Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients.

BACKGROUND: Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein-Barr virus (EBV) status in GC. METHODS: We performed a tissue microarray analysis in 487 advanced GC patients who underwent gastrectomy. PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (TIICs), the densities of TILs, and MMR status were evaluated by immunohistochemistry. EBV was detected by in situ hybridization. RESULTS: PD-L1 expression on TCs and TIICs, MMR deficiency, and EBV positivity were identified in 22.8, 61.4, 5.1, and 5.1 % cases respectively. PD-L1 expression was more frequently observed in the elderly (TCs P = 0.002), in males (TCs P = 0.029; TIICs P = 0.043), in patients with poorly differentiated adenocarcinoma with solid-type histological features (TCs P < 0.001; TIICs P < 0.001), in patients with MMR deficiency (TCs P < 0.001; TIICs P < 0.001), and in patients with EBV positivity (TCs P = 0.001; TIICs P = 0.050). Strong association was observed between PD-L1 expression and high densities of CD3-positive, CD8-positive, or forkhead box P3 positive TILs (TCs P < 0.001; TIICs P < 0.001). Neither PD-L1 expression on TCs nor that on TIICs was an independent prognostic factor in multivariate analysis. CONCLUSIONS: In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.

[The pharmacist's role in smoking cessation].

Since they have very good opportunities to aid smokers in quitting smoking at clinics or pharmacies, pharmacists play an important role in encouraging smoking cessation. They should be aware of the significance of tobacco abstinence. Therapeutic assistance for cessation includes drug treatment of nicotine dependence and counseling based on behavioral science for psychological dependence. Particularly in drug treatment, pharmacists are able to exercise their professional knowledge by assisting smoking cessation from a pharmaceutical viewpoint. It is possible for any pharmacist to provide a brief smoking cessation intervention, such as asking a patient whether or not they smoke and advising them, if they smoke, to stop smoking.

Determination of antihyperglycemic biguanides in serum and urine using an ion-pair solid-phase extraction technique followed by HPLC-UV on a pentafluorophenylpropyl column and on an octadecyl column.

An HPLC-UV method was established for the determination of metformin and buformin in biological fluids. Metformin was not retained on particles packed in conventional solid-phase extraction cartridges; in contrast, buformin was retained too firmly and not eluted with a solvent for recovery. However, both drugs were retained on particles that had been treated with an ion-pair reagent of heptanesulfonate or dodecylsulfate and recovered almost completely. The recovered fraction was subjected to HPLC on a pentafluorophenylpropyl column which was suitable for the determination of both biguanides in serum and in urine. Limits of quantitation were low enough for clinical use, and reproducibility was high with an RSD of 0.9-2.3%. HPLC on a conventional octadecyl column was suitable only for the determination of buformin in serum since interfering peaks appeared on the chromatograms of urine samples. The method was applied to analysis of some clinical specimens.

Innovative questionnaire examining psychological nicotine dependence, "The Kano Test for Social Nicotine Dependence (KTSND)".

A smoking habit is maintained by psychological and physical nicotine dependence. We thought up a new concept, "social nicotine dependence", which is a part of psychological dependence, and developed a new questionnaire, "The Kano Test for Social Nicotine Dependence (KTSND)" version 2. The KTSND has ten questions with a total score of 30. In order to investigate the validity of the KTSND, we applied it to the employees of 10 pharmaceutical companies and collected 344 respondents. The total KTSND scores of 18.4+/-5.2 (mean +/- SD, n = 105) for smokers were significantly higher than those of 14.2 +/- 6.1 (n= 88) for ex-smokers, and 12.1 +/- 5.6 (n = 151) for non-smokers. Each question produced significantly different scores among these groups. Smokers were subclassified by factors of physical nicotine dependence, namely, "number of cigarettes smoked per day" and "time until the first cigarette of the day". The total scores did not reflect these physical factors. On the other hand, the total KTSND scores reflected one of the psychological nicotine dependence factors, namely, "the stages for quitting smoking". The KTSND scores were significantly different among 4 groups: 22.4 +/- 6.3 for immotives, 19.0 +/- 3.9 for precontemplators, 16.1 +/- 3.8 for contemplators and 14.5 +/- 5.9 for preparers. These results showed that the KTSND reflected the smoking status and the stages for quitting smoking. We consider that the KTSND is a useful method to evaluate psychological aspects of smoking.