Purpose: Atypical hyperplasia (AH) management remains controversial due to variable malignant disease progression rates. While Western studies report 10% to 25% upgrade rates, data from Asian populations, particularly from referral academic centers, are limited. We aimed to identify predictive factors for malignant upgrade in Korean women with AH at academic hospitals. Methods: This retrospective multi-institutional study analyzed 340 patients diagnosed with AH on initial biopsy who underwent subsequent excision at five Korean academic hospitals from 2000 to 2022. Malignant upgrade was defined as ductal carcinoma in situ or invasive cancer on the final pathology. Multivariate logistic regression was used to identify independent predictors of upgrades. Results: Among 340 patients (319 atypical ductal hyperplasia, 20 atypical lobular hyperplasia, and 1 mixed), 128 (37.6%) experienced a malignant upgrade, 98 (76.6%) to ductal carcinoma in situ, and 30 (23.4%) to invasive cancer. In multivariate analysis, multifocal atypia (odds ratio [OR], 25.61; 95% confidence interval [CI], 11.20–58.55; P<0.001) and Breast Imaging-Reporting and Data System 4c-5 lesions (OR, 11.02; 95% CI, 1.43–84.86; P=0.021) were significant predictors. Multifocal atypia showed an 84.4% upgrade rate. Core needle biopsy had higher upgrade rates than vacuum-assisted biopsy (45.2% vs. 20.0%; P<0.001). The upgrade rates decreased from 50% to 25% over the study period (P<0.05). Conclusion The 37.6% upgrade rate in this tertiary referral cohort exceeded that in Western reports, with multifocal atypia emerging as the strongest predictor. These findings support immediate excision for multifocal atypia while allowing individualized management for unifocal lesions with favorable imaging in Korean tertiary care settings.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Papillary thyroid cancer (PTC), a common malignancy among women of reproductive age, is increasingly common during pregnancy because of routine prenatal imaging. However, the optimal timing for surgical treatment remains controversial. This study aimed to assess the safety and practicality of performing thyroid surgery during pregnancy through a comparative analysis of perioperative and pathological outcomes between pregnant and nonpregnant women. Methods: We conducted a retrospective case-control study of 100 female patients aged 20–39 years who underwent thyroid surgery for PTC between January 2019 and December 2024. Patients were grouped into pregnant (n = 14) and nonpregnant (n = 86) cohorts. Clinical, surgical, and pathological data were compared. Results: Most pregnant patients underwent surgery during the second trimester. The operative duration was significantly shorter in the pregnant group than in the nonpregnant group (71.4 ± 26.35 minutes vs. 87.2 ± 5.17 minutes, P = 0.025), and there was a trend towards a lower drain volume on postoperative day 1 (25.2 ± 15.23 mL vs. 32.7 ± 0.18 mL, P = 0.077).No significant differences were observed in terms of complication rates. Despite a higher frequency of extrathyroidal extension (P = 0.003) and advanced T stage (P = 0.038) in the pregnant group, the surgical outcomes were favorable. One neonate experienced mild intraventricular hemorrhage that resolved without sequelae. Conclusion Thyroid surgery during pregnancy, particularly in the second trimester, appears feasible in selected patients.Given the small sample and retrospective nature of this study, larger prospective studies are needed to validate these findings.

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

The aim of this study was to identify the anatomical feature of retaining ligament and fat compartment on the lower eyelid and infraorbital region using a histological method, and to investigate clear definitions for them which could be used generally in the clinical area. Eighteen specimens from eight fresh Korean cadavers were stained with Masson trichrome or hematoxylin and eosin. The ligamentous and fascial fibrous tissue were clearly identified. The ligamentous fibrous tissue which traversed in the superficial and deep fat layer was skin ligament and orbicularis retaining ligament (ORL). The fascial fibrous tissue enclosed the orbicularis oculi muscle (OOc) and circumferencial adipose tissue. Based on the ligamentous and fascial structure, three fat compartments, septal, suborbicularis oculi and infraorbital fat compartment, could be identified.The OOc attached to orbital rim and dermis by ORL and skin ligament, and the muscle fascicle and fat fascicle provided the connection point to the ORL and skin ligament as enclosing all muscle and fat tissue. The combination of the force made by the skin ligament in the lower eyelid and ORL may decide the level and form of the infraorbital grooves.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.