Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.8%) were obtained using a new harvesting method, and metabolic profiles of samples representing different Gleason scores (GS) were acquired by high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine the ability to predict cancer aggressiveness by comparing low grade (GS = 6, n = 30) and high grade (GS≥7, n = 81) cancer with normal adjacent tissue (n = 47). High grade cancer tissue was distinguished from low grade cancer tissue by decreased concentrations of spermine (p = 0.0044) and citrate (p = 7.73·10−4), and an increase in the clinically applied (total choline+creatine+polyamines)/citrate (CCP/C) ratio (p = 2.17·10−4). The metabolic profiles were significantly correlated to the GS obtained from each tissue sample (r = 0.71), and cancer tissue could be distinguished from normal tissue with sensitivity 86.9% and specificity 85.2%. Overall, our findings show that metabolic profiling can separate aggressive from indolent prostate cancer. This holds promise for the benefit of applying in vivo magnetic resonance spectroscopy (MRS) within clinical MR imaging investigations, and HR-MAS analysis of transrectal ultrasound-guided biopsies has a potential as an additional diagnostic tool.
Gleason scores from biopsy and RP specimens. Concordance was evaluated using the κ coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses.
RESULTSThe Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy-based Gleason score more often under-graded (38%) than overgraded (9%) the RP-based Gleason score. Pathology units that examined > 40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lowervolume units. The rate of upgrading from a Gleason score of ≤ 6 in the biopsy to ≥ 7 in the RP specimen increased with increasing preoperative prostate-specific antigen serum levels, and with increasing intervals between biopsy and RP.
CONCLUSIONSThe concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.
SUMMARY BackgroundProton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and give hypergastrinemia secondary to gastric hypoacidity. PPI treatment therefore induces enterochromaffin-like (ECL) cell hyperplasia. Longterm hypergastrinemia in rodents and man also leads to ECL cell neoplasia. Whether long-term PPI treatment will induce ECL cell neoplasia in man has been disputed.
Although the overall frequency of lymphocele formation was high, clinically significant lymphoceles were scarce. LPLND was associated with a statistically significant lower frequency of lymphocele formation compared to OPLND.
We present a safe and standardized method for procurement of a high quality fresh frozen prostate slice, suitable for gene expression analysis and MR spectroscopy.
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