Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer

International Journal of Clinical Oncology - This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced...     

Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel flexible light-emitting diode unit

Background

Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410?nm, 510?nm, 545?nm, 580?nm, and 630?nm. Although only red light around 635?nm and blue light around 400?nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.

Correction to: Features of the gut prokaryotic virome of Japanese patients with Crohn’s disease

Journal of Gastroenterology -     

Clinical characteristic of esophageal cancer without lugol-voiding lesions in the background esophagus

Lugol chromoendoscopy is useful for the detection of early esophageal squamous cell cancer (ESCC). Multiple lugol-voiding lesions (LVLs) on lugol chromoendoscopy are associated with a very high risk of multiple cancers arising in the esophagus. Due to the widespread use of narrow band image technology in many institutions, esophageal cancer without LVLs in the background esophagus is sometimes detected. This retrospective study aims to clarify the clinical characteristic of esophageal cancer without LVLs in the background esophagus. A total of 191 consecutive patients with 204 ESCCs had undergone endoscopic submucosal dissection (ESD) from 2011 and 2014. Amongst these lesions, the number of LVLs in the background esophagus per endoscopic view was counted excluding main lesion, and the grading was divided into no LVLs ESCC (nL-ESCC) group and LVLs ESCC (L-ESCC) group. This study evaluated the clinical characteristics and the cumulative incidence of metachronous ESCC after ESD in both groups. Thirty-six patients with 36 lesions and 155 patients with 168 lesions were separated into the nL-ESCC group and L-ESCC group, respectively. On multivariate analysis, the nL-ESCC group was found to be more common in females, who were non-drinkers, or with erosive esophagitis. During follow-up periods, the cumulative incidence of metachronous ESCC at 3-years was 14.4% and 0.00% in the L-ESCC and nL-ESCC groups, respectively (P < 0.01). Our study showed that esophageal cancer without LVLs in the background esophagus was mostly occurred in females, who were non-drinkers, or with erosive esophagitis, which are uncommon features of ESCC.     

Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate,in cynomolgus monkeys

1. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species.

2. Following intravenous (iv) administration of DS-8201a, the linker was stable in plasma, and systemic DXd exposure was low. DXd was rapidly cleared following iv dosing. Biodistribution studies revealed that intact DS-8201a was present mostly in the blood without tissue-specific retention. The major pathway of excretion for DXd was the faecal route following iv administration of radiolabelled DS-8201a. The only detectable metabolite in the urine and faeces was unmetabolized DXd. DXd is a substrate of organic anion transporting polypeptides, P-gp, and breast cancer resistance protein.

3. In conclusion, the stable linker in circulation and the high clearance of DXd upon release resulted in the low systemic exposure to DXd. Furthermore, the minimal tissue-specific retention and rapid excretion of DXd into faeces as its unmetabolized form with potentially limited impact on drug???drug interaction as a victim were also critical elements of the PK profile of DS-8201a.

     

Use of a Web-Based Physical Activity Record System to Analyze Behavior in a Large Population: Cross-Sectional Study

BackgroundThe use of Web-based physical activity systems has been proposed as an easy method for collecting physical activity data. We have developed a system that has exhibited high accuracy as assessed by the doubly labeled water method.ObjectiveThe purpose of this study was to collect behavioral data from a large population using our Web-based physical activity record system and assess the physical activity of the population based on these data. In this paper, we address the difference in physical activity for each urban scale.MethodsIn total, 2046 participants (aged 30-59 years; 1105 men and 941 women) participated in the study. They were asked to complete data entry before bedtime using their personal computer on 1 weekday and 1 weekend day. Their residential information was categorized as urban, urban-rural, or rural. Participant responses expressed the intensity of each activity at 15-minute increments and were recorded on a Web server. Residential areas were compared and multiple regression analysis was performed.ResultsMost participants had a metabolic equivalent (MET) ranging from 1.4 to 1.8, and the mean MET was 1.60 (SD 0.28). The median value of moderate-to-vigorous physical activity (MVPA, ≥3 MET) was 7.92 MET-hours/day. A 1-way ANCOVA showed that total physical activity differed depending on the type of residential area (F_2,2027=5.19, P=.006). The urban areas (n=950) had the lowest MET-hours/day (mean 37.8, SD, 6.0), followed by urban-rural areas (n=432; mean 38.6, SD 6.5; P=.04), and rural areas (n=664; mean 38.8, SD 7.4; P=.002). Two-way ANCOVA showed a significant interaction between sex and area of residence on the urban scale (F_2,2036=4.53, P=.01). Men in urban areas had the lowest MET-hours/day (MVPA, ≥3 MET) at mean 7.9 (SD 8.7); men in rural areas had a MET-hours/day (MVPA, ≥3 MET) of mean 10.8 (SD 12.1, P=.002). No significant difference was noted in women among the 3 residential areas. Multiple regression analysis showed that physical activity consisting of standing while working was the highest contributor to MVPA, regardless of sex.ConclusionsWe were able to compile a detailed comparison of physical activity because our Web-based physical activity record system allowed for the simultaneous evaluation of physical activity from 2046 Japanese people. We found that rural residents had greater total physical activity than urban residents and that working and transportation behaviors differed depending on region type. Multiple regression analysis showed that the behaviors affected MVPA. People are less physically active while working, and sports and active transportation might be effective ways of increasing physical activity levels.