Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

No clear survival benefit of azacitidine for lower‐risk myelodysplastic syndromes: A retrospective study of Nagasaki

The efficacy of azacitidine (AZA) on survival of lower risk (LR) ‐ myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long‐term survival benefit of AZA for patients with LR‐MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR‐MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis‐stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection‐related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR‐MDS patients.     

Pediatric bowel preparation: Sodium picosulfate,magnesium oxide,citric acid vs polyethylene glycol,a randomized trial

BACKGROUND Bowel preparation in children can be challenging.AIM To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid(SPMC) bowel preparation in children.METHODS Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ? dose × 2, SPMC 1 dose × 2, or polyethylene glycol(PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders(rating of ‘excellent' or ‘good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events(AEs) and laboratory evaluations.RESULTS 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ? dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was ‘very easy' or ‘easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG.CONCLUSION SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.     

Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

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.

     

Clinical Features,Treatment, and Visual Outcomes of Japanese Patients with Posterior Scleritis

ABSTRACT

Purpose: The purpose of this study is to describe clinical features and visual outcomes of Japanese patients with posterior scleritis.

Methods: Clinical records of 10 patients (13 eyes) presenting between 2006 and 2016 were retrospectively reviewed.

Results: The mean age was 50.1 ± 20.8 years; 50% were women, and three patients had bilateral disease. Associated anterior scleritis (11 eyes, 85%) and serous retinal detachment (8 eyes, 62%) were common at presentation. Treatment consisted of corticosteroids (all patients) and immunosuppressive agents (seven patients). The mean subfoveal choroidal thickness was significantly reduced over follow-up [611 μm at baseline, 298 μm (p < 0.01) at 1 month, and 238 μm (p < 0.01) at 1 year]. Recurrent inflammation was observed in six patients. A best-corrected visual acuity of 0.8 or better was achieved in all 13 eyes at 3 years and 71% of eyes at 5 years.

Conclusion: Although 60% of patients with posterior scleritis had recurrence, visual outcomes were favorable.