Lightner, Amy L.

BACKGROUND: Outcomes after total abdominal colectomy with ileosigmoid or ileorectal anastomosis for Crohn’s colitis and risk factors for requirement of a permanent ileostomy remain poorly understood, particularly in the biologic era. OBJECTIVE: This study aimed to determine long-term ostomy-free survival after ileosigmoid or ileorectal anastomosis for Crohn’s colitis and potential risk factors for requirement of an ileostomy. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted at a single-institution IBD tertiary referral center. PATIENTS: Patients diagnosed with Crohn’s disease and undergoing ileosigmoid or ileorectal anastomosis between 2006 and 2018 were selected. MAIN OUTCOME MEASURE: Long-term ostomy-free survival and hazard ratios of potential predictors of ileostomy requirement were the primary outcomes measured. RESULTS: One hundred nine patients (56% female) underwent ileosigmoid or ileorectal anastomosis for Crohn’s disease. The majority of surgical procedures were completed in 2 or 3 stages (53%). The indication for total abdominal colectomy was predominantly medically refractory disease (77%), with dysplasia the second leading indication (13%). At an overall mean follow-up of 3 years, 16 patients had undergone either proctectomy or diversion with the rectum in situ. This resulted in ostomy-free survival estimates at 5 and 10 years of 78% (95% CI, 68-90) and 58% (95% CI, 35–94). A positive distal microscopic margin was the only risk factor for later requirement of a permanent ileostomy (HR, 5.4; 95% CI, 1.7–17.2). LIMITATIONS: This study is limited because it is a retrospective study at a tertiary referral center. CONCLUSIONS: Long-term ostomy-free survival can be achieved in the majority of patients who undergo restoration of intestinal continuity after total abdominal colectomy for Crohn’s colitis. A positive distal microscopic margin was independently associated with long-term anastomotic failure, and it should be accounted for when risk stratifying patients for postoperative prophylactic medical therapy. See Video Abstract at http://links.lww.com/DCR/B111. ¿QUÉ FACTORES ESTÁN ASOCIADOS CON LA EVENTUAL NECESIDAD DE UNA ILEOSTOMÍA DESPUÉS DE UNA COLECTOMÍA ABDOMINAL TOTAL Y UNA ANASTOMOSIS ILEOSIGMOIDEA O ILEORRECTAL PARA LA COLITIS DE CROHN EN LA ERA BIOLÓGICA? ANTECEDENTES: Los resultados después de la colectomía abdominal total con anastomosis ileosigmoidea o ileorrectal para la colitis de Crohn y los factores de riesgo para el requerimiento de una ileostomía permanente siguen siendo poco conocidos, particularmente en la era biológica. OBJETIVO: Determinar la supervivencia a largo plazo sin ostomía después de una anastomosis ileosigmoidea o ileorrectal para la colitis de Crohn y los factores de riesgo potenciales para la necesidad de una ileostomía. DISEÑO: Estudio de cohorte retrospectivo. AJUSTE: Centro de referencia de tercel nivel para enfermedad inflamatoria intestinal de una sola institución. PACIENTES: Pacientes diagnosticados con enfermedad de Crohn y sometidos a anastomosis ileosigmoidea o ileorrectal entre 2006 y 2018 MEDIDA DE RESULTADO PRINCIPAL: Supervivencia a largo plazo sin ostomías y cocientes de riesgo de predictores potenciales de requerimiento de ileostomía RESULTADOS: 109 pacientes (56% mujeres) se sometieron a anastomosis ileosigmoidea o ileorrectal por enfermedad de Crohn. La mayoría de los procedimientos quirúrgicos se completaron en 2 o 3 etapas (53%). La indicación de colectomía abdominal total fue predominantemente enfermedad médicamente refractaria (77%), con displasia la segunda indicación principal (13%). En un seguimiento medio general de 3 años, 16 pacientes se habían sometido a una proctectomía o a una derivación con el recto in situ. Esto dio como resultado estimaciones de supervivencia sin ostomía a los 5 y 10 años de 78% (intervalo de confianza del 95%: 68–90) y 58% (intervalo de confianza del 95%: 35–94), respectivamente. Un margen microscópico distal positivo fue el único factor de riesgo para el requerimiento posterior de una ileostomía permanente (razón de riesgo: 5.4; intervalo de confianza del 95%, 1.7–17.2). LIMITACIONES: Estudio retrospectivo en un centro de referencia de tercer nivel. CONCLUSIONES: La supervivencia a largo plazo sin ostomía se puede lograr en la mayoría de los pacientes que se someten a la restauración de la continuidad intestinal después de la colectomía abdominal total por colitis de Crohn. Un margen microscópico distal positivo se asoció de forma independiente con la insuficiencia anastomótica a largo plazo, y debe tenerse en cuenta cuando se trata de pacientes con estratificación de riesgo para el tratamiento médico profiláctico postoperatorio. Consulte Video Resumen en http://links.lww.com/DCR/B111.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the standard operative approach for ulcerative colitis (UC) or inflammatory bowel disease unclassified (IBDu) patients with medical refractory disease or dysplasia. Pouchitis or denovo Crohn’s disease are frequent adverse outcomes. The presence of small bowel (SB) mucosal inflammation before surgery might be an important predictor of these outcomes after surgery. Although small bowel follow through (SBFT) with barium has been the traditional imaging modality, cross sectional imaging using CT enterography (CTE) or MR enterography (MRE) have become increasingly utilized for preoperative SB assessment. The aim of this study was to assess changes in the utilization of SBFT versus CTE/MRE in UC and IBDu patients undergoing IPAA. METHODS: Prospectively generated clinical profiles on consecutive UC and IBDu patients undergoing IPAA between November 2006 and August 2019 were reviewed. Patients were classified into 2 groups: Group A (2006-2012) and Group B (2013-2019). Each patient was evaluated for preoperative SB imaging within their respective group. Baseline demographics were compared between groups. Imaging modalities included SBFT, CTE, MRE or ‘no imaging’. RESULTS: The study cohort of 354 patients had a mean age of 37.3 years (SD 17.1) years and included 50% males. Group A included 196 (55%) patients and Group B included 158 (45%) patients. Groups were comparable in terms of age, gender, and indication for surgery. Patients in Group A had a significantly longer disease duration (115 vs 85 months, P = 0.01) and greater number of IBDU patients (37% vs 22%, P < 0.01) versus UC patients (64% vs 77%, P < 0.01). When comparing imaging modalities, there was a significantly higher use of SBFT in Group A (44% vs 4%, P < 0.01), significantly higher use of CTE and MRE in Group B (11% vs 27%, P < 0.01 and 7% vs 40%, P < 0.01, respectively), and no difference in ‘no imaging’ between the two groups (32% vs 29%, P = 0.56). CONCLUSION(S): Cross sectional imaging using CTE or MRE has become the preferred modality of preoperative SB imaging in UC and IBDu patients undergoing IPAA.

Abstract Background Crohn’s rectovaginal fistulizing disease remains notoriously difficult to treat. A phase I clinical trial to evaluate the safety and feasibility of a novel protocol using a mesenchymal stem cell (MSC)–coated Gore Bio-A fistula plug for the treatment of medically and surgically refractory Crohn’s rectovaginal fistulas was conducted. Methods Five patients underwent an autologous subcutaneous adipose tissue harvest via a 2-cm abdominal wall incision at time of exam under anesthesia (EUA) with seton placement. MSCs were isolated, expanded, and impregnated on the plug. After 6 weeks, patients returned to the operating room for placement of the MSC-coated plug. The primary end points were safety and feasibility; the secondary end point was clinical and radiographic healing at 6 months. Results Five female patients (median age [range], 49 [38–53] years) with a median disease duration (range) of 23 (7–34) years who were on biologic (n = 5) or combination therapy (n = 3) had successful harvest and expansion of MSCs and delivery of the Gore Bio-A plug. There were no serious adverse events or adverse events related to the MSCs or plug during the 6-month follow-up. At 6 months, 3 patients had complete cessation of drainage, and 2 had &gt;50% reduction in drainage; all had a persistent fistula tract identified on magnetic resonance imaging and EUA at 6 months. Conclusions Surgical placement of an autologous adipose-derived MSC-coated fistula plug in diverted patients with Crohn’s rectovaginal fistulas was safe and feasible. All patients had a reduction in the size of their fistula tract, and 3 of 5 had cessation of drainage, but none achieved complete healing. This was a phase I clinical trial of autologous mesenchymal stem cells on a plug for rectovaginal Crohn’s fistulas.

INTRODUCTION: Treatment options for patients with moderate-severe ulcerative colitis (UC) are increasing. The appropriateness of their use in mild-moderate UC is less clear, as is the role of surgical intervention. Our aim was to define the appropriateness of therapeutic options in a range of clinical scenarios in mild-moderate UC METHODS: We applied the RAND/UCLA Appropriateness Method to rate appropriateness of treatment choices in patients with mild-moderate UC; severe disease (likely to need hospitalization or surgery within 2 weeks) was excluded. A literature review was presented to the BRIDGe group, a panel of 13 IBD specialists, as well as 1 external IBD expert and 2 IBD surgical experts. 12 chapters were constructed including failed 5-ASA, steroid or thiopurine therapy, and primary/secondary non-response to biologics or tofacitinib. Scenarios were also divided by disease extent (proctitis vs more extensive) and activity (mild vs moderate) creating 260 scenarios in all. Panellists used a modified Delphi method to anonymously rate the appropriateness of a therapy on a 1-9 scale (1-3 not appropriate, 4-6 uncertain, 7-9 appropriate). Disagreement was assessed using a validated index (DI) and was defined as a DI > 1. The panellists then convened in person to discuss areas of disagreement, followed by a second round of rating. Scenarios rated a median of 7 or higher were deemed appropriate and those rated 3 or lower were deemed inappropriate. Scenarios rated 4-6 were considered uncertain, as were any with a DI > 1 RESULTS: Appropriateness was agreed in 131 and inappropriateness in 47 scenarios. Greatest disagreement was around the use of thiopurines, but no scenario had a DI > 1. There were 82 scenarios were rated uncertain. Biologics and tofacitinib were more likely to be rated appropriate for treatment resistance and greater disease activity; disease extent less likely to influence decision making. Surgery was felt to be appropriate in 8 scenarios, generally in more extensive and active disease that had failed to respond to medical therapy. Surgery was felt to be inappropriate in 16 scenarios and was uncertain in 24 CONCLUSION: Although there was little disagreement amongst an expert panel of IBD physicians and surgeons, there remained uncertainty about the use of medical and surgical therapy in nearly one third of situations in patients with mild-moderate UC. These results could be used to guide the design of clinical trials for these patient groups in order to guide best practice.

BACKGROUND: Controversy in performing hemorrhoidectomy and anal skin tag excision in patients with IBD stems from dated reports of nonhealing wounds resulting in proctectomy. OBJECTIVE: This study aimed to determine the safety of interventional management of hemorrhoids or anal skin tags in patients with Crohn’s disease or ulcerative colitis. DESIGN: This study is a retrospective review of patient records from 2000 to 2017. SETTING: The patient records were retrieved from a multistate health system. PATIENTS: Adult patients with IBD undergoing interventional management of hemorrhoids or skin tags were included. MAIN OUTCOME MEASURE: The primary outcome measured was the long-term requirement of proctectomy. RESULTS: Ninety-seven patients (n = 49 Crohn’s disease, 48 ulcerative colitis) underwent interventional management of hemorrhoids or anal skin tags (n =35 rubber band ligation, 27 anal skin tag excision, 21 hemorrhoidectomy, 14 excision/incision of thrombosed hemorrhoid). Thirty-day complications were observed in 5 patients (n = 4 urinary retention, 1 perianal abscess). Five patients with Crohn’s disease eventually required proctectomy at a median of 7 years after skin tag excision (range, 6 months to 10 years), but none were secondary to impaired wound healing. Two patients with ulcerative colitis who had previously undergone IPAA were subsequently diagnosed with Crohn’s disease of the pouch after skin tag excision. No other long-term complications were seen in patients with ulcerative colitis. LIMITATIONS: The study’s retrospective design does not allow identification of patients with IBD who underwent only medical management of their hemorrhoids. There is also selection bias in which patients were selected for interventional management of their disease. CONCLUSIONS: The requirement for proctectomy after hemorrhoidectomy/skin tag excision appears to be secondary to the natural disease course of perianal Crohn’s disease rather than perianal intervention. Selective hemorrhoidectomy and skin tag excision in patients with well-controlled luminal disease should be considered. See Video Abstract at http://links.lww.com/DCR/B55. HEMORROIDECTOMÍA ASOCIADA A LA EXCISIÓN DE PLICOMAS EN CASOS DE ENFERMEDAD INFLAMATORIA INTESTINAL: ¿ANUNCIO DE FATALIDAD O SIMPLEMENTE EVOLUCIÓN NATURAL DE LA ENFERMEDAD? ANTECEDENTES: Está controvertida la realización de una hemorroidectomía asociada a la excisión de plicomas ano-cutáneos en pacientes con enfermedad inflamatoria intestinal, así lo han demostrado informes detallados sobre la no cicatrisación de las heridas conllevando a una proctectomía. OBJETIVO: Determinar los margenes de seguridad en casos de tratamiento instrumental de hemorroides asociadas a la excisión de plicomas ano-cutáneos en pacientes portadores de colitis ulcerosa o enfermedad de Crohn. DISEÑO: Revisión retrospectiva de historias clinicas de pacientes entre 2000 y 2017. ENTORNO: Servicio Multiestatal de Salud. PACIENTES: Adultos con enfermedad inflamatoria intestinal sometidos a tratamiento instrumental de hemorroides asociado a la excisión de plicomas ano-cutáneos. RESULTADO PRINCIPALES: Requisitos a largo plazo para una proctectomía. RESULTADOS: Noventa y siete pacientes (49 con enfermedad de Crohn, 48 con colitis ulcerosa) se sometieron a un tratamiento instrumental de hemorroides asociada a la excisión de plicomas ano-cutáneos (35 ligadura con bandas elásticas, 27 excisión de plicomas ano-cutáneos, 21 hemorroidectomías, 14 excisiones / incisiones de hemorroides trombosadas) Se observaron complicaciones a los 30 días en cinco pacientes (4 con retención urinaria, 1 absceso perianal). Cinco pacientes con enfermedad de Crohn requirieron proctectomía en una media de 7 años después de la excisión de los plicomas ano-cutáneos (rango, 6 meses a 10 años), pero ninguno fue secundario a la mala cicatrización de la herida. Dos pacientes con colitis ulcerosa que previamente se habían sometido a una anastomosis colo-anal protegia por ilestomía fueron diagnosticados posteriormente con enfermedad de Crohn localizada en la ostomía después de la excisión de plicomas ano-cutáneos. No se observaron complicaciones a largo plazo en pacientes con colitis ulcerosa. LIMITACIONES: El diseño retrospectivo del estudio no permite la identificación de pacientes con enfermedad inflamatoria intestinal que se sometieron únicamente al tratamiento médico de las hemorroides. También existe un sesgo de selección de pacientes escogidos para tratamiento instrumental de la enfermedad hemorroidaria. CONCLUSIONES: El requisito de proctectomía después de la hemorroidectomía / excisión de plicomas anocutáneos parece ser secundario al curso de la enfermedad natural de la enfermedad de Crohn perianal en el sitio de la intervención perianal. Se debe considerar la hemorroidectomía selectiva y la excisión de plicomas ano-cutáneos solo en pacientes con enfermedad endoluminal controlada. Vea el video del resumen en http://links.lww.com/DCR/B55.

BACKGROUND: The evidence regarding the association of preoperative biologic exposure and postoperative outcomes remains controversial for both antitumor necrosis factor agents and vedolizumab and largely unknown for ustekinumab. OBJECTIVE: The purpose of this study was to determine differences in the rates of 30-day postoperative overall infectious complications and intra-abdominal septic complications among the 3 classes of biologic therapies as compared with no biologic therapy. DESIGN: This was a retrospective review. SETTINGS: The study was conducted at an IBD referral center. PATIENTS: Adult patients with Crohn’s disease who received an antitumor necrosis factor, vedolizumab, ustekinumab, or no biologic therapy within 12 weeks of a major abdominal operation between May 20, 2014, and December 31, 2017, were included. MAIN OUTCOMES MEASURES: Thirty-day overall postoperative infectious complications and intra-abdominal septic complications were measured. RESULTS: A total of 712 patients with Crohn’s disease were included; 272 patients were exposed to an antitumor necrosis factor agents, 127 to vedolizumab, 38 to ustekinumab, and 275 to no biologic therapy within the 12 weeks before an abdominal operation. Patients exposed to a biologic were more likely to be taking a concurrent immunomodulator, but there was no difference in concurrent corticosteroid usage. The particular class of biologic was not independently associated with total overall infectious complications. Vedolizumab was associated with an increased rate of intra-abdominal sepsis on univariate analysis but not on multivariable analysis. Combination immunosuppression was associated with both an increased rate of overall postoperative infectious complications and intra-abdominal sepsis. LIMITATIONS: The study was limited by its retrospective design and single-center data. CONCLUSIONS: The overall rate of total infectious complications or intra-abdominal septic complications was not increased based on preoperative exposure to a particular class of biologic. Rates increased with combination immunosuppression of biologic therapy with corticosteroids and previous abdominal resection. See Video Abstract at http://links.lww.com/DCR/B24. BIOLÓGICOS Y COMPLICACIONES POSTOPERATORIAS DE 30 DÍAS DESPUÉS DE LAS OPERACIONES ABDOMINALES PARA LA ENFERMEDAD DE CROHN: ¿EXISTEN DIFERENCIAS EN LOS PERFILES DE SEGURIDAD?: ANTECEDENTES: La evidencia sobre la asociación de la exposición biológica preoperatoria y los resultados postoperatorios sigue siendo controvertida controversial tanto para los agentes del factor de necrosis tumoral (anti-TNF) como para el vedolizumab, y en gran parte desconocida para el ustekinumab. OBJETIVO: Determinar las diferencias en las tasas de complicaciones infecciosas generales postoperatorias de 30 días y complicaciones sépticas intraabdominales entre las tres clases de terapias biológicas en comparación con ninguna terapia biológica. DISEÑO: Revisión retrospectiva. AMBIENTE: centro de referencia de la enfermedad inflamatoria intestinal. PACIENTES: Pacientes adultos con enfermedad de Crohn que recibieron un factor de necrosis antitumoral, vedolizumab, ustekinumab o ningún tratamiento biológico dentro de las 12 semanas de una operación abdominal mayor entre el 5/20/2014 y el 12/31/2017. PRINCIPALES MEDIDAS DE RESULTADOS: Complicaciones infecciosas postoperatorias generales de 30 días, complicaciones sépticas intraabdominales. RESULTADOS: Se incluyeron setecientos doce pacientes con enfermedad de Crohn; 272 pacientes fueron expuestos a un anti-TNF, 127 a vedolizumab, 38 a ustekinumab y 275 a ninguna terapia biológica dentro de las 12 semanas previas a una operación abdominal. Los pacientes expuestos a un producto biológico tenían más probabilidades de tomar un inmunomodulador concurrente, pero no hubo diferencias en el uso simultáneo de corticosteroides. La clase particular de productos biológicos no se asoció de forma independiente con las complicaciones infecciosas totales. Vedolizumab se asoció con una mayor tasa de sepsis intraabdominal en el análisis univariable, pero no en el análisis multivariable. La inmunosupresión combinada se asoció tanto con una mayor tasa de complicaciones infecciosas postoperatorias generales como con sepsis intraabdominal. LIMITACIONES: Diseño retrospectivo, datos de centro único. CONCLUSIONES: La tasa general de complicaciones infecciosas totales o complicaciones sépticas intraabdominales no aumentó en función de la exposición preoperatoria a una clase particular de productos biológicos. Las tasas aumentaron con la combinación de inmunosupresión de la terapia biológica con corticosteroides y resección abdominal previa. Vea el Resumen del Video en http://links.lww.com/DCR/B24.

Abstract Background Clinical trials utilizing mesenchymal stem cells (MCSs) for the treatment of perianal Crohn disease are expanding. Most enrolled Crohn patients are being actively treated with corticosteroids, immunomodulators, and biologic therapy for their luminal and perianal disease at the time of enrollment and treatment. Aim We sought to broaden the understanding of the effect of corticosteroids, immunomodulators, and biologic therapy on the viability and function of MCSs. This information is important for tailoring inclusion and exclusion criteria of clinical trials. Methods Human adipose–derived mesenchymal stem cells (hAMCSs) were harvested and isolated from healthy patient donors. At Passage 3, hAMCSs were treated with 7 commonly used immunosuppressive therapies used to treat Crohn disease at increasing concentrations: dexamethasone, methotrexate, azathioprine, 6-mercaptopurine, infliximab, vedolizumab, and ustekinumab. Cell proliferation, migration, and cytokine secretion were analyzed at Day 4. Results Dexamethasone and azathioprine and 6-mercaptopurien affected cell proliferation and migration. Dexamethasone even resulted in cell death at high physiologic concentrations. The same drugs also had the most profound impacts on IL-6, IL-8, and monocyte chemoattractant protein-1 secretion profiles. Biologic therapies, including anti-tumor necrosis factor, anti-interleukin, and anti-integrins, had the smallest impact on hAMSC proliferation, migration, and cytokine secretion profile. Conclusions In clinical trials with MCSs, a washout period may be recommended for corticosteroids and immunomodulators to minimize any effect of systemic immunosuppression on MSC function and efficacy.

Abstract Introduction The impact of ustekinumab on adverse postoperative outcomes in Crohn’s disease (CD) remains largely unknown. We determined the difference in 90-day postoperative complication rates among CD patients exposed to ustekinumab within 12 weeks prior to an abdominal operation as compared to patients not exposed to biologic therapy. Methods A retrospective chart review of all adults with CD who underwent an abdominal operation between October 1, 2017 and December 31, 2018 at a single tertiary medical center was performed. Data collection included patient demographics, concurrent immunosuppression, serum laboratory values, operative values, and 90-day outcomes including superficial surgical site infection (sSSI), intra-abdominal sepsis, overall infectious complications, readmission, and reoperation rates. The primary outcome was the 90-day rate of intra-abdominal sepsis. Results Fifty-seven CD patients received ustekinumab and 277 received no biologic therapy in the 12 weeks prior to major abdominal surgery. Ustekinumab-exposed patients were younger, less likely to have diabetes mellitus or active tobacco exposure, were more often obese, and more often taking a concurrent immunomodulator. Ustekinumab remained an independent predictor of intra-abdominal sepsis on multivariable logistic regression. Immunomodulator exposure was associated with significantly increased rates of sSSI and overall complication rates. Conclusions Ustekinumab is associated with increased rates of 90-day postoperative intra-abdominal sepsis following a major abdominal operation for CD.

Abstract Background Proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical procedure of choice for medically refractory ulcerative colitis and familial adenomatous polyposis. While rare, a pouch volvulus can occur. We aimed to determine the frequency, presentation, and management approach of pouch volvulus in patients with IPAA. Methods A systematic search of published literature was performed by a medical reference librarian on 10 August 2018 and two independent reviewers identified relevant publications, extracted data, and assessed the methodological quality based on a validated tool. A retrospective review of the Mayo Clinic electronic medical records identified one case of pouch volvulus between January 2008 and August 2018. Results The frequency of pouch volvulus from one large published study reporting long-term outcomes of IPAA was 0.18% (3/1,700). A total of 22 patients (18 ulcerative colitis) were included (median age 32 years, 73% females). Median time to volvulus after IPAA was 36 months while median interval to volvulus diagnosis from symptom onset was 24 hours. Abdominal pain was the most commonly reported symptom (76%). The diagnosis was made primarily by abdominal computed tomography (13/17 patients, 76%). Endoscopic treatment was successful in 1 of 11 patients (9%). Surgery was performed in 20 patients and pouch-pexy and pouch excision were the most frequent surgical operations. A redo IPAA was performed in five patients (25%). Conclusion Pouch volvulus is a rare but serious complication of IPAA and should be suspected even in the absence of obstruction symptoms. Endoscopic treatment often fails and surgery is effective when performed early.