Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn's disease.

BACKGROUND: Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence (POR) of Crohn's disease (CD). However, its prognostic value is uncertain, in part, due to difficulties studying it non-invasively. AIM: To evaluate the prognostic value of pre-operative radiographic mesenteric parameters for early endoscopic POR (ePOR). METHODS: We conducted a retrospective cohort study of CD subjects ≥ 12 years who underwent ileocecal or small bowel resection between 1/1/2007 to 12/31/2021 with computerized tomography abdomen/pelvis ≤ 6 months pre-operatively and underwent ileocolonoscopy ≤ 15 months post-operatively. Visceral adipose tissue (VAT) volume (cm3), ratio of VAT:subcutaneous adipose tissue (SAT) volume, VAT radiodensity, and ratio of VAT:SAT radiodensity were generated semiautomatically. Mesenteric lymphadenopathy (LAD, largest lymph node > 10 mm) and severe vasa recta (VR) engorgement (diameter of the VR supplying diseased bowel ≥ 2 × VR supplying healthy bowel) were derived manually. The primary outcome was early ePOR (Rutgeert's score ≥ i2 on first endoscopy ≤ 15 months post-operatively) and the secondary outcome was ePOR severity (Rutgeert's score i0-4). Regression analyses were performed adjusting for demographic and disease-related characteristics to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: Of the 139 subjects included, 45% of subjects developed early ePOR (n = 63). VAT radiodensity (aOR 0.59, 95%CI: 0.38-0.90) and VAT:SAT radiodensity (aOR 8.54, 95%CI: 1.48-49.28) were associated with early ePOR, whereas, VAT volume (aOR 1.23, 95%CI: 0.78-1.95), VAT:SAT volume (aOR 0.80, 95%CI: 0.53-1.20), severe VR engorgement (aOR 1.53, 95%CI: 0.64-3.66), and mesenteric LAD (aOR 1.59, 95%CI: 0.67-3.79) were not. Similar results were observed for severity of ePOR. CONCLUSION: VAT radiodensity is potentially a novel non-invasive prognostic imaging marker to help risk stratify CD patients for POR.

Preoperative CT Indices Predict Nonreach Before IPAA.

BACKGROUND: IPAA aims to restore continence to patients after total proctocolectomy. However, some patients have inadequate small-bowel mesenteric length to achieve reconstruction. No preoperative risk stratification tools of native anatomy exist. OBJECTIVE: We report CT-guided measurements of anatomic landmarks to predict nonreach before IPAA. DESIGN: This is a single-institution retrospective analysis of a prospective database. SETTING: This study was conducted at Cedars-Sinai between January 2007 and December 2021. PATIENTS: Patients with IBD undergoing a 2- or 3-stage IPAA with a preoperative abdominal CT using either an enterography protocol or IV contrast sufficient to visualize mesenteric vasculature were included in the study. CT mesenteric indices were assessed, including total length (representing length required for the pouch to reach the anal canal), mesenteric length (inherent length of small-bowel mesentery), and mobilization length (the difference between total length and mesenteric length). MAIN OUTCOME MEASURES: The primary outcome was IPAA nonreach. The secondary outcomes were association of clinical variables and CT mesenteric indices. RESULTS: Six of 59 patients (10%) experienced nonreach. Mobilization length was longer in the nonreach group by 5.8 cm ( p = 0.01), and mesenteric length was shorter by 3.5 cm ( p = 0.04). Mobilization length ≥17 cm provided 100% sensitivity and 69% specificity (OR 1.46, area under the curve 0.84, p = 0.004) for nonreach. Similarly, a mesenteric length <14.6 cm demonstrated 100% sensitivity and 49% specificity for IPAA nonreach (area under the curve 0.75, p = 0.03). LIMITATIONS: The retrospective nature of the study precluded a standardized imaging protocol. External validation will be required because of the small sample size. CONCLUSIONS: CT-based measurements of length, specifically mesenteric and mobilization length, predict nonreach before IPAA. This method is noninvasive, readily available, and may be useful for preoperative patient counseling and operative planning. See Video Abstract at http://links.lww.com/DCR/C140 . LOS NDICES DE TOMOGRAFA COMPUTARIZADA PREOPERATORIA PREDICEN LA AUSENCIA DE ALCANCE ANTES DE LA ANASTOMOSIS DEL RESERVORIO ILEALANAL: ANTECEDENTES:La anastomosis del reservorio ileoanal tiene como objetivo restaurar la continencia en los pacientes después de una proctocolectomía total. Sin embargo, algunos pacientes tienen una longitud mesentérica del intestino delgado inadecuada para lograr la reconstrucción. No existen herramientas de estratificación del riesgo preoperatorio de la anatomía nativa.OBJETIVO:Informamos mediciones guiadas por tomografía computarizada de puntos de referencia anatómicos para predecir la falta de alcance antes de la anastomosis ileoanal con reservorio.DISEÑO:Este es un análisis retrospectivo de una sola institución de una base de datos prospectiva.AJUSTE:Este estudio se realizó en Cedars-Sinai entre Enero de 2007 y Diciembre de 2021.PACIENTES:Pacientes con enfermedad inflamatoria intestinal que se someten a una anastomosis anal con reservorio ileal en 2 o 3 etapas con una tomografía computarizada abdominal preoperatoria utilizando un protocolo de enterografía o contraste intravenoso suficiente para visualizar la vasculatura mesentérica. Se evaluaron los índices mesentéricos de tomografía computarizada, incluida la longitud total (que representa la longitud requerida para que la bolsa alcance el canal anal), la longitud mesentérica (longitud inherente del mesenterio del intestino delgado) y la longitud de movilización (la diferencia entre la longitud total y la longitud mesentérica).PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue falta de alcance de la anastomosis del reservorio ileoanal. Los resultados secundarios fueron la asociación de variables clínicas y los índices mesentéricos de tomografía computarizada.RESULTADOS:Seis de 59 (10%) pacientes experimentaron falta de alcance. La longitud de movilización fue mayor en el grupo sin alcance en 5,8 cm ( p = 0,01) y la longitud mesentérica fue menor en 3,5 cm ( p = 0,04). La longitud de movilización ≥17 cm proporcionó una sensibilidad del 100% y una especificidad del 69% (OR 1,46, AUC 0,84, p = 0,004) para la falta de alcance. De manera similar, una longitud mesentérica <14,6 cm demostró una sensibilidad del 100% y una especificidad del 49% para la falta de alcance de la anastomosis del reservorio ileoanal (AUC 0,75, p = 0,03).LIMITACIONES:La naturaleza retrospectiva del estudio impidió un protocolo de imágenes estandarizado. Se requerirá una validación externa debido al pequeño tamaño de la muestra.CONCLUSIONES:Las mediciones de longitud basadas en tomografía computarizada, específicamente la longitud mesentérica y de movilización, predicen la falta de alcance antes de la anastomosis anal con bolsa ileo. Este método no es invasivo, está fácilmente disponible y puede ser útil para el asesoramiento preoperatorio del paciente y la planificación quirúrgica. Consulte el Video Resumen en https://links.lww.com/DCR/C140 . (Traducción-Dr. Yesenia Rojas-Khalil ).

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.

Abdominal Visceral Fat Area and Chronic Pouchitis after Ileal Pouch-Anal Anastomosis.

Chronic pouchitis (CP) after ileal pouch-anal anastomosis is a significant clinical problem. Adipose tissues produce antiinflammatory cytokines and chemokines. We evaluated the association between abdominal visceral fat area (VFA) and CP. Patients with a preoperative CT evaluation were included. The diagnosis of CP was confirmed in all cases by endoscopy with afferent ileal limb intubation. Patients were allocated into groups of high VFA and low VFA. The study cohort of 52 patients had a median body mass index of 22 (range, 14-32). Indications for surgery were medically refractory disease in 46 (88%) patients and cancer/dysplasia in six (12%) patients. Median VFA was 27.1 (range, 1-144). Six (12%) patients developed CP. Low VFA patients were significantly younger (29 vs 45 years; P < 0.0001), had lower body mass index (20.4 vs 24.7; P < 0.0001), had surgery more commonly for medically refractory disease than for cancer or dysplasia (100 vs 77%; P = 0.02), and had a higher incidence of CP than high VFA patients (23 vs 0%; P = 0.02). Multiple linear regression analysis demonstrated that only low VFA was associated with CP (P = 0.009). An association is present between VFA and CP after ileal pouch-anal anastomosis, implicating adipocytes in the pathogenesis of inflammatory bowel disease.