Endovascular management of renal angiomyolipomas: Do coils have a benefit in terms of clinical success rates?

PURPOSE This study evaluated single center results of endovascular treatment in renal angiomyolipoma (AML) to determine whether there is clinical relevance of adding proximal coil embolization to distal particle embolization in terms of safety, efficacy and retreatment rates. METHODS A retrospective analysis was performed to evaluate patients undergoing transarterial embolization for renal AMLs from January 2007 to October 2020. Parameters regarding patient and tumor characteristics, embolization technique, treatment outcome and complications were recorded. Patients were divided into two groups as A (only particle group) and B (particle + coil group) based on the type of embolic agent used for treatment. Comparative analysis was performed between the two groups in terms of tumor size reduction, retreatment and complication rates. RESULT Forty-two patients (37 (88.1%) female, 5 (11.9%) male) harboring 48 AMLs were included in the study. The mean age was 43.46 (range 20 to 78). The technical success rate was 95.8% (46 of 48 procedures). The mean size reduction was 1.94±1 cm (p < 0.001) after treatments however, no significant difference was seen between groups in terms of tumor size reduction. Retreatment rates were 3.1% (1 of 32 cases) in group A and 14.3% (2 of 14 cases) in group B (p = 0.21). No significant difference was found between groups in terms of bleeding and complication rates during the perioperative period. Mean follow-up duration was 26.48±25.71 (range from 2 to 102) months. CONCLUSION In this study, no clear supplementary benefit was observed in terms of safety, and efficacy with the adjunction of coils to distal particle embolization in the management of AMLs.

Safety of Minimally Invasive Surgical Techniques in Large Adrenal Lesions: A Single-Centre Study.

OBJECTIVE: To compare perioperative outcomes of minimally invasive surgery for ≥5 cm and <5 cm adrenal lesions. STUDY DESIGN: Retrospective cohort study. PLACE AND DURATION OF STUDY: Hacettepe University School of Medicine, Ankara, Turkey, between October 2007 and September 2019. METHODOLOGY: Data of 83 patients operated for adrenal lesions was collected retrospectively. Patients were categorized into two groups based on the size of the adrenal gland as <5 cm and ≥5 cm. The groups were compared in terms of perioperative outcomes. RESULTS: The median age of the patients was 51 (41-60) years, with a female-to-male ratio of 27/56. The median follow-up period was 27 (11.5-91) months. Of 83 adrenal masses, 60 (72.3%) were in the <5 cm group and 23 (27.7%) were in the ≥5 cm group. Fifteen (18.1%) patients underwent adrenalectomy for lung cancer metastasis, whereas three (3.6%) for renal cell carcinoma metastasis. The overall rate of post-operative complications was 10.8%. Post-operative complication rates were similar in each group (p=0.433). Operation time was found to be significantly higher in patients with large adrenal masses (p=0.003). CONCLUSION: Minimally invasive surgical techniques have the same perioperative results in the group with adrenal lesions ≥5 cm compared to <5 cm and may be safely employed in this group of patients. KEY WORDS: Laparoscopy, Robotic assisted laparoscopy, Adrenalectomy, Metastasectomy, Adrenal gland neoplasms.

Can Aortic and Renal Arteries Calcium Scores Be New Factors to Predict Post-Operative Renal Function After Nephron Sparing Surgery?

INTRODUCTION: This study aims to investigate whether the calcification of renal arteries and aorta may be risk factors for developing chronic kidney disease (CKD) after Nephron sparing surgery (NSS). MATERIALS AND METHODS: The patients that underwent either open or laparoscopic NSS from 2000 to 2019 in 4 different centers were retrospectively assessed. Of these patients, 328 had a non-contrast-enhanced computer tomography. Calcium scores of the renal arteries and abdominal aorta were measured in the non-contrast-enhanced images with the calcium score plugin (version 2.0) of Horos™. Univariate and multivariate logistic regression analysis was performed to determine significant risk factors for developing CKD at the last check-up. Roc curve analysis was performed to determine the optimal cut-off values of age and abdominal aorta calcium scores. RESULTS: A total of 302 patients, of which 52 (16,6%) with CKD and 252 (83,4%) without CKD at the last check-up, were included in the analysis. The mean warm ischemia duration was significantly higher in patients with CKD (18,79±6,72 vs 16,38±5,57 minutes, p=0,016). The mean size of the tumor diameter and the number of the patients with ≥stage T1b were higher in the group with CKD (p=0,024 and 0,005, respectively). The median calcium scores of the aorta and renal arteries were higher in the group with CKD (p<0,001 and p<0,001, respectively). In multivariate analysis, age >60 years (OR:3,65, p=0,022), calcium score of the aorta (OR:4,07, p=0,029), tumor diameter (OR:1,03, p=0,026) and pre-operative CKD stage (OR:10,13, p<0,001) found the be significant factors for predicting last check-up CKD. CONCLUSION: The calcium score of the aorta may be used as an additional risk factor to predict post-operative CKD risk after NSS with sensitivity over 80%.

Comparison of clamping strategies in minimally invasive partial nephrectomy for cT1 tumors.

OBJECTIVES: To determine whether artery only (AO) clamping promises any advantage over artery and vein (AV) clamping in patients undergoing partial nephrectomy with minimally invasive surgical techniques. MATERIAL AND METHODS: We retrospectively analyzed the data of 68 partial nephrectomy patients who were treated with minimally invasive techniques (robot-assisted laparoscopic or pure laparoscopic) for solitary, unilateral, cT1 renal masses during the period of 2008-2019 in a single institution. Patients were divided into two groups according to clamping strategy (AO and AV). The two groups were compared to each other in terms of perioperative outcomes and long-term functional results. RESULTS: The mean patient age and median follow-up period were 56.8 ± 10.8 years and 13.5 (9-44.5) months, respectively. Warm ischemia time, estimated blood loss, transfusion rate and length of hospital stay were similar between the two groups, while operative time was significantly higher in the AO clamping group (p = .726, p = .604, p = .675, p = .103, and p = .038, respectively). Patients who underwent AV clamping had a significantly lower estimated glomerular filtration rate (eGFR) and higher chronic kidney disease rates six months postoperatively (p = .001 and p = .044, respectively) and at the last follow-up (p = .020 and p = .048, respectively). The percentage of eGFR change at six months and the last follow-up was higher in the AV clamp group but the difference was not statistically significant (p = .056 and p = .082, respectively). CONCLUSIONS: Our findings suggest AO clamping is safe and comparable to AV clamping. In our study, AO clamping was found to be superior to AV in terms of long-term eGFR preservation.

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.

Minimally Invasive Partial Nephrectomy in the Era of Robotic Surgery.

OBJECTIVES: The objectives of the study were to compare the operative features, complication rates, functional, and pathological outcomes of laparoscopic partial nephrectomy (LPN) and robotic-assisted partial nephrectomy (RPN). METHODS: The demographics, perioperative, and follow-up data of patients who underwent partial nephrectomy between January 2007 and April 2020 with minimally invasive methods were retrospectively analyzed. Patients with minimum 3 months follow-up were enrolled in the present study. Perioperative and pathological outcomes were compared between the patients underwent LPN and RPN. RESULTS: A total of 85 patients (65 LPN and 20 RPN) were included in the present study. The mean patient age at the time of surgery was 56.31±10.48 years. Female-to-male ratio was 30/55. Patients in the RPN group had higher R.E.N.A.L. and PADUA scores (p=0.039 and p=0.030, respectively). Median warm ischemia time, median operation time, median intraoperative estimated blood loss, mean post-operative hemoglobin change, and median hospitalization time were similar between groups (p=0.133, p=0.753, p=0.079, p=0.882, and p=0.473, respectively). Artery-only clamping rate was significantly higher in RPN group (p=0.033). The cost of RPN was significantly greater than LPN (p<0.001). Transfusion rates, post-operative complication rates, percent of estimated glomerular filtration rate change at the last follow-up, and trifecta achievement were similar between the groups (p=0.622, p=0.238, p=0.428, and p=0.349, respectively). CONCLUSION: In this series, similar perioperative and functional outcomes were achieved by RPN compared to LPN in more complex renal masses.

Pathology associated with adherent perirenal fat and its clinical effect.

INTRODUCTION: The dissection of perirenal fat is of critical importance to kidney surgery and ease of dissection is more important when using minimally invasive approaches. This study aimed to determine the clinical, radiological, and pathological significance of adherent perirenal fat (APF). MATERIALS AND METHODS: This prospective study included 22 patients scheduled for partial nephrectomy and 40 patients for donor nephrectomy. Intraoperative fat dissection time was recorded, and the complexity of perirenal fat dissection was surgeon-classified as easy, moderate, and difficult. Perirenal fat and subcutaneous fat thickness were measured. Measurement of perirenal fat depth and the Hounsfield unit (HU) for both perirenal and subcutaneous fields were performed using computed tomography (CT) images. All specimens were submitted for histopatological analysis. Researchers in each arm were blinded to other researchers' data. RESULTS: Mean age of the patients was 51.3 ± 12.7 years. Mean perirenal fat dissection time was 15.0 ± 13.5 minutes. Patient demographics, BMI, nor occupational status differed between the 3 complexity of perirenal fat dissection groups. Radiological findings showed that there was a significant correlation between perirenal fat depth and complexity of perirenal fat dissection (P < .05), but not with HU measurements or subcutaneous fat thickness. Surgeon classification of the complexity of perirenal fat dissection was in accordance with the duration of dissection (P < .05). Perinephric fat contained more fibrous tissue in the patients with histologically proven APF than in those without (P < .05). CONCLUSIONS: APF is a challenge during kidney surgery. Difficult dissection prolongs the duration of perirenal fat dissection and surgery. Perirenal fat thickness measured via preoperative CT might be used to predict APF.

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.

The stone crescent of Anatolia.

OBJECTIVES: To assess the largest stone composition data available and to present the variations in the stone composition according to gender and different climatic environments in Turkey. METHODOLOGY: Data for a total of 24 768 urinary stone patients from the Turkish Mineral Research and Exploration Institute were evaluated. X-ray diffraction crystallography was used for analysis and the Köppen-Trewartha classification was used to assess the climatic features of the cities. After the assessment, the cities were divided into two groups-those with a continental climate (Dc) were defined as inland areas and the others (Non-Dc) were defined as coastal areas. RESULTS: The male-to-female ratio was 2.2:1. Amongst the patients, 53.7% had pure stones, while 46.3% had mixed-type stones. The most common type of stone was calcium oxalate in both pure and mixed stone groups. Given the climate patterns, the stone ratio between regions with a Dc climate and a Non-Dc climate was approximately 2:3. Cystine and uric acid stones were observed more frequently in inland regions, while calcium oxalate, whewellite, and struvite stones were observed more frequently in coastal areas (P = .005, P < .001, P < .001, P = .002, P = .002, respectively). Calcium oxalate stones were found at a higher rate in men, while cysteine, struvite, and calcium phosphate stones were more common in women (P < .001, P = .003, P < .001, P < .001, respectively). CONCLUSION: This study provides the most comprehensive data on the stone disease in Turkey. Considering the distribution of stone disease in Turkey, the frequency of analysed stones had parallels with the temperature averages and climate features, presenting crescent-like distribution.

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.

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.

Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy.

PURPOSE: Programmed cell death-1 ligand-1 (PD-L1) expression has been associated with prognostic implications in urologic malignancies. We aimed to investigate prognostic significance of pre- and post-treatment PD-L1 expression in patients treated with BCG for high-grade non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection + ≥ 6 BCG instillations between 2004 and 2017. PD-L1 immunohistochemistry (IHC) scoring was done on 0-3 scale, and cut-off for positive and high-level PD-L1 expression was set to ≥ 1% and ≥ 5% staining of tumor-infiltrating immune cells (IC), respectively. Clinicopathologic characteristics and oncologic outcomes [recurrence-free (RFS) and progression-free survival (PFS)] were compared, stratified by PD-L1 positivity. The prognostic role of PD-L1 was assessed using Kaplan-Meier, and univariate and multivariate Cox regression analyses. RESULTS: Pre-treatment, 46.2% and 6.8% of high-grade NMIBC demonstrated positive and high-level PD-L1 expression, respectively. Positive PD-L1 expression was associated with submucosal invasion and refractory-tumor recurrence. PD-L1 expression was not associated with RFS or PFS in regression analysis. Post-treatment, 55.1% and 11.6% of recurrent tumors demonstrated positive and high-level PD-L1 expression, respectively. Down-regulation of PD-L1 expression was noted in patients with refractory recurrence (p = 0.012). CONCLUSION: Pre-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD-L1 expression did not have prognostic value for PFS or RFS; therefore, further research is necessary to identify novel biomarkers for prediction of disease outcomes in high-grade NMIBC.

Feasibility of Boari Bladder Flap Procedure in Patients With Heterotrophic Renal Transplant.

OBJECTIVES: Our goal was to investigate the safety and efficacy of the Boari bladder flap procedure in patients who received either allogeneic or autotransplant of kidneys. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with either allogeneic or autotransplant of kidneys who also underwent Boari bladder flap procedures between January 2007 and January 2018. Boari bladder flap was preferred in management of ureteral com-plications after allogeneic renal transplant or it was combined with renal autotransplant when ureteral length was not sufficient to allow ureterovesical anastomosis in patients with ureteral injury. RESULTS: Boari bladder flap procedures were performed in 14 patients who had undergone heterotrophic renal transplant. Nine patients had undergone allogeneic renal transplant, and 5 patients had renal auto-transplant. The mean age of patients was 41.7 ± 13.4 years. The 5 patients with renal autotransplant procedures had simultaneous Boari flap procedures due to ureteral avulsion during retrograde ureter-orenoscopic surgery for urolithiasis. For the entire cohort, mean preoperative and postoperative (at month 1) serum creatinine levels were 1.42 ± 0.71 and 1.13 ± 0.43 mg/dL, respectively. At last visit, the mean creatinine level was 1.94 ± 1.88 mg/dL. CONCLUSIONS: The Boari bladder flap procedure can be a safe and relevant choice in the management of challenging complications after heterotrophic (either allogeneic or autotransplant) renal transplant, allowing minimally invasive urologic surgery, no need for use of bowel segments, and no potential risk for the contralateral kidney.

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.

Clinicopathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer following definitive therapy.

OBJECTIVE: To demonstrate the effect of clinicopathological factors on 68Ga-PSMA-11 PET/CT positivity at the time of biochemical recurrence (BCR) of localized prostate cancer (PCa) following definitive therapy. METHODS: We retrospectively reviewed our institutional database for PCa patients who had BCR and subsequently underwent 68Ga-PSMA-11 PET/CT between April 2014 and February 2018. A total of 51 patients who were metastasis-free before PSMA imaging and previously treated with definitive therapy (radical prostatectomy or external beam radiotherapy) for localized disease (pT1c-T3b pN0-1 cM0) were included. RESULTS: 37 out of 51 patients (72.5%) had positive 68Ga-PSMA-11 PET/CT scans. Age at diagnosis, Gleason score (GS), D'Amico risk status of PCa, initial PSA level before treatment and PSA doubling time were not associated with PSMA positivity. Pre-scan PSA levels of > 0.2 ng/ml and PSA velocity of ≥ 1 ng/ml/year were significantly associated with increased PSMA positivity, whereas history of androgen deprivation therapy showed a trend towards significance. The optimal cutoffs for distinguishing between positive and negative scans were ≥ 0.71 ng/ml for pre-scan PSA and ≥ 1.22 ng/ml/yr for PSA velocity. In multivariable analysis, log pre-scan PSA and pre-scan PSA level > 0.2 ng/ml remained significant predictors for PSMA positivity, whereas the association of PSA velocity and of ADT was lost. CONCLUSIONS: In BCR of localized PCa following definitive therapy, pre-scan PSA was strongly associated with positive 68Ga-PSMA-11 scan, even at PSA levels ranging from 0.2 to 1.0 ng/ml. Therefore, clinical and pathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer need to be further elucidated.

68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer.

BACKGROUND: 68Ga-PSMA Positron Emission Tomography/Computerized Tomography (PET/CT) has shown promising results for the detection of recurrent prostate cancer (RPCa). However, the diagnostic value of this method is yet to be validated. The aim of this study was to determine the influence of clinical and biochemical variables on the detection rate of 68Ga-PSMA PET/CT in patients with RPCa. METHODS: This is a prospective study of 121 patients who underwent 68Ga-PSMA-PET/CT and conventional imaging (CI) for RPCa. Detection rates were analyzed and correlated with various clinical and biochemical variables such as Gleason score GS), androgen deprivation therapy (ADT), trigger PSA (tPSA), PSA doubling-time (PSAdt) and PSA velocity (PSAv). RESULTS: 68Ga-PSMA-PET/CT showed at least one focus of pathological 68Ga-PSMA uptake in 92/121 (76%) of patients. Nodal metastases (in 47% of patients) were the most common site of recurrent disease followed by bones (36%) and prostate (32%). Out of 121 patients, 57 (47%) had only positive findings on PSMA scan verified by biopsy or follow-up. The majority of these lesion were located in the lymph nodes (31/57, 54,5%), which were below the detection limit of CT. Univariate analysis showed higher detection rate of PET/CT with increasing tPSA, PSAv and short PSAdt. Best cutoff for tPSA, PSAv and PSAdt was 0.5 ng/ml, 2.25 ng/ml/year and 8.65 months, respectively. The detection rate of PSMA-PET/CT was higher in patients with high grade tumors (GS > 7, 23.7% vs 76.3%) and in patients who were on ADT during of PSMA scan (76.3% vs 96%). In multiple logistic regression analysis, PSAdt and concurrent ADT were identified as predictors of positive 68Ga-PSMA-PET/CT. CONCLUSION: 68Ga-PSMA-PET/CT is useful for re-staging patients with RPCa and has improved performance compared with CI for disease detection. Detection rates are improved in patients on ADT and with short PSAdt.

FOXA1 knock-out via CRISPR/Cas9 altered Casp-9, Bax, CCND1, CDK4, and fibronectin expressions in LNCaP cells.

Prostate cancer is one of the most common types of cancer in men and the leading cause of death in developed countries. With the aid of molecular and genetic profiling of cancers, cancer molecular subtypes are paving the way for tailored cancer therapy. FOXA1 has been identified as one of the seven molecular subtypes of prostate cancer. FOXA1 is involved in a variety of metabolic process such as glucose homeostasis and deregulation of its expression is crucial in prostate cancer progression. In this study, we investigated the effects of FOXA1 gene knock-out on the expression levels of various cancer cell metabolism and cell cycle-related protein expressions. FOXA1 gene was knocked-out by using CRISPR/Cas9 technique. While FOXA1 gene knock-out significantly altered Casp-9, Bax, CCND1, CDK4, and fibronectin protein expressions (P < 0.05, fold change: ∼40, 4.5, 2.5, 4.5, and 4, respectively), it did not affect the protein expression levels of Casp-3, Bcl-2, survivin, ß-catenin, c-Myc, and GSK-3B. Knocking-out FOXA1 gene in androgen-dependent LNCaP prostate cancer cells inhibited CCND1 protein expression. Our pre-clinical results demonstrate the importance of FOXA1 as a drug target in the treatment of prostate cancer. Impact statement Knock-out studies offer a unique way of studying the function of genes especially for developmentally lethal genes. FOXA1 has prominent roles both in breast and prostate cancer pathogenesis due to its role in ER receptor signaling pathway. FOXA1 has also been identified as one of the seven molecular subtypes of primary prostate cancer. In the present study, we used an efficient gene knock-out method, CRISPR/Cas9, in order to investigate FOXA1 function on LNCaP prostate cancer cells in vitro. FOXA1 knock-out altered cell-cycle regulator CCND1 protein expression levels. Therefore, our results suggest that FOXA1 might be a plausible drug target for prostate cancer treatment.

The Safety and Efficacy of Adjuvant Hemostatic Agents During Laparoscopic Nephron-Sparing Surgery: Comparison of Tachosil and Floseal Versus No Hemostatic Agents.

PURPOSE: To compare the effectiveness of TachoSil and Floseal during laparoscopic nephron-sparing surgery (LNSS), and to evaluate postoperative complications, especially hemorrhage and urinary leakage. MATERIALS AND METHODS: The medical records of all patients that underwent LNSS for a small renal mass (SRM) performed by the same experienced surgeon were retrospectively analyzed. The patients were divided into the following 3 groups, based on hemostatic agent: group 1: no adjuvant hemostatic agent (no AHA); group 2: TachoSil; group 3: Floseal. RESULTS: The study included 79 patients; no AHA group: n = 18; TachoSil group: n = 25; Floseal group: n = 36. The 3 groups were similar in terms of diameter [29.6 ± 11.5 mm, 26.4 ± 13.4 mm and 30.4 ± 9.6 mm, respectively (P = .218)] and PADUA scores [6.9 ± 0.9, 6.7 ± 1 and 6.9 ± 0.9, respectively (P =.540)]. Mean duration of surgery was significantly shorter in the Floseal group (120.9 ± 23.1 minutes) than in the no AHA group (156.6 ± 34.4 minutes). Mean ischemia time was longest in the no AHA group (24.3 ± 4 minutes) and shortest in the Floseal group(21.3 ± 4.3 minutes). Intra-abdominal (IA) catheter drainage on postoperative day 1 was significantly higher in the no AHA group thanin the TachoSil and Floseal groups [156.9 ±78.3 mL vs. 72.6 ± 64.5 and 60.8 ± 30.2 mL, respectively (P < .05)]. Mean duration of hospitalization was 3.2 ± 0.5 days in the no AHA group that was significantly longer than in the Floseal group (2.8 ± 0.7 days) (P = .043). There were not any differences in intraoperative complications, the transfusion rate, surgical margin positivity, or postoperative complications between the 3 groups (P = .596, P =.403, P = 1.0, P = .876, respectively). However, pseudoaneurism as a late term complication occurred in 27.7% patients in the no AHA group. CONCLUSION: TachoSil and Floseal are safe and effective adjuvant treatments for patients undergoing LNSS. They might be useful especially in preventing pseudo aneurisms, shortening intraoperative ischemia time and hospital stay and decreasing postoperative drainage. Shortened operation and warm ischemia time may also be attributed to long learning curve of LNSS.

Acute renal failure due to small cell neuroendocrine carcinoma of the left kidney: A case report.

The majority of small cell carcinoma (SCC) cases originate from the lungs. SCC of the kidneys is rare. Among genitourinary tumors, renal cell carcinoma is the most common type of tumor to be associated with paraneoplastic syndromes. The majority of paraneoplastic syndromes disappear following nephrectomy in renal cell carcinoma cases. The present case involved the assessment of a female patient with SCC of the left kidney. The patient was diagnosed with acute renal failure and underwent a laparoscopic left radical nephrectomy. Surgical intervention removed the need for dialysis; the patient was under follow-up observation every week without any requirement for dialysis for 8 months and received adjuvant carboplatin-etoposide chemotherapy. Surgery is an option for dialysis-dependent patients with a renal tumor. The removal of the tumor burden may restore renal function and eliminate paraneoplastic syndromes.