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.

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.
Humans ; Korea* ; Lung Diseases ; Medical Overuse ; Pulmonary Disease, Chronic Obstructive*

PURPOSE: A hybrid-dynamic conformal arc therapy (HDCAT) technique consisting of a single half-rotated dynamic conformal arc beam and static field-in-field beams in two directions was designed and evaluated in terms of dosimetric benefits for radiotherapy of lung cancer. MATERIALS AND METHODS: This planning study was performed in 20 lung cancer cases treated with the VERO system (BrainLAB AG, Feldkirchen, Germany). Dosimetric parameters of HDCAT plans were compared with those of three-dimensional conformal radiotherapy (3D-CRT) plans in terms of target volume coverage, dose conformity, and sparing of organs at risk. RESULTS: HDCAT showed better dose conformity compared with 3D-CRT (conformity index: 0.74 ± 0.06 vs. 0.62 ± 0.06, p < 0.001). HDCAT significantly reduced the lung volume receiving more than 20 Gy (V20: 21.4% ± 8.2% vs. 24.5% ± 8.8%, p < 0.001; V30: 14.2% ± 6.1% vs. 15.1% ± 6.4%, p = 0.02; V40: 8.8% ± 3.9% vs. 10.3% ± 4.5%, p < 0.001; and V50: 5.7% ± 2.7% vs. 7.1% ± 3.2%, p < 0.001), V40 and V50 of the heart (V40: 5.2 ± 3.9 Gy vs. 7.6 ± 5.5 Gy, p < 0.001; V50: 1.8 ± 1.6 Gy vs. 3.1 ± 2.8 Gy, p = 0.001), and the maximum spinal cord dose (34.8 ± 9.4 Gy vs. 42.5 ± 7.8 Gy, p < 0.001) compared with 3D-CRT. CONCLUSIONS: HDCAT could achieve highly conformal target coverage and reduce the doses to critical organs such as the lung, heart, and spinal cord compared to 3D-CRT for the treatment of lung cancer patients.
Heart ; Humans ; Lung Neoplasms ; Lung ; Organs at Risk ; Radiotherapy ; Radiotherapy, Conformal ; Spinal Cord

BACKGROUND: Cervical cytology for uterine cervical cancer screening has transitioned from conventional smear (CS) to liquid-based cytology (LBC), which has many advantages. The aim of this study was to compare the proportion of unsatisfactory specimens from CS versus LBC at multiple institutions including general hospitals and commercial laboratories. METHODS: Each participating institution provided a minimum of 500 Papanicolaou (Pap) test results for analysis. Pap tests were classified according to the participating institution (commercial laboratory or general hospital) and the processing method (CS, ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were classified as technical problems, scant cellularity, or complete obscuring factors. RESULTS: A total of 38,956 Pap test results from eight general hospitals and three commercial laboratories were analyzed. The mean unsatisfactory rate of LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the LBC method, samples from general hospitals had lower unsatisfactory rates than those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of unsatisfactory results in LBC were due to the scant cellularity. CONCLUSIONS: Unsatisfactory rate of cervical cancer screening test results varies according to the institution and the processing method. LBC has a significantly lower unsatisfactory rate than CS.
Hand ; Hospitals, General ; Mass Screening* ; Methods ; Papanicolaou Test ; Uterine Cervical Neoplasms*

Neurilemmomas are relatively uncommon, slowly growing tumors which originate from Schwann cells. Intrathoracic neurilemmomas often occur in the chest wall and posterior mediastinum, but endobronchial neurilemmomas are exceedingly rare. These tumors in trachea or bronchus are usually detected by radiologic examinations, mostly computed tomography scan of chest. An 88-year-old man was admitted for management of pneumonia in left lower lobe and parapneumonic effusion. On bronchoscopic examination, there was a small polypoid nodule less than 1 cm in diameter mimicking an endobronchial inflammatory polyp at the bifurcation of the right anterior segmental bronchus and lateral segmental bronchus and under auto-fluorescence imaging, the nodule showed reddish brown area with defined margin. The bronchoscopic biopsy revealed that the bronchial nodule was endobronchial neurilemmoma. This is an interesting case of endobronchial neurilemmoma mimicking a bronchial polyp that is detected incidentally via bronchoscopy.
Aged, 80 and over ; Biopsy ; Bronchi ; Bronchoscopy ; Humans ; Mediastinum ; Neurilemmoma* ; Optical Imaging ; Pneumonia ; Polyps* ; Schwann Cells ; Thoracic Wall ; Thorax ; Trachea

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

PURPOSE: Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma. METHODS: BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb. RESULTS: Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen. CONCLUSIONS: sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.
Adaptive Immunity ; Animals ; Asthma* ; Bacillus ; Cell Wall ; Eosinophils ; Immune System ; Inflammation* ; Lung ; Mice* ; Mycobacterium bovis ; Mycolic Acids* ; Ovalbumin ; Spleen ; T-Lymphocytes ; T-Lymphocytes, Regulatory

In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. We used snake venom (4 microg/ml) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cell growth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30-40% was decreased in cancer cell growth by snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins such as that Bax, and cleaved caspase-3 as well as the expression of various death receptor proteins like DR3, DR4 and Fas was also further increased. Moreover, consistent with cancer cell growth inhibition, the DNA binding activity of NF-kappaB was also further inhibited after treatment of snake venom activated NK-92MI cells. Thus, the present data showed that activated NK cells could further inhibit lung cancer cell growth.
Caspase 3 ; Cell Line ; Coculture Techniques ; DNA ; Killer Cells, Natural* ; Lung Neoplasms* ; NF-kappa B* ; Snake Venoms*

PURPOSE: Bacillus Calmette-Guerin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma. METHODS: BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb). RESULTS: BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects. CONCLUSIONS: BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs.
Animals ; Asthma ; Bacillus* ; Bronchoalveolar Lavage ; Dendritic Cells* ; Eosinophils ; Immunoglobulin E ; Immunoglobulin G ; Inflammation ; Lung ; Mice ; Mycobacterium bovis ; Ovalbumin ; T-Lymphocytes, Regulatory*

Lymphangiomas are rare congenital benign tumors arising from the lymphatic system, and are mostly encountered in the neck and axillary regions of pediatric patients (95%). Lymphangioma of the pancreas is extremely rare accounting for less than 1% of these tumors. We report here on a case of pancreatic cystic lymphangioma. A 54-year-old woman presented with intermittent postprandial abdominal discomfort and radiating back pain. Abdominal computed tomography scan revealed 8 x 6.5 cm hypodense cystic mass arising from the tail of the pancreas without septa or solid component. The initial impression was a pancreatic pseudocyst. The patient underwent distal pancreatectomy with splenectomy. The histopathologic and immunohistochemical study helped make the diagnosis of a pancreatic cystic lymphangioma. Herein, we report a case of pancreatic cystic lymphangioma mimicking pancreatic pseudocyst and review the relevant medical literature.
Accounting ; Back Pain ; Female ; Humans ; Lymphangioma ; Lymphangioma, Cystic ; Lymphatic System ; Middle Aged ; Neck ; Pancreas ; Pancreatectomy ; Pancreatic Cyst ; Pancreatic Pseudocyst ; Splenectomy