PubMed | Saga University, Institute of Biomedical Research and Innovation, General Hospital, Kyoto University and 4 more.
Type: Journal Article | Journal: Cancer science | Year: 2016
Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. EGFR T790M has been observed in half of lung cancer patients who have acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Effectiveness of monitoring T790M via plasma DNA during treatment with EGFR-TKI has not been established as an alternative to re-biopsy. This was a prospective multicenter observational study involving non-small cell lung cancer patients carrying EGFR L858R or exon 19 deletions, treated with EGFR-TKI. The primary objective was to determine whether T790M could be detected using plasma DNA in patients with progressive disease (PD). T790M was examined using the mutation-biased PCR and quenching probe (MBP-QP) method, a sensitive, fully-automated system developed in our laboratory. Eighty-nine non-small cell lung cancer patients were enrolled from seven hospitals in Japan. Sequential examinations revealed T790M in plasma DNA among 40% of patients who developed PD. Activating mutations, such as L858R and exon 19 deletions, were detected in 40% of patients using plasma DNA, and either T790M or activating mutations were observed in 62%. Dividing into four periods (before PD, at PD, at discontinuation of EGFR-TKI and subsequently), T790M was detected in 10, 19, 24 and 27% of patients, respectively. Smokers, males, patients having exon 19 deletions and patients who developed new lesions evidenced significantly frequent presence of T790M in plasma DNA. Monitoring T790M with plasma DNA using MBP-QP reflects the clinical course of lung cancer patients treated with EGFR-TKI. Detection of T790M with plasma DNA was correlated with EGFR mutation type, exon 19 deletions and tumor progression. Re-biopsy could be performed only in 14% of PD cases, suggesting difficulty in obtaining re-biopsy specimens in practice. Monitoring T790M with plasma DNA reflects the clinical course, and is potentially useful in designing strategies for subsequent treatment.
PubMed | National Cheng Kung University, Yonsei University, University of Ulsan, Harvard University and 17 more.
Type: | Journal: JAMA oncology | Year: 2016
REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline -fetoprotein (FP).To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial.Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8).Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks.Overall survival (OS), defined as time from randomization to death from any cause.In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P=.06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline FP levels of 400 ng/mL (to convert ng/mL to g/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P=.01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P=.04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6.In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline FP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline FP levels of 400 ng/mL or more.clinicaltrials.gov Identifier: NCT01140347.
PubMed | Saga ken Medical Center Koseikan, Chiba University, Aichi Cancer Center Research Institute and Chiba Institute of Science
Type: | Journal: Neurochemistry international | Year: 2016
Brain-derived neurotrophic factor (BDNF) and its high affinity receptor tyrosine kinase receptor B (TrkB) are involved in neuronal survival, maintenance, differentiation and synaptic plasticity. Deficiency of BDNF was reported to be associated with psychological disorders such as depression. Hence we examined proliferative effect of 11 candidate TrkB agonistic compounds in TrkB-expressing SH-SY5Y cells, via a hypothesis that some candidate compounds identified in our previous in silico screening for a small molecule targeting the BDNF binding domain of TrkB should activate TrkB signaling. In the present study, two promising compounds, 48 and 56, were identified and subsequently assessed for their ability to induce TrkB phosphorylation invitro and invivo. Likewise those seen in BDNF, the compounds mediated TrkB phosphorylation was blocked by the Trk inhibitor, K252a. Since BDNF-TrkB signaling deficiency is associated with the pathogenesis of depression and reactivation of this signaling by antidepressants is a cause of the pathogenic state recovery, the compounds were subjected to the assessment for forced swim test, which is a mouse model of depression. We found that compound 48 significantly reduced mouse immobility time compared with the control vehicle injection, suggesting the confirmation of hypothetical antidepressant-like efficacy of 48 compound invivo. Thus, our present study demonstrated that compound 48, selected through in silico screening, is a novel activator of TrkB signaling and a potential antidepressant molecule.
PubMed | Saga Ken Medical Center Koseikan, Saga University and Kokura Medical Center
Type: Journal Article | Journal: Journal of anesthesia | Year: 2016
The present study was conducted to investigate changes in uncuffed endotracheal tube (ETT) leak during laparoscopic surgery. The study included 31 patients aged between 1 and 6years scheduled for elective laparoscopic inguinal herniorrhaphy. Inspiratory and expiratory tidal volumes (TVi and TVe) were measured during mechanical ventilation, and ETT leak was calculated using the formula-ETT leak=(TVi-TVe)/TVi100(%), assessed at the following time-points-5min after the start of mechanical ventilation (T1, baseline), just before the start of surgery (T2), 5min after the induction of pneumoperitoneum with 15 Trendelenburg tilt (T3), and at the end of surgery (T4). Additionally, leak pressure was assessed after successful tracheal intubation (T0, baseline) at T2, T3 and T4. Uncuffed ETT leak significantly decreased at T3 compared with T1 (baseline). Leak pressure significantly increased at T3 and T4 compared with T0 (baseline). Further studies are needed in order to determine whether the results are universal and associated with clinically significant outcomes.
PubMed | Miyazaki Prefectural Miyazaki Hospital, National Hospital Organization Kyushu Cancer Center, Saga Ken Medical Center Koseikan and Oita Prefectural Hospital
Type: | Journal: Japanese journal of clinical oncology | Year: 2016
To assess the characteristics of biochemical recurrence in the late period (>5 years after radical prostatectomy) and the differences in the predictors of biochemical recurrence in different periods, we conducted a multicenter retrospective study.We reviewed 478 men who underwent radical prostatectomy for clinically localized prostate cancer. All of the patients were followed up for at least 5 years. The cohort was then divided into three groups; no recurrence group, recurrence <5 years after surgery group and recurrence 5 years after surgery group. The background characteristics of each group were compared using the Biochemical recurrence occurred in 135 men. In 113 (84%) of the patients, biochemical recurrence occurred at <5 years after surgery; in 22 (16%), it occurred at 5 years after surgery. The proportion of men with a low preoperative prostate-specific antigen level was significantly larger in the latter group (P = 0.0023). A preoperative prostate-specific antigen level and a positive surgical margin were significant predictors of biochemical recurrence at <5 years after surgery (hazard ratio: 1.03 and 3.20). A positive surgical margin was also a significant predictor of biochemical recurrence at 5 years after surgery (hazard ratio: 3.03); however, a high preoperative prostate-specific antigen level was not.Biochemical recurrence occurred at 5 years after surgery in 16% of the patients. A positive surgical margin predicted biochemical recurrence in both the early and late periods.
Yamaguchi T.,Saga ken Medical Center Koseikan |
Tsuchiya T.,EP Expert Doctors Team Tsuchiya |
Nakahara S.,Dokkyo Medical University |
Fukui A.,EP Expert Doctors Team Tsuchiya |
And 4 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2016
Background: Low-voltage zones (LVZs) represent fibrotic tissue and are substrates for atrial fibrillation (AF). We hypothesized that LVZ-based substrate modification along with pulmonary vein isolation (PVI) would improve outcomes in persistent AF (PeAF) patients with LVZs, whereas PVI alone would work in patients without LVZs. Methods and Results: Voltage mapping of the left atrium (LA) was performed during sinus rhythm in 101 PeAF patients in whom LVZ was defined as an area with bipolar electrograms <0.5 mV. Thirty-nine patients had LVZs and underwent ablation of the entire LVZ area after PVI (LVZabl group). In the remaining 62 patients without LVZs, PVI alone was performed with no further substrate modifications (PVI group). An additional group of 16 consecutive PeAF patients with LVZ did not undergo any substrate modification after PVI and were used as a comparison group (LVZnon-abl group) despite having similar size of LVZs to that in the LVZabl group. After a single session, 28 (72%) patients in the LVZabl group had no recurrence, whereas 49 (79%) patients in the PVI group had no recurrence during 18 ± 7 months of follow-up (log-rank, P = 0.400). In the LVZnon-abl group, only 6 patients (38%) had no recurrence during 32 ± 7 months of follow-up, even after a mean number of sessions of 1.8 (log-rank, P < 0.001, compared with the LVZabl group). Conclusions: Additional LVZ-based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF. © 2016 Wiley Periodicals, Inc.
Sadamatsu K.,Saga ken Medical Center Koseikan |
Nakano Y.,Saga ken Medical Center Koseikan
Internal Medicine | Year: 2016
Objective The aim of this study was to investigate whether the use of low frame rate fluoroscopy at 7.5 frames per second during coronary intervention could reduce radiation exposure in Japanese patients. Methods From December 10, 2014 to March 20, 2015, 84 consecutive patients with coronary artery disease who underwent coronary intervention in our institution were retrospectively collected and then divided into two groups: the LR group (fluoroscopy at 7.5 frames per second) and the OR group (fluoroscopy at 15 frames per second), according to the frame rate of fluoroscopy that was used in their treatment. Results There were no differences in the patient backgrounds or the procedural characteristics of the two groups. Although there were no differences in the contrast volume or fluoroscopy time, the total air kerma at the interventional reference point, which is used to monitor the patient’s radiation dose, was significantly lower in the LR group than in the OR group (701.4±427.9 vs. 936.8±623.9 mGy, p=0.02). Conclusion Low frame rate fluoroscopy at 7.5 frames per second is safe and feasible for use during coronary interventions and an easy and useful strategy for reducing the radiation to which patients are exposed during coronary intervention. © 2016 The Japanese Society of Internal Medicine.
Kakiuchi T.,Saga University |
Moritsuka T.,Saga ken Medical Center Koseikan
Acta Hepatologica Japonica | Year: 2014
Saga prefecture has been reported to be the most prevalence area of hepatitis C virus (HCV) infection in Japan. We investigated the results of medical screening for anti-HCV and HCV-RNA on the island of Saga. Anti-HCV testing was performed on 289 individuals, and the results showed that 22 were positive for anti- HCV, and 11 were positive for HCV-RNA. A blood transfusion history was a significant predictor of anti- HCV positive status, while no such relationship was found for HCV-RNA positivity. The HCV-RNA spontaneous loss rate was 45% . The vertical transmission from pregnant females to the infants may have led to the highest of anti-HCV positive ratio and the HCV- RNA disappearance ratio. © 2014 The Japan Society of Hepatology.
PubMed | Saga Ken Medical Center Koseikan, Saga University and Imari Arita Kyoritsu Hospital
Type: Journal Article | Journal: Hepatology research : the official journal of the Japan Society of Hepatology | Year: 2016
Sarcopenia, initially proposed as decreased of muscle mass and strength, is associated with aging and malignant diseases. The aim of the present study was to determine whether there is a correlation between sarcopenia and the recurrence of hepatocellular carcinoma (HCC) after curative treatment.We conducted a retrospective analysis of consecutive naive patients with HCC who underwent curative resection or radiofrequency ablation. To eliminate the influence of cause or the severity of liver damage, subjects were limited to those with HCC with hepatitis C-related cirrhosis and Child-Pugh class A liver function. Patients were assessed using computed tomographic measurement of muscle mass at the level of the third lumbar (L3) vertebrae, the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined by using previously published, sex-specific cut-off value.Sarcopenia was present in 61 of 92 patients. Patients median age was 71.5years (range, 47-84), and the baseline characteristics of patients were comparable between patients with and without sarcopenia except for sex, serum albumin level, prothrombin time, diabetes mellitus and body mass index. Recurrence rates at 1, 3 and 5years were 39.1%,77.1%,81.7% for patients with sarcopenia and 23.5%,59.5% and 75.7% for patients without sarcopenia, respectively (P=0.03). Multivariate Cox analysis revealed that sarcopenia and preoperative -fetoprotein of more than 40ng/mL were significant independent factors for recurrence.Sarcopenia is a risk factor for recurrence in patients with HCC who were treated with curative treatment.
PubMed | Saga Ken Medical Center Koseikan
Type: Journal Article | Journal: Surgical case reports | Year: 2016
Duodenal varices are a low-frequency cause of gastrointestinal bleeding; however, greater than 40% mortality has been reported after the initial bleeding episode.This report describes a 72-year-old woman with bleeding duodenal varices treated by surgery after failure of balloon-occluded retrograde transvenous obliteration (B-RTO). The patient presented with profuse melena. Emergent upper endoscopy was immediately performed, and bleeding duodenal varices in the second portion of the duodenum were seen. Endoscopic band ligation was attempted first followed by B-RTO; however, the combined procedures failed. Laparotomy under general anesthesia was then performed, and the venous collaterals were cannulated using an 18-gauge needle. Following intraoperative angiography, the venous collateral was ligated on the peripheral side of the needle entry point, and ethanolamine oleate was injected into the afferent collateral vessel. Endoscopic examination on postoperative day 4 showed embolization of the duodenal varices. The patient was discharged on postoperative day 11.This technique is simple and effective, and we believe it is a potential alternative surgical treatment for duodenal varices with portal hypertension.