SLC7A11 and the glutathione pathway as novel prognostic markers in resectable pancreatic ductal adenocarcinoma: A metabolomics study of clinical specimens.

BACKGROUND/OBJECTIVES: Despite the poor prognosis associated with pancreatic ductal adenocarcinoma (PDAC), there remains a lack of clarity regarding the metabolic pathways and their significant impact on its phenotype. Therefore, we aimed to utilize metabolomics to capture changes in clinical PDAC tissues and elucidate the significant metabolic pathways close to its phenotypes. METHODS: This basic research was retrospectively validated using database research, immunohistochemistry, and protein analysis based on the findings obtained from metabolomics using clinical tissues collected from prospectively registered patients with PDAC. mRNA expression analysis using a database and protein analysis using archived clinical specimens was performed to validate the candidate pathways identified using metabolomics. Between-group comparisons were analyzed using paired t-tests and log-rank test, and Kaplan-Meier curves illustrated survival times. RESULTS: Patients subjected to metabolomics revealed a significant increase in glutathione disulfide levels in PDAC tissues when compared to normal pancreatic tissues. The Cancer Genome Atlas database analysis revealed significant changes in glutathione pathway-related mRNAs in PDAC compared to that in the normal pancreas. Protein analysis of previously resected specimens demonstrated a significant increase in SLC7A11 expression in PDAC tissues. The abundance ratio of SLC7A11 isoforms was associated with the post-operative prognosis in resectable PDAC. CONCLUSION: Glutathione disulfide levels were significantly increased in clinical PDAC metabolomics. Additionally, increased mRNA and protein expression in SLC7A11 was observed in PDAC. Furthermore, the SLC7A11 isoform abundance ratio may be a valuable prognostic marker in patients with resectable PDAC.

Effects of neoadjuvant chemotherapy for patients with obstructive colon cancer: A multicenter propensity score-matched analysis (YCOG2101).

Aim: Obstructive colon cancer is locally advanced colon cancer with poor prognosis. However, the effect of neoadjuvant chemotherapy (NAC) on obstructive colon cancer remains unclear. Therefore, this study aimed to investigate the safety and efficacy of NAC in patients with obstructive colon cancer. Methods: From January 2012 to December 2017, we collected patient data for clinical stage II/III obstructive colon cancer at seven Yokohama Clinical Oncology Group (YCOG) institutions. The long-term outcomes of the NAC and non-NAC groups were analyzed retrospectively after adjusting for patients' background characteristics using propensity score matching. Results: Among the 202 eligible patients, propensity score matching extracted 51 patients each for the NAC and non-NAC groups. After matching, the groups showed no marked differences in the background factors. All the patients in the NAC group underwent diverting stoma construction. Nineteen patients (37.3%) experienced grade 3-4 adverse events during NAC. The incidence of postoperative complications was similar between groups. The 5-year progression-free survival rates were 75.8% in the NAC group and 63.0% in the non-NAC group (p = 0.22, log-rank test). The 5-year overall survival rates were 88.5% in the NAC group and 78.8% in the non-NAC group (p = 0.09, log-rank test). Conclusion: Although NAC was feasible for obstructive colon cancer after diverting stoma construction, its effects on long-term outcomes could not be proven.

Redo laparoscopic colorectal resection: a retrospective analysis with propensity score matching.

PURPOSE: Reports of redo laparoscopic colorectal resection (Re-LCRR) are scarce. In order to evaluate the safety and short-term outcomes of Re-LCRR, we performed a matched case-control analysis of patients who underwent this procedure for colorectal cancer. METHOD: This was a retrospective, monocentric study that included patients who underwent Re-LCRR for colorectal cancer between January 2011 and December 2019 at our institution. The patients were compared to a 2:1 matched sample. Matching was conducted based on age, sex, BMI, surgical procedure, and clinical stage. RESULT: Twenty-nine patients underwent Re-LCRR (RCRR group) and were compared to 58 patients selected by matching who underwent LCRR as primary resection (PCRR group). The median of age of the 29 patients of RCRR group was 75 (IQR 56-81) years and the RCRR group included 14 males. The median operative time of the RCRR group was 167 (IQR 126-232) minutes, and the median intraoperative blood loss was 5 (IQR 2-35) ml. In the RCRR group, there were no cases that required conversion to laparotomy. The short-term outcomes of the two groups did not differ to a statistical extent with respect to operative time (p = 0.415), intraoperative blood loss (p = 0.971), rate of conversion to laparotomy (p = 0.477), comorbidity (p = 0.215), and postoperative hospital stay (p = 0.809). No patients in either group experienced postoperative anastomotic leakage or required re-operation due to postoperative complications, and there was no procedure-related death. However, in terms of oncological factors, although there was no difference in the number of cases with a positive radical margin between the two groups (p = 1.000), the number of harvested lymph nodes in the RCRR group was significantly lower than that in the PCRR group (p = 0.015) and the RCRR group included 10 cases with less than 12 harvested lymph nodes. CONCLUSION: Re-LCRR is associated with good short-term results and can be safely performed; however, the number of harvested lymph nodes is significantly reduced in comparison to primary resection cases, and further studies are needed to evaluate its long-term prognosis.

Preoperative prevalence and risk factors of deep-vein thrombosis in Japanese surgical patients with ulcerative colitis: a retrospective investigational study.

PURPOSE: The purpose of this study was to clarify the perioperative deep-vein thrombosis (DVT) prevalence and its risk factors in surgical ulcerative colitis (UC) patients by comparing the results with those in surgical colorectal cancer (CRC) patients at a high risk of perioperative venous thrombosis. METHODS: This retrospective, observational study included patients who underwent surgery for UC or CRC between January 2013 and October 2019. Consecutive surgical patients with a positive D-dimer assay result (≥ 1.0 µg/ml) underwent lower-extremity venous ultrasonography. The prevalence and risk factors for preoperative DVT were examined in UC patients. RESULTS: A total of 101 UC patients and 593 CRC patients were deemed eligible. Among the D-dimer positive cases, there were no significant differences between the two groups in the preoperative DVT prevalence (UC: 21.8% vs. CRC: 28.8%, p = 0.151), distal type (18.8% vs. 27.2%, p = 0.086), or proximal type (5.9% vs. 4.2%, p = 0.434). Furthermore, multivariate analyses showed that an older age, overweight status, poor ASA status, and a high preoperative dose of steroid were independent risk factors for preoperative DVT in UC surgical patients. CONCLUSIONS: The risk of perioperative thrombosis in UC patients was considered similar to that in CRC, so active thromboprophylaxis should be administered to UC patients while paying attention to bleeding. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000042004 ( http://www.umin.ac.jp/ctr/index.htm ).

Near-Infrared Imaging Using Indocyanine Green for Laparoscopic Lateral Pelvic Lymph Node Dissection for Clinical Stage II/III Middle-Lower Rectal Cancer: A Propensity Score-Matched Cohort Study.

BACKGROUND: The examination of the efficacy of near-infrared 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).IMÁGENES CASI-INFRARROJAS UTILIZANDO VERDE DE INDOCIANINA EN LA DISECCIÓN LAPAROSCÓPICA DE GANGLIOS LINFÁTICOS PÉLVICOS LATERALES EN CASOS DE CÁNCER DE RECTO MEDIO-INFERIOR DE ESTADIO CLÍNICO II / III: ESTUDIO DE COHORTES CON PUNTUACIÓN DE PROPENSIÓNANTECEDENTES:El examen de la eficacia de las imágenes casi-infrarrojas utilizando le verde de indocianina en la disección laparoscópica de los ganglios linfáticos pélvicos laterales sigue siendo insuficiente.OBJETIVO:El objetivo de este estudio fue examinar si las imágenes casi-infrarrojas contribuyeron a un aumento en el número total de ganglios linfáticos pélvicos laterales recolectados durante su disección laparoscópica.DISEÑO:Estudio retrospectivo, multi-institucional con emparejamiento por puntuación de propensión.AJUSTES:Estudio realizado dentro el marco establecido por el Grupo de Oncología Clínica de Yokohama, Japón.PACIENTES:La población estudiada incluyó pacientes consecutivos con cáncer de recto medio-bajo (estadio clínico II a III) que se sometieron a una disección laparoscópica de los ganglios linfáticos pélvicos laterales entre enero de 2013 y febrero de 2018.PRINCIPALES RESULTADOS MEDIDAS:El número total de ganglios linfáticos pélvicos laterales extraídos se comparó en la disección laparoscópica de ganglios linfáticos pélvicos laterales con y sin imágenes casi-infrarrojas.RESULTADOS:Se incluyeron un total de 172 pacientes elegibles; 84 de estos pacientes se sometieron a cirugía laparoscópica con imágenes casi-infrarrojas. Después del emparejamiento por puntuación de propensión, 58 pacientes fueron emparejados en cada uno de los grupos de luz casi-infrarroja y los sin luz. El tiempo de operación en el grupo de luz casi-infrarroja fue significativamente más largo que en el grupo sin luz (426 frente a 369 min), y la cantidad de pérdida de sangre intraoperatoria en el grupo de luz casi-infrarroja fue significativamente menor que en el grupo sin luz (13 frente a 110 ml). El número total de ganglios linfáticos pélvicos laterales recolectados en el grupo de luz casi-infrarroja fue significativamente mayor que en el grupo sin luz (14 frente a 9). No hubo diferencias significativas en las tasas de complicaciones posoperatorias de los dos grupos.LIMITACIONES:Las limitaciones del presente estudio incluyen su diseño retrospectivo.CONCLUSIONES:Este estudio reveló que la disección laparoscópica de los ganglios linfáticos pélvicos laterales combinada con imágenes casi-infrarrojas podría aumentar el número total de ganglios linfáticos pélvicos laterales recolectados sin afectar la preservación funcional. Consulte Video Resumen en http://links.lww.com/DCR/B800. (Traducción-Dr. Xavier Delgadillo)Este estudio se registró en el Registro de Ensayos Clínicos de Japón como UMIN000041372 (http://www.umin.ac.jp/ctr/index.htm).

Study protocol: a multicenter randomized controlled trial of the multifaceted workload reduction of the anti-adhesion barrier for diverting ileostomy in laparoscopic rectal surgery, YCOG 2005 (ADOBARRIER study).

BACKGROUND: There are few randomized controlled trials on the efficacy of spray-type anti-adhesion material during diverting ileostomy in laparoscopic rectal cancer surgery. PURPOSE: This study will assess whether or not spraying an anti-adhesion material during diverting ileostomy could reduce the surgeon's multifaceted workload in ileostomy closure. METHODS: Patients with laparoscopic or robotic surgery for rectal cancer scheduled for low anterior resection and diverting ileostomy will be enrolled in the ADOBARRIER study (multicenter, single-blind, randomized controlled trial). The target sample size is set at 120 cases, which will be randomly divided into an anti-adhesion material-using group and a non-using group at a ratio of 1:1. The primary endpoint is the multifaceted workload of the surgeon of ileostomy closure using SURG-TLX between groups with and without usage of the anti-adhesion material during diverting ileostomy construction; the secondly endpoint is the operative time, amount of intraoperative blood loss, degree of adhesions, and extent of intra-abdominal adhesions when the ileostomy is closed. CONCLUSIONS: This RCT will evaluate the efficacy and safety of spray-type anti-adhesion material for diverting ileostomy construction. The results of this study are expected to facilitate decision-making regarding the use of anti-adhesion material. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials (jRCT) in October 2020 as jRCTs032200155.

Evaluating the Effect of Intraoperative Near-Infrared Observation on Anastomotic Leakage After Stapled Side-to-Side Anastomosis in Colon Cancer Surgery Using Propensity Score Matching.

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. EVALUACIN DEL EFECTO DE LA OBSERVACIN INTRAOPERATORIA CON INFRARROJO CERCANO SOBRE LA FUGA ANASTOMTICA DESPUS DE UNA ANASTOMOSIS LATEROLATERAL CON ENGRAPADORA EN LA CIRUGA DE CNCER DE COLON MEDIANTE EL EMPAREJAMIENTO POR PUNTAJES DE PROPENSIN: 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.

Comparison of the continuation and discontinuation of perioperative antiplatelet therapy in laparoscopic surgery for colorectal cancer: A retrospective, multicenter, observational study (YCOG 1603).

AIM: The present study aimed to examine the effect of continuing antiplatelet therapy in the perioperative period for patients undergoing laparoscopic resection for colorectal cancer who had received preoperative antiplatelet therapy. METHODS: This retrospective, multicenter, observational study included patients who underwent laparoscopic surgery for colorectal cancer between January 2011 and May 2020. The study population was limited to patients who used antiplatelet therapy preoperatively. RESULTS: A total of 214 colorectal cancer patients who received antiplatelet therapy preoperatively were included in the present study. Eighty-nine patients underwent surgery under the continuation of antiplatelet therapy, and 125 patients underwent surgery under the discontinuation of antiplatelet therapy before surgery. There were no significant differences between the two groups with regard to intraoperative blood loss (P = .889), intraoperative blood transfusion (P = 1.000), and conversion to laparotomy (P = 1.000). There were no significant differences between the two groups in the incidence of postoperative hemorrhagic complications (Clavien-Dindo Grade ≥II, P = .453; Grade ≥III, P = .572) or three-point major adverse cardiovascular events (P = .268). However, there were two cases of postoperative non-fatal stroke in the discontinued antiplatelet therapy group. CONCLUSIONS: The present study revealed that there were no significant differences in the surgical outcomes and postoperative complications between colorectal cancer patients who underwent laparoscopic resection with the continuation of antiplatelet therapy in the perioperative period and those in whom antiplatelet therapy was discontinued during the perioperative period. From the viewpoint of cardiovascular and cerebrovascular risk, it may be better for patients undergoing laparoscopic surgery for colorectal cancer to continue antiplatelet therapy. This study was registered with the Japanese Clinical Trials Registry as UMIN000038707 (http://www.umin.ac.jp/ctr/index.htm).

The incidence, risk factors, and new prediction score for fluorescence abnormalities of near-infrared imaging using indocyanine green in laparoscopic low anterior resection for rectal cancer.

PURPOSE: Several studies have reported the efficacy of near-infrared imaging using indocyanine green in laparoscopic low anterior resection (LAR), but a detailed examination of its fluorescence abnormalities is still insufficient. The purpose of this study was to clarify the incidence of fluorescence abnormalities and to create a new prediction score in laparoscopic LAR. METHODS: This was a retrospective, multicenter study that included patients with rectal cancer who underwent laparoscopic LAR from September 2014 to November 2018. RESULTS: A total of 336 patients were included. The transection line was changed due to fluorescence abnormalities in 5.4% (18/336) of cases, and the median length of additional resection was 70 mm. Anastomotic leakage of Clavien-Dindo grade ≥ II occurred in 6.0% (20/336). The gender and the intraoperative pre-planned proximal margin (IpPM) were significant factors for fluorescence abnormalities. We devised the fluorescence abnormality prediction score (FAPS) derived from the gender, IpPM, and tumor height from the anal verge (TumorAV). The area under the curve of the FAPS was 0.784 (95% CI: 0.677-0.891). When the cutoff was 4, the sensitivity was 0.833, and the specificity was 0.626. The preoperative pre-planned proximal margin (PpPM) was calculated as follows: PpPM (mm) = 189 (mm) - TumorAV (mm) + 61 × Male (1/0). The proximal margin should be set to be larger than the PpPM to avoid fluorescence abnormalities. CONCLUSION: The incidence of fluorescence abnormalities in laparoscopic LAR was 5.4%. If the FAPS is used, the PpPM may be set from the viewpoint of the blood perfusion. TRIAL REGISTRATION: Japanese Clinical Trials Registry: UMIN000032654 ( http://www.umin.ac.jp/ctr/index.htm ).

The comparison of health-related quality of life and patient satisfaction between single-incision and multiport laparoscopic colectomy for cancer: A sub-study of a randomized, prospective clinical trial.

AIM: The present study clarified the effect on the health-related quality of life and patient satisfaction of single-incision laparoscopic colectomy compared with multiport laparoscopic colectomy for colorectal cancer. METHODS: We conducted a multicenter, randomized, control trial comparing single-incision and multiport laparoscopic colectomy for colon cancer. We performed a pre-planned secondary analysis of health-related quality of life and patient satisfaction data of 200 patients. Health-related quality of life was evaluated using the Japanese 36-item Short Form Health Survey (SF-36) version 2.0 before surgery and at 1 month after surgery. Patient satisfaction was compared using seven questionnaires at 1 month after surgery. RESULTS: One hundred patients were assigned to each group. After excluding 18 patients (9.0%) who did not complete the SF-36, 182 patients (91.0%) were included in the analysis (92 cases of single-incision laparoscopic colectomy and 90 cases of multiport laparoscopic colectomy). The SF-36 scores at 1 month after surgery were not significantly different between the two arms. The role physical, bodily pain, vitality and physical component summary were significantly lower at 1 month after surgery than before in both groups. However, the role emotional was significantly lower after surgery than before only in the single-incision laparoscopic colectomy group. In terms of patient satisfaction at 1 month after surgery, there were no significant differences in any of the seven items on the questionnaire. CONCLUSIONS: Single-incision laparoscopic colectomy was similar to multiport laparoscopic colectomy in terms of health-related quality of life and patient satisfaction. However, single-incision laparoscopic colectomy may be inferior than multiport laparoscopic colectomy in terms of the role emotional.

Incidence and risk factors for fluorescence abnormalities on near-infrared imaging using indocyanine green in stapled functional end-to-end anastomosis in laparoscopic colectomy.

PURPOSE: Recently, several studies have suggested that near-infrared (NIR) imaging using indocyanine green (ICG) may contribute to the reduction of anastomotic leakage (AL) after colorectal cancer (CRC) surgery. However, few reports have focused on the usefulness of NIR imaging for AL after stapled functional end-to-end anastomosis (stapled FEEA). The purpose of this study was to clarify the frequency of fluorescence abnormalities on NIR imaging, in cases reconstructed with stapled FEEA. METHODS: This retrospective study included patients with colon or appendiceal cancer who underwent laparoscopic colectomy with stapled FEEA reconstruction between March 2016 and August 2019. RESULTS: A total of 400 patients who were managed at our three institutions were included in the present study. The rate of Clavien-Dindo (CD) grade > III AL was 1.0% (4/400). The median length of postoperative hospital stay was 7 days (IQR 25-75th percentile 6-8 days). In 11 patients (2.8%), the transection line was changed by NIR imaging, due to fluorescence abnormalities. The rate of transverse colon involvement in anastomosis was significantly higher in cases with fluorescence abnormalities than in cases with normal fluorescence (p = 0.035). CONCLUSIONS: The frequency of fluorescence abnormalities on NIR was 2.8% in cases of colon resection with reconstruction by using stapled FEEA. There was a probability of abnormal fluorescence on NIR in cases where the transverse colon was involved in the anastomosis. This means that NIR may have potential benefit in such cases. TRIAL REGISTRATION: UMIN000039977.

Regorafenib is transported by the organic anion transporter 1B1 and the multidrug resistance protein 2.

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 3H-estrone sulfate by HEK293/OATP1B1 cells in a dose-dependent manner, but did not affect its elimination by P-glycoproteins. The concentration of regorafenib was significantly lower in LLC-PK1/multidrug resistance protein 2 (MRP2) cells than in LLC-PK1 cells treated with the MRP2 inhibitor, MK571. MK571 abolished the inhibitory effects of regorafenib on intracellular accumulation in LLC-PK1/MRP2 cells. The uptake of regorafenib was significantly higher in HEK293/OATP1B1 cells than in OATP1B1-mock cells. Transport kinetics values were estimated to be Km=15.9 µM and Vmax=1.24 nmol/mg/min. No significant difference was observed in regorafenib concentrations between HEK293/OATP1B3 and OATP1B3-mock cells. These results indicated that regorafenib is a substrate for MRP2 and OATP1B1, and also suggest that the substrate preference of regorafenib may implicate the pharmacokinetic profiles of regorafenib.

Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine and poor prognosis in AML patients.

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 malignancies. A previous study identified mature miR-126-3p as an onco-microRNA that is generated from the pre­microRNA, 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 miR­126-3p (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.