Clinical prediction model for primary aldosteronism subtyping and special focus on adrenal volumetric assessment.

PURPOSE: Our aim was to develop a prediction model based on a simple score with clinical, laboratory, and imaging findings for the subtype diagnosis of primary aldosteronism (PA). The contribution of adrenal volumetric assessment to PA subtyping was also investigated. METHODS: Thirty-five patients with adequate cannulation in adrenal venous sampling (AVS) were included. Laboratory data, the saline infusion test (SIT), and the AVS results of patients with PA were retrospectively evaluated. Volumetric assessment was performed using magnetic resonance imaging (MRI) and the ratio of adrenal volumes was calculated after adjusting for gender- and side-specific mean reference values of both adrenal glands. RESULTS: The AVS was consistent with unilateral PA in 49% and bilateral in 51% of the patients. Hypertension as a reason for work-up, the highest aldosterone/lowest potassium value higher than 12, the percentage of plasma aldosterone concentration (PAC) reduction after SIT by equal or less than 43.5%, the use of oral potassium replacement, unilateral disease at pre-AVS imaging, and a ratio of adjusted adrenal volumes equal to or below 1.7 were indicative of unilateral disease in univariate logistic regression analysis concerning the distinction of PA subtyping (p < 0.05). Multivariate logistic regression analysis also revealed that adrenal volumetric assessment has an impact on PA subtyping (p < 0.05). In the prediction model, when each of the six parameters that were significant in the univariate logistic regression analysis was assigned one point, < 4 predicted bilateral PA, whereas ≥ 4 predicted unilateral PA (AUC:0.92, p < 0.001). CONCLUSION: This prediction model before AVS may serve as a convenient and practical approach, while an adjusted adrenal volumetric assessment can make a positive contribution to PA subtyping.

How many cores should be taken from each region of interest when performing a targeted transrectal prostate biopsy?

Background: The number of core biopsies required per region of interest (ROI) is controversial, as is the localization of the core to be taken from a lesion. This study aimed to determine the ideal biopsy core number and location in a multiparametric magnetic resonance imaging guided targeted prostate biopsy (TPB), without reducing the clinically significant prostate cancer (csPC) detection rate. Materials and methods: Data of patients who had PI-RADS ≥3 lesions on multiparametric magnetic resonance imaging and underwent a TPB in our clinic between October 2020 and January 2022 were reviewed, retrospectively. The first and second cores were taken from the central part of the ROI, whereas the third and fourth cores were taken from the right and left peripheries of the ROI. We compared the csPC detection success of single-, 2-, 3-, and 4-core samplings. Results: Software-based transrectal TPB was performed on 251 ROIs in a total of 167 patients. Internal Society of Urological Pathology Grade Group ≥2 cancer was detected in at least one core in 64 (25.4%) lesions. Moreover, csPC was detected in 42 (65.6%) ROIs in first-core biopsies; in 59 (92.2%) ROIs in first- and second-core biopsies; in 62 (96.9%) ROIs in first-, second-, and third-core biopsies; and in 64 (100%) ROIs in first-, second-, third-, and fourth-core biopsies. Using McNemar's test for comparison, a significant difference was found in terms of csPC detection success between performing first-core and second-core biopsies (65.6 - 92.2%, p < 0.001); by contrast, no significant difference was observed in csPC detection success between 2-core and 3-core biopsies (92.2% - 96.9%, p = 0.24). Furthermore, no significant difference existed between performing second-core and fourth-core biopsies in terms of csPC detection success (92.2%-100%, p = 0.07). Conclusion: We concluded that taking 2-core biopsies from the center of each ROIs during a transrectal TPB is sufficient for diagnosing csPC.

Oncological outcomes of papillary versus clear cell renal cell carcinoma in pT1 and pT2 stage: Results from a contemporary Turkish patient cohort.

OBJECTIVES: To compare overall survival (OS), recurrence free survival (RFS), and cancer-specific survival (CSS) in the long-term follow-up of T1 and T2 clear-cell-Renal Cell Carcinoma (ccRCC) and papillary Renal Cell Carcinoma (pRCC) patients, as well as to determine the risk factors for recurrence and overall mortality. MATERIAL AND METHOD: Data of patients with kidney tumors obtained from the Urologic Cancer Database - Kidney (UroCaD-K) of Turkish Urooncology Association (TUOA) were evaluated retrospectively. Out of them, patients who had pathological T1-T2 ccRCC and pRCC were included in the study. According to the two histological subtype, recurrence and mortality status, RFS, OS and CSS data were analyzed. RESULTS: RFS, OS and CSS of pRCC and ccRCC were found to be similar. Radiological local invasion was shown to be a risk factor for recurrence in pRCC, and age was the only independent factor affecting overall mortality. CONCLUSIONS: There were no differences in survivals (RFS, OS and CSS) of patients with localized papillary and clear cell RCC. While age was the only factor affecting overall mortality, radiological local invasion was a risk factor for recurrence in papillary RCC.

Adjuvant Treatment Approaches after Radical Prostatectomy with Lymph Node Involvement.

OBJECTIVE: The aim of this study was to evaluate the adjuvant treatment preferences and effects on disease progression in patients with pathologically positive lymph node prostate cancer. METHODS: Patients who underwent radical prostatectomy from the prostate cancer database of the Turkish Urooncology Association with lymph node involvement were included in the study. Database includes prostate cancer patients from many experience Urooncology centers of Turkey. Adjuvant treatment approaches and the factors that effect the PSA recurrrence was analysed. RESULTS: Postoperative median 2 (1-3) lymph nodes were found to be positive, and the median lymph node density was reported as 0.13 (0.07-0.25). Seventy-four percent of patients received adjuvant treatment postoperatively. Seventy four of the patients (46.54%) received hormonal therapy in combination with radiotherapy; 47 of them (29.55%) received only hormonal treatment and 20(12.57%) only received radiotherapy. The number of lymph nodes removed was less in the group requiring adjuvant treatment, and this group had a higher rate of surgical margin positivity and seminal vesicle invasion. In addition, adjuvant treatment group had a statistically significant higher lymph node density. There was no significant difference in Kaplan-Meier method comparing 5-year PSA recurrence-free survival in patients with and without adjuvant therapy. When the patient clustered as non-adjuvant, only hormonal therapy and hormonal therapy with radiotherapy, a significant survival advantage was found in the hormonal therapy with radiotherapy group compared to the other two groups (p=0.043). CONCLUSION: No significant difference was found between two groups in terms of time until PSA recurrence during our follow-up. In subgroup analysis survival advantage was found in the hormonal therapy with radiotherapy group compared to non-adjuvant and only hormonal therapy groups.

Effect of pelvic lymph node dissection and its extent on oncological outcomes in intermediate-risk prostate cancer patients: A multicenter study of the Turkish Uro-oncology Association.

BACKGROUND: Pelvic lymph node dissection (PLND) is the gold standard method for lymph node staging in prostate cancer. We aimed to evaluate the effect of PLND combined with radical prostatectomy (RP) on oncological outcomes in D'Amico intermediate-risk prostate cancer (IRPC) patients. METHODS: Patients with D'Amico IRPC were included in the study. In the overall cohort and subgroups (biopsy International Society of Urological Pathology [ISUP] grade group 2 and 3), patients were divided into two groups as PLND and no-PLND. More extensive PLND, defined as a number of removed nodes (NRN) ≥ 75th percentile. RESULTS: After exclusion, a total of 631 patients were included: 351 (55.6%) had PLND and 280 (44.4%) had no-PLND. The mean age was 63.1 ± 3.60 years. The median NRN was 8.0 (1.0-40.0). The mean follow-up period was 47.7 ± 37.5 months. The lymph node involvement (LNI) rate was 5.7% in the overall cohort, 3.9% in ISUP grade 2, and 10.8% in ISUP grade 3. Patients with PLND were associated with more aggressive clinicopathologic characteristics but no significant difference in biochemical recurrence-free survival (BCRFS) was found between patients with PLND and no-PLND (p = 0.642). In the subgroup analysis for ISUP grades 2 and 3, no significant difference in BCRFS outcomes was found in patients with PLND and No-PLND (p = 0.680 and p = 0.922). Also, PLND extent had no effect on BCRFS (p = 0.569). The multivariable Cox regression model adjusted for preoperative tumor characteristics revealed that prostate specific antigen (PSA) (HR: 1.18, 95% CI: 1.01-1.25; p = 0.048) was an independent predictor of biochemical recurrence (BCR). The optimum cut-off value for PSA, which can predict BCRFS, was assigned to be 7.81 ng/ml, with an AUC of 0.63 (95% CI: 0.571-0.688). The highest sensitivity and specificity were 0.667 and 0.549. CONCLUSION: Overall and cancer-specific survival analyzes were not evaluated because not enough events were observed. Neither PLND nor its extent improved BCRFS outcomes in IRPC. The LNI rate is low in patients with biopsy ISUP grade 2 and the BCR rate is low in those with PSA < 7.81 ng/dl so PLND can be omitted in these IRPC patients.

Sextant Biopsy-Based Criteria for Clinically Insignificant Prostate Cancer Are Also Valid for the 12-Core Prostate Biopsy Scheme: A Multicenter Study of Urooncology Association, Turkey.

BACKGROUND: Epstein criteria based on sextant biopsy are assumed to be valid for 12-core biopsies. However, very scarce information is present in the current literature to support this view. OBJECTIVES: To investigate the validity of Epstein criteria for clinically insignificant prostate cancer (PCa) in a cohort of the currently utilized 12-core prostate biopsy (TRUS-Bx) scheme in patients with low-risk and intermediate-risk PCa. METHOD: Pathological findings were separately evaluated in the areas matching the sextant biopsy (6-core paramedian) scheme and in all 12-core schemes. Patients were divided into 2 groups according to the final pathology report of RP as true clinically significant PCa (sPCa) and insignificant PCa (insPCa) groups. Predictive factors (including Epstein criteria) and cutoff values for the presence of insPCa were separately evaluated for 6- and 12-core TRUS-Bx schemes. Then, different predictive models based on Epstein criteria with or without additional biopsy findings were created. RESULTS: A total of 442 patients were evaluated. PSA density, biopsy GS, percentage of tumor and number of positive cores, PNI, and HG-PIN were independent predictive factors for insPCa in both TRUS-Bx schemes. For the 12-core scheme, the best cutoff values of tumor percentage and number of positive cores were found to be ≤50% (OR: 3.662) and 1.5 cores (OR: 2.194), respectively. The best predictive model was found to be that which added 3 additional factors (PNI and HG-PIN absence and number of positive cores) to Epstein criteria (OR: 6.041). CONCLUSIONS: Using a cutoff value of "1" for the number of positive biopsy cores and absence of biopsy PNI and HG-PIN findings can be more useful for improving the prediction model of the Epstein criteria in the 12-core biopsy scheme.

miR-148a, miR-152 and miR-200b promote prostate cancer metastasis by targeting DNMT1 and PTEN expression.

MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the 'epigenetic-based miRNA (epi-miRNA)-mRNA' regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (~5 and ~6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant ~2 to ~5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the 'epi-miRNA-mRNA' bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted.

The role of histopathological and biochemical parameters for predicting metastatic disease on 68 Ga-PSMA-11 PET in prostate cancer.

BACKGROUND: The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on 68 Ga-PSMA PET images. METHODS: Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent 68 Ga-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). RESULTS: The mean age of patients was 66.8 ± 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA ≤ 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high-risk group (ISUP 4-5 or total PSA > 20 ng/ml or PSAD ≥ 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). CONCLUSIONS: In this study, 68 Ga-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high-risk patients.

Predicting factors of acute kidney injury after partial nephrectomy and its impact on long-term renal function: A multicentre study of the Turkish Urooncology Association.

OBJECTIVES: To investigate the predictors of acute kidney injury (AKI) after partial nephrectomy and the impact of AKI stage on long-term kidney function. METHODS: Data of 1055 patients who underwent partial nephrectomy between January 2008 and January 2018 at seven separate tertiary centres were analysed. AKI was defined according to AKI Network criteria. The association between pre-operative and perioperative factors and AKI was evaluated using logistic regression analysis. Recovery of at least 90% of baseline glomerular filtration rate 1 year after partial nephrectomy, change of 1 year glomerular filtration rate compared with baseline glomerular filtration rate and stage ≥3 chronic kidney disease (CKD) progression were assessed according to the stage of AKI. RESULTS: AKI was recorded in 281 (26.7%) of 1055 patients after partial nephrectomy, and of these patients, 197 (70.1%) had stage 1, 77 (27.4%) had stage 2 and 7 (2.5%) had stage 3. Higher tumour complexity and baseline glomerular filtration rate were independent predictors for AKI. The proportion of recovering 90% of baseline glomerular filtration rate at 1 year for any patient who had stage ≤1 vs stage 2-3 of AKI was 78.2% (95% CI: 73.2%-83.7%) and 23.8% (95% CI: 14.7%-38.7%), respectively (P < .001). The risk of stage ≥3 CKD progression for any patient who had stage ≤1 vs stage 2-3 of AKI was 6.2% (95% CI: 4.1%-9.2%) and 63.1% (95% CI: 52.5%-75.6%), respectively (P < .001). CONCLUSIONS: AKI adversely affects renal function in the long-term after partial nephrectomy and stage 2-3 significantly increases the risk of CKD in the long term.

How accurate is radiological imaging for perirenal fat and renal vein invasion in renal cell carcinoma?

OBJECTIVE: To evaluate the accuracy of radiological staging, especially renal venous and perirenal fat invasion, in renal cell carcinoma (RCC). MATERIAL AND METHODS: Data of 4823 renal tumour patients from Renal Tumor Database of Association of Uro-oncology in Turkey were evaluated. Of 4823 patients, 3309 RCC patients had complete radiological, and histopathological data were included to this study. The Pearson chi-squared test (χ2 ) was used to compare radiological and histopathological stages. RESULTS: The mean (SD) age of 3309 patients was 58 (12.3). Preoperative radiological imaging was performed using computed tomography (CT) (n = 2510, 75.8%) or magnetic resonance imaging (MRI) (n = 799, 24.2%). There was a substantial concordance between radiological and pathological staging (к = 0.52, P < .001). Sensitivities of radiological staging in stages I, II, III and IV were 90.7%, 67.3%, 27.7% and 64.2%, respectively. The sensitivity in stage III was lower than the other stages. Subanalysis of stage IIIa cases revealed that, for perirenal fat invasion and renal vein invasion, sensitivity values were 15.4% and 11.3%, respectively. CONCLUSIONS: There was a substantial concordance between radiological (CT and/or MRI) and pathological T staging in RCC. However, this is not true for T3 cases. Sensitivity of preoperative radiological imaging in patients with pT3a tumours is insufficient and lower than the other stages. Consequently, preoperative imaging in patients with T3 RCC has to be improved, in order to better inform the patients regarding prognosis of their disease.

The effect of risk factors on surgical and oncological results in high-risk prostate cancer: A multicentre study of the urooncology society, Turkey.

PURPOSE: To evaluate the effect of risk factors and selected surgical methods on operative and oncological results of patients undergoing radical prostatectomy (RP) with high-risk prostate cancer (HRPC). METHODS: Retrospective analysis of patients who underwent RP for HRPC from 13 urology centres between 1990 and 2019 was performed. Groups were created according to the risk factors of D'Amico classification. Patients with one risk factor were included in group 1 where group 2 consisted of patients with two or three risk factors. RESULTS: A total of 1519 patients were included in this study and 1073 (70.6%) patients were assigned to group 1 and 446 (29.4%) patients to group 2. Overall (biochemical and/or clinical and/or radiological) progression rate was 12.4% in group 1 and 26.5% in group 2 (P = .001). Surgical procedure was open RP in 844 (55.6%) patients and minimally invasive RP in 675 (44.4%) patients (laparoscopic and robot-assisted RP in 230 (15.1%) and 445 (29.3%) patients, respectively). Progression rates were similar in different types of operations (P = .22). Progression rate was not significantly different in patients who either underwent pelvic lymph node dissection (PLND) or not in each respective group. CONCLUSION: RP alone is an effective treatment in the majority of patients with HRPC and PLND did not affect the progression rates after RP. According to the number of pre-operative high-risk features, as the number of risk factors increases, there is a need for additional treatment.

Factors affecting long-term renal functions after partial vs radical nephrectomy for clinical T1 renal masses: A Multicentre Study of the Urooncology Association, Turkey.

PURPOSE: To compare the functional outcomes of patients who underwent partial (PN) or radical nephrectomy (RN) for clinical T1 (cT1) renal tumours using the Kidney Cancer Database of the Urooncology Association, Turkey. METHODS: We retrospectively reviewed 1004 patients who underwent PN and RN for cT1 renal tumours at multiple academic tertiary centres between 2000 and 2018. Patients with preoperative end-stage chronic kidney disease and/or metastatic disease were excluded. RESULTS: There were 452 patients in the PN group and 552 patients in the RN group. The median follow-ups were 74.9 and 83.7 months in RN and PN cohort. The eGFR was significantly reduced in both groups on postoperative day 1 (PN = 13.7 vs RN = 19.1 mL/min/1.73 m2 : P < .001). In the PN group, eGFR showed a tendency to recover according to a quadratic pattern and reached preoperative levels in the first and third years (95.6 ± 28.8 mL/min/1.73 m2 and 96.9 ± 28.9 mL/min/1.73 m2 , respectively), with no significant difference between the eGFRs in the 1st and 3rd years (P = .710). To define groups at risk, different cut-off values for the GFR were considered. Among patients with a baseline GFR < 90, the RN cohort had significantly lower eGFRs in the first and third years than the PN cohort (P = .02). Logistic regression showed that comorbidities, coronary artery disease, diabetes and hypertension had no adverse impacts on the changes in the eGFR (P = .60, P = .13, and P = .13, respectively). CONCLUSION: For the treatment of stage T1 kidney tumours, open or laparoscopic partial nephrectomy has the benefit to preserve renal function.

Upregulation of potential regulatory signaling molecules correlate with androgen receptor splice variants AR-V7 and AR-V567es in prostate cancer metastasis.

AIM: Androgen receptor splice variants (AR-Vs) produced by alternative splicing of the AR play an important role in the treatment resistance and progression of prostate cancer (PCa). In this study, two most common AR variants and how they associate with the inflammatory response (NF-Kß) and regulatory transcriptional activity (HSP-27) genes were investigated in patients with PCa and metastatic PCa (Met-PCa). METHODS: Our study was carried out with the whole blood obtained from 25 healthy control subjects, 25 PCa patients and 39 Met-PCa patients. We examined the expression levels of AR, AR-V7 and AR-V567es genes via Real-time PCR and those of HSP-27 and NF-Kß via ELISA method. RESULTS: AR, AR-V7 and AR-V567es expressions were observed in 84.61%, 64.1%, 23.07% of Met-PCa patients respectively. The expression levels of full-length AR and variants (AR-V7 and AR-V567es) were associated with the prostate cancer stage. In the Met-PCa, the expression levels of AR, AR-V7 and AR-V567es were associated with the Gleason Scores but not with the PSA levels. AR-V7 expression levels in stage T4 patients significantly increased. NF-Kß and HSP-27 protein levels were significantly higher in Met-PCa patients. DISCUSSION: Our findings highlight the targeting of the proteostasis and inflammation pathways through inhibiting HSP-27 and NF-Kß. This might be a valuable strategy to overcome anti-androgen resistance and improve drug therapy in Met-PCa patients whose gene expression levels of AR-V7 and AR-V567es variants are high.

Comparison of TRUS and combined MRI-targeted plus systematic prostate biopsy for the concordance between biopsy and radical prostatectomy pathology.

AIM: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing conventional 12-core TRUS-Bx at radical prostatectomy specimens (RP). METHODS: Consecutive patients diagnosed prostate cancer (127 with combination of both targeted biopsy (TBx) plus systematic biopsies (SBx) and separate patient cohort of 330 conventional TRUS-Bx without mpMRI) with a PSA level of <20 ng/mL prior to RP were included. The primary end point was the grade group concordance between biopsy and RP pathology according to biopsy technique. RESULTS: Clinically significant prostate cancer detection was 51.2% for TRUS-Bx, 49.5% for SBx, 67% for TBx and 75.7% for TBx + SBx. Upgrading and downgrading of at least one Gleason Grade Group (GGG) was recorded in 43.3%/ 6.7% patients of the TRUS-Bx and in 20.5%/ 22% of the TBX + SBx group, respectively (all P < .001). Concordance level was detected to be significantly higher for ISUP 1 in combined TBx + SBx method compared to conventional TRUS-Bx (61.3% vs 37.9%, P = .014). In ISUP 1 exclusively, significant upgrading was seen in TRUS-Bx (62.1%) when compared to TBx (41.4%) and TBx + SBx (38.7%). CONCLUSIONS: MRI-targeted biopsies detected more significant PCa than TRUS-Bx but, superiority in significant cancer detection appears as a result of inadvertant selective sampling of small higher grade areas. Within an otherwise low grade cancer and does not reflect accurate GGG final surgical pathology. TBx + SBx has the greatest concordance in ISUP Grade 1 with less upgrading which is utmost important for active surveillance.

Comparative analysis of epi-miRNA expression levels in local/locally advanced and metastatic prostate cancer patients.

Abnormal expression of enzymes involved in epigenetic mechanisms, such as DNA methyl transferases, can trigger large chaos in cellular gene expression networks and eventually lead to cancer progression. In our study, which is a pioneer in the literature that clinicopathologically evaluates the expression of 30 epi-miRNAs in prostate cancer (PCa), we investigated which of the new miRNA class epi-miRNAs could be an effective biomarker in the diagnosis and progression of PCa. In this study, the expression levels of 30 epi-miRNAs in whole blood samples from 25 control, 25 PCa and 40 metastatic PCa patients were investigated by the Quantitative Real-Time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific qPCR method. The correlations between miRNA expression levels and clinicopathological parameters (Gleason Score (GS), PSA levels, TNM Staging) in different stages of PCa groups as well as disease-specific expression levels were examined. We found a hypomethylation in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p) (p < 0.05). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in metastatic stage. This study is novel in the sense that our findings draw attention to the important role of miRNAs as diagnostic and prognostic biomarkers in PCa.

Factors Affecting Surgical Margin Positivity after Radical Prostatectomy in the Turkish Population: A Multicenter Study of the Urooncology Association.

BACKGROUND: The prediction of positive surgical margins (SM) after radical prostatectomy (RP) is important for planning the surgical modality and adjuvant therapy in patients with prostate cancer (PCa). OBJECTIVES: To investigate factors affecting SM positivity in patients diagnosed with PCa who underwent RP using the PCa database of the Urooncology Association (Turkey). METHODS: Patients who underwent RP due to clinically T1c-T3 PCa and who had detailed SM data for the RP specimen were included in the study. Pathological data of 12 core transrectal ultrasound prostate biopsies and RP were evaluated. Patients were divided into 2 groups (SM positive and SM negative) according to SM status after RP. Data were compared between the groups. Factors affecting SM positivity, the number of positive SM sites, and the location of positive SM were separately evaluated with regression models. RESULTS: A total of 2,643 patients from 6 different centers (median age: 63 years) with a prostate-specific antigen (PSA) level of 7.3 ng/mL were investigated in the study. BMI, PSA, biopsy Gleason score (GS), and perineural invasion (PNI) were found to be independent predictive factors for SM positivity and the number of positive SM locations, respectively (p < 0.05). According to the positive SM location, PSA was found to be associated with positive SM in apex, anterior prostate, and bladder neck locations. Also, according to posterolateral SM status, PNI and nerve-sparing RP (nsRP) rates were 21.3 and 44% for patients with negative posterolateral SM, and rates were 35.4 and 50.6% for patients with positive posterolateral SM, respectively (p < 0.05). In patients who underwent nsRP, positive SM was present in 22.2% of patients who did not have PNI on prostate biopsy, whereas positive SM was present in 40.6% of patients with PNI (p < 0.001). Similarly, 10.9% of patients without PNI had positive posterolateral SM, whereas 17.3% of patients with PNI had positive posterolateral SM (p = 0.031). CONCLUSIONS: BMI, PSA, biopsy GS, and biopsy PNI positivity were found to be predictive factors affecting SM positivity. The most important factors affecting posterolateral positive SM were biopsy PNI and nsRP, indicating that the nsRP approach may cause positive SM in the posterolateral margin of the prostate (neurovascular bundle location) in patients with positive PNI on biopsy.

Correlation of Prostate-Imaging Reporting and Data Scoring System scoring on multiparametric prostate magnetic resonance imaging with histopathological factors in radical prostatectomy material in Turkish prostate cancer patients: a multicenter study of the Urooncology Association.

BACKGROUND: Histopathological features after radical prostatectomy (RP) provide important information for the prognosis of prostate cancer (PCa). The possible correlations between Prostate-Imaging Reporting and Data Scoring System (PIRADS) scores in multiparametric magnetic resonance imaging (mpMRI) may also be predictive for prognosis. In this study, we aimed to evaluate the correlation of PIRADS scores with histopathological data. METHODS: A total of 177 patients who underwent preoperative mpMRI and RP for PCa from eight institutions were included in the study. Correlation of PIRADS score in preoperative mpMRI with adverse histopathological factors in RP specimen was investigated using univariate and multivariate analyses. RESULTS: The relationship between PIRADS score and postoperative extracapsular extension, lymphovascular invasion, and seminal vesicle involvement was significant (P < 0.001, P = 0.032, and P = 0.007, respectively). Although the PIRADS score was significantly correlated with the number of dissected lymph nodes (p = 0.026), it had no significant correlation with the number of positive nodes (P = 0.611). Total Gleason score, extracapsular extension, seminal vesicle invasion, and number of lymph nodes were found to be independent factors, which correlated with high PIRADS scores in ordinal logistic regression analysis. CONCLUSION: PIRADS scoring system in mpMRI showed a statistically significant correlation with adverse histopathological factors in RP specimen. A higher PIRADS score may help to predict a higher Gleason score, indicating clinically important PCa as well as poor prognotic factors such as extracapsular extension, lymphovascular invasion, and seminal vesicle invasion that may indicate a higher risk of recurrence and the need for additional treatment.

Cucurbitacin B and cisplatin induce the cell death pathways in MB49 mouse bladder cancer model.

IMPACT STATEMENT: Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.

The effectiveness of RENAL nephrometry score in ablated renal tumors via radiofrequency ablation or cryoablation

Background/aim: This study aimed to evaluate the clinical efficacy of radiofrequency ablation (RFA) and cryotherapy and to scrutinize the therapeutic success of the RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score in terms of possible complications and the predictive status of oncological results. Materials and methods: Forty-five patients with biopsy-proven renal cell carcinomas (32 males, 13 females) treated with RFA and cryotherapy were included. Patients were 22­90 years old (average: 59.2 years). Statistical analyses were performed using SPSS for Windows. Results: A total of 79 lesions with dimensions varying between 0.9 and 4.5 cm (average: 2.2 cm) were ablated. Complete ablation was achieved for 72 (91.1%) lesions. Six repeat RFA sessions were applied for 4 (5%) lesions with residue/recurrence. The average RENAL nephrometry scores of lesions that underwent complete ablation and those that developed residue/recurrence were 6.3 and 7.7, respectively. The average recurrence-free survival time was 34.8 months (range: 3­55 months), while it was 44.6 months (range: 6­55 months) for cryotherapy and 28.6 months (range: 3­50 months) for RFA. Conclusion: Ablative therapies are minimally invasive and effective methods for treating small renal tumors. RENAL nephrometry scoring is a valuable system for standardizing renal tumors and evaluating the success of ablative therapies, possible complications, and oncological results.

Hsp-27 and NF-κB pathway is associated with AR/AR-V7 expression in prostate cancer cells.

In the present study, NF-κB inhibitor BAY 11-7082 and/or Hsp-27 inhibitor KRIBB-3 agents were used to investigate the molecular mechanisms mediating androgen receptor expression on prostate cancer cell lines. The decrease observed in androgen receptor and p65 expressions, particularly at 48 h, in parallel with the decrease in the phosphorylation of the p-IKK α/ß and p-Hsp-27 proteins in the LNCaP cells, indicated that androgen receptor inactivation occurred after the inhibition of the NF-κB and Hsp-27. In 22Rv1 cells, androgen receptor variant-7 was also observed to be decreased in the combined dose of 48 h. The association of this decrease with the decrease in androgen receptor and p65 expressions is a supportive result for the role of NF-κB signaling in the formation of androgen receptor variant. In androgen receptor variant-7 siRNA treatment in 22Rv1 cell lines, decrease of expression of androgen receptor variant-7 as well as decrease of expression of androgen receptor and p65 were observed. The decrease statistically significant in androgen receptor and p65 expressions was even greater when siRNA treatment was followed with low dose and time (6 h) combined treatment after transfection. We also showed that increased Noxa and decreased Bcl-2 protein level, indicated that apoptotic induction after this combination. In conclusion, inhibition of NF-κB and Hsp-27 is also important, along with therapies for androgen receptor variant-7 inhibition.