Ömer Acar

Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process.

There is an ongoing need for an accurate imaging modality which can be used for staging purposes, metastatic evaluation, predicting biologic aggresiveness and investigating recurrent disease in prostate cancer. Prostate specific membrane antigen, given its favorable molecular characteristics, holds a promise as an ideal target for prostate cancer‐specific nuclear imaging. In this study, we evaluated our initial results of PSMA based PET/CT imaging in prostate cancer.

Grading of Classical Testicular Microlithiasis Has No Effect on the Prevalence of Associated Testicular Tumors

Aim: To evaluate the role of further grading of classical testicular microlithiasis (CTM) on the prevalence of associated testicular tumors. Methods: Patients diagnosed with CTM using scrotal ultrasound over a 5-year period from a referral radiology clinic were included in this study. Patients with CTM were categorized as group 1 (grade I; 5–10 microliths/image), group 2 (grade II 10–20 microliths/image), and group 3 (grade III > 20 microliths/image). Other pathological findings were also recorded. The prevalence of testicular cancer was compared statistically between groups using the χ2 test. Results: Seventy-eight of 4,310 (1.8%) patients were found to have CTM. Of these, 17 (21.7%) had ultrasonographically detected testicular cancer. In patients without CTM (n = 4,232), 58 (1.1%) testicular cancers were found. This accounted to a 19.7-fold increase in the detection rate of testicular cancer in patients with CTM compared to patients without CTM. The rates of testicular cancer detected in groups 2 and 3 were 25 (6/24) and 26.6% (4/15), respectively (p > 0.05), while it was 17.9% (7/39) in group 1. Conclusions: CTM is an uncommon incidental finding in patients undergoing testicular ultrasonography, and grading of CTM plays no role in the prevalence of testicular cancer.

New Therapeutics to Treat Castrate-Resistant Prostate Cancer

The effective treatment of castrate-resistant prostate cancer (CRPC) has proven to be very challenging. Until recently, docetaxel was the only therapeutic demonstrated to extend overall patient survival. Yet recently, a considerable number of new therapeutics have been approved to treat CRPC patients. These remarkable advances now give new tools for the therapeutic management of late-stage prostate cancer. In this review, we will examine mechanistic and clinical data of several newly approved therapeutics including the chemotherapeutic cabazitaxel, antiandrogen enzalutamide, endocrine disruptor abiraterone acetate, immunotherapy sipuleucel-T, and bone-targeting radiopharmaceutical alpharadin. In addition, we will examine other promising therapeutics that are currently in Phase III trials.

Positional changes in voiding dynamics of children with non-neurogenic bladder dysfunction.

OBJECTIVES To investigate the effect of certain positions on voiding dynamics in children with non-neurogenic bladder dysfunction. METHODS A total of 29 patients (10 male, 19 female) with non-neurogenic overactive bladder were enrolled. None of the patients had voiding phase dysfunction. Male patients were told to urinate in three positions (sitting, squatting, standing). Female patients did not void while standing. During voiding, maximum urinary flow rate (Qmax), detrusor pressure at maximal flow (Pdet-Qmax), and intra-abdominal pressure at maximal flow (Pabd-Qmax) were recorded. After voiding in one position, the bladder was re-distended. The same procedures were repeated for the three different positions. Then patients were told to perform three drinking-voiding cycles without the catheter in place. After recording Qmax, residual urine was measured with ultrasonography. The differences between these parameters were analyzed. RESULTS The mean (+/- standard deviation) patient age was 11.10 +/- 2.94 years (range, 6-16 years). In girls, the mean Pdet-Qmax value in the sitting and squatting positions was 43.11 +/- 16.74 cm H(2)O and 35.21 +/- 10.67 cm H(2)O, respectively (P = .028). Girls voided with a significantly higher Qmax in sitting and squatting positions than boys, regardless of the presence of a catheter. The mean Pdet-Qmax value in the squatting position was 59.20 +/- 20.45 cm H(2)O in boys and 35.21 +/- 10.67 cm H(2)O in girls. The presence of a catheter significantly lowered mean maximal urinary flow rates in sitting and squatting positions. CONCLUSIONS This is the first study to demonstrate the effect of voiding positions on pressure flow study results in children. Our results show that voiding dynamics are influenced by different voiding positions in children with non-neurogenic bladder dysfunction.

Final Gleason Score Prediction Using Discriminant Analysis and Support Vector Machine Based on Preoperative Multiparametric MR Imaging of Prostate Cancer at 3T

Objective. This study aimed at evaluating linear discriminant analysis (LDA) and support vector machine (SVM) classifiers for estimating final Gleason score preoperatively using multiparametric magnetic resonance imaging (mp-MRI) and clinical parameters. Materials and Methods. Thirty-three patients who underwent mp-MRI on a 3T clinical MR scanner and radical prostatectomy were enrolled in this study. The input features for classifiers were age, the presence of a palpable prostate abnormality, prostate specific antigen (PSA) level, index lesion size, and Likert scales of T2 weighted MRI (T2w-MRI), diffusion weighted MRI (DW-MRI), and dynamic contrast enhanced MRI (DCE-MRI) estimated by an experienced radiologist. SVM based recursive feature elimination (SVM-RFE) was used for eliminating features. Principal component analysis (PCA) was applied for data uncorrelation. Results. Using a standard PCA before final Gleason score classification resulted in mean sensitivities of 51.19% and 64.37% and mean specificities of 72.71% and 39.90% for LDA and SVM, respectively. Using a Gaussian kernel PCA resulted in mean sensitivities of 86.51% and 87.88% and mean specificities of 63.99% and 56.83% for LDA and SVM, respectively. Conclusion. SVM classifier resulted in a slightly higher sensitivity but a lower specificity than LDA method for final Gleason score prediction for prostate cancer for this limited patient population.

Conspicuity of Peripheral Zone Prostate Cancer on Computed Diffusion-Weighted Imaging: Comparison of cDWI1500, cDWI2000, and cDWI3000

Introduction and Objective. Disadvantages associated with direct high b-value measurements may be avoided with use of computed diffusion-weighted imaging (cDWI). The purpose of this study is to assess the diagnostic performance of cDWI image sets calculated for high b-values of 1500, 2000, and 3000 s/mm2. Materials and Methods. Twenty-eight patients who underwent multiparametric MRI of the prostate and radical prostatectomy consecutively were enrolled in this retrospective study. Using a software developed at our institute, cDWI1500, cDWI2000, and cDWI3000 image sets were generated by fitting a monoexponential model. Index lesions on cDWI image sets were scored by two radiologists in consensus considering lesion conspicuity, suppression of background prostate tissue, distortion, image set preferability, and contrast ratio measurements were performed. Results. Lesion detection rates are the same for computed b-values of 2000 and 3000 s/mm2 and are better than b-values of 1500 s/mm2. Best lesion conspicuity and best background prostate tissue suppression are provided by cDWI3000 image set. cDWI2000 image set provides the best zonal anatomical delineation and less distortion and was chosen as the most preferred image set. Average contrast ratio measured on these image sets shows almost a linear relation with the b-values. Conclusion. cDWI2000 image set with similar conspicuity and the same lesion detection rate, but better zonal anatomical delineation, and less distortion, was chosen as the preferable image set.

Residual valve and stricture after posterior urethral valve ablation: How to evaluate?

OBJECTIVE To investigate the clinical and radiological parameters of posterior urethral valve (PUV) patients with residual valve or strictures after primary valve ablation. PATIENTS AND METHODS A total of 127 PUV patients were treated in our clinic between 1986 and 2009. We retrospectively reviewed the records of 101 patients, who had at least 1 year of follow-up data, regarding the presence of valve remnants or urethral strictures after PUV ablation. RESULTS A total of 21 patients (20.8%) underwent repeat-urethroscopy and, of these, residual valve leaflets or stricture were detected in 10 patients (10/101, 9.9%). In 2 of these 10 (20%), the urethra had been found to be normal on the first voiding cystourethrogram following ablation. However, these two boys underwent re-urethroscopy due to persistent vesicoureteral reflux in one and persistent hydroureteronephrosis in the other, and valve remnants were detected. The remaining 8 cases had radiological signs consistent with persistent infravesical obstruction in the early period. Obstruction was due to urethral stricture and residual valve remnants in 2 and 6 cases, respectively. CONCLUSIONS There was clinical suspicion of residual valve in about 20% of the cases and in half of these the urethra was found to be normal on urethroscopy. The possible presence of residual valve remnants after primary valve ablation should be confirmed by careful clinical, radiological and endoscopic evaluation.

Determining the origin of synchronous multifocal bladder cancer by exome sequencing

BackgroundSynchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours.MethodsTo better understand the genetic lineage of these tumours we conducted exome sequencing of synchronous multifocal pTa urothelial bladder cancers at a high depth, using multiple samples from three patients.ResultsPhylogenetic analysis of high confidence single nucleotide variants (SNV) demonstrated that the sequenced multifocal bladder cancers arose from a clonal origin in all three patients (bootstrap value 100 %). Interestingly, in two patients the most common type of tumour-associated SNVs were cytosine mutations of TpC* dinucleotides (Fisher’s exact test p < 10−41), likely caused by APOBEC-mediated deamination. Incorporating these results into our clonal model, we found that TpC* type mutations occurred 2-5× more often among SNVs on the ancestral branches than in the more recent private branches (p < 10−4) suggesting that TpC* mutations largely occurred early in the development of the tumour.ConclusionsThese results demonstrate that synchronous multifocal bladder cancers frequently arise from a clonal origin. Our data also suggests that APOBEC-mediated mutations occur early in the development of the tumour and may be a driver of tumourigenesis in non-muscle invasive urothelial bladder cancer.

How Does the Presence of Antenatally Detected Caliectasis Predict the Risk of Postnatal Surgical Intervention

OBJECTIVE To determine the effect of antenatally detected caliectasis on the postnatal surgical intervention rate. METHODS From 2006 to 2010, 56 patients with an anteroposterior diameter (APD) of 7-20 mm on the prenatal ultrasound scan performed in the third trimester of pregnancy were included in the present study. In these 56 patients, other anomalies (vesicoureteral reflux, posterior urethral valves, duplex system, megaureter) were excluded, and the postnatal clinical and radiologic follow-up data were available. The mean follow-up was 12.82 ± 10.72 months. These 56 patients were divided into 2 groups: those with (n = 32) and without (n = 24) caliectasis. In the caliectasis group, the mean follow-up was 13.6 ± 12.09 months and was 11.7 ± 8.70 months in the group without caliectasis. The statistical correlation between the postnatal operation rates and the presence of caliectasis (APD range 7-20 mm in third trimester) was investigated using the chi-square test. RESULTS In the study group (n = 56) with an APD range of 7-20 mm in the third trimester, postnatal surgical treatment (pyeloplasty) was performed in 12 (37.5%) and 3 (12.5%) of the children with and without caliectasis, respectively (P = .037). The risk of postnatal surgical treatment increased threefold in patients with an APD of 7-20 mm and a diagnosis of caliectasis (relative risk 3.0, 95% confidence interval 1.07-8.40). CONCLUSION In our study, the presence of concomitant caliectasis within the APD range of 7-20 mm on the third trimester ultrasound scan increased the risk of surgical treatment threefold. During prenatal counseling, the presence of caliectasis requires more rigorous follow-up.

Which method is the most reliable in determination of bladder capacity in children with idiopathic overactive bladder? A comparison of maximum voided volume, uroflowmetry and maximum cystometric capacity

OBJECTIVE To compare uroflowmetry, maximum cystometric capacity and maximum voided volume in terms of bladder capacity (BC) estimation in children with idiopathic overactive bladder. MATERIALS AND METHODS A total of 84 children with idiopathic overactive bladder were enrolled. Bladder diaries were kept by parents to measure maximum voided volume. The sum of voided volume and post-void residual urine represented uroflowmetric BC. Maximum cystometric capacity was recorded for each patient. Patients with and without urge incontinence and both sexes were compared, and correlations were tested between estimated capacities, patient age and continence status. RESULTS Mean age was 10.88 (range 6-16) years. There were 52 females and 32 males. A total of 48 patients had urge incontinence (group 1), and the remaining 36 (group 2) did not. Mean bladder capacities were 165.44ml for uroflowmetry, 204.37ml for cystometry and 260.07ml for bladder diary. Maximum cystometric capacity and capacity in terms of maximum voided volume by diary were significantly higher in patients without urge incontinence. There were significant correlations between age and all other variables, and between the presence of urge incontinence and all variables except maximum cystometric capacity. There were significant differences between bladder capacities estimated by the three methods; however, on age-adjusted re-analysis this significance was lost. CONCLUSION There is no significant difference between BCs estimated by uroflowmetry, maximum cystometric capacity and maximum voided volume in children with idiopathic overactive bladder. Bladder diary is a reliable and non-invasive way of estimating BC in this patient population.