Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Purpose: Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM. Materials and Methods: Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed. Results: Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05). Conclusion GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients.The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold.Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cellmediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.

Background/Aims: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. Methods: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. Results: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of “PPI and H2RA” (HR, 1.58; p = 0.010) as well as “PPI, H2RA, and MPA” (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, “MPA and PPI or H2RA” was not associated with an increased risk of osteoporotic fracture. Conclusions This study found that the combined use of “PPI and H2RA” was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Background/Aims: Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). Methods: An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Results: Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Conclusions Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

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.

Objective: : With the recent increase in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the role of neurosurgeons in AIS treatment has become increasingly important. This study aimed to assess the outcomes of patients with AIS treated by neurosurgeons and neurologists in the emergency room (ER) of a tertiary hospital in South Korea. Methods: : From January 2020 to June 2021, 536 patients with AIS within 24 hours of symptom onset were admitted to our hospital via the ER. Based on the type of doctors who provided initial care for AIS in the ER, patients were divided into two groups : (a) neurosurgeon group (n=119, 22.2%) and (b) neurologist group (n=417, 77.8%). Results: : Intravenous tissue plasminogen activator (tPA) was administered in 82 (15.3%) of 536 patients (n=17 [14.3%] in the neurosurgeon group and n=65 [15.6%] in the neurologist group). The door-to-tPA time was not significantly different between both groups (median, 53 minutes; interquartile range [IQR], 45–58 vs. median, 54 minutes; IQR, 46–74; p=0.372). MT was performed in 69 patients (12.9%) (n=25, 36.2% in the neurosurgeon group and n=44, 63.8% in the neurologist group). The neurosurgeon group achieved a shorter door-to-puncture time than the neurologist group (median, 115 minutes; IQR, 107–151 vs. median, 162 minutes; IQR, 117–189; p=0.049). Good clinical outcomes (3-month modified Rankin Scale 0–2) did not differ significantly between the two groups (96/119 [80.7%] vs. 322/417 [77.2%], p=0.454). Conclusion : The neurosurgeon group showed similar door-to-treatment time and clinical outcomes to the neurologist group in patients with AIS in the ER. This study suggests that neurosurgeons have comparable abilities to care for patients with AIS in the ER.