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: The purpose of this study was to evaluate the clinical characteristics and treatment outcomes of alveolar soft part sarcoma (ASPS) of the extremities and trunk and investigate the prognostic factors. Materials and Methods: Forty patients presenting with ASPS in the extremities or trunk between 2001 and 2021 were reviewed retrospectively. We evaluated the clinical manifestations at presentation, local recurrence, and metastasis after treatment. The survival rates and prognostic factors affecting survival were analyzed. Only patients who were followed up for more than one year were included in the study. The mean follow-up time was 58 months (range, 12–120). Results: The average age of the patients was 26 years (range, 12–54) and the primary tumor developed mainly in the thigh (23 patients, 57.5%). The average size of the tumor was 8.7 cm and metastasis at presentation was seen in 28 (70%) patients. The overall survival rates at five-years and 10-years were 53.7% and 34.5%, respectively. Metastasis at presentation was related to poor survival (p=0.001). Conclusion ASPS in the extremities or trunk present with a high rate of metastasis and patients with metastasis showed poorer survival.In the future, further efforts to develop novel therapies like target therapy or immunotherapy for the treatment of metastatic patients are warranted.

Purpose: Giant cell tumor (GCT) of the proximal femur is relatively rare, with only a few case series reported thus far. This study aimed to evaluate the clinical outcomes of GCT of the proximal femur treated with intralesional curettage and expand the understanding of their characteristics and treatment considerations. Materials and Methods: Fifteen cases treated with curettage for GCT of the proximal femur between 2007 and 2020 were reviewed. The median follow-up was 46 months (25–150 months). There were 10 males and 5 females with a median age of 26 years (17–71 years). After curettage, the bone defect was filled with either an allograft (7 cases) or bone cement (8 cases). Results: The postoperative complications were local recurrences in three cases (20.0%), including malignant transformation in one case and a femur neck fracture in one case (6.7%) following curettage and strut allograft. Among the 15 cases, 13 (86.7%) retained their native joint at the last follow-up. No patients developed degenerative changes or osteonecrosis. Conclusion The results of proximal femoral GCT with curettage were acceptable despite local recurrences in three cases (20.0%), and femur neck fracture in one case. An appropriate surgical approach and reconstruction according to the extent of the lesion are necessary for successful treatment.

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder.Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamicpituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed:dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PVpositive neurons were increased in the DG, CA3, presubiculum, and parasubiculum.Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

Background: Mechanical failures of tumor endoprosthesis in the distal femur usually require revision surgery. We investigated if the proximal femur host bone can be salvaged by onlay and overlapping allograft in revision surgeries due to aseptic loosening and stem fractures. Methods: We retrospectively reviewed 18 patients (7 men and 11 women) with osteosarcoma around the knee. The entire cohort was classified into three subgroups (no bone graft: 6, onlay allograft: 7, and overlapping allograft: 5) according to our treatment strategy. Results: The median interval from the initial surgery to the revision was 94.5 months (range, 21–219 months), and the median follow-up period from the revision surgery was 88.0 months (range, 24–179 months). At the last follow-up, 9 of the 18 patients maintained their endoprostheses, and the 5-year prosthesis survival rate was 57.9%. Limb survival was 100%. Five-year prosthesis survival rate was 66.7% in the no bone graft group, 85.7% in the onlay allograft group while 30.0% in the overlapping allograft group. In the no bone graft group and onlay allograft group, 66.7% (4/6) and 57.1% (4/7) maintained their revision prostheses while no prostheses survived in the overlapping allograft group. Recurrent stem loosening was observed in 14.2% (1/7) and 60.0% (3/5) of the onlay allograft and overlapping allograft groups, respectively, despite allograft bone union. The complication rate was 66.7% (12/18) in the entire cohort. The most common type of complication was infection (n = 6), followed by aseptic loosening (n = 4) and mechanical failure (n = 2). Conclusions This study indicates that onlay allograft can be used as a supportive method in revising failed endoprosthesis if the extent of host bone destruction is extensive. However, applying overlapping allograft to secure bone stock showed a high rate of mechanical failures and infection in the long term. Future studies with a larger cohort are necessary to assess the prognostic factors for the higher complication rate in overlapping allograft and the need for overlapping allograft. Surveillance with consideration of the risk of anteromedial osteolysis in allograft and efforts for prevention of periprosthetic infection are essential.

Purpose: This study examined the prevalence of osteoarthritis of the knee after curettage and polymethylmethacrylate (PMMA) application for giant cell tumor of the bone (GCTB) and factors affecting the development of osteoarthritis of the knee. Materials and Methods: Fifty-five patients with GCTB of the distal femur who were treated with curettage and PMMA filling between June 2001 and June 2016 were reviewed retrospectively. The development of osteoarthritis of the knee, as Kellgren–Lawrence grade 3 or 4, was determined by radiography of the latest follow-up data. This study evaluated the influence of the factors on the development of osteoarthritic changes. Only patients followed up for more than five years were included and the median follow-up was 77 months (range, 60–237 months). Results: Osteoarthritis of the knee was observed in 10 patients (18%) of whom three showed preoperative arthritic changes and did not progress. Seven (13%) patients experienced progression of the arthritic changes after surgery at a median of five years (range, 4–12 years). On the other hand, none of them received total knee arthroplasty. Among seven patients who showed progression of arthritis, four patients presented with a pathologic fracture initially and showed arthritic changes at a median of 4.5 years after surgery. The other three patients showed arthritic changes after ten years or more. Pathologic fractures (p=0.0001) and subchondral bone involvement (p=0.011) were significant risk factors for the development of osteoarthritis. Conclusion The incidence of development of osteoarthritis of the knee after curettage and PMMA application at distal femoral GCTB was 13%, but none of these patients received further surgery, such as total knee arthroplasty. The pathologic fracture and subchondral bone involvement are risk factors for arthritic changes in the midterm follow-up.

Purpose: Periprosthetic fractures of a tumor prosthesis are rare but have difficulties in achieving sound fixation because of the poor bone quality, which increases the risk of loosening or re-fracture, even after bone union. A cortical strut onlay allograft was adopted for peri-prosthetic fractures after hip arthroplasty into the periprosthetic fracture of a tumor prosthesis, assuming that it would assist in firm fixation, shorten the time to union, and increase the bone stock, thereby, lower the chance of loosening and re-fracture. Materials and Methods: This study reviewed 27 patients (30 cases) of periprosthetic fracture of tumor prosthesis. Sixteen cases (allograft group) had augmentation with an onlay allograft, while 14 cases (conventional group) had internal fixation or conservative treatment.The following were assessed; mode of periprosthetic fracture, difference in the time to union between a strut cortical onlay allograft and without it, and survival of prosthesis, complication, and functional outcome between the two groups. Results: According to the unified classification system (UCS), 21 cases were type B (70.0%; B1, 14; B2, 1; B3, 6) and 9 cases were type C.The five-, 10-year survival of the 30 reconstructions by Kaplan–Meier plot was 84.5%±4.18% and 42.2%±7.83%, respectively. The average time to bone union of the entire cohort was 5.1 months (range, 2.0–11.2 months). The allograft group (3.5 months) showed a shorter period for union than the conventional group (7.2 months) (p<0.0001). All four cases of major complications occurred in the conventional group. Two cases with loosening and anterior angulation were treated with a change of prosthesis, and another with infection underwent amputation. The remaining case with loosening had conservative management. At the final follow-up, the average Musculosketal Tumor Society score of the allograft group (26.1) was better than that of the conventional group (20.9). Conclusion Bone union in periprosthetic fractures of a tumor prosthesis can be achieved, but the minimization of complications is important. An onlay allograft facilitates firm fixation and increases the bone stock with a shortened time to union. This simple method can minimize the risk of loosening, joint contracture, and re-fracture.

The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.