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: This study aimed to investigate the incidence, risk factors, and clinical course of nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy, focusing on the role of adjuvant chemotherapy and other metabolic changes. Methods: A retrospective analysis was conducted on 189 patients who underwent pancreaticoduodenectomy between 2013 and 2016. NAFLD was diagnosed using computed tomography (CT) imaging, defined as a liver-tospleen attenuation ratio <0.9. Sarcopenia and sarcopenic obesity were assessed using preoperative CT scans. Logistic regression analysis was performed to identify risk factors for NAFLD development. Results: The cumulative incidence of NAFLD increased over time, with rates of 15.9% at one year, 20.4% at three years, and 35.2% at five years post-pancreaticoduodenectomy. Adjuvant chemotherapy was identified as the only significant independent predictor of NAFLD development (odds ratio, 2.74; 95% confidence interval, 1.16-6.70; P=0.023). No significant associations were found between NAFLD and pancreatic enzyme replacement therapy (PERT), sarcopenia, or sarcopenic obesity. Serial analysis of NAFLD status in long-term survivors revealed dynamic changes, with some patients experiencing spontaneous remission or recurrence. Conclusion NAFLD is a common, progressive complication following pancreaticoduodenectomy, particularly in patients receiving adjuvant chemotherapy. Although no significant associations with PERT or sarcopenia were observed, these areas warrant further investigation. Long-term monitoring and targeted management strategies are recommended to address NAFLD in this population. Future prospective studies are needed to elucidate the natural history and contributing factors of NAFLD after pancreaticoduodenectomy.

Purpose: This study aimed to investigate the incidence, risk factors, and clinical course of nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy, focusing on the role of adjuvant chemotherapy and other metabolic changes. Methods: A retrospective analysis was conducted on 189 patients who underwent pancreaticoduodenectomy between 2013 and 2016. NAFLD was diagnosed using computed tomography (CT) imaging, defined as a liver-tospleen attenuation ratio <0.9. Sarcopenia and sarcopenic obesity were assessed using preoperative CT scans. Logistic regression analysis was performed to identify risk factors for NAFLD development. Results: The cumulative incidence of NAFLD increased over time, with rates of 15.9% at one year, 20.4% at three years, and 35.2% at five years post-pancreaticoduodenectomy. Adjuvant chemotherapy was identified as the only significant independent predictor of NAFLD development (odds ratio, 2.74; 95% confidence interval, 1.16-6.70; P=0.023). No significant associations were found between NAFLD and pancreatic enzyme replacement therapy (PERT), sarcopenia, or sarcopenic obesity. Serial analysis of NAFLD status in long-term survivors revealed dynamic changes, with some patients experiencing spontaneous remission or recurrence. Conclusion NAFLD is a common, progressive complication following pancreaticoduodenectomy, particularly in patients receiving adjuvant chemotherapy. Although no significant associations with PERT or sarcopenia were observed, these areas warrant further investigation. Long-term monitoring and targeted management strategies are recommended to address NAFLD in this population. Future prospective studies are needed to elucidate the natural history and contributing factors of NAFLD after pancreaticoduodenectomy.

Purpose: This study aimed to investigate the incidence, risk factors, and clinical course of nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy, focusing on the role of adjuvant chemotherapy and other metabolic changes. Methods: A retrospective analysis was conducted on 189 patients who underwent pancreaticoduodenectomy between 2013 and 2016. NAFLD was diagnosed using computed tomography (CT) imaging, defined as a liver-tospleen attenuation ratio <0.9. Sarcopenia and sarcopenic obesity were assessed using preoperative CT scans. Logistic regression analysis was performed to identify risk factors for NAFLD development. Results: The cumulative incidence of NAFLD increased over time, with rates of 15.9% at one year, 20.4% at three years, and 35.2% at five years post-pancreaticoduodenectomy. Adjuvant chemotherapy was identified as the only significant independent predictor of NAFLD development (odds ratio, 2.74; 95% confidence interval, 1.16-6.70; P=0.023). No significant associations were found between NAFLD and pancreatic enzyme replacement therapy (PERT), sarcopenia, or sarcopenic obesity. Serial analysis of NAFLD status in long-term survivors revealed dynamic changes, with some patients experiencing spontaneous remission or recurrence. Conclusion NAFLD is a common, progressive complication following pancreaticoduodenectomy, particularly in patients receiving adjuvant chemotherapy. Although no significant associations with PERT or sarcopenia were observed, these areas warrant further investigation. Long-term monitoring and targeted management strategies are recommended to address NAFLD in this population. Future prospective studies are needed to elucidate the natural history and contributing factors of NAFLD after pancreaticoduodenectomy.

Purpose: This study aimed to investigate the incidence, risk factors, and clinical course of nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy, focusing on the role of adjuvant chemotherapy and other metabolic changes. Methods: A retrospective analysis was conducted on 189 patients who underwent pancreaticoduodenectomy between 2013 and 2016. NAFLD was diagnosed using computed tomography (CT) imaging, defined as a liver-tospleen attenuation ratio <0.9. Sarcopenia and sarcopenic obesity were assessed using preoperative CT scans. Logistic regression analysis was performed to identify risk factors for NAFLD development. Results: The cumulative incidence of NAFLD increased over time, with rates of 15.9% at one year, 20.4% at three years, and 35.2% at five years post-pancreaticoduodenectomy. Adjuvant chemotherapy was identified as the only significant independent predictor of NAFLD development (odds ratio, 2.74; 95% confidence interval, 1.16-6.70; P=0.023). No significant associations were found between NAFLD and pancreatic enzyme replacement therapy (PERT), sarcopenia, or sarcopenic obesity. Serial analysis of NAFLD status in long-term survivors revealed dynamic changes, with some patients experiencing spontaneous remission or recurrence. Conclusion NAFLD is a common, progressive complication following pancreaticoduodenectomy, particularly in patients receiving adjuvant chemotherapy. Although no significant associations with PERT or sarcopenia were observed, these areas warrant further investigation. Long-term monitoring and targeted management strategies are recommended to address NAFLD in this population. Future prospective studies are needed to elucidate the natural history and contributing factors of NAFLD after pancreaticoduodenectomy.

Purpose: This study aimed to investigate the incidence, risk factors, and clinical course of nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy, focusing on the role of adjuvant chemotherapy and other metabolic changes. Methods: A retrospective analysis was conducted on 189 patients who underwent pancreaticoduodenectomy between 2013 and 2016. NAFLD was diagnosed using computed tomography (CT) imaging, defined as a liver-tospleen attenuation ratio <0.9. Sarcopenia and sarcopenic obesity were assessed using preoperative CT scans. Logistic regression analysis was performed to identify risk factors for NAFLD development. Results: The cumulative incidence of NAFLD increased over time, with rates of 15.9% at one year, 20.4% at three years, and 35.2% at five years post-pancreaticoduodenectomy. Adjuvant chemotherapy was identified as the only significant independent predictor of NAFLD development (odds ratio, 2.74; 95% confidence interval, 1.16-6.70; P=0.023). No significant associations were found between NAFLD and pancreatic enzyme replacement therapy (PERT), sarcopenia, or sarcopenic obesity. Serial analysis of NAFLD status in long-term survivors revealed dynamic changes, with some patients experiencing spontaneous remission or recurrence. Conclusion NAFLD is a common, progressive complication following pancreaticoduodenectomy, particularly in patients receiving adjuvant chemotherapy. Although no significant associations with PERT or sarcopenia were observed, these areas warrant further investigation. Long-term monitoring and targeted management strategies are recommended to address NAFLD in this population. Future prospective studies are needed to elucidate the natural history and contributing factors of NAFLD after pancreaticoduodenectomy.

Background/Aims: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events, including endocrine dysfunctions, which can have serious consequences on patient health and quality of life. The clinical course and characteristics of immune-related hypophysitis (irH) are not well established. This study aimed to analyze the clinical course and characteristics of irH. Methods: This single-center, retrospective study analyzed data from electronic medical records of Asan Medical Center, spanning January 2017 through June 2021. It included adult patients with solid tumors who underwent thyroid and adrenal function tests, along with gonadotropin and/or growth hormone evaluations, following the initiation of ICI treatment within the same period. The study explored the clinical characteristics of ICI-treated patients with and without irH, the incidence of irH, the time to irH onset, and the associated hormonal changes. Results: Twenty-one patients were included in this analysis. Clinical characteristics did not differ significantly between the irH (n = 13) and non-irH (n = 8) groups. Deficiency rates in the irH group were 23.1% for thyroid-stimulating hormone (n = 3), 76.9% for adrenocorticotropic hormone (n = 10), 61.5% for gonadotropin (n = 8), and 15.4% for growth hormone (n = 2). The overall incidence was 0.9 per person-year, with 6-month and 1-year cumulative incidences of 38.8% and 57.1%, respectively. The median time from ICI initiation to irH diagnosis was 7.7 months. Time to levothyroxine replacement was shorter in the irH group. Conclusions The findings provide evidence that could facilitate the prediction of ICI-induced irH based on clinical course and characteristics.

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.