIENTES CON COLITIS ULCERATIVA UNA REVISIN DE PACIENTES OPERADOS EN UN CENTRO PRINCIPAL DE EII: ANTECEDENTES:El reservorio ileoanal es el tratamiento quirúrgico de elección para los pacientes con colitis ulcerativa intratable. La enfermedad perianal es una característica que a menudo está presente en la enfermedad de Crohn y con poca frecuencia en la colitis ulcerativa.OBJETIVO:El objetivo del estudio es identificar la incidencia y los factores asociados con el desarrollo de fístula perianal posoperatoria en pacientes sometidos a reservorio ileoanal por colitis ulcerativa.DISEÑO:Base de datos recopilada prospectivamente en el momento de la cirugía con seguimiento subsecuente.ENTORNO CLÍNICO:El estudio se llevó a cabo en una única institución de gran volumen.PACIENTES:Estudiamos una serie de 475 pacientes consecutivos con diagnóstico preoperatorio de colitis ulcerativa a los que se les realizó reservorio ileoanal.PRINCIPALES MEDIDAS DE VALORACIÓN:La incidencia de fístula perianal posoperatoria y los factores que se correlacionan con su desarrollo fueron las principales medidas de resultado del estudio.RESULTADOS:El número total de pacientes que desarrollaron fístulas perianales fue 44 de 475 (9%). Once pacientes con fístula perianal (25%) requirieron volver a la ileostomía, de los cuales 7 tuvieron resección del reservorio. Los pacientes que desarrollaron fístula perianal posoperatoria tenían edad más temprana al inicio de la enfermedad, menor edad en el momento de la cirugía inicial y tenían más probabilidades de ser clasificados posteriormente como colitis indeterminada o enfermedad de Crohn. Los pacientes que desarrollaron fístulas perianales también fueron más propensos a desarrollar dehiscencia parcial o estenosis de la anastomosis ileoanal.LIMITACIONES:Este estudio abarca casi 40 años durante los cuales ha evolucionado el procedimiento quirúrgico.CONCLUSIONES:Edad temprana al inicio de la enfermedad, menor edad al momento de la cirugía, diagnóstico postoperatorio de enfermedad de Crohn y colitis indeterminada fueron los factores que se correlacionaron con las fístulas perianales. El retraso en la cicatrización de la anastomosis ileoanal con separación parcial y/o estenosis también se correlacionó con la aparición de fístulas perianales. La gravedad de la inflamación rectal en el momento de la cirugía o la presencia de anastomosis con grapas versus anastomosis manual no se correlacionó con el desarrollo de fístulas perianales. Consulte Video Resumen en http://links.lww.com/DCR/B705.

Accuracy of magnetic resonance imaging in defining dentate line in anal fistula.

PURPOSE: To retrospectively assess the accuracy of magnetic resonance imaging (MRI) in defining dentate line in anal fistula. MATERIALS AND METHODS: Seventy patients with anal fistulas were assessed by dynamic contrast-enhanced MRI. The distance from the dentate line to the anal verge for all patients was measured by MRI. To mitigate interference, 35 patients with anal fistulas whose internal openings were located on the dentate line were excluded from this study. Two observers independently judged the positional relationship between the internal opening and the MRI-defined dentate line, and compared with the results observed by surgeon to assess the accuracy. RESULTS: The distance between the MRI-defined dentate line and the anal verge depended on the location of the internal opening and the morphology of the anal canal mucosa. The distance based on the location the internal opening and the morphology of the anal canal mucosa was 18.2 ± 8.1 mm and 20.0 ± 5.3 mm on oblique coronal T2WI, respectively. Compared with the results observed by the surgeon, the accuracy of evaluating the positional relationship between the internal opening and the dentate line from the morphology of the anal canal mucosa on MRI exceeded 89.9%. Taking 18.2-20.0 mm as the distance between the dentate line and the anal verge on the MRI image, the accuracy of evaluating the relationship between the position of the internal opening and the dentate line was over 85.7%. Considering both the dentate line and the anal canal mucosa, the accuracy of evaluating the relationship between the internal opening and the dentate line was over 91.5%. The results of MRI-defined dentate line were in good agreement with the results of intraoperative surgeon evaluation, and the κ values were 0.70, 0.63, and 0.78, respectively. CONCLUSION: MRI has high accuracy in defining the dentate line in anal fistulas.

Safety of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Complex Perianal Fistulas Not Associated With Crohn's Disease: A Phase I Clinical Trial.

BACKGROUND: Anal fistula treatment aims to eradicate the fistula, preserve the sphincter, prevent recurrence, and allow an early return to daily activities for the patient. Because of the difficulty of achieving these goals, stem cell-based therapy has emerged for the treatment of complex perianal fistula with promising results. OBJECTIVE: The objective of this study was to evaluate the safety of allogeneic mesenchymal stem cells in the treatment of complex anal fistula in patients without Crohn's disease. DESIGN: This was a prospective nonrandomized phase I clinical trial. SETTINGS: This study was conducted at a second-level hospital. PATIENTS: Twenty consecutive patients diagnosed with a complex fistula were included. INTERVENTIONS: All patients received 40 × 106 allogeneic mesenchymal stem cells. In patients with 2 tracts, 20 × 106 stem cells were applied on each tract. MAIN OUTCOME MEASURES: The patients were discharged 24 hours after the procedure and were evaluated at 1, 2, 4, 8, 16, and 24 weeks after the application. The long-term follow-up was performed 1 year after the procedure. RESULTS: The procedure was performed in a total of 20 patients from October 1, 2016, to October 31, 2017; 1 patient was eliminated from the final data analysis. No adverse effects were reported within the first 24 hours, and all the patients were discharged asymptomatic. Three patients (15%) presented with perianal abscess. In 1 patient, the abscess appeared at the fourth week, and, in the other 2 patients, the abscess was diagnosed at week 8. Complete closure was achieved in 13 (69%) patients. LIMITATIONS: This was a nonrandomized controlled trial. CONCLUSION: The use of allogeneic mesenchymal stem cells as a treatment is a safe option for the management of complex perianal fistula not associated with Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B443. SEGURIDAD DE LAS CLULAS MADRE MESENQUIMALES ALOGNICAS DERIVADAS DEL TEJIDO ADIPOSO PARA EL TRATAMIENTO DE FSTULAS PERIANALES COMPLEJAS NO ASOCIADAS CON LA ENFERMEDAD DE CROHN ENSAYO CLNICO DE FASE I: ANTECEDENTES:El tratamiento de la fístula anal tiene como objetivo erradicar la fístula, preservar el esfínter, prevenir la recurrencia y permitir un retorno temprano a las actividades diarias del paciente. Debido a la dificultad de alcanzar estos objetivos, ha surgido una terapia basada en células madre para el tratamiento de la fístula perianal compleja con resultados prometedores.OBJETIVO:El objetivo de este estudio fue evaluar la seguridad de las células madre mesenquimales alogénicas en el tratamiento de la fístula anal compleja en pacientes sin enfermedad de Crohn.DISEÑO:Este fue un ensayo clínico prospectivo no aleatorizado de fase I.AMBIENTE:Este estudio se realizó en un hospital de segundo nivel.PACIENTES:Veinte pacientes consecutivos diagnosticados de fístula compleja.INTERVENCIONES:Todos los pacientes recibieron 40 x 106 células madre mesenquimales alogénicas, en pacientes con dos tractos, se aplicaron 20 x 106 células madre en cada tracto.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron dados de alta 24 horas después del procedimiento y fueron evaluados 1, 2, 4, 8, 16, 24 semanas después de la aplicación. El seguimiento a largo plazo se realizó un año después del procedimiento.RESULTADOS:El procedimiento se realizó en un total de 20 pacientes desde el 1 de octubre de 2016 al 31 de octubre de 2017; un paciente fue eliminado del análisis de datos final. No se informaron efectos adversos en las primeras 24 horas, todos los pacientes fueron dados de alta asintomáticos. Tres pacientes (15%) presentaron absceso perianal. En un paciente, el absceso apareció a la cuarta semana y en los otros dos pacientes el absceso se diagnosticó en la octava semana. El cierre completo se logró en 13 (69%) de los pacientes.LIMITACIONES:Este fue un ensayo controlado no aleatorio.CONCLUSIÓN:El uso de células madre mesenquimales alogénicas como tratamiento es una opción segura para el manejo de la fístula perianal compleja no asociada con la enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B443.

Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial.

BACKGROUND: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas. DESIGN: This is a randomized controlled trial. SETTINGS: This study was conducted at a single center. PATIENTS: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included. INTERVENTIONS: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery. MAIN OUTCOME MEASURES: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated. RESULTS: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups. LIMITATIONS: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study. CONCLUSIONS: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607. CLINICAL TRIALS REGISTRATION: URL: https://www.clinicaltrials.gov. Identifier: NCT04326907. EFICACIA Y SEGURIDAD DEL TRATAMIENTO DE LA FSTULA ANAL COMPLEJA IDIOPTICA UTILIZANDO TEJIDO ADIPOSO CENTRIFUGADO AUTLOGO QUE CONTIENE CLULAS PROGENITORAS UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:Las células madre mesenquimales derivadas del tejido adiposo se han utilizado con éxito para promover la curación de la fístula anal con preservación de esfínter.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia y seguridad del uso de tejido adiposo autólogo centrifugado en el proceso de cicatrización de fístulas anales complejas de origen criptoglandular.DISEÑO:Ensayo controlado aleatorio.ENTORNO CLÍNICO:Estudio unicéntrico.PACIENTES:Se incluyeron pacientes con fístulas perianales complejas no asociadas a Enfermedad de Crohn. No se incluyeron las fístulas rectovaginales.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente para recibir tratamiento con inyección de tejido adiposo centrifugado (grupo experimental) y sin inyección (grupo de control) en combinación con cirugía de fístula.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado primario se definió como la proporción de pacientes con cierre completo de la fístula a las 4 semanas (resultado a corto plazo) y 6 meses después de la cirugía (resultado a largo plazo). La curación se definió cuando orificio externo se cerró sin secreción perianal en la valoración clínica. El resultado secundario fue la seguridad que se evaluó mediante el análisis de los eventos adversos (EA) hasta 3 meses después de la cirugía. La resonancia magnética pélvica se realizó a los 3 meses para garantizar la seguridad y la precisión clínica de la curación. Se evaluó el dolor postoperatorio, el regreso al trabajo / actividades diarias, el cierre persistente a los 6 meses, la incontinencia fecal y la satisfacción del paciente.RESULTADOS:Cincuenta y ocho pacientes que recibieron inyección de tejido adiposo centrifugado y 58 pacientes que no recibieron inyección de tejido adiposo centrifugado se incluyeron en el análisis de seguridad y eficacia. Después de 4 semanas, la tasa de curación fue del 63,8% en el grupo experimental en comparación con el 15,5% en el grupo de control (p <0,001). No se registraron eventos adversos importantes. El dolor anal posoperatorio fue significativamente menor en el grupo de inyección. El tiempo necesario para volver al trabajo / actividades diarias fue significativamente menor en el grupo experimental (3 días) con respecto al grupo de control (17 días). A los 6 meses, el cierre persistente fue similar en los dos grupos (86,2% vs 81%). La puntuación de incontinencia fecal a los 6 meses después de la cirugía fue idéntica a la puntuación preoperatoria. La satisfacción del paciente fue muy alta en ambos grupos.LIMITACIONES:Ausencia de cegamiento, falta de correlación entre el contenido de células madre y el resultado clínico.CONCLUSIONES:La inyección de tejido adiposo centrifugado autólogo puede representar una opción segura, eficaz y económica para el tratamiento de la fístula anal compleja.Registro de ensayos clínicos: www.clinicaltrials.gov, identificador NCT04326907; No patrocinado.Consulte Video Resumen en http://links.lww.com/DCR/B607.

Clinical, microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn's disease.

Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next-generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α and IL-1ß). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, non-branching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.

Photodynamic Therapy for the Treatment of Complex Anal Fistula.

BACKGROUND AND OBJECTIVES: To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula. STUDY DESIGN/MATERIALS AND METHODS: This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i-PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow-up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5-aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J). RESULTS: In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3-5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure-related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow-up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively. CONCLUSION: i-PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Developing a core outcome set for fistulising perianal Crohn's disease.

OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.

Adenocarcinoma within anorectal fistulae: different clinicopathological characteristics between Crohn's disease-associated type and the usual type.

Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal fistulae has a poor prognosis; however, little is known about the clinicopathological differences between Crohn's disease-associated adenocarcinoma within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We retrospectively searched patients' charts and pathology archives at Tokyo Yamate Medical Center and Tokyo Medical and Dental University Hospital for adenocarcinoma within anorectal fistulae. Clinical and pathological data were collected and immunohistochemical examinations were conducted. Overall survival rate was estimated using the Kaplan-Meier method. Prognostic factors of overall survival were assessed using univariate and multivariate Cox regression analyses. We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of 82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae were diagnosed at a younger age and at a more advanced stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic and histological types were also different between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae included more ulcerative types and high-grade adenocarcinomas. The rate of lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma within anorectal fistulae. Immunohistochemically, the expression of E-cadherin, p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae exhibited worse overall survival than those with usual adenocarcinoma within anorectal fistulae, and vascular invasion was the strongest significant independent predictor of overall survival in patients with adenocarcinoma within anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae have different clinicopathological characteristics and should be considered separate clinical entities.

Treatment of complex recurrent fistula-in-ano by surgery combined to autologous bone marrow-derived mesenchymal stroma cells and platelet-rich plasma injection.

PURPOSE: We report a case of successful management of complex recurrent cryptoglandular fistula-in-ano by surgery combined with autologous bone marrow-derived mesenchymal stroma cells (MSCs) and platelet-rich plasma (PRP) injection. METHODS: Clinical, radiological, and surgical data of the patient were reviewed, as well as the current literature on complex fistula-in-ano. RESULTS: A 37-year-old man with a recurrent cryptoglandular perianal fistula was addressed to our department. Inflammatory bowel disease was excluded by clinical history, endoscopy, and blood tests. Physical examination and MRI showed an anterior external orifice on the midline, 5 cm from the anal verge, with an internal orifice on the same line. Surgery combined to injection of MSC-PRP solution was successfully performed. MSC-PRP solution was prepared while the patient was under general anesthesia: bone marrow MSCs were obtained by centrifugation of a tibial puncture specimen and PRP from a peripheral whole blood sample of the patient. There were no adverse events post-operatively. Clinical and MRI examination 4 months after treatment confirmed the absence of perianal fistula. More than 2 years after surgery, there has been no recurrence. CONCLUSIONS: Treatment of complex recurrent cryptoglandular fistula-in-ano by surgery combined to autologous bone marrow-derived MSCs and PRP injection seems safe in selected patients, allowing long-term healing. This procedure seems promising but further evaluation by clinical trials is warranted.

Anal fistula plug vs rectal advancement flap for the treatment of complex cryptoglandular anal fistulas: a systematic review and meta-analysis of studies with long-term follow-up.

AIM: The aim was to compare the effectiveness of the anal fistula plug (AFP) with the rectal advancement flap (RAF) for complex cryptoglandular anal fistulas. METHODS: We conducted a literature search to identify relevant available articles published without language restriction from Embase and PubMed databases and the Cochrane Library. Studies comparing outcomes with the AFP vs RAF for complex cryptoglandular anal fistulas were eligible for inclusion. RESULTS: A total of 11 articles with 810 patients were included in this meta-analysis. Four RCTs and one observational clinical study provided long-term follow-up. The pooled analysis of all 11 studies indicated that there was no significant difference between the AFP and RAF in terms of healing rate, recurrence rate and incidence of fistula complications. However, the pooled results of studies with long-term follow-up revealed that the RAF group had a significantly higher healing rate (OR 0.32, 95% CI 0.13, 0.78, P = 0.01) and lower recurrence rate (OR 4.45, 95% CI 1.45, 13.65, P = 0.009) than the AFP group. CONCLUSIONS: For the treatment of complex cryptoglandular anal fistulas, the RAF was superior to the AFP in terms of healing and recurrence rate after pooling of randomized controlled trials with long-term follow-up, even though a comparison based on the pooling of all studies showed no significant difference.

A rare case of rectal cancer with perianal metastasis: a case report.

BACKGROUND: Cancer metastasis from colon cancer to an anal fistula is very rare. We herein reported a rare case in which local excision was performed for metastatic anal fistula cancer originating from rectal cancer. CASE PRESENTATION: A 68-year-old man was referred to our institution with a diagnosis of rectal cancer. He had complained of anal fistula for 5 years. Based on a recent history of cerebral infarction, Hartmann's operation was performed to treat the rectal cancer after the administration of preoperative chemotherapy for 3 months. However, 1 month after Hartmann's operation, the anal fistula was found to have worsened. Pelvic magnetic resonance imaging (MRI) revealed tumor formation at the perianal lesion. Metastatic anal fistula cancer originating from the rectal cancer was diagnosed based on the examination of the biopsied tissue. We selected local excision because the anal tumor had not invaded the surrounding tissue. There has been no recurrence in the 31 months after the curative operation. CONCLUSION: Metastatic cancer should be ruled out when treating left-sided colon cancer with anal fistula. Local excision is one possible treatment for metastatic anal fistula cancer.

Perianal fistulas in adult patients with Crohn's disease in Germany - a retrospective cross-sectional analysis of claims data from German sickness funds.

INTRODUCTION: Perianal fistulas (PF) are presumably a frequent extraintestinal manifestation of Crohn's disease (CD), causing significant functional impairment. This study aims to gain representative data on the prevalence, characteristics, and treatment of CD patients suffering from PF in Germany. MATERIALS AND METHODS: A retrospective cross-sectional analysis of claims data from several German company health insurance funds included adult patients with CD and PF in 2015. The dataset comprised in- and outpatient services with diagnoses, drug prescriptions, and other patient data. It is representative for age, gender, and region and allows extrapolation to the total German statutory health insurance (SHI) population. A systematic literature review was conducted to discuss these results in the international context. RESULTS: A CD prevalence of 299 per 100 000 and a PF prevalence in CD patients of 3.4 % was observed in this cross-sectional study. PF are most prevalent in young age groups (< 24 to 39). One-third of patients with PF received biologics and surgery. Surgical procedures were performed in 31.3 % of PF patients in the inpatient setting and in 4.4 % of PF patients in the outpatient setting. All complicated perianal fistula patients received at least 1 inpatient surgery and 44.8 % received biologic therapy. DISCUSSION: This claims data analysis in German patients estimates a CD prevalence in the SHI population that corresponds well to previously reported data. The prevalence rate for PF in CD patients is comparable with a previous cross-sectional German claims data analysis but is markedly lower than cumulative risks reported in longitudinal cohort studies. PF patients are young and treatment intensive with one-third requiring biologic treatment or inpatient surgery.

Rectal ulcer and pseudomalignant epithelial changes after prostate seed brachytherapy: A rare complication with a diagnostic pitfall.

BACKGROUND: Implant brachytherapy (IBT) is a well-recognized treatment modality for early stage prostate cancer. Rectal ulcer and rectourethral fistula complicating IBT may cause an alteration of the normal anatomic landmarks. In this context, pseudomalignant radiation-induced changes within prostatic epithelium may be misinterpreted as a primary rectal malignancy. Such challenging and misleading findings have not been described, and may not be recognized as such. MATERIALS AND METHODS: We present the clinical and pathologic aspects of two patients who underwent IBT for low stage prostate cancer that was complicated by deep rectal ulcer. Both patients underwent extensive palliative surgical resection for disease control. RESULTS: The histologic changes in both cases were noteworthy for extensive necrosis and inflammation of the prostate, associated with loss of recto-prostatic anatomical landmarks. Prostatic glands showed striking radiation-induced atypia and pseudomalignant epithelial changes extending to the rectal ulcer bed, with no residual viable tumor. The first patient had undergone a biopsy of the rectal ulcer bed that was misinterpreted as a rectal adenocarcinoma prior to surgery. The similarity between atypical glands of the biopsy and the benign prostatic tissue with radiation-induced atypia in resection specimen confirmed their benign nature. CONCLUSIONS: Deep rectal ulcer complicating IBT may lead to distortion of the normal recto-prostatic anatomical landmarks, resulting in detection of pseudo-malignant prostatic glands at the ulcer base. Such findings may be mistaken for a primary rectal malignancy in limited biopsy material if not familiar to the pathologist.

Anal Fistula Laser Closure: the length of fistula is the Achilles' heel.

BACKGROUND: Laser closure is a novel sphincter-saving technique for the treatment of anal fistula. The aim of this study was to report middle term results of laser treatment without closure of the internal orifice and to identify prognostic factors to improve selection criteria and maximize healing. METHODS: A retrospective observational study was conducted on patients treated with laser for transphinteric anal fistula. A diode laser emitting laser energy of 12W at a wavelength of 1470 nm was used. The relationship between fistula healing and age, sex, previous fistula surgery, location of fistula, and length of fistula tract was investigated. A successful outcome was defined by the complete healing of the surgical wound and external opening for at least 6 months. RESULTS: Thirty patients (16 males, median age 52 years, range 26-72 years) underwent laser fistula closure between January 2015 and December 2016. Cure was achieved in 10 patients (33.3%). The mean follow-up was 11.30 months (range 6-24 months). Patients with persistent or recurrent fistula were offered repeat surgery. Eventually 4 underwent laser treatment once more. Two patients were cured leading to an overall healing rate of 40% (12 out of 30). Only 4 minor complications occurred (13.3%). No worsening of anal continence was registered. Only fistula length had a statistically significant correlation with successful treatment. Fistula tracts shorter than 30 mm were associated with a primary healing rate of 58.3% while tracts longer than 30 mm were cured in only 16.6% of cases (p < 0.02). CONCLUSIONS: Laser closure is a safe and effective treatment for transphinteric anal fistula. The fistula length is the only significant prognostic factor when closing anal fistulas exclusively with laser: shorter fistulas have a better outcome.

Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial.

BACKGROUND: Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. METHODS: We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov, number NCT01541579. FINDINGS: 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2-30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5-31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). INTERPRETATION: Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. FUNDING: TiGenix.

Comparison of histopathology and real-time polymerase chain reaction (RT-PCR) for detection of Mycobacterium tuberculosis in fistula-in-ano.

PURPOSE: Histopathology is commonly used to diagnose tuberculosis in fistula-in-ano. The aim was to compare the sensitivity of polymerase chain reaction and histopathology in detecting tuberculosis in fistula-in-ano. METHODS: The histopathology and polymerase chain-reaction of tissue (fistula tract) was done in all the consecutive operated cases. When pus sample was also available, polymerase chain reaction-pus was also done RESULTS: Three hundred forty seven samples (179 patients) were tested over 2 years (median 6.5 months). The mean age was 38.8 ± 10.7 years, and male/female was 170/9. Histopathology and polymerase chain reaction of tissue (fistula tract) was done in 152 and 165 patients, respectively. Polymerase chain reaction (pus) could be done in 30 patients. Overall, tuberculosis was detected in 20/179 (11.2%) patients. Of these, tuberculosis was detected by histopathology (tissue) in 1/152 (0.7%) and by polymerase chain reaction (tissue) in 14/165 (8.5%) patients. In pus, polymerase chain reaction detected tuberculosis in 6/30 (20%) patients. Both polymerase chain reaction of tissue and pus were positive in one patient. Polymerase chain reaction (tissue) and polymerase chain reaction (pus) were significantly more sensitive than histopathology (tissue) for detecting tuberculosis [histopathology 1/152 vs. polymerase chain reaction (tissue) 14/165, p = 0.0009] [histopathology 1/152 vs. polymerase chain reaction (pus) 6/30, p < 0.0001]. In 20 patients detected to have tuberculosis, four drug anti-tubercular therapy was recommended for 6 months. The therapy was completed in 13 patients and 12/13 (92.3%) were cured. The therapy is continuing in 3/20 patients. Four patients did not take the therapy. None of them was cured. CONCLUSIONS: Polymerase chain reaction was significantly more sensitive than histopathology in detecting tuberculosis in fistula-in-ano. Histopathology might be missing out tuberculosis in many patients leading to recurrence of the fistula.

Perianal Pediatric Crohn Disease Is Associated With a Distinct Phenotype and Greater Inflammatory Burden.

OBJECTIVES: Data on the outcomes of children with perianal Crohn disease (pCD) are limited, although its presence is often used for justifying early use of biologics. We aimed to assess whether pCD in children is associated with more severe outcomes as found in adults. METHODS: Data were extracted from the ImageKids database, a prospective, multicenter, longitudinal cohort study. The study enrolled 246 children at disease onset or thereafter. All patients underwent comprehensive clinical, endoscopic, and radiologic evaluation at enrollment; 98 children had repeat evaluation at 18 months. RESULTS: Of the 234 included patients (mean age 14.2 ±â€Š2.4 years; 131 [56%] boys), 57 (24%) had perianal findings, whereas only 21 (9%) had fistulizing perianal disease. Children with pCD had reduced weight and height z scores compared with non-pCD patients (-0.9 vs -0.35, P = 0.03 and -0.68 vs -0.23, respectively; P = 0.04), higher weighted pediatric CD activity index (32 [interquartile range 16-50] vs 20 [8-37]; P = 0.004), lower serum albumin (3.6 ±â€Š0.7 vs 4.5 ±â€Š0.8, P = 0.016), and higher magnetic resonance enterography global inflammatory score (P = 0.04). Children with pCD had more rectal (57% vs 38%, P = 0.04), and jejunal involvement (31% vs 11% P = 0.003) and a higher prevalence of granulomas (64% vs 23%, P = 0.0001). Magnetic resonance enterography-based damage scores did not differ between groups. Patients with skin tags/fissures only, had similar clinical, endoscopic, and radiologic characteristics as patients with no perianal findings. CONCLUSIONS: Pediatric patients with pCD with fistulizing disease have distinct phenotypic features and a predisposition to a greater inflammatory burden.

Surgical treatment of trans-sphincteric anal fistulas with the Fat GRAFT technique: a minimally invasive procedure.

AIM: Anal fistulas are common pathologies with a significant social impact; however, their treatment is often complex and the recurrence rate can be significant. Some surgical treatments for fistula are also associated with the risk of sphincter injury. In this technical note, we aim to evaluate the feasibility and efficacy of the Fat GRAFT technique (Fat Grafting in Anal Fistula Treatment) in the treatment of recurrent anal fistulas. METHOD: All patients presenting with recurrent trans-sphincteric anal fistulas over an 18-month period were included. After abdominal fat harvesting and fat preparation, fat grafting was performed in the track and peripheral area of the fistula. The internal and external openings of the fistula were closed to maximally preserve the retention of the adipocyte graft in the fistula. RESULTS: Eleven patients underwent the Fat GRAFT procedure (seven men, four women). The average re-injected volume for each fistula was 21 ml (range 10-30 ml). The postoperative course was uneventful. At 6 months three patients developed recurrence (73% healed). There were no postoperative complications. CONCLUSION: The Fat GRAFT technique appears to be a promising technique with a low risk of anal incontinence, in contrast to other techniques. This method was effective in > 70% of patients in a single session.

Three-dimensional endoanal ultrasound is accurate and reproducible in determining type and height of anal fistulas.

AIM: Surgical treatment of high anal fistulas is associated with the potential risk of faecal incontinence and recurrence. The primary aim of this study was to determine the accuracy of three-dimensional endoanal ultrasound (3D-EAUS) in the assessment of height and type of anal fistulas, compared to the intra-operative findings (gold standard). The secondary aim was to evaluate the inter-observer reproducibility of 3D-EAUS. METHOD: The study design was a prospective analysis of retrospective data. 299 patients (202 men), mean age 45.3 years, who underwent surgery for anal fistulas, were included. All patients were preoperatively assessed by 3D-EAUS. Two readers independently reviewed the volumes to determine the type and height of fistulas. Sensitivity, specificity, positive and negative predictive values, proportion of agreements and Cohen's kappa coefficient (κ) were calculated for both examiners. Ultrasound findings were compared with intra-operative data (reference standard), evaluated blindly by the surgeons. RESULTS: At surgery, 201 (67%) were transsphincteric, 49 (16%) suprasphincteric, 47 (16%) intersphincteric and two (1%) extrasphincteric fistulas. Intra-operatively, 177 (59%) were low and 122 (41%) high fistulas. The overall accuracy of 3D-EAUS was 91% for fistula type (271/299 fistulas: 97% transsphincteric, 100% intersphincteric, 57% suprasphincteric, 0% extrasphincteric) and 92% for fistula height (275/299 fistulas: 80% high and 100% low). Both readers reported very good agreement with surgery in the assessment of fistula type (proportion of agreement 0.88, κ = 0.89) and height (proportion of agreement 0.90, κ = 0.91). CONCLUSIONS: 3D-EAUS is an accurate and reproducible modality for the assessment of type and height of anal fistulas.