Purpose: In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea. Materials and Methods: This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs. Results: Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020. Conclusion This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Objective: Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer. Materials and Methods: We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017–May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated. Results: The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS (P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference (P ≥ 0.57). The ABUS–HHUS agreement was 95.9% (236/246; Cohen’s kappa = 0.883). Conclusion Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS.

Objective: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women. Materials and Methods: Seven healthy premenopausal women (median age, 37 years; range, 33–49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm2 (b800), 1200 sec/mm2 (b1200), and a synthetic 1500 sec/mm2 (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADCBPS) and fibroglandular tissue (ADCFGT). Changes in the visual grade, BPS volume (%), ADCBPS, and ADCFGT during the menstrual cycle were descriptively analyzed. Results: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADCBPS in the EFP. Four of the seven volunteers showed the highest ADCBPS in the early luteal phase (ELP) and the lowest ADCFGT in the late follicular phase (LFP). Conclusion Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADCBPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADCBPS was more common in ELP. The lowest ADCFGT was more frequent in LFP.

Purpose: There is limited data on the midterm results of endovascular treatment for acute type B aortic dissection (TBAD) with malperfusion syndrome (MS), particularly in Asia. This study aimed to investigate the clinical outcomes of endovascular treatment of acute TBAD with MS. Materials and Methods: We retrospectively analyzed 27 patients who underwent endovascular treatment for acute TBAD with MS. Results: Among the 27 patients with TBAD and MS, malperfusion was observed in the isolated renal (44.4%), visceral (7.4%) and iliofemoral (25.9%) arteries, as well as their combinations (22.2%). The patients underwent thoracic endovascular aortic repair (TEVAR) only (25.9%), selective stenting only in arteries affected by malperfusion (22.2%), or combined treatment with TEVAR and selective stenting (51.9%). Primary technical success was achieved in all the patients. No inhospital mortality or early death within 30 days after operation occurred. The rates of stroke, limb ischemia, acute kidney injury, and reintervention at 30 days were 7.4%, 3.7%, 25.9%, and 3.7%, respectively. The mean follow-up period was 4.3±3.1 years. During the follow-up, the rates of death, stroke, maintenance hemodialysis, aneurysmal change, and reintervention were 0%, 3.7%, 7.4%, 7.4%, and 7.4%, respectively. Two patients required reintervention due to limb ischemia and aneurysmal changes in the distal portion of the stent graft. Computed tomography scans revealed a significant increase in aortic diameters in patients who underwent selective stenting compared to those who underwent TEVAR over a 3-year period, with changes in aortic area measuring 878.9 mm2 vs. 188.4 mm2 at the middle of the lesion (P=0.037), 303.7 mm2 vs. 22.8 mm2 at the level of the celiac trunk (P=0.025), and 442.9 mm2 vs. 37.3 mm2 at the level of the renal artery (P=0.019). Conclusion The endovascular treatment of acute TBAD with MS demonstrated a high primary technical success rate and promising short- and midterm clinical outcomes.

Purpose: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes. Materials and Methods: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups’ surgical outcomes were compared using propensity score matching (PSM) analysis. Results: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients’ baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group. Conclusion Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.

Purpose: There are many studies regarding the increased relationship between pregnancy outcomes of singleton with endometriosis. However, there was limited evidence of twin pregnancies with endometriosis. This study aimed to compare the pregnancy outcomes and complications in twin pregnancies with or without endometriosis in a single institution. Materials and Methods: From January 2011 to July 2022, a retrospective analysis of twin pregnancies was conducted. The endometriosis group included patient with histological or visual confirmation before pregnancy or during cesarean section. Pregnancy outcomes and complications were compared between the two groups. Results: Out of 1714 patients examined, 127 (7.4%) were included in the endometriosis group. Maternal body mass index (BMI) was lower in the endometriosis group (p<0.001). There were no significant differences in maternal age, mode of conception, chorionicity, and pregnancy outcomes, such as gestational age at delivery (p=0.835) and the preterm birth rate (p=0.579). The endometriosis group had a significantly higher rate of obstetrical complication: small for gestational age (SGA) <10% (p=0.029). However, after adjustment for BMI, the endometriosis group showed no statistical significance in obstetrical complications, including SGA (adjusted odds ratio, 1.568; 95% confidence interval, 0.984–2.499; p=0.059). Conclusion Twin pregnancies with endometriosis were not related to adverse effects on pregnancy outcomes and obstetrical complications. To confirm these outcomes, further large prospective studies are required.

Purpose: Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)–based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea. Materials and Methods: A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions. Results: NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples. Conclusion This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

Purpose: The aims of this study were to evaluate the cumulative recurrence, reoperation, and pregnancy rates after ovarian endometrioma surgery at a single institution for more than a 5-year follow-up period. Materials and Methods: This study was conducted as a retrospective chart review of patients with ovarian endometrioma who underwent surgery between January 2008 and March 2016. Study subjects included premenopausal women with at least 5 years of follow-up. Exclusion criteria were patients with stage I or II ovarian endometrioma, those who underwent hysterectomy or bilateral oophorectomy, and presence of residual ovarian lesions on the first postoperative ultrasonography at 3–6 months. Recurrence was defined as a cystic mass by ultrasonography. Results: A total of 756 patients were recruited. The median follow-up duration was 85.5 months (interquartile range, 71–107 months). Recurrent endometrioma was detected in 27.9% patients, and reoperation was performed in 8.3% patients. Cumulative rates at 24, 36, 60, and 120 months were 5.8%, 8.7%, 15.5% and 37.6%, respectively, for recurrence and 0.1%, 0.5%, 2.9%, and 15.1%, respectively, for reoperation. After multivariable analysis, age ≤31 years [hazard ratio (HR)=2.108; 95% confidence interval (CI)=1.522–2.921; p<0.001], no subsequent pregnancy (HR=1.851; 95% CI=1.309–2.617; p<0.001), and postoperative hormonal treatment ≤15 months (HR=2.869; 95% CI=2.088–3.941; p<0.001) were significant risk factors for recurrent endometrioma. Among 315 patients who desired pregnancy, 54.0% were able to have a successful pregnancy and delivery. Conclusion Considering that longer postoperative hormonal treatment is the sole modifiable factor for recurrent endometrioma, we recommend long-term hormonal treatment until subsequent pregnancy, especially in younger women.

Purpose: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. Methods: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. Results: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). Conclusion Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.