The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case-control study.

PURPOSE: We investigated the relationship between the distribution of the IL-1RN, TNF-ß and IL-4 polymorphism and the clinical features of bladder cancer. MATERIALS AND METHODS: A total of 100 patients with bladder carcinoma and 102 healthy control subjects were enrolled in the study. The IL-1RN, IL-4 and TNF-ß gene polymorphisms were identified by PCR restriction fragment length polymorphism-based analysis. Allelic frequencies were compared between patient and the controls. Tumor stage, histopathological grade, tumor size/number and smoking condition were evaluated with IL-1RN, IL-4 and TNF-ß gene polymorphisms. RESULTS: Allele distribution frequencies of IL-1RN and IL-4 gene polymorphisms were significantly different between patients and control groups. However, allele distribution of TNF-ß gene was not statistically significant. There was no difference in allele distribution of the three genes in both groups regarding stage, tumor size, number of tumors and smoking condition. Although allele distribution of IL-4 gene showed significant difference considering histopathological grades in both smoking and total patients group, allele distribution of IL-1RN and TNF-ß was not different. CONCLUSION: The present research suggests that the IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer. In the future, clinical improvements on diagnosis, treatment and prognosis of bladder carcinoma are expected owing to development of more sensitive and specific tests for genetic polymorphisms of cytokines that are effective on inflammation.

Effect of seminal plasma calcitonin levels on sperm mobility.

This study investigated the effect of the seminal and blood plasma calcitonin levels on the sperm motility in idiopathic infertile patients. The number of sperm cells and their motility were evaluated in the spermiograms of 52 idiopathic infertile patients. The levels of seminal plasma calcitonin were studied with double antibody technique using a DPC kit. Fifty-two patients were divided into 2 groups according to the motility rates of sperm and 20 healthy volunteers were assigned to a control group. The difference between the groups was evaluated by using Kruskall-Wallis and Mann-Whitney U tests, and the correlation of seminal and blood calcitonin levels with sperm motility were determined. The difference in motility rates between the 3 groups was statistically significant (p = .000, p < .05). Blood plasma calcitonin levels were in normal ranges in all cases and no significant difference was found among the 3 groups (chi2 = 2.7219, p = .2589, p > .05). While sperm motility was correlated with seminal calcitonin levels (r = .8581), blood calcitonin levels did not show a correlation with sperm motility rate (r = -.0265). Moreover, there was no correlation between seminal and blood plasma levels of calcitonin (r = -.0010). Motility rates decreased in the patients with low seminal calcitonin levels and seminal calcitonin levels had a significant effect on sperm motility.

Urinary bladder cancer test: a new urinary tumor marker in the follow-up of superficial bladder cancer.

OBJECTIVES: To study the diagnostic performance of the Urinary Bladder Cancer (UBC) test in patients with superficial bladder carcinoma. METHODS: One hundred one patients in follow-up for superficial bladder cancer (pTa, pT1, carcinoma in situ) were recruited for this study. Each patient underwent cystoscopy and transurethral resection or biopsy, with subsequent histologic confirmation in the case of abnormalities. In addition, specimens were assessed with an immunoenzymometric assay for cytokeratin expression (the UBC test), and the urinary creatinine concentration was determined to correct for different degrees of urinary dilution. Different methods were applied to calculate the diagnostic value of the UBC test. RESULTS: Both noncorrected and corrected median values of the UBC test were comparable between patients with and without a recurrent bladder tumor. The overall sensitivity, specificity, and positive and negative predictive values of the noncorrected UBC test was 20.7%, 84.7%, 35.3%, and 72.6%, respectively. For the corrected UBC test, the corresponding values were 20.7%, 79.2%, 28.6%, and 71.3%. The area under the receiver operating characteristic curve was not significantly different from 0.50, indicating no diagnostic value of the UBC test in this study. CONCLUSIONS: The diagnostic value of this new urinary marker appears insufficient for the follow-up of patients with superficial bladder cancer.

A germline homozygote deletion of the glutathione-S-transferase Mu1 gene predisposes to bladder cancer.

INTRODUCTION AND OBJECTIVES: Numerous studies have shown smoking and specific occupational exposures to be risk factors for bladder cancer. The risk of bladder cancer may be modified by the activity of carcinogen metabolizing enzymes. The glutathione-S-transferase Mu1 enzyme (GSTM1) detoxifies arylepoxides which are formed after exposure to certain polycyclic aromatic hydrocarbons and possibly aromatic amines. Approximately 40% of Caucasians lack GSTM1 activity due to a homozygous deletion of the GSTM1 locus on chromosome 1p13 (GSTM1 0/0 genotype). The aim of this study was to evaluate the combined effect of smoking and GSTM1 genotype on the risk of bladder cancer. MATERIALS AND METHODS: Sixty-one patients with transitional cell carcinoma of the bladder and 69 controls matched for age and sex were enrolled from the outpatient clinic. Lifestyle information was collected with a standardized questionnaire. DNA was extracted from white blood cells. The GSTM1 genotype was determined by a PCR-based method. RESULTS: 92% of the 61 patients had a history of smoking compared with 81% of the controls. There was a significant dose-response relationship for pack-years of smoking (trend test: p = 0.003). The proportion of GSTM1 0/0 genotype among patients was 62% compared with 43% among controls (odds ratio = 2.1; 95% CI 1.1-4. 3). The expected interaction between smoking and GSTM1 genotype was not observed. CONCLUSIONS: This study confirms the findings that a germline homozygous deletion of the GSTM1 gene predisposes to bladder cancer. An interaction with smoking was not found.

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.

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.

Can sensitivity of voided urinary cytology or bladder wash cytology be improved by the use of different urinary portions?

OBJECTIVE: To improve sensitivity by using different portions of voided urine cytology (VUC) and bladder wash material cytology (BWC). MATERIALS AND METHODS: 52 patients with biopsy-proven superficial transitional cell carcinoma (TCC) of the bladder were studied. Voided urine specimens were divided into a first stream, mid-stream and terminal stream. Bladder wash material was also divided into a first portion, mid-portion and last portion. All portions were investigated for cytology abnormalities. RESULTS: Sensitivity for the detection of malignant cells was 34.6, 38.5 and 38.5% for the first, mid- and terminal stream of VUC and 34.6, 38.5 and 34.6% for the first, mid- and last portion of BWC, respectively. The sensitivity of VUC was 20-25% for grade I, 30-40% for grade II, and 50-75% for grade III tumors, respectively. The sensitivity of BWC was 25% for grade I, 35-45% for grade II, and 33-50% for grade III tumors, respectively. There was no statistical significant difference for sensitivities between either grades (p = 0.06) or portions or streams (p = 0.3) of VUC and BWC. CONCLUSIONS: In this small group of patients, we did not find any significant difference, but we found highest sensitivity in grade III tumors with the terminal portion of the voided urine when compared to other portions of VUC. Therefore, we believe that further study in a large series is necessary to investigate this approach of differentiated BWC and especially VUC.

Bladder cancer in women.

Bladder cancer is seen mainly in men. The incidence in women is increasing, but is still approximately three to four times lower than in men. In particular transitional cell cancers seem relatively more common in men then in women (ratio 4:1), but non-transitional cell cancer is also more frequent in men (ratio 2.7: 1). As for men, smoking is the most important known factor for bladder cancer in women. Coffee-drinking also showed a weak correlation, the odds ratio being found to be twice as high for women (5.2) as for men (2.6). It was estimated that the percentage of bladder cancers attributed to occupational exposure in the United States is 11% in women, compared to 21% in men. Urinary tract infections are related to bladder cancer. The role of human papilloma virus infections, important in cervical cancer, is unclear in bladder cancer development. Surprisingly, bladder cancer is more often of a higher stage at initial diagnosis in women. With current tumor markers no explanation for the different prognosis in men and women can be postulated. The treatment of superficial bladder cancer tumors is similar for men and women. In recent years orthotopic bladder replacement has improved quality of life after cystectomy in invasive disease.

Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer.

PURPOSE: We study toxicity and efficacy of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or high risk superficial bladder cancer compared to the use of intravesical mitomycin C alone. MATERIALS AND METHODS: Patients with intermediate and high risk papillary superficial bladder cancer and carcinoma in situ were randomized after transurethral resection between 4 weekly instillations with 40 mg. mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or 10 weekly instillations with mitomycin C (group 2, 92 patients). RESULTS: The frequency of bacterial and chemical cystitis, and other local side effects was similar in both groups. Allergic reactions, including skin rash, were more frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p = 0.08), and other systemic side effects were more frequent in the sequential group (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of 92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70) were similar in both groups. CONCLUSIONS: We did not find any major differences in toxicity or treatment efficacy with intravesical mitomycin C and the sequential use of BCG or mitomycin C for intermediate and high risk superficial papillary bladder cancer.

Bacille Calmette-Guérin in superficial transitional cell carcinoma.

The mechanisms by which BCG exerts its antitumour activity remain unclear. Attachment of BCG to the bladder via FN has been shown to be an important step in initiating its antitumorigenic activity. The mechanism(s) by which BCG operates requires LAK cells, BCG-activated killer cells, T lymphocytes (CD4) helper cells and CD8 suppressor/cytotoxic cells) and monocytes. The optimal route of administration is intravesical. The efficacy of a BCG vaccine depends on the viability, dose and strain. Differences in efficacy and side-effects have not been shown between different strains. Low-dose regimens successfully protect from recurrences, with fewer side-effects. The initial schedule of BCG is a course of six instillations in 6 weeks; when the patient fails this course, two possibilities arise. The first is maintenance therapy; response rates improve but there is more local and systemic toxicity. The second is a further 6-week course, and this seems most useful in those with a sustained response to the initial treatment. The clinical response to BCG therapy can be monitored using cytokine measurements or p53 determinations. Toxicity remains a major problem in BCG treatment and triple antituberculosis combination therapy should be given for 3 months in those with severe systemic side-effects. The use of prophylactic isoniazid is not recommend to decrease side-effects. The clinical results of BCG have been good, with success rates of 58-100%, with a minimal follow-up of one year in prophylaxis. BCG seems superior to intravesical therapy, but at the cost of inducing more adverse effects. BCG is not indicated for low- and intermediate-risk patients, in whom chemotherapy is the first choice. BCG can also be used to eliminate tumour after an incomplete TUR, or in patients who are unfit for surgery, with a 60-70% success rate. The primary and best treatment for CIS is intravesical BCG; encouraging results have been reported, with success rate of 42-83% after a minimal follow-up of one year. Although currently BCG seems to be the choice for high-risk superficial TCC, many questions remain unanswered, especially about the mechanism(s) of action, the optimal dose and clinical schedule.

Transurethral resection of the prostate and laser prostatectomy under local anesthesia.

OBJECTIVE: To perform transurethal resection of the prostate (TURP) and transurethral laser ablation prostatectomy (TULAP) under appropriate local anesthesia. PATIENTS AND METHODS: A total of 54 patients were examined in this study. We carried out TURP in 42 and TULAP in 12 of them under local anesthesia with lignocaine chloride. Patient's discomfort was recorded by means of a four-point descriptive pain scale. RESULTS: We had perfect pain control in the majority of the patients. Patient's acceptance was very high. No patient required conversion to general anesthesia. Complications due to local anesthesia were not observed. CONCLUSION: We believe that ours is a simple, safe and effective procedure.

Chlamydial infections and male infertility.

Chlamydial infections may be difficult to diagnose due to the silent symptoms and difficulty in culturing. An infectious process may impair fertility by adversely affecting sperm functions, resulting in testicular damage or causing obstruction of the genital tract. In our study, we tried to find Chlamydial antigen by using EIA (Enzyme Immune Assay) and to compare the Ag(+) and Ag(-) groups according to semen parameters. Except for semen volume, we found significant differences in density, morphology, motility and viability (intervolume p > 0.05, interdensity p < 0.01, intermorphology p < 0.001, intermotility p < 0.001 and interviability p < 0.001).