MicroRNAs (miRs) have been shown to negatively regulate gene expression by binding to mRNAs, and they play an important role in various physiological processes and ma lignancies. A previous study identified mature miR-126-3p as an onco-microRNA that is generated from the pre-microRNA, miR-126. Although miR-126 also generates mature miR-126-5p, its function is less clear. In the present study, the relationship between miR-126-5p/3p expression levels and overall survival in 109 patients with acute myeloid leukemia (AML) who received intensive therapy were evaluated. Higher expression levels above the median value of miR-126-5p/3p were correlated with a poorer overall survival. The hazard ratio and 95% confidence intervals (95% CI) for the higher expression group relative to the lower expression group of miR-126-5p/3p were 2.098 (95% CI: 1.075–4.228) and 1.958 (95% CI: 1.001–3.927), respectively. An interaction was not observed between the hazard ratios of miR-126-5p and miR-126-3p (p=0.73). Transfection of the mimic miR-126-5p into the AML cell line, KG-1, resulted in a decrease in the sensitivity to cytarabin and the expression level of Klotho mRNA as well as the elevation in the phosphorylation of Akt. The results of the present study demonstrated that higher expression levels of miR-126-5p/3p in patients with AML resulted in a poorer prognosis. Furthermore, miR-126-5p elevated the phosphorylation of Akt.

BACKGROUND: Recent studies have clarified that near-infrared observation using indocyanine green has the advantage of evaluating perfusion of the anastomotic site, especially in rectal cancer surgery, resulting in a reduction in anastomotic leak. OBJECTIVE: The aim of this study was to evaluate the efficacy of near-infrared observation for reducing the anastomotic leak after stapled side-to-side anastomosis in colon cancer surgery. DESIGN: This was a retrospective propensity score case-matched study. SETTINGS: The study was conducted at 3 institutions in the Yokohama Clinical Oncology Group. PATIENTS: From January 2011 to December 2019, patients who underwent colon cancer surgery with stapled side-to-side anastomosis were included. MAIN OUTCOME MEASURES: The main outcome was the percentage of anastomotic leak within 30 days after surgery. RESULTS: A total of 1034 patients were collected. There were 532 patients who underwent near-infrared observation and 502 who did not. A total of 370 patients were matched to the near-infrared and non-near-infrared groups. In the near-infrared group, 12 patients (3.2%) were judged to have poor perfusion (4 patients) and no perfusion (8 patients), so the planned transection point was changed. There were no cases of anastomotic leak among these 12 patients. The anastomotic leak rates were 3.5% (13/370) in the non-near-infrared group and 0.8% (3/370) in the near-infrared group. The anastomotic leak and reoperation rates were significantly lower in the near-infrared group than in the non-near-infrared group (OR, 0.224; 95% CI, 0.063–0.794, p = 0.001; OR, 0.348; 95% CI, 0.124–0.977, p = 0.036). LIMITATIONS: Although we reduced selection bias by performing propensity score matching, this was a retrospective study and was not randomized. CONCLUSION: This large-scale case-matched study showed that assessing perfusion by near-infrared observation significantly reduced the anastomotic leak and reoperation rates after stapled side-to-side anastomosis in colon cancer surgery and may be better suited to colo-colonic anastomosis. Video Abstract at http://links.lww.com/DCR/B513. Japanese Clinical Trials Registry: UMIN-CTR000039977 EVALUACIÓN DEL EFECTO DE LA OBSERVACIÓN INTRAOPERATORIA CON INFRARROJO CERCANO SOBRE LA FUGA ANASTOMÓTICA DESPUÉS DE UNA ANASTOMOSIS LATERO-LATERAL CON ENGRAPADORA EN LA CIRUGÍA DE CÁNCER DE COLON MEDIANTE EL EMPAREJAMIENTO POR PUNTAJES DE PROPENSIÓN ANTECEDENTES: Estudios recientes han aclarado que la observación con infrarrojo cercano con verde de indocianina tiene la ventaja de evaluar la perfusión del sitio anastomótico, especialmente en la cirugía de cáncer de recto, lo que resulta en una reducción de la fuga anastomótica. OBJETIVO: El objetivo de este estudio fue evaluar la eficacia de la observación con infrarrojo cercano para reducir la fuga anastomótica después de una anastomosis latero-lateral con engrapadora en la cirugía de cáncer de colon. DISEÑO: Este fue un estudio retrospectivo emparejado con puntaje de propensión. AJUSTE: El estudio se llevó a cabo en tres instituciones del Grupo de Oncología Clínica de Yokohama. PACIENTES: Desde enero de 2011 hasta diciembre de 2019, se incluyeron pacientes que se sometieron a cirugía de cáncer de colon con anastomosis latero-lateral con engrapadora. PRINCIPALES MEDIDAS DE RESULTADO: El resultado principal fue el porcentaje de fuga anastomótica dentro de los 30 días posteriores a la cirugía. RESULTADOS: Se recogió un total de 1034 pacientes. Hubo 532 pacientes que se sometieron a observación con infrarrojo cercano y 502 que no. Un total de 370 pacientes fueron emparejados con los grupos de infrarrojo cercano y no infrarrojo cercano. En el grupo de infrarrojo cercano, se consideró que 12 casos (3,2%) tenían mala perfusión (4 casos) y ninguna perfusión (8 casos), por lo que se cambió el punto de transección planificado. No hubo casos de fuga anastomótica entre estos 12 casos. Las tasas de fuga anastomótica fueron del 3,5% (13/370) en el grupo sin infrarrojo cercano y del 0,8% (3/370) en el grupo con infrarrojo cercano. Las tasas de fuga anastomótica y de reintervención fueron significativamente menores en el grupo con infrarrojo cercano que en el grupo sin infrarrojo cercano (razón de posibilidades 0,224, intervalo de confianza del 95% 0,063-0,794, p = 0,001; razón de posibilidades 0,348, intervalo de confianza del 95% 0,124 -0,977, p = 0,036, respectivamente). LIMITACIONES: Aunque se redujo el sesgo de selección al realizar el emparejamiento por puntaje de propensión, este fue un estudio retrospectivo y no fue aleatorio. CONCLUSIÓN: Este estudio de casos emparejados a gran escala demostró que la evaluación de la perfusión mediante la observación con infrarrojo cercano redujo significativamente la fuga anastomótica y las tasas de reintervención después de la anastomosis latero-lateral con engrapadora en la cirugía de cáncer de colon y puede ser más adecuada para la anastomosis colo-colónica. Consulte Video Resumen en http://links.lww.com/DCR/B513. Registro japonés de ensayos clínicos: UMIN-CTR000039977

Regorafenib is a small molecule inhibitor of tyrosine kinases, and has been shown to improve the outcomes of patients with advanced colorectal cancer and advanced gastrointestinal stromal tumors. The transport profiles of regorafenib by various transporters were evaluated. HEK293/organic anion transporting polypeptide 1B1 (OATP1B1) cells exhibited increased drug sensitivity to regorafenib. Regorafenib inhibited the uptake of Key words regorafenib; IC 50 ; multidrug resistance protein 2; organic anion transporting polypeptide 1B1; vectorial drug transport Regorafenib has been developed as a molecular targeted medicine for patients with metastatic colorectal cancer and advanced gastrointestinal stromal tumors, and inhibits certain tyrosine kinases. The biological effects of receptor tyrosine kinase activation are mediated by a complex cascade of intracellular signaling molecules that are potential targets for therapy, including the Raf, mitogen-activated protein extracellular kinase (MEK), and extracellular signal-regulated kinase (ERK) pathways. 1) Regorafenib is a multikinase inhibitor that targets Raf serine/threonine kinases and the vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor (PDGF) receptor-β, c-Kit, Flt3, and p38 tyrosine kinases, which blocks VEGF-and PDGF-dependent angiogenesis.2)

BACKGROUND:The examination of the efficacy of nearinfrared imaging using indocyanine green in laparoscopic lateral pelvic lymph node dissection remains insufficient. OBJECTIVE:The aim of this study was to examine whether near-infrared imaging contributed to an increase in the total number of harvested lateral pelvic lymph nodes in laparoscopic lateral pelvic lymph node dissection.DESIGN: This was a retrospective, multi-institutional study with propensity score matching. SETTINGS:We conducted this study within the framework of the Yokohama Clinical Oncology Group in Japan. PATIENTS:The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic lateral pelvic lymph node dissection between January 2013 and February 2018. MAIN OUTCOME MEASURES:The total number of harvested lateral pelvic lymph nodes was compared in laparoscopic lateral pelvic lymph node dissection with and without near-infrared imaging.RESULTS: A total of 172 eligible patients were included; 84 of these patients underwent laparoscopic surgery with near-infrared imaging. After propensity score matching, 58 patients were matched in each of the near-infrared and the non-near-infrared groups. The operation time in the near-infrared group was significantly longer than that in the non-near-infrared group (426 vs 369 min), and the amount of intraoperative blood loss in the near-infrared group was significantly smaller than that in the non-near-infrared group (13 vs 110 mL). The total number of harvested lateral pelvic lymph nodes in the near-infrared group was significantly higher than that in the non-near-infrared group (14 vs 9). There were no significant differences in the postoperative complication rates of the 2 groups. LIMITATIONS:The limitations of the present study include its retrospective design. CONCLUSIONS:This study revealed that laparoscopic lateral pelvic lymph node dissection combined with near-infrared imaging could increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. See Video Abstract at http:// links.lww.com/DCR/B800. This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 (http://www.umin.ac.jp/ctr/ index.htm).