N. Aydin Mungan

Gender differences in stage-adjusted bladder cancer survival.

OBJECTIVES Gender differences have been observed in the prognosis of patients with bladder cancer. It has also been suggested that these differences are caused by a worse stage distribution at diagnosis among women. The purpose of this study was to evaluate whether women with bladder cancer have a worse prognosis even after adjustment for disease stage at first presentation. METHODS Data on patients with bladder cancer diagnosed between 1973 and 1996 and registered by one of the nine population-based Surveillance, Epidemiology, and End Results (SEER) cancer registries in the United States (n = 80,305) were obtained from the National Cancer Institute public domain SEER*Stat 2.0 package. Similar data on patients with bladder cancer diagnosed between 1987 and 1994 and registered by two population-based registries in the Netherlands (n = 1722) were obtained through the Comprehensive Cancer Centers, Amsterdam and South. Survival rates adjusted for mortality owing to other causes (ie, relative survival) were calculated for men and women within each category of the American Joint Committee on Cancer (SEER data) and TNM (Netherlands data) stage groupings.Results. In the United States, the 5-year relative survival rate of male patients with bladder cancer was calculated to be 79.5% (95% confidence interval 79.0% to 80.0%). Among women, the 5-year relative survival rate was significantly worse: 73.1% (95% confidence interval 72.2% to 74.0%). The male versus female 5-year survival rate among stage groups I, II, III, and IV was 96.5% versus 93.7%, 65.5% versus 59.6%, 58.8% versus 49.6%, and 27.1% versus 15.2%, respectively. The (sparser) data from the Netherlands were less conclusive. Women with Stage II and Stage IV disease fared worse than men but the reverse seemed to be true in Stage I disease. CONCLUSIONS Female patients with bladder cancer have a worse prognosis than male patients. It is unlikely that the difference can explained entirely by the more frequent diagnosis of higher stages at first presentation among women.

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10−12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.

Gender differences in stage distribution of bladder cancer

OBJECTIVES To compare stage distribution between men and women with bladder cancer at first presentation. METHODS The population-based Netherlands Cancer Registry was used to investigate stage differences of newly diagnosed bladder cancer, including upper urinary tract tumors in female and male patients. RESULTS The stage distribution at first presentation for both bladder cancer and upper urinary tract tumors was slightly worse in female patients with transitional cell carcinoma than in male patients. The stage differences were more clear in non-transitional cell carcinoma (squamous cell carcinoma, adenocarcinoma, and sarcoma) of the bladder, with female patients presenting with higher stages. Because of the large numbers, these gender differences in stage distribution were statistically significant in both TCC (P <0.0001) and non-TCC (P <0.0001). CONCLUSIONS Treating physicians should be aware that female patients are more frequently diagnosed with higher stages at the first presentation for bladder cancer and upper urinary tract tumors.

Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors

Cationic nanoparticles of chitosan (CS), poly-epsilon-caprolactone coated with chitosan (CS-PCL) and poly-epsilon-caprolactone coated with poly-L-lysine (PLL-PCL) were developed to encapsulate intravesical chemotherapeutic agent Mitomycin C (MMC) for longer residence time, higher local drug concentration and prevention of drug loss during bladder discharge. Nanoparticle diameters varied between 180 and 340 nm depending on polymer used for preparation and coating. Zeta potential values demonstrated positive charge expected from cationic nanoparticles. MMC encapsulation efficiency depended on hydrophilicity of polymers since MMC is water-soluble. Encapsulation was increased by 2-fold for CS-PCL and 3-fold for PLL-PCL as a consequence of hydrophilic coating. Complete drug release was obtained with only CS-PCL nanoparticles. On the other hand, CS and PLL-PCL nanoparticles did not completely liberate MMC due to strong polymer-drug interactions which were elucidated with DSC studies. As far as cellular interaction was concerned, CS-PCL was the most efficient formulation for uptake of fluorescent markers Nile Red and Rhodamine123 incorporated into nanoparticles. Especially, CS-PCL nanoparticles loaded with Rhodamine123 sharing hydrophilic properties with MMC were selectively incorporated by bladder cancer cell line, but not by normal bladder epithelial cells. CS-PCL nanoparticles seem to be promising for MMC delivery with respect to anticancer efficacy tested against MB49 bladder carcinoma cell line.

Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: Safety and efficacy

Mitomycin C (MMC) has shown potent efficacy against a wide spectrum of cancers and is clinical first choice in superficial bladder tumors. However, intravesical chemotherapy with MMC has been ineffective due to periodical discharge of the bladder and instability of this drug in acidic pH, both resulting in high rate of tumor recurrence and insufficiency to prevent progression. Nanocarriers may be a promising alternative for prolonged, effective and safe intravesical drug delivery due to their favorable size, surface properties and optimum interaction with mucosal layer of the bladder wall. Hence, the aim of this study was to evaluate and optimize cationic core-shell nanoparticles formulations (based on chitosan (CS) and poly-ϵ-caprolactone (PCL)) in terms of antitumor efficacy after intravesical administration in bladder tumor induced rat model. Antitumor efficacy was determined through the parameters of survival rate and nanoparticle penetration into the bladder tissue. Safety of the formulations were evaluated by histopathological evaluation of bladder tissue as well as observation of animals treated with MMC bound to nanoparticles. Results indicated that chitosan coated poly-ϵ-caprolactone (CS-PCL) nanoparticles presented the longest survival rate among all treatment groups as evaluated by Kaplan-Meier plotting. Histopathological evaluation revealed that cationic nanoparticles were localized and accumulated in the bladder tissue. As intravesical chemotherapy is a local therapy, no MMC was quantified in blood after intravesical instillation indicating no systemic uptake for the drug which could have subsequently led to side effects. In conclusion, core-shell type cationic nanoparticles may be effective tools for the intravesical chemotherapy of recurrent bladder tumors.

Prolonged retention and in vivo evaluation of cationic nanoparticles loaded with Mitomycin C designed for intravesical chemotherapy of bladder tumours

To overcome the recurrence problem in bladder tumours; nanoparticles with positive surface charge may improve interaction with biological membranes for intravesical administration. The aim of this study was to design, develop and evaluate (in vitro–in vivo) cationic nanoparticles based on chitosan, poly-L-lysine or polycaprolactone for the effective intravesical delivery of chemotherapeutic agent MMC in a rat model. Poly-L-lysine-coated polycaprolactone nanoparticles and chitosan-coated polycaprolactone nanoparticles were prepared by the double emulsion technique. Chitosan nanoparticles were prepared by ionic gelation. It was found that nanoparticle formulations of 160–320 nm in size can be produced in 14–35% encapsulation efficiency. Variability in the particle size of nanoparticles depended on the preparation method. Encapsulation was increased by two-fold for CS–PCL as a result of the double emulsion technique. Commercial MMC product in solution form and cationic nanoparticle formulations were compared for in vivo bladder retention properties and effect of formulations on urine volume.

Nocturnal enuresis and allergy

Objective To investigate whether an interaction exists between nocturnal enuresis and allergy. Material and methods Thirty-seven (20 boys, 17 girls) children with monosymptomatic nocturnal enuresis were recruited. We studied an allergy panel that included total IgE, 10 examples of inhalant-specific IgE, 10 examples of food-specific IgE, eosinophilic cationic protein (ECP) and Phadiotop. The same panel was studied in a control group of 18 children without monosymptomatic nocturnal enuresis. Results We did not determine statistically significant differences between the enuretic group and the control group in terms of levels of total IgE, the 10 examples of inhalant-specific IgE and Phadiotop. However, two (soybean and hazelnut) of the 10 food-specific IgE and ECP levels did differ significantly between the two groups. Conclusions This first specific IgE study showed that there may be a relationship between nocturnal enuresis and soybean and hazelnut food allergens. Our findings may explain some cases of nocturnal enuresis. However, further studies are necessary to explain the underlying mechanisms and management of this disorder.

Values for free/total prostate-specific antigen ratio as a function of age: necessity of reference validation in a Turkish population.

Abstract Background: The aim of this study was to evaluate age-related changes in free/total prostate-specific antigen (f/t PSA) ratio, focusing on the avoidance of unnecessary prostate biopsies. Methods: A total of 898 men aged 30–88 years without a history of prostate surgery and disease were enrolled into the study. Serum tPSA, fPSA and f/t PSA ratios were determined for the study population and for different age categories. All males who had suspicious digital rectal examination and tPSA >4 ng/mL underwent transrectal ultrasonography-guided prostate biopsy. Receiver operating characteristic (ROC) curves for each group were generated by plotting the sensitivity vs. 1–specificity for the f/t PSA ratio. The sensitivity and specificity were obtained using different f/t PSA ratio cutoffs for different age groups. Results: Prostate cancer was detected in 63 patients (7%). Age-specific cutoffs were determined according to likelihood ratios at the levels of 10%, 15% and 15% f/t PSA ratio for ages 50–59, 60–69 and ≥70 years, respectively. However, a single cutoff of 10% is recommended across all age ranges (positive likelihood ratio 2.36). ROC curves demonstrated that the area under the curve (AUC) was significant for all patients with initial PSA of 4–10 ng/mL (AUC 0.703–0.796), except for the ≥70-year age group (AUC 0.549). Conclusions: The current study showed that the use of f/t PSA ratio in patients with PSA levels of 4–10 ng/mL should enhance the specificity of PSA screening and decrease the number of unnecessary biopsies. f/t PSA levels may show dissimilarities according to age and ethnicity, so further studies are warranted to identify this relationship. Clin Chem Lab Med 2007;45:912–6.

Garlic supplemented diet attenuates gentamicin nephrotoxicity ın rats

PURPOSE To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. MATERIALS AND METHODS Twenty four healthy male Wistar rats, weighing between 220 - 260 grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. RESULTS The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). CONCLUSIONS In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples.

Unusual Sonographic Appearance of Scrotal Calculi Without Hydrocele

Scrotal calculi are rare benign lesions of the scrotum. Scrotal calculi associated with hydrocele are occasionally reported, but to the best of the authors’ knowledge, scrotal calculi without hydrocele have not been previously reported. In this study, three cases of scrotal calculi without hydrocele are presented.