This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin ® . A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (C max ) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795–0.9614) and 0.8630 (0.8472–0.8791) in the fasting study and 1.0926 (1.0102–1.1818) and 0.9998 (0.9675–1.0332) in the fed study, respectively. The time to reach C max of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

This study performed the forensic anthropological sex estimation of Koreans in a non-metric way by reconstructing three-dimensional (3D) computed tomography (CT) images of skulls. The skull CT images used in this study were 100 (51 males, 49 females), and all CT images were taken with a slice thickness of 0.75 mm and then reconstructed into 3D images using the MIMICS 23.0 program. Using the reconstructed 3D image, measurements were repeated twice. The sex determination was male if the 4 point to 5 point was relatively more in five landmarks, and female if the points of 1 to 2 were relatively more. Results of the study show that, 88 of the 100 cases matched the actual sex. Among the 12 discrepant cases, ten cases were mismatched with the actual sex even though the estimation and repeated estimation readout of sexestimating were the same. Two cases, were “unknown,” showing different sexes in the first and repeated estimations. In conclusion, this study indicated that a forensic anthropological analysis from 3D images provided accurate point information on the landmarks of skulls, showing as high an accuracy as the sex estimation method using real bones. The ten cases of sex mismatch, except the two “Unknown” cases, are considered to be errors that did not consider differences in population groups. In further studies, further establishing a nonmetric, specifically Korean methods to increase the accuracy and reliability of sex estimation is need.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

The risk of malignancy after transplantation is higher than that of general population. Laparoscopic surgery has become a standard treatment of gastric cancer. However, there are no case reports evaluating totally laparoscopic gastrectomy in patients with previous liver transplantation. Herein we report our experience with a liver transplant recipient who underwent totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. A 63 year-old man underwent orthotopic liver transplantation (OLT) for cryptogenic liver cirrhosis. 8 years later, gastric cancer was diagnosed during the follow-up. Endoscopic submucosal dissection was performed and additional surgical resection was needed. TLDG and D1+ lymph node dissection was performed, and the patient was discharged on the 8th post-operative day without any complications. To the best of our knowledge, this is the first case of de novo gastric cancer treated with TLDG after OLT. This suggests that TLDG is a feasible for patients after OLT.
Follow-Up Studies ; Gastrectomy ; Humans ; Laparoscopy ; Liver Cirrhosis ; Liver Transplantation ; Liver ; Lymph Node Excision ; Stomach Neoplasms ; Transplant Recipients

Mucormycosis is an extremely rare but potentially life-threatening fungal infection. Gastrointestinal (GI) mucormycosis is very rare and occurs primarily in highly malnourished patients, especially in infants and children. A 55-year-old man with end-stage renal disease due to diabetic nephropathy, who had undergone deceased donor kidney transplantation 2 years prior, complained of abdominal pain and distension with a 3-day duration. Computed tomography revealed diffuse gastric wall thickening, and a huge amount of grey colored necrotic debris surrounded by erythematous erosive mucosa was observed at the antrum to upper body by GI endoscopy. The microscopic examination obtained from a GI endoscopic specimen demonstrated peptic detritus with numerous non-septate mucor hyphae in the mucosa and submucosa. Mucormycosis was diagnosed based on the clinical findings and morphological features. A total gastrectomy was performed and an antifungal agent was administered. A microscopic examination of the surgical specimen demonstrated invasive mucormycosis with numerous fungal hyphae with invasion into the mucosa to subserosa. The patient and graft were treated successfully by total gastrectomy and antifungal therapy.
Abdominal Pain ; Child ; Diabetic Nephropathies ; Endoscopy ; Gastrectomy ; Humans ; Hyphae ; Infant ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney* ; Middle Aged ; Mucor ; Mucormycosis* ; Mucous Membrane ; Stomach ; Tissue Donors ; Transplant Recipients* ; Transplants

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)
Artemisia ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Endoscopy ; Gastritis* ; Humans ; Seoul

PURPOSE: The purpose of this study was to investigate the accuracy and reliability of the semi-automated ultrasonographic volume measurement tool, virtual organ computer-aided analysis (VOCAL), for measuring the volume of parathyroid glands. METHODS: Volume measurements for 40 parathyroid glands were performed in patients with secondary hyperparathyroidism caused by chronic renal failure. The volume of the parathyroid glands was measured twice by experienced radiologists by two-dimensional (2D) and three-dimensional (3D) methods using conventional sonograms and the VOCAL with 30°angle increments before parathyroidectomy. The specimen volume was also measured postoperatively. Intraclass correlation coefficients (ICCs) and the absolute percentage error were used for estimating the reproducibility and accuracy of the two different methods. RESULTS: The ICC value between two measurements of the 2D method and the 3D method was 0.956 and 0.999, respectively. The mean absolute percentage error of the 2D method and the 3D VOCAL technique was 29.56% and 5.78%, respectively. For accuracy and reliability, the plots of the 3D method showed a more compact distribution than those of the 2D method on the Bland-Altman graph. CONCLUSION: The rotational VOCAL method for measuring the parathyroid gland is more accurate and reliable than the conventional 2D measurement. This VOCAL method could be used as a more reliable follow-up imaging modality in a patient with hyperparathyroidism.
Follow-Up Studies ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Secondary* ; Imaging, Three-Dimensional ; Kidney Failure, Chronic ; Methods* ; Organ Size ; Parathyroid Glands ; Parathyroidectomy ; Ultrasonography