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Background: Definitive concurrent chemoradiation is the current standard of care for all stage I anal canal squamous cell carcinoma. Local excision as primary treatment for selected stage I lesions has been reported in the literature but is not currently recommended by major guidelines. We herein compared the oncologic outcomes of patients with stage I anal canal squamous cell carcinoma treated with local excision alone versus chemoradiation to determine if there are any significant differences in outcomes including disease free survival, overall survival (OS) and local failure rate. Methods: A retrospective review of all patients treated for stage I anal canal squamous cell carcinoma between 1990 and 2016 was conducted. Data collected included baseline demographics, staging studies, pathology, treatment received, relapse pattern and survival. Results: A total of 57 patients were treated for stage I anal canal squamous cell carcinoma between 1990 and 2016; 13 were treated with local excision alone and 44 were treated with chemoradiation therapy. Baseline characteristics in both cohorts of patients were comparable. Median follow-up duration of the local excision and the chemoradiation cohorts were 106 and 70 months, respectively. Of the 13 patients in local excision cohort, two patients had disease recurrence, at 21 and 97 months from the diagnosis. Both patients were long term survivors with salvage treatment. In chemoradiation cohort, 1 out of 44 patients had a local recurrence at 1 year who underwent curative resection. Five-year progression free survival (PFS) of subjects in local excision cohort and chemoradiation cohort were 91% and 83%, respectively (P=0.57). Conclusions: Local excision as primary treatment may be safe and effective for a selected group of stage I anal canal squamous cell carcinoma patients.

Minimally invasive approaches have become the standard of care for ileal pouch-anal anastomoses (IPAA). There are few reports comparing outcomes following a laparoscopic versus robotic approach. Our aim was to determine if there were any differences in the 30-day postoperative outcomes following IPAA performed laparoscopically versus robotically. A retrospective chart review of all laparoscopic and robotic IPAA performed between January 1, 2015 and June 30, 2018 was carried out. Patients included were adult patients who underwent a proctectomy and IPAA utilizing either a laparoscopic or robotic approach. Data collected included patient demographics, operative variables, and 30-day postoperative outcomes. A total of 132 patients had a minimally invasive IPAA; 58 were performed laparoscopically and 74 robotically. Less than half the patients were female (n = 55; 41.7%) with a median age of 37 years (range 18-68 years). The majority of patients had a diagnosis of ulcerative colitis (n = 103; 78.0%) with medically refractory disease (n = 87; 65.9%). A greater proportion of patients in the laparoscopic cohort had a prolonged length of stay (n = 27; 46.6% versus n = 18; 24.3%; p < 0.001) and a two-stage approach (n = 56; 96.6% versus n = 37; 50%; p < 0.001), but there were no differences in the rates between the laparoscopic versus robotic cohorts of superficial surgical site infection (6.9% versus 6.8%; p = 0.99), peripouch abscess (15.5% versus 6.8%; p = 0.11), anastomotic leak (6.9% versus 2.7%; p = 0.21), pelvic abscess (15.5% versus 6.8%; p = 0.11), and pelvic sepsis (15.5% versus 6.8%; p = 0.11), readmission (24.1% versus 17.6%; p = 0.35) or reoperation (6.9% versus 5.4%; p = 0.72). On multivariable analysis, only male sex remained predictive of prolonged length of stay, and a robotic approach trended toward a decreased rate of prolonged length of stay. Laparoscopic and robotic IPAA have equivalent postoperative morbidity underscoring the safety of the continued expansion of the robotic platform for pouch surgery.

Ileal pouch anal anastomosis is the preferred operation for restoration of intestinal continuity in patients with ulcerative colitis due to favorable functional outcomes and quality of life. However, up to 30% can develop postoperative complications, of which pelvic sepsis is the most dreaded due to impaired pouch function and increased rates of pouch failure. Several modifiable risk factors are associated with postoperative pelvic sepsis including obesity, poor nutritional status, anemia, and immunosuppressive therapy. While the evidence regarding the effect of immunosuppressive therapy on adverse postoperative outcomes is controversial, there is mounting data to suggest the operation performed at the time of immunosuppression exposure is critical for subsequent pouch outcomes. This has resulted in an increased number of pouches being performed as a modified 2-stage or 3-stage approach, a conservative yet safe approach to avoid potential deleterious effects of immunosuppression at the critical step of pouch formation.

BACKGROUND Intra-abdominal sepsis complicates

Aim Short-term morbidity and long-term functional outcome of patients with an ileal pouch-anal anastomosis (IPAA) exposed to pelvic external beam radiation therapy (EBRT) remains unknown. We report the largest series to date regarding the effects of pelvic EBRT on: (i) 30-day postoperative outcomes; and (ii) long-term functional outcome following IPAA. Method A retrospective chart review was conducted of patients who received EBRT before or after IPAA between 1980 and 2017 across three international inflammatory bowel disease referral centres. Results Nineteen patients were included. Indications for EBRT were rectal adenocarcinoma (n = 13), prostate adenocarcinoma (n = 4) or anal squamous cell carcinoma (ASCC) (n = 2). EBRT was given prior to IPAA in 12 (63%) patients and after IPAA in seven (37%). In EBRT before IPAA, patients had a median of 5 (range: 4-8) daytime bowel movements, 1 (range: 0-5) night-time bowel movement, no daytime incontinence, and only one patient used pads at a median follow up of 25 (range: 11-163) months; one patient underwent pouch excision 15 months after IPAA. In EBRT after IPAA, patients reported a median of 8 (range: 5-10) daytime and 2 (range: 0-5) night-time bowel movements, 80% had either daytime or night-time incontinence and 80% used pads at a median follow up of 90 (range: 25-315) months. Conclusion Pelvic EBRT administered prior to IPAA is associated with acceptable long-term function outcome. However, when pelvic EBRT is given to an IPAA in situ, most patients experience poor long-term pouch function without pouch failure.

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.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.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 Plt; .01). Radiographic disease severity was associated with increasing Rutgeerts' score (Plt; .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).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.

BACKGROUND Anal squamous cell carcinoma has rarely been reported in the setting of ulcerative colitis. OBJECTIVE This study aimed to understand the prognosis of anal squamous cell carcinoma in the setting of ulcerative colitis. DESIGN This is a retrospective review. SETTING This study was conducted at a referral center. PATIENTS Adult patients with both ulcerative colitis (556.9/K51.9) and anal squamous cell carcinoma (154.3/C44.520) between January 1, 2000 and August 1, 2019 were included. MAIN OUTCOMES MEASURES The primary outcomes measured are treatment and survival of anal squamous cell carcinoma. RESULTS Of the 13,499 patients with ulcerative colitis treated, 17 adult patients with ulcerative colitis and anal dysplasia and/or anal squamous cell carcinoma were included in the study: 6 had a diagnosis of anal squamous cell carcinoma, 8 had high-grade squamous intraepithelial lesions, and 3 had low-grade squamous intraepithelial lesions. There were 4 men (23%) and a median age of 55 years (range, 32-69) years. At diagnosis, 6 had an IPAA, of which 5 had active pouchitis, 1 had an ileorectal anastomosis with active proctitis, 1 had a Hartmann stump with disuse proctitis, 5 had pancolitis, and 4 had left-sided colitis. Of the 6 with anal squamous cell carcinoma, all received 5-fluorouracil and mitomycin C with external beam radiation therapy. Four patients had an IPAA, all of whom required intestinal diversion or pouch excision because of treatment intolerance. At a median follow-up of 60 months, 3 patients died: one at 0 months (treatment-related myocardial infarction), one at 60 months (metastatic anal squamous cell carcinoma), and one at 129 months (malignant peripheral nerve sheath tumor); the remaining patients had no residual disease. LIMITATIONS This study was limited because of its retrospective nature and small number of patients. CONCLUSION Anal squamous cell carcinoma in the setting of ulcerative colitis is extremely rare. In the setting of IPAA, diversion may be necessary to prevent radiation intolerance. Careful examination of the perianal region should be performed at the time of surveillance endoscopy. See Video Abstract at http://links.lww.com/DCR/B582. CARCINOMA ANAL DE CLULAS ESCAMOSAS EN COLITIS ULCEROSA PUEDE EL POUCH MODIFICAR LOS RESULTADOS DE LOS PROTOCOLOS DE TRATAMIENTO TRADICIONAL ANTECEDENTES:La incidencia de cancer anal de celulas escamosas es muy baja en pacientes con colitis ulcerosa.OBJETIVO:Comprender el pronostico del cancer anal de celulas escamosas en el contexto de la colitis ulcerosa.DISENO:Revision retrospectiva.AJUSTE:Centro de referencia.PACIENTES:Pacientes adultos con colitis ulcerosa (556.9 / K51.9) y cancer anal de celulas escamosas (154.3 / C44.520) entre el 1 de enero de 2000 y el 1 de agosto de 2019.RESULTADOS PRINCIPALES:Tratamiento y sobrevida del cancer anal de celulas escamosas.RESULTADOS:De 13.499 pacientes en tratamiento por colitis ulcerosa, diecisiete presentaron displasia y/o cancer de celulas escamosas: 6 con cancer, 8 con lesiones intraepiteliales escamosas con displasia de alto grado y 3 con displasia de bajo grado.Cuatro son hombres (23 %) con una mediana de 55 anos (rango 32-69). Al realizar el diagnostico 6 tenian pouch, 5 con pouchitis activa; 1 con ileorecto anastomosis con proctitis activa y 1 con operacion de Hartman y munon con colitis por desuso; ademas 5 tenian pancolitis y 4 tenian colitis izquierdaTodos los casos con cancer anal de celulas escamosas (6 pacientes), fueron tratados con 5-FU mas Mitomicina y radioterapia externa. Cuatro pacientes tenian pouch, todos requirieron derivacion intestinal o escision del pouch por intolerancia al tratamiento.En la mediana de seguimiento de 60 meses, tres pacientes fallecieron: uno a los 0 meses (infarto de miocardio relacionado con el tratamiento), uno a los 60 meses (cancer de celulas escamosas metastasico) y uno a los 129 meses (tumor maligno de la vaina del nervio periferico); el resto no presentaba enfermedad residual.LIMITACIONES:Revision retrospectiva, numero pequeno de pacientes.CONCLUSION:El cancer anal de celulas escamosas en el contexto de la colitis ulcerosa es extremadamente raro. En el contexto de IPAA, la derivacion puede ser necesaria para prevenir la intolerancia a la radiacion. Se debe realizar un examen cuidadoso de la region perianal en el momento de la endoscopia de control. Consulte Video Resumen en http://links.lww.com/DCR/B582.

BACKGROUND Patients with IBD are at increased risk of venous thromboembolism. OBJECTIVE This study aims to define the economic burden associated with inpatient venous thromboembolism after surgery for IBD that presently remains undefined. DESIGN This study is a retrospective, cross-sectional analysis using the National Inpatient Sample from 2004 to 2014. SETTING Participating hospitals across the United States were sampled. PATIENTS The International Classification of Diseases, 9th Revision codes were used to identify patients with a primary diagnosis of IBD. INTERVENTIONS Major abdominopelvic bowel surgery was performed. MAIN OUTCOME MEASURES The primary outcome measured was the occurrence of inpatient venous thromboembolism. Univariate and multivariable patient- and hospital-level logistic regression models were used to compare patient characteristics, hospital characteristics, and outcomes between venous thromboembolism and non-venous thromboembolism cohorts. Total average direct costs were then compared between cohorts, and the resulting difference was extrapolated to the national population. RESULTS Of 26,080 patients included, inpatient venous thromboembolism was identified in 581 (2.2%). On multivariable analysis, diagnosis of ulcerative colitis, transfer status, length of preoperative hospitalization, and insurance status were independently associated with inpatient venous thromboembolism. Patients with venous thromboembolism were observed to be associated with an increased median length of stay (17.6 vs 6.7 days; p < 0.001) and higher inpatient mortality (5.0% vs 1.1%; OR 4.7, SE 3.2-7.0; p < 0.001). After adjusting for clinically relevant covariates, the additional cost associated with each inpatient venous thromboembolism was $31,551 (95% CI, $29,136-$33,965). LIMITATIONS Our study is limited by the administrative nature of the National Inpatient Sample database, which limits our ability to evaluate the impact of clinical covariates (eg, use of venous thromboembolism chemoprophylaxis, steroid use, and nutrition status). CONCLUSION Inpatient venous thromboembolism in abdominopelvic surgery for IBD is an infrequent, yet costly, morbid complication. Given the magnitude of patient morbidity and economic burden, venous thromboembolism prevention should be a national quality improvement and research priority. See Video Abstract at http://links.lww.com/DCR/B544. DEFINICIN IMPACTO ECONMICO DE LA TROMBOEMBOLIA VENOSA PERIOPERATORIA EN LA ENFERMEDAD INFLAMATORIA INTESTINAL EN LOS ESTADOS UNIDOS ANTECEDENTES:Pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de tromboembolismo venoso (TEV).OBJETIVO:Definir el impacto economico de TEV hospitalaria despues de la cirugia por EII, que en la actualidad permanece indefinida.DISENO:Un analisis transversal retrospectivo utilizando la Muestra Nacional de Pacientes Internos (NIS) de 2004 a 2014.ENTORNO CLINICO:Hospitales participantes muestreados en los Estados Unidos.PACIENTES:Se utilizaron los codigos de la 9a edicion de la Clasificacion Internacional de Enfermedades (ICD-9) para identificar a los pacientes con diagnostico primario de EII.INTERVENCIONES:Cirugia mayor abdominopelvica intestinal.PRINCIPALES MEDIDAS DE VALORACION:Incidencia de TEV en pacientes hospitalizados, utilizando modelos de regresion logistica univariado y multivariable a nivel de pacientes y hospitales para comparar las caracteristicas de los pacientes, las caracteristicas del hospital y los resultados entre las cohortes de TEV y no TEV. Se compararon los costos directos promedio totales entre cohortes y la diferencia resultante extrapolando a la poblacion nacional.RESULTADOS:De 26080 pacientes incluidos, se identifico TEV hospitalario en 581 (2,2%). En analisis multivariable, el diagnostico de colitis ulcerosa, el estado de transferencia (entre centros hospitalarios), la duracion de la hospitalizacion preoperatoria y el nivel de seguro medico se asociaron de forma independiente con la TEV hospitalaria. Se observo que los pacientes con TEV se asociaron con un aumento de la duracion media de la estancia (17,6 versus a 6,7 dias; p

BACKGROUND Individuals with Lynch syndrome (LS) and hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. The interplay between immunosuppression, a comorbid inflammatory condition (CID), and HNPCC on cancer risk is unclear. AIM To evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC. METHODS Individuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were identified. We compared the proportion of patients with cancer in LS/HNPCC group with and without a CID. We also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive medications. RESULTS A total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no CID. Cancer occurred in 84.2% with a CID compared to 76.7% without a CID (P = 0.74) with no difference in age at first cancer diagnosis 45.5 ± 14.6 vs 43.8 ± 7.1 years (P = 0.67). LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID (P = 0.54). Nine of 21 (42.9%) patients were exposed to biologics or immunomodulators for the treatment of their CID. Cancer after diagnosis of CID was seen in 7 (77.8%) of exposed individuals vs 5 (41.7%) individuals unexposed to biologics/immunomodulators (P = 0.18). All 7 exposed compared to 3/5 unexposed developed a LS specific cancer. The exposed and unexposed groups were followed for a median 10 years and 8.5 years, respectively. The hazard ratio for cancer with medication exposure was 1.59 (P = 0.43, 95%CI: 0.5-5.1). CONCLUSION In patients with LS/HNPCC, the presence of a concurrent inflammatory condition, or use of immunosuppressive medication to treat the inflammatory condition, might not increase the rate of cancer occurrence in this limited study.

Background Fecal diversion with an ileostomy is selectively used in cases of medically refractory Crohn’s proctocolitis or advanced perianal disease. The aim of this study was to evaluate clinical improvement after fecal diversion in Crohn’s disease (CD) and factors associated with clinical improvement. Methods A retrospective chart review of adult CD patients undergoing ileostomy formation for distal disease between 2000 and 2019 at 2 CD referral centers was conducted. The primary outcome was the rate of clinical improvement with diversion that allowed for successful restoration of intestinal continuity. Secondary outcomes included the rate of clinical and endoscopic improvement after fecal diversion, ileostomy morbidity, need for subsequent total proctocolectomy and end ileostomy, and factors associated with a clinical response to fecal diversion. Results A total of 132 patients with a median age of 36 years (interquartile range, 25–49) were included. Mean duration of disease was 16.2 years (10.4) years. Indication for surgery was medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%). Medications used before surgery included corticosteroids (n = 59; 45%), immunomodulators (n = 55; 42%) and biologics (n = 82; 62%). The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16). At a median follow-up of 35.3 months (interquartile range, 10.6–74.5), 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms. There were no significant predictors of clinical improvement. Conclusions The use of a “temporary” ileostomy is largely ineffective in achieving clinical response.

Perianal fistulas affect approximately 2 in 10,000 people, causing symptoms such as pain and discharge, which can have a debilitating effect on a patient's quality of life. Surgical treatment, which can offer a potential cure or palliation of symptoms, must be considered carefully in cases with extensive sphincter involvement. In complex cases, the use of preoperative magnetic resonance imaging (MRI) can help to determine the best course of operative action. This review describes common and contemporary surgical procedures for perianal fistula, highlighting technical features, as well as important surgical considerations associated with each method and how these can be assessed radiologically. We focus on the anatomical features and MRI findings that take procedural elements into account and help determine the most appropriate method of treatment. The aim of this article is to provide a basis for informed and focused discussion between surgeons and radiologists to ensure the most appropriate procedure is selected for each case, with the ultimate aim of obtaining the most favourable outcomes for patients.

Aim The literature regarding monoclonal antibodies and increased postoperative complications in inflammatory bowel disease remains controversial. There have been no studies investigating tofacitinib. The aim of this work was to determine preoperative exposure to the small-molecule inhibitor tofacitinib and postoperative outcomes. Method We conducted a retrospective review of all adult patients exposed to tofacitinib within 4 weeks of total abdominal colectomy for medically refractory ulcerative colitis between 1 January 2018 and 1 September 2020 at four inflammatory bowel disease referral centres. Data collected included patient demographics and 90-day postoperative morbidity, readmission and reoperation rates. Results Fifty-three patients (32 men, 60%) with ulcerative colitis underwent a total abdominal colectomy (n = 50 laparoscopic, 94%) for medically refractory disease. Previous exposure to monoclonal antibodies included infliximab (n = 34), adalimumab (n = 35), certolizumab pegol (n = 5), vedolizumab (n = 33) and ustekinumab (n = 10). Twenty-seven (51%) patients were on concurrent prednisone at a median daily dose of 30 mg by mouth (range 5-60 mg). There were no postoperative deaths. Ninety-day postoperative complications included ileus (n = 7, 13.2%), superficial surgical site infection (n = 4, 7.5%), intra-abdominal abscess (n = 2, 3.8%) and venous thromboembolism (VTE) (n = 7, 13.2%). Locations of VTE included portomesenteric venous thrombus (n = 4), internal iliac vein (n = 2) and pulmonary embolism (n = 1). Nine (17%) patients were readmitted to hospital and five (9%) patients had a reoperation. Conclusion Mirroring the recently issued US Food and Drug Administration black box warning of an increased risk of VTE in medically treated ulcerative colitis patients taking tofacitinib, preoperative tofacitinib exposure may present an increased risk of postoperative VTE events. Consideration should be given for prolonged VTE prophylaxis on hospital discharge.

Background Precision or individualized medicine is increasingly pervasive across medical and surgical disciplines. However, the concept has not been introduced in regenerative medicine. Main body Targeted and engineered cellular and acellular therapy, specific to individuals or disease states, could significantly improve the efficacy of these autologous therapies. Currently, generic mesenchymal stem cell therapy is being widely used across multiple pathologies, some of which may not respond well to mesenchymal stem cell therapy. Engineered cell therapy may be a way to address this generic one-size-fits-all approach. Conclusions The future of regenerative medicine lies in the concept of precision cell-based therapy.

Background Crohn's disease is a relative contraindication to IPAA due to perceived increased rates of pouch failure. Objective This study aimed to determine pouch functional outcomes and failure rates in patients with a known preoperative diagnosis of Crohn's disease. Data sources A database search was performed in Ovid Medline In-Process & Other NonIndexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Ovid Cochrane Database of Systematic Reviews. Study selection The published human studies that reported short-term postoperative outcomes and/or long-term outcomes following IPAA in adult (≥18 years of age) Crohn's disease populations were selected. Intervention Ileal pouch anal anastomoses were constructed in patients who had Crohn's disease diagnosed preoperatively or through proctocolectomy pathology. Main outcomes measures The primary outcomes measured were long-term functional outcomes (to maximal date of follow-up) and the pouch failure rate. Results Of 7019 records reviewed, 6 full articles were included in the analysis. Rates of pelvic sepsis, small-bowel obstruction, pouchitis, anal stricture, and chronic sinus tract were 13%, 3%, 31%, 18%, and 28%. Rates of incontinence, urgency, pad usage in the day, pad usage at night, and need for antidiarrheals were 24%, 21%, 19%, 20%, and 28%, and mean 24-hour stool frequency was 6.3 bowel movements at a mean 69 months of follow-up. The overall pouch failure rate was 15%; no risk factors for pouch failure were identified. Limitations This investigation was limited by the small number of studies with significant study heterogeneity. Conclusion In patients with known preoperative Crohn's disease, IPAA construction is feasible with functional outcomes equivalent to patients with ulcerative colitis, but, even in highly selected patients with Crohn's disease, pouch failure rates remain higher than in patients with ulcerative colitis.

Background Mesenchymal stem cells (MSCs) are a well-established immunomodulatory agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune responses is controversial, and its significance in the pathogenesis remains IBD undefined. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains unknown due to the lack of side-by-side comparative investigation. We herein compared MSCs and MSC-derived EVs for the treatment of IBD using a DSS-induced colitis model. Methods A DSS-induced colitis model was used. At day 4, mice received adipose-derived MSCs, MSC-derived EVs, or placebo. Weight loss, stool consistency, and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results MSCs and EVs demonstrated equivalent immunosuppressive function in DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Furthermore, both MSCs and EVs have an equivalent ability to inhibit inflammation in the DSS colitis model by inhibiting JAK, JNK 1/2, and STAT3 signaling. Conclusions These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.

Background Recent studies have reported conflicting data on the risk of postoperative complications in patients with Crohn's disease (CD) exposed to ustekinumab (UST) preoperatively. We performed a systematic review and meta-analysis to better assess and quantify the risk of postoperative complications in this population undergoing major abdomino-pelvic surgery. Methods We conducted a comprehensive search of multiple electronic databases and conference proceedings (earliest inception through October 2020) to identify studies that reported the postoperative outcomes in CD patients with preoperative UST exposure. We estimated and compared the pooled rates of postoperative complications, including intra-abdominal sepsis, surgical site infection, any infection, any adverse event, readmission, and reoperation. Results A total of 5 studies were included in the analysis. The last dose of the drug was at most 16 weeks prior to abdomino-pelvic surgery. A total of 172 CD patients (61% female; median age 35 years) were included. The pooled rate of any complication and any infectious complications was 23.5% (95% confidence interval [CI] 16-33.1) and 20.2% (95%CI 10.3-35), respectively. There was no difference in rates of intra-abdominal sepsis between the UST group (7.2%, 95%CI 3-16.4) and the anti-tumor necrosis factor (TNF) group (11.9%, 95%CI 5.9-22.5; P = 0.4). The rates of readmission and reoperation in the UST group were 17.4% (95%CI 7.9-34) and 14.6% (95%CI 9-22.7), respectively. Conclusions The postoperative complication rate in patients with preoperative UST exposure may be similar to that for anti-TNF medication. Preoperative exposure to UST does influence postoperative complication risk. Future prospective studies are needed to validate these findings.

Purpose of review Perianal Crohn's disease is a morbid and disabling condition, notoriously difficult to successfully treat with conventional medical and surgical therapies. Mesenchymal stem cells (MSCs) are an emerging novel therapy for perianal Crohn's disease. Recent findings Over 300 patients with perianal Crohn's disease have now been treated with MSCs in the context of clinical trials. All trials have demonstrated safety, and efficacy superior to conventional therapy with biologics and surgical intervention. This was consistent despite the heterogeneity in study protocols including variability in cell dosing, mode of delivery, repeat dosing, and allogeneic versus autologous donors. Sustained healing to 1 year has also been demonstrated in a recent extension of the largest phase III study confirming superior efficacy of MSCs to placebo at 1-year follow-up. However, several outstanding questions regarding the use of MSCs for perianal Crohn's disease remain, which, if answered, could enhance MSCs' treatment efficacy. These include defining the optimal MSC donor, optimal MSC source (e.g., bone marrow versus adipose tissue), investigating a potential alloimmune response following allogeneic cellular delivery, and determining the optimal mode for MSC delivery. In addition to these unanswered questions, significant challenges in the required infrastructure and cost required for cell-based therapies may drive future research toward identifying novel acellular therapies. Summary Novel regenerative therapies offer promising new treatment options for perianal Crohn's disease, without the risk of opportunistic infection seen with biologics and incontinence with surgical techniques. Future research will help define the optimal MSC product and treatment protocol, and may even expand our horizon of regenerative medicine into acellular therapy as well as cell-based therapies.

Background Patients with IBD are at increased risk for developing colorectal cancer. However, overall survival and disease-free survival for rectal cancer alone in patients with IBD has not been reported. Objective This study aimed to determine overall survival and disease-free survival for patients with rectal cancer in IBD versus non-IBD cohorts. Design This is a retrospective cohort study. Setting This study was conducted at an IBD referral center. Patients All consecutive adult patients with IBD diagnosed with rectal cancer and at least 1 year of postsurgery follow-up were included and matched in a 1:2 fashion (age, sex, preoperative stage) with patients with rectal cancer who did not have IBD. Main outcomes measures Five-year overall survival and disease-free survival, 30-day postoperative complication, readmission, reoperation, and mortality rates were measured. Methods Survival rates were calculated using Kaplan-Meier estimates. The association of risk factors and long-term outcomes was assessed using Cox proportion hazard models. Results A total of 107 study patients with IBD who had rectal cancer were matched to 215 control patients; preoperative stages were as follows: 31% with stage I, 19% with stage II, 40% with stage III, and 10% with stage IV. Differences were observed (IBD vs non-IBD) in neoadjuvant chemotherapy (33.6% vs 52.6%, p = 0.001) and preoperative radiotherapy (35.5% vs 53.5%, p = 0.003). Postoperative complication rates were similar. On surgical pathology, patients with IBD had more lymphovascular invasion (12.9% vs 5.6%, p = 0.04) and positive circumferential resection margins (5.4% vs 0.9%, p = 0.03). On multivariable analysis, the diagnosis of IBD did not significantly impact long-term mortality (HR, 0.91; 95% CI, 0.53-1.57; p = 0.73) or disease-free survival (HR, 1.36; 95% CI, 0.84-2.21; p = 0.22). Limitations This study was limited by its retrospective design and the use of single-center data. Conclusions Patients have rectal cancer with IBD and without IBD have similar long-term and disease-free survival, despite lower rates of neoadjuvant treatment and higher margin positivity in patients with IBD. See Video Abstract at http://links.lww.com/DCR/B271. ?LA ENFERMEDAD INFLAMATORIA INTESTINAL ACARREA PEORES RESULTADOS EN PACIENTES CON CANCER RECTAL? UN ANALISIS DE CASOS-COINCIDENTES: Los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de desarrollar cancer colorrectal. Sin embargo, no se ha informado la supervivencia general y la supervivencia libre de enfermedad para el cancer rectal solo en pacientes con EII.Determinar la supervivencia general y la supervivencia libre de enfermedad para pacientes con cancer rectal en cohortes con EII versus sin EII.Estudio de cohorte retrospectivo.Centro de referencia para enfermedad inflamatoria intestinal.todos los pacientes adultos con EII diagnosticados con cancer rectal, consecutives, y al menos un ano de seguimiento postoperatorio se incluyeron y se emparejaron de manera 1: 2 (edad, sexo, etapa preoperatoria) con pacientes con cancer rectal sin EII.Se midieron la supervivencia general a cinco anos y la supervivencia libre de enfermedad, complicaciones postoperatorias a los 30 dias, reingreso, reoperacion y tasas de mortalidad.Las tasas de supervivencia se calcularon utilizando estimaciones de Kaplan-Meier. La asociacion de factores de riesgo y resultados a largo plazo se evaluo mediante modelos de riesgo de proporcion de Cox.Un total de 107 pacientes con EII y cancer rectal se compararon con 215 pacientes de control; las etapas preoperatorias fueron las siguientes: 31% de Etapa I, 19% de Etapa II, 40% de Etapa III y 10% de Etapa IV. Se observaron diferencias (EII versus no EII) en quimioterapia neoadyuvante (33.6% frente a 52.6%, p = 0.001) y radioterapia preoperatoria (35.5% frente a 53.5%, p = 0.003). Las tasas de complicaciones postoperatorias fueron similares. En la patologia quirurgica, los pacientes con EII tuvieron mas invasion linfovascular (12.9% frente a 5.6%, p = 0.04) y margenes de reseccion circunferencial positivos (5.4% frente a 0.9%, p = 0.03). En el analisis multivariable, el diagnostico de EII no tuvo un impacto significativo en la mortalidad a largo plazo (HR 0.91; IC del 95%: 0.53-1.57, p = 0.73) o la supervivencia libre de enfermedad (HR 1.36; IC del 95%: 0.84-2.21, p = 0.22)Diseno retrospectivo, centro unico de datos.Los pacientes con EII y sin EII con cancer rectal tienen una supervivencia similar a largo plazo y libre de enfermedad, a pesar de las tasas mas bajas de tratamiento sneoadyuvante y un mayor margen positivo en pacientes con EII. Consulte Video Resumen en http://links.lww.com/DCR/B271.

The ileocecal region is most commonly involved in patients with Crohn's disease (CD).In the management of ileocecal CD, this review discusses the underlying clinical issues with perioperative management and surgical intervention.Despite advances in medical treatments, surgery is required in a proportion of patients. Preoperative optimization including weaning of corticosteroids, initiation of enteral feeds, venous thromboembolism prophylaxis and smoking cessation may lead to improved postoperative outcomes. Several surgical approaches regarding anastomotic technique and range of mesentery division are now attempted to reduce the incidence of postoperative recurrence. Disease recurrence is common after surgery for CD. Early endoscopic assessment and subsequent treatment adjustment are optimal strategies for the prevention of recurrence after ileocolonic resection.

Background The surgical management of large bowel obstruction (LBO) is heterogeneous and influenced by multiple variables. The aim of this study was to analyze and compare the surgical interventions and outcomes of patients necessitating surgery for LBO. Methods Patients with LBO between 2000 and 2017 were included. Main outcomes measures are intraoperative findings, operative management, post-operative outcomes and stoma closure rates. Results 133 patients were included with predominately left-sided obstruction (82%). The most common etiology was colorectal cancer (44%) followed by extrinsic malignant compression (29%). The most common operation performed was fecal diversion without resection (46%). This group had significantly more stage 4 carcinoma, carcinomatosis and had the lowest stoma closure rate (16%). Eighty-six percent of the operated patients underwent fecal diversion, of these, 27% had stoma reversal at 6 months. Patients that had a resection and anastomosis with diverting loop ileostomy were most likely to undergo stoma reversal (p = 0.005) and had the lowest number of patients with stage-IV carcinoma. Conclusions In this single institution analysis, the management of LBO entails high operative and stoma rates, with less than 30% of patient undergoing stoma closure. Resection, anastomosis and DLI had the highest chance of stoma reversal.

BACKGROUND There is no study to date examining the safety of initiating or restarting biologic therapy after major abdominal surgery for Crohn's disease. OBJECTIVE The purpose of this study was to determine differences in the rates of 90-day superficial surgical site infections, intra-abdominal sepsis, and overall postoperative infectious complications among patients who were initiated on or restarted a biologic within 90 days postoperatively compared with those who were not. DESIGN This was a retrospective cohort study. SETTINGS The study was conducted at an IBD referral center. PATIENTS Adult patients with Crohn's disease who received a biologic therapy within 90 days of a major abdominal operation between May 20, 2014, and December 31, 2018, were included. MAIN OUTCOMES MEASURES Ninety-day superficial surgical site infection, intra-abdominal sepsis, and overall postoperative infectious complications were measured. RESULTS A total of 680 patients with Crohn's disease were included: 351 were initiated on biologic therapy within 90 days after surgery and 329 were not. Patients exposed to biologic therapy postoperatively were younger (p < 0.001), had a lower BMI (p = 0.0014), were less often diabetic (p = 0.0011), and were more often exposed preoperatively to biologics (p < 0.0001) and immunomodulators (p < 0.0001) but not corticosteroids (p = 0.8399). Of those exposed postoperatively, nearly all (93.7%) had been on a biologics preoperatively, and most resumed the same biologic (68.0%). The median time to starting biologic therapy postoperatively was 31 days (range, 7-89 d). Postoperative biologic exposure was not associated with an increased risk of superficial surgical site infection (HR = 1.02 (95% CI, 0.95-1.09) per week; p = 0.59), intra-abdominal sepsis (HR = 1.07 (95% CI, 0.99-1.16); p = 0.73), or overall postoperative infectious complications (HR = 1.02 (95% CI, 0.98-1.07); p = 0.338); the overall rates of each at 90 days was 13%, 8%, and 28%. LIMITATIONS The study was limited by its retrospective design and single-center data. CONCLUSIONS Postoperative initiation or resumption of biologic therapy did not increase 90-day rates of superficial surgical site infection, intra-abdominal sepsis, or total infectious complications after major abdominal surgery for Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B207. ?SON SEGUROS LOS FARMACOS BIOLOGICOS EN EL POSTOPERATORIO INMEDIATO? UNA EVALUACION DE UN SOLO CENTRO DE PACIENTES QUIRURGICOS CONSECUTIVOS CON ENFERMEDAD DE CROHN: No hay ningun estudio hasta la fecha que examine la seguridad de iniciar o reiniciar la terapia biologica despues de una cirugia abdominal mayor en enfermedad de Crohn.Determinar las diferencias en las tasas a 90 dias de infecciones del sitio quirurgico superficial, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales entre los pacientes en que se inicio o reinicio un biologico dentro de los 90 dias despues de la operacion en comparacion con aquellos que no lo recibieron.Estudio de cohorte retrospectivo.Centro de referencia de enfermedad inflamatoria intestinal.Pacientes adultos con enfermedad de Crohn que recibieron una terapia biologica dentro de los 90 dias de una operacion abdominal mayor entre el 20 de mayo de 2014 y el 31 de diciembre de 2018.Infeccion superficial del sitio quirurgico, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales a 90 dias.Se incluyeron un total de 680 pacientes con enfermedad de Crohn: 351 se iniciaron en terapia biologica dentro de los 90 dias posteriores a la cirugia y 329 no. Los pacientes expuestos a terapia biologica despues de la operacion eran mas jovenes (p

BACKGROUND & AIMS: Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA. METHODS: We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital. RESULTS: Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%–52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%–33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%–22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P