Oncologic and Functional Outcomes of Pelvic Perineal Reconstruction by Perineal Colostomy and Malone Procedure After Abdominoperineal Resection.

BACKGROUND: Abdominoperineal resection is the standard curative surgical technique for locally advanced adenocarcinoma of the lower rectum and squamous cell carcinoma of the anal canal after chemoradiotherapy. However, it requires a definitive abdominal colostomy that modifies the body appearance. OBJECTIVE: The study aim was to evaluate the combination of abdominoperineal resection with perineal colostomy reconstruction and Malone antegrade continence enema. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at the Toulouse Hospital Digestive Surgery Department. PATIENTS: All of the patients with advanced adenocarcinoma or squamous cell carcinoma who underwent abdominoperineal resection with perineal colostomy reconstruction and Malone antegrade continence enema (n = 80) between December 1999 and December 2016 were included. MAIN OUTCOME MEASURES: The main outcome was the 5-year overall survival rate. RESULTS: The 5-year overall survival was 74.89% (95% CI, 62.91%-83.50%), and the median recurrence-free survival was 107.6 months (95% CI, 65.1-198.1 mo). The median follow-up was 91.0 months (95% CI, 70.4-116.6 mo). R0 resection was obtained in 64 patients (80.0%). The median Cleveland Clinic Incontinence Score (to assess the functional outcomes) was 9.0 (interquartile range, 1.0-18.0), and it was lower in patients with advanced adenocarcinoma than with squamous cell carcinoma (7.0 (interquartile range, 2.0-18.0) vs 11.0 (interquartile range, 1.0-17.0); p = 0.01). Eleven patients (13.8%) reported perineal stains during the night, and 19 patients (23.8%) needed drugs to reduce colon motility. The rate of severe complications (Clavien-Dindo >II) was 11.7% (n = 9). Definitive colostomy was performed in 15 patients (18.8%). LIMITATIONS: This retrospective study included a small number of patients from a single center. Moreover, the functional outcome was tested with self-report questionnaires (risk of response bias). CONCLUSIONS: This study suggests that abdominoperineal resection associated with perineal reconstruction by perineal colostomy and Malone antegrade continence enema is safe and may improve patient quality of life. See Video Abstract at http://links.lww.com/DCR/B629. RESULTADOS ONCOLGICOS Y FUNCIONALES DE LA RECONSTRUCCIN PLVIPERINEAL MEDIANTE COLOSTOMA PERINEAL Y PROCEDIMIENTO DE MALONE DESPUS DE LA RESECCIN ABDOMINOPERINEAL: ANTECEDENTES:La resección abdominoperineal es la técnica quirúrgica curativa estándar para el tratamiento del adenocarcinoma localmente avanzado del recto inferior y el carcinoma a células escamosas del canal anal, después de radio-quimioterapia. Sin embargo, requiere una colostomía abdominal definitiva que modifica la apariencia corporal.OBJETIVO:El propósito del presente estudio fue el evaluar la combinación de la resección abdominoperineal con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone.DISEÑO:Estudio retrospectivo.AJUSTES:Servicio de Cirugía Digestiva del Hospital de Toulouse, Francia.PACIENTES:Se incluyeron todos los pacientes con adenocarcinoma avanzado o carcinoma de células escamosas que se sometieron a resección abdominoperineal con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone (n = 80) entre diciembre de 1999 y diciembre de 2016.PRINCIPALES MEDIDAS DE RESULTADO:El principal resultado fue la tasa de sobrevida global a 5 años.RESULTADOS:La sobrevida global a 5 años fue de 74,89% (IC del 95%, 62,91 a 83,50) y la mediana de supervivencia libre de recurrencia fue de 107,6 meses (IC del 95%, 65,1 a 198,1). La mediana de seguimiento fue de 91,0 meses (IC del 95%, 70,4-116,6). La resección R0 se obtuvo en 64 pacientes (80,0%). La mediana de puntuación de la escala de incontinencia de la Cleveland Clinic (para evaluar los resultados funcionales) fue de 9,0 [1,0; 18,0], y fue menor en pacientes con adenocarcinoma avanzado que con carcinoma de células escamosas (7,0 [2,0; 18,0] versus 11,0 [1,0; 17,0]; p = 0,01). Once pacientes (13,8%) refirieron manchado perineal nocurno y 19 pacientes (23,8%) necesitaron fármacos para reducir la motilidad del colon. La tasa de complicaciones graves (Clavien-Dindo > II) fue del 11,7% (n = 9). Se realizó colostomía definitiva en 15 (18,8%) pacientes.LIMITACIONES:Este estudio retrospectivo incluyó un pequeño número de pacientes y de un solo centro. Además, el resultado funcional se probó con cuestionarios de autoinforme (riesgo de sesgo de respuesta).CONCLUSIONES:Este estudio sugiere que la resección abdominoperineal asociada con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone es segura y puede mejorar la calidad de vida de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B629.

Combination treatment of resveratrol and capsaicin radiosensitizes pancreatic tumor cells by unbalancing DNA repair response to radiotherapy towards cell death.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers because it is highly resistant to every available therapeutic strategy, in particular conventional chemotherapy or radiotherapy (RT). Sensitizing tumor cells to existing treatments remains a good option to obtain fast and applicable results. Considering that ionizing radiations induce radiolysis-derived reactive oxygen species (ROS), we hypothesized that ROS-inducing bioactive food components (BFCs) could exacerbate ROS-related cell damages, including DNA double stranded breaks (DSBs), leaving the cellular ROS scavenging systems overwhelmed, and precipitating tumor cell death. Combination of resveratrol and capsaicin radiosensitized radiosensitive tumor cells, but RT did not increase BFC combination toxicity in radioresistant tumor cells. BFC addition to RT increased ROS production and led to significant tumor volume reduction in xenografted mouse preclinical model. Strikingly, BFCs inhibited RT-induced DNA damage molecular response by strongly limiting the first steps of DSB repair, and by keeping cells in cell cycle, provoking exacerbated intrinsic apoptosis. This study positions BFCs as potent radiosensitizers when combined, and identifies an actionable molecular pathway by resveratrol and capsaicin combination.

Resveratrol and capsaicin used together as food complements reduce tumor growth and rescue full efficiency of low dose gemcitabine in a pancreatic cancer model.

Pancreatic adenocarcinoma, highly resistant to all current anti-cancer treatments, necessitates new approaches promoting cell death. We hypothesized that combined actions of several Bioactive Food Components (BFCs) might provide specific lethal effect towards tumor cells, sparing healthy cells. Human tumor pancreatic cell lines were tested in vitro for sensitivity to resveratrol, capsaicin, piceatannol, and sulforaphane cytotoxic effects. Combination of two or three components showed striking synergetic effect with gemcitabine in vitro. Each BFC used alone did not affect pancreatic tumor growth in a preclinical in vivo model, whereas couples of BFCs had anti-tumor activity. In addition, tumor toxicity was similar using gemcitabine alone or a combination of BFCs and two thirds of gemcitabine dose. Moreover, BFCs enhanced fibrotic response as compared to gemcitabine treatment alone. Reactive oxygen species (ROS) and apoptosis increases were observed, while cell cycle was very mildly affected. This study raises the possibility to use BFCs as beneficial food complements in the therapy of pancreatic adenocarcinoma, especially for patients unable to receive full doses of chemotherapy.