clinicaltrials.gov Identifier: NCT02431455.
DCs are critical in initiating immune responses by cross-priming of tumor antigens to T cells. Previous results showed that NK cells inhibited DC-mediated cross-presentation of tumor Ags both in vivo and in vitro. In this study, enhanced Ag presentation was observed in draining lymph nodes in TRAIL−/− and DR5−/− mice compared to that of wild-type mice. NK cells inhibit DC cross-priming of tumor antigens in vitro, but not direct presentation of endogenous antigens. NK cells lacking TRAIL but not perforin were not able to inhibit DC cross-priming of tumor Ags. DCs that lack expression of TRAIL receptor DR5 were less susceptible to NK cell-mediated inhibition of cross-priming and cross-linking of DR5 receptor led to reduced generation of MHC class I-antigen peptide complex, followed by attenuated cross-priming of CD8+ T cells. In addition, key molecules involved in the TRAIL/DR5 pathway during DC/NK cell interactions were determined. In summary, these data indicate a novel alternative pathway for DC/NK cell interactions in anti-tumor immunity and may reflect homeostasis of both DCs and NK cells for regulation of CD8+ T cell function in physiological conditions.
BACKGROUND: The optimal strategy for colonic polyps not amenable to traditional endoscopic polypectomy is unknown. Endoscopic step up is a promising strategy for definitive treatment. OBJECTIVE: The purpose of this study was to determine whether endoscopic step up leads to improved outcomes and decreased costs compared with planned colectomy for endoscopically unresectable colon polyps. DESIGN: This was a retrospective review of a prospective database. SETTING: The study was conducted at a tertiary referral center. PATIENTS: Consecutive patients referred for endoscopically unresectable colon polyps 15 to 50 mm in size were included. INTERVENTIONS: Patients underwent planned colectomy or endoscopic step up at the surgeon’s discretion. Endoscopic step up began with diagnostic colonoscopy in the operating room. If the polyp was amenable to endoscopic removal, endoscopic mucosal resection or endoscopic submucosal dissection was performed with progression to combined endoscopic–laparoscopic surgery or laparoscopic colectomy, as indicated. MAIN OUTCOME MEASURES: The primary outcome was 30-day adverse events. We also examined length of stay, hospital charges, insurer payments, and polyp recurrence. RESULTS: A total of 52 patients underwent planned colectomy (48 laparoscopic), and 38 underwent endoscopic step up (28 endoscopic mucosal resection, 2 endoscopic submucosal dissection, 6 combined endoscopic-laparoscopic surgery, and 2 colectomy). Compared with planned colectomy, endoscopic step-up patients had fewer complications (13% vs 33%; p = 0.03) and shorter length of stay (median, 0 vs 4 d; p < 0.001). There was 1 readmission in the endoscopic step-up group and 5 in the planned colectomy group. Endoscopic step-up patients had lower hospital costs ($4790 vs $13,004; p < 0.001) and insurer payments ($2431 vs $19,951; p < 0.001). One-year polyp recurrence-free survival was 84% (95% CI, 67%–93%) in endoscopic step-up patients. All of the recurrences were benign, <1 cm, and managed endoscopically. LIMITATIONS: The study was limited by its nonrandomized design and short follow-up. CONCLUSIONS: An endoscopic step-up approach to colon polyps is associated with less morbidity, decreased healthcare costs, and colon preservation in 95% of patients. Additional studies are needed to evaluate long-term quality of life and polyp recurrence in this group. See Video Abstract at http://links.lww.com/DCR/B188. Endoscopic Step Up: Una Alternativa a Colectomía Para Preservación de Colon Con los Propósitos de Mejorar Resultados y Reducir Costos en Pacientes Con Pólipos Neoplásicos Avanzados ANTECEDENTES: Se desconoce la estrategia óptima para los pólipos de colon no susceptibles a la polipectomia endoscópica tradicional. Endoscopic Step Up es una estrategia prometedora para el tratamiento definitivo. OBJETIVO: Determinar si Endoscopic Step Up produce mejores resultados y menores costos en comparación con la colectomía programada para pólipos de colon endoscópicamente no resecables. DISEÑO: Revisión retrospectiva de una base de datos prospectiva. ENTORNO CLINICO: Centro de referencia de tercer nivel. PACIENTES: Pacientes consecutivos remitidos para pólipos de colon endoscópicamente irresecables de tamaño 15-50 mm. INTERVENCIONES: Los pacientes se sometieron a colectomía programada o Endoscópico Step Up a discreción del cirujano. Endoscopic Step Up comenzó con una colonoscopia diagnóstica en el quirófano. Si el pólipo era susceptible de extirpación endoscópica, la resección endoscópica de la mucosa o la disección submucosa endoscópica se realizaba con progresión a cirugía endoscópica-laparoscópica combinada o colectomía laparoscópica, según a cosnideraciones clínicas en el transoperatorio. PRINCIPALES MEDIDAS DE VALORACION: El resultado primario fue los eventos adversos a 30 días. Duración de la estadía hospitalaria, los cargos hospitalarios, los pagos de las aseguradoras y la recurrencia de pólipos también fueron examinados. RESULTADOS: Un total de 52 pacientes se sometieron a colectomía programada (48 laparoscópicas) y 38 se sometieron a Endoscopic Step Up (28 resección endoscópica de la mucosa, 2 disección submucosa endoscópica, 6 cirugía endoscópica-laparoscópica combinada y 2 colectomía). En comparación con la colectomía programada los pacientes endoscópicos Step Up tuvieron menos complicaciones (13% versus 33%, p = 0.03) y una estadía hospitalaria más corta (mediana 0 versus 4 días, p <0.001). Hubo 1 reingreso hospitalario en el grupo Endoscopic Step Up y 5 en el grupo de colectomía programada. Los pacientes endoscópicos Step Up tuvieron costos hospitalarios más bajos ($ 4,790 versus $ 13,004, p <0,001) y pagos de la aseguradora ($ 2,431 versus $ 19,951, p <0,001). La supervivencia libre de recurrencia de pólipos a un año fue del 84% (IC 95% 67-93) en pacientes endoscópicos Step Up. Todas las recurrencias fueron benignas, <1 cm, y manejadas endoscópicamente. LIMITACIONES: Diseño no aleatorizado y seguimiento corto. CONCLUSIONES: El abordaje endoscópico Step Up para pólipos de colon se asocia con menos morbilidad, disminución de los costos de atención médica y preservación del colon en el 95% de los pacientes. Se ocupan más estudios para evaluar la calidad de vida a largo plazo y la recurrencia de pólipos en este grupo. Consulte Video Resumen en http://links.lww.com/DCR/B188. (Traducción—Dr Adrián Ortega Robles)
We sought to determine the accuracy of the Model for End-Stage Liver Disease and the Mayo Clinic Postoperative Mortality Risk in Patients with Cirrhosis Calculator in patients with ascites who underwent colorectal surgery. The National Surgical Quality Improvement Program database was queried for patients with ascites who underwent a major colorectal operation. Predicted 90-day mortality rate based on the Model for End-Stage Liver Disease and 30-day mortality based on the Mayo Clinic Postoperative Mortality Risk in Patients with Cirrhosis Calculator were compared with observed 30-day mortality. The cohort contained 3137 patients with ascites who underwent a colorectal operation. The Model for End-Stage Liver Disease predicted that 252 (8 %) of patients with ascites undergoing colorectal operations would die within 90 days postoperatively, yet we observed 821 deaths (26 % mortality) within 30 days after surgery (p < 0.001). The Mayo Clinic Postoperative Mortality Risk in Patients with Cirrhosis Calculator predicted that 491 (16.6 % mortality) of patients with ascites undergoing colorectal operations would die within 30 days postoperatively, yet we observed 707 (23.9 % mortality) at 30 days (p < 0.01). We concluded that the current risk prediction models significantly under predict mortality in patients with ascites who underwent colorectal surgery.
BACKGROUND: Hospital readmission and anastomotic leak following colorectal resection have a negative impact on patients, surgeons, and the health care system. Novel markers of patients unlikely to experience these complications are of value in avoiding readmission. OBJECTIVE: This study aimed to determine the predictive value of C-reactive protein for readmission and anastomotic leak within 30 days following colorectal resection. DESIGN: This is a retrospective review of a prospectively compiled single-institution database. PATIENTS: From January 1, 2013, to July 20, 2017, consecutive patients undergoing elective colorectal resection with anastomosis without the presence of proximal intestinal stoma, who had C-reactive protein measured on postoperative day 3, were included. MAIN OUTCOME MEASURES: The primary outcome measured was the predictive value of C-reactive protein measured on postoperative day 3 for readmission or anastomotic leak within 30 days after colorectal resection. RESULTS: Of the 752 patients examined, 73 (10%) were readmitted within 30 days of surgery and 17 (2%) had an anastomotic leak. Mean C-reactive protein in patients who neither had an anastomotic leak nor were readmitted (127 ± 77 mg/L) was lower than for patients who were readmitted (157 ± 96 mg/L, p = 0.002) and lower than for patients who had an anastomotic leak (228 ± 123 mg/L, p = 0.0000002). The area under the receiver operating characteristic curve for the diagnostic accuracy of C-reactive protein for readmission was 0.59, with a cutoff value of 145 mg/L, generating a 93% negative predictive value. The area under the curve for the diagnostic accuracy of C-reactive protein for anastomotic leak was 0.76, with a cutoff value of 147 mg/L generating a 99% negative predictive value. LIMITATIONS: This study was limited by its retrospective design and because all patients were treated at a single center. CONCLUSIONS: Patients with a C-reactive protein below 145 mg/L on postoperative day 3 after colorectal resection have a low likelihood of readmission within 30 days, and a very low likelihood of anastomotic leak. See Video Abstract at http://links.lww.com/DCR/A761.
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