No abstract

Fifty-two patients with laryngeal cancer who underwent radical neck dissections were studied to provide further information on the prognosis of various clinical and histopathological parameters. Extracapsular spread (ECS) was found in 31% of patients with N1 nodes, and in 60% of patients with histopathologically positive nodes. The 5-year survival rate of histopathological findings was as follows: patients with no pathological evidence of neck metastasis (81%), patients with neck metastasis confined to the lymph node (no ECS) (76%), and patients with ECS (17%). The difference in survival rate between patients with no ECS and patients with ECS was statistically significant (P = .001). Staging classification, T-stage classification, the number of malignant nodes, the diameter of malignant nodes, and combined therapy had no prognostic importance. The most significant factor was the presence of extracapsular spread.

No abstract

1. TAK-438, vonoprazan fumarate, is a novel orally active potassium-competitive acid blocker, developed as an antisecretory drug. In this study, we investigated the in vitro metabolism of C-labeled TAK-438. In human hepatocytes, M-I, M-II, M-III and M-IV-Sul were mainly formed, and these were also detected in clinical studies. N-demethylated TAK-438 was also formed as an in vitro specific metabolite. Furthermore, CYP3A4 mainly contributed to the metabolism of TAK-438 to M-I, M-III, and N-demethylated TAK-438, and CYP2B6, CYP2C19 and CYP2D6 partly catalyzed the metabolism of TAK-438. The sulfate conjugation by SULT2A1 also contributed to the metabolism of TAK-438 to form TAK-438 N-sulfate, and CYP2C9 mediated the formation of M-IV-Sul from TAK-438 N-sulfate. The metabolite M-IV, which could be another possible intermediate in the formation of M-IV-Sul, was not observed as a primary metabolite of TAK-438 in any of the in vitro studies. 2. In conclusion, TAK-438 was primarily metabolized by multiple metabolizing enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, and a non-CYP enzyme SULT2A1, and the influence of the CYP2C19 genotype status on gastric acid suppression post TAK-438 dosing could be small. The multiple metabolic pathways could also minimize the effects of co-administrated CYP inhibitors or inducers on the pharmacokinetics of TAK-438.

No abstract