Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. Methods: This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. Results: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. Conclusion This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Background: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia. Methods: This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1,000 IU tablets for 6 months. Results: A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean±standard error of change in propeptide of type I collagen after 3 months was -6.87±2.56% in the experimental group and 1.22±2.54% in the control group. After 6 months, it was -21.07±2.75% in the experimental group and 1.26±2.71% in the control group. The difference between the 2 groups was -22.33% (p<0.01). The change of C-terminal telopeptide was -12.55±4.05% in the experimental group and 11.02±4.03% in the control group after 3 months. It was -22.0±3.95% and 10.20±3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (p<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups. Conclusions The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.

Classifying patients with osteoporosis according to fracture risk and establishing adequate treatment strategies is crucial to effectively treat osteoporosis. The Korean Society for Bone and Mineral Research has issued a position statement regarding appropriate treatment strategies for postmenopausal osteoporosis. According to previous fragility fracture history, bone mineral density (BMD) test results, fracture risk assessment tool, and several clinical risk factors, fracture risk groups are classified into low, moderate, high, and very-high-risk groups. In high-risk groups, bisphosphonates (BPs) and denosumab are recommended as first-line therapies. Sequential BP treatment after denosumab discontinuation is required to prevent the rebound phenomenon. In the very high-risk group, anabolic drugs (teriparatide or romosozumab) are recommended as a first-line therapy; sequential therapy with antiresorptive agents is required to maintain BMD gain and reduce fracture risk. Fracture risk was reassessed annually, and the treatment plan was determined based on the results, according to the osteoporosis treatment algorithm for fracture risk.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒). Conclusion The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.

Objectives: . We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. Methods: . In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. Results: . No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. Conclusions . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.