Effects of Tegoprazan Versus Esomeprazole on Nighttime Heartburn and Sleep Quality in Gastroesophageal Reflux Disease: A Multicenter Double-blind Randomized Controlled Trial.

Background/Aims: Patients with gastroesophageal reflux disease (GERD) frequently experience nighttime heartburn and sleep disturbance. Tegoprazan is a new potassium-competitive acid blocker that can rapidly block acid secretion. This study aims to evaluate the efficacy of tegoprazan compared with esomeprazole in relieving nighttime heartburn and sleep disturbances. Methods: Patients with erosive esophagitis, nighttime heartburn, and sleep disturbances were randomized to receive tegoprazan 50 mg or esomeprazole 40 mg for 2 weeks. The primary endpoint was time to first nighttime heartburn-free interval. The percentage of nighttime heartburn-free days was also compared between the 2 groups. Results: A total of 46 patients were enrolled in this study. Time to the first nighttime heartburn-free interval was shorter with tegoprazan than with esomeprazole but the difference was not statistically significant (1.5 days vs 3 days, P = 0.151). The percentage of nighttime heartburn-free days was higher in the tegoprazan group but the difference was insignificant (57.8% vs 43.1%, P = 0.107). Adverse events occurred in 2 patients. They were mild in severity. Conclusions: Tegoprazan may induce faster relief of nighttime heartburn symptoms and may improve sleep disorders associated with nighttime heartburn. Further large-scale studies are required to validate our findings.

Randomised clinical trial: comparison of tegoprazan and placebo in non-erosive reflux disease.

BACKGROUND: Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease. AIM: To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD. METHODS: In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated. RESULTS: Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted. CONCLUSIONS: Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD. Registration number: ClinicalTrials.gov identifier NCT02556021.

Randomised clinical trial: tegoprazan, a novel potassium-competitive acid blocker, or lansoprazole in the treatment of gastric ulcer.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. AIMS: To assess whether tegoprazan is non-inferior to lansoprazole in terms of efficacy and safety in patients with gastric ulcers. METHODS: In this phase 3, double-blind, active control, multicentre study, 306 gastric ulcer patients were randomised to one of three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg once daily for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed ulcers confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms and safety were assessed. RESULTS: In the full analysis set, the cumulative healing rates at week 8 were 94.8% (91/96) for the tegoprazan 50 mg, 95.0% (94/99) for the tegoprazan 100 mg and 95.7% (89/93) for the lansoprazole 30 mg groups. At week 4, the respective healing rates were 90.6% (87/96), 91.9% (91/99), and 89.2% (83/93). In per protocol analysis, 4-week healing rates were 95.4% (84/88), 94.6% (88/93) and 92.9% (79/85) for tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg, respectively. Both doses of tegoprazan were non-inferior to lansoprazole in ulcer healing at 4 and 8 weeks. The incidence of drug-related treatment-emergent adverse events did not differ among groups. The increase in serum gastrin concentration was not higher in tegoprazan-treated patients than in lansoprazole-treated patients. CONCLUSIONS: Tegoprazan 50 or 100 mg were not inferior to lansoprazole 30 mg once daily in the treatment of gastric ulcers.

Molecular analysis of small tissue samples obtained via transbronchial lung biopsy using radial probe endobronchial ultrasound.

BACKGROUND: Radial probe endobronchial ultrasound using a guide sheath (EBUS-GS) is used to diagnose peripheral lung cancer. The aim was to identify the accuracy of molecular analysis that were performed with EBUS-GS specimens in patients with non-small cell lung cancer (NSCLC). METHOD: From December 2015 to September 2017, we retrospectively studied 91 patients with peripheral NSCLC who underwent surgery after EBUS-GS. Epidermal growth factor receptor (EGFR) mutational and anaplastic lymphoma kinase (ALK) translocation status obtained from surgical specimens served as the references. RESULTS: Compared to the reference data, EGFR mutational testing of EBUS-GS specimens was in 97% agreement, and the κ coefficient was 0.931 (P< 0.001). In addition, on ALK translocation testing, the results of all 91 patients were in agreement with the reference data (concordance rate of 100%, κ coefficient 1.000; P< 0.001). CONCLUSION: We found that EBUS-GS could be used for molecular diagnosis, such as EGFR mutational and ALK translocation status, in patients with peripheral NSCLC.

Trends in endpoint selection in clinical trials of advanced breast cancer.

PURPOSE: The selection of appropriate endpoints is crucial for the evaluation of clinical benefits and approval of novel anticancer agents. To our knowledge, this is the first study to evaluate endpoint selection and the shift in trends in phase II and phase III trials of advanced breast cancer treatment. METHODS: All phase II and phase III trials of advanced breast cancer registered in the ClinicalTrials.gov registry between October 2000 and September 2012 were included in our study. Two study periods were considered for comparison: October 2000 to September 2007 (cohort A) and October 2007 to September 2012 (cohort B). Information on primary and secondary outcome measures, as well as trial characteristics, was extracted by two independent reviewers. RESULTS: Of the 398 phase II and 120 phase III trials, the most frequently intended primary endpoint was progression-free survival (phase II: 28.1 %; phase III: 50.0 %). For phase II trials, a shifting trend in primary outcome was observed from cohort A to cohort B: the use of objective response rate, the most frequently intended primary outcome, significantly declined (cohort A: 60.6 %; cohort B: 39.0 %; P < 0.001), while the use of progression-free survival significantly increased (cohort A: 35.9 %; cohort B: 66.1 %; P < 0.001). CONCLUSIONS: Progression-free survival is the most frequently intended primary outcome measure in phase II and phase III trials of advanced breast cancer treatment, with a shifting trend observed from objective response rate to progression-free survival in phase II trials.

Lotus leaf alleviates hyperglycemia and dyslipidemia in animal model of diabetes mellitus.

The purpose of this study was to investigate the effects of lotus leaf on hyperglycemia and dyslipidemia in animal model of diabetes. Inhibitory activity of ethanol extract of lotus leaf against yeast α-glucosidase was measured in vitro. The effect of lotus leaf on the postprandial increase in blood glucose levels was assessed in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without lotus leaf extract (500 mg/kg) was administered to the rats after an overnight fast, and postprandial plasma glucose levels were monitored. Four-week-old db/db mice were fed a basal diet or a diet containing 1% lotus leaf extract for 7 weeks after 1 week of acclimation to study the chronic effect of lotus leaf. After sacrifice, plasma glucose, insulin, triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein (HDL)-CHOL, and blood glycated hemoglobin levels were measured. Lotus leaf extract inhibited α-glucosidase activity by 37.9%, which was 1.3 times stronger than inhibition by acarbose at a concentration of 0.5 mg/mL in vitro. Oral administration of lotus leaf extract significantly decreased the area under the glucose response curve by 35.1% compared with that in the control group (P < 0.01). Chronic feeding of lotus leaf extract significantly lowered plasma glucose and blood glycated hemoglobin compared with those in the control group. Lotus leaf extract significantly reduced plasma TG and total CHOL and elevated HDL-CHOL levels compared with those in the control group. Therefore, we conclude that lotus leaf is effective for controlling hyperglycemia and dyslipidemia in an animal model of diabetes mellitus.

Adenocarcinoma with sarcomatous dedifferentiation arising from mature cystic teratoma of the anterior mediastinum.

Mediastinal teratoma with malignant transformation (TMT) is a very rare condition. A 44-year-old man presented with a large cystic mass of the anterior mediastinum. The tumor was surgically removed. The cystic mass was well demarcated, with an irregularly thickened wall. Histologically, the cystic wall was mainly lined by non-ciliated columnar epithelium and focally by squamous epithelium. A nodular part of the cystic wall revealed well-differentiated adenocarcinoma composed of tubulopapillary structures. Deep in the nodular tissue, neoplastic glands merged into undifferentiated sarcomatous cells. Immunohistochemically, CK7, CK19, and smad-4 were strongly and diffusely positive in adenocarcinoma. CD10 was focally positive on the luminal surface of the glands, and MUC5AC was also focally positive. TTF-1, cdx-2, and CK20 were negative in the adenocarinoma. Sarcomatous area showed diffuse strong positivity for vimentin, but was negative for the aforementioned epithelial markers. About 10 months postoperatively, a left pleural effusion had developed with multiple pleural nodules on computed tomography scan of the chest. The cytologic diagnosis from pleural fluid was metastatic adenocarcinoma. To our knowledge, in the English literature, this is the first case of adenocarcinoma with sarcomatous transformation that has developed in a mature cystic teratoma of the mediastinum and shows pleural metastasis.