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Introduction: There is no consensus on how to investigate men with negative transrectal ultrasound guided prostate biopsy (TRUS-B) but ongoing suspicion of cancer. Three strategies used are transperineal (TP-B), transrectal saturation (TS-B) and MRI-guided biopsy (MRI-B). We compared cancer yields of these strategies. Methods: Papers were identified by search of Pubmed, Embase and Ovid Medline. Included studies investigated biopsy diagnostic yield in men with at least one negative TRUS-B and ongoing suspicion of prostate cancer. Data including age, PSA, number of previous biopsy episodes, number of cores at re-biopsy, cancer yield, and Gleason score of detected cancers were extracted. Meta-regression analyses were used to analyse the data. Results: Forty-six studies were included; 12 of TS-B, 14 of TP-B, and 20 of MRI-B, representing 4,657 patients. Mean patient age, PSA and number of previous biopsy episodes were similar between the strategies. The mean number of biopsy cores obtained by TP-B and TS-B were greater than MRI-B. Cancer detection rates were 30·0%, 36·8%, and 37·6% for TS-B, TP-B, and MRI-B respectively. Meta-regression analysis showed that MRI-B had significantly higher cancer detection than TS-B. There were no significant differences however between MRI-B and TP-B, or TP-B and TS-B. In a sensitivity analysis incorporating number of previous biopsy episodes (36 studies) the difference between MRI-B and TP-B was not maintained resulting in no significant difference in cancer detection between the groups. There were no significant differences in median Gleason scores detected comparing the three strategies. Conclusions: In the re-biopsy setting, it is unclear which strategy offers the highest cancer detection rate. MRI-B may potentially detect more prostate cancers than other modalities and can achieve this with fewer biopsy cores. However, well–designed prospective studies with standardised outcome measures are needed to accurately compare modalities and define an optimum re-biopsy approach. [ABSTRACT FROM AUTHOR]

Several studies on pregnancy-associated cancers have suggested an association with congenital anomalies in offspring. Previous studies have included maternal cancers diagnosed up to 2 years after pregnancy; however, long latency periods of some cancers mean that cancers diagnosed many years postpartum might have been present during pregnancy in a preclinical state. This paper considers the association between maternal cancers diagnosed from 2 years prior to pregnancy until the mother reaches 50 years of age, and congenital anomalies, as diagnosed at birth or within the first year of life. The current population-based study looks at associations of cancers in mothers with congenital anomalies in their children. Children were followed up from birth to diagnosis of a congenital anomaly, death, emigration or end of follow-up (whichever occurred first). A total of 56,016 children (2.6%) were considered exposed to a maternal cancer of any type; and they had a hazard ratio (HR) of 1.04 (95% confidence interval [CI]: 1.00, 1.09) compared with unexposed children. The greatest HR was seen among children whose mothers had been diagnosed with cancers before or during pregnancy (HR: 1.37, 95% CI: 1.07, 1.75). Similar results were seen when paternal cancers were used as a ‘negative control’. Statistically significant associations were seen for some specific congenital anomalies of organ systems (congenital anomalies of the musculoskeletal system [HR: 1.13, 95% CI: 1.02, 1.25]) and for some specific types of maternal cancer (leukaemia [HR: 1.31, 95% CI: 1.01, 1.61], The results of the main analyses suggest a small increase in risk of congenital anomalies in offspring of mothers diagnosed with cancer from 2 years before pregnancy, until the mother reaches 50 years of age; with the greatest increase seen for exposure in the pre-pregnancy and pregnancy period. These results may reflect shared causes for some cancers and some congenital anomalies. The similar results seen for paternal cancers indicate that the cause may be genetic or related to the families’ social and environmental conditions. [ABSTRACT FROM AUTHOR]

Background: The incidence and/or diagnosis of a major disease may activate weight change. Patterns of weight change associated with diagnoses have not been systematically documented. Methods: We use data on adults ages 30+ in the National Health and Nutrition Examination Survey (NHANES) from 1999–2014. Self-reported current weight and weight one year prior are used to estimate percent weight change in the last year. We use self-reported data on arthritis, diabetes, cancer, cardiovascular disease, liver conditions, and respiratory disease diagnoses to compare weight change among individuals never diagnosed with these conditions, individuals diagnosed 0–1 years ago, and individuals diagnosed 2+ years ago. Multinomial logistic regressions adjust for the presence of multiple conditions. Results: 17.7% of the adult population experienced weight loss of 5.0% or more in the year prior to survey. Individuals diagnosed with any of the conditions were less likely to maintain their weight than those without a diagnosis. Arthritis, diabetes, cancer, cardiovascular disease, and liver conditions were associated with net weight loss, whereas respiratory diseases were associated with higher probabilities of both losing and gaining weight. Among those losing 10% or more, 56.7% had been diagnosed with one of the conditions. Cancer was associated with the highest probability of unintentional weight loss and diabetes with the highest probability of intentional weight loss. Conclusions: Disease-associated weight changes leave a distinct imprint on patterns of weight change in the population. Individuals losing at least 10% of their weight in the last year have likely been diagnosed with one of the six conditions. [ABSTRACT FROM AUTHOR]

Background: To evaluate screening and treatment strategies, large-scale real-world data on liver disease-related outcomes are needed. We sought to validate health administrative data for identification of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma among patients with known liver disease. Methods: Primary patient data were abstracted from patients of the Toronto Center for Liver Disease with viral hepatitis (2006–2014), and all patients with liver disease from the Kingston Health Sciences Centre Hepatology Clinic (2013). We linked clinical information to health administrative data and tested a range of coding algorithms against the clinical reference standard. Results: A total of 6,714 patients had primary chart data abstracted. A single physician visit code for cirrhosis was sensitive (98–99%), and a single hospital diagnostic code for cirrhosis was specific (91–96%). The most sensitive algorithm for decompensated cirrhosis was one cirrhosis code with any of: a hospital diagnostic code, death code, or procedure code for decompensation (range 88–99% across groups). The most specific was one cirrhosis code and one hospital diagnostic code (range 89–98% across groups). Two physician visit codes or a single hospital diagnostic code, death code, or procedure code combined with a code for cirrhosis were sensitive and specific for hepatocellular carcinoma (sensitivity 94–96%, specificity 93–98%). Conclusion: These sensitive and specific algorithms can be used to define patient cohorts or detect clinical outcomes using health administrative data. Our results will facilitate research into the adequacy of screening and treatment for patients with chronic viral hepatitis or other liver diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the value of spectral CT in the differential diagnosis of benign from malignant pleural effusion. Method and materials: 14 patients with benign pleural effusion and 15 patients with malignant pleural effusion underwent non-contrast spectral CT imaging. These patients were later verified by the combination of disease history, clinical signs and other information with the consensus of surgeons and radiologists. Various Spectral CT image parameters measured for the effusion were as follows: CT numbers of the polychromatic 140kVp images, monochromatic images at 40keV and 100keV, the material density contents from the water, fat and blood-based material decomposition images, the effective atomic number and the spectral curve slope. These values were statistically compared with t test and logistic regression analysis between benign and malignant pleural effusion. Results: The CT value of benign and malignant pleural effusion in the polychromatic 140kVp images showed no differences (12.61±3.39HU vs. 14.71±5.03HU) (P>0.05), however, they were statistically different on the monochromatic images at 40keV (43.15±3.79 vs. 39.42±2.60, p = 0.005) and 100keV (9.11±1.38 vs. 6.52±2.04, p<0.001). There was difference in the effective atomic number value between the benign (7.87±0.08) and malignant pleural effusion (7.90±0.02) (P = 0.02). Using 6.32HU as the threshold for CT value measurement at 100keV, one could obtain sensitivity of 100% and specificity of 66.7% with area-under-curve of 0.843 for differentiating benign from malignant effusion. In addition, age and disease history were potential confounding factors for differentiating malignant pleural effusion from benign, since the older age (61.13±12.51 year-old vs48.57±12.33 year-old) as well as longer disease history (70.00±49.28 day vs.28.36±21.64 day) were more easily to be found in the malignant pleural effusion group than those in the benign pleural effusion group. By combining above five factors, one could obtain sensitivity of 100% and specificity of 71.4% with area-under-curve of 0.933 for differentiating benign from malignant effusion. Conclusion: The CT value measurement at both high and low energy levels and the effective atomic number obtained in a single spectral CT scan can assist the differential diagnosis of benign from malignant pleural effusion.Combining them with patient age and disease history can further improve diagnostic performance. Clinical relevance/Application: Clinical findings and Spectral CT imaging can provide significant evidences about the nature of pleural effusion. [ABSTRACT FROM AUTHOR]

Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses (‘gained’ genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease. [ABSTRACT FROM AUTHOR]

Glioma is the most common malignant intracranial tumour. Recently, several publications have suggested that miRNAs can be used as potential diagnostic biomarkers of glioma. Here we performed a meta-analysis to identify the diagnostic accuracy of differentially expressed circulating miRNAs in gliomas. Using PubMed, Medline and Cochrane databases, we searched for studies which evaluated a single or panel of miRNAs from circulating blood as potential biomarkers of glioma. Sixteen publications involving 23 studies of miRNAs from serum or plasma met our criteria and were included in this meta-analysis. The pooled diagnostic parameters were calculated by random effect models and overall diagnostic performance of altered miRNAs was illustrated by the summary receiver operator characteristic (SROC) curves. The pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) from each study were calculated. The pooled PLR, NLR and Diagnostic Odds Ratio were 6.39 (95% CI, 4.61–8.87), 0.15 (95% CI, 0.11–0.21) and 41.91 (95% CI, 23.15–75.88), respectively. The pooled sensitivity, specificity and area under the curve (AUC) were 0.87 (95% CI, 0.82–0.91), 0.86 (95% CI, 0.82–0.90) and 0.93 (95% CI, 0.91–0.95), respectively. This meta-analysis demonstrated that circulating miRNAs are capable of distinguishing glioma from healthy controls. Circulating miRNAs are promising diagnostic biomarkers for glioma and can potentially be used as a non-invasive early detection. [ABSTRACT FROM AUTHOR]

Background: Advances in bronchoscopy and CT-guided lung biopsy have improved the evaluation of small pulmonary lesions (PLs), leading to an increase in preoperative histological diagnosis. We aimed to evaluate the efficacy and safety of transbronchial lung biopsy using radial endobronchial ultrasound and virtual bronchoscopic navigation (TBLB-rEBUS&VBN) and CT-guided transthoracic needle biopsy (CT-TNB) for tissue diagnosis of small PLs. Methods: A systematic search was performed in five electronic databases, including MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, Web of Science, and Scopus, for relevant studies in May 2016; the selected articles were assessed using meta-analysis. The articles were limited to those published after 2000 that studied small PLs ≤ 3 cm in diameter. Results: From 7345 records, 9 articles on the bronchoscopic (BR) approach and 15 articles on the percutaneous (PC) approach were selected. The pooled diagnostic yield was 75% (95% confidence interval [CI], 69–80) using the BR approach and 93% (95% CI, 90–96) using the PC approach. For PLs ≤ 2 cm, the PC approach (pooled diagnostic yield: 92%, 95% CI: 88–95) was superior to the BR approach (66%, 95% CI: 55–76). However, for PLs > 2 cm but ≤ 3 cm, the diagnostic yield using the BR approach was improved to 81% (95% CI, 75–85). Complications of pneumothorax and hemorrhage were rare with the BR approach but common with the PC approach. Conclusions: CT-TNB was superior to TBLB-rEBUS&VBN for the evaluation of small PLs. However, for lesions greater than 2 cm, the BR approach may be considered considering its diagnostic yield of over 80% and the low risk of procedure-related complications. [ABSTRACT FROM AUTHOR]

Background: Research has shown that women with disabilities face additional challenges in accessing and using healthcare services compared to non-disabled women. However, relatively little is known about the utilisation of cancer screening services for women with disabilities. This study addresses this gap by examining the utilisation of the Papanicolaou test and mammography for disabled women in Chile. Methods: We used cross-sectional data, taken from a 2015 nationally-representative survey. Initially, we employed logistic regressions to test for differences in utilisation rates for the Papanicolaou test (66,281 observations) and the mammogram (35,294 observations) between disabled and non-disabled women. Next, logistic regressions were used to investigate the demographic, socioeconomic, and health-related factors affecting utilisation rates for cancer screening services for disabled women (sample sizes: 5,823 observations for the Papanicolaou test and 5,731 observations for the mammogram). Results: Disabled women were less likely to undergo screening tests than non-disabled women. For the Papanicolaou test and mammography, the multivariable regression models showed that living in rural areas, having higher education, being affiliated with a private health insurance company, giving a good health self-assessment score, and being under medical treatment for other illnesses were associated with higher utilisation rates. On the other hand, being single, inactive with regard to employment, and having a better income were linked with lower utilisation. While utilisation rates for both disabled and non-disabled women have increased since 2006, the utilisation disparity has slightly increased. Conclusions: This study shows the influence of various factors in the utilisation rates of preventive cancer screening services for disabled women. To develop effective initiatives targeting inequalities in the utilisation of cancer screening tests, it is important to move beyond an exclusively single-disease approach and acknowledge the complexity of the patient population. [ABSTRACT FROM AUTHOR]

Background: Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer. Methods: Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography. Results: The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (p = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both p < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively). Conclusion: Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression. [ABSTRACT FROM AUTHOR]

Background: Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing.Methods and Findings: We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds.Conclusions: This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers. [ABSTRACT FROM AUTHOR]

Background: The National Lung Screening Trial (NLST) results indicate that computed tomography (CT) lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria.Methods and Findings: This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP), Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars), and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure) were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars) per life-year gained (compared to annual screening between ages 60-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago), which was considered optimal at a cost-effectiveness threshold of $50,000 Canadian dollars ($41,114 May 1, 2015, US dollars). If 50% lower or higher attributable costs were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $38,240 ($31,444 May 1, 2015, US dollars) or $48,525 ($39,901 May 1, 2015, US dollars), respectively. If 50% lower or higher costs for CT examinations were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $28,630 ($23,542 May 1, 2015, US dollars) or $73,507 ($60,443 May 1, 2015, US dollars), respectively. This scenario would screen 9.56% (499,261 individuals) of the total population (ever- and never-smokers) at least once, which would require 4,788,523 CT examinations, and reduce lung cancer mortality in the total population by 9.05% (preventing 13,108 lung cancer deaths), while 12.53% of screen-detected cancers would be overdiagnosed (4,282 overdiagnosed cases). Sensitivity analyses indicated that the overall results were most sensitive to variations in CT examination costs. Quality of life was not incorporated in the analyses, and assumptions for follow-up procedures were based on data from the NLST, which may not be generalizable to a population-based setting.Conclusions: Lung cancer screening with stringent smoking eligibility criteria can be cost-effective in a population-based setting. [ABSTRACT FROM AUTHOR]

Purpose: The outcome of sarcoma has been suggested in retrospective and non-exhaustive studies to be better through management by a multidisciplinary team of experts and adherence to clinical practice guidelines (CPGs). The aim of this prospective and exhaustive population based study was to confirm the impact of adherence to CPGs on survival in patients with localized sarcoma. Experimental design: Between 2005 and 2007, all evaluable adult patients with a newly diagnosis of localized sarcoma located in Rhone Alpes region (n = 634), including 472 cases of soft-tissue sarcoma (STS), were enrolled. The prognostic impact of adherence to CPGs on progression-free survival (PFS) and overall survival (OS) was assessed by multivariate Cox model in this cohort. Results: The median age was 61 years (range 16–92). The most common subtypes were liposarcoma (n = 133, 28%), unclassified sarcoma (n = 98, 20.7%) and leiomyosarcoma (n = 69, 14.6%). In the initial management phase, from diagnosis to adjuvant treatment, the adherence to CPGs for patients with localized STS was 36% overall, corresponding to 56%, 85%, 96% and 84% for initial surgery, radiation therapy, chemotherapy and follow-up, respectively. Adherence to CPGs for surgery was the strongest independent prognostic factor of PFS, along with age, gender, grade, and tumor size. For OS, multivariate analysis adherence to CPGs for surgery was a strong independent prognostic factor, with an important interaction with a management in the regional expert centers. Conclusions: This study demonstrates impact of CPGs and treatment within an expert center on survival for STS patients in a whole population-based cohort. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. Methodology/Principal Findings: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included. We found that the median progression-free survival (PFS) was higher in the BV group than in the standard therapy (ST) group (pooled hazard ratio, 0.73; 95%CI, 0.62–0.86; P = 0.0001). Compared with ST, BV improved the PFS rate at 6 months (OR 3.33, 95% CI 2.73–4.06, p<0.00001) and 12 months (OR 2.10, 95% CI 1.74–2.54, p<0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR, 1.01; 95%CI, 0.83–1.23; P = 0.95). The BV group had higher survival rates at 6 months (OR, 1.41; 95% CI, 1.09–1.84; P = 0.01) and 12 months (OR, 1.23; 95% CI, 1.02–1.48; P = 0.03), but a low survival rate at the 36-month follow-up (OR, 0.57; 95% CI, 0.32–0.98; P = 0.04). For the incidence of adverse events, three adverse outcomes were found to be significantly different between BV and ST groups, including hypertension (8.37% vs. 1.62%, p<0.000001), proteinuria (7.65% vs. 0%, p<0.001), and fatigue (14.54% vs. 9.01%, p = 0.05). Conclusions/Significance: Our study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS, maintaining the quality of life and functional status. However, the long-term use of BV is associated with a higher incidence of adverse events and mortality. Study Registration: This research was registered at PROSPERO. (Registration Number: CRD42016038247). [ABSTRACT FROM AUTHOR]

Often, for medical decisions based on test scores, a single decision threshold is determined and the test results are dichotomized into positive and negative diagnoses. It is therefore important to identify the decision threshold with the least number of misclassifications. The proposed method uses trichotomization: it defines an Uncertain Interval around the point of intersection between the two distributions of individuals with and without the targeted disease. In this Uncertain Interval the diagnoses are intermixed and the numbers of correct and incorrect diagnoses are (almost) equal. This Uncertain Interval is considered to be a range of test scores that is inconclusive and does not warrant a decision. It is expected that defining such an interval with some precision, prevents a relatively large number of false decisions, and therefore results in an increased accuracy or correct classifications rate (CCR) for the test scores outside this Uncertain Interval. Clinical data and simulation results confirm this. The results show that the CCR is systematically higher outside the Uncertain Interval when compared to the CCR of the decision threshold based on the maximized Youden index. For strong tests with a very small overlap between the two distributions, it can be difficult to determine an Uncertain Interval. In simulations, the comparison with an existing method for test-score trichotomization, the Two-graph Receiver Operating Characteristic (TG-ROC), showed smaller differences between the two distributions for the Uncertain Interval than for TG-ROC’s Intermediate Range and consequently a more improved CCR outside the Uncertain Interval. The main conclusion is that the Uncertain Interval method offers two advantages: 1. Identification of patients for whom the test results are inconclusive; 2. A higher estimated rate of correct decisions for the remaining patients. [ABSTRACT FROM AUTHOR]

Purpose: Minimal axial diameter (MIAD) in magnetic resonance imaging (MRI) was recognized as the most useful parameter in diagnosing lateral retropharyngeal lymph (LRPL) nodes in nasopharyngeal carcinoma (NPC). This study aims to explore the additional nodal parameters in MRI and positron emission tomography–computed tomography for increasing the prediction accuracy. Materials and Methods: A total of 663 LRPL nodes were retrospectively collected from 335 patients with NPC. The LRPL nodes ascertained on follow-up MRI were considered positive for metastases. First, the optimal cutoff value of each parameter was derived for each parameter. In addition, neural network (NN) nodal evaluation was tested for all combinations of three parameters, namely MIAD, maximal axial diameter (MAAD), and maximal coronal diameter (MACD). The optimal approach was determined through brute force attack, and the results of two methods were compared using a bootstrap sampling method. Second, the mean standard uptake value (NSUVmean) was added as the fourth parameter and tested in the same manner for 410 nodes in 219 patients. Results: In first and second analysis, the accuracy rate (percentage) for the MIAD was 89.0% (590/663) and 89.0% (365/410), with the optimal cutoff values being 6.1 mm and 6.0 mm, respectively. With the combination of all three and four parameters, the accuracy rate of the NN was 89% (288/332) and 88.8% (182/205), respectively. In prediction, the optimal combinations of the three and four parameters resulted in correct identification of three (accuracy: 593/663, 89.4%) and six additional nodes (371/410, 90.5%), representing 4% (3/73) and 13.3% (6/45) decreases in incorrect prediction, respectively. Conclusion: NPC LRPL nodes with an MIAD ≥ 6.1 mm are positive. Among nodes with an MIAD < 6.1 mm, if the NSUVmean ≥ 2.6 or MACD ≥ 25 mm and MAAD ≥ 8 mm, the nodes are positive; otherwise, they are negative. [ABSTRACT FROM AUTHOR]

Background: Glioma remains a diagnostic challenge because of its variable clinical presentation and a lack of reliable screening tools. Long noncoding RNAs (lncRNAs) regulate gene function in a wide range of pathophysiological processes and are therefore emerging biomarkers for prostate cancer, hepatic cancer, and other tumor diseases. However, the effective use of lncRNAs as biomarkers for the diagnosis of glioma remains unproven. Methods: This study included 42 glioma patients and 10 healthy controls. lncRNA and mRNA microarray chips were used to identify dysregulated lncRNAs in tumor tissue and tumor-adjacent normal tissue, and SYBR Green–based miRNA quantitative real-time reverse transcription polymerase chain reactions were used to validate upregulated lncRNAs. A receiver operating characteristic curve analysis was conducted to evaluate the diagnostic accuracy of the lncRNA identified as the candidate biomarker. Results: miR210HG levels were significantly higher in tumor tissue than in tumor-adjacent normal tissue in participating glioma patients. Serum miR210HG levels were also significantly higher in glioma patients than in healthy controls. The receiver operating characteristic curve showed that serum miR210HG was a specific diagnostic predictor of acute pulmonary embolism with an area under the curve of 0.8323 (95% confidence interval, 0.7347 to 0.9299, p < 0.001). Conclusion: Our findings indicate that miR210HG could be an important biomarker for the diagnosis of glioma, and, as such, large-scale investigations are urgently needed to pave the way from basic research to clinical use. [ABSTRACT FROM AUTHOR]

Current screening methods towards prostate cancer (PCa) are not without limitations. Research work has been on-going to assess if there are other better tests suitable for primary or secondary screening of PCa to supplement the serum prostate specific antigen (PSA) test, which fails to work accurately in a grey zone of 4-10ng/ml. In this pilot study, the potential roles of urinary polyamines as prostate cancer biomarkers were evaluated. PCa, benign prostatic hyperplasia (BPH) patients and healthy controls (HC) showing PSA>4.0ng/ml were enrolled in the study. Their urine samples were obtained, and the urinary levels of putrescine (Put), spermidine (Spd) and spermine (Spm) were determined by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS). Receiver operating characteristics (ROC) curve and Student’s t-test were used to evaluate their diagnostic accuracies. Among the three biogenic polyamines, Spm had demonstrated a good diagnostic performance when comparing their levels in PCa patients with BPH patients (1.47 in PCa vs 5.87 in BPH; p<0.0001). Results are in accordance with transrectal ultrasound prostatic biopsy (TRUSPB) results, with an area under curve (AUC) value of 0.83±0.03. Therefore urinary Spm shows potential to serve as a novel PCa diagnostic biomarker, which in turn can help to address the limited sensitivity and specificity problem of serum PSA test. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with ductal carcinoma in situ (DCIS) diagnosed on preoperative biopsy. We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy could be used to distinguish between DCIS lesions with or without an invasive component. Our institutional review board approved this combined retrospective and prospective study. Tissue samples were collected from 30 patients with pure DCIS and from 30 with DCIS accompanying invasive carcinoma. All patients were diagnosed with DCIS by preoperative core-needle biopsy and underwent surgical resection. The metabolic profiling of tissue samples was performed by HR-MAS 1H NMR spectroscopy. All observable metabolite signals were identified and quantified in all tissue samples. Metabolite intensity normalized by total spectral intensities was compared according to the tumor type using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). By univariate analysis, the metabolite concentrations of choline-containing compounds obtained with HR-MAS 1H NMR spectroscopy did not differ significantly between the pure DCIS and DCIS accompanying invasive carcinoma groups. However, the GPC/PC ratio was higher in the pure DCIS group than in the DCIS accompanying invasive carcinoma group (p = 0.004, Bonferroni-corrected p = 0.064), as well as the concentration of myo-inositol and succinate. By multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles could clearly discriminate between pure DCIS and DCIS accompanying invasive carcinoma. Our preliminary results suggest that HR-MAS MR metabolomics on breast tissue may be able to distinguish between DCIS lesions with or without an invasive component. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the role of 18F-FDG PET/CT integrated imaging in differentiating malignant from benign pleural effusion. Methods: A total of 176 patients with pleural effusion who underwent 18F-FDG PET/CT examination to differentiate malignancy from benignancy were retrospectively researched. The images of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were visually analyzed. The suspected malignant effusion was characterized by the presence of nodular or irregular pleural thickening on CT imaging. Whereas on PET imaging, pleural 18F-FDG uptake higher than mediastinal activity was interpreted as malignant effusion. Images of 18F-FDG PET/CT integrated imaging were interpreted by combining the morphologic feature of pleura on CT imaging with the degree and form of pleural 18F-FDG uptake on PET imaging. Results: One hundred and eight patients had malignant effusion, including 86 with pleural metastasis and 22 with pleural mesothelioma, whereas 68 patients had benign effusion. The sensitivities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging in detecting malignant effusion were 75.0%, 91.7% and 93.5%, respectively, which were 69.8%, 91.9% and 93.0% in distinguishing metastatic effusion. The sensitivity of 18F-FDG PET/CT integrated imaging in detecting malignant effusion was higher than that of CT imaging (p = 0.000). For metastatic effusion, 18F-FDG PET imaging had higher sensitivity (p = 0.000) and better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with CT imaging (Kappa = 0.917 and Kappa = 0.295, respectively). The specificities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were 94.1%, 63.2% and 92.6% in detecting benign effusion. The specificities of CT imaging and 18F-FDG PET/CT integrated imaging were higher than that of 18F-FDG PET imaging (p = 0.000 and p = 0.000, respectively), and CT imaging had better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with 18F-FDG PET imaging (Kappa = 0.881 and Kappa = 0.240, respectively). Conclusion: 18F-FDG PET/CT integrated imaging is a more reliable modality in distinguishing malignant from benign pleural effusion than 18F-FDG PET imaging and CT imaging alone. For image interpretation of 18F-FDG PET/CT integrated imaging, the PET and CT portions play a major diagnostic role in identifying metastatic effusion and benign effusion, respectively. [ABSTRACT FROM AUTHOR]

We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN amplification (MNA) status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86%) and very high specificity (95%). The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00–24.78), and 1.41 (95% confidence interval, 0.63–3.14) for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status. [ABSTRACT FROM AUTHOR]

Introduction: Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score.Methods and Findings: Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator. Using this approach, a new five-stratum risk stratification system was produced, and its prognostic power was compared against the current system, with PCSM as the outcome. The results were analysed using a Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks regression, and concordance indices. In the training set, the new risk stratification system identified distinct subgroups with different risks of PCSM in pair-wise comparison (p < 0.0001). Specifically, the new classification identified a very low-risk group (Group 1), a subgroup of intermediate-risk cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96-2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk (Group 3, HR 3.35 [95% CI 2.04-5.49]) (p < 0.0001). High-risk cancers were also sub-classified by the new system into subgroups with lower and higher PCSM risk: Group 4 (HR 5.03 [95% CI 3.25-7.80]) and Group 5 (HR 17.28 [95% CI 11.2-26.67]) (p < 0.0001), respectively. These results were recapitulated in the testing set and remained robust after inclusion of competing risks. In comparison to the current risk stratification system, the new system demonstrated improved prognostic performance, with a concordance index of 0.75 (95% CI 0.72-0.77) versus 0.69 (95% CI 0.66-0.71) (p < 0.0001). In an external cohort, the new system achieved a concordance index of 0.79 (95% CI 0.75-0.84) for predicting PCSM versus 0.66 (95% CI 0.63-0.69) (p < 0.0001) for the current NICE risk stratification system. The main limitations of the study were that it was registry based and that follow-up was relatively short.Conclusions: A novel and simple five-stratum risk stratification system outperforms the standard three-stratum risk stratification system in predicting the risk of PCSM at diagnosis in men with primary non-metastatic prostate cancer, even when accounting for competing risks. This model also allows delineation of new clinically relevant subgroups of men who might potentially receive more appropriate therapy for their disease. Future research will seek to validate our results in external datasets and will explore the value of including additional variables in the system in order in improve prognostic performance. [ABSTRACT FROM AUTHOR]

Background: A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models. Methods: An anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments. Results: 89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models. Conclusion: A new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In vivo validation showed high-specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic performance of an automated analysis tool for the assessment of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) of the prostate. Methods: A fully automated analysis tool was used for a retrospective analysis of mpMRI sets (T2-weighted, T1-weighted dynamic contrast-enhanced, and diffusion-weighted sequences). The software provided a malignancy prediction value for each image pixel, defined as Malignancy Attention Index (MAI) that can be depicted as a colour map overlay on the original images. The malignancy maps were compared to histopathology derived from a combination of MRI-targeted and systematic transperineal MRI/TRUS-fusion biopsies. Results: In total, mpMRI data of 45 patients were evaluated. With a sensitivity of 85.7% (with 95% CI of 65.4–95.0), a specificity of 87.5% (with 95% CI of 69.0–95.7) and a diagnostic accuracy of 86.7% (with 95% CI of 73.8–93.8) for detection of prostate cancer, the automated analysis results corresponded well with the reported diagnostic accuracies by human readers based on the PI-RADS system in the current literature. Conclusion: The study revealed comparable diagnostic accuracies for the detection of prostate cancer of a user-independent MAI-based automated analysis tool and PI-RADS-scoring-based human reader analysis of mpMRI. Thus, the analysis tool could serve as a detection support system for less experienced readers. The results of the study also suggest the potential of MAI-based analysis for advanced lesion assessments, such as cancer extent and staging prediction. [ABSTRACT FROM AUTHOR]

Objective: Parents report psychological distress in association with their child's cancer. Reliable tools are needed to screen parental distress over the cancer trajectory. This study aimed to estimate the stability and repeatability of the Distress Thermometer (DT) and the Depression and Anxiety items of the Edmonton Symptom Assessment System-revised (ESAS-r-D; -A) in parents of children diagnosed with cancer. Methods: Fifty parents (28 mothers, median age = 44) of clinically stable survivors of childhood solid and brain tumours completed questionnaires about their own distress (DT, ESAS-r-D; -A, Brief Symptom Inventory-18: BSI-18, Patient Health Questionnaire-9: PHQ-9, Generalized Anxiety Disorder-7: GAD-7) and their children’s quality of life (QoL; Peds Quality of Life: PedsQL) twice, with a month interval between the two assessments. At retest, parents also evaluated life events that occurred between the two time points. Hierarchical regressions explored moderators for the temporal stability of test measures. Results: Stability estimates were ICC = .78 for the DT, .55 for the ESAS-r-D, and .47 for the ESAS-r-A. Caseness agreement between test and retest was substantial for the DT, fair for the ESAS-r-D, and slight for the ESAS-r-A. Repeatability analyses indicated that the error range for the DT was more than 2 pts below/above actual measurement, whereas it was more than 3 pts for the ESAS-r-A, and 2.5 for the ESAS-r-D. Instability of the DT could be explained by changes in children’s physical QoL, but not by other components of QoL or life events. No moderators of stability could be identified for the ESAS-r items. Conclusions: The DT appears to be a fairly stable measure when the respondent's condition is stable yet with a relatively wide error range. Fluctuations in distress-related constructs may affect the temporal stability of the DT. The lower stability of ESAS-r items may result from shorter time-lapse instructions resulting in a greater sensitivity to change. Findings support future research on the DT as a reliable instrument in caregivers. [ABSTRACT FROM AUTHOR]

Background: The appropriate management of the large number of lung nodules detected during the course of routine medical care presents a challenge. We aimed to evaluate the usual clinical practice in solitary pulmonary nodule (SPN) management and associated radiation exposure. Methods: We examined 893 radiology reports of consecutive patients undergoing chest computed tomography (CT) and radiography at two public hospitals in Spain. Information on diagnostic procedures from SPN detection and lung cancer diagnosis was collected prospectively for 18 months. Results: More than 20% of patients with SPN detected on either chest radiograph (19.8%) or CT (26.1%) underwent no additional interventions and none developed lung cancer (100% negative predictive value). 346 (72.0%) patients with SPN detected on chest radiograph and 254 (61.5%) patients with SPN detected on CT had additional diagnostic tests and were not diagnosed with lung cancer. In patients undergoing follow-up imaging for SPNs detected on CT median number of additional imaging tests was 3.5 and the mean cumulative effective dose was 24.4 mSv; for those detected on chest radiograph the median number of additional imaging tests was 2.8 and the mean cumulative effective dose was 10.3 mSv. Conclusions: Patients who did not have additional interventions were not diagnosed of lung cancer. There was an excessive amount of interventions in a high percentage of patients presenting SPN, which was associated with an excess of radiation exposure. [ABSTRACT FROM AUTHOR]

Recent studies suggest that extracellular vesicles may be the key to timely diagnosis and monitoring of genito-urological malignancies. In this study we investigated the composition and content of extracellular vesicles found in the urine of healthy donors and prostate cancer patients. Urine of 14 PCa patients and 20 healthy volunteers was clarified by low-speed centrifugation and total extracellular vesicles fraction was obtain by high-speed centrifugation. The exosome-enriched fraction was obtained by filtration of total extracellular vesicles through a 0.1 μm pore filter. Transmission electron microscopy showed that cell-free urine in both groups contained vesicles from 20 to 230 nm. Immunogold staining after ultrafiltration demonstrated that 95% and 90% of extracellular vesicles in healthy individuals and cancer patients, respectively, were exosomes. Protein, DNA and RNA concentrations as well as size distribution of extracellular vesicles in both fractions were analyzed. Only 75% of the total protein content of extracellular vesicles was associated with exosomes which amounted to 90–95% of all vesicles. Median DNA concentrations in total extracellular vesicles and exosome-enriched fractions were 18 pg/ml and 2.6 pg/ml urine, correspondingly. Urine extracellular vesicles carried a population of RNA molecules 25 nt to 200 nt in concentration of no more than 290 pg/ml of urine. Additionally, concentrations of miR-19b, miR-25, miR-125b, and miR-205 were quantified by qRT-PCR. MiRNAs were shown to be differently distributed between different fractions of extracellular vesicles. Detection of miR-19b versus miR-16 in total vesicles and exosome-enriched fractions achieved 100%/93% and 95%/79% specificity/sensitivity in distinguishing cancer patients from healthy individuals, respectively, demonstrating the diagnostic value of urine extracellular vesicles. [ABSTRACT FROM AUTHOR]

Despite being the basis of one of the most effective interventions in lung cancer, little is known about the patterns of epidermal growth factor receptor (EGFR) mutation testing in the general population. We assessed the frequencies and determinants of EGFR testing and erlotinib treatment among a population-based sample. A random sample (n = 1,358) of patients diagnosed in 2010 with histologically-confirmed NSCLC, as reported to the Surveillance Epidemiology and End Results (SEER) program, had their medical records abstracted and treating physicians queried. Logistic regression was used to identify factors associated with EGFR testing and erlotinib treatment. Survival was examined using Cox proportional hazards regression. The frequency of EGFR testing was 16.8% overall and 22.6% for stage IV adenocarcinoma patients. Given an EGFR mutation, 33.6% of all patients and 48.3% of stage IV patients received erlotinib. Among stage IV patients, increased age, Medicaid/no/unknown insurance status, death within 2 months of diagnosis and comorbidity were inversely associated with EGFR testing; erlotinib treatment was less likely among smokers and patients with non-adenocarcinomas. EGFR-mutation was associated with improved survival, albeit only among stage IV adenocarcinomas. Less than a quarter of NSCLC patients diagnosed in 2010 received EGFR testing and less than half of the patients with EGFR-mutant stage IV tumors received erlotinib. Significant disparities were observed in EGFR mutation testing by health insurance status, comorbidity and age. A national strategy is imperative to ensure that resources and processes are in place to efficiently implement molecular testing of cancer. [ABSTRACT FROM AUTHOR]

Objective: To describe the experience of parenting a child diagnosed with cancer by examining particularly negative and positive experiences reported by parents of childhood cancer survivors and parents of children lost to cancer. Methods: 168 parents (88 mothers, 80 fathers) participated. Data were collected five years after the end of successful treatment or the child’s death. The parents’ experiences were identified by open-ended semi-structured questions about particularly negative and positive experiences of the child’s cancer. An inductive approach was used in which the manifest verbal content of the answers was analysed using content analysis. Results: The analysis revealed eight categories of negative experience (child late effects; distressing events; healthcare; impaired relationships; long-term psychological consequences; own reactions; surrounding institutions; the fact that the child got cancer) and seven categories of positive experience (healthcare; improved relationships; long-term consequences for the child; personal development; support systems; treatment outcome; unexpected joy). The categories were related to past events or to the present situation. The findings indicate variations in experiences between parents of survivors and bereaved parents, and between fathers and mothers, as some experiences were only reported by parents of survivors and some experiences were only reported by mothers. Conclusions: The results highlight the importance of past and present events to parents, and accordingly the long-lasting impact of paediatric cancer on parents. The results also point to the wide range of negative as well as positive experiences involved in parenting a child diagnosed with cancer, and provide a comprehensive understanding of the overall experience for parents of children with cancer. Specifically, the findings give guidance to healthcare providers by illustrating the need to provide healthcare personnel with continuous training in communication skills, offering parents opportunities to meet other parents in the same situation and increasing the access to psychosocial supportive services and psychological care. [ABSTRACT FROM AUTHOR]

Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab. [ABSTRACT FROM AUTHOR]

Objective: Despite recent advances in imaging and core or endoscopic biopsies, a percentage of patients have a major lung resection without diagnosis. We aimed to assess the feasibility of a rapid tissue preparation/analysis to discriminate cancerous from non-cancerous lung tissue. Methods: Fresh sample preparations were analyzed with the Microflex LTTM MALDI-TOF analyzer. Each main reference spectra (MSP) was consecutively included in a database. After definitive pathological diagnosis, each MSP was labeled as either cancerous or non-cancerous (normal, inflammatory, infectious nodules). A strategy was constructed based on the number of concordant responses of a mass spectrometry scoring algorithm. A 3-step evaluation included an internal and blind validation of a preliminary database (n = 182 reference spectra from the 100 first patients), followed by validation on a whole cohort database (n = 300 reference spectra from 159 patients). Diagnostic performance indicators were calculated. Results: 127 cancerous and 173 non-cancerous samples (144 peripheral biopsies and 29 inflammatory or infectious lesions) were processed within 30 minutes after biopsy sampling. At the most discriminatory level, the samples were correctly classified with a sensitivity, specificity and global accuracy of 92.1%, 97.1% and 95%, respectively. Conclusions: The feasibility of rapid MALDI-TOF analysis, coupled with a very simple lung preparation procedure, appears promising and should be tested in several surgical settings where rapid on-site evaluation of abnormal tissue is required. In the operating room, it appears promising in case of tumors with an uncertain preoperative diagnosis and should be tested as a complementary approach to frozen-biopsy analysis. [ABSTRACT FROM AUTHOR]

We compared the efficacy of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) for the diagnosis of renal cystic lesions via a meta-analysis to determine the value of CEUS in the prediction of the malignant potential of complex renal cysts. Eleven studies were evaluated: 4 control studies related to CEUS and CECT, 3 studies related to CEUS and 4 studies related to CECT. According to the random effects model, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for CEUS/CECT were 0.95/0.90, 0.79/0.85, 4.39/5.00, and 0.10/0.15, respectively. The areas under the summary receiver operating characteristic (AUCs-SROC) curves for the two methods were 94.24% and 93.39%, and the estimated Q values were 0.8805 and 0.8698, respectively. Comparing the Q index values of CEUS and CECT revealed no significant difference between the two methods (P>0.05). When compared with conventional CECT, CEUS is also useful for diagnosing renal cystic lesions in the clinic. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC). Methods and Materials: A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C) for comparative analysis. Results: The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months. Conclusions: The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors. [ABSTRACT FROM AUTHOR]

Blood-circulating miRNAs could be useful as a biomarker to detect lung cancer early. We investigated the serum levels of four different miRNAs in patients with non-small cell lung cancer (NSCLC) and assessed their diagnostic value for NSCLC. Serum samples from 112 NSCLC patients and 104 controls (20 current smokers without lung cancer, 23 pneumonia patients, 21 gastric cancer patients, and 40 healthy controls) were subjected to Taqman probe-based quantitative reverse transcription–polymerase chain reaction (RT-PCR). The data showed that the serum levels of miR-182, miR-183, and miR-210 were significantly upregulated and that the miR-126 level was significantly downregulated in NSCLC patients, compared with the healthy controls. Further receiver operating characteristic (ROC) curve analysis revealed that the serum miR-182, miR-183, miR-210, or miR-126 level could serve as a diagnostic biomarker for NSCLC early detection, with a high sensitivity and specificity. The combination of these four miRNAs with carcinoembryonic antigen (CEA) further increased the diagnostic value, with an area under the curve (AUC) of 0.965 (sensitivity, 81.3%; specificity, 100.0%; and accuracy, 90.8%) using logistic regression model analysis. In addition, the relative levels of serum miR-182, miR-183, miR-210, and miR-126 could distinguish NSCLC or early-stage NSCLC from current tobacco smokers without lung cancer and pneumonia or gastric cancer patients with a high sensitivity and specificity. Data from the current study validated that the four serum miRNAs could serve as a tumor biomarker for NSCLC early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. Method: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. Results/ Discussion: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). Conclusion: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status. [ABSTRACT FROM AUTHOR]

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population. [ABSTRACT FROM AUTHOR]

Objective: Meningioma of the cranio-cervical junction is a rare diagnosis and demand a thorough surgical planning as radical excision of these tumors is difficult. In this context recurrence is most likely due to regrowth of residual tumor. The aim of this study was to evaluate the clinical course of patients operated for craniocervical meningioma (CCM) and to investigate the histological features of these tumors and their impact on recurrence rate. Methods: All patients who were operated for CCM at our institution between 2003 and 2012 were identified. Presenting symptoms, MRI findings, surgical approaches and recurrence rate were reviewed retrospectively using medical charts. Histological features of the included tumors were studied focusing on subtypes and MIB-1 immunoreactivity and compared with MIB-1 immunoreactivity in an age and gender-matched control group of patients with supratentorial meningioma. Results: 18 patients with CCM with a mean age of 56.2 years and median follow-up of 60 months were included in the study. Sensory or motor deficit was the most frequent presenting symptom followed by neck pain and lower cranial nerve palsy. Simpson grade II resection was achieved in 16 patients and Simpson grade III resection in two patients. Mortality, morbidity and recurrence rates were 16.7%, 5.5% and 5.5%, respectively. According to the WHO-grading all were found to be grade I meningiomas. Histological subtypes included meningotheliomatous (10), transitional (2), fibrillar (2), angiomatous (3) and secretory (1) meningioma. The mean MIB-1 labeling index in the study group was significantly higher than in the control group, (7.2% and 3.6%, respectively), p < 0.05. There was no correlation between MIB-1 levels and tumor recurrence. Conclusions: CCM seems to have a benign character. Despite a significantly higher MIB-1 index, a high rate of recurrence was not observed. Therefore, approaches with high morbidity are not justified. Nevertheless, in view of the challenging approaches with limited access to the lesion, CCM should be considered a distinctive clinical subgroup. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. Summary Background Data: Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. Methods: Bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, linear regression, multiple regression, and receiver operating characteristic (ROC) curve analysis. Results: Bile from 83 patients was analyzed: 42 with benign disease and 41 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower median biliary CEACAM6 levels than patients in the malignant cohort (7.5 ng/ml vs. 40 ng/ml; p = <.001). ROC curve analysis determined CEACAM6 to be a positive predictor cholangiocarcinoma with a CEACAM6 level >14 ng/ml associated with 87.5% sensitivity, 69.1% specificity, and a likelihood ratio of 2.8 (AUC 0.74). Multiple regression analysis suggested elevated alkaline phosphatase and the presence of biliary endoprostheses may influence CEACAM6 levels. Conclusion: Biliary CEACAM6 can identify patients with extrahepatic cholangiocarcinoma with a high degree of sensitivity and should be investigated further as a potential screening tool. [ABSTRACT FROM AUTHOR]

Objective: Fine needle aspiration cytology (FNAC) for diagnosis of a parotid gland tumor is widely used but its sensitivity is low and non-diagnostic rate is relatively high. In contrast, core needle biopsy (CNB) has a higher sensitivity and lower rate of sampling errors but has a higher risk of injury to adjacent organs such as facial nerve than FNAC. Screening of patients with parotid gland tumors to identify cases of pleomorphic adenoma (PA) and Warthin tumor (WT) may allow CNB to be confined to patients without PA and WT. We established an algorithm for preoperative diagnosis and management of parotid gland tumor using diffusion-weighted MRI and 99mTc pertechnetate scintigraphy. This algorithm was developed with the goal of maximal reduction of the number of patients in whom CNB is required. The purpose of the study is to validate our algorithm prospectively. Methods: A prospective study was conducted in 71 cases who were newly diagnosed with parotid gland tumor and 53 cases were enrolled in the study. In the algorithm, PA (high apparent diffusion coefficient (ADC) mean≥1.5×10−3 mm2/s) and non-PA (low ADCmean<1.5×10−3 mm2/s) cases are first distinguished based on the ADCmean on diffusion-weighed MRI. Second, among suspected non-PA cases, WT and non-WT are distinguished using technetium-99m pertechnetate scintigraphy. CNB is then performed only in probable non-PA and non-WT cases. Results: Although CNB was only required in 40% (21/53) of all cases, we made a preoperative histopathological diagnosis with an accuracy of 87% (46/53) and we correctly diagnosed whether a tumor was benign or malignant with an accuracy of 96% (51/53). Preoperative surgical planning had to be changed during surgery in only one case (2%) Conclusions: Our algorithm is valuable in terms of clinical practice with highly potential for preoperative diagnosis and with less risk of CNB procedure. [ABSTRACT FROM AUTHOR]

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively assess the value of dual-energy CT (DECT) in differentiating malignancy and benignity of solitary pulmonary nodules. Materials and Methods: Sixty-three patients with solitary pulmonary nodules detected by CT plain scan underwent contrast enhanced CT scans in arterial phase (AP) and venous phase (VP) with spectral imaging mode for tumor type differentiation. The Gemstone Spectral Imaging (GSI) viewer was used for image display and data analysis. Region of interest was placed on the relatively homogeneous area of the nodule to measure iodine concentration (IC) on iodine-based material decomposition images and CT numbers on monochromatic image sets to generate spectral HU curve. Normalized IC (NIC), slope of the spectral HU curve (λHU) and net CT number enhancement on 70keV images were calculated. The two-sample t-test was used to compare quantitative parameters. Receiver operating characteristic curves were generated to calculate sensitivity and specificity. Results: There were 63 nodules, with 37 malignant nodules (59%) and 26 benign nodules (41%). NIC, λHU and net CT number enhancement on 70keV images for malignant nodules were all greater than those of benign nodules. NIC and λHU had intermediate to high performances to differentiate malignant nodules from benign ones with the areas under curve of 0.89 and 0.86 respectively in AP, 0.96 and 0.89 respectively in VP. Using 0.30 as a threshold value for NIC in VP, one could obtain sensitivity of 93.8% and specificity of 85.7% for differentiating malignant from benign solitary pulmonary nodules. These values were statistically higher than the corresponding values of 74.2% and 53.8% obtained with the conventional CT number enhancement. Conclusions: DECT imaging with GSI mode provides more promising value in quantitative way for distinguishing malignant nodules from benign ones than CT enhancement numbers. [ABSTRACT FROM AUTHOR]

Background: There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19–9 (CA 19–9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. Methods: CA 19–9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. Results: The combination of CA 19–9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19–9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Conclusions: Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis. [ABSTRACT FROM AUTHOR]

Aim: To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. Methods: Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared. Results: Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90–120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. Conclusions: Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC. [ABSTRACT FROM AUTHOR]

In this study we developed, characterized and validated in vitro a functional superparagmagnetic iron-oxide based magnetic resonance contrast agent by conjugating a commercially available iron oxide nanoparticle, Molday ION Rhodamine-B Carboxyl (MIRB), with a deimmunized mouse monoclonal antibody (muJ591) targeting prostate-specific membrane antigen (PSMA). This functional contrast agent is intended for the specific and non-invasive detection of prostate cancer cells that are PSMA positive, a marker implicated in prostate tumor progression and metastasis. The two-step carbodiimide reaction used to conjugate the antibody to the nanoparticle was efficient and we obtained an elemental iron content of 1958±611 per antibody. Immunofluorescence microscopy and flow cytometry showed that the conjugated muJ591:MIRB complex specifically binds to PSMA-positive (LNCaP) cells. The muJ591:MIRB complex reduced cell adhesion and cell proliferation on LNCaP cells and caused apoptosis as tested by Annexin V assay, suggesting anti-tumorigenic characteristics. Measurements of the T2 relaxation time of the muJ591:MIRB complex using a 400 MHz Innova NMR and a multi-echo spin-echo sequence on a 3T MRI (Achieva, Philips) showed a significant T2 relaxation time reduction for the muJ591:MIRB complex, with a reduced T2 relaxation time as a function of the iron concentration. PSMA-positive cells treated with muJ591:MIRB showed a significantly shorter T2 relaxation time as obtained using a 3T MRI scanner. The reduction in T2 relaxation time for muJ591:MIRB, combined with its specificity against PSMA+LNCaP cells, suggest its potential as a biologically-specific MR contrast agent. [ABSTRACT FROM AUTHOR]

Background: Distinguishing early gastric cancer is challenging with current imaging techniques. Narrow band imaging (NBI) is effective for characterizing gastric lesions. Objectives: The aim of this meta-analysis was to estimate the diagnostic accuracy of NBI in the gastric intestinal metaplasia (GIM). Methods: We performed data analysis using Meta-DiSc (version 1.4) and STATA (version 11.0) software. To assess study quality and potential for bias, we used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results: Six studies involving 347 patients were included. On a per-patient basis, the sensitivity of NBI for diagnosis of GIM was 0.65 (95% CI  =  0.56–0.74), and the specificity was 0.93 (95% CI  =  0.88–0.97). The area under the summary receiver operating characteristic (SROC) curve was 0.8731. However, on a per-lesion basis, the sensitivity and specificity of NBI were 0.69 (95% CI  =  0.63–0.74) and 0.91 (95% CI  =  0.87–0.94), respectively. The SROC was 0.9009. The pooled sensitivity and specificity of magnification endoscopy (NBI-ME) were 0.76 (95% CI  =  0.61–0.87) and 0.89 (95% CI  =  0.80–0.94), respectively, on per-patient analysis. On a per-lesion basis, the pooled sensitivity and specificity of NBI-ME were 0.84 (95% CI  =  0.76–0.89) and 0.93 (95% CI  =  0.89–0.96), respectively. Heterogeneity was observed with an I2 for diagnostic odds ratio (DOR) of 0.01% and 85.8%, respectively. There was no statistical significance for the evaluation of publication bias. Conclusions: Our meta-analysis shows that NBI is a useful tool for differential diagnosis of GIM with relatively low sensitivity and high specificity. [ABSTRACT FROM AUTHOR]

Robust detection of prostatic cancer is a challenge due to the multitude of variants and their representation in MR images. We propose a pattern recognition system with an incremental learning ensemble algorithm using support vector machines (SVM) tackling this problem employing multimodal MR images and a texture-based information strategy. The proposed system integrates anatomic, texture, and functional features. The data set was preprocessed using B-Spline interpolation, bias field correction and intensity standardization. First- and second-order angular independent statistical approaches and rotation invariant local phase quantization (RI-LPQ) were utilized to quantify texture information. An incremental learning ensemble SVM was implemented to suit working conditions in medical applications and to improve effectiveness and robustness of the system. The probability estimation of cancer structures was calculated using SVM and the corresponding optimization was carried out with a heuristic method together with a 3-fold cross-validation methodology. We achieved an average sensitivity of 0.844±0.068 and a specificity of 0.780±0.038, which yielded superior or similar performance to current state of the art using a total database of only 41 slices from twelve patients with histological confirmed information, including cancerous, unhealthy non-cancerous and healthy prostate tissue. Our results show the feasibility of an ensemble SVM being able to learn additional information from new data while preserving previously acquired knowledge and preventing unlearning. The use of texture descriptors provides more salient discriminative patterns than the functional information used. Furthermore, the system improves selection of information, efficiency and robustness of the classification. The generated probability map enables radiologists to have a lower variability in diagnosis, decrease false negative rates and reduce the time to recognize and delineate structures in the prostate. [ABSTRACT FROM AUTHOR]

Background and Aim: Circulating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients. Patients and Methods: We initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined. Results: Seven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75–0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36–6.55], P = 0.006; HR 3.84 [1.02–14.41], P = 0.029; HR 4.18 [1.21–14.50], P = 0.024, respectively). Conclusion: The seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC. [ABSTRACT FROM AUTHOR]

We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfite-converted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3% and 100% respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8% sensitivity and 66.7% specificity, with overall accuracy of 88.7%. A PHYMA score was developed for each sample based on the state of methylation in the PHYMA signature. Increasing PHYMA score was significantly associated with higher Gleason score and Gleason primary grade. Men with higher PHYMA scores have poorer survival on univariate (p = 0.0038, HR = 3.89) and multivariate analyses when controlled for (i) clinical stage (p = 0.055, HR = 2.57), and (ii) clinical stage and Gleason score (p = 0.043, HR = 2.61). We further performed bisulfite genomic sequencing on 2 relatively unknown genes to demonstrate robustness of the assay results. PHYMA is thus a signature with high sensitivity and specificity for discriminating tumors from BPH, and has a potential role in early detection and in predicting survival. [ABSTRACT FROM AUTHOR]

Objective: To quantitatively assess the imaging characteristics of sellar lesion in dual-energy computed tomography (CT) imaging for differentiation of sellar meningiomas and pituitary adenomas during the arterial phase (AP) and venous phase (VP). Materials and Methods: 51 patients with sellar/parasellar tumors (33 macroadenomas and 18 meningiomas) were examined with CT spectral imaging during the AP and the VP. Iodine concentrations were derived from iodine-based material-decomposition CT images and normalized to the iodine concentration in the aorta. The difference in Normalized iodine concentrations (NICs), HU curve slope (λHU), and mean CT values of lesions between the AP and VP were calculated. The two-sample t test was performed to compare quantitative parameters between sellar meningiomas and pituitary adenomas. Results: NICs, λHU, and mean CT values in patients with sellar meningiomas differed significantly from those in patients with pituitary adenomas: Mean NICs were 43.52 mg/mL±1.35 versus 9.23 mg/mL ±2.44, respectively, during the AP and 52.13 mg/mL ±1.04 versus 24.37 mg/mL ±2.23 respectively, during the VP. λHU were −3.03±3.42 versus −0.53±0.23, respectively, during the AP and −2.96±0.41 versus −0.47±0.25, respectively, during the VP. Mean CT values were 193.63±2.08 versus 63.98±2.85, respectively, during the AP and 203.98±0.18 versus 77.66±0.91, respectively, during the VP. The combination of NIC and Mean CT value during VP had highest sensitivity (90.9%) and specificity (100%) among all phases. Conclusion: Quantitative dual-energy CT imaging has promising potential for diagnostic differentiation of sellar meningiomas and pituitary adenomas. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of ultrasonography (US) with the current clinical standard of endoscopy for a diagnosis of nasopharyngeal carcinoma (NPC). Methods: A total of 150 patients suspected of having NPC underwent US and endoscopy. A diagnosis was obtained from an endoscopic biopsy collected from each suspected tumor and was compared with a biopsy obtained from a normal nasopharynx. The diagnostic accuracy of US and endoscopy for NPC was evaluated using receiver operating curve (ROC) analysis performed by MedCalc Software. Results: The sensitivity, specificity, and accuracy of US versus endoscopy for this cohort were 90.1%, 84.8%, and 87.3% for US, and 88.7%, 97.5%, and 93.3% for endoscopy, respectively. Both US and endoscopy exhibited good diagnostic accuracy for NPC with area under the curve (AUC) values of 0.929 and 0.938, respectively. However, this difference was not significant (Z = 0.36, P = 0.72). Conclusion: US is a useful tool for the detection of tumors in endoscopically suspicious nasopharynx tissues, and also for the detection of subclinical tumors in endoscopically normal nasopharynx tissues. [ABSTRACT FROM AUTHOR]