Can we predict chemotherapy response in patients with metastatic testicular cancer? Role of thrombocytosis as a novel marker.

BACKGROUND: Primary treatment of choice for advanced germ cell tumors is 3 to 4 cycles of combination bleomycin-etoposide-cisplatin (BEP) chemotherapy. Although most patients treated for advanced germ cell tumors (GCT) will be cured, approximately 30% will fail to achieve a durable complete response (CR). Thrombocytosis has been found to be related with significantly shorter survival in many cancers. However, its role in testicular cancer patients has not been studied previously. The objective of this study was to investigate the relationship between thrombocytosis and chemotherapy response in patients with metastatic testicular cancer. METHODS: Records of 113 patients with advanced stage testicular cancer were reviewed. Treatment outcomes were classified as complete clinical response (cCR), partial clinical response (pCR), complete pathological response (cPR) and treatment failure and the relationship with thrombocytosis was investigated. Logistic regression analysis was performed to identify factors associated with treatment failure. RESULTS: Totally 103 patients met the eligibility criteria. Thrombocytosis was detected in 26 (25.2%) patients. Treatment failure was observed in 14 (53.8%) and 28 (36.4%) of the patients in the thrombocytosis and non-thrombocytosis groups respectively (P=0.037). Thrombocytosis and IGCCCG high-risk group are found as independent prognostic factors for treatment failure in multivariate analysis. CONCLUSIONS: Thrombocytosis is seen in 25% of patients with testicular GCT and it is found to be associated with poorer chemotherapy response in metastatic patients. It can be used to predict the response to chemotherapy.

What is the best option for 10-20mm renal pelvic stones undergoing ESWL in the pediatric population: stenting, alpha blockers or conservative follow-up?

OBJECTIVE: In this study we aimed to identify the effect of three different modalities (stenting, doxazosin and conservative follow-up) on stone free rates and complication rates for 10-20mm renal pelvic stones in pediatric patients who underwent shock wave lithotripsy. PATIENTS AND METHODS: In this study data from 241 renal units (RUs) of 195 consecutive patients with 10-20mm renal pelvis stones were analyzed retrospectively. There were 3 groups in the study; 56 (23.2%) RUs with ureteral stenting were categorized as group 1, and 39 (16.2%) RUs that received doxazosin were categorized as group 2. The remaining 146 (60.6%) RUs without history of ureteral stenting or alpha-blockers usage were categorized as group 3. Patient demographics, stone characteristics, stone free rates (SFRs), time to stone expulsion and complications were documented and compared in each group. RESULTS: Mean age of the population was 6.6 years and mean stone size was 13.8 ± 2.9 mm. Demographic characteristics of the 3 groups were not significantly different. SFRs of the three groups were 89.2%, 87.1% and 82.1% (p = 0.275). Mean time to stone expulsion for groups 1 and 2 were 17.4 and 21.8 days respectively and significantly lower than that in group 3 (31.3 days). CONCLUSIONS: Ureteral stenting or doxazosin for shockwave lithotripsy (SWL) is not superior to watchful waiting in terms of SFR and complications however both modalities shorten the stone expulsion time for 10-20mm renal pelvis stones in the pediatric population.

Is top-down vs bottom-up radiological evaluation after febrile urinary tract infection really less stressful for the child and family? Challenging the dogma.

PURPOSE: We evaluated whether stress levels in children and parents during radiological evaluation after febrile urinary tract infection are really lower using the top-down approach, where (99m)technetium dimercaptosuccinic acid renal scintigraphy is used initially, than the bottom-up approach, where voiding cystourethrography is initially performed and repeated examinations are easier for all. MATERIALS AND METHODS: We prospectively evaluated 120 children 3 to 8 years old. Pain ratings were obtained using the Faces Pain Scale-Revised, and conversation during the procedure was evaluated using the Child-Adult Medical Procedure Interaction Scale-Revised by 2 independent observers. To evaluate parental anxiety, the State-Trait Anxiety Inventory form was also completed. Following a documented febrile urinary tract infection children were randomized to the top-down or bottom-up group. A third group of 44 children undergoing repeat voiding cystourethrography and their parents were also evaluated. RESULTS: Child ratings of pain using the Faces Pain Scale-Revised were not significantly different between the top-down group following (99m)technetium dimercaptosuccinic acid renal scintigraphy (2.99 on a scale of 10) and the bottom-up group following voiding cystourethrography (3.21). Also the Faces Pain Scale-Revised was not significantly different in the repeat voiding cystourethrography group (3.35). On the Child-Adult Medical Procedure Interaction Scale-Revised there was negative correlation between child coping and child distress, as well as rate of child distress and adult coping promoting behavior. Parental state anxiety scores were significantly less in the top-down and repeat voiding cystourethrography groups than in the bottom-up group. CONCLUSIONS: Although the top-down approach and repeat voiding cystourethrography cause less anxiety for caregivers, these values do not correlate to pain scale in children. This finding might be due to lack of appropriate evaluation tools of pediatric pain and anxiety. However, the theory that the top-down approach is less invasive, and thus less stressful, requires further research. The Child-Adult Medical Procedure Interaction Scale-Revised data indicate that influences in adult-child interaction are bidirectional.

Can factors affecting complication rates for ureteric re-implantation be predicted? Use of the modified Clavien classification system in a paediatric population.

OBJECTIVE: To determine preoperative predictive factors of postoperative complications of ureteric re-implantation in children by using the modified Clavien classification system (MCCS), which has been widely used for complication rating of surgical procedures. PATIENTS AND METHODS: In all, 383 children who underwent ureteric re-implantation for vesico-ureteric reflux (VUR) and obstructing megaureters between 2002 and 2011 were included in the study. Intravesical and extravesical ureteric re-implantations were performed in 338 and 45 children, respectively. Complications were evaluated according to the MCCS. Univariate and multivariate analyses were used to determine predictive factors affecting complication rates. RESULTS: In all, 247 girls and 136 boys were studied. The mean (sd) age was 46 (25) months and the mean (sd) follow-up was 49.4 (27.8) months. The mean (sd) hospitalisation time was 4.7 (1.6) days. Complications occurred in 76 (19.8%) children; 34 (8.9%) were MCCS grade I, 22 (5.7%) were grade II and 20 (5.2%) were grade III. Society of Fetal Urology (SFU) grade 3-4 hydronephrosis, obstructing megaureters, a tailoring-tapering and folding procedure, refractory voiding dysfunction and a duplex system were statistically significant predictors of complications on univariate analysis. Prior injection history, paraureteric diverticula, stenting, gender, age, operation technique (intra vs extravesical) were not significant predictors of complications. In the multivariate analysis refractory voiding dysfunction, a tailoring-tapering and folding procedure, obstructing megaureters (diameter of >9 mm) and a duplex system were statistically significant predictors of complications. CONCLUSION: Ureteric re-implantation remains a valid option for the treatment of certain patients with VUR. Refractory voiding dysfunction, a tailoring-tapering and folding procedure, obstructing megaureters (diameter of >9 mm) and associated duplex systems were the main predictive factors for postoperative complications. Use of a standardised complication grading system, such as the MCCS, should be encouraged to allow the valid comparison of complication rates between series.

Nocturnal lagophthalmos in children with urofacial syndrome (Ochoa): a novel sign.

The urofacial syndrome is a rare condition that occurs in both genders and characterized by uropathy and facial abnormalities. Early diagnosis is crucial for the management and prognosis of urinary problems. Paradoxical inversion of facial musculature when smiling, giving an appearance of crying associated with severe urinary tract dysfunction is typical in these patients. Although facial signs and symptoms are generally ignored and shadowed by the dominant bladder symptoms, we have recently realized a unique but constant finding in majority of these patients, nocturnal lagophthalmos which is described as inability to close the eyelids during sleep. We report 15 patients with urofacial syndrome (Ochoa) whom mostly had admitted with major urological symptoms and 12 of the cases had nocturnal lagophthalmos. Lagophthalmos may lead to keratitis, corneal abrasion, infection, vascularization, and in extreme cases, ocular perforation, endophthalmitis and loss of the eye. Basic modalities like lubricant drops during the day and ointments at night are usually enough to protect the cornea from exposure keratopathy. In moderate to severe cases, overnight taping of the lid or the use of a moisture chamber might be necessary. Majority of our patients responded to basic therapy. Conclusion Nocturnal lagophthalmos is a novel symptom described in patients with urofacial syndrome. The pediatricians and urologists should be careful about this symptom to prevent eye damage and quality of life problems.

Does the number of cycles of cisplatin based chemotherapy have any effect on renal function in patients with testicular germ cell tumor?

PURPOSE: We assessed the effects of the number of cisplatin, etoposide and bleomycin cycles on long-term renal function. MATERIALS AND METHODS: A total of 157 patients with primary testicular germ cell tumors were treated between 1995 and 2013, of whom 113 (72%) received chemotherapy as the primary intervention. Data were collected retrospectively. The estimated glomerular filtration rate was determined using the Modification of Diet in Renal Disease (MDRD) formula based on pretreatment and last followup visit serum creatinine measurements. Patients who did not receive chemotherapy were compared to those who received cisplatin based chemotherapy. The chemotherapy group was also divided into 3 subgroups according to the number of chemotherapy cycles (2, 3, or 4 or more). RESULTS: At the last followup visit serum creatinine and the estimated glomerular filtration rate significantly differed between the chemotherapy and nonchemotherapy groups. The decrease in the median estimated glomerular filtration rate was significantly greater in the chemotherapy than the nonchemotherapy group (p<0.001). New onset stage 3 chronic kidney disease was observed in 19 patients (12.1%) in the chemotherapy group, including 0%, 5.9%, 13.8% and 20.9% who received 0, 2, 3, or 4 or more chemotherapy cycles, respectively. Except for the difference between the nonchemotherapy group and the 2-cycle chemotherapy group the differences between the groups in new onset chronic stage 3 kidney disease were statistically significant. CONCLUSIONS: Patients with testicular tumors who received cisplatin based chemotherapy showed a significant decrease in the estimated glomerular filtration rate and a significant increase in new onset stage 3 chronic kidney disease compared to patients who received no cycle. However, in patients at high risk with stage I nonseminomatous germ cell tumor who elected 2 cycles of cisplatin, etoposide and bleomycin the chemotherapy had no statistically significant effect on these parameters compared to those in patients who received no chemotherapy.

Do antibiotic prophylaxis and/or circumcision change periurethral uropathogen colonization and urinary tract infection rates in boys with VUR?

BACKGROUND: To evaluate the effect of circumcision and/or antibiotic prophylaxis on periurethral flora and associated bacteriuria in male children with and without vesicoureteral reflux (VUR). PATIENTS AND METHODS: The study included 91 boys with low-grade VUR and 106 healthy boys (control) without VUR. The boys with VUR were randomized as antibiotic prophylaxis only and antibiotic prophylaxis plus circumcision. The boys without VUR were randomized as circumcision group and followed-up group without circumcision. Periurethral swab and urine cultures were obtained from the participants at the beginning of the study, and at 1st, 3rd, 6th, 9th, and 12th month. The groups were compared in terms of positive periurethral and urine cultures. RESULTS: The positive periurethral culture rate was significantly lower in the circumcised boys at all measurement times. The positive urine culture rate in the circumcised boys was lower than in the uncircumcised boys. Subgroup analysis based on age groups showed that age did not affect these statistical differences. CONCLUSION: Circumcision decreases colonization of periurethral bacterial pathogenic flora. In boys with low-grade VUR, circumcision plus antibiotic prophylaxis prevented recurrent and febrile urinary tract infections.

Effect of performing varicocelectomy before intracytoplasmic sperm injection on clinical outcomes in non-azoospermic males.

OBJECTIVE: To compare laboratory outcomes and pregnancy rates of infertile couples, in which male partners have treated and untreated clinical varicocele before performing ICSI. MATERIALS AND METHODS: The data of 306 couples in whom ICSI was performed due to infertility were evaluated retrospectively. All of the males had clinical varicocele, and patients were evaluated in two groups. Group A (n = 168) included patients who underwent successful varicocele repair and Group B (n = 138) included patients with clinical varicocele at the time of ICSI and no history of varicocele repair. Semen analysis, demographic factors and live birth and pregnancy rates were recorded. RESULTS: There were 168 patients (54.9 %) in group A and 138 patients (45.1 %) group B. Groups were similar for demographic factors. Semen analysis results were significantly better after varicocelectomy. Pregnancy rates were higher in group A (62.5 vs. 47.1 %, p = 0.001). Live birth rates were also higher in group A (47.6 vs. 29.0 %, p = 0.0002). In the logistic regression analysis, varicocelectomy was found to increase the rates of viable pregnancy (OR 2.02, 95 % CI 1.25-3.87; p = 0.032), live births (OR 2.12, 95 % CI 1.26-3.97; p = 0.026). CONCLUSION: Performing varicocelectomy improves the pregnancy and live birth rates by ICSI in infertile couples in whom the male partner has clinical varicocele. Varicocelectomy should be offered before ICSI to infertile men with clinical varicocele. However, further prospective randomized studies are needed to confirm benefit of varicocelectomy before ICSI.

LRIG2 mutations cause urofacial syndrome.

Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.

Mayer-Rokitansky-Küster-Hauser syndrome accompanied by renal cell carcinoma: a case report.

Mayer-Rokitansky-Küster-Hauser anomaly originates from agenesis of the Müllerian duct including agenesis of the uterus and the vagina because of abnormal development of the uterine ducts. This syndrome may be accompanied by the upper urinary tract anomalies such as unilateral renal agenesis, ectopia of 1 or both kidneys, renal hypoplasia, horseshoe kidney, and hydronephrosis. We report a 16-year-old girl, with unilateral renal agenesis, herniating ovary, and renal cell carcinoma in her solitary kidney, associated with Mayer-Rokitansky-Küster-Hauser syndrome-the first case in the literature to our knowledge.

The effect of varicocele on sperm morphology and DNA maturity: does acridine orange staining facilitate diagnosis?

OBJECTIVE: The aim of this study was to determine whether Acridine Orange (AO) can be used as a routine procedure in a physician's office to detect sperm deoxyribonucleic acid (DNA) fragmentation in patients with varicoceles. MATERIAL AND METHODS: Forty-five patients with a mean age of 30.4 years, who had been diagnosed with varicoceles by physical examination and 30 healthy males with a mean age of 28.3 years and without any signs of varicoceles were included in this study. Doppler Ultrasonography was performed to each individual in addition to physical examination. Semen analyses were performed by the same biologist. Sperm morphology was evaluated according to the World Health Organization (WHO) criteria and Kruger's strict criteria. After routine semen analysis, the samples were fixed separately for further examination with AO staining. RESULTS: In routine semen analyses, total sperm count, total motile sperm count, and fast direct forward motile and direct forward motile sperm counts were significantly lower in patients with varicoceles, and the immotile sperm count was significantly higher in patients with varicoceles compared to the control group. Kruger's examination revealed a lower sperm count with normal morphology in patients with varicoceles. After AO staining, the ratio of spermatozoa demonstrating red and green coloration were 6.5±11.0% and 93.5±11.0%, respectively in the varicocele group and 1.0±1.0% and 99.0±1.0%, respectively in the control group (p<0.001). CONCLUSION: Semen analysis using AO staining can be performed under a clinician's office conditions with a fluorescent microscope without any additional equipment. Further studies are needed to validate the AO staining with more extensively used and well-known methods. Therefore, AO staining can be used as a simple and reliable method that can be performed daily in a physician's office in infertility and andrology clinics.

Inflammatory myofibroblastic tumor of the bladder in a 10-year-old girl.

Inflammatory myofibroblastic tumors (IMTs) of the bladder are rarely encountered bladder tumors during the pediatric age. The unknown malignant potential of these tumors causes controversy for their treatment and follow-up. We report a 10-year-old girl who was referred to our clinic with dysuria and enuresis. The clinicopathological evaluation was compatible with IMT and a bladder preserving approach was used. There was no recurrence in the first year of follow-up examinations.

Does the diameter of dextranomer microspheres affect the success in endoscopic treatment of vesicoureteral reflux?

OBJECTIVE: To evaluate whether the polymer microsphere diameter affects the success rate in the endoscopic treatment of vesicoureteral reflux. METHODS: In our consecutive series, 56 patients underwent subureteral injection with Dexell and 60 patients were treated with Deflux. Patients were evaluated with pediatric lower urinary tract scoring system, uroflowmetry, and a residual urine volume and voiding diary at the time of injection and control. Patients with grade V reflux, duplex systems, paraureteral diverticula, or refractory lower urinary tract symptoms were excluded. The numbers of renal units with grade II-III vesicoureteral reflux were 78 and 73 in the first (Deflux) and second (Dexell) groups, respectively. The numbers of renal units with grade IV reflux were 24 and 17 in the first and second groups, respectively. The resolution rate was determined by voiding cystourethrogram at the third postoperative month. Postoperative febrile urinary tract infections and de novo scars in dimercaptosuccinic acid were noted. Groups were compared by the χ(2) test. RESULTS: Mean follow-up time and mean age of the children were not significantly different. The number of nondilating and dilating renal units was not significantly different. Resolution rates were similar between the groups (79.5 and 78%, respectively). There was no significant difference in terms of resolution rates when dilating and nondilating urinary systems were separately analyzed. The average volumes used per renal unit were 0.9 and 1.6 mL in the first and second groups, respectively (P < .005). Postoperative febrile urinary tract infection and de novo scar formation rates were similar. CONCLUSION: The diameter of dextranomer microsphere does not affect the short-term success rate in endoscopic treatment of vesicoureteral reflux. Multicentric, randomized and prospective studies are required for long-term clinical results.