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Inflammatory bowel disease (IBD) patients are at risk for Clostridioides difficile infection (CDI). The majority of published outcomes data feature medically treated patients. We aimed to analyze outcomes in a large cohort of surgical IBD patients diagnosed with CDI.All patients with IBD in the ACS NSQIP Colectomy and Proctectomy (2015-2019) modules were identified. The IBD-CDI and IBD cohorts were propensity score weighted on demographic and surgical factors and compared.In the entire unmatched cohort (n = 12,782), 119/0.93% patients were diagnosed with CDI (74.2% Crohn's/25.7% UC/Indeterminate colitis) within 30-days of surgery. After propensity score weighting, IBD-CDI was associated with increased risk of readmission (OR 4.55 [3.09-6.71], p 0.001), reoperation (3.17 [1.81-5.52], p 0.001) and any complication (2.16 [1.47-3.17], p 0.001). Any SSI (2.58 [1.67-3.98]), organ space SSI (2.49 [1.51-4.11], both p 0.001), prolonged ventilation (4.03 [1.39-11.69],p = 0.01), acute renal failure (15.06 [4.26-53.26],p 0.001), stroke (12.36 [1.26-121.06],p = 0.03), sepsis (2.4 [1.39-4.15],p = 0.002) and septic shock (3.29 [1.36-7.96],p = 0.008) were also higher in the IBD-CDI cohort. Mean length of stay was increased by 39% in CDI patients.Post colonic resection, IBD-CDI patients have worse outcomes than IBD patients without CDI. These patients represent a particularly vulnerable cohort who require close monitoring for the development of postoperative complications.

The prevalence of inflammatory bowel disease (IBD) continues to rise with the increasing rates in the developing world and the improving longevity of IBD patients. A diagnosis of colonic IBD is associated with an increased risk of colorectal cancer (CRC) and this accounts for approximately 15% of the estimated mortality from IBD. CRC in IBD appears to be a pathologically distinct entity and progress is being made to understand the unique components of this process with a view to better predicting outcomes and potentially improving surveillance, treatments, and eventually modifying risk. In the interim, patients are entered into surveillance programs designed to identify at-risk patients early and improve outcomes. Dramatic evolution of technology in this area has changed the landscape of surveillance and dysplasia management over the last decade and promises to continue to do so. This review aims to provide a contemporary overview of IBD-associated CRC in terms of its epidemiology, pathogenesis, surveillance, and management.

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.We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution.This was a retrospective study of a prospectively maintained pouch registry.This study was conducted at a quaternary IBD referral center.Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch.The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival.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%.This was a retrospective review; referral bias may limit the generalizability.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 .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 ).

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.

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.The purpose of this study was to investigate healing rates of gracilis interposition in patients with refractory rectovaginal fistulas.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.The study was conducted at a colorectal surgery department at a tertiary center in the United States.All patients were adult females with a diagnosis of a rectovaginal fistula who underwent gracilis interposition for definitive closure.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.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), and4 (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.The study was limited by its retrospective nature.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 .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), y4 (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 ).

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.

Background Postoperative recurrence [POR] of Crohn’s disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. Aims To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. Methods This was a retrospective study of adult Crohn’s disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts’ score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. Results In 535 Crohn’s disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23–4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04–2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04–4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31–4.87]; p = 0.006] for surgical recurrence. Conclusion IASC is associated with an increased risk for endoscopic and surgical POR of Crohn’s disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR.

Treatment of Crohn's disease (CD) focuses on providing acceptable quality of life for the affected individual by optimizing medical therapy, endoscopic procedures, and surgical intervention. Biologics have changed the medical management of moderate to severe CD. However, despite their introduction, the need for surgical resection in CD has not drastically changed, with two-thirds of the patients still requiring an intestinal resection. Patient outcomes are optimized by focusing on preoperative management and intraoperative technical aspects to maximize bowel preservation. This article reviews some of the important principles of Crohn's surgery to help guide surgeons when approaching this challenging patient population.

Mesenchymal stem cells have been used for the treatment of perianal Crohn's fistulizing disease by direction injection. However, no studies to date have included patients with proctitis, anal canal involvement, and multiple branching tracts.To determine safety and efficacy of mesenchymal stem cells for refractory perianal Crohn's disease.Phase IB/IIA randomized control trial.Tertiary inflammatory bowel disease referral center.Adult Crohn's patients with perianal fistulizing disease.75 million mesenchymal stem cells were administered with a 22G 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.Adverse and serious adverse events at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes at the same time points.A total of 23 patients were enrolled and treated; 18 were treatment and 5 were control. There were no adverse or serious adverse events reported related to mesenchymal stem cells therapy. At six months, 83% of the treatment group and 40% of the control 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 six months; none significantly decreased in the control group.Single institution and single blinded.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.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease.Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence.One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86).Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Surgical intervention for Crohn's disease involving the colon is often a total proctocolectomy with end ileostomy. There are limited data regarding postoperative small bowel recurrence rates in the recent era.The purpose of this study was to determine the rate of small bowel Crohn's disease recurrence following total proctocolectomy and secondarily define risk factors for disease recurrence.This was a retrospective cohort study.The study was conducted at four hospitals within a single healthcare system.Patients were those with Crohn's disease undergoing total proctocolectomy with end ileostomy between 2009-2019.Main outcome measures were clinical, endoscopic, radiographic, and/or surgical Crohn's disease recurrence.In total, 193 patients were included with a median follow-up of 1.8 years (IQR 0.4-4.6). Overall, 74.6% (n = 144) of patients had been previously exposed to biologic therapy, and 51.3% (n = 99) had a history of small bowel Crohn's disease. Postoperatively, 14.5% (n = 28) of patients received biologic therapy. Crohn's disease recurrence occurred in 23.3% (n = 45) of patients with an estimated median 5-year recurrence rate of 40.8% (95% CI' 30.2-51.4). Surgical recurrence occurred in 8.8% (n = 17) of patients with an estimated median 5-year recurrence rate of 16.9% (95% CI' 8.5-25.3). On multivariable analysis, prior small bowel surgery for Crohn's disease (HR 2.61; 95% CI' 1.42-4.81) and Crohn's diagnosis at age18 years (HR 2.56; 95% CI' 1.40-4.71) were associated with Crohn's recurrence. In patients without prior small bowel Crohn's disease, 14.9% (n = 14) had Crohn's recurrence with an estimated 5-year overall recurrence rate of 31.1% (95% CI' 13.3-45.3) and 5-year surgical recurrence rate of 5.7% (95% CI' 0.0-12.0).The study was limited by its retrospective design and lack of consistent follow-up on all patients.Greater than one third of patients who underwent total proctocolectomy for Crohn's disease were estimated to have small bowel Crohn's recurrence at 5 years after surgery. Patients with a history of small bowel surgery for Crohn's and diagnosis at any early age may benefit from more intensive postoperative surveillance and consideration for early medical prophylaxis. See Video Abstract at http://links.lww.com/DCR/B762.ANTECEDENTES:La cirugia para la enfermedad de Crohn que involucra el colon es a menudo una proctocolectomía total con ileostomía terminal. Hay datos limitados con respecto a las tasas de recurrencia posoperatoria de la enfermedad de Crohn del intestino delgado en la actualidad.OBJETIVO:Buscamos determinar la tasa de recurrencia de la enfermedad de Crohn del intestino delgado después de la proctocolectomía total y, en segundo lugar, definir los factores de riesgo de recurrencia de la enfermedad.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Cuatro hospitales de un mismo sistema sanitario.PACIENTES:Pacientes con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2009-2019.PRINCIPALES MEDIDAS DE VALORACIÓN:Recurrencia clínica, endoscópica, radiográfica y / o quirúrgica de la enfermedad de Crohn.RESULTADOS:Se incluyeron 193 pacientes con un seguimiento promedio de 1,8 años (IQR 0,4-4,6). El 74,6% (n = 144) de los pacientes habían recibido previamente terapia biológica y el 51,3% (n = 99) tenían antecedentes de enfermedad de Crohn del intestino delgado. Después de la operación, el 14,5% (n = 28) de los pacientes recibieron terapia biológica. La recurrencia de la enfermedad de Crohn ocurrió en el 23,3% (n = 45) de los pacientes con una tasa de recurrencia media estimada a los 5 años del 40,8% (IC del 95%: 30,2-51,4). La recidiva quirúrgica se produjo en el 8,8% (n = 17) de los pacientes con una tasa de recidiva media estimada a los 5 años del 16,9% (IC del 95%: 8,5-25,3). En el análisis multivariable, la cirugía previa del intestino delgado para la enfermedad de Crohn (HR 2,61, IC del 95%: 1,42-4,81) y el diagnóstico de Crohn a la edad18 (HR 2,56, IC del 95%: 1,40-4,71) se asociaron con la recurrencia de Crohn. En pacientes sin enfermedad previa de Crohn del intestino delgado, el 14,9% (n = 14) tuvo recurrencia de Crohn con una tasa de recurrencia general estimada a 5 años del 31,1% (IC del 95%: 13,3-45,3) y una tasa de recurrencia quirúrgica a 5 años del 5,7% (IC del 95%: 0,0-12,0).LIMITACIONES:Diseño retrospectivo, falta de seguimiento constante de todos los pacientes.CONCLUSIONES:Se estimó que más de un tercio de los pacientes que se sometieron a proctocolectomía total tenían recurrencia de Crohn del intestino delgado a los 5 años después de la cirugía. Los pacientes con antecedentes de cirugía por enfermedad de Crohn del intestino delgado y diagnóstico a una edad temprana pueden beneficiarse de una vigilancia posoperatoria más intensiva y la consideración de una profilaxis médica temprana. Consulte Video Resumen en http://links.lww.com/DCR/B762. (Traducción- Dr. Ingrid Melo).

Background Despite highly effective therapies, many children develop medically refractory ulcerative colitis (UC) and undergo proctocolectomy with ileal pouch–anal anastomosis (IPAA). We sought to determine the incidence, risk, and burden of pouchitis in the first 2 years following the final stage of IPAA in pediatric UC patients. Methods Within the IQVIA Legacy PharMetrics Adjudicated Claims Database, we identified pediatric patients with UC who underwent proctocolectomy with IPAA between January 1, 2007, and June 30, 2015. We utilized International Classification of Diseases–Ninth Revision–Clinical Modification or International Classification of Diseases–Tenth Revision–Clinical Modification codes to identify patients with UC and Current Procedural Terminology codes to identify colectomy and IPAA. Continuous variables were compared using t tests and Wilcoxon rank sum testing, while categorical variables were compared using chi-square testing. Results A total of 68 patients with an IPAA were identified. In the first 2 years following IPAA, the cumulative incidence of pouchitis was 54%. Patients with pouchitis required more outpatient visits in the first 2 years after IPAA (mean 21.8 vs 10.2; P = .006) and were more likely to be hospitalized compared with patients without pouchitis (46% vs 23%; P = .045). Patients with pouchitis also demonstrated higher mean total costs in year 1 and year 2 ($27 489 vs $8032 [P = .001] and $27 699 vs $6058 [P = .003], respectively). Conclusions Our findings confirm the high incidence of pouchitis demonstrated in earlier single-center studies of pediatric patients undergoing proctocolectomy with IPAA for UC. Identification of risk factors for pouchitis would be useful to optimize early intervention.

Background We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn’s disease (CD). Methods CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation. Results Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62). Conclusions CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

BACKGROUND OR PURPOSE Enteric Crohn's disease (CD) is characterized by transmural inflammation resulting in inflammatory, stricturing, or penetrating phenotypes. However, data regarding the relationship between stricturing and penetrating behavior is lacking. The incidence of penetrating CD in the absence of a stricture is unclear. The aim of this study is to assess if enteric fistulae in adult patients undergoing abdominal surgery for symptomatic CD occur in isolation. METHODS Resection or repair of enteric CD fistulae performed in a quaternary care referral center (2009-2017) was analyzed. Fistulae associated with pelvic or continent pouch, rectal stump, or ano-vagina were excluded. Fistulae were stratified based on origin, tract, target, and relationship to stricture. Strictures were stratified as inflammatory or fibrostenotic. RESULTS Five hundred consecutive operative reports were reviewed. A total of 490 fistulae were evaluated. Two hundred ninety-nine fistulae were in patients undergoing index surgery. Incidence of CD fistulae not associated with stricture was 14.9% in total, but only 8% in the index surgery cohort. The majority of fistulae originated from the ileum (95%). CD fistulae originating from the stomach or duodenum were not identified in the index cohort. Fistulae within an inflammatory stricture were likely to include an intra-abdominal abscess (p < 0.001). Fistulae associated with a fibrostenotic stricture were more likely to originate proximal to the stricture (p < 0.001). The incidence of fistula-associated adenocarcinoma was 0.6%. CONCLUSIONS Symptomatic CD fistulae in the absence of stricture are uncommon. Caution should be exercised when making a diagnosis of CD in the presence of enteric fistulae, but an absence of stricture, particularly in patients with prior abdominal surgery.

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.Assess therapeutic safety and feasibility in the completed STOMP trial.Prospective single-arm phase I clinical trial.Tertiary academic medical center.Adults (18-65) with complex single tract Crohn's disease perianal fistula who have failed conventional therapy.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.Patients were followed for a total of 8 visits through 12 months. Safety was the primary endpoint; clinical healing and MRI response were secondary endpoints.Twenty patients (12 female, mean age 36 years) were treated with the stem cell-loaded plug. Of the 20 patients enrolled, three were not included in the 12 month analysis due to 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.The main limitations are the small sample size and restrictive inclusion criteria.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.

Inflammatory bowel disease patients with continent ileostomies may require revision surgeries. There remains a paucity of data regarding outcomes after re-do continent ileostomy.Evaluate the outcomes following re-do continent ileostomy.Retrospective cohort study.High volume, specialized colorectal surgery department.We identified patients who underwent re-do continent ileostomy (defined as neo-pouch construction or major operations changing the pouch configuration) for inflammatory bowel disease between 1994 and 2020.Patient demographics, short- and long-term outcomes, and quality-of-life.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 re-do continent ileostomy was 16.8 years. One hundred twenty-two patients (73%) who underwent re-do 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 re-do continent ileostomy (86%). After a median follow-up of 4 years, 48 (29%) patients 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 time interval between the primary and re-do continent ileostomy was associated with long-term pouch failure (p = 0.003). Cox regression multivariate analysis confirmed that shorter interval between surgeries was independently associated with pouch failure (p = 0.014). The mean Global Quality-of-Life score was 0.61 (± 0.23) among the 70 patients who responded to the questionnaire.Retrospective, single-center study. Low response rate for Quality-of-Life questionnaire.Re-do continent ileostomy surgery is associated with long-term pouch retention rate of 79% and satisfactory quality-of-life. Therefore, re-do surgery should be offered to patients who are motivated to keep their continent ileostomy. See Video Abstract at http://links.lww.com/DCR/C87.

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.

Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion.This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented.Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak.Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Perianal disease is a particularly morbid phenotype of Crohn's disease, affecting up to one third of patients, with a significantly diminished quality of life. Conventional medical therapy and surgical interventions have limited efficacy. Medical treatment options achieve long-term durable remission in only a third of patients. Therefore, most patients undergo an operation, leaving them with a chronic seton or at risk of incontinence with multiple interventions. Mesenchymal stem cell therapy is an emerging therapy without risk of incontinence and improved efficacy as compared with conventional therapy. Laser therapy is another new intervention. Unfortunately, up to 40% of patients still require a stoma related to perianal fistulizing disease.

Aim In patients with anorectal Crohn's disease, it remains uncertain whether a total proctocolectomy with end ileostomy or proctectomy with end colostomy should be recommended due to the unknown rate of disease recurrence in the remaining colon. Methods A retrospective review of all patients with a known diagnosis of Crohn's disease who underwent a proctectomy with end colostomy for distal Crohn's disease between January 1, 2010 and January 1, 2019 at two IBD referral centres was conducted. Data collected included patient demographics, surgical variables at the time of proctectomy, and postoperative clinical, endoscopic and surgical recurrence rates. Results A total of 63 patients were included; mean age was 47 years (SD 15 years) and 32 (50.8%) were female. The majority of patients underwent a proctectomy with end colostomy (n = 56; 88.9%) while the remaining seven patients (11.1%) underwent a proctectomy with end colostomy and concurrent ileocectomy. A total of 55 patients (87.3%) had proctitis, 51 (81%) had perianal fistulating disease, and 34 (54%) had anal canal stenosis or ulceration. Most patients had medically refractory disease (n = 54; 85.7%) versus neoplasia (n = 9; 14.3%). The median length of long-term follow-up was 17.7 months (IQR: 4.72, 38.7 months). During that time, 14 (22.2%) experienced clinical recurrence, 10 of 34 evaluated (29.4%) had endoscopic recurrence, and 3 (4.76%) required a completion total abdominal colectomy for recurrent medically refractory disease in the colon. Conclusion Colonic recurrence remains low following proctectomy and descending colostomy suggesting this operative management strategy is reasonable in Crohn's patients with distal disease.

Background and Aims Mesenchymal stem cells [MSCs] have been used for the treatment of perianal Crohn’s fistulising disease by direction injection. No studies to date have included patients with an ileal pouch-anal anastomosis [IPAA] in situ. Methods A phase IB/IIA, randomised, control trial of bone marrow-derived, allogeneic MSCs via direct injection to treat adult patients with a peripouch fistula[s] was conducted; 75 million MSCs were administered with a 22 G needle, with repeat injection at 3 months if complete clinical and radiographic healing was not achieved. Adverse and serious adverse events at post-procedure Day 1, Week 2, Week 6, Month 3, Month 6, and Month 12 were assessed. Clinical healing, radiographic healing per pelvic magnetic resonance imaging [MRI], and patient-reported outcomes were assessed at the same time points. Results A total of 22 patients were enrolled and treated; 16 were treated and six were controls. There were no adverse or serious adverse events related to MSC therapy. At 6 months, 31% of the treatment group and 20% of the control had complete clinical and radiographic healing. When stratifying the treatment group into perianal [n = 7] and ano-vaginal [n = 8] fistulas, 6-month healing in the treatment groups was 57% and 0%, respectively. The perianal Crohn’s disease activity index [PCDAI], Wexner incontinence score, and van Assche score all significantly decreased in treatment patients at 6 months; only the PCDAI decreased in the control group. Conclusion Bone marrow-derived, allogeneic MSCs offer a safe and effective alternative treatment approach for peripouch fistulas in the setting of a Crohn’s like phenotype of the pouch [ClinicalTrials.gov Identifier: NCT04519684.]

Background and Aims Rectovaginal fistula occurs in up to 10–20% of women with Crohn’s disease, significantly affecting their quality of life. We sought to determine outcomes of single and repeat operative interventions. Methods A retrospective review of all adult patients with a Crohn’s-related rectovaginal fistula, who underwent an operation between 1995 and 2021, was performed. Data collected included patient demographics, Crohn’s-related medical treatment, surgical intervention, postoperative outcomes, and fistula outcomes. Results A total of 166 patients underwent 360 operations; mean age was 42.8 [+/-13.2] years; 34 [20.7%] patients were current and 58 [35.4%] former smokers. The most commonly performed procedure was: a local approach [n = 160, 44.5%] using fibrin glue, fistulotomy/fistulectomy, or seton placement; followed by a transvaginal/transanal approach [n = 113, 31.4%] with an advancement flap repair [including Martius advancement flap] and episoproctotomy; a transabdominal approach [n = 98, 27.2%] including proctectomy or re-do anastomosis; and finally gracilis muscle interposition [n = 8, 2.2%]. The median number of operative interventions per patient was 2 [1.0–3.0] procedures. The overall fistula healing rate per patient was 71.7% [n = 119] at a median follow-up of 5.5 [1.2–9.8] years. Factors that impaired healing included former smoking (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31–0.87, p = 0.014) and seton insertion [OR 0.42, 95% CI 0.21–0.83, p = 0.012]. Conclusion Over two-thirds of Crohn’s-related rectovaginal fistulas can achieve closure with multiple surgical interventions. Smoking and seton usage negatively affect healing rates and should be avoided.

AIM Experience of endoscopic submucosal dissection (ESD) for colorectal lesions in the setting of inflammatory bowel disease (IBD) remains limited. The aim of this work was to determine the safety, feasibility and oncological outcomes of ESD in patients with IBD. METHOD A retrospective review of all adult patients (≥18 years) with a known diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) who underwent advanced colonoscopy and ESD between 1 January 2014 and 1 October 2020. Data collected included patient demographics, disease characteristics, pathological variables and procedure-related complication rates. RESULTS A total of 25 patients were included: 19 (76%) were male with a median age of 63 years and disease duration of more than 10 years. Sixteen had UC and nine had CD; the majority were taking corticosteroids, immunomodulators or monoclonal antibodies at the time of ESD. The median procedure time was 41 min and the majority (n = 18; 72%) utilized chromoendoscopy. The median lesion size was 30 mm: eight had low-grade dysplasia, nine had high-grade dysplasia and three had adenocarcinoma and underwent oncological resection. None had surgical intervention for complication of ESD or perforation. A total of 23 (88%) had a complete R0 resection. Over a median follow-up of 19 months, three were found to have dysplasia excised in polyps and none had subsequent adenocarcinoma. CONCLUSION ESD in the setting of IBD is safe and effective for complete removal of large neoplastic lesions, allowing for ongoing endoscopic surveillance and organ preservation rather than surgical intervention.

Aim Despite good overall outcomes in most patients undergoing ileal pouch-anal anastomosis (IPAA), there is still hesitation about performing an IPAA in older patients due to the comorbidity burden and concern about incontinence. The aim of this work was to identify short- and long-term outcomes in older patinets undergoing IPAA to determine the perioperative safety and long-term functional success of IPAA in older patients. Method A literature search was performed for all publications on IPAA in adults aged ≥50 years that reported short- and long-term outcomes. Data extraction included demographics, 30-day outcomes, long-term functional outcomes and pouch failure. Data were further separated by age group (50-65 and ≥65 years). Outcomes were compared between age groups. Study quality and risk of bias was assessed using the Newcastle-Ottawa Scale. Results Of 1053 publications reviewed, 13 full papers were included in the analysis. The overall 30-day morbidity and mortality rates were 47.3% and 1.3%, respectively. Thirty-day postoperative rates of small bowel obstruction and pelvic sepsis were 7.6% and 9.9%, respectively. After a median follow-up time of 62 months, rates of pouchitis, incontinence and pouch failure were 13.9%, 17.5% and 7.5%, respectively. There was no statically significant difference in rates of short- or long-term functional outcomes based on age 50-65 versus ≥65 years. Conclusion Increasing age did not increase the rate of short- or long-term outcomes, including pouch failure. These data suggest that the decision for IPAA construction should not be based on age alone.

Although patients with ulcerative colitis (UC) are at increased risk of rectal cancer compared to the general population, it remains unclear whether their oncologic outcomes are different than sporadic rectal cancer (S-RC).We aimed to compare survival and oncologic outcomes in S-RC versus UC-associated rectal cancer (UC-RC).We performed a retrospective case-control study of patients who underwent surgical resection for rectal cancer between 2005 and 2015. Data collected included patient demographics, intraoperative variables, postoperative outcomes, and oncological outcomes.A total of 138 patients were included; 92 patients with S-RC and 46 with UC-RC. Both groups were comparable in terms of demographics, oncologic characteristics, oncologic treatment strategies, perioperative complications and operative factors except for preoperative radiotherapy. At a median follow-up time of 3.7 years the 3-and 5-year OS rates; the 1-and 3-year DFS rates were comparable between the groups.Ulcerative colitis-associated rectal cancer patients have similar survival and oncologic outcomes as sporadic rectal cancer patients.

There have been no studies into the direct injection of mesenchymal stem cells (MSCs) for luminal ulcerative colitis (UC). Our aim was to investigate the efficacy of MSCs delivered locally via endoscopic delivery, as is done in the setting of perianal disease, to treat the local site of inflammation directly.A phase IB/IIA randomized control clinical trial of remestemcel-L, an ex vivo expanded allogeneic bone marrow-derived MSC product, at a dose of 150 million MSCs versus placebo (2:1 fashion) delivered via direct injection using a 23-gauge sclerotherapy needle at the time of colonoscopy was designed to assess the safety and efficacy of endoscopic delivery of MSCs for UC. The main outcome measures were adverse events, Mayo score and Mayo endoscopic severity score at 2 weeks, 6 weeks and 3 months post-MSC delivery.Six patients were enrolled and treated; four received MSCs and two placebo. All had been on prior anti-tumour necrosis factor or anti-integrin therapy. There were no adverse events related to MSCs. In the treatment group (n = 4), the Mayo endoscopic severity score decreased in all patients by 2 weeks after MSC delivery. At 3 months, all patients were extremely satisfied or satisfied with their MSC treatment based on the inflammatory bowel disease patient-reported treatment impact (IBD-PRTI), and treatment response was described as excellent or good in all patients. In the control group (n = 2), the Mayo endoscopic severity score did not increase as a result of being off alternative therapy. At 3 months, patients were dissatisfied according to the IBD-PRTI, and treatment response was poor or unchanged.MSCs may offer a safe therapeutic option for the treatment of medically refractory UC. Early data suggest improved clinical and endoscopic scores by 2 weeks after MSC delivery.

Background Postoperative recurrence (POR) of Crohn’s disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). Methods We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). Results We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. Conclusion Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

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. ispartof: GASTROENTEROLOGY vol:163 issue:4 pages:950-964 ispartof: location:United States status: published

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.

Background Anorectal stricturing is a particularly morbid manifestation of Crohn's disease resulting in a diminished quality of life related to pain, incontinence, and recurrent operative interventions. Objective To determine the role of medical therapy, endoscopic dilation, and surgical intervention for the treatment of isolated anorectal stricturing. Data sources An organized search of MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews was performed from January 1, 1990 through May 1, 2020. Study selection Full text papers which included management of isolated anorectal strictures in the setting of Crohn's disease. Intervention(s) Medical and surgical management. Main outcome measures Symptomatic relief, need for proctocolectomy. Results Our search identified a total of 553 papers; after exclusion based on title (n = 430) and abstract (n = 47), 76 underwent full text review with 65 relevant to the management of anorectal strictures. A summary of the retrospective reports suggests that medical therapy can help control luminal inflammation, but fibrosis may ultimately set in resulting in a need for endoscopic or surgical intervention. Surgical options are limited in the anal canal due to inflammation and ulceration and concomitant perianal fistulizing disease. While fecal diversion can provide symptomatic relief, successful restoration of intestinal continuity remains uncommon and most patients ultimately undergo a total proctocolectomy with end ileostomy. Limitations Limited literature published, all retrospective in nature. Conclusions Despite significant advances in medical and surgical therapy in Crohn's disease over the last decades, there is clearly an unmet need in the management of anorectal strictures in Crohn's disease.