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.

OBJECTIVE: To investigate the diagnostic performance of coronary computed tomography angiography (CCTA), stress dual-energy computed tomography perfusion (DE-CTP), stress perfusion single-photon emission computed tomography (SPECT), and the combinations of CCTA with myocardial perfusion imaging (CCTA + DE-CTP and CCTA + SPECT) for identifying coronary artery stenosis that causes myocardial hypoperfusion. Combined invasive coronary angiography (ICA) and stress perfusion cardiac magnetic resonance (SP-CMR) imaging are used as the reference standard. MATERIALS AND METHODS: We retrospectively reviewed the records of 25 patients with suspected coronary artery disease, who underwent CCTA, DE-CTP, SPECT, SP-CMR, and ICA. The reference standard was defined as ≥ 50% stenosis by ICA, with a corresponding myocardial hypoperfusion on SP-CMR. RESULTS: For per-vascular territory analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 96, 96, 68, 93, and 68%, respectively, and specificities were 72, 75, 89, 85, and 94%, respectively. The areas under the receiver operating characteristic curve (AUCs) were 0.84 ± 0.05, 0.85 ± 0.05, 0.79 ± 0.06, 0.89 ± 0.04, and 0.81 ± 0.06, respectively. For per-patient analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 100, 100, 89, 100, and 83%, respectively; the specificities were 14, 43, 57, 43, and 57%, respectively; and the AUCs were 0.57 ± 0.13, 0.71 ± 0.11, 0.73 ± 0.11, 0.71 ± 0.11, and 0.70 ± 0.11, respectively. CONCLUSION: The combination of CCTA and DE-CTP enhances specificity without a loss of sensitivity for detecting hemodynamically significant coronary artery stenosis, as defined by combined ICA and SP-CMR.
Angiography* ; Area Under Curve ; Constriction, Pathologic ; Coronary Angiography* ; Coronary Artery Disease* ; Coronary Stenosis ; Coronary Vessels* ; Humans ; Magnetic Resonance Imaging* ; Myocardial Perfusion Imaging ; Myocardium ; Perfusion* ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Tomography, Emission-Computed* ; Tomography, Emission-Computed, Single-Photon

OBJECTIVE: To evaluate the feasibility of coronary artery calcium scoring based on three virtual noncontrast-enhanced (VNC) images derived from single-source spectral dual-energy CT (DECT) as compared with true noncontrast-enhanced (TNC) images. MATERIALS AND METHODS: This prospective study was conducted with the approval of our Institutional Review Board. Ninety-seven patients underwent noncontrast CT followed by contrast-enhanced chest CT using single-source spectral DECT. Iodine eliminated VNC images were reconstructed using two kinds of 2-material decomposition algorithms (material density iodine-water pair [MDW], material density iodine-calcium pair [MDC]) and a material suppressed algorithm (material suppressed iodine [MSI]). Two readers independently quantified calcium on VNC and TNC images. The Spearman correlation coefficient test and Bland-Altman method were used for statistical analyses. RESULTS: Coronary artery calcium scores from all three VNC images showed excellent correlation with those from the TNC images (Spearman's correlation coefficient [ρ] = 0.94, 0.88, and 0.89 for MDW, MDC, and MSI, respectively; p < 0.001 for all pairs). Measured coronary calcium volumes from VNC images also correlated well with those from TNC images (ρ = 0.92, 0.87, and 0.91 for MDW, MDC, and MSI, respectively; p < 0.001 for all pairs). Among the three VNC images, coronary calcium from MDW correlated best with that from TNC. The coronary artery calcium scores and volumes were significantly lower from the VNC images than from the TNC images (p < 0.001 for all pairs). CONCLUSION: The use of VNC images from contrast-enhanced CT using dual-energy material decomposition/suppression is feasible for coronary calcium scoring. The absolute value from VNC tends to be smaller than that from TNC.
Calcium* ; Coronary Artery Disease ; Coronary Vessels* ; Ethics Committees, Research ; Humans ; Iodine ; Prospective Studies ; Tomography, X-Ray Computed

PURPOSE: We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. METHODS: Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. RESULTS: There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R2 = 0.428, P < 0.001). CONCLUSION: Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis.
Fatty Liver ; Humans ; Liver ; Liver Transplantation ; Living Donors* ; Magnetic Resonance Imaging* ; Population Characteristics ; Tissue Donors ; Transplant Donor Site

PURPOSE: Hepatic resection is a standard method of treatment for colorectal liver metastases (CRLM). However, the pathologic factors of metastatic lesions that affect tumor recurrence are less well defined in CRLM. The aim of this study was to evaluate the risk factors for recurrence of CRLM, focusing on histopathologic factors of metastatic lesions of the liver. METHODS: From January 2003 to December 2008, 117 patients underwent curative hepatic resection for CRLM were reviewed. Tumor size and number, differentiation, tumor budding, angio-invasion, dedifferentiation and tumor infiltrating inflammation of metastatic lesions were investigated. RESULTS: The mean number of hepatic tumors was 2 (range, 1-8). The mean size of the largest tumor was 2.9 cm (range, 0.3-18.5 cm) in diameter. The moderate differentiation of the hepatic tumor was the most common in 86.3% of the patients. Tumor budding, angio-invasion, and dedifferentiation were observed in 81%, 34%, and 12.8% of patients. Inflammation infiltrating tumor was detected in 6.8% of patients. Recurrence after hepatic resection appeared in 69 out of 117 cases (58.9%). Recurrence-free survival at 1, 2 and 5 years were 62.4%, 43.6%, and 34.3%. The multivariate analysis showed the number of metastases > or =3 (P = 0.007), the tumor infiltrating inflammation (P = 0.047), and presence of dedifferentiation (P = 0.020) to be independent risk factors for tumor recurrence. CONCLUSION: Histopathological factors, i.e., dedifferentiation and tumor infiltrating inflammation of the metastatic lesion, could be one of the risk factors of aggressive behavior as well as the number of metastases even after curative resection for CRLM.
Colorectal Neoplasms ; Humans ; Inflammation ; Liver* ; Multivariate Analysis ; Neoplasm Metastasis* ; Recurrence* ; Risk Factors

JL1, a specific epitope on CD43, is a potential biomarker for the diagnosis of acute leukemia. Although qualitative assays for detecting leukemia-specific CD43 exist, there is a need to develop quantitative assays for the same. Here, we developed two novel monoclonal antibodies (mAbs), 2C8 and 8E10, recognizing different epitopes on CD43. These clones are capable of pairing with YG5, another mAb against JL1 epitope, because they were selectively obtained using sandwich ELISA. Antigens recognized by 2C8 and 8E10 were confirmed as CD43 by western blotting using the CD43-hFC recombinant protein. When expression on various leukemic cell lines was investigated, 2C8 and 8E10 displayed a disparity in the distribution of the epitope. Enzyme assays revealed that these mAbs recognized a sialic acid-dependent epitope on CD43. Using normal thymus and lymph node paraffin-embedded tissues, we confirmed a difference in the epitopes recognized by the two mAbs that was predicted based on the maturity of the cells in the tissue. In summary, we developed and characterized two mAbs, 2C8 and 8E10, which can be used with YG5 in a sandwich ELISA for detecting leukemia-specific CD43.
Antibodies, Monoclonal ; Blotting, Western ; Cell Line ; Clone Cells ; Diagnosis ; Enzyme Assays ; Enzyme-Linked Immunosorbent Assay ; Epitopes* ; Leukemia ; Lymph Nodes ; Thymus Gland

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.
Adult ; Aged ; Area Under Curve ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/etiology ; Graft Rejection/prevention & control ; Humans ; Immunosuppressive Agents/blood/*pharmacokinetics ; Leukopenia/etiology ; Liver/pathology ; Liver Failure/*therapy ; *Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs & derivatives/blood/pharmacokinetics ; ROC Curve ; Retrospective Studies ; Tacrolimus/therapeutic use ; Tissue Donors

OBJECTIVES: Colonoscopy is a popular tool for screening for colon cancer throughout the world. The incidence of polypectomy and follow-up colonoscopy are persistently increasing but the studies about follow-up test after polypectomy are still lack of its domestic sources. This study is designed to look into the recurrence rate of colon polyps and risk factors after polypectomy. METHODS: This is a retrospective study by reviewing medical charts of 147 patients who underwent polypectomy and follow-up colonoscopy from Jan. 2000 to Mar. 2008. The Kudo classification was used to describe the polyps found in the colonoscopy. The follow-up period was defined as the term between polypectomy and the first colonoscopy follow up. RESULTS: Seventy six point two percent of the enrolled patient were male and the mean age was 56.5 +/- 8.1. Mean follow-up period was 24.9 +/- 13.7 (6 - 65) months. The cumulative recurrence rate of 1 year was 11.6%. The rate of 2 years was 36.7% and that of 3 years was 55.8%. The number of polyps was the factor which statistically showed significant relation of its recurrence rate. The histological morphology characteristic of polyps could be one independent factor which may be associated to the recurrence of polyps. CONCLUSIONS: The importance of colonoscopy follow up after polypectomy was clearly emphasized through the cumulative recurrence rate of 55.8%. Therefore, there is a need for more domestic studies with a large number of patients about the recurrence of polyps after polypectomy.
Adenomatous Polyps* ; Classification ; Colon* ; Colonic Neoplasms ; Colonic Polyps ; Colonoscopy ; Follow-Up Studies ; Humans ; Incidence ; Male ; Mass Screening ; Polyps ; Recurrence* ; Retrospective Studies ; Risk Factors