Transition Zone Prostate Research Articles

MP17-20 PHOSPHODIESTERASE TYPE 5 (PDE5) IN THE HUMAN PROSTATE: RELATION TO KEY ENZYMES OF THE NITRIC OXIDE/CYCLIC GMP SIGNALING

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-20 PHOSPHODIESTERASE TYPE 5 (PDE5) IN THE HUMAN PROSTATE: RELATION TO KEY ENZYMES OF THE NITRIC OXIDE/CYCLIC GMP SIGNALING Stefan Ueckert, Andreas Bannowsky, Markus Kuczyk, and Petter Hedlund Stefan UeckertStefan Ueckert More articles by this author , Andreas BannowskyAndreas Bannowsky More articles by this author , Markus KuczykMarkus Kuczyk More articles by this author , and Petter HedlundPetter Hedlund More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.609AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The significance of the nitric oxide (NO)/cyclic GMP pathway in the control of prostate smooth musculature actually serves as a rationale for the clinical development of the phosphodiesterase type 5 (PDE5, cyclic GMP PDE) inhibitor tadalafil to treat lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). However, the potential relevance of the nitric oxide (NO)/cyclic GMP signaling in the human prostate is still discussed controversly. For example, it has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by the effects of this class of drugs on the urinary bladder rather than the prostate (Chapple C.R., Roehrborn C.G., Eur. Urol. 49: 651-659, 2006). This prompted us to evaluate in the human prostate the expression of key proteins of the NO pathway, namely the neuronal nitric oxide synthase (nNOS), cyclic GMP, and cyclic GMP-binding protein kinase type I (isoforms alpha und beta = cGKIα, cGKIβ), in relation to the PDE5. METHODS Slices (10 µm) of specimens taken from the transition zone (TZ) of the human prostate were exposed to antibodies directed against cyclic GMP, PDE5A, nNOS, cGKIα or cGKIβ, followed by the application of fluorochrome-labeled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy. RESULTS In the smooth muscle (SM) portion of the TZ, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα and cGKIβ, as well as with the cyclic cAMP-binding protein kinase A (cAK). SM bundles were seen innervated by slender varicose nerve fibers characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP (vasoactive intestinal polypeptide). CONCLUSIONS The results are in support of the hypothesis of a role of the cyclic GMP signaling in the control of the TZ of the prostate and also give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e218 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Stefan Ueckert More articles by this author Andreas Bannowsky More articles by this author Markus Kuczyk More articles by this author Petter Hedlund More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP17-14 DEPLETION OF PERIPHERAL SEROTONIN SYNTHESIS INDUCES BENIGN PROSTATIC GROWTH IN MICE: MORE EVIDENCE FOR THE NEW “NEUROENDOCRINE THEORY” IN BPH ETIOLOGY

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-14 DEPLETION OF PERIPHERAL SEROTONIN SYNTHESIS INDUCES BENIGN PROSTATIC GROWTH IN MICE: MORE EVIDENCE FOR THE NEW “NEUROENDOCRINE THEORY” IN BPH ETIOLOGY Paulo Mota, Emanuel Carvalho-Dias, Alice Miranda, Olga Martinho, Cristina Nogueira-Silva, Natalia Alenina, Michael Bader, Riccardo Autorino, Estevão Lima, and Jorge Correia-Pinto Paulo MotaPaulo Mota More articles by this author , Emanuel Carvalho-DiasEmanuel Carvalho-Dias More articles by this author , Alice MirandaAlice Miranda More articles by this author , Olga MartinhoOlga Martinho More articles by this author , Cristina Nogueira-SilvaCristina Nogueira-Silva More articles by this author , Natalia AleninaNatalia Alenina More articles by this author , Michael BaderMichael Bader More articles by this author , Riccardo AutorinoRiccardo Autorino More articles by this author , Estevão LimaEstevão Lima More articles by this author , and Jorge Correia-PintoJorge Correia-Pinto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.603AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ageing and testosterone cause almost inexorably benign prostatic hyperplasia (BPH) in Human males, however the etiology of BPH is unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and is present in high concentration in normal prostatic transition zone. In BPH neuroendocrine cells and 5-HT are significantly decreased comparatively to normal prostatic transition zone. Previously, we have demonstrated in several in vitro models that 5-HT inhibitis non-malignant prostatic growth through androgen receptor down-regulation and we suggested a new Neuroendocrine Theory for BPH etiology. Here, we investigated in vivo the effects of peripheral inhibition of 5-HT synthesis on mice prostate gland. METHODS peripheral 5-HT synthesis is critical dependent of the presence of TPH1, so we used transgenic mice depleted from TPH1 (Tph1-/-) to study the in vivo effect of peripheral serotonin depletion. Male wild-type and Tph1-/- mice were sacrificed at different time points: 7, 12, 16 and 20 weeks-old. For pharmacological studies, wild-type and Tph1-/- mice with 19 week-old were treated with daily intraperitoneal injections of 0,9% saline or 5-HT (100 mg/Kg) during 10 consecutive days.Prostate gland mass was determined and proceeded for histology, western blotting, immunofluorescence and qRT-PCR of AR expression. RESULTS We showed that Tph1 knockout mice depleted from peripheral 5-HT have significant higher prostate mass comparatively to wild-type (p < 0,001) and 5-HT treatment of Tph1 knockout mice restores prostate mass to levels of wild-type (p < 0,001) (figure A and B). We demonstrated also that the benign prostatic growth in Tph1 knockout mice is associated with up-regulation of AR and 5-HT treatment restores de expression of AR (p<0,05) (Figure C and D). CONCLUSIONS In vivo, 5-HT depletion induces benign prostatic growth in mice trough AR up-regulation. 5-HT depletion in transition zone of aging human male could be the etiologic factor for BPH etiology. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e216-e217 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Paulo Mota More articles by this author Emanuel Carvalho-Dias More articles by this author Alice Miranda More articles by this author Olga Martinho More articles by this author Cristina Nogueira-Silva More articles by this author Natalia Alenina More articles by this author Michael Bader More articles by this author Riccardo Autorino More articles by this author Estevão Lima More articles by this author Jorge Correia-Pinto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A Patient with Anterior, Apical, Transitional Zone Prostate Cancer Missed Twice by Standard Biopsy.

A Patient with Anterior, Apical, Transitional Zone Prostate Cancer Missed Twice by Standard Biopsy.

Diagnosis of typical and atypical transition zone prostate cancer and its mimics at multiparametric prostate MRI.

Many of the current clinical screening methods for prostate cancer (PCa) such as prostate-specific antigen (PSA) testing or transrectal ultrasound-guided prostate biopsy lack sensitivity and specificity for diagnosis of PCa of the transition zone (TZ). Recent technical advances in multiparametric-MRI have markedly improved detection of PCa of the TZ. However, there are many diagnostic challenges that we still encounter in our daily practice that compromise the accuracy of the diagnosis. By performing both MRI-guided and ultrasound/MRI fusion-guided biopsies, we have gained extensive experience in the diagnosis of PCa of the TZ. Biopsy-proven examples including but not limited to typical and atypical PCa of the TZ as well as a wide variety of its mimics will be presented. Recognition of the MR features of typical and atypical PCa of the TZ and its mimics on multiparametric-MRI along with findings that help to differentiate these mimics from PCa is important in establishing an accurate diagnosis and in guiding clinical management.

Prostate transitional zone volume-based nomogram for predicting prostate cancer and high progression prostate cancer in a real-world population.

To evaluate and compare the efficacy of prostate volume (PV), transitional zone volume (TZV), and prostate volume index (PVI, the ratio of TZV to peripheral zone volume) in the identification of men at risk of prostate cancer (PCa) and high-progression PCa (HPPCa) at the initial biopsy (IBX) in a real-world population. From Jul 2014 to Aug 2016, data on 1144 patients who had undergone the initial prostate biopsies were prospectively collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors for PCa and HPPCa. Based on independent predictors, nomogram models were developed and internally validated to assess a man's risk of harboring PCa and HPPCa. The detection rates of PCa and HPPCa were 43.09% (493/1144) and 39.16% (448/1144), respectively. In the multivariate analyses, age, PSA, TZV, DRE, and TRUS instead of PV or PVI were independent predictors for PCa and HPPCa, percent free PSA was independent predictor for PCa not for HPPCa. Such independent predictors were finally included in the nomogram models. The AUCs of TZV-based nomogram models were 87.0% for PCa and 87.7% for HPPCa, which were higher than that of PSA alone or other predictive models. TZV is a better predictive biomarker than PV or PVI for PCa and HPPCa, we recommend adding TZV but not PV or PVI to the nomogram models to improve the predictive accuracy of PCa and HPPCa at IBX.

A Study on the Correlations between Total Prostate Volume and Prostate Transition Zone Volume Assessed Using Blood and Ultrasound Tests: in the Healthy Korean Men in Thirties

A Study on the Correlations between Total Prostate Volume and Prostate Transition Zone Volume Assessed Using Blood and Ultrasound Tests: in the Healthy Korean Men in Thirties

A prospective study of calorimetric estimation of blood loss in TURP cases

Introduction: BEP is hyperplasia of prostatic stromal epithelial cells to form discreate nodules in transitional zone of prostate. It leads to constriction of urethral opening which gives rise to associated lower urinary tract symptoms such as frequency, urgency, nocturia. Initially disease can be managed by drug treatment but eventually most of the patients require surgical management. TURP remains gold standard treatment. Blood loss during and after procedure is major problem. This study was planned to evaluate the approximate blood loss with the help of simple technique of colorimatry. Method: This study is carried out on 50 patients with BEP who underwent TURP in our institute from October 2014 and June 2015. Irrigation fluid collected during TURP, post operative day 1 & 2 subjected to calorimetric estimation of blood loss using Drabkin’s reagent. Results: The results were suggestive of approximate average blood loss during TURP procedure as 267 ml, post operative day 1 blood loss 98.9ml and post operative day 2 loss was 58.1ml. However the average blood loss changes according to the size of prostate and duration of the procedure. Conclusion: calorimetric estimation of blood loss during and post operative period is an easy, economically feasible, quick method to guide the management of blood requirement for the patient. This can be useful in patients with BEP and bleeding diathesis.

\u201cTextural analysis of multiparametric MRI detects transition zone prostate cancer\u201d

ObjectivesTo evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour.MethodsSixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had ‘significant’ TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis.ResultsADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83).ConclusionTextural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion.Key Points• MR textural features of prostate transition zone may discriminate significant prostatic cancer.• Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram.• TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity.• The utility of MR texture analysis in prostate cancer merits further investigation.

MP39-20 ARE THERE ANY APPROPRIATE CRITERIA FOR RECOMMENDING PROSTATE BIOPSY IN PATIENTS OVER 75 YEARS OLD?

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2016MP39-20 ARE THERE ANY APPROPRIATE CRITERIA FOR RECOMMENDING PROSTATE BIOPSY IN PATIENTS OVER 75 YEARS OLD? Yu Teranishi, Takeo Kosaka, Kazuhiro Matsumoto, Shinya Morita, Kazunobu Shinoda, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikuchi, Hiroshi Asanuma, Akira Miyajima, and Mototsugu Oya Yu TeranishiYu Teranishi More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Shinya MoritaShinya Morita More articles by this author , Kazunobu ShinodaKazunobu Shinoda More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Toshiaki ShinojimaToshiaki Shinojima More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Hiroshi AsanumaHiroshi Asanuma More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.145AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Appropriate criteria for recommending prostate biopsy are controversial, especially in elderly men. In this study, we investigated the diagnostic value of prostate-specific antigen (PSA) and its multiple factors in men over 75 years of age to avoid overdiagnosis and reduce unnecessary biopsy procedures. METHODS A total of 2498 men underwent a transrectal prostate biopsy between 2004 and 2011 at Keio University Hospital in Tokyo. We retrospectively reviewed the records of 458 men who were over 75 years old. Patients with PSA levels between 4.0 and 10.0 ng/ml were divided into two groups: one with a negative biopsy and Gleason score of 6 or less, the other with a Gleason score of 7 or more. The clinical values of age, prostate volume (P vol), prostate transition zone volume (Tz vol), prostate-specific antigen density (PSAD), and prostate-specific antigen density of the transition zone (PSATzD) for the detection of prostate cancer were compared using receiver operating characteristic (ROC) curves and by calculating the sensitivity, specificity, positive predictive value, and negative predictive value. The same was conducted for PSA levels between 10.0 and 20.0 ng/ml and over 20.0 ng/ml. RESULTS Among the patients with PSA levels between 4.0 and 10.0 ng/ml, the mean (± SD) age, PSA, P vol, Tz vol, PSAD, and PSATzD were 77.7 ± 2.5 years, 6.7 ± 1.6 ng/ml, 38.2 ± 21.5 cm3,19.0 ± 14.9 cm3, 0.22 ± 0.12, and 0.54 ± 0.39, respectively, in men with positive biopsy. There were significant differences in PSA (P=0.001), P vol (P<0.001), Tz vol (P<0.001), PSAD (P<0.001), and PSATzD (P<0.001). A total of 153 men had a negative biopsy and Gleason score 6 or less, and 92 a Gleason score 7 or more. Statistical analysis to compare these 153 men and 92 men revealed a significant difference in PSAD only (P<0.001). The area under the curve of ROC of PSAD was 0.711. The sensitivity, specificity, positive predictive value, and negative predictive value were 76.1%, 52.69%, 49.3%, and 78.6%, respectively, by setting the cut-off value to PSAD 0.15. Among the patients with PSA levels between 10.0 and 20.0 ng/ml and with PSA levels over 20.0 ng/ml, there was no difference in PSAD. CONCLUSIONS Patients 75 or older with a PSA level between 4.0 and 10.0 ng/ml and PSAD less than 0.15 are unlikely to have prostate cancer and therefore it may be possible to avoid overdiagnosis, thereby reducing unnecessary biopsies. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e549 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yu Teranishi More articles by this author Takeo Kosaka More articles by this author Kazuhiro Matsumoto More articles by this author Shinya Morita More articles by this author Kazunobu Shinoda More articles by this author Ryuichi Mizuno More articles by this author Toshiaki Shinojima More articles by this author Eiji Kikuchi More articles by this author Hiroshi Asanuma More articles by this author Akira Miyajima More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Quantitative Stereological Estimations of Structural Patterns of the Glandular Tree in Benign Hyperplasia of Prostate

Background: Benign prostate hyperplasia (BPH) is the most common benign disease of human prostate. Currently BPH is associated with unregulated proliferation of connective tissue and glandular epithelium within the prostatic transition zone, and it has been described as relevant characteristic of BPH—the increase of the total number of cells, and not only an increase in cell size. To date, there are few studies on the quantitative morphology of glandular tree of BPH compared with normal prostate. The scarce investigations about this particular suggest that the glandular tree branches and expands as the hyperplastic transformation occurs in the prostate. Methods: To verify if this gland expansion and branching was similar to that occurs in the normal prostate, this study deals with the estimation of several stereological parameters as: labeling index for the proliferating cell nuclear antigen to quantify the rate of proliferation of prostate epithelium, average thickness of glandular epithelium, fraction of the volume occupied by the epithelium relative to the total prostate volume, connectivity density of prostate glands, to quantify the branching of prostate glands, and the average volume and the volume-weighted mean glandular volume of prostate acini to assess the mean size of the prostate acini and its variability. Results: All these estimates have been performed in prostate specific antigen immunostained sections from prostates of young men (controls) and in adenomectomy specimens from the adenofibromiomatous variety of BPH. Conclusion: We conclude that the epithelial proliferation is not the only factor intervening in the development of BPH. In addition, a more prolonged survival of epithelial population, together with some degree of hypertrophy of acini expressed by the increase of volume fraction and thickness of acinar epithelium, is relevant in order to the growth and expansion of the BPH glandular tree that shows more abundant and heterogeneous acinar sprouts than in normal prostate.

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.

Transition zone prostate specific antigen density improves prostate cancer detection in Iranian men.

Background:Prostate specific antigen (PSA) as a tumor marker has extensively changed the diagnosis of prostate cancer (PCa). With the advent of PSA, the majority of patients are diagnosed with nonpalpable early stage PCa. However, PSA lacks specificity and many patients undergo unnecessary biopsies due to an elevated serum PSA level.Objectives:This study aimed to assess the sensitivity and specificity of transition zone PSA density (TZPSAD) in detection of PCa.Patients and Methods:This study was performed on 1712 men underwent trans-rectal ultrasound guided prostate biopsy in our institution between March 2008 and March 2013. A total of 1120 men with PSA < 20 ng/mL and normal digital rectal exam were selected for evaluation. Transition zone PSA density was calculated in all patients and the receiver operating characteristic (ROC) curve was used to analyze the accuracy of TZPSAD for the diagnosis of PCa.Results:Among 1120 men who were eligible for enrolment, prostate cancer was detected in 265 patients. Mean serum PSA levels were 9.7 ± 4.3 ng/mL and 8.5 ± 3.7 ng/mL in patients with and without PCa, respectively (P < 0.001). Mean value for TZPSAD was 1.18 ± 1.19 ng/mL/mL in patients with PCa, whereas it was 0.55 ± 0.84 ng/mL in men without cancer (P < 0.001). Optimal cut-off value for TZPSAD was 0.32 ng/mL. At this cut-off value, the sensitivity and specificity values for TZPSAD were 85% and 45%, respectively. Applying the TZPSAD for PCa screening decreased 50% of unnecessary biopsies.Conclusions:Using TZPSAD as an adjunct to PSA may improve the specificity of PSA in the diagnosis of PCa and decrease the number of unnecessary prostatic biopsies in Iranian men with serum PSA level < 20 ng/mL.

Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.

ObjectivesWe aimed to develop logistic regression (LR) models for classifying prostate cancer within the transition zone on multi-parametric magnetic resonance imaging (mp-MRI).MethodsOne hundred and fifty-five patients (training cohort, 70 patients; temporal validation cohort, 85 patients) underwent mp-MRI and transperineal-template-prostate-mapping (TPM) biopsy. Positive cores were classified by cancer definitions: (1) any-cancer; (2) definition-1 [≥Gleason 4 + 3 or ≥ 6 mm cancer core length (CCL)] [high risk significant]; and (3) definition-2 (≥Gleason 3 + 4 or ≥ 4 mm CCL) cancer [intermediate–high risk significant]. For each, logistic-regression mp-MRI models were derived from the training cohort and validated internally and with the temporal cohort. Sensitivity/specificity and the area under the receiver operating characteristic (ROC-AUC) curve were calculated. LR model performance was compared to radiologists’ performance.ResultsTwenty-eight of 70 patients from the training cohort, and 25/85 patients from the temporal validation cohort had significant cancer on TPM. The ROC-AUC of the LR model for classification of cancer was 0.73/0.67 at internal/temporal validation. The radiologist A/B ROC-AUC was 0.65/0.74 (temporal cohort). For patients scored by radiologists as Prostate Imaging Reporting and Data System (Pi-RADS) score 3, sensitivity/specificity of radiologist A ‘best guess’ and LR model was 0.14/0.54 and 0.71/0.61, respectively; and radiologist B ‘best guess’ and LR model was 0.40/0.34 and 0.50/0.76, respectively.ConclusionsLR models can improve classification of Pi-RADS score 3 lesions similar to experienced radiologists.Key Points• MRI helps find prostate cancer in the anterior of the gland • Logistic regression models based on mp-MRI can classify prostate cancer • Computers can help confirm cancer in areas doctors are uncertain about

Multi-parametric MRI findings of transitional zone prostate cancers: correlation with 3-dimensional transperineal mapping biopsy.

A preliminary project to correlate MR findings with mapping prostate biopsy to help differentiate malignant transitional zone lesions form benign prostatic hyperplasia (BPH) nodules. Institutional IRB approved retrospective study with 14 patients suspected of having prostate cancer who underwent both prostate 3T MRI using endorectal coil and 3D transperineal mapping prostate biopsy. MR exams were independently reviewed by two abdominal radiologists blinded to pathology with disagreement resolved by consensus. An MRI lesion was defined as having hypointense T2 signal subjectively without corresponding T1 high signal intensity and low signal on ADC maps in the central gland. Mapping biopsy consisted of systematic transperineal US guided biopsy with 55-108 cores per patient. Twenty-nine lesions were detected on MRI. Of these, 13 correlated with Gleason 6 or higher biopsy samples. 16 were biopsy negative. Among the various MRI characteristics assessed, lack of T2 hypointense rim demonstrated the highest specificity (93%) and positive predictive value (89%). Highest sensitivity (85%) and negative predictive value (78%) were seen with ill-defined nodules. When suspicious MR characteristics were combined, the specificity and PPV rose to 100% while sensitivity decreased to 45% and NPV decreased to 73%. Preliminary study indicates MR findings which can help differentiate a BPH nodule from transitional zone prostate cancers which could help direct biopsy in the large and growing number of people suspected of having prostate cancer. Further work will be needed for validation.

Individualized prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men.

To individualize prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men. A total of 406 men aged over 70 years old with prostate-specific antigen levels between 4.0 and 20.0 ng/ml, normal digital rectal examination results and diagnosed by transrectal needle biopsy were retrospectively analyzed. The patients were divided into a no/favorable-risk cancer group or an unfavorable-risk cancer group based on their Gleason score and the number of positive cores. Prostate-specific antigen levels, percent free prostate-specific antigen level, prostate transition zone volume and the number of previous biopsies were used to discriminate between the two groups. The optimal individualized prostate-specific antigen threshold values based on the other variables that gave a sensitivity of 95% for the detection of unfavorable-risk cancer were calculated using a boosting method for maximizing the area under the receiver operating characteristic curve. A total of 66 men had favorable-risk cancer, and 139 had unfavorable-risk cancer. The area under the receiver operating characteristic curve of the combination model determined by the boosting method for maximizing the area under the receiver operating characteristic curve was 0.852. The sensitivity and specificity of the threshold values for the detection of unfavorable-risk cancer were 95 and 36%, respectively. By using the threshold values, 100 (25%) of the subjects with no/favorable-risk cancer could have avoided undergoing biopsies, with a <5% risk of missing the detection of unfavorable-risk cancer. These individualized prostate-specific antigen threshold values may be useful for determining an indication of prostate biopsy for elderly men to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy.

Effect of Tadalafil Once Daily on Prostate Blood Flow and Perfusion in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Randomized, Double-blind, Multicenter, Placebo-controlled Trial

To assess effects of tadalafil vs placebo on prostatic blood flow measured by transrectal ultrasonography in men aged≥45years with moderate-to-severe benign prostatic hyperplasia-lower urinary tract symptoms. After screening and washout, patients were randomized to placebo (n= 50) or tadalafil 5mg (n= 47) once daily for 8weeks. Transrectal ultrasonography was performed at baseline, 4, and 8weeks. The primary efficacy measure was the prostate transition zone (TZ) resistive index (RI). Secondary efficacy measures were RI in the peripheral zone and bladder neck, color pixel intensity (CPI), and color pixel density (CPD) in all 3 regions. Outcomes were assessed using mixed-model repeated-measures analyses. The overall treatment effect (tadalafil vs placebo) for the change from baseline through week 8 in prostate TZ RI was not statistically significant (least squares mean change: placebo,-0.01; tadalafil, 0.00; P= .118), nor was the change from baseline in prostate TZ CPI (P= .564) or CPD (P= .592). Results were similar for all flow measures in prostate peripheral zone and bladder neck. The adverse event profile was consistent with previous studies with no new safety findings. Tadalafil for 8weeks in men with BPH-LUTS did not result in detectable decreases in arterial RI or increases in CPI or CPD in the prostate or bladder neck. Detection of changes may not be possible because of already low baseline RI, insufficient sensitivity of techniques used, or may have been confounded by methodologic variability across sites. Alternatively, other possible mechanisms not assessed in this study may be more prominently involved.

Transperineal Ultrasound-Guided 12-Core Prostate Biopsy: An Extended Approach to Diagnose Transition Zone Prostate Tumors

ObjectiveTransperineal ultrasound-guided (TPUS) 12-core prostate biopsy was evaluated as an initial strategy for the diagnosis of prostate cancer, The distribution of prostate cancer lesions was assessed with zone-specific biopsy.MethodsFrom January 2010 to December 2012, 287 patients underwent TPUS-guided 12-core prostate biopsy. Multiple cores were obtained from both the peripheral zone (PZ) and the transition zone (TZ) of the prostate. Participants' clinical data and the diagnostic yield of the cores were recorded and prospectively analyzed as a cross-sectional study.ResultsThe diagnostic yield of the 12-core prostate biopsy was significantly higher compared to the 6-core scheme (42.16 vs. 21.6%). The diagnostic yield of the 10-core prostate biopsy was significantly higher compared to the 6-core scheme (37.6 vs. 21.6%). The 12-core scheme improved the diagnostic yield in prostates >50 ml (12-core scheme: 28.1% vs. 10-core scheme: 20.4%; p = 0.034).ConclusionsThe 12-core biopsy scheme is a safe and effective approach for the diagnosis of prostate cancer. TZ biopsies in patients with larger prostates should be included in the initial biopsy strategy.

Transition Zone Prostate Cancer: Incremental Value of Diffusion-weighted Endorectal MR Imaging in Tumor Detection and Assessment of Aggressiveness

To evaluate the incremental value of using diffusion-weighted magnetic resonance (MR) imaging in addition to T2-weighted imaging for the detection of prostate cancer in the transition zone and the assessment of tumor aggressiveness. This retrospective HIPAA-compliant institutional review board-approved study included 156 consecutive patients (median age, 59.2 years) who underwent MR imaging before radical prostatectomy. Two readers who were blinded to patient data independently recorded their levels of suspicion on a five-point scale of the presence of transition zone tumors on the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion-weighted imaging and T2-weighted imaging together. Apparent diffusion coefficients (ADCs) were measured in transition zone cancers and glandular and stromal benign prostatic hyperplasia. Areas under the receiver operating characteristic curves were used to evaluate detection accuracy, and generalized linear models were used to test ADC differences between benign and malignant prostate regions. Whole-mount step-section histopathologic examination was the reference standard. In overall tumor detection, addition of diffusion-weighted imaging to T2-weighted imaging improved the areas under the receiver operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75 and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027 for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares mean ADCs (× 10(-3) mm(2)/sec) in glandular and stromal benign prostatic hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 + 3, 3 + 4, 4 + 3, and ≥ 4 + 4, respectively). Use of diffusion-weighted imaging in addition to T2-weighted imaging improved detection of prostate cancer in the transition zone, and tumor ADCs were inversely associated with tumor Gleason scores in the transition zone.

Pilot study of a novel tool for input-free automated identification of transition zone prostate tumors using T2- and diffusion-weighted signal and textural features

To present results of a pilot study to develop software that identifies regions suspicious for prostate transition zone (TZ) tumor, free of user input. Eight patients with TZ tumors were used to develop the model by training a Naïve Bayes classifier to detect tumors based on selection of most accurate predictors among various signal and textural features on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Features tested as inputs were: average signal, signal standard deviation, energy, contrast, correlation, homogeneity and entropy (all defined on T2WI); and average ADC. A forward selection scheme was used on the remaining 20% of training set supervoxels to identify important inputs. The trained model was tested on a different set of ten patients, half with TZ tumors. In training cases, the software tiled the TZ with 4 × 4-voxel "supervoxels," 80% of which were used to train the classifier. Each of 100 iterations selected T2WI energy and average ADC, which therefore were deemed the optimal model input. The two-feature model was applied blindly to the separate set of test patients, again without operator input of suspicious foci. The software correctly predicted presence or absence of TZ tumor in all test patients. Furthermore, locations of predicted tumors corresponded spatially with locations of biopsies that had confirmed their presence. Preliminary findings suggest that this tool has potential to accurately predict TZ tumor presence and location, without operator input.

Transition Zone Prostate Cancer: Incremental Value of Diffusion-weighted Endorectal MR Imaging in Tumor Detection and Assessment of Aggressiveness

To evaluate the incremental value of using diffusion-weighted magnetic resonance (MR) imaging in addition to T2-weighted imaging for the detection of prostate cancer in the transition zone and the assessment of tumor aggressiveness. This retrospective HIPAA-compliant institutional review board-approved study included 156 consecutive patients (median age, 59.2 years) who underwent MR imaging before radical prostatectomy. Two readers who were blinded to patient data independently recorded their levels of suspicion on a five-point scale of the presence of transition zone tumors on the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion-weighted imaging and T2-weighted imaging together. Apparent diffusion coefficients (ADCs) were measured in transition zone cancers and glandular and stromal benign prostatic hyperplasia. Areas under the receiver operating characteristic curves were used to evaluate detection accuracy, and generalized linear models were used to test ADC differences between benign and malignant prostate regions. Whole-mount step-section histopathologic examination was the reference standard. In overall tumor detection, addition of diffusion-weighted imaging to T2-weighted imaging improved the areas under the receiver operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75 and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027 for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares mean ADCs (× 10(-3) mm(2)/sec) in glandular and stromal benign prostatic hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 + 3, 3 + 4, 4 + 3, and ≥ 4 + 4, respectively). Use of diffusion-weighted imaging in addition to T2-weighted imaging improved detection of prostate cancer in the transition zone, and tumor ADCs were inversely associated with tumor Gleason scores in the transition zone.