Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer.

OBJECTIVE: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. METHODS: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. RESULTS: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. CONCLUSIONS: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.

A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy.

Lung cancer, the leading cause of cancer death worldwide, is most frequently detected through imaging tests. In this study, we investigated serum microRNAs (miRNAs) as a possible early screening tool for resectable lung cancer. First, we used serum samples from participants with and without lung cancer to comprehensively create 2588 miRNAs profiles; next, we established a diagnostic model based on the combined expression levels of two miRNAs (miR-1268b and miR-6075) in the discovery set (208 lung cancer patients and 208 non-cancer participants). The model displayed a sensitivity of 99% and specificity of 99% in the validation set (1358 patients and 1970 non-cancer participants) and exhibited high sensitivity regardless of histological type and pathological TNM stage of the cancer. Moreover, the diagnostic index markedly decreased after lung cancer resection. Thus, the model we developed has the potential to markedly improve screening for resectable lung cancer.

Assessment of the Diagnostic Utility of Serum MicroRNA Classification in Patients With Diffuse Glioma.

Importance: A blood-based screening tool for detecting diffuse glioma is necessary to improve clinical outcomes. Objectives: To establish models using serum microRNAs to distinguish patients with diffuse glioma from control individuals without cancer (the Glioma Index) and to differentiate glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic brain tumors (the 3-Tumor Index). Design, Setting, and Participants: This retrospective, case-control diagnostic study included 157 patients with diffuse glioma and 109 patients with central nervous system (CNS) diseases other than diffuse glioma diagnosed from August 1, 2008, through May 1, 2016, and 314 sex- and age-matched controls without cancer. Samples of patients with diffuse glioma and controls were randomly divided into training and validation set 1, and those of patients with CNS diseases other than diffuse glioma were allocated to an exploratory set. Samples of patients with GBM, PCNSL, and metastatic brain tumors were randomly divided into training and validation set 2. Data were analyzed from April 1, 2018, to March 31, 2019. Main Outcomes and Measures: The expression of 2565 microRNAs was assessed, and the diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and accuracy. Results: A total of 580 patients were included in the analysis (309 [53.3%] male; median age, 57 years [range, 10-87 years]). In training set 1, 100 patients with diffuse glioma (median age, 56 years [range, 14-87 years]; 55 male [55.0%]) were compared with 200 control patients (median age, 56 years [range, 14-87 years]; 105 male [52.5%]), and the Glioma Index was constructed using 3 microRNAs (miR-4763-3p, miR-1915-3p, and miR-3679-5p). In validation set 1, the AUC was 0.99 (95% CI, 0.99-1.00); sensitivity, 0.95 (95% CI, 0.89-1.00); and specificity, 0.97 (95% CI, 0.93-1.00). The Glioma Index classified 39 of 42 PCNSL samples (92.9%) and 25 of 28 metastatic brain tumor samples (89.3%) as positive and 2 of 2 spinal tumors (100%) as negative in the exploratory set. In training set 2, 68 patients with GBM, 34 with PCNSL, and 23 with metastatic brain tumor were compared, and the 3-Tumor Index was constructed using 48 microRNAs. The 3-Tumor Index had an accuracy of 0.80, positively detecting 16 of 17 GBM samples (94.1%), 4 of 5 metastatic brain tumor samples (80.0%), and 4 of 8 PCNSL samples (50.0%) in validation set 2. Conclusions and Relevance: This study appears to have identified promising serum microRNA combinations for detecting diffuse glioma and for assessing histologic features of brain tumors.

Development and External Validation of a Nomogram Predicting the Probability of Significant Gleason Sum Upgrading among Japanese Patients with Localized Prostate Cancer.

Objective. The aim of this study is to develop a prognostic model capable of predicting the probability of significant upgrading among Japanese patients. Methods. The study cohort comprised 508 men treated with RP, with available prostate-specific antigen levels, biopsy, and RP Gleason sum values. Clinical and pathological data from 258 patients were obtained from another Japanese institution for validation. Results. Significant Gleason sum upgrading was recorded in 92 patients (18.1%) at RP. The accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 88.9%. Overall AUC was 0.872 when applied to the validation data set. Nomogram predictions of significant upgrading were within 7.5% of an ideal nomogram. Conclusions. Nearly one-fifth of Japanese patients with prostate cancer will be significantly upgraded. Our nomogram seems to provide considerably accurate predictions regardless of minor variations in pathological assessment when applied to Japanese patient populations.

External validation and head-to-head comparison of Japanese and Western prostate biopsy nomograms using Japanese data sets.

The objective of this study was to perform external validation of a previously developed prostate biopsy nomogram (the CHIBA nomogram) and to compare it with previously published nomograms developed in Japanese and overseas populations. Two different cohorts of patients were used: one from the Chiba Cancer Center (n = 392) in which transperineal 16-core biopsy was performed, and another from Chibaken Saiseikai Narashino Hospital (n = 269) in which transrectal 16-core biopsy was carried out. All patients were Japanese men with serum prostate-specific antigen levels less than 10 ng/mL. The predictive accuracy of our CHIBA nomogram and of four other published nomograms (Finne's sextant biopsy-based logistic regression model, Karakiewicz's sextant biopsy-based nomogram, Chun's 10-core biopsy-based nomogram and Kawakami's three-dimensional biopsy-based nomogram) was quantified based on area under the curve derived from receiver operating characteristic curves. Head-to-head comparison of area under the curve values demonstrated that our nomogram was significantly more accurate than all other models except Chun's (P = 0.012 vs Finne's, P = 0.000 vs Karakiewicz's, and P = 0.003 vs Kawakami's). Our nomogram appears to be more useful for the Japanese population than Western models. Moreover, external validation demonstrates that its predictive accuracy does not vary according to biopsy approach. This is the first report to demonstrate that the predictive accuracy of a nomogram is independent from the biopsy method.

Development of a new nomogram for predicting the probability of a positive initial prostate biopsy in Japanese patients with serum PSA levels less than 10 ng/mL.

OBJECTIVES: Although several nomograms for prostate cancer detection have been developed for Western populations, the models constructed on Japanese data would be more useful for the Japanese population because of various differences between Western and Asian populations. We previously developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from Japanese males. In the present study, a predictive model for Japanese males with a prostate-specific antigen (PSA) < 10 ng/mL was developed to guide decision-making for prostate biopsies. METHODS: The age, total PSA level, free to total PSA ratio, prostate volume, and the digital rectal examination findings of 1037 Japanese males with a PSA < 10 ng/mL undergoing initial prostate biopsy as part of individual screening were analyzed. For study validation, 20% of these data was randomly reserved. Logistic regression analysis estimated relative risk, 95% confidence intervals, and P-values. RESULTS: Age and the independent predictors of a positive biopsy result (elevated PSA, decreased free to total PSA ratio, small prostate volume, and abnormal digital rectal examination findings) were used to develop a predictive nomogram. The area under the receiver operating characteristic curve was significantly higher for the model (73.0%) than for PSA alone (55.0%). If externally validated, the use of this nomogram could reduce unnecessary biopsies by 26% and overall prostate biopsies by 7.8%. CONCLUSIONS: This predictive nomogram could provide more precise risk-analysis information for individual Japanese patients with PSA levels less than 10 ng/mL and may help to identify patients who need a prostate biopsy.

Micelles of pulmonary surfactant in human amniotic fluid at term.

Studies using in vitro analysis have shown that the interaction between pulmonary surfactant and vernix caseosa could explain the appearance of amniotic fluid turbidity. That phenomenon is interpreted based on the "roll-up" hypothesis. We tested the roll-up hypothesis by examining the presence of micelles of pulmonary surfactant in human amniotic fluid at term. Amniotic fluid samples were collected from each of six healthy pregnant women at term and at 16 wk of gestation. These samples were stained negatively and analyzed using an electron microscope. Ultrastructures present in amniotic fluid were compared with the structure of micelles derived from suspended surfactant TA isolated from bovine lung. Surfactant TA formed spheroidal and rod-shaped micelles 10-70 nm in diameter above the critical micelle concentration. Identical micelle particles were described in human amniotic fluid at term. In addition, surfactant protein B was identified in the micelle fraction of amniotic fluid. However, no micelles were found in human amniotic fluid taken at 16 wk of gestation. Our results support the view that pulmonary surfactant could induce the detachment of vernix caseosa and increase the turbidity of the amniotic fluid.

Development of a nomogram to predict probability of positive initial prostate biopsy among Japanese patients.

OBJECTIVES: Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower among Asian men, nomograms based on Western populations cannot be directly applied to Japanese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Japanese male population. METHODS: Data were collected from 834 Japanese male referrals who underwent initial prostate biopsies as individual screening. We analyzed age, total prostate-specific antigen (PSA) level, free/total PSA (f/t PSA) ratio, prostate volume, and digital rectal examination findings. Of these data, we randomly reserved 20% for study validation. Logistic regression analysis estimated relative risk, 95% confidence intervals, and P values. RESULTS: Independent predictors of a positive biopsy result included elevated PSA levels, decreased f/T PSA ratio, advanced age, small prostate volume, and abnormal digital rectal examination findings. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver operating characteristic curve for the model was 81.8%, which was significantly greater than that of the prediction based on PSA alone (area under the receiver operating characteristic curve 67.8%). If externally validated, applying this model could reduce unnecessary biopsy procedures by 32% and reduce the overall need for prostate biopsies by 26%. CONCLUSIONS: In this study of a Japanese population, incorporating clinical and laboratory data into a prebiopsy nomogram significantly improved the prediction of prostate cancer compared with predictions based solely on the individual factors.

Determination of cadmium, zinc, nickel and cobalt in tobacco by reversed-phase high-performance liquid chromatography with 2-(8-quinolylazo)-4,5-diphenylimidazole as a chelating reagent.

A sensitive and selective method has been developed for the simultaneous determination of cadmium, zinc, nickel and cobalt. The method is based on the chelation of metal ions with 2-(8-quinolylazo)-4,5-diphenylimidazole (QAI) and the subsequent reversed-phase (RP) high-performance liquid chromatographic separation and spectrophotometric detection of the metal chelates. The chelates were separated on an RP column with acetonitrile-water containing ethylenediamine tetraacetic acid and sodium acetate (pH 7.5). Though Zn(II) and Cd(II) chelates with azo compounds were generally labile in the RP column, these chelates with QAI were successfully detected. When analyses were carried out at 575 nm and at 0.001 absorbance unit full scale, the peak height calibration curves were linear up to 2.0 ng for Cd(II), 2.4 ng for Zn(II), 0.14 ng for Ni(II) and 0.72 ng for Co(II) in 100-microL injections, respectively; the detection limits (3sigma, three times of the standard deviation for the blank signal) for Cd(II), Zn(II), Ni(II) and Co(II) were 4.8, 24, 2.4 and 7.2 pg in 100 microL of injected solution, respectively. The proposed method was successfully applied to the analysis of tobacco without any preliminary concentration or separation.