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.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Purpose: This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. Materials and Methods: The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. Results: The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. Conclusion Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

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.

In order to provide a physiological solution for patients with breast cancer-related lymphedema (BCRL), the surgeon must understand where and how the pathology of lymphedema occurred. Based on each patient’s pathology, the treatment plan should be carefully decided and individualized. At the authors’ institution, the treatment plan is made individually based on each patient’s symptoms and relative factors. Most early-stage patients first undergo decongestive therapy and then, depending on the efficacy of the treatment, a surgical approach is suggested. If the patient is indicated for surgery, all the points of lymphatic flow obstruction are carefully examined. Thus a BCRL patient can be considered for lymphaticovenous anastomosis (LVA), a lymph node flap, scar resection, or a combination thereof. LVA targets ectatic superficial collecting lymphatics, which are located within the deep fat layer, and preoperative mapping using ultrasonography is critical. If there is contracture on the axilla, axillary scar removal is indicated to relieve the vein pressure and allow better drainage. Furthermore, removing the scars and reconstructing the fat layer will allow a better chance for the lymphatics to regenerate. After complete removal of scar tissue, a regional fat flap or a superficial circumflex iliac artery perforator flap with lymph node transfer is performed. By deciding the surgical planning for BCRL based on each patient’s pathophysiology, optimal outcomes can be achieved. Depending on each patient’s pathophysiology, LVA, scar removal, vascularized lymph node transfer with a sufficient adipocutaneous flap, and simultaneous breast reconstruction should be planned.

Angiolipoma is a benign fatty neoplasm that has components of proliferating blood vessels. These types of lesions commonly occur in the subcutaneous tissue of the limbs and trunk. Angiolipoma in the gastrointestinal tract is extremely rare, and the final diagnosis generally depends on histological examination of the excised biopsy. In most previously reported cases, the lesions were diagnosed and treated with surgical management. In this study, we report a case of gastric angiolipoma of approximately 4 cm in size that was diagnosed and treated with endoscopic submucosal dissection.

In order to provide a physiological solution for patients with breast cancer-related lymphedema (BCRL), the surgeon must understand where and how the pathology of lymphedema occurred. Based on each patient’s pathology, the treatment plan should be carefully decided and individualized. At the authors’ institution, the treatment plan is made individually based on each patient’s symptoms and relative factors. Most early-stage patients first undergo decongestive therapy and then, depending on the efficacy of the treatment, a surgical approach is suggested. If the patient is indicated for surgery, all the points of lymphatic flow obstruction are carefully examined. Thus a BCRL patient can be considered for lymphaticovenous anastomosis (LVA), a lymph node flap, scar resection, or a combination thereof. LVA targets ectatic superficial collecting lymphatics, which are located within the deep fat layer, and preoperative mapping using ultrasonography is critical. If there is contracture on the axilla, axillary scar removal is indicated to relieve the vein pressure and allow better drainage. Furthermore, removing the scars and reconstructing the fat layer will allow a better chance for the lymphatics to regenerate. After complete removal of scar tissue, a regional fat flap or a superficial circumflex iliac artery perforator flap with lymph node transfer is performed. By deciding the surgical planning for BCRL based on each patient’s pathophysiology, optimal outcomes can be achieved. Depending on each patient’s pathophysiology, LVA, scar removal, vascularized lymph node transfer with a sufficient adipocutaneous flap, and simultaneous breast reconstruction should be planned.

Angiolipoma is a benign fatty neoplasm that has components of proliferating blood vessels. These types of lesions commonly occur in the subcutaneous tissue of the limbs and trunk. Angiolipoma in the gastrointestinal tract is extremely rare, and the final diagnosis generally depends on histological examination of the excised biopsy. In most previously reported cases, the lesions were diagnosed and treated with surgical management. In this study, we report a case of gastric angiolipoma of approximately 4 cm in size that was diagnosed and treated with endoscopic submucosal dissection.