Guy Hidas

Extracorporeal shock wave lithotripsy in prepubertal children: 22-year experience at a single institution with a single lithotriptor.

PURPOSEnThe sophistication of percutaneous nephrolithotomy and ureteroscopy challenges the efficacy of ESWL for urolithiasis in prepubertal patients. We evaluated our long-term experience with ESWL in these patients and determined its efficiency.nnnMATERIALS AND METHODSnWe retrospectively reviewed the charts of all prepubertal patients who underwent ESWL. We evaluated the need for tubing, the 3-month stone-free rate, the need for additional ESWL, and the effect of stone size and location, and cystinuria on the 3-month stone-free rate.nnnRESULTSnBetween 1986 and 2008, 119 males and 97 females with a mean age of 6.6 years who had urolithiasis underwent ESWL using the Dornier HM3 lithotriptor. We treated 157 children with renal calculi with an average +/- SD diameter of 14.9 +/- 8.9 mm, of whom 66 (42%) required a tube in the urinary system. The 3-month stone-free rate was 80% and 31 patients (19.7%) needed an additional procedure. Stone location did not affect the stone-free rate but stone size did. We treated 59 patients for ureteral stones with an average stone length of 9.5 +/- 4.8 mm, of whom 41 (69%) required tube insertion. The 3-month stone-free rate was 78% and 13 patients (22%) needed an additional procedure. The 3-month stone-free rate did not depend on stone location or size. The rate was 37.5% in patients with cystinuria and 82.5% in all others (p <0.0001). Six patients (2.8%) had complications.nnnCONCLUSIONSnThe 3-month stone-free rate after ESWL in prepubertal patients is 80% and 20% of patients require additional procedures. ESWL is most effective for kidney stones less than 11 mm. ESWL has inferior results for cystine stones compared to other calculi. Complications are rare.

Determination of Renal Stone Composition with Dual-Energy Computed Tomography: An Emerging Application

Urinary tract stone disease is common in the Western world. Nonenhanced computed tomography (CT) is the method of choice for stone diagnosis; however, it has a limited role in predicting stone type. Knowledge of stone composition is currently determined by postoperative assessment of stone fragments. A noninvasive tool for accurate characterization of stone composition would improve patient management. Dual-energy CT aids in the differentiation among calcium, uric acid, and cystine stones. In this review we describe the role of dual-energy CT for in vitro and in vivo analysis of urinary stones. We illustrate the technique, review the literature, and discuss future directions.

β-TrCP Inhibition Reduces Prostate Cancer Cell Growth via Upregulation of the Aryl Hydrocarbon Receptor

Background Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR) signaling plays a pivotal role in development and progression. The initial treatment for advanced prostate cancer is suppression of androgen signaling. Later on, essentially all patients develop an androgen independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. β-TrCP is an E3 ligase that targets various substrates essential for many aspects of tumorigenesis. Methodology/Principal Findings Here we show that β-TrCP depletion suppresses prostate cancer and identify a relevant growth control mechanism. shRNA targeted against β-TrCP reduced prostate cancer cell growth and cooperated with androgen ablation in vitro and in vivo. We found that β-TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR) mediating the therapeutic effect. This phenomenon could be ligand independent, as the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) did not alter prostate cancer cell growth. We detected high AhR expression and activation in basal cells and atrophic epithelial cells of human cancer bearing prostates. AhR expression and activation is also significantly higher in tumor cells compared to benign glandular epithelium. Conclusions/Significance Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining β-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients.

Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: A case-control study

BACKGROUNDnMuscle-invasive bladder cancer is most commonly treated by radical cystectomy. Patients who are too sick to go through this surgery or who are unwilling to accept the mutilation associated with it are referred to chemoradiation. We compared the results of these 2 modalities using age-matched populations.nnnPARTICIPANTS AND METHODSnBetween 1998 and 2008, 33 patients were treated with chemoradiation for biopsy-proven T2-4aN0M0 urothelial bladder cancer. For every patient treated with chemoradiation, an age-matched patient who underwent radical cystectomy on the same year was selected for comparison. Mean radiotherapy dose was 62 Gy (standard deviation = 8.4) and median follow-up of both groups was approximately 36 months.nnnRESULTSnThe groups were similar in age, proportion of men, and length of follow-up. However, the Charlson comorbidity index was significantly lower for operated patients (3.45 vs. 4.36, P = 0.01). Furthermore, 2 patients (6%) in the chemoradiation group had salvage cystectomy (one for disease recurrence and another for bladder shrinkage). The 2- and 5-year overall survival rates after surgery were 74.4% and 54.8%, respectively, and after chemoradiation were 70.2% and 56.6% (P = 0.8), respectively. The 2- and 5-year disease-free survival rates after surgery were 67.8% and 63.2%, respectively, and after chemoradiation were 63% and 54.3% (P = 0.89), respectively. Side effects were mild in both groups, with grade 3+toxicity seen in only 2 operated and 4 irradiated patients.nnnCONCLUSIONSnDespite having a significantly higher comorbidity index, patients treated with chemoradiation had similar overall and disease-free survival rates with low toxicity. Treatment with chemoradiation should be considered in patients with T2-4aN0M0 bladder cancer.

The Response of Variant Histology Bladder Cancer to Intravesical Immunotherapy Compared to Conventional Cancer

Background High-grade urothelial carcinomas (UCs) often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with bacillus Calmette–Guerin (BCG). We compared the response, to treatment with BCG, of UC containing glandular, squamous, nested, and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade UC. Methods A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. Forty-one patients with Ta or T1, confirmed by second look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation, 13 patients with squamous differentiation, 9 patients with glandular differentiation, and 7 patients with nested variants. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings Patients with variant tumors had similar clinical features to patients with conventional disease, including age, male to female ratio, stage, the presence of Tis, and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC, including 5-year recurrence-free survival (63.5 Vs. 71.5%, pu2009=u20090.05), 5-year progression (≥T2)-free survival (60 Vs. 82.5%, pu2009=u20090.002), 5-year disease-specific survival (73 Vs. 92.5%, pu2009=u20090.0004), and overall survival (66 Vs. 89.5%, 0.05). Interpretation A patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5u2009years compared to 7.5% chance for a patient with conventional high-grade UC.

Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR – COUP-TF1 – which could possibly play a role in human prostate cancer.

Pregnancy Rates after Testicular Torsion

PURPOSEnTo our knowledge the effect of testicular torsion on the pregnancy rate is unknown. In this study we focused on the pregnancy rate, which is the ultimate index of fertility status.nnnMATERIALS AND METHODSnWe reviewed the records of 273 patients who presented to our emergency room with testicular torsion between 1994 and 2014. Study inclusion criteria included being in a relationship with the intent to conceive for at least 1 year, age greater than 25 years and a normal contralateral testis. Patients with primary infertility, those who were unwilling to participate or unreachable and those with a history of undescended testis and/or varicocele were excluded from analysis. Patients were contacted by telephone and interviewed according to a standardized questionnaire. Pregnancy rates in the orchiopexy and orchiectomy groups were compared to each other and to the accepted pregnancy rate in the literature.nnnRESULTSnA total of 63 patients met study inclusion criteria, including 41 and 22 in the orchiopexy and orchiectomy groups, respectively. The pregnancy rate in the orchiopexy and orchiectomy groups was 90.2% and 90.9%, respectively (p = 1.0). The accepted pregnancy rate in the general population is 82% to 92%. Mean ± SD time to pregnancy in the orchiopexy and orchiectomy groups was 6.6 ± 5.50 and 7.2 ± 5.4 months, respectively (p = 0.27).nnnCONCLUSIONSnSeveral studies suggest decreased fertility potential in patients with a history of testicular torsion. However, in the current study in couples in which the male had a history of testicular torsion the pregnancy rate and the interval to pregnancy were within the accepted range of the general population.

The growth rate of “clinically significant” renal cancer

Surveillance studies of enhancing renal masses report on a mean tumor growth rate of about 0.3xa0cm/year. In most of these studies however, only small tumors in elderly patients were followed. In the current report, we attempt to evaluate the growth rate of “clinically significant” renal carcinomas defined as tumors that were treated immediately upon diagnosis. 46 patients (mean age 64xa0years SD 11xa0years) were treated for renal carcinoma. All had a cross-sectional imaging studies performed 6–60xa0months prior to diagnosis of kidney cancer demonstrating no tumor. Tumor growth rate was calculated by dividing tumor’s largest diameter by the time interval between the normal kidney imaging and diagnosis of renal cancer. Mean tumor diameter was 4.5xa0cm (SD 2.4xa0cm). Mean time period from the normal imaging to diagnosis of renal cancer was 33.6xa0months (SD 18xa0months). According to the proposed model, the average growth rate of “clinically significant” renal carcinomas was 2.13xa0cm/year (SD 1.45, range 0.2–6.5xa0cm/year). Tumor growth rate correlated inversely with patient’s age (pxa0=xa00.007). Patient gender or Fuhrman’s grade did not correlate however. The growth rate of “clinically significant” renal cancer appears to be higher than the rate reported in surveillance trials. Renal tumors tend to grow faster in young patients. As such, variable growth rate should be taken into account when considering active surveillance in young patients and when designing trials for evaluation of anti-cancer agents.

Do we really need kidneys-ureters-bladder radiography to predict stone radiopacity before treatment with shockwave lithotripsy? Development and internal validation of a novel predictive model based on computed tomography parameters.

Abstract Purpose: To produce and validate a predictive model based on CT parameters for calculating the probability of a stone to be visible on fluoroscopy of shockwave lithotripsy (SWL) and to compare its accuracy to that of kidneys-ureters-bladder (KUB) radiography. Methods: We retrospectively analyzed 306 patients (sample group) who underwent an SWL between March 2011 and August 2012. A multivariate analysis of several parameters extracted from the preoperative CT scan was conducted to identify independent predictors for radiopacity on SWL fluoroscopy. The results were used for the creation of a predictive model. Internal validation was made on a group of 75 patients (validation group) treated from September 2012 until December 2012. Predictive accuracy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration plot. The ROC curve was also used for comparing the predictive accuracy of the model to that of KUB radiography. Results: From 306 evaluated stones, 238 (77.8%) ...PURPOSEnTo produce and validate a predictive model based on CT parameters for calculating the probability of a stone to be visible on fluoroscopy of shockwave lithotripsy (SWL) and to compare its accuracy to that of kidneys-ureters-bladder (KUB) radiography.nnnMETHODSnWe retrospectively analyzed 306 patients (sample group) who underwent an SWL between March 2011 and August 2012. A multivariate analysis of several parameters extracted from the preoperative CT scan was conducted to identify independent predictors for radiopacity on SWL fluoroscopy. The results were used for the creation of a predictive model. Internal validation was made on a group of 75 patients (validation group) treated from September 2012 until December 2012. Predictive accuracy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration plot. The ROC curve was also used for comparing the predictive accuracy of the model to that of KUB radiography.nnnRESULTSnFrom 306 evaluated stones, 238 (77.8%) were visible on fluoroscopy. Results of the multivariate analysis revealed that stone size (P<0.001), stone attenuation (P<0.001), location in the midureter (P<0.001), the distance between the stone and the anterior abdominal wall (P<0.001), and fat thickness of the anterior abdominal wall (P=0.001) were all independent predictors for stone radiopacity on fluoroscopy. A predictive model was produced based on the above parameters. The model demonstrated high calibration and areas under the curve of 0.923 and 0.965 in the sample and validation group, respectively, while its predictive performance was significantly higher (P<0.001) of that of KUB radiography (area under the curve=0.727).nnnCONCLUSIONSnThis novel model can estimate with high accuracy stone radiopacity on SWL fluoroscopy using parameters of CT scan and thus it can be used as an alternative to KUB radiography for treatment planning.

Retrograde versus Antegrade Approach for the Management of Large Proximal Ureteral Stones

Objective. To evaluate and compare the efficacy and safety of retrograde versus antegrade ureteroscopic lithotripsy for the treatment of large proximal ureteral stones. Patients and Methods. We retrospectively analyzed the medical records of patients with proximal ureteral stones >15u2009mm, treated in our institution from January 2011 to January 2016. Intraoperative parameters, postoperative outcomes, and complications were recorded and compared between the two techniques. Results. Our analysis included 57 patients. Thirty-four patients (59.6%) underwent retrograde and 23 patients (40.4%) underwent antegrade ureteroscopy. There was no significant difference in patients demographics and stone characteristics between the groups. Stone-free rate was significantly higher (p = 0.033) in the antegrade group (100%) compared to retrograde one (82.4%). Fluoroscopy time, procedure duration, and length of hospitalization were significantly (p < 0.001) lower in retrograde approach. On the other hand, the need for postoperative stenting was significantly lower in the antegrade group (p < 0.001). No difference was found between the groups (p = 0.745) regarding postoperative complications. Conclusions. Antegrade ureteroscopy is an efficient and safe option for the management of large proximal ureteral stones. It may achieve high stone-free rates compared to retrograde ureteroscopy with the drawback of longer operative time, fluoroscopy time, and length of hospitalization.