Intra-operative Radiation Therapy for Colorectal or Anal Cancer at Risk for Margin-Positive Resection: Initial Results of a Single-Institution Registry.

PURPOSE: Pelvic recurrence of rectal or anal cancers is associated with considerable morbidity and mortality. We report our initial experience with an aggressive intra-operative radiotherapy (IORT) program. METHODS: Patients with locally advanced or recurrent rectal or anal cancers considered to have a high likelihood of R1 or R2 resection after multi-disciplinary review underwent surgical excision and IORT using a high-dose-rate afterloader (Ir-192) and HAM applicator. Endpoints included local or distant recurrence, and acute and late toxicity graded using the American College of Surgeons (ACS) NSQIP and the LENT-SOMA scale. RESULTS: Twenty-one patients, largely with prior history of both pelvic external beam radiotherapy (EBRT, median 50.4 Gy) and surgical resection, underwent excision with IORT (median dose 12.5 Gy, range 10-15). Median follow-up was 20 months. Twelve (57%) patients had failure at the IORT site. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF at 1 year 75% for R0 vs 15% for R1/2, p = 0.0065) but not re-irradiation EBRT or IORT dose (p > 0.05). Twelve, 5, and 13 patients experienced local, regional, and distant failure, respectively; 3 (14%) patients were disease-free at last follow-up. The most frequent acute toxicity was sepsis/abscess (24%). One patient (5%) required a ureteral stent; no patients developed neuropathy attributable to IORT. CONCLUSIONS: In patients treated with excision and IORT for locally recurrent cancer, R0 resection is a critical determinant of local control. For patients with R1/2 resection, poor disease-free outcomes warrant consideration of a different treatment strategy.

High Complication Rate After Early Ileostomy Closure: Early Termination of the Short Versus Long Interval to Loop Ileostomy Reversal After Pouch Surgery Randomized Trial.

BACKGROUND: In patients with ulcerative colitis who undergo IPAA, a diverting ileostomy is used to diminish the severity of anastomotic complications. Typically, the ileostomy is closed after an interval of 2 to 4 months. The safety of earlier closure of the ileostomy after pouch surgery is unknown. OBJECTIVE: This study aimed to compare postoperative outcomes in patients randomly assigned to early (7-12 days) or late (≥8 weeks) ileostomy closure after ileal pouch construction. DESIGN: This was a multicenter, prospective randomized trial. SETTING: The study was conducted at colorectal surgical units at select United States hospitals. PATIENTS: Adults with ulcerative colitis who underwent 2- or 3-stage proctocolectomy with IPAA were included. MAIN OUTCOME MEASURES: The primary outcomes included Comprehensive Complication Index at 30 days after ileostomy closure. The secondary outcomes included complications, severe complications, reoperations, and readmissions within 30 days of ileostomy closure. RESULTS: The trial was stopped after interim analysis because of a high rate of complications after early ileostomy closure. Among 36 patients analyzed, 1 patient (3%) had unplanned proctectomy with end-ileostomy. Of the remaining 35 patients, 28 patients (80%) were clinically eligible for early closure and underwent radiologic assessment. There were 3 radiologic failures. Of the 25 remaining patients, 22 patients (88%) were randomly assigned to early closure (n = 10) or late closure (n = 12), and 3 patients were excluded. Median Comprehensive Complication Index was 14.8 (0-54) and 0 (0-23) after early and late closure (p = 0.02). One or more complications occurred in 7 patients (70%) after early closure and in 2 patients (17%) after late closure (p = 0.01)' and complications were severe in 3 patients (30%) after early closure and 0 patients after late closure (p = 0.04). Reoperation was required in 1 patient (10%) and 0 patients (p = 0.26) after early closure and readmission was required in 7 patients (70%) and 1 patient (8%) after late closure (p = 0.003). LIMITATIONS: This study was limited by early study closure and selection bias. CONCLUSIONS: Early closure of a diverting ileostomy in patients with ulcerative colitis who underwent IPAA is associated with an unacceptably high rate of complications. See Video Abstract at http://links.lww.com/DCR/C68. ALTA TASA DE COMPLICACIONES DESPUS DEL CIERRE PRECOZ DE LA ILEOSTOMA TERMINACIN TEMPRANA DEL ENSAYO ALEATORIZADO DE INTERVALO CORTO VERSUS LARGO PARA LA REVERSIN DE LA ILEOSTOMA EN ASA DESPUS DE LA CIRUGA DE RESERVORIO ILEAL: ANTECEDENTES:En los pacientes con colitis ulcerosa que se someten a una anastomosis del reservorio ileoanal, se utiliza una ileostomía de derivación para disminuir la gravedad de las complicaciones de la anastomosis. Por lo general, la ileostomía se cierra después de un intervalo de 2 a 4 meses. Se desconoce la seguridad del cierre más temprano de la ileostomía después de la cirugía de reservorio.OBJETIVO:Comparar los resultados posoperatorios en pacientes asignados al azar al cierre temprano (7-12 días) o tardío (≥ 8 semanas) de la ileostomía después de la construcción de un reservorio ileal.DISEÑO:Este fue un ensayo aleatorizado prospectivo multicéntrico.ESCENARIO:El estudio se realizó en unidades quirúrgicas colorrectales en hospitales seleccionados de los Estados Unidos.PACIENTES:Se incluyeron adultos con colitis ulcerosa que se sometieron a proctocolectomía en 2 o 3 tiempos con anastomosis ileoanal con reservorio.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios incluyeron el Índice Integral de Complicaciones a los 30 días después del cierre de la ileostomía. Los resultados secundarios incluyeron complicaciones, complicaciones graves, reoperaciones y readmisiones dentro de los 30 días posteriores al cierre de la ileostomía.RESULTADOS:El ensayo se detuvo después del análisis interino debido a una alta tasa de complicaciones después del cierre temprano de la ileostomía. Entre los 36 pacientes analizados, 1 (3%) tuvo una proctectomía no planificada con ileostomía terminal. De los 35 pacientes restantes, 28 (80%) fueron clínicamente elegibles para el cierre temprano y se sometieron a una evaluación radiológica. Hubo 3 fracasos radiológicos. De los 25 pacientes restantes, 22 (88 %) se asignaron al azar a cierre temprano (n = 10) o tardío (n = 12) y 3 fueron excluidos. La mediana del Índice Integral de Complicaciones fue de 14,8 (0-54) y 0 (0-23) después del cierre temprano y tardío (p = 0,02). Una o más complicaciones ocurrieron en 7 pacientes (70%) después del cierre temprano y 2 (17%) pacientes después del cierre tardío (p = 0,01) y fueron graves en 3 (30%) y 0 pacientes, respectivamente (p = 0,04). Requirieron reintervención en 1 (10%) y 0 (p = 0,26) y reingreso en 7 (70%) y 1 (8%) pacientes (p = 0,003).LIMITACIONES:Este estudio estuvo limitado por el cierre temprano del estudio; sesgo de selección.CONCLUSIONES:El cierre temprano de una ileostomía de derivación en pacientes con colitis ulcerosa con anastomosis de reservorio ileoanal se asocia con una tasa inaceptablemente alta de complicaciones. Consulte Video Resumen en http://links.lww.com/DCR/C68. (Traducción-Dr. Felipe Bellolio).

Endoscopic Phenotype of the J Pouch in Patients With Inflammatory Bowel Disease: A New Classification for Pouch Outcomes.

BACKGROUND & AIMS: Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis who have undergone colectomy. Pouchitis has been considered a single entity despite a broad array of clinical and endoscopic patterns. We developed a novel classification system based on the pattern of inflammation observed in pouches and evaluated the contributing factors and prognosis of each phenotype. METHODS: We identified 426 patients (384 with ulcerative colitis) treated with proctocolectomy and IPAA who subsequently underwent pouchoscopies at the University of Chicago between June 1997 and December 2019. We retrospectively reviewed 1359 pouchoscopies and classified them into 7 main pouch phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted 6 months after ileostomy takedown. Logistic regression analysis was used to assess factors contributing to each phenotype. Pouch survival was estimated by the log-rank test and the Cox proportional hazards model. RESULTS: Significant contributing factors for afferent limb involvement were a body mass index of 25 or higher and hand-sewn anastomosis, for inlet involvement the significant contributing factor was male sex; for diffuse inflammation the significant contributing factors were extensive colitis and preoperative use of anti-tumor necrosis factor drugs, for cuffitis the significant contributing factors were stapled anastomosis and preoperative Clostridioides difficile infection. Inlet stenosis, diffuse inflammation, and cuffitis significantly increased the risk of pouch excision. Diffuse inflammation was associated independently with pouch excision (hazard ratio, 2.69; 95% CI, 1.34-5.41; P = .005). CONCLUSIONS: We describe 7 unique IPAA phenotypes with different contributing factors and outcomes, and propose a new classification system for pouch management and future interventional studies.

Nonspecific, Acute Pouchitis in Patients With Familial Adenomatous Polyposis: Less Common Than We Think.

BACKGROUND: Nonspecific acute pouchitis is common in patients with ulcerative colitis who undergo IPAA, but there is disagreement about the rate at which this occurs in patients with familial adenomatous polyposis. OBJECTIVE: This study aimed to define the rate at which nonspecific acute pouchitis occurs in patients with familial adenomatous polyposis. SETTING: This study was conducted at a hereditary colorectal cancer center in a large academic medical center. DESIGN: This is a retrospective cohort study using prospectively gathered data. PATIENTS: Patients with familial adenomatous polyposis who have had IPAA were included. INTERVENTIONS: Symptoms, pouchoscopy and pouch radiography, and pouch biopsy were evaluated. MAIN OUTCOME MEASURES: The primary outcomes measured were the presence of nonspecific acute pouchitis and the alternative diagnosis of pouch dysfunction. RESULTS: There were 250 patients with familial adenomatous polyposis who had undergone IPAA; 38 (15.2%) had been labeled as having "pouchitis": 23 men and 15 women. Median age was 55 years (range, 18-90 years). No patient had nonspecific, acute pouchitis as defined by our criteria. In 9 cases, the diagnosis was derived from benign ulcers common in ileal pouches. Stool frequency was the most common symptom associated with the "pouchitis" label, but actual causes for the frequency included poor pouch emptying, poor eating habits, poor bowel habits, and afferent limb syndrome. Median stool frequency was 9, ranging from 4 to 15 per day. Every patient had at least 1 pouch endoscopy, and the median number was 19 per patient (range, 1-21). Nine patients had pouch biopsies to rule out inflammation; all showed chronic active enteritis, a normal finding in ileal pouches. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: We could not confirm any case of nonspecific acute pouchitis in patients with familial adenomatous polyposis. Those caring for patients with familial adenomatous polyposis who have a pouch should seek causes for pouch-related symptoms other than "pouchitis." See Video Abstract at http://links.lww.com/DCR/B666.POUCHITIS AGUDA INESPECÍFICA EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: MENOS COMÚN DE LO QUE PENSAMOSANTECEDENTES:La pouchitis aguda e inespecífica es común en pacientes con colitis ulcerativa, sometidos a anastomosis de bolsa ileoanal, pero no hay acuerdo sobre la frecuencia en que se presenta en pacientes con poliposis adenomatosa familiar (PAF).OBJETIVO:Definir la frecuencia en la que se presenta pouchitis aguda inespecífica en pacientes con poliposis adenomatosa familiar.ENTORNO CLINICO:Centro de cáncer colorrectal hereditario en un gran centro médico académico.DISEÑO:Estudio de cohorte retrospectivo utilizando datos recopilados prospectivamente.PACIENTES:Pacientes con poliposis adenomatosa familiar sometidos a bolsa con anastomosis ileoanal.INTERVENCIONES:Síntomas, proctoscopia, radiografía y biopsia de bolsa ileoanal.PRINCIPALES MEDIDAS DE VALORACION:Presencia de pouchitis aguda inespecífica; diagnósticos alternos de disfunción de la bolsa ileal.RESULTADOS:De 250 pacientes con poliposis adenomatosa familiar sometidos a una anastomosis anal de la bolsa ileal; 38 (15,2%), habían sido etiquetados como "pouchitis", 23 hombres y 15 mujeres. La mediana de edad fue de 55 años (rango de 18 a 90 años). Ningún paciente tuvo pouchitis aguda inespecífica según lo definido por nuestros criterios. En 9 casos el diagnóstico se derivó de úlceras benignas frecuentes en bolsas ileales. La frecuencia de las evacuaciones fue el síntoma más común asociado con la etiqueta "pouchitis", pero las causas reales de la frecuencia, incluyeron un mal vaciado de la bolsa, malos hábitos alimenticios, malos hábitos intestinales y síndrome de asa aferente. La frecuencia media de las evacuaciones fue de 9, con un rango de 4 a 15 por día. A cada paciente se le realizó al menos una endoscopia de la bolsa: la mediana fue de 19 por paciente (rango de 1 a 21). A 9 pacientes se les realizó biopsia de bolsa para descartar inflamación: todos mostraron enteritis activa crónica, un hallazgo normal en las bolsas ileales.LIMITACIONES:Naturaleza retrospectiva del estudio.CONCLUSIONES:No pudimos confirmar ningún caso de pouchitis aguda e inespecífica en pacientes con PAF. Aquellos que atienden a pacientes con PAF con bolsa ileal, deben buscar otras causas para los síntomas relacionados con la bolsa que no sean "pouchitis". Consulte Video Resumen en http://links.lww.com/DCR/B666. (Traducción-Dr. Fidel Ruiz Healy).

Does Concomitant Pelvic Organ Prolapse Repair at the Time of Rectopexy Impact Rectal Prolapse Recurrence Rates? A Retrospective Review of the Prospectively Collected Pelvic Floor Disorders Consortium Quality Improvement Database Pilot.

BACKGROUND: Pelvic organ prolapse is reported in 30% of women presenting with rectal prolapse. Combined repair is a viable option to avoid the need for future pelvic floor interventions. However, the added impact of adding a modicum of middle compartment suspension by closing the pouch of Douglas during a rectal prolapse repair has not been studied. OBJECTIVE: The study aimed to assess the impact of middle compartment suspension on the durability of rectal prolapse repair. We also aimed to determine whether adding some form of pouch of Douglas closure to achieve middle compartment suspension leads to any improvements in the rates or severity of postoperative constipation or in the rates or severity of postoperative fecal incontinence. DESIGN: This study was a retrospective analysis of a multicenter prospective database. SETTING: Data were analyzed from the Pelvic Floor Disorders Consortium Quality Improvement in Rectal Prolapse Surgery database. Deidentified surgeons at more than 20 sites (75% academic, 81% high volume) self-reported patient demographics, previous repairs, symptoms of fecal incontinence and obstructed defecation, and operative details, including addition of concomitant gynecologic repairs, use of mesh, posterior or ventral dissection, and sigmoidectomy. PATIENTS: Patients were included who underwent abdominal repair for rectal prolapse. INTERVENTIONS: Abdominal rectopexy procedures with and without middle compartment suspension were compared. Middle compartment suspension was defined as excision and closure of the pouch of Douglas with some degree of colpopexy or culdoplasty. MAIN OUTCOME MEASURES: The primary outcome of prolapse recurrence and secondary outcomes of incontinence and constipation were calculated via univariate and multivariable regression by comparing those who underwent rectopexy with and without middle compartment suspension. RESULTS: Of the 198 patients (98% female, age 60.2 ± 15.6 years) who underwent abdominal repairs (59% robotic), 138 patients (70%) underwent some concomitant middle compartment suspension. Patients who had an added middle compartment suspension seemed to have lower early rectal prolapse recurrences. On multivariable regression to control for age, previous repairs, and the use of mesh, addition of some form of pouch of Douglas repair was associated with a decrease in short-term recurrences. LIMITATIONS: Our data need to be interpreted cautiously. Future studies are critically needed to further explore this observation, with an a priori, prospective definition of middle compartment suspension, validated measurement of concomitant pathology, and longer follow-up. CONCLUSION: Our results suggest that some middle compartment suspension at the time of rectal prolapse repair may improve short-term durability of rectal prolapse repair. See Video Abstract at http://links.lww.com/DCR/C30 . LA REPARACIN CONCOMITANTE DEL PROLAPSO DE RGANOS PLVICOS EN EL MOMENTO DE LA RECTOPEXIA AFECTA LAS TASAS DE RECURRENCIA DEL PROLAPSO RECTAL UNA REVISIN RETROSPECTIVA DE UNA BASE DE DATOS RECOPILADA PROSPECTIVAMENTE DEL CONSORCIO SOBRE LA MEJORA DE LA CALIDAD DE TRASTORNOS DEL PISO PLVICO: ANTECEDENTES:El prolapso de órganos pélvicos se informa en el 30 % de las mujeres que presentan prolapso rectal y la reparación combinada es una opción viable para evitar la necesidad de futuras intervenciones del suelo pélvico. Sin embargo, no se ha estudiado el impacto adicional de agregar un mínimo de suspensión del compartimento medio cerrando el fonde de saco de Douglas durante una reparación de prolapso rectal.OBJETIVO:Nuestro objetivo fue evaluar el impacto de la suspensión del compartimento medio con respecto a la durabilidad de la reparación del prolapso rectal. Quisimos de igual manera determinar si el agregado de algún tipo de cierre del fondo de saco de Douglas para lograr la suspensión del compartimento medio conduce a alguna mejora en las tasas o la gravedad del estreñimiento posoperatorio así como en las tasas o la gravedad de la incontinencia fecal posoperatoria.DISEÑO:Análisis retrospectivo de una base de datos prospectiva.ESCENARIO:Base de datos Multicenter Pelvic Floor Disorders Consortium Prospective Quality Improvement. Cirujanos no identificados en >20 sitios (75% académicos, 81% de alto volumen) datos demográficos de pacientes auto informados, reparaciones previas, síntomas de incontinencia fecal y defecación obstruida, y detalles quirúrgicos, incluida la suma de reparaciones ginecológicas concomitantes, uso de malla, disección anterior o posterior y sigmoidectomía.INTERVENCIONES:Se compararon los procedimientos de rectopexia abdominal con y sin suspensión del compartimento medio). La suspensión del compartimento medio se definió como la escisión y cierre del fondo de saco de Douglas con algún grado de colpopexia o culdoplastia.RESULTADOS:El resultado principal de la recurrencia del prolapso y los resultados secundarios de incontinencia y estreñimiento se calcularon mediante regresión uni y multivariable al comparar los que fueron sometidos a rectopexia con y sin suspensión del compartimento medio.PACIENTES:Pacientes sometidos a reparación abdominal por prolapso rectal.RESULTADOS:De los 198 pacientes (98% mujeres, edad 60,2 ± 15,6 años) sometidas a reparaciones abdominales (59% robótica), 138 (70%) fueron sometidas igualmente y de manera concomitante a alguna suspensión del compartimento medio. Los pacientes a los que se les añadió una suspensión del compartimento medio parecían tener menores recurrencias tempranas del prolapso rectal y, en la regresión multivariable para controlar la edad, las reparaciones previas y el uso de malla, la adición de alguna forma de reparación del fondo de saco de Douglas se asoció con una disminución de las recurrencias a corto plazo.LIMITACIONES:Nuestros datos deben interpretarse con cautela. Se necesitan de manera critica, estudios futuros para explorar más a fondo esta observación, con una definición prospectiva a priori de la suspensión del compartimento medio, una medición validada de la patología concomitante y un seguimiento más prolongado.CONCLUSIONES:Nuestros resultados sugieren que alguna suspensión del compartimento medio en el momento de la reparación del prolapso rectal puede mejorar la durabilidad a corto plazo de la reparación del prolapso rectal. Consulte Video Resumen en http://links.lww.com/DCR/C30 . (Traducción-Dr. Osvaldo Gauto ).

Using Wearable Biosensors to Predict Length of Stay for Patients with IBD After Bowel Surgery.

BACKGROUND AND AIMS: It remains unknown whether ambulation or sleep predicts postoperative length of stay for patients with IBD. We aim to identify the utility of wearable biosensors in predicting postoperative length of stay for patients with IBD. METHODS: Associations of postoperative length of stay with step count/sleep duration/sleep efficiency measured by wearable biosensors were examined. The best-fitting multivariable linear regression model predicting length of stay was constructed using stepwise model selection. RESULTS: Final sample included 37 patients. Shorter sleep duration on postoperative day 4 (r = 0.51, p = 0.043) or 5 (r = 0.81, p = 0.0045) or higher sleep efficiency on postoperative day 5 (r = - 0.77, p = 0.0098) was associated with a shorter length of stay. Additionally, a more positive change in sleep efficiency from postoperative day 4-5 was associated with a shorter length of stay (r = - 0.77, p = 0.024). The best-fitting multivariable linear regression model revealed Clavien-Dindo grade 1 (p = 0.045) and interaction between Clavien-Dindo grade 2/3a and mean daily steps (p = 0.00038) are significant predictors of length of stay. The following variables were not significantly associated with length of stay: mean daily steps/sleep duration/sleep efficiency, average rate of change in these three variables, and changes in step count between successive postoperative days 1-5, sleep duration between successive postoperative days 2-5, and sleep efficiency between successive postoperative days 2-4. CONCLUSION: We demonstrated the utility of activity and sleep data from wearable biosensors in predicting length of stay. Patients with more severe complications may benefit more (i.e., reduced postoperative length of stay) from increased ambulation. However, overall, sleep duration/efficiency did not predict length of stay.

Histopathology of Colectomy Specimens Predicts Endoscopic Pouch Phenotype in Patients with Ulcerative Colitis.

BACKGROUND: The endoscopic appearance in patients with "pouchitis" after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) can be quite heterogenous. Patients with an endoscopic phenotype resembling Crohn's disease (CD) are at high risk of pouch loss. AIMS: We aimed to assess how the histopathology of colectomy specimens predicts endoscopic pouch phenotypes in UC. METHODS: We retrospectively assessed pouchoscopies from patients with UC who underwent IPAA and classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb involvement, (3) inlet involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch with fistulas noted ≥ 6 months from ileostomy takedown. We assessed the clinical and pathological data including deep, focal inflammation, granulomas, and terminal ileal involvement in the colectomy specimens. Logistic regression analysis was performed to identify contributing factors to each phenotype. RESULTS: This study included 1,203 pouchoscopies from 382 patients with UC. On multivariable analysis, deep inflammation was significantly associated with pouch fistulas (Odds ratio 3.27; 95% confidence interval 1.65-6.47; P = 0.0007). Of the 75 patients with deep inflammation, only two patients (2.7%) were diagnosed with CD based on pathology review. Terminal ileal involvement significantly increased the risk of afferent limb involvement (Odds ratio 2.96; 95% confidence interval 1.04-8.47; P = 0.04). There were no significant associations between other microscopic features and phenotypes. CONCLUSIONS: We identify histologic features of colectomy specimens in UC that predict subsequent pouch phenotypes. Particularly, deep inflammation in the resected colon was significantly associated with pouch fistulas, a pouch phenotype with poor prognosis.

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

Preliminary Report From the Pelvic Floor Disorders Consortium: Large-Scale Data Collection Through Quality Improvement Initiatives to Provide Data on Functional Outcomes After Rectal Prolapse Repair.

BACKGROUND: The surgical management of rectal prolapse is constantly evolving, yet numerous clinical trials and meta-analyses studying operative approaches have failed to make meaningful conclusions. OBJECTIVE: The purpose of this study was to report on preliminary data captured during a large-scale quality improvement initiative to measure and improve function in patients undergoing rectal prolapse repair. DESIGN: This was a retrospective analysis of prospectively collected surgical quality improvement data. SETTINGS: This study was conducted at 14 tertiary centers specializing in pelvic floor disorders from 2017 to 2019. PATIENTS: A total of 181 consecutive patients undergoing external rectal prolapse repair were included. MAIN OUTCOME MEASURES: Preoperative and 3-month postoperative Wexner incontinence score and Altomare obstructed defecation score were measured. RESULTS: The cohort included 112 patients undergoing abdominal surgery (71 suture rectopexy/56% minimally invasive, 41 ventral rectopexy/93% minimally invasive). Those offered perineal approaches (n = 68) were older (median age, 75 vs 62 y; p < 0.01) and had more comorbidities (ASA 3-4: 51% vs 24%; p < 0.01) but also reported higher preintervention rates of fecal incontinence (Wexner 11.4 ± 6.4 vs 8.6 ± 5.8; p < 0.01). Patients undergoing perineal procedures had similar incremental improvements in function after surgery as patients undergoing abdominal repair (change in Wexner, -2.6 ± 6.4 vs -3.1 ± 5.6, p = 0.6; change in Altomare, -2.9 ± 4.6 vs -2.7 ± 4.9, p = 0.8). Similarly, patients undergoing posterior suture rectopexy and ventral mesh rectopexy had similar incremental improvements in overall scores; however, patients undergoing ventral mesh rectopexy had a higher decrease in the need to use pads after surgery. LIMITATIONS: The study was limited by its retrospective data analysis and 3-month follow-up. CONCLUSIONS: Functional outcomes improved in all of the patients undergoing prolapse surgery. Larger cohorts are necessary to show superiority among surgical procedures. Quality improvement methods may allow for systematic yet practical acquisition of information and data analysis. We call for the creation of a robust database to benefit this patient population. See Video Abstract at http://links.lww.com/DCR/B581. REPORTE PRELIMINAR DEL CONSORCIO DE TRASTORNOS DEL PISO PLVICO RECOLECCIN DE DATOS A GRAN ESCALA MEDIANTE INICIATIVAS DE MEJORAMIENTO DE LA CALIDAD PARA PROPORCIONAR INFORMACIN SOBRE LOS RESULTADOS FUNCIONALES: ANTECEDENTES:El tratamiento quirúrgico del prolapso rectal está evolucionando constantemente, sin embargo, numerosos estudios clínicos y metaanálisis que evalúan los tratamientos quirúrgicos no han logrado demostrar conclusiones significativas.OBJETIVO:Reportar datos preliminares obtenidos a gran escala durante una iniciativa de mejoramiento de la calidad para medir y mejorar la función en pacientes sometidos a reparación de prolapso rectal.DISEÑO:Análisis retrospectivo de datos recolectados prospectivamente de mejoramiento de la calidad quirúrgica.ENTORNO CLINICO:Este estudio se realizó en 14 centros terciarios especializados en trastornos del piso pélvico del 2017 al 2019.PACIENTES:Un total de 181 pacientes consecutivos sometidos a reparación de prolapso rectal externo.PRINCIPALES MEDIDAS DE VALORACION:Escala de incontinencia de Wexner y de defecación obstruida de Altomare preoperatoria y tres meses postoperatoria.RESULTADOS:El cohorte incluyó 112 pacientes sometidos a cirugía abdominal (71 rectopexia con sutura / 56% minimally invasive, 41 rectopexia ventral / 93% minimally invasive). Aquellos a los que se les realizaron abordajes perineales (n = 68) eran mayores (edad media de 75 vs. 62, p <0,01) y tenían mayorcomorbilidades (ASA 3-4: 51% vs. 24%, p <0,01), además reportaron una mayor tasa de incontinencia fecal previo a la intervención (Wexner 11,4 ± 6,4 vs. 8,6 +/- 5,8, p <0,01). Posterior a la cirugía, los pacientes sometidos a procedimientos perineales tuvieron mejoría progresiva en la función similar que los pacientes sometidos a reparación abdominal (cambio en Wexner -2,6 ± 6,4 vs. -3,1 ± 5,6, p = 0,6; cambio en Altomare -2,9 ± 4,6 vs. -2,7 ± 4,9, p = 0,8). De manera similar, los pacientes con rectopexia posterior con sutura y rectopexia ventral con malla tuvieron mejoría progresiva similares en las escalas generales; no obstante, pacientes con rectopexia ventral con malla tuvieron una mayor disminución en la necesidad de usar paños protectores después de la cirugía.LIMITACIONES:Análisis de datos retrospectivo y seguimiento de tres meses.CONCLUSIONES:Los resultados funcionales mejoraron en todos los pacientes sometidos a cirugía de prolapso. Se necesitan cohortes más grandes para demostrar superioridad entre los procedimientos quirúrgicos. Métodos de mejoramiento de la calidad pueden permitir la adquisición sistemática, pero práctica de información y análisis de datos. Hacemos un llamado para la creación de una base de datos sólida para beneficiar a esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B581. (Traducción- Dr Francisco M. Abarca-Rendon).

Combined mechanical and oral antibiotic bowel preparation is associated with prolonged recurrence-free survival following surgery for colorectal cancer.

BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.

The Correlation between Vitamin D Levels and the Risk of Postoperative Recurrence in Crohn's Disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with disease activity in Crohn's disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. METHODS: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6-12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. RESULTS: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of <15, 15-30, and >30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08-0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively). CONCLUSION: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

Patient Acceptance of Routine Serial Postoperative Endoscopy Following Low Anterior Resection (LAR) and Its Ability to Detect Biomarkers in Anastomotic Lavage Fluid.

BACKGROUND: Various reports have now established that postoperative endoscopy to examine and intervene in the process of anastomotic healing is both feasible and safe. Here we present our preliminary experience with serial postoperative endoscopy to determine its feasibility, patient acceptance and the ability to obtain and the utility of perianastomotic material for molecular analysis. METHODS: Patients undergoing LAR with ileostomy for rectal cancer were recruited for study to undergo routine serial endoscopic surveillance (SES) at three time points during the course of LAR: intraoperatively, before discharge (postoperative day 3-7) and at follow-up (postoperative day 10-28). At each endoscopy, images were captured, anastomotic tissues were lavaged and lavage fluid was retrieved. Fluid samples were analyzed using proteomics, zymography, ELISA and bacteria via 16S rRNA gene amplicon sequencing and culture of collagenolytic strains. RESULTS: SES is feasible and acceptable to this limited set of patients following LAR. Biologic analysis of perianastomotic fluids was able to detect the presence of proteins, microbiota and inflammatory mediators previously identified at anastomotic sites in animals with pathologic healing. CONCLUSION: SES can be implemented in patients undergoing LAR with a high degree of patient compliance and capture of biologic information and imaging. Application of this approach has the potential to uncover, for the first time, the natural history of normal versus pathologic anastomotic healing in patients undergoing anastomotic surgery.

Identification of Collagenolytic Bacteria in Human Samples: Screening Methods and Clinical Implications for Resolving and Preventing Anastomotic Leaks and Wound Complications.

BACKGROUND: Bacteria that produce collagen-digesting enzymes (collagenolytic bacteria) have been shown to play a critical and previously unappreciated role in anastomotic leak pathogenesis by breaking down host tissue extracellular matrix proteins. Detection of these bacteria is labor intensive, and no screening method currently exists. OBJECTIVES: We evaluated a rapid screening method developed to detect the presence of these collagenolytic bacteria in clinical samples, such as drain fluid, anastomotic tissue, or feces. DESIGN: We compared a new method of detecting collagenolytic bacterial species with a previously used technique using samples from a murine experimental model and then demonstrated the utility of this screening method in samples from patients with anastomotic complications. SETTINGS: All of the laboratory work and previous murine experiments were performed in Dr Alverdy's laboratory at the University of Chicago under institutional review board-approved protocols. PATIENTS: Samples from patients with challenging wound complications were provided by participating clinicians with verbal patient consent. Given the small number of patients, this was determined to be institutional review board exempt. MAIN OUTCOME MEASURES: Whether this analysis can influence patient management and outcomes will require additional study. RESULTS: This screening method detects numerous strains of bacteria with collagenolytic properties, including the collagenolytic species that have been implicated previously in anastomotic leak. Once collagenolytic strains are identified, they can be speciated and tested for antibiotic resistance using standard laboratory techniques. LIMITATIONS: This study is limited by the small number of patient samples tested. CONCLUSIONS: We demonstrated the potential applicability of this assay to evaluate rare and complex anastomotic complications that often require analysis beyond standard culture and sensitivity assays. Future applications of this method may allow the development of strategies to prevent anastomotic leak related to collagenolytic bacteria. See Video Abstract at http://links.lww.com/DCR/A962.

Exposure to Anti-tumor Necrosis Factor Medications Increases the Incidence of Pouchitis After Restorative Proctocolectomy in Patients With Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication after IPAA in patients with ulcerative colitis. Antibiotics represent the mainstay of treatment, suggesting a crucial role of dysbiosis in the pathogenesis of this condition. Anti-tumor necrosis factor agents have been shown to adversely impact the gut microbiome and local host immunity. OBJECTIVE: The aim of this study is to assess the effect of prior exposure to biologics on the development of pouchitis in patients who have ulcerative colitis. DESIGN: This is a retrospective case-control study. SETTINGS: This study was conducted at a tertiary-care IBD center. PATIENTS: Consecutive patients with ulcerative colitis who underwent restorative proctocolectomy between 2000 and 2010 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the incidence of pouchitis. RESULTS: Four hundred seventeen patients with ulcerative colitis who underwent IPAA were included. The incidence of pouchitis was 40.4%. There were no differences in patient demographics, disease-specific factors, surgical approach, and short-term postoperative complications between patients who developed pouchitis compared to those that did not. Patients exposed to anti-tumor necrosis factor agents or preoperative steroids were significantly more likely to develop pouchitis (anti-tumor necrosis factor: 47.9% vs 36.5%, p = 0.027; steroids: 41.7% vs 23.3%, p = 0.048). However, on multivariable analysis, only anti-tumor necrosis factor therapy was an independent predictor for pouchitis (p = 0.05). Pouchitis was not associated with adverse long-term outcomes. LIMITATIONS: The retrospective design was a limitation of this study. CONCLUSION: In a large cohort of patients undergoing IPAA for ulcerative colitis with at least a 5-year follow-up, anti-tumor necrosis factor exposure was the only independent risk factor for the development of pouchitis. These agents may "precondition" the pouch to develop pouchitis through alterations in the microbiome and/or local host immunity of the terminal ileum. See Video Abstract at http://links.lww.com/DCR/B19. LA EXPOSICIÓN A MEDICAMENTOS ANTI-TNF AUMENTA LA INCIDENCIA DE POUCHITIS DESPUÉS DE LA PROCTOCOLECTOMÍA RESTAURADORA EN PACIENTES CON COLITIS ULCEROSA:: La pouchitis es la complicación más frecuente después de la anastomosis anal de bolsa ileal en pacientes con colitis ulcerosa. Los antibióticos representan el pilar del tratamiento, lo que sugiere un papel crucial de la disbiosis en la patogénesis de esta afección. Se ha demostrado que los agentes anti-TNF tienen un impacto adverso en la microbiota intestinal y en la inmunidad local del huésped.El objetivo de este estudio es evaluar el efecto de la exposición previa a terapía biológica sobre el desarrollo de la pouchitis en pacientes con colitis ulcerosa.Estudio retrospectivo de casos y controles.Centro de tercer nivel de atención en enfermedades inflamatorias intestinales.Pacientes consecutivos con colitis ulcerosa que se sometieron a proctocolectomía restaurativa entre 2000-2010.Incidencia de pouchitis.Cuatrocientos diecisiete pacientes con colitis ulcerativa se sometieron a anastomosis anal de bolsa ileal. La incidencia de pouchitis fue del 40.4%. No hubo diferencias en la demografía del paciente, los factores específicos de la enfermedad, el abordaje quirúrgico y las complicaciones postoperatorias a corto plazo entre los pacientes que desarrollaron pouchitis en comparación con los que no lo hicieron. Los pacientes expuestos a agentes anti-TNF o esteroides preoperatorios fueron significativamente más propensos a desarrollar pouchitis (anti-TNF: 47.9% vs 36.5%, p = 0.027; esteroides: 41.7% vs 23.3%, p = 0.048). Sin embargo, en el análisis multivariable, solo la terapia anti-TNF fue un predictor independiente para la pouchitis (p = 0.05). La pouchitis no se asoció con resultados adversos a largo plazo.Diseño retrospectivo.En una gran cohorte de pacientes sometidos a anastomosis anal de bolsa ileal para la colitis ulcerosa con al menos 5 años de seguimiento, la exposición a terapía anti-TNF fue el único factor de riesgo independiente para el desarrollo de pouchitis. Estos agentes pueden "precondicionar" la bolsa para desarrollar una pouchitis a través de alteraciones en el microbioma y / o inmunidad local del huésped del íleon terminal. Vea el Resumen del video en http://links.lww.com/DCR/B19.

Abnormal Pouchogram Predicts Pouch Failure Even in Asymptomatic Patients.

BACKGROUND: Anastomotic complications after restorative total proctocolectomy with IPAA for ulcerative colitis alter functional outcomes and quality of life and may lead to pouch failure. Routine contrast enema of the pouch assesses anastomotic integrity before ileostomy reversal, but its clinical use is challenged. OBJECTIVE: The purpose of this research was to assess the relationship among preoperative clinical characteristics, abnormal pouchography, and long-term pouch complications. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at a tertiary care center between 2000 and 2010. PATIENTS: Ulcerative colitis patients with IPAA undergoing pouchography before ileostomy closure were included. MAIN OUTCOME MEASURES: Patient demographics, incidence of pouch-related complications, and findings on pouchogram were recorded. Primary outcome was pouch failure, defined as excision or permanent diversion of the ileoanal pouch. Independent predictors of pouch failure were determined by multivariate regression. RESULTS: A total of 262 patients with ulcerative colitis were included. Contrast extravasation was seen in 27 patients (10.3%): 14 (51.9%) were clinically asymptomatic at the time of pouchogram. Six (22.2%) of 27 patients with extravasation developed pouch failure despite normalization of the pouchogram before ileostomy closure. Forty patients (15.3%) were found to have pouch-anal anastomotic stenosis; only 1 developed pouch failure. Pre-IPAA serum albumin and hemoglobin levels were inversely associated with contrast extravasation (serum albumin: OR = 0.42; hemoglobin: OR = 0.77; p < 0.05). Contrast extravasation was associated with delayed takedown operation (average = 67 d), increased risk (OR = 5.25; p < 0.01), and shorter time (median = 32.0 vs 72.5 mo; HR = 5.88; p < 0.05) to pouch failure, as well as increased risk of pouch-related complications (p < 0.05). LIMITATIONS: The study was limited by its retrospective nature and small number of patients who developed pouch failure. CONCLUSIONS: Pouchography before ileostomy takedown is useful in identifying patients with ulcerative colitis at risk for postoperative complications. Radiologic resolution of IPAA-related leak does not reliably predict healing; caution is warranted in this subgroup. See Video Abstract at http://links.lww.com/DCR/A818.

Outcome of elective switching to vedolizumab in inflammatory bowel disease patients under tumor necrosis factor antagonist-maintained clinical remission.

BACKGROUND AND AIM: Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. METHODS: Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. RESULTS: A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. CONCLUSIONS: Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.

Ustekinumab Is Effective for the Treatment of Chronic Antibiotic-Refractory Pouchitis.

BACKGROUND: Chronic antibiotic-refractory pouchitis (CARP) occurs in up to 15% of patients with ulcerative colitis (UC) following proctocolectomy with ileal pouch-anal anastomosis (IPAA). AIM: To investigate the effectiveness of ustekinumab in the treatment of CARP. METHODS: This was a retrospective single-center study of UC patients with an IPAA, who subsequently developed CARP and received ustekinumab with standard Crohn's disease (CD) dosing between 2016 and 2018. Patients with CD of the pouch were excluded. Demographic, clinical, and endoscopic data were collected. Outcomes included a change in the endoscopic subscore of the Pouchitis Disease Activity Index (PDAI), change in the ulcerated surface area, clinical response, and the number of bowel movements per 24 h. RESULTS: Twenty-four patients with CARP were included for analysis. Median follow-up time was 12.9 months (IQR 7.9-16). Twelve patients (50%) had a clinical response with the median number of bowel movements within 24 h decreasing from 8 (IQR, 5-12) to 6 (IQR, 5-8) P = 0.002. Thirteen patients had pouchoscopies available post-ustekinumab treatment. In these patients, the median endoscopic subscore of the PDAI decreased from 5 (IQR, 3-6) to 4 (IQR, 2-5), P = 0.016. Likewise, among these thirteen patients, nine (69%) had an ulcerated surface area > 10% before ustekinumab treatment; after treatment with ustekinumab, only four patients (31%) still had an ulcerated surface area of > 10%. CONCLUSIONS: This is the largest study of ustekinumab treatment for patients with chronic antibiotic-refractory pouchitis. We found that ustekinumab therapy led to the improvement in clinical and endoscopic endpoints.

Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.

OBJECTIVE: The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery. BACKGROUND: We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth. METHODS: Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration. RESULTS: PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa. CONCLUSIONS: Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.