Ömer Gülpınar

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.

Hydrodilation of the ureteral orifice in children renders ureteroscopic access possible without any further active dilation.

PURPOSE We review our experience with hydrodilation of the ureteral orifice for ureteroscopic access in children. MATERIALS AND METHODS We retrospectively reviewed the results of 30 ureteroscopic procedures performed in 26 children who were followed for 6 months. Ureteral access was obtained with the assistance of a hand irrigation pump without any further active dilation in all cases. RESULTS A total of 26 patients (86.7%) were completely stone-free after 1 procedure. There was no major complication such as ureteral perforation or avulsion. Mild flank pain was observed in 8 cases (26.7%). Predominant symptoms of bladder spasm were observed in 6 cases (20%). At 6-month followup no patient had pyelonephritis or demonstrated hydronephrosis related to ureteral stricture. CONCLUSIONS Our study shows that hydrodilation of the ureteral orifice in children renders ureteroscopic access possible with no additional active dilation and no associated complications.

Clinical comparision of intravesical hyaluronic acid and hyaluronic acid-chondroitin sulphate therapy for patients with bladder pain syndrome/interstitital cystitis.

INTRODUCTION Patients with a history of bladder pain syndrome/interstitial cystitis (BPS/IC) and who responded poorly or unsatisfactorily with previous treatment were compared taking intravesical hyaluronic acid (HA) or hyaluronic acid-chondroitin sulphate (HA-CS). METHODS Patients were treated with intravesical instillation with 50 mL sterile sodium hyalurinic acid (Hyacyst, Syner-Med, Surrey, UK) (n = 32) and sodium hyaluronate 1.6% sodium chondroitin sulphate 2% (Ialuril, Aspire Pharma, UK) (n = 33). Intravesical instillations were performed weekly in first month, every 15 days in the second month and monthly in third and fourth months, for a total of 8 doses. Patients were evaluated using a visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, cystometric bladder capacity and voided volume at the beginning and at 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. RESULTS In total, 53 patients met the study criteria. There were 30 patients in the HA-CS group (mean age: 48.47) and 23 patients in the HA group (mean age: 49.61) (p > 0.05). The initial PST was positive in 71.7% patients (38/53) overall with no difference between groups (p > 0.05). Responses for VAS, ICCS, ICPS, 24-hour frequency/nocturia statistically improved in both groups at 6 months. There was no significant difference in symptomatic improvement (p > 0.05). Eight patients had mild adverse events. CONCLUSION HA and HA/CS instillation can be effective in BPS/IC patients who do not respond to conservative treatment. An important limitation of our study is that the HA dosage of the 2 treatment arms were different. It would be more appropriate with same HA dosage in both groups; however, there was no commercially available glycosaminoglycan (GAG) substance with same HA dosage for single and combination therapy. Large, long-term randomized studies are required to determine if there is a difference between these treatments.

Diagnosis of bladder outlet obstruction in men with lower urinary tract symptoms: comparison of near infrared spectroscopy algorithm and pressure flow study in a prospective study.

OBJECTIVE To investigate the efficacy of near infrared spectroscopy (NIRS) and an algorithm on the diagnosis of bladder outlet obstruction in men with lower urinary tract symptoms (LUTS). METHODS Male patients with LUTS were recruited and underwent uroflowmetry and urodynamic pressure flow study (PFS) with simultaneous transcutaneous NIRS monitoring. Next, the postvoid residual urine volume was measured using ultrasonography. Data analysis first classified each subject as obstructed or unobstructed using the standard pressure flow data and nomogram and compared these results with the NIRS algorithm, which analyzed the pattern of change of the NIRS data plus the measurements of the postvoid residual urine volume and peak flow rate on uroflowmetry. RESULTS A total of 65 patients were enrolled in the present study. Of these patients, 10 with equivocal PFS findings and 2 with concurrent urinary tract infection were excluded. Of the 53 patients, 29 and 24 were classified as obstructed and unobstructed according to the PFS outcomes, respectively. The International Prostate Symptom Score and uroflowmetry peak flow rate demonstrated significant differences between the obstructed and unobstructed patients. The NIRS algorithm correctly identified 25 patients diagnosed as obstructed (86.2%) and 21 diagnosed as unobstructed (87.5%) according to the PFS findings. CONCLUSION The NIRS algorithm could be a noninvasive option for the diagnosis of bladder outlet obstruction in men with LUTS, with 86.2% and 87.5% sensitivity and specificity, respectively.

Effect of Type 2 Diabetes Mellitus on Prognosis of Nonmetastatic Renal Cell Cancer

Purpose We evaluated the prognostic value of type 2 diabetes mellitus (DM) in patients treated surgically for localized renal cell carcinoma (RCC). Materials and Methods Between 1995 and 2011, 588 patients with renal tumor diagnoses were treated surgically and 492 patients with pathologically confirmed nonmetastatic RCC diagnoses were included in the study. The associations of clinical and pathologic parameters with a type 2 DM diagnosis were evaluated. Kaplan-Meier estimations for disease-specific survival (DSS) and overall survival (OS) were generated according to type 2 DM diagnosis, and the log-rank test was used to compare survival according to the variables. Results The mean age of the patients was 56.7±12 years (range, 15 to 84 years; median, 58 years) and the mean length of follow-up was 35.9±28 months (range, 1 to 145 months; median, 34.3 months). Of the 492 patients, 62 (12.6%) had a diagnosis of DM at the time of surgery (group I) and 430 did not have DM (group II). The mean age and the incidence of clear cell RCC histological subtype were significantly higher in group I than in group II (p<0.001 and p=0.036, respectively). Although DSS and OS were lower in group I, this difference was not significant. Type 2 DM was not detected as an independent prognostic factor for DSS and OS. Conclusions This study investigated the role and effect of DM on the prognosis of localized RCC that was treated surgically. The present study did not detect DM as an independent prognostic factor for RCC.

Should repeated TESE be performed following a failed TESE in men with Klinefelter Syndrome

The main goal of this study was to evaluate the success rate of repeated Testicular Sperm Extraction (TESE) in Klinefelter Syndrome (KS). Eighteen patients with the diagnosis of KS who had undergone micro TESE previously were re‐evaluated between May 2007 and May 2012. Testes were measured and testicular volume was calculated by orchidometer and by scrotal ultrasonography in all patients All patients underwent repeated micro TESE. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone levels and testicular volume of the patients with and without successful sperm retrieval were compared statistically. A p value of less than 0.05 was considered statistically significant. The mean age of the patients was 30.3 years. The mean testicular volume was 2.08 and 2.1 mL for right and left testes respectively. The comparisons of serum FSH, LH, testosterone levels and testicular volume between patients with and without successful sperm retrieval did not show any significant difference. Three of the 18 patients who underwent repeated micro TESE, had successful sperm retrieval and repeated TESE failed in 15 patients. Three patients with successful sperm retrieval underwent intracytoplasmic sperm injection using retrieved testicular spermatozoa. Two embryos for each patient which were determined as healthy were transferred to the wives of the patients. Pregnancy occured in one of them and a healthy female infant was born. We conclude that consideration and hope must be given for a repeated micro TESE in patients with KS, even with a minimal chance of success.

The value of perioperative mitomycin C instillation in improving subsequent bacillus calmette-guerin instillation efficacy in intermediate and high-risk patients with non-muscle invasıve bladder cancer: a prospective randomized study

PURPOSE We evaluated the efficacy of perioperative mitomycin C (MMC) instillation to improve subsequent bacillus Calmette-Guérin (BCG) instillation efficacy in intermediate and high risk patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS From November 2004 to May 2006, 51 patients with intermediate or high risk NMIBC were enrolled in this prospective randomized trial. In group A, patients were treated with perioperative MMC (40 mg MMC in 40 mL saline was administered within 6 hours of surgery) followed by delayed (at least 15 days from surgery) BCG instillations (once a week for 6 weeks, 5 x 108 colony-forming units in 50 mL saline). Patients in group B were treated with delayed BCG instillations alone. The primary end points were recurrence-free interval and recurrence rate. RESULTS There were 25 and 26 patients in groups A and B, respectively. Median follow-up was 41.3 months (range 8 to 64) in group A and 40.9 months (range 6 to 68) in group B. Recurrence rate was 36 % (9 of 25) and 19.3 % (5 of 26) in group A and B, respectively (p = 0.052). Median time to the first recurrence was 8 months in group A and 7 months in group B (p = 0.12). CONCLUSIONS The present study showed no statistically significant difference in terms of recurrence rate and median time to first recurrence between intermediate or high-risk patients with NMIBC who were treated with early single dose instillation of MMC plus delayed BCG and those who were treated with only BCG.

Time between First and Second Transurethral Resection of Bladder Tumors in Patients with High-Grade T1 Tumors: Is It a Risk Factor for Residual Tumor Detection?

Purpose: We evaluated the risk factors for residual tumor detection after transurethral resection of bladder tumors (TURBT) in patients with newly diagnosed high-grade T1 transitional cell carcinoma of the bladder. Patients and Methods: Overall 132 patients underwent TURBT for primary bladder tumors and were diagnosed as high-grade T1 bladder cancer. Patients with incomplete resections were excluded from the study. Clinical and pathologic characteristics of the patients were compared and multivariate analysis was performed to determine independent prognostic factors. Results: Residual tumor was demonstrated in 57 (43.1%) of the patients. The residual tumor rate was significantly lower in patients with solitary tumors, tumors <3 cm in diameter, muscle presence in the initial TURBT pathologic sample and treated by an expert surgeon. In patients with solitary bladder tumors, tumors at the dome and posterior wall of the bladder exhibited higher rates of residual tumor (p < 0.0001). The time elapsed between first and second TURBT was significantly shorter in patients without residual tumor compared to patients with residual tumor at second TURBT (32.6 ± 9.1 vs. 39.3 ± 10.9 days, respectively, p = 0.001). Multivariate analysis demonstrated that time elapsed between first and second TURBT is the most important parameter for residual tumor detection. Conclusion: Our study revealed that multiple tumors, tumors >3 cm in size, absence of detrusor muscle in the initial TURBT specimen, TURBT performed by trainees and finally, as a new finding, prolonged interval between first and second TURBT are independent predictors for residual tumor detection in patients with high-grade T1 tumors.

A prospective, randomized comparative study of monopolar transurethral resection of the prostate versus photoselective vaporization of the prostate with GreenLight 120-W laser, in prostates less than 80 cc

Objective: In this study we aimed to compare photoselective vaporization (PVP) with the GreenLight 120-W Laser and monopolar transurethral resection as surgical treatments of prostates less than 80 cc in men with obstructive benign prostatic hyperplasia. Methods: From February 2009 to March 2012 we allocated 101 patients with a prostate glands of less than 80 cc; patients were randomly assigned for surgical treatment with monopolar transurethral resection of the prostate (TURP) (n = 62) or PVP (n = 39). Serum prostate specific antigen (PSA), International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), maximum flow rate (Qmax) postmicturition residual (PMR), transrectal ultrasound volumes (TRUS), postvoid urine residual (PVR), complications, re-operations and hospitalization time were collected. The patients were seen in the follow up at 6, 12 and 24 months. Results: Median age was 69 (56–87) years old in the TURP group and 67 (51–87) years old in the PVP group. Mean preoperative prostate volume was 55 cc (40–72) and 60 cc (41–75) cc in the TURP group versus the PVP group. There was no statistically difference in subjectively (IPSS, SHIM) and objectively (Qmax-PMR) parameters and postoperatively complication rates between the two groups (p > 0.05). A significant difference was observed in the PVP group with a 2 (1–4) days hospital stay compared with 5 (3–9) days for the TURP group (p < 0.001). Conclusion: Prostate PVP and TURP are effective surgical treatments for benign prostatic hyperplasia. Postoperative functional improvements were durable and equivalent in the two groups. The two techniques have a similar complication rate.

The prognostic significance of preoperative leukocytosis and neutrophil-to-lymphocyte ratio in patients who underwent radical cystectomy for bladder cancer

INTRODUCTION We evaluated the prognostic effects of hematologic parameters of preoperative leukocytosis and neutrophil-to-lymphocyte ratio (NLR) in patients who underwent radical cystectomy for bladder cancer. METHODS We retrospectively reviewed the medical records of 363 patients who underwent radical cystectomy for bladder cancer between January 1990 and June 2013. In total, 286 patients were included in the study. Age, gender, pathologic stage, lymph node involvement, preoperative hydronephrosis, histologic sub-type, surgical margin status, and lymphovascular invasion were recorded for each patient. Univariate and multivariate analysis were performed to determine the prognostic value of the preoperative clinical and laboratory parameters on disease-specific survival (DSS). Additionally, the correlation between leukocytosis and other factors were evaluated. RESULTS According to the univariate analysis preoperative leukocytosis and NLR were detected as negative prognostic factors on DSS. Preoperative leukocytosis, NLR, stage, lymph node involvement, histologic subtype, grade and age were independent prognostic factors for DSS, on multivariate analysis. Patients with leukocytosis had higher stage, grade and lymphovascular invasion. CONCLUSIONS Inexpensive, reproducible, and readily available peripheral blood count components of white blood cell count and NLR were independent prognostic factors, which can stratify DSS risks in bladder cancer patients who underwent radical cystectomy.