Tarık Esen

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.

Impact of Case Volumes on the Outcomes of Percutaneous Nephrolithotomy

BACKGROUND Previous studies have demonstrated relationships between case volumes and outcomes in surgery. Little is known about the impact of case volumes on the outcomes of percutaneous nephrolithotomy (PCNL). OBJECTIVE To investigate the influence of case volumes on the efficacy and safety outcomes of PCNL. DESIGN, SETTING, AND PARTICIPANTS From November 2007 to December 2009, prospective data were collected by the Clinical Research Office of the Endourological Society from consecutive patients over a 1-yr period in 96 centers globally. Data of 3933 patients in the Global PCNL study database were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients were divided into low- and high-volume groups based on the median annual case volume of their respective treatment center. Preoperative characteristics and outcomes were compared between the two groups. Case volume was treated as a continuous variable. The relationship between case volume and stone-free (SF) rate, complication rate, and duration of hospital stay was explored using multivariate regression analysis. RESULTS AND LIMITATIONS SF rates were higher in high-volume centers (82.5% vs 75.1%; p value <0.001). Complication rates were lower in high-volume centers (15.9% vs 21.7%; p value 0.002), whereas the mean (standard deviation [SD]) duration of stay was shorter in high-volume centers (3.4 [2.6] vs 4.9 [3.7] d; p value <0.001). SF rate increased with case volume, whereas complication rate and duration of stay diminished with increasing case volumes after adjusting for stone burden, urine culture status, American Society of Anesthesiologists score, and the presence of staghorn stones. The highest SF rates were observed in centers with >120 cases per year. CONCLUSIONS Centers that perform high numbers of PCNLs per year achieve better results. Both the efficacy and safety outcomes of PCNL improve with the number of surgeries performed in a given center per year.

GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro

STUDY QUESTION Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.

Phosphodiesterase type 5 inhibitors and kidney disease

Chronic kidney disease (CKD) represents a worldwide health problem. Traditionally, the nephroprotective treatment for CKD aims to slow progression to end-stage renal disease and includes dietary protein restriction, correction of metabolic acidosis, and renin–angiotensin system blockers. However, current standard therapeutic options may not be enough for preventing CKD progression in a subset of patients making necessary to develop novel therapeutic options to further slow renal function loss. Phosphodiesterase type 5 (PDE5) inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension. However, recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects, such as cardioprotection and cerebrovascular protection. In the current review, we summarize PDE5 inhibitors’ utility in disease states and clinical conditions related to kidney disease such as systemic hypertension and acute and chronic kidney injury and discuss the mechanisms explaining possible kidney protective roles of PDE5 inhibitors. A recently completed phase 2 trials demonstrated that the long-acting PDE5 inhibitor PF-00489791 decreased albuminuria in patients with overt diabetic nephropathy when added on top of renin–angiotensin system blockade.

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.

Isolated upper pole access in percutaneous nephrolithotomy: a large-scale analysis from the CROES percutaneous nephrolithotomy global study.

PURPOSE We analyzed the indications for and outcomes of percutaneous nephrolithotomy using upper pole access. MATERIALS AND METHODS Between 2007 and 2009 prospective data were collected by the Clinical Research Office of the Endourological Society (CROES) from consecutive patients at 96 centers globally. Data on 4,494 patients were included in this analysis. Patients were divided into upper and lower pole access groups based on the location of percutaneous renal access. Preoperative characteristics and outcomes were compared between the 2 groups by univariate and multivariate tests. RESULTS The upper pole access group had more staghorn stones (21.7% vs 15.5%, p <0.001) and a greater stone burden (mean ± SD 476 ± 390.5 vs 442 ± 344.9 mm(2), p = 0.091). Mean operative time was 92.4 ± 46.1 and 75.1 ± 41.3 minutes in the upper and lower pole groups, respectively (p <0.001). The stone-free rate was lower in the upper pole access group (77.1% vs 81.6%, p = 0.030). The overall complication rate was higher in the upper pole group with a higher incidence of hydrothorax (5.8% vs 1.5%) but a lower incidence of pelvic perforation (1.8% vs 3.2%). Mean hospital stay was longer in the upper pole group (p = 0.048). Success and complication rates were similar in upper pole access subgroups, defined as definitive (staghorn and isolated upper calyceal stones) and elective (pelvic, middle calyceal and lower pole stones) indications. CONCLUSIONS Isolated upper pole access is indicated in a select group of patients with complex stones. Upper calyceal and staghorn stones are more commonly managed by upper pole access, which is associated with a higher complication rate and longer hospital stay as well as a lower stone-free rate due to procedure complexity.

Hemangioma of the glans penis treated with Nd:YAG laser.

Hemangioma of the glans penis is a rare entity and usually has been treated with surgical excision or cryotherapy which carry suboptimal cosmetic results and bleeding problem. We present a 18-year-old male patient with hemangioma of the glans penis who was treated with Nd:YAG laser with excel lent cosmetic results.

Hydatid disease of the kidney caused by Echinococcus multilocularis: A rare clinical entity

Hydatid disease of the urinary tract is extremely rare and constitutes approximately 4% of all cases of hydatid disease. The Echinococcus multilocularis is a relatively rare form of echinococcus as the cause of renal hydatid disease. We describe a patient who had renal hydatidosis which is rarely caused by the E. multilocularis.

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.