Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer.

Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.

Comparison of Coronary Computed Tomography Angiography Image Quality With High-concentration and Low-concentration Contrast Agents: The Randomized CONCENTRATE Trial.

PURPOSE: To confirm that the image quality of coronary computed tomography (CT) angiography with a low tube voltage (80 to 100 kVp), iterative reconstruction, and low-concentration contrast agents (iodixanol 270 to 320 mgI/mL) was not inferior to that with conventional high tube voltage (120 kVp) and high-concentration contrast agent (iopamidol 370 mgI/mL). MATERIALS AND METHODS: This prospective, multicenter, noninferiority, randomized trial enrolled a total of 318 patients from 8 clinical sites. All patients were randomly assigned 1: 1: 1 for each contrast medium of 270, 320, and 370 mgI/mL. CT scans were taken with a standard protocol in the high-concentration group (370 mgI/mL) and with 20 kVp lower protocol in the low-concentration group (270 or 320 mgI/mL). Image quality and radiation dose were compared between the groups. Image quality was evaluated with a score of 1 to 4 as subject image quality. RESULTS: The mean HU, signal-to-noise ratio, and contrast-to-noise ratio of the 3 groups were significantly different (all P<0.0001). The signal-to-noise ratio and contrast-to-noise ratio of the low-concentration groups were significantly lower than those of the high-concentration group (P<0.05). However, the image quality scores were not significantly different among the 3 groups (P=0.745). The dose length product and effective dose of the high-concentration group were significantly higher than those of the low-concentration group (P<0.0001 and 0.003, respectively). CONCLUSIONS: The CT protocol with iterative reconstruction and lower tube voltage for low-concentration contrast agents significantly reduced the effective radiation dose (mean: 3.7±2.7 to 4.1±3.1 mSv) while keeping the subjective image quality as good as the standard protocol (mean: 5.7±3.4 mSv).

Comparison of Extraction Methods and Extraction Optimization in Aqueous Two-Phase System for Ethyl Carbamate Analysis in Model Systems for Maesil Wine.

Ethyl carbamate (EC) is a known carcinogen, and therefore its intake is regulated internationally. The objectives of this study were to compare the EC recovery yields under different liquid-liquid extraction (LLE) conditions and to investigate the optimum conditions of the aqueous two-phase system (ATPS) for EC extraction. Our results showed that for the LLE method, addition of 15% NaCl improved the EC yield by 15%, and dichloromethane as the extraction solvent showed a slightly higher yield (about 5%) than chloroform. However, there was little difference in the yield when mixing was performed using an ultrasonic bath compared to a vortex mixer. Using response surface methodology with central composite design to analyze the ATPS results, optimal extraction was found to occur at 21.5°C for 2.8 h in the sample containing 70% alcohol and 15% phosphate, showing a recovery yield of 75.64%. This information can be applied to alcoholic beverages and other fermented food products to analyze EC with better extraction methods, depending on the types of food.

Comprehensive Comparison of 22C3 and SP263 PD-L1 Expression in Non-Small-Cell Lung Cancer Using Routine Clinical and Conditioned Archives.

PD-L1 harmonization studies revealed a strong correlation between the 22C3 and SP263 assays in non-small-cell lung cancer (NSCLC). However, the assays' characteristics have yet to be validated in a variety of clinical and analytical settings. The results of 431 NSCLC samples tested concurrently in routine clinical practice with the PD-L1 22C3 and SP263 assays were reviewed, and both assays were performed on 314 archives of surgically resected NSCLCs to assess PD-L1 expression in relation to variables such as FFPE block age and FFPE section storage condition. In routine clinical samples, 22C3 showed the highest concordance rate with 94.5% of SP263 tumor proportion score (TPS) ≥50% and 92.3% of SP263 TPS ≥1%, while SP263 showed a concordance rate with 79.6% of 22C3 TPS ≥50% and 89.9% of 22C3 TPS ≥1%. In the archival analysis, the high TPS of 22C3 and SP263 (versus TPS 1%) were significantly associated with a more recent block (<3 years versus ≥3 years) (p = 0.007 and p = 0.009, respectively). Only the TPS of 22C3 was reduced when FFPE sections were stored at room temperature compared to SP263. However, when stored at 4 °C, the storage duration had no effect on expression in either assay. For 22C3 TPS 1−49 percent and ≥50 percent (OR = 1.73, p = 0.006 and OR = 1.98, p = 0.002, respectively). There was a considerably larger chance of preserved 22C3 expression in recent room-temperature paraffin section storage, although SP263 demonstrated preserved expression in prolonged room-temperature section storage. Despite the good association between PD-L1 22C3 and SP263 in routine clinical samples, FFPE blocks older than 3 years and sections held at room temperature for more than 1 week may result in an underestimation of PD-L1 status, particularly for the 22C3 test. However, the SP263 assay was more sensitive under these conditions.

Plant Extracts as Possible Agents for Sequela of Cancer Therapies and Cachexia.

Cancer is a leading cause of the death worldwide. Since the National Cancer Act in 1971, various cancer treatments were developed including chemotherapy, surgery, radiation therapy and so forth. However, sequela of such cancer therapies and cachexia are problem to the patients. The primary mechanism of cancer sequela and cachexia is closely related to reactive oxygen species (ROS) and inflammation. As antioxidant properties of numerous plant extracts have been widely reported, plant-derived drugs may have efficacy on managing the sequela and cachexia. In this study, recent seventy-four studies regarding plant extracts showing ability to manage the sequela and cachexia were reviewed. Some plant-derived antioxidants inhibited cancer proliferation and inflammation after surgery and others prevented chemotherapy-induced normal cell apoptosis. Also, there are plant extracts that suppressed radiation-induced oxidative stress and cell damage by elevation of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and regulation of B-cell lymphoma 2 (BcL-2) and Bcl-2-associated X protein (Bax). Cachexia was also alleviated by inhibition of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) by plant extracts. This review focuses on the potential of plant extracts as great therapeutic agents by controlling oxidative stress and inflammation.

PD-L1 expression in ROS1-rearranged non-small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1.

BACKGROUND: The aim of the current study was to investigate the prevalence and clinicopathologic characteristics of ROS1-rearranged non-small cell lung cancer (NSCLC) in routine genotypic screening in conjunction with the study of PD-L1 expression, a biomarker for first-line treatment decisions. METHODS: Reflex simultaneous genotypic screening for EGFR by peptide nucleic acid clamping, and ALK and ROS1 by fluorescence in situ hybridization (FISH) was performed on consecutive NSCLC cases at the time of initial pathologic diagnosis. We evaluated genetic aberrations, clinicopathologic characteristics, and PD-L1 tumor proportion score (TPS) using a PD-L1 22C3 assay kit. RESULTS: In 407 consecutive NSCLC patients, simultaneous genotyping identified 14 (3.4%) ROS1 and 19 (4.7%) ALK rearrangements, as well as 106 (26%) EGFR mutations. These mutations were mutually exclusive and were found in patients with similar clinical features, including younger age, a prevalence in women, adenocarcinoma, and advanced stage. The PD-L1 assay was performed on 130 consecutive NSCLC samples. High PD-L1 expression (TPS ≥ 50%) was observed in 29 (22.3%) tumors. PD-L1 expression (TPS ≥ 1%) was significantly associated with wild type EGFR, while ROS1 rearrangement was associated with high PD-L1 expression. Of the 14 cases with ROS1 rearrangement, 12 (85.7%) showed PD-L1 expression and 5 (35.7%) showed high PD-L1 expression. CONCLUSION: In the largest consecutive routine Asian NSCLC cohort analyzed to date, we found that high PD-L1 expression frequently overlapped with ROS1 rearrangement, while it negatively correlated with EGFR mutations.

Comparison of coronary computed tomography angiography image quality with high- and low-concentration contrast agents (CONCENTRATE): study protocol for a randomized controlled trial.

BACKGROUND: With the development of computed tomography (CT) technology, coronary CT angiography can be acquired with low doses of radiation and contrast agent without a loss of diagnostic performance. The primary objective of the CONCENTRATE study is to prove the noninferiority of the enhancement effect of low-concentration contrast agents compared to a high-concentration contrast agent of the coronary artery and myocardium with coronary CT angiography. METHODS/DESIGN: The CONCENTRATE study is a prospective, multicenter, noninferiority, randomized trial evaluating the enhancement effect of low-concentration contrast agents (270 and 320 mg iodine/ml) compared with a high-concentration contrast agent (370 mg iodine/ml) in the coronary artery and myocardium of coronary artery CT angiography. The primary efficacy measurement is the enhancement of coronary arteries as measured in Hounsfield units. The target population comprises 318 patients with suspected coronary artery disease who have been referred for clinically indicated nonemergent coronary CT angiography. Eligible participants are randomized for three different concentrations of the contrast agent in a 1:1:1 allocation ratio to one of three arms. The CONCENTRATE trial is a double-blind study, where the subjects and the outcome assessor are blinded to the concentration of the contrast agent used for coronary the CT angiography. Eight clinical sites in Korea are participating in this trial. DISCUSSION: The CONCENTRATE study will determine whether low-concentration contrast agents are able to provide diagnostic image quality in coronary CT angiography. TRIAL REGISTRATION: NCT02549794 . Registered on 14 September 2015.

ADRM1 gene amplification is a candidate driver for metastatic gastric cancers.

We searched for candidate target genes in metastatic gastric cancer, using comparative genomic hybridization (CGH) and mRNA expression array analysis of endoscopic biopsy samples collected from 32 patients. Recurrent amplicons included 17q21.2 (36,569,293-37,307,055), 8q24.13-q24.21 (126,357,475-130,159,285), and 20q13.33 (60,211,249-61,382,787). In this paper, we focused on the 1.1-Mb genomic region containing 24 genes in chromosome 20q13.33 (from 60,211,249 to 61,382,787), the third most frequent amplicon that was amplified in three of 32 patients (9.4 %), with log2 tumor/reference ratios ranging from 0.6 to 1.5. Of three genes in the 20q13.33 amplicon, ADRM1 was chosen for functional analyses. ADRM1 knockdown suppressed the proliferation of two human gastric cancer cells, SNU-601 and SNU-216. Overexpression of Adrm1 promoted cell proliferation of conditionally-immortalized, mouse ImSt gastric epithelial cells, with increased S1 phase fraction and decreased expression of p21(Cip1). These results collectively indicate that ADRM1 promoted gastric epithelial cell proliferation by cell cycle progression. Therefore, ADRM1 is a candidate target gene in the chromosome 20q13.33 amplicon that may possibly be linked to development of gastric cancer.

Complications of pneumoconiosis: radiologic overview.

A wide spectrum of pulmonary complications occurs in patients with pneumoconiosis. Those complications include chronic obstructive pulmonary disease, hemoptysis, pneumothorax, pleural disease, tuberculosis, autoimmune disease, anthracofibrosis, chronic interstitial pneumonia, and malignancy. Generally, imaging workup starts with plain chest radiography. However, sometimes, plain radiography has limited role in the diagnosis of pulmonary complications of pneumoconiosis because of overlapping pneumoconiotic infiltration. Computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI) are potentially helpful for the detection of pulmonary complications in patients with pneumoconiosis. CT, with its excellent contrast resolution, is more sensitive and specific method than plain radiograph in the evaluation of pulmonary abnormalities. CT is useful in detecting lung parenchymal abnormalities caused by infection, anthracofibrosis, and chronic interstitial pneumonia. Also, CT is valuable in distinguishing localized pneumothorax from bullae and aiding the identification of multiloculated effusions. US can be used in detection of complicated pleural effusions and guidance of the thoracentesis procedure. MRI is useful for differentiating between progressive massive fibrosis and lung cancer. Radiologists need to be familiar with the radiologic and clinical manifestations of, as well as diagnostic approaches to, complications associated with pneumoconiosis. Knowledge of the various imaging features of pulmonary complications of pneumoconiosis can enhance early diagnosis and improve the chance to cure.

Lipid MALDI profile classifies non-small cell lung cancers according to the histologic type.

We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may assist with the histopathologic diagnosis of non-small cell lung cancers (NSCLCs). Twenty-one pairs of frozen, resected NSCLCs and adjacent normal tissue samples were initially analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. A lipid profile that could differentiate cancer and adjacent normal samples with a median accuracy of 92.9% was discovered. Several phospholipids including phosphatidylcholines (PC) {34:1} were overexpressed in lung cancer. Squamous cell carcinomas and adenocarcinomas were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set. MALDI MS image of 11 discriminatory lipids validated their differential expression according to the histologic type in cancer cells of bronchoscopic biopsy samples. PC {32:0} [M+Na](+) (m/z 756.68) and ST-OH {42:1} [M-H](-) (m/z 906.89) were overexpressed in adenocarcinomas. Thus, lipid profiles accurately distinguish tumor from adjacent normal tissue and classify non-small cell lung cancers according to the histologic type.

Histology-directed matrix-assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers.

To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.

Ventricular septal aneurysms in adults: findings of cardiac CT images and correlation with clinical features.

BACKGROUND: With the increasing use of multidetector computed tomography (MDCT), the number of incidentally detected ventricular septal aneurysms (VSAs) in adults has increased. However, to date, there are not sufficient well-organized data regarding VSAs in adults on MDCT. PURPOSE: To evaluate the CT findings of ventricular septal aneurysms (VSAs) in adults and correlate the findings with clinical features. MATERIAL AND METHODS: We performed a retrospective review of the cardiac CT reports in our electronic database of 3402 patients who underwent ECG-gated cardiac CT scans using a 64-slice multidetector CT or dual-source CT from October 2006 to December 2009 at our institute. Among them, eight patients were diagnosed with a VSA. We evaluated the location, size, and morphology of VSAs on cardiac CT angiographies (CCTAs) and correlated the findings with the clinical features of the patients. RESULTS: On CCTAs, all eight patients were found to have VSAs in the membranous portion of the interventricular septum and toward the right ventricle. The VSAs were 10-22 mm at their longest diameter and had wide necks. The VSAs were lobulated along the outer margin and were incidental findings in all patients. Four of the eight patients had a conduction abnormality such as first-degree atrio-ventricular block or incomplete right bundle branch block seen on ECG, whereas the other four patients had normal ECGs. CONCLUSION: VSA in adults is usually detected incidentally. It is seen in the membranous portion of the interventricular septum with a lobulated shape on CCTA. It is occasionally associated with a conduction anomaly.

Detection of pulmonary embolism using 64-slice multidetector-row computed tomography: accuracy and reproducibility on different image reconstruction parameters.

BACKGROUND: Direct comparison of different image reconstruction parameters to detect pulmonary embolism (PE) using 64-slice multidetector-row computed tomography (MDCT) is absent and the most accurate image reconstruction parameters have not yet been proven. PURPOSE: To compare different image reconstruction parameters for detecting PE using 64-slice MDCT in patients suspected of having an acute PE. MATERIAL AND METHODS: Forty patients who underwent pulmonary CT angiography with 64-slice MDCT for a suspected PE were included. Different image reconstruction parameters were used for each patient: axial and coronal images with slice thicknesses of 0.625 mm, 1.3 mm, and 2.5 mm and axial maximum intensity projection (MIP) images with slab thicknesses of 1.3 mm, 2.5 mm, and 5 mm. Four experienced radiologists reviewed the images. The diagnosis of a PE was based on consensus review of axial 0.625 mm slice thickness images by two chest radiologists with allowing multiplanar reconstruction. Accuracy and reproducibility (kappa value) were evaluated. RESULTS: In 15 of 40 patients, a PE was diagnosed. For detecting lobar PEs, axial images with a slice thickness of 1.25 mm and all coronal re-formatted images showed comparable results to axial images with a slice thickness of 0.625 mm. For detecting segmental PEs, axial images with a slice thickness of 1.25 mm and coronal images with a slice thickness of 0.625 mm re-formatted images showed comparable results to axial images of a slice thickness of 0.625 mm. For detecting subsegmental PEs, axial images with a slice thickness of 0.625 mm showed the highest sensitivity. Better reproducibility was obtained when the thinner slice thickness reconstructions were in axial and coronal images. However, reproducibility of MIP images with slab thicknesses of 2.5 mm and 5 mm was similar for detecting segmental and subsegmental PEs. CONCLUSION: Thin-slice reconstruction of less than 1 mm is mandatory for visualization of PE at the subsegmental level.