Objective Multidector computed tomography (MDCT) is now commonly used for the evaluation of coronary artery disease. Because MDCT images include many non-cardiac organs and the patient population evaluated is highly susceptible to extracardiac diseases, this study was designed to evaluate the prevalence of extracardiac findings in the MDCT evaluation of ischemic heart disease. Methods From March 2007 to March 2008, a total of six-hundred twenty patients, who underwent 64-slice MDCT evaluations for chest pain, or dyspnea, were enrolled in this study. Cardiac and non-cardiac findings were comprehensively evaluated by a radiologist. Results Enrolled patients included 306 men (49.4%), with a mean age of 66 years. Significant coronary artery stenosis was found in 41.6%of the patients. A total of 158 extracardiac findings were observed in 110 (17.7%) patients. Commonly involved extracardiac organs were lung (36.7%), hepatobiliary system (21.5%), thyroid (19.6%), kidney (10.8%), spine (9.7%) and breast (0.6%). Of those 110 patients, 50 (45.5%) patients underwent further diagnostic investigations. Malignant disease was detected in three (2.7%) patients (lung cancer, pancreatic cancer, and thyroid cancer). Conclusions Extracardiac findings are frequently present and should be a concern in the MDCT evaluation of chest pain syndrome.

Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer CellFree Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. Conclusions Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.
Adolescent ; Adult ; Breast Neoplasms/complications/*diagnosis/therapy ; Combined Modality Therapy ; Exons ; Female ; Genotype ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/complications/*diagnosis/therapy ; Middle Aged ; Multimodal Imaging ; Mutation, Missense ; Pedigree ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53/genetics ; Young Adult

Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.
Adolescent ; Adult ; Breast Neoplasms/complications/*diagnosis/therapy ; Combined Modality Therapy ; Exons ; Female ; Genotype ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/complications/*diagnosis/therapy ; Middle Aged ; Multimodal Imaging ; Mutation, Missense ; Pedigree ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53/genetics ; Young Adult

PURPOSE: To compare the level of accuracy of intraocular pressure (IOP) measurements of a rebound tonometer (RT) Icare(R), and non-contact tonometer (NCT), using Goldmann Applanation tonometer (GAT) as a reference to evaluate the influence of central corneal thickness (CCT) on IOP readings in the Korean population. METHODS: In a prospective study of 273 eyes, IOP was measured with RT, GAT, and NCT and compared to CCT measurements. Patients were assigned to one of 3 groups based on IOP measurements of GAT and 1 of 2 groups based on CCT. The comparison of the IOP values of RT, GAT, and NCT was performed between the IOP and CCT groups, and the differences among tonometers were evaluated. RESULTS: The RT showed statistically significant correlation with the GAT compared to the NCT. The CCT was related to RT measurements. The RT values compared to the GAT was underestimated in thin corneas and overestimated in thick corneas. CONCLUSIONS: There was a significant correlation between the RT and the GAT measurements compared with the NCT. However, RT is influenced by CCT and correlates less with GAT in low IOP ranges, suggesting that corneal thickness should be taken into consideration during such measurements.
Cornea ; Eye ; Humans ; Intraocular Pressure ; Peptides ; Prospective Studies ; Reading

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients’ perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions Considering the importance of knowing a patient’s BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.

Objective: A simultaneous detection of germline and somatic mutations in ovarian cancer (OC) using tumor materials is considered to be cost-effective for BRCA1/2 testing. However, there are limited studies of the analytical performances according to various sample types. The aim of this study is to propose a strategy for routine BRCA1/2 next-generation sequencing (NGS) screening based on analytical performance according to different sample types. Methods: We compared BRCA1/2 NGS screening assay using buffy coat, fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) from 130 samples. Results: The rate of repeated tests in a total of buffy coat, FF and FFPE was 0%, 8%, and 34%, respectively. The accuracy of BRCA1/2 NGS testing was 100.0%, 99.9% and 99.9% in buffy coat, FFPE and FF, respectively. However, due to the presence of variant allele frequency (VAF) shifted heterozygous variants, tumor materials (FFPE and FF) showed lower sensitivity (95.5%–99.0%) than buffy coat (100%). Furthermore, FFPE showed 51.4% of the positive predictive value (PPV) on account of sequence artifacts. When performed in the post-filtration process, PPV was increased by approximately 20% in FFPE. Buffy coat showed 100% of sensitivity, specificity and accuracy in BRCA1/2 NGS test. Conclusions On the comparison of the analytical performance according to different sample types, the buffy coat was not affected by sequencing artifacts and VAF shifted variants. Therefore, the blood test should be given priority in detecting germline BRCA1/2 mutation, and tumor materials could be suitable to detect somatic mutations in OC patients without identifying germline BRCA1/2 mutation.

BACKGROUND: Health maintenance and monitoring of transplant candidates, the great majority of whom are undergoing chronic dialysis, can be a determinant of post-transplant prognosis. New issues such as malignancy, inflammation, cardiovascular disease, and psychosocial problems might arise among potential recipients, which may lead to cancellation of the transplantation. METHODS: A questionnaire, including questions regarding follow-up monitoring, was sent to 66 transplant centers, and responses to the survey were obtained from 35 centers (53%). A similar questionnaire was sent to 217 wait-listed patients, and 164 (76%) responded. RESULTS: Regular contact between the transplant center and patients was maintained by only 37% of the centers. No consistent pattern of contact was observed for 11%. Sixty percent of the centers monitored patients by telephone. Three-fourths of the transplant centers monitored their patients annually or every 6 months. A cancer screening program was run by only 17% of the centers, and 29% did not routinely request cardiac screening. Most centers (83%) informed their patients of the features of marginal kidneys. However, many patients (69%) reported not hearing about marginal kidneys, and 43% indicated that a cadaver transplant was cancelled because of a cadaver donor problem. CONCLUSIONS: Our survey indicates that the necessity for routine follow-up monitoring is broadly recognized by 86% of transplant centers and 78% of wait-listed patients However, no formal monitoring guidelines currently exist for wait-listed patients in Korea. Therefore, guidelines are absolutely necessary for improving the quality of post-transplant life.
Cadaver ; Cardiovascular Diseases ; Dialysis ; Early Detection of Cancer ; Follow-Up Studies ; Hearing ; Humans ; Inflammation ; Kidney ; Kidney Transplantation ; Korea ; Mass Screening ; Prognosis ; Surveys and Questionnaires ; Telephone ; Tissue Donors ; Transplants ; Waiting Lists

Artifacts ; Blood Buffy Coat ; Gene Frequency ; Hematologic Tests ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Screening ; Ovarian Neoplasms ; Sensitivity and Specificity ; Tissue Preservation

Background: In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods: Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed. Results: The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors. Conclusions The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.