Background: Following success of the phase III PROfound trial, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib was approved by the US Food and Drug Administration in May 2020 for adult patients with deleterious homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). As locally adopted multigene panel next-generation sequencing (NGS) assays for selecting PARP inhibitor candidates have not been thoroughly evaluated, we compared the analytical performance of the FoundationOne CDx (Foundation Medicine, Inc., Cambridge, MA, USA) (central laboratory) and other NGS assays (local laboratory) with samples from the PROfound trial in Korea. Methods: One hundred PROfound samples (60 HRR mutation [HRRm] cases and 40 non-HRRm cases) were analyzed. The results of HRR gene mutation analysis were compared between the FoundationOne CDx and two other NGS assays [SureSelect Custom Design assay (Agilent Technologies, Inc., Santa Clara, CA, USA) and Oncomine Comprehensive assay (Thermo Fisher Scientific, Inc., Waltham, MA, USA)]. Results: The positive percent agreement for single nucleotide variants (SNVs) and insertion/deletions (indels) between the central laboratory and local laboratory was 98.7%–100.0%. The negative percent agreement and overall percent agreement (OPA) for SNVs and indels between central and local laboratories were both 100%. Compared with that of the FoundationOne CDx assay, the OPA for copy number variations of the Oncomine Comprehensive and SureSelect Custom assays reached 99.8%–100%. Most mCRPC patients harboring a deleterious genetic variant were successfully identified with both local laboratory assays. Conclusions The NGS approach at a local laboratory showed comparable analytical performance for identifying HRRm status to the FoundationOne CDx assay used at the central laboratory.

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

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.

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

BACKGROUND: Thyroid incidentalomas detected by 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) have been reported in 1% to 4% of the population, with a risk of malignancy of 27.8% to 74%. We performed a retrospective review of FDG-avid thyroid incidentalomas in cancer screening subjects and patients with nonthyroid cancer. The risk of malignancy in thyroid incidentaloma and its association with the maximal standardized uptake value (SUVmax) in 18F-FDG PET/CT were evaluated to define the predictor variables in assessing risk of malignancy. METHODS: A total of 2,584 subjects underwent 18F-FDG PET/CT for metastatic evaluation or cancer screening from January 2005 to January 2010. Among them, 36 subjects with FDG-avid thyroid incidentalomas underwent further diagnostic evaluation (thyroid ultrasonography-guided fine needle aspiration cytology [FNAC] or surgical resection). We retrospectively reviewed the database of these subjects. RESULTS: Of the 2,584 subjects who underwent 18F-FDG PET/CT (319 for cancer screening and 2,265 for metastatic evaluation), 52 (2.0%) were identified as having FDG-avid thyroid incidentaloma and cytologic diagnosis was obtained by FNAC in 36 subjects. Of the subjects, 15 were proven to have malignant disease: 13 by FNAC and two by surgical resection. The positive predictive value of malignancy in FDG-avid thyroid incidentaloma was 41.7%. Median SUVmax was higher in malignancy than in benign lesions (4.7 [interquartile range (IQR), 3.4 to 6.0] vs. 2.8 [IQR, 2.6 to 4.0], P=0.001). CONCLUSION: Thyroid incidentalomas found on 18F-FDG PET/CT have a high risk of malignancy, with a positive predictive value of 41.7%. FDG-avid thyroid incidentalomas with higher SUVmax tended to be malignant.
Biopsy, Fine-Needle ; Diagnosis ; Early Detection of Cancer ; Electrons ; Fluorodeoxyglucose F18 ; Humans ; Incidental Findings ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Prevalence ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms

Cardiogenic shock after stress-induced cardiomyopathy is very rare and serious, and a reversible, clinical consequence of untreated adrenal insufficiency that is attributable to Sheehan's syndrome. A 53-year-old female presented with confusion, congestive heart failure, and hypotension. Endocrine testing, prior medical history, and brain MRI confirmed the presence of hypopituitarism and secondary adrenal insufficiency owing to undiagnosed Sheehan's syndrome. After glucocorticoid replacement therapy, her cardiac function recovered completely. Stress-induced cardiomyopathy should be considered as a possible cause of unexplained heart failure in patients with Sheehan's syndrome and adrenal insufficiency.
Adrenal Insufficiency ; Brain ; Cardiomyopathies* ; Female ; Heart Failure ; Humans ; Hypopituitarism* ; Hypotension ; Magnetic Resonance Imaging ; Middle Aged ; Shock, Cardiogenic

BACKGROUND: The composite summary score (range, 0-24) of abdominal aortic calcification (AAC) devised by Kauppila et al is a simple method of assessing AAC severity. However, few studies have been conducted to determine an optimal AAC cutoff score for the prediction of mortality or to investigate the relation between mineral metabolism and AAC progression using the scoring system. METHODS: The medical records of 112 patients on hemodialysis who had undergone simple lateral lumbar radiography every 6 months from August 2009 were reviewed. Patients were followed until November 2012, and the relationship between the degree of AAC at baseline and mortality was evaluated. In addition, the relationship between the progression of AAC and serum concentrations of calcium and phosphate was evaluated in the 75 patients who were successfully followed until November 2012. RESULTS: The mean AAC score at baseline was 5.5+/-4.8, and the cutoff calcification score for the prediction of mortality was 7.75 (sensitivity=61%, specificity=81%). Patients were allocated to Group A (baseline total calcification score < or =8.0, n=85) or Group B (baseline total calcification score>8.0, n=27), and multivariate analysis showed that Group B was an independent risk factor of all-cause mortality and cardiovascular events. Of the 75 patients successfully followed, 51 showed AAC progression (Group 1) and 24 showed no change or improvement (Group 2). Group 1 was found to have significantly higher mean serum corrected calcium levels during the 2nd year and 3rd year of follow-up than Group 2. Furthermore, repeated-measures analysis of variance showed higher monthly corrected calcium concentrations (P=0.099) and mean corrected calcium levels during the 1st year, 2nd year, and 3rd year of follow-up (P=0.062) in Group 1, but without statistical significance. The cutoff values of mean corrected calcium of the 2nd year and 3rd year for the prediction of AAC progression during follow-up years were 8.96mg/dL and 9.45mg/dL, respectively. Serum phosphate levels and corrected calciumxphosphate values were similar in Groups 1 and 2. CONCLUSION: Patients with an AAC score of>8 at baseline seem to be at higher risk of mortality during follow-up. Of the serum variables examined, such as corrected calcium, phosphate, and corrected calciumxphosphate, corrected calcium was found to be marginally associated with AAC progression. However, a larger-scale prospective study is required to confirm our findings.
Aorta, Abdominal ; Calcium* ; Follow-Up Studies ; Humans ; Kidney Failure, Chronic ; Medical Records ; Metabolism ; Mortality* ; Multivariate Analysis ; Radiography ; Renal Dialysis* ; Risk Factors ; Vascular Calcification

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world and is the only major disease that is continuing to increase in both prevalence and mortality. The second Korean National Health and Nutrition Survey revealed that the prevalence of COPD in Korean subjects aged > or =45 years was 17.2% in 2001. Further surveys on the prevalence of COPD were not available until 2007. Here, we report the prevalence of spirometrically detected COPD in Korea, using data from the fourth Korean National Health and Nutrition Survey (KNHANES IV) which was conducted in 2007~2009. METHODS: Based on the Korean Statistical Office census that used nationwide stratified random sampling, 10,523 subjects aged > or =40 years underwent spirometry. Place of residence, levels of education, income, and smoking status, as well as other results from a COPD survey questionnaire were also assessed. RESULTS: The prevalence of COPD (defined as forced expiratory volume in 1 sec/forced vital capacity <0.7 in subjects aged > or =40 years) was 12.9% (men, 18.7%; women, 7.5%). In total, 96.5% of patients with COPD had mild-to-moderate disease; only 2.5% had been diagnosed by physicians, and only 1.7% had been treated. The independent risk factors for COPD were smoking, advanced age, and male gender. CONCLUSION: The prevalence of COPD was 12.9% in the KNHANES IV data. Most patients with COPD were undiagnosed and untreated. Based on these results, a strategy for early COPD intervention is warranted in high risk subjects.
Aged ; Censuses ; Female ; Forced Expiratory Volume ; Humans ; Hypogonadism ; Korea ; Male ; Mitochondrial Diseases ; Nutrition Surveys ; Ophthalmoplegia ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Surveys and Questionnaires ; Risk Factors ; Smoke ; Smoking ; Spirometry ; Vital Capacity

To investigate potential health risks associated with exposure to metals from an abandoned metal mine, the authors studied people living near an abandoned mine (n=102) and control groups (n=149). Levels of cadmium, copper, arsenic, lead, and zinc were measured in the air, soil, drinking water, and agricultural products. To assess individual exposure, biomarkers of each metal in blood and urine were measured. beta2-microglobulin, alpha1-microglobulin, and N-acetyl-beta-glucosaminidase and bone mineral density were measured. Surface soil in the study area showed 2-10 times higher levels of metals compared to that of the control area. Metal concentrations in the groundwater and air did not show any notable differences between groups. Mean concentrations of cadmium and copper in rice and barley from the study area were significantly higher than those of the control area (p<0.05). Geometric means of blood and urine cadmium in the study area were 2.9 microgram/L and 1.5 microgram/g Cr, respectively, significantly higher than those in the control area (p<0.05). There were no differences in the levels of urinary markers of early kidney dysfunction and bone mineral density. The authors conclude that the residents near the abandoned mine were exposed to higher levels of metals through various routes.
Aged ; Cadmium/*blood/*urine ; Copper/blood/urine ; Environmental Exposure ; *Environmental Monitoring ; Female ; *Food Contamination ; Hordeum ; Humans ; Korea ; Lead/blood/urine ; Male ; Middle Aged ; *Mining ; Oryza sativa ; Risk Factors ; Soil Pollutants/analysis ; Water Pollutants, Chemical/analysis ; Zinc/blood/urine

Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis that are predominantly observed in children, affecting their skin, joints, gut and kidneys. The renal prognosis of HS nephritis is known to be worse in adults than in children. It is defined by tissue deposition of IgA. In most HSP patients, serum complement levels are usually normal. However, some authors reported abnormalities of serum complement levels in children-onset HSP. The authors report here a rare adult-onset case of HSP combined with post-infectious glomerulonephritis, especially hypocomplementemia and subepithelial 'hump'- like electron dense deposits.
Adult ; Child ; Complement System Proteins ; Electrons ; Glomerulonephritis ; Humans ; Immunoglobulin A ; Joints ; Kidney ; Nephritis ; Prognosis ; Purpura ; Purpura, Schoenlein-Henoch ; Skin ; Vasculitis