Perianal fistulizing Crohn's disease-associated anorectal and fistula cancers: systematic review and expert consensus.

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSION: Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Salvage Surgery: An Effective Therapy in the Management of Ileoanal Pouch Prolapse.

BACKGROUND: Restorative proctocolectomy with IPAA is the surgical treatment of choice for patients requiring surgery for IBD and, less frequently, for other pathologies. Pouch prolapse is a rare complication that compromises pouch function and negatively affects patients' quality of life. OBJECTIVE: This study aimed to describe our experience from a single high-volume center in this infrequent condition. DESIGN: Restrospective cohort study of a prospectively maintained, Institutional Review Board-approved database. SETTINGS: All consecutive eligible patients with IPAA and pouch prolapse were identified from 1990 to 2021. PATIENTS: Patients with full-thickness prolapse treated by pouch pexy were included. INTERVENTIONS: Pouch pexy (with/without mesh). MAIN OUTCOME MEASURES: Success rate of pouch pexy, defined as no recurrence of prolapse. RESULTS: A total of 4791 patients underwent IPAA; 7 (0.1%) were diagnosed with full-thickness prolapse. An additional 18 patients who underwent IPAA and had full-thickness prolapse were referred from outside institutions. Among 25 included patients, 16 (64.0%) were women, and the overall mean age was 35.6 ± 13.4 years. The time interval from initial pouch formation to prolapse was 4.2 (interquartile range, 1.1-8.5) years. Nine patients (36.0%) underwent previous treatment for prolapse. All patients presented with symptoms and physical examination compatible with full-thickness prolapse. Twenty patients (80.0%) underwent surgical pouch pexy without mesh and 5 (20.0%) had pouch pexy with mesh placement. A diverting ileostomy was performed in 1 patient (4.0%) before pouch pexy and in 8 patients (32.0%) at the time of surgical prolapse correction. After surgery, recurrent prolapse was noted in 3 patients (12.0%) at a median of 6.9 (interquartile range, 5.2-8.3) months. LIMITATIONS: Retrospective study, small sample size thus prone to selection, and referral biases, which may limit the generalizability of our findings. CONCLUSION: Pouch prolapse can be effectively treated with salvage surgery. Surgical intervention is safe and provides acceptable outcomes. See Video Abstract. CIRUGA DE RESCATE UNA TERAPIA EFICAZ EN EL MANEJO DEL PROLAPSO DE LA BOLSA ILEOANAL: ANTECEDENTES:La proctocolectomía restauradora con anastomosis reservorio ileoanal es el tratamiento quirúrgico de elección para aquellos pacientes que requieren cirugía por enfermedad inflamatoria intestinal y, con menor frecuencia, por otras patologías. El prolapso de la bolsa es una complicación rara que compromete la función de la bolsa y afecta de manera negativa la calidad de vida de los pacientes.OBJETIVO:Describir nuestra experiencia de un solo centro de alto volumen en esta condición poco frecuente.DISEÑO:Estudio de cohorte retrospectivo de una base de datos mantenida prospectivamente aprobada por el IRB.AJUSTES/PACIENTES:Fueron identificados y elegibles de manera consecutiva todos los pacientes con anastomosis de bolsa ileoanal y prolapso de bolsa entre 1990 y 2021. Se incluyeron pacientes con prolapso de bolsa de espesor total tratados con pexia.INTERVENCIONES:Pexia de la bolsa (con/sin malla).PRINCIPALES MEDIDAS DE RESULTADO:Tasa de éxito de la pexia de la bolsa, definida como ausencia de recurrencia del prolapso.RESULTADOS:Un total de 4.791 pacientes fueron sometidos a anastomosis de bolsa ileoanal; siete (0,1%) fueron diagnosticados con prolapso de espesor total. Otros 18 pacientes con anastomosis de reservorio ileoanal fueron derivados de instituciones externas. De entre los 25 pacientes incluidos, 16 (64,0 %) eran mujeres y la edad media promedio fue de 35,6+/-13,4 años. El intervalo de tiempo desde la creación inicial de la bolsa hasta el prolapso fue de 4,2 (IQR 1,1-8,5) años. Nueve (36,0 %) pacientes fueron sometidos a tratamiento previo para el prolapso (fisioterapia n = 4, pexia de la bolsa n = 2, pexia de la bolsa con malla n = 2, resección de la mucosa n = 1). Todos los pacientes presentaron síntomas y exploración física compatibles con prolapso de espesor total. Veinte (80,0%) pacientes se sometieron a pexia de bolsa quirúrgica sin malla y cinco (20,0%) se sometieron a pexia de bolsa con colocación de malla. Se realizó una ileostomía de derivación en un (4,0%) paciente antes de la pexia de la bolsa y en ocho (32,0%) pacientes en el momento de la corrección quirúrgica del prolapso. Posterior a la cirugía, se observó prolapso recurrente en tres pacientes (12,0 %) con una mediana de 6,9 (IQR 5,2-8,3) meses.LIMITACIONES:Estudio retrospectivo, pequeño tamaño de muestra, por lo tanto, propenso a sesgos de selección y referencia que pueden limitar la generalización de nuestros hallazgos.CONCLUSIÓN:El prolapso de la bolsa ileoanal puede tratarse de manera efectiva mediante la cirugía de rescate. La intervención quirúrgica es segura y proporciona resultados aceptables. (Traducción-Dr. Mauricio Santamaria ).

Tofacitinib Is Associated With Increased Risk of Postoperative Venous Thromboembolism in Patients With Ulcerative Colitis.

BACKGROUND: In 2019, the Food and Drug Administration issued a black box warning for increased risk of venous thromboembolism in patients with rheumatoid arthritis exposed to tofacitinib. There are limited data regarding postoperative venous thromboembolism risk in patients with ulcerative colitis exposed to tofacitinib. OBJECTIVE: To assess whether preoperative exposure to tofacitinib is associated with increased odds of postoperative venous thromboembolism. DESIGN: Retrospective review. SETTINGS: Tertiary academic medical center. PATIENTS: Consecutive patients exposed to tofacitinib within 4 weeks before total abdominal colectomy or total proctocolectomy, with or without ileostomy, from 2014 to 2021, matched 1:2 for tofacitinib exposure or no exposure. INTERVENTION: Tofacitinib exposure versus no exposure. MAIN OUTCOME MEASURES: Ninety-day postoperative venous thromboembolism rate. RESULTS: Forty-two patients with tofacitinib exposure and 84 case-matched patients without tofacitinib exposure underwent surgery for medically refractory ulcerative colitis. Nine (22.0%) tofacitinib-exposed patients and 7 (8.5%) unexposed patients were diagnosed with venous thromboembolism within 90 days of surgery. In univariate logistic regression, patients exposed to tofacitinib had 3.01 times increased odds of developing venous thromboembolism within 90 days after surgery compared to unexposed patients ( p = 0.04; 95% CI, 1.03-8.79). Other venous thromboembolism risk factors were not significantly associated with venous thromboembolisms. Venous thromboembolisms in both groups were most commonly portomesenteric vein thromboses (66.7% in the tofacitinib-exposed group and 42.9% in the unexposed group) and were diagnosed at a mean of 23.2 days (range, 3-90 days) postoperatively in the tofacitinib-exposed group and 7.9 days (1-19 days) in the unexposed group. There were no statistically significant differences in location or timing between the 2 groups. LIMITATIONS: Retrospective nature of the study and associated biases. Reliance on clinically diagnosed venous thromboembolisms may underreport the true incidence rate. CONCLUSIONS: Tofacitinib exposure before surgery for medically refractory ulcerative colitis is associated with 3 times increased odds of venous thromboembolism compared with patients without tofacitinib exposure. See Video Abstract . TOFACITINIB SE ASOCIA CON UN MAYOR RIESGO DE TROMBOEMBOLISMO VENOSO POSTOPERATORIO EN PACIENTES CON COLITIS ULCEROSA: ANTECEDENTES:En 2019, la FDA emitió una advertencia de recuadro negro sobre un mayor riesgo de tromboembolismo venoso en pacientes con artritis reumatoide expuestos a tofacitinib. Hay datos limitados sobre el riesgo de tromboembolismo venoso postoperatorio en pacientes con colitis ulcerosa expuestos a tofacitinib.OBJETIVO:Evaluar si la exposición preoperatoria a tofacitinib se asocia con mayores probabilidades de tromboembolismo venoso postoperatorio.DISEÑO:Revisión retrospectiva.LUGARES:Centro médico académico terciario.PACIENTES:Pacientes consecutivos expuestos a tofacitinib dentro de las 4 semanas previas a la colectomía abdominal total o proctocolectomía total, con o sin ileostomía, entre 2014 y 2021, emparejados 1:2 para exposición a tofacitinib o ninguna exposición.INTERVENCIÓN(S):Exposición a tofacitinib versus ninguna exposición.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de tromboembolismo venoso posoperatorio a los 90 días.RESULTADOS:Cuarenta y dos pacientes con exposición a tofacitinib y 84 pacientes de casos similares sin exposición a tofacitinib se sometieron a cirugía por colitis ulcerosa médicamente refractaria. Nueve (22,0%) pacientes expuestos a tofacitinib y 7 (8,5%) pacientes no expuestos fueron diagnosticados con tromboembolismo venoso dentro de los 90 días posteriores a la cirugía. En la regresión logística univariada, los pacientes expuestos a tofacitinib tuvieron 3,01 veces más probabilidades de desarrollar un tromboembolismo venoso dentro de los 90 días posteriores a la cirugía en comparación con los no expuestos ( p = 0,04, IC del 95 %: 1,03-8,79). Otros factores de riesgo de tromboembolismo venoso no se asociaron significativamente con el tromboembolismo venoso. Los tromboembolismos venosos en ambos grupos fueron más comúnmente trombosis de la vena portomesentérica (66,7% en los expuestos a tofacitinib y 42,9% en los no expuestos) y se diagnosticaron en una media de 23,2 días (rango, 3-90 días) después de la operación en los expuestos a tofacitinib y 7,9 días. (1-19 días) en los grupos no expuestos, respectivamente. No hubo diferencias estadísticamente significativas en la ubicación o el momento entre los dos grupos.LIMITACIONES:Carácter retrospectivo del estudio y sesgos asociados. La dependencia de tromboembolismos venosos diagnosticados clínicamente puede subestimar la tasa de incidencia real.CONCLUSIONES:La exposición a tofacitinib antes de la cirugía para la colitis ulcerosa médicamente refractaria se asocia con probabilidades 3 veces mayores de tromboembolismo venoso en comparación con los pacientes sin exposición a tofacitinib. (Traducción-Dr. Mauricio Santamaria ).

The mode of delivery does not influence the occurrence of post-partum perianal disease flares in patients with inflammatory bowel disease.

INTRODUCTION: Perianal disease occurs in up to 34% of inflammatory bowel disease (IBD) patients. An estimated 25% of women will become pregnant after the initial diagnosis, thus introducing the dilemma of whether mode of delivery affects perianal disease. The aim of our study was to analyze whether a cesarean section (C-section) or vaginal delivery influence perianal involvement. We hypothesized the delivery route would not alter post-partum perianal manifestations in the setting of previously healed perianal disease. METHODS: All consecutive eligible IBD female patients between 1997 and 2022 who delivered were included. Prior perianal involvement, perianal flare after delivery and delivery method were noted. RESULTS: We identified 190 patients with IBD who had a total of 322 deliveries; 169 (52%) were vaginal and 153 (48%) were by C-section. Nineteen women (10%) experienced 21/322 (6%) post-partum perianal flares. Independent predictors were previous abdominal surgery for IBD (OR, 2.7; 95% CI, 1-7.2; p = 0.042), ileocolonic involvement (OR, 3.3; 95% CI, 1.1-9.4; p = 0.030), previous perianal disease (OR, 22; 95% CI, 7-69; p < 0.001), active perianal disease (OR, 96; 95% CI, 21-446; p < 0.001) and biologic (OR, 4.4; 95% CI,1.4-13.6; p < 0.011) or antibiotic (OR, 19.6; 95% CI, 7-54; p < 0.001) treatment. Negative association was found for vaginal delivery (OR, 0.19; 95% CI, 0.06-0.61; p < 0.005). Number of post-partum flares was higher in the C-section group [17 (11%) vs. 4 (2%), p = 0.002]. CONCLUSIONS: Delivery by C-section section was not protective of ongoing perianal disease activity post-delivery, but should be recommended for women with active perianal involvement.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Gracilis Flap Repair for Reoperative Rectovaginal Fistula.

BACKGROUND: Surgical treatment of recurrent rectovaginal fistulas is notoriously difficult. Placement of the gracilis muscle between the vagina and anus is an advanced technique used to close persistent fistulas. We have utilized this procedure for recalcitrant fistulas and hypothesized that a gracilis interposition would offer a good treatment option for patients with refractory rectovaginal fistulas, regardless of underlying etiology. OBJECTIVE: The purpose of this study was to investigate healing rates of gracilis interposition in patients with refractory rectovaginal fistulas. DESIGN: Following institutional review board approval, a retrospective review of all adult female patients with a diagnosis of rectovaginal fistula between January 2009 and August 2020 was performed; those who underwent gracilis interposition for definitive fistula closure were included for analysis. SETTINGS: The study was conducted at a colorectal surgery department at a tertiary center in the United States. PATIENTS: All patients were adult females with a diagnosis of a rectovaginal fistula who underwent gracilis interposition for definitive closure. MAIN OUTCOME MEASURES: Patient demographics, etiology of rectovaginal fistula, previous surgical intervention, presence of intestinal diversion, operative details, 30-day morbidity, recurrence of fistula, and time to recurrence. Fistula closure was defined as lack of clinical symptoms following stoma closure, negative fistula detection on gastrograffin enema' and absence of an internal opening at examination under anesthesia. RESULTS: Twenty-two patients were included who had a median age of 43 years (range, 19-64 years) and median body mass index of 31 kg/m 2 (range, 22-51). Median time between prior attempted surgical repair and gracilis surgery was 7 months (range, 3-17). The number of previously attempted repairs were 1-2 (n = 8), 3-4 (n = 9), and > 4 (n = 5). The most recent attempted surgical repair was rectal advancement flap (n = 7), transperineal +/- Martius flap (n = 4), episioproctotomy (n = 3), transvaginal repair (n = 2), and other (n = 6). All patients had fecal diversion at the time of gracilis surgery. Thirty-day postoperative surgical site infection at the graft/donor site was 32% (n = 7). At a median follow-up of 22 months (range 2-62), fistula closure was 59% (n = 13). Gracilis interposition was successful in all inflammatory bowel disease patients. LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS: Gracilis interposition is an effective operative technique for reoperative rectovaginal fistula closure. Patients should be counseled regarding the possibility of graft/donor site infection. See Video Abstract at http://links.lww.com/DCR/B763 . REPARACIN CON COLGAJO DE GRACILIS PARA LA FSTULA RECTOVAGINAL REOPERATORIA: ANTECEDENTES:El tratamiento quirúrgico de las fístulas rectovaginales recurrentes es muy difícil. La colocación del músculo gracilis entre la vagina y el ano es una técnica avanzada que se utiliza para cerrar las fístulas persistentes. Hemos utilizado este procedimiento para las fístulas recalcitrantes y planteamos la hipótesis de que una interposición del gracilis ofrecería una buena opción de tratamiento para pacientes con fístulas rectovaginales refractarias, independientemente de la etiología subyacente.OBJETIVO:Investigar las tasas de curación de la interposición del gracilis en pacientes con fístulas rectovaginales refractarias.DISEÑO:Tras la aprobación de la junta de revisión institucional, se realizó una revisión retrospectiva de todas las pacientes adultas con un diagnóstico de fístula rectovaginal entre enero de 2009 y agosto de 2020; los que se sometieron a interposición de gracilis para el cierre definitivo de la fístula se incluyeron para el análisis.AJUSTE:Departamento de cirugía colorrectal de un centro terciario en Estados Unidos.PACIENTES:Todas las pacientes adultas con diagnóstico de fístula rectovaginal que se sometieron a interposición de gracilis para cierre definitivo.PRINCIPALES MEDIDAS DE RESULTADO:datos demográficos del paciente, etiología de la fístula rectovaginal, intervención quirúrgica previa, presencia de derivación intestinal, detalles quirúrgicos, morbilidad a los 30 días, recurrencia de la fístula y tiempo hasta la recurrencia. El cierre de la fístula se definió como la ausencia de síntomas clínicos después del cierre del estoma, la detección negativa de la fístula en el enema de gastrograffin y la ausencia de una abertura interna en el examen bajo anestesia.RESULTADOS:Se incluyeron 22 pacientes que tenían una mediana de edad de 43 años (rango 19-64 años) y una mediana de índice de masa corporal de 31 kg / m2 (rango 22-51). La mediana de tiempo entre el intento previo de reparación quirúrgica y la cirugía del gracilis fue de 7 meses (rango 3-17). El número de reparaciones previamente intentadas fue: 1-2 (n = 8), 3-4 (n = 9), y >4 (n = 5). El intento de reparación quirúrgica más reciente fue el colgajo de avance rectal (n = 7), el colgajo transperineal +/- Martius (n = 4), la episioproctotomía (n = 3), la reparación transvaginal (n = 2) y otros (n = 6). Todos los pacientes tenían derivación fecal en el momento de la cirugía gracilis. La infección del sitio quirúrgico posoperatorio a los 30 días en el sitio del injerto / donante fue del 32% (n = 7). Con una mediana de seguimiento de 22 meses (rango 2-62), el cierre de la fístula fue del 59% (n = 13). La interposición de Gracilis fue exitosa en todos los pacientes con enfermedad inflamatoria intestinal.LIMITACIONES:Carácter retrospectivo de los datos.CONCLUSIONES:La interposición de Gracilis es una técnica quirúrgica eficaz para el cierre reoperatorio de la fístula rectovaginal. Se debe asesorar a los pacientes sobre la posibilidad de infección del sitio del injerto / donante. Consulte Video Resumen en http://links.lww.com/DCR/B763 . (Traducción-Dr. Ingrid Melo ).

Long-term Outcomes of Perianal Fistulas in Pediatric Crohn's Disease.

BACKGROUND: Approximately 30% of Crohn's disease-related perianal fistulas heal in the adult population with conventional medical and surgical interventions. This healing rate remains unknown in pediatric patients. OBJECTIVE: This study aimed to determine the healing rate of pediatric perianal Crohn's fistulas and identify factors associated with healing. DESIGN: Retrospective case series. SETTING: A quaternary referral center. PATIENTS: Patients aged <18 years with a Crohn's perianal fistula, seen between January 1, 1991, and August 1, 2021, were included in the study. INTERVENTIONS: Multivariable logistic regression to identify factors independently associated with perianal fistula healing. MAIN OUTCOME MEASURES: Healing of Crohn's perianal fistula at the date of last clinical encounter, defined as the clinical note reporting a healed fistula or normal perianal examination. RESULTS: A total of 91 patients aged <18 years with a Crohn's disease-related perianal fistula were identified (59% female, 76% white). The mean (SD) age at Crohn's diagnosis was 12 (±4) years. The mean follow-up after Crohn's diagnosis was 10 (±7) years. Overall, 89% of patients had a perianal fistula, 2% had an anovaginal fistula, and 10% had an ileal pouch-associated fistula. Patients underwent a median (interquartile range) of 2 (1-5) operations. A seton was placed in 60% of patients, 47% underwent abscess drainage, and 44% underwent fistulotomy or fistulectomy. Fistula healing occurred in 71% of patients over a median of 1.3 (0.4-2.5) years. Seven patients (7%) underwent proctectomy, and 3 (3%) underwent ileal pouch excision. After multivariable adjustment, younger age at diagnosis of perianal fistula was associated with an increased likelihood of healing (OR 0.56 for each increased year; 95% CI, 0.34-0.92). LIMITATIONS: Retrospective, single institution. CONCLUSIONS: Over two-thirds of fistulas heal in pediatric Crohn's disease patients with conventional surgical and medical intervention. Younger age at fistula development is associated with an increased likelihood of healing. See Video Abstract at http://links.lww.com/DCR/C185 . RESULTADOS A LARGO PLAZO DE LAS FSTULAS PERIANALES EN LA ENFERMEDAD DE CROHN EN PACIENTES PEDITRICOS: ANTECEDENTES:Aproximadamente el 30% de las fístulas perianales relacionadas con la enfermedad de Crohn se curan en la población adulta con intervenciones médicas y quirúrgicas convencionales. Esta tasa de curación sigue siendo desconocida en pacientes pediátricos.OBJETIVO:Determinar la tasa de curación de las fístulas de Crohn perianales en población pediátrica e identificar los factores asociados con la curación.DISEÑO:Serie de casos retrospectiva.ESCENARIO:Un centro de referencia cuaternario.PACIENTES:Pacientes menores de 18 años con fístula(s) perianal(es) por enfermedad de Crohn, atendidos entre el 1 de enero de 1991 y el 1 de agosto de 2021.INTERVENCIONES:Regresión logística multivariable para identificar factores asociados de forma independiente con la cicatrización de la fístula perianal.PRINCIPALES MEDIDAS DE RESULTADO:Curación de la fístula perianal de Crohn en la fecha del último encuentro clínico, definida como la nota clínica que informa una fístula curada o un examen perianal normal.RESULTADOS:Se identificó un total de 91 pacientes <18 años de edad con una fístula perianal relacionada con la enfermedad de Crohn (59% mujeres, 76% blancos). La edad media (DE) al diagnóstico de Crohn fue de 12 (±4) años. El seguimiento medio tras el diagnóstico de Crohn fue de 10 (±7) años. En general, el 89 % de los pacientes tenía fístula perianal, el 2 % tenía fístula anovaginal y el 10 % de los pacientes tenía fístula asociada a reservorio ileal. Los pacientes fueron sometidos a una mediana (RIC) de 2 (1-5) operaciones. En el 60% de los pacientes se colocó sedal, en el 47% se drenó el absceso y en el 44% se realizó fistulotomía o fistulectomía. La curación de la fístula se produjo en el 71% de los pacientes durante una mediana de 1,3 (0,4-2,5) años. Siete pacientes (7%) se sometieron a proctectomía y 3 (3%) se sometieron a escisión del reservorio ileal. Después del ajuste multivariable, la edad más joven en el momento del diagnóstico de la fístula perianal se asoció con una mayor probabilidad de curación (OR 0,56 por cada año de aumento, IC del 95%, 0,34-0,92).LIMITACIONES:Retrospectivo, institución única.CONCLUSIONES:Más de dos tercios de las fístulas se curan en pacientes pediátricos con enfermedad de Crohn con intervención médica y quirúrgica convencional. Una edad más joven en el momento del desarrollo de la fístula se asocia con una mayor probabilidad de curación. Consulte Video Resumen en http://links.lww.com/DCR/C185 . (Traducción--Dr. Felipe Bellolio ).

A Phase IB/IIA Study of Ex Vivo Expanded Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease.

BACKGROUND: Mesenchymal stem cells have been used for the treatment of perianal Crohn's fistulizing disease by direct injection. However, no studies to date have included patients with proctitis, anal canal involvement, and multiple branching tracts. OBJECTIVE: This study aimed to determine safety and efficacy of mesenchymal stem cells for refractory perianal Crohn's disease. DESIGN: Phase IB/IIA randomized controlled trial. SETTINGS: Tertiary IBD referral center. PATIENTS: Adult Crohn's disease patients with perianal fistulizing disease. INTERVENTION: Seventy-five million mesenchymal stem cells were administered with a 22-G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved. MAIN OUTCOMES MEASURES: Adverse and serious adverse events occurred at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per MRI, and patient-reported outcomes were collected at the same time points. RESULTS: A total of 23 patients were enrolled and treated; 18 were treatment patients and 5 were control. There were no adverse or serious adverse events reported related to mesenchymal stem cell therapy. At 6 months, 83% of the treatment group and 40% of the control group had complete clinical and radiographic healing. The perianal Crohn's disease activity index, Wexner incontinence score, and VanAssche score had all significantly decreased in treatment patients at 6 months; none significantly decreased in the control group. LIMITATIONS: Single institution and single blinded. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C128 . UN ESTUDIO DE FASE IB/IIA DE CLULAS MADRE MESENQUIMALES DERIVADAS DE MDULA SEA ALOGNICA EXPANDIDA EX VIVO PARA EL TRATAMIENTO DE LA ENFERMEDAD DE CROHN FISTULIZANTE PERIANAL: ANTECEDENTES:Las células madre mesenquimales se han utilizado para el tratamiento de la enfermedad fistulizante de Crohn perianal mediante inyección dirigida. Sin embargo, ningún estudio hasta la fecha ha incluido pacientes con proctitis, afectación del canal anal y vías de ramificación múltiples.OBJETIVO:Determinar la seguridad y eficacia de las células madre mesenquimales para la enfermedad de Crohn perianal refractaria.DISEÑO:Ensayo de control aleatorizado de fase IB/IIA.AJUSTES:Centro de referencia de enfermedad inflamatoria intestinal terciaria.PACIENTES:Pacientes adultos con enfermedad de Crohn con enfermedad fistulizante perianal.INTERVENCIÓN:Se administraron 75 millones de células madre mesenquimales con una aguja 22G mediante inyección directa después del legrado y cierre primario del trayecto de la fístula. Se administró una inyección repetida de 75 millones de células madre mesenquimales a los 3 meses si no se lograba una curación clínica y radiográfica completa.PRINCIPALES MEDIDAS DE RESULTADOS:eventos adversos y adversos graves en el día 1, la semana 2, la semana 6, el mes 3, el mes 6 y el mes 12 después del procedimiento. Curación clínica, curación radiográfica por imagen de resonancia magnética y resultados informados por el paciente en los mismos puntos de tiempo.RESULTADOS:Un total de 23 pacientes fueron reclutados y tratados; 18 fueron de tratamiento y 5 de control. No se informaron eventos adversos o adversos graves relacionados con la terapia con células madre mesenquimales. A los seis meses, el 83 % del grupo de tratamiento y el 40 % del control tenían una curación clínica y radiográfica completa. El índice de actividad de la enfermedad de Crohn perianal, la puntuación de incontinencia de Wexner y la puntuación de VanAssche habían disminuido significativamente en los pacientes de tratamiento a los seis meses; ninguno disminuyó significativamente en el grupo de control.LIMITACIONES:Institución única y simple ciego.CONCLUSIONES:Las células madre mesenquimales derivadas de la médula ósea ofrecen un d tratamiento alternativo seguro y eficaz para la enfermedad de Crohn fistulizante perianal grave. Consulte Video Resumen en http://links.lww.com/DCR/C128 . (Traducción-Dr Yolanda Colorado ).

Durable Response in Patients With Refractory Fistulizing Perianal Crohn's Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial.

BACKGROUND: Refractory perianal Crohn's disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose-derived mesenchymal stem cells. OBJECTIVE: This study aimed to assess therapeutic safety and feasibility in the completed STOMP (stem cells on matrix plugs) phase 1 clinical trial. DESIGN: Prospective single-arm phase I clinical trial. SETTING: Tertiary academic medical center. PATIENTS: Adults (aged 18-65 y) with complex single-tract Crohn's disease perianal fistula who have failed conventional therapy were included in this study. INTERVENTION: Autologous adipose-derived mesenchymal stem cells were isolated, ex vivo culture expanded, and seeded onto a commercially available bioabsorbable fistula plug. Six weeks later, patients returned to the operating room for removal of the seton and placement of the stem cell-loaded plug. MAIN OUTCOME MEASURES: Patients were followed up for a total of 8 visits through 12 months. Safety was the primary end point; clinical healing and MRI response were secondary end points. RESULTS: Twenty patients (12 females; mean age 36 y) were treated with the stem cell-loaded plug. Of the 20 patients enrolled, 3 were not included in the 12-month analysis because of study withdrawal. Through 12 months, no patient experienced a serious adverse event related to the stem cell-loaded plug. Four patients experienced 7 serious adverse events and 12 patients experienced 22 adverse events. Complete clinical healing occurred in 14 of 18 patients at 6 months and 13 of 17 patients at 12 months. MRI response was observed in 12 of 18 patients at 6 months. LIMITATIONS: The main limitations were the small sample size and restrictive inclusion criteria. CONCLUSIONS: A stem cell-loaded plug can safely and effectively deliver cell-based therapy for patients with single-tract fistulizing perianal Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C70 . RESPUESTA DURADERA OBSERVADA EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE REFRACTARIA MEDIANTE EL USO DE CLULAS MADRE MESENQUIMALES AUTLOGAS EN UNA MATRIZ DISOLUBLE RESULTADOS DEL ENSAYO DE FASE I STEM CELL ON MATRIX PLUG: ANTECEDENTES:La enfermedad de Crohn perianal refractaria sigue siendo notoriamente difícil de tratar. Desarrollamos una tecnología novedosa utilizando un tapón de fístula bioabsorbible disponible comercialmente para administrar células madre mesenquimales derivadas de tejido adiposo autólogo.OBJETIVO:Evaluar la seguridad y viabilidad terapéutica en el ensayo finalizado STOMP.DISEÑO:Ensayo clínico prospectivo de fase I de un solo brazo.AJUSTE:Centro médico académico terciario.PACIENTES:Adultos (18-65) con fístula perianal compleja de la enfermedad de Crohn de un solo tracto que han fracasado con la terapia convencional.INTERVENCIÓN:Se aislaron células madre mesenquimales derivadas de tejido adiposo autólogo, se expandieron en cultivo ex vivo y se sembraron en un tapón de fístula bioabsorbible disponible comercialmente. Seis semanas después, los pacientes regresaron al quirófano para retirar el setón y colocar el tapón cargado de células madre.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron seguidos durante un total de 8 visitas durante 12 meses. La seguridad fue el criterio principal de valoración; la curación clínica y la respuesta a la resonancia magnética fueron criterios de valoración secundarios.RESULTADOS:Veinte pacientes (12 mujeres, edad media 36 años) fueron tratados con el tapón cargado de células madre. De los 20 pacientes inscritos, tres no se incluyeron en el análisis de 12 meses porque se retiraron del estudio. A lo largo de 12 meses, ningún paciente experimentó un evento adverso grave relacionado con el tapón cargado de células madre. Cuatro pacientes experimentaron 7 eventos adversos graves y 12 pacientes experimentaron 22 eventos adversos. La curación clínica completa ocurrió en 14 de 18 pacientes a los 6 meses y en 13 de 17 pacientes a los 12 meses. La respuesta a la resonancia magnética se observó en 12 de 18 pacientes a los 6 meses.LIMITACIONES:Las principales limitaciones son el tamaño pequeño de la muestra y los criterios de inclusión restrictivos.CONCLUSIONES:Un tapón cargado de células madre se puede administrar de manera segura y efectiva, una terapia basada en células para pacientes con enfermedad de Crohn perianal fistulizante de un solo tracto. Consule Video Resumen en http://links.lww.com/DCR/C70 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Redo Continent Ileostomy in Patients With IBD: Valuable Lessons Learned Over 25 Years.

BACKGROUND: Patients with IBD with continent ileostomies may require revision surgeries. There remains a paucity of data regarding outcomes after redo continent ileostomy. OBJECTIVE: This study aimed to evaluate patient outcomes after redo continent ileostomy. DESIGN: Retrospective cohort study. SETTINGS: This study was conducted at a high-volume, specialized colorectal surgery department. PATIENTS: We identified patients who underwent redo continent ileostomy (defined as neo-pouch construction or major operations changing the pouch configuration) for IBD between 1994 and 2020. MAIN OUTCOME MEASURES: The main outcomes measured were patient demographics, short- and long-term outcomes, and quality of life. RESULTS: A total of 168 patients met inclusion criteria; 102 (61%) were female, the mean age was 51 years (±13.1), and the mean BMI was 24.4 (±3.9). The median time between primary and redo continent ileostomy was 16.8 years. One hundred twenty-two patients (73%) who underwent redo surgery had ulcerative colitis, 36 (21%) had Crohn's disease, and 10 (6%) had indeterminate colitis. Slipped nipple valve and valve stricture were the most common indications for redo continent ileostomy (86%). After a median follow-up of 4 years, 48 patients (29%) required a subsequent reoperation and 27 (16%) had pouch failure requiring pouch excision. The pouch survival rate was 89% at 3 years, 84% at 5 years, and 79% at 10 years. On univariate analysis, a shorter interval between the primary and redo continent ileostomy was associated with long-term pouch failure ( p = 0.003). Cox regression multivariate analysis confirmed that a shorter interval between surgeries was independently associated with pouch failure ( p = 0.014). The mean Cleveland Clinic Global Quality of Life score was 0.61 (± 0.23) among the 70 patients who responded to the questionnaire. LIMITATIONS: The main limitations were that this was a retrospective, single-center study and that it had a low response rate for the Global Quality of Life questionnaire. CONCLUSIONS: Redo continent ileostomy surgery is associated with a long-term pouch retention rate of 79% and satisfactory quality of life. Therefore, redo surgery should be offered to patients who are motivated to keep their continent ileostomy. See Video Abstract at http://links.lww.com/DCR/C87 . REHACER LA ILEOSTOMA CONTINENTE EN PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL VALIOSAS LECCIONES APRENDIDAS DURANTE AOS: ANTECEDENTES:Los pacientes con enfermedad inflamatoria intestinal con ileostomías continentes pueden requerir cirugías de revisión. Sigue habiendo escasez de datos con respecto a los resultados después de volver a realizar la ileostomía continente.OBJETIVO:Evaluar los resultados después de rehacer la ileostomía continente.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:Departamento especializado en cirugía colorrectal de alto volumen.PACIENTES:Identificamos pacientes que se sometieron a una nueva ileostomía continente (definida como construcción de una nueva bolsa u operaciones mayores que cambian la configuración de la bolsa) por enfermedad inflamatoria intestinal entre 1994 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Datos demográficos de los pacientes, resultados a corto y largo plazo y calidad de vida.RESULTADOS:Un total de 168 pacientes cumplieron con los criterios de inclusión; 102 (61%) eran mujeres, la edad media fue de 51 años (±13,1) y el IMC medio fue de 24,4 (±3,9). La mediana de tiempo entre la ileostomía primaria y la nueva ileostomía continente fue de 16,8 años. Ciento veintidós pacientes (73%) que se sometieron a una nueva cirugía tenían colitis ulcerosa, 36 (21%) tenían enfermedad de Crohn y 10 (6%) tenían colitis indeterminada. El deslizamiento de la válvula del pezón y la estenosis de la válvula fueron las indicaciones más comunes para rehacer la ileostomía continente (86%). Después de una mediana de seguimiento de 4 años, 48 (29%) pacientes requirieron una reintervención posterior y 27 (16%) tuvieron falla de la bolsa que requirió la escisión de la bolsa. La tasa de supervivencia de la bolsa fue del 89 % a los 3 años, del 84% a los 5 años y del 79% a los 10 años. En el análisis univariable, un intervalo de tiempo más corto entre la ileostomía continente primaria y la nueva se asoció con falla de la bolsa a largo plazo (p = 0,003). El análisis multivariable de regresión de Cox confirmó que el intervalo más corto entre cirugías se asoció de forma independiente con el fracaso de la bolsa (p = 0,014). La puntuación media de la Calidad de Vida Global fue de 0,61 (± 0,23) entre los 70 pacientes que respondieron al cuestionario.LIMITACIONES:Estudio retrospectivo de un solo centro. Baja tasa de respuesta al cuestionario de Calidad de Vida.CONCLUSIÓN:La cirugía de ileostomía continente se asocia con una tasa de retención de la bolsa a largo plazo del 79% y una calidad de vida satisfactoria. Por lo tanto, se debe ofrecer una nueva cirugía a los pacientes que están motivados para mantener su ileostomía continente. Consulte Video Resumen en http://links.lww.com/DCR/C87 . (Traducción-Dr. Felipe Bellolio ).

Leaks From the Tip of the J-pouch: Diagnosis, Management, and Long-term Pouch Survival.

BACKGROUND: The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from the tip of the J-pouch are a known complication, but there is a paucity of literature regarding this type of leak. OBJECTIVE: We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution. DESIGN: This was a retrospective study of a prospectively maintained pouch registry. SETTING: This study was conducted at a quaternary IBD referral center. PATIENTS: Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch. MAIN OUTCOME MEASURES: The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival. RESULTS: We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, whereas 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3% of patients but only discovered during surgical exploration in 25.6% of patients. Some 63.5% of patients were diagnosed only after loop ileostomy closure, whereas 32.4% of patients were diagnosed before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive nonoperative approach was attempted in 48.6% of patients but was successful in only 10.8% of patients overall. Surgical repair was attempted in 89.2% of patients, whereas 4.5% of patients had pouch excision. Salvage operations (n = 63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair, and reanastomosis (9.5%). Ultimately' 10 patients (13.5%) required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%. LIMITATIONS: This was a retrospective review; referral bias may limit the generalizability. CONCLUSIONS: Leaks from the tip of the J-pouch have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority of patients and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50 . FUGAS DEL EXTREMO DE LA BOLSA EN J DIAGNSTICO, MANEJO Y SUPERVIVENCIA A LARGO PLAZO DE LA BOLSA: ANTECEDENTES:El estándar de atención para el tratamiento quirúrgico de la colitis ulcerosa es la proctocolectomía restauradora con bolsa ileal en J. Las fugas del extremo de la bolsa en J son una complicación conocida, pero hay escasez de literatura sobre este tipo de fuga.OBJETIVO:Describir el diagnóstico, manejo y resultados clínicos a largo plazo de las fugas del extremo de la bolsa en J en nuestra institución.DISEÑO:Estudio retrospectivo de registro de bolsa mantenido prospectivamente.ENTORNO CLINICO:Centro de referencia de enfermedad inflamatoria intestinal cuaternaria.PACIENTES:Pacientes con bolsas ileales en J diagnosticadas con fugas del extremo de la J.PRINCIPALES MEDIDAS DE VALORACIÓN:Tasa de rescate de la bolsa, tipo de procedimientos de rescate y supervivencia a largo plazo de la bolsa Kaplan-Meier.RESULTADOS:Identificamos 74 pacientes con fugas del extremo de la bolsa en J. El dolor (68,9%) y el absceso pélvico (40,9%) fueron las presentaciones más comunes, mientras que el 10,8% de los pacientes presentaron abdomen agudo. La fuga se diagnosticó por imagen y/o endoscopia en el 74,3%, pero solo se descubrió durante la exploración quirúrgica en el 25,6%. El 63,5% fueron diagnosticados solo después del cierre de la ileostomía en asa, mientras que el 32,4% lo fueron antes del cierre de la ileostomía. Los métodos más comunes utilizados para el diagnóstico fueron la endoscopia (31,1%) y el enema de gastrografín (28,4%). Se intentó un abordaje no quirúrgico definitivo en el 48,6%, pero tuvo éxito en solo el 10,8% de los pacientes en general. Se intentó la reparación quirúrgica en el 89,2% de los pacientes, mientras que en el 4,5% se realizó la escisión del reservorio. Las operaciones de rescate (n = 63) incluyeron la reparación con sutura o grapas del extremo de la J (65%), la escisión del reservorio con neo-reservorio (25,4%) y la desconexión, reparación y reanastomosis del reservorio (9,5%). Finalmente, 10 (13,5%) pacientes requirieron la escisión de la bolsa, lo que se asocio con una alta tasa de supervivencia general de la bolsa a los 5 años del 86,3%.LIMITACIONES:Revisión retrospectiva; el sesgo de referencia puede limitar la generalización.CONCLUSIONES:Las fugas del extremo de la bolsa en J tienen presentaciones clínicas variables y requieren un alto índice de sospecha. La cirugía de rescate de la bolsa se requiere en la mayoría y se asocia con una alta tasa de rescate de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/C50 . (Traducción- Dr. Ingrid Melo ).

Redo Ileocolic Resection Is Not an Independent Risk Factor for Anastomotic Leak in Recurrent Crohn's Disease.

BACKGROUND: Redo ileocolic resection for recurrent Crohn's disease is associated with increased technical complexity and higher complication rates compared to primary resection. Literature concerning redo surgery for recurrent Crohn's disease is scarce and it is controversial whether a redo is a risk factor for postoperative anastomotic leak. OBJECTIVE: This study aimed to hypothesized that redo ileocolic resection for Crohn's disease is an independent risk factor for anastomotic leak. DESIGN: Retrospective, case-control study from 1994 to 2019 with multivariate analysis and propensity score weighting. SETTING: Quaternary, IBD-referral center. PATIENTS: Adult patients aged >18 years were included in the study. INTERVENTIONS: Primary or redo ileocolic resection with an anastomosis, with or without diverting ileostomy. MAIN OUTCOME MEASURES: Thirty-day anastomotic leak rate. RESULTS: A total of 991 patients (56% primary and 44% redo ileocolic resections) were included. Patients who underwent redo resection were significantly older with more comorbidities, fewer medications, and less fistulizing disease compared to the primary group. On univariate analysis, patients who underwent redo resection had more overall complications (50.5% vs 36.2%, p < 0.001), and the cumulative number of prior ileocolic resections was significantly associated with increased risk for overall morbidity ( p < 0.001). There were 31 (3%) anastomotic leaks; leak rates did not differ between groups ( p = 0.60). Multivariable analysis indicated that extensive adhesiolysis ( p < 0.001), ileostomy omission ( p = 0.009), and intraoperative abscess/fistula ( p = 0.02) were independently associated with leaks but not redo resection ( p = 0.27). Patients with 0, 1, 2, or 3 of these risk factors had observed leak rates of 1.1%, 1.3%, 6.0%, and 11.6.% ( p = 0.03), respectively. LIMITATIONS: The limitations of this study were selection bias, referral bias, and single quaternary center. CONCLUSIONS: Compared to primary procedures, redo ileocolic resection for recurrent Crohn's disease is associated with increased overall morbidity but not anastomotic leak. See Video Abstract at http://links.lww.com/DCR/C132 . LA RESECCIN ILEOCLICA REHECHA NO ES UN FACTOR DE RIESGO INDEPENDIENTE DE FUGA ANASTOMTICA EN LA ENFERMEDAD DE CROHN RECURRENTE: ANTECEDENTES:La resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor complejidad técnica y mayores tasas de complicaciones en comparación con la resección primaria. La literatura sobre la reintervención quirúrgica para la enfermedad de Crohn recurrente es escasa y es controvertido si una redo es un factor de riesgo para la fuga anastomótica posoperatoria.OBJETIVO:Tenemos la hipótesis de que rehacer la resección ileocólica para la enfermedad de Crohn es un factor de riesgo independiente para la fuga anastomótica.DISEÑO:Estudio retrospectivo de casos y controles de 1994 a 2019 con análisis multivariado y ponderación de puntuación de propensión.AJUSTE:Centro de referencia de enfermedad inflamatoria intestinal de cuarto nivel.PACIENTES:Pacientes adultos >18 años.INTERVENCIONES:Resección ileocólica primaria o rehecha con una anastomosis, con o sin derivación de ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de fuga anastomótica a los 30 días.RESULTADOS:Se incluyeron un total de 991 pacientes (56% resecciones primarias y 44% resecciones ileocólicas rehechas). Los pacientes de reintervención eran significativamente mayores con más comorbilidades, menos medicamentos y menos enfermedad fistulizante en comparación con el grupo primario. En el análisis univariado, los pacientes reoperados tuvieron más complicaciones generales (50,5% frente a 36,2%, p < 0,001) y el número acumulado de resecciones ileocólicas previas se asoció significativamente con un mayor riesgo de morbilidad general ( p < 0,001). Hubo 31 (3%) fugas anastomóticas; las tasas de fuga no difirieron entre los grupos ( p = 0,6). El análisis multivariado indicó que la adhesiolisis extensa ( p < 0,001), la omisión de ileostomía ( p = 0,009) y el absceso/fístula intraoperatorios ( p = 0,02) se asociaron de forma independiente con fugas, pero no con nueva resección ( p = 0,27). Los pacientes con 0, 1, 2 o 3 de estos factores de riesgo observaron tasas de fuga del 1,1%, 1,3%, 6,0% y 11,6% ( p = 0,03), respectivamente.LIMITACIONES:Sesgo de selección, Sesgo de referencia, un centro de cuarto nivelCONCLUSIÓN:En comparación con los procedimientos primarios, la resección ileocólica para la enfermedad de Crohn recurrente se asocia con una mayor morbilidad general, pero no con una fuga anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C132 . (Traducción-Dr. Mauricio Santamaria ).

Venous Thromboembolism in Patients Admitted for IBD: An Enterprise-Wide Experience of 86,000 Hospital Encounters.

BACKGROUND: Recommendations regarding venous thromboembolism prophylaxis in patients admitted to the hospital for IBD continue to evolve. OBJECTIVE: This study aimed to determine the 90-day rate and risk factors of deep venous thromboembolism and pulmonary embolism in cohorts of patients with IBD admitted to medical and surgical services. DESIGN: This was a retrospective review. SETTING: The study was conducted at a quaternary IBD referral center. PATIENTS: The study included adult patients ( > 18 y of age) with a known diagnosis of either ulcerative colitis or Crohn's disease who had an inpatient hospital admission for IBD between January 1, 2002, and January 1, 2020. MAIN OUTCOME MEASURES: The primary outcome measures were 90-day rate of deep venous thromboembolism and pulmonary embolism among admitted patients. RESULTS: A total of 86,276 hospital admissions from 16,551 patients with IBD occurred between January 1, 2002, and January 1, 2020. A total of 35,992 patients (41.7%) were given subcutaneous heparin for venous thromboembolism prophylaxis, and 8188 patients (9.49%) were given enoxaparin for venous thromboembolism prophylaxis during the inpatient hospital admission. From the date of hospital admission, the 90-day rate of deep venous thromboembolism was 4.3% (n = 3664); of these, 1731 patients (47%) were diagnosed during the admission and 1933 patients (53%) were diagnosed after discharge. From the date of hospital admission, the 90-day rate of pulmonary embolism was 2.4% (n = 2040); of these, 960 patients (47%) were diagnosed during admission and 1080 patients (53%) were diagnosed after discharge. LIMITATIONS: The study was limited by its retrospective nature and unmeasured severity of the disease. CONCLUSIONS: Patients admitted for IBD had a 90-day deep venous thromboembolism event rate of 4.3% and pulmonary embolism event rate of 2.4%. More than half of the events occurred after discharge, and venous thromboembolism events were higher among patients with IBD admitted to a medical service than those admitted to a surgical service. See Video Abstract at http://links.lww.com/DCR/B947 . TROMBOEMBOLIA VENOSA EN PACIENTES INGRESADOS CON ENFERMEDAD INFLAMATORIA INTESTINAL UNA EXPERIENCIA EN TODA LA EMPRESA DE ENCUENTROS HOSPITALARIOS: ANTECEDENTES:Recomendaciones sobre la profilaxis de tromboembolia venosa en pacientes ingresados con enfermedad inflamatoria intestinal (EII) continúa evolucionando.OBJETIVO:Determinar la tasa a 90 días y los factores de riesgo de tromboembolia venosa profunda y embolia pulmonar en cohortes de pacientes ingresados con EII médico y quirúrgico.DISEÑO:Esta fue una revisión retrospectiva.AJUSTE:El estudio se llevó a cabo en un centro cuaternario de derivación de EII.PACIENTES:Se incluyeron pacientes adultos (> 18 años) con diagnóstico conocido de colitis ulcerosa o enfermedad de Crohn que fueron hospitalizados por EII entre el 1 de Enero de 2002 y el 1 de Enero de 2020.PRINCIPALES MEDIDAS DE RESULTADOS:Las medidas principales fueron la tasa de tromboembolia venosa profunda a 90 días y la embolia pulmonar entre los pacientes ingresados.RESULTADOS:Un total de 86.276 ingresos hospitalarios de 16.551 pacientes con EII ocurrieron entre el 1 de Enero de 2002 y el 1 de Enero de 2020. A un total de 35.992 (41,7%) se les administró heparina subcutánea para profilaxis de tromboembolia venosa y a 8.188 (9,49%) se les administró enoxaparina para profilaxis de tromboembolia venosa durante el ingreso hospitalario. A partir de la fecha de ingreso hospitalario, la tasa de tromboembolia venosa profunda a 90 días fue del 4,3% (n = 3.664); de estos 1.731 (47%) se diagnosticaron durante el ingreso y 1.933 (53%) se diagnosticaron después del alta. Desde la fecha de ingreso hospitalario, la tasa de embolia pulmonar a los 90 días fue de 2,4% (n = 2.040); De estos, 960 (47%) fueron diagnosticados durante el ingreso y 1.080 (53%) fueron diagnosticados después del alta.LIMITACIONES:El estudio fue retrospectivo y no se midió la gravedad de la enfermedad.CONCLUSIÓNES:Los pacientes ingresados por EII tuvieron una tasa de tromboembolia venosa profunda y de eventos de embolia pulmonar de 4,3% y 2,4%, respectivamente, a 90 días. Más de la mitad de los eventos ocurrieron después del alta y los eventos de TEV fueron más altos entre los pacientes de EII médicos que quirúrgicos. Consulte Video Resumen en http://links.lww.com/DCR/B947 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Mesenchymal stem cells: A novel treatment option for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a progressive liver disease for which there is no effective therapy. Hepatocytes and cholangiocytes from a PSC patient were cocultured with mesenchymal stem cells (MSCs) to assess in vitro change. A single patient with progressive PSC was treated with 150 million MSCs via direct injection into the common bile duct. Coculture of MSCs with cholangiocytes and hepatocytes showed in vitro improvement. Local delivery of MSCs into a single patient with progressive PSC was safe. Radiographic and endoscopic evaluation showed stable distribution of multifocal structuring in the early postoperative period. MSCs may be effective for the treatment of PSC.

Prolonged diversion after ileal pouch-anal anastomosis: Is it safe to wait?

AIM: Diverting loop ileostomy reversal (DLI-R) is routinely performed from 2-6 months following ileal pouch-anal anastomosis (IPAA). The safety of delayed reversal after IPAA is not well-defined. The aim of this study was to determine if prolonged diversion is associated with adverse outcomes compared to routine closure. METHODS: Adult patients undergoing primary IPAA with DLI from 2000 to 2021 were included in this retrospective cohort study from our institutional database. Patients were stratified into tertiles based on timing of reversal: Routine (56-116 days), Delayed (117-180 days), or Prolonged (>6 months). Univariate analysis compared categorical variables between groups. Patients reversed at <8 weeks were excluded. RESULTS: In total, 2615 patients underwent DLI-R following IPAA (3-stage 61%, 2-stage 39%; mean age 39.9 years). DLI-R was performed as Routine, Delayed and Prolonged in 1908 (72.9%), 426 (16.4%) and 281 (10.8%), respectively. Overall, DLI-R related complications occurred in 12.4% (n = 324). The complication rate in the Routine group was 11% (n = 210), in the Delayed group was 12.2% (n = 52) and in the Prolonged group was 22.1% (n = 62). Reasons for prolonged diversion in the Prolonged group were complications at the time of IPAA in 207 (73.9%) or patient preference/scheduling in 73 (26.1%). DLI-R >6 months after IPAA due to complications had higher rates of overall complications following ileostomy reversal (OR 2.6, 95% CI 1.85-3.72, p < 0.001) whereas when DLI-R was delayed due to preference/scheduling outcomes were not different than the Routine group (p = 0.28). CONCLUSION: Prolonged time to ileostomy reversal after IPAA is probably safe without increased risk of complications when due to patient preference.

Assessing prognostic factors of long-term survival after surgery for colorectal gastrointestinal stromal tumours.

AIM: Due to their rarity, the management of colorectal gastrointestinal stromal tumours (CR GISTs) is still under debate. The aim of this study was to assess prognostic factors. METHOD: We performed a retrospective review of patients who underwent surgery with curative intent for CR GIST at our centre from 2002 to 2019. Factors associated with overall (OS) and recurrence-free survival (RFS) were analysed. RESULTS: Fifty-six patients were included [median age 63 years, 29 (52%) female, 30 (54%) Miettinen high-risk, 40 (71%) with rectal GIST]. Nineteen (34%) patients received perioperative (neoadjuvant and/or adjuvant) imatinib. All cases of colonic GIST had an R0 resection, compared with 28 (70%) of rectal GISTs. After a median follow-up of 97 months (interquartile range 48-155 months), 14 (25%) deaths and 14 (25%) recurrences occurred. In the high-risk cohort, factors associated with improved RFS were R0 resection (OR 0.19, 95% CI 0.1-0.5, p = 0.002) and perioperative imatinib (OR 0.33, 95% CI 0.42-0.97, p = 0.04). Patients who had received perioperative imatinib had longer RFS (60% vs. 11% at 5 years, p = 0.006) but not OS. In rectal GISTs, 5-year OS was 85% for R0 and 70% for R1 resections (p = 0.164) and 5-year RFS was 85% for R0 and 12% for R1 resection (p < 0.001). When stratifying patients by perioperative imatinib, there were no differences in OS or RFS in the R0 or R1 groups. CONCLUSION: Perioperative imatinib and R0 resection were associated with improved RFS in high-risk patients with CR GIST. In patients with rectal GIST, R1 resection was associated with worse RFS irrespective of perioperative imatinib treatment.

Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons.

The American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) are dedicated to ensuring high-quality innovative patient care for surgical patients by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus as well as minimally invasive surgery. The ASCRS and SAGES society members involved in the creation of these guidelines were chosen because they have demonstrated expertise in the specialty of colon and rectal surgery and enhanced recovery. This consensus document was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. While not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, healthcare workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. This clinical practice guideline represents a collaborative effort between the American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and was approved by both societies.

Effect of Crohn's disease mesenteric mesenchymal stem cells and their extracellular vesicles on T-cell immunosuppressive capacity.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal intestinal tract and has characteristic hypertrophic adipose changes observed in the mesentery. To better understand the role of the mesentery in the pathophysiology of Crohn's disease (CD), we evaluated the immunomodulatory potential of mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) derived from Crohn's patients. MSCs and EVs were isolated from the mesentery and subcutaneous tissues of CD patients and healthy individuals subcutaneous tissues, and were analysed for differentiation, cytokine expression, self-renewal and proliferation. The varying capacity of these tissue-derived MSCs and EVs to attenuate T-cell activation was measured in in vitro and an in vivo murine model. RNA sequencing of inflamed Crohn's disease mesentery tissue revealed an enrichment of T-cell activation compared to non-inflamed subcutaneous tissue. MSCs and MSC-derived EVs isolated from Crohn's mesentery lose their ability to attenuate DSS-induced colitis compared to subcutaneous tissue-derived cell or EV therapy. We found that treatment with subcutaneous isolated MSCs and their EV product compared to Crohn's mesentery MSCs or EVs, the inhibition of T-cell proliferation and IFN-γ, IL-17a production increased, suggesting a non-inflamed microenvironment allows for T-cell inhibition by MSCs/EVs. Our results demonstrate that Crohn's patient-derived diseased mesentery tissue MSCs lose their immunosuppressive capacity in the treatment of colitis by distinct regulation of pathogenic T-cell responses and/or T-cell infiltration into the colon.

Adipose tissue-derived mesenchymal stem cells' acellular product extracellular vesicles as a potential therapy for Crohn's disease.

The breakdown of gastrointestinal tract immune homeostasis leads to Crohn's disease (CD). Mesenchymal stem cells (MSCs) have demonstrated clinical efficacy in treating CD in clinical trials, but there is little known about the mechanism of healing. Considering the critical roles of macrophage polarization in CD and immunomodulatory properties of MSCs, we sought to decipher the interaction between adipose-derived MSCs and macrophages, including their cytokine production, regulation of differentiation, and pro-/anti-inflammatory function. RNA extraction and next generation sequencing was performed in adipose tissue from healthy control patients' mesentery (n = 3) and CD mesentery (n = 3). Infiltrated macrophage activation in the CD mesentery was tested, MSCs and extracellular vesicles (EVs) were isolated to compare the regulation of macrophage differentiation, cytokines production, and self-renewal capacities in vitro. CD patients' mesentery has increased M1 macrophage polarization and elevated activation. MSCs and their derived EVs, isolated from inflamed Crohn's mesentery, leads to a rapid differentiation of monocytes to a M1-like polarized phenotype. Conversely, MSCs and their derived EVs from healthy, non-Crohn's patients results in monocyte polarization into a M2 phenotype; this is seen regardless of the adipose source of MSCs (subcutaneous fat, omentum, normal mesentery). EVs derived from MSCs have the ability to regulate macrophage differentiation. Healthy MSCs and their associated EVs have the ability to drive monocytes to a M2 subset, effectively reversing an inflammatory phenotype. This mechanism supports why MSCs may be an effective therapeutic in CD and highlights EVs as a novel therapeutic for further exploration.

Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence. METHODS: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status. RESULTS: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years). CONCLUSIONS: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.