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Simple Summary: Radical prostatectomy, the standard treatment for localized or locally advanced prostate cancer, generally provides good disease control and favorable long-term survival. However, about 40% of patients experience biochemical recurrence, and a significant number of them develop clinical progression. If identified in advance, those patients could receive specially tailored follow-up and counseling. Current guidelines recommend the first prostate-specific antigen tests three months after surgery, but prostate-specific antigen levels should be undetectable within four weeks. Early testing at 4–8 weeks after surgery could thus be useful for determining patient prognosis. We reviewed the medical literature to study persistence of prostate-specific antigens, progression of prostate cancer, and survival of patients. We found that prostate cancer was more likely to recur in patients with or without lymph nodal involvement who had prostate-specific antigen persistence at 4–8 weeks. We performed a systematic review and meta-analysis to assess the prognostic value of prostate-specific antigen (PSA) persistence 4–8 weeks after radical prostatectomy (RP) in patients with prostate cancer, using studies from Medline, Scopus, and Cochrane Library, on 10 October 2020. Studies were eligible if they compared patients with postoperative PSA persistence 4–8 weeks after RP to those without such persistence to assess the value of PSA persistence in prognosticating biochemical recurrence (BCR), disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM) by multivariable analysis. Our review and analysis included nine studies published between 2008 and 2019 with 14,455 patients. Of those studies, 12.0% showed postoperative PSA persistence. PSA persistence was associated with BCR (HR: 4.44, 95% CI: 2.84–6.93), disease recurrence (HR: 3.43, 95% CI: 1.62–7.25), and CSM (HR: 2.32, 95% CI: 1.83–2.95). We omitted meta-analysis on the association of PSA persistence with OM due to an insufficient number of studies. PSA persistence was associated with disease recurrence in a sub-group of patients with pathological nodal involvement (HR: 5.90, 95% CI: 3.76–9.24). Understanding detection of PSA persistence at 4–8 weeks after RP might be useful for patient counseling, follow-up scheduling, and clinical decision-making regarding adjuvant therapies. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have high potential as sources of biomarkers for non-invasive diagnostics. Thus, a simple and productive method of EV isolation is demanded for certain scientific and medical applications of EVs. Here we aim to develop a simple and effective method of EV isolation from different biofluids, suitable for both scientific, and clinical analyses of miRNAs transported by EVs. The proposed aggregation–precipitation method is based on the aggregation of EVs using dextran blue and the subsequent precipitation of EVs using 1.5% polyethylene glycol solutions. The developed method allows the effective isolation of EVs from plasma and urine. As shown using TEM, dynamic light scattering, and miRNA analyses, this method is not inferior to ultracentrifugation-based EV isolation in terms of its efficacy, lack of inhibitors for polymerase reactions and applicable for both healthy donors and cancer patients. This method is fast, simple, does not need complicated equipment, can be adapted for different biofluids, and has a low cost. The aggregation–precipitation method of EV isolation accessible and suitable for both research and clinical laboratories. This method has the potential to increase the diagnostic and prognostic utilization of EVs and miRNA-based diagnostics of urogenital pathologies. [ABSTRACT FROM AUTHOR]

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline BRCA (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.'s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline BRCA mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. "Discordant: Opposite classification" was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of BRCA 1 by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. "Discordant: Laboratory's uncertain classification" was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required. [ABSTRACT FROM AUTHOR]

The tumour-to-breast volume ratio (TBVR) is a metric that may help surgical decision making. In this retrospective Ethics-Committee–approved study, we assessed the correlation between magnetic resonance imaging (MRI)-derived TBVR and the performed surgery. The TBVR was obtained using a fully manual method for the segmentation of the tumour volume (TV) and a growing region semiautomatic method for the segmentation of the whole breast volume (WBV). Two specifically-trained residents (R1 and R2) independently segmented T1-weighted datasets of 51 cancer cases in 51 patients (median age 57 years). The intraobserver and interobserver TBVR reproducibility were calculated. Mann-Whitney U, Spearman correlations, and Bland-Altman statistics were used. Breast-conserving surgery (BCS) was performed in 31/51 cases (61%); mastectomy was performed in 20/51 cases (39%). The median TBVR was 2.08‰ (interquartile range 0.70–9.13‰) for Reader 1, and 2.28‰ (interquartile range 0.71–9.61‰) for Reader 2, with an 84% inter-reader reproducibility. The median segmentation times were 54 s for the WBV and 141 s for the TV. Significantly-lower TBVR values were observed in the breast-conserving surgery group (median 1.14‰, interquartile range 0.49–2.55‰) than in the mastectomy group (median 10.52‰, interquartile range 2.42–14.73‰) for both readers (p < 0.001). Large scale prospective studies are needed in order to validate MRI-derived TBVR as a predictor of the type of breast surgery. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is one of the most common male cancers worldwide. Until now, there is no consensus about using urinary metabolomic profiling as novel biomarkers to identify PC. In this study, urine samples from 50 PC patients and 50 non-cancerous individuals (control group) were collected. Based on 1H nuclear magnetic resonance (1H-NMR) analysis, 20 metabolites were identified. Subsequently, principal component analysis (PCA), partial least squares-differential analysis (PLS-DA) and ortho-PLS-DA (OPLS-DA) were applied to find metabolites to distinguish PC from the control group. Furthermore, Wilcoxon test was used to find significant differences between the two groups in metabolite urine levels. Guanidinoacetate, phenylacetylglycine, and glycine were significantly increased in PC, while L-lactate and L-alanine were significantly decreased. The receiver operating characteristics (ROC) analysis revealed that the combination of guanidinoacetate, phenylacetylglycine, and glycine was able to accurately differentiate 77% of the PC patients with sensitivity = 80% and a specificity = 64%. In addition, those three metabolites showed significant differences in patients stratified for Gleason score 6 and Gleason score ≥7, indicating potential use to detect significant prostate cancer. Pathway enrichment analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and the SMPDB (The Small Molecule Pathway Database) revealed potential involvement of KEGG "Glycine, Serine, and Threonine metabolism" in PC. The present study highlights that guanidinoacetate, phenylacetylglycine, and glycine are potential candidate biomarkers of PC. To the best knowledge of the authors, this is the first study identifying guanidinoacetate, and phenylacetylglycine as potential novel biomarkers in PC. [ABSTRACT FROM AUTHOR]