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Background:To evaluate whether genotyping for 18 prostate cancer founder variants is helpful in identifying high-risk individuals and for determining optimal screening regimens.Methods:A serum PSA level was measured and a digital rectal examination (DRE) was performed on 2907 unaffected men aged 40-90. Three hundred and twenty-three men with an elevated PSA (4 ng ml−1) or an abnormal DRE underwent a prostate biopsy. All men were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA and C61G), for four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395 and I157T), for one allele in NBS1 (657del5), for one allele in HOXB13 (G84E), and for nine low-risk single-nucleotide polymorphisms (SNPs).Results:On the basis of an elevated PSA or an abnormal DRE, prostate cancer was diagnosed in 135 of 2907 men (4.6%). In men with a CHEK2 missense mutation I157T, the cancer detection rate among men with an elevated PSA or an abnormal DRE was much higher (10.2%, P=0.0008). The cancer detection rate rose with the number of SNP risk genotypes observed from 1.2% for men with no variant to 8.6% for men who carried six or more variants (P=0.04). No single variant was helpful on its own in predicting the presence of prostate cancer, however, the combination of all rare mutations and SNPs improved predictive power (area under the curve=0.59; P=0.03).Conclusion:These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal. [ABSTRACT FROM AUTHOR]

Urolithiasis is a well-known disease. Stones can form in all parts of the urinary tract. Diagnosis and treatment usually do not create clinical problems. However from time to time in daily practice doctors are confronted with casuistic cases. Here, we report a 54-year-old man with a large stone localized to the urethra. Because of the size of the stone, confirmed on radiography, and the presence of a cutaneous fistula, open surgery was performed. Due to urethral stricture, the patient required a second stage of reconstructive surgery. This case emphasizes that unusual presentation of urolithiasis may occur, and different surgical approaches as well as other surgical manipulations in such cases must be considered.

Vitamin D affects bone metabolism and calcium-phosphate metabolism. Its deficiency leads to bone mineralization disorders and is the cause of abnormal skeletal development from fetal life to the period of completed skeletal growth. In later periods of life, vitamin D deficiency leads to bone metabolism disorders, i.e., osteoporosis. Disturbance of the balance between osteoblasts responsible for bone formation and osteoclasts associated with bone resorption results in reduced bone mass and bone weakening, and consequently leads to susceptibility to fractures. Analysis of genetic variants of the vitamin D receptor ( VDR ) concerns their relationship with metabolic bone diseases, and the results of previous studies assessing the relationship of polymorphisms with bone mineral density, fracture risk, or osteoporosis are not clear. Therefore, the aim of our study was to determine the effect of rs1544410 and rs11568820 polymorphisms of the VDR gene on the risk of developing osteoporosis in the Polish population. The study included 197 women with osteoporosis, 98 women with osteopenia, and 147 healthy controls. The real-time PCR method was used to determine the rs1544410 and rs11568820 polymorphisms of the VDR1 gene. Analysis of the results in the group with osteopenia showed that for the rs1544410 polymorphism, heterozygous GA genotypes occurred in 37.8% of the study group and 47.6% of the controls (OR = 0.60; 95%CI: 0.34-1.05), and homozygous AA in 15.3% of the study group and 17.0% of the controls (OR = 0.68; 95%CI: 0.32-1.44) ( p = 0.185, AIC = 332.4; AIC-Akaike information criterion). The best model for this variant turned out to be the dominant model OR = 0.62; 95%CI: 0.37-1.04; p = 0.071, AIC = 330.5. In the case of the rs11568820 polymorphism of the VDR gene, the GG genotype was more common in women with osteopenia compared to controls (75.5% vs. 70.1%). Genotypes containing at least one mutant A allele were present in 24.5% of women with osteopenia and 29.9% of controls (OR = 0.76; 95%CI: 0.43-1.36; p = 0.349; AIC = 332.9). Analyzing the rs1544410 polymorphism in women with osteoporosis, the GA genotype was present in 42.1% of the study group and 47.6% of patients with normal bone density (OR = 0.74; 95%CI: 0.46-1.19), and the AA genotype in 15.7% of the study group and 17.0% of controls (OR = 0.78; 95%CI: 0.41-1.46) ( p = 0.441). In the case of the rs11568820 polymorphism, the GA genotype occurred in 22.3% of the study subjects and 27.2% of the control patients (OR = 0.76; 95%CI: 0.46-1.25), and the AA genotype in 2.0% of the study subjects and 2.7% of the controls (OR = 0.69; 95%CI: 0.17-2.83) ( p = 0.511). For both variants, the model with the lowest AIC value was the dominant model, in which for the rs1544410 variant OR = 0.75; 95%CI: 0.48-1.17; p = 0.203; AIC = 472.0 was obtained, while for rs11568820-OR = 0.75; 95%CI: 0.47-1.22; p = 0.250; AIC = 472.3. The obtained results indicate that the rs1544410 and rs11568820 polymorphisms of the VDR gene do not affect the development of osteoporosis in the Polish population.

The aim of the project was to evaluate the association between selenium (Se) and zinc (Zn) levels in blood and serum and kidney cancer mortality. In a prospective group of 284 consecutive, unselected patients with kidney cancer, we evaluated their 10-year survival rate in relation to the levels of Se and Zn in their blood and serum. Micronutrient levels were measured using an inductively coupled plasma mass spectrometer. Patients were divided into quartiles based on the distribution of Se and Zn levels arranged in increasing order. The following variables were taken into account in the multivariable models: age at diagnosis, gender, smoking, type of surgery and histopathological examination results. We observed a statistically significant association of all-cause mortality when subgroups with low blood selenium levels were compared to patients with high selenium levels (HR = 7.74; p < 0.001). We found, in addition, that this correlation was much stronger when only men were assessed (HR = 11.6; p < 0.001). We did not find a statistically significant association for zinc alone. When we combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV), we observed the hazard ratio for kidney cancer death to be 12.4; p = 0.016. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR was 2.53; p = 0.008. Our study suggests that selenium levels, combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV) and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients.

Introduction: The role of PALB2 in carcinogenesis remains to be clarified. Our main goal was to determine the prevalence of PALB2 (509&#95;510delGA and 172&#95;175delTTGT) mutations in bladder and kidney cancer patients from Polish population., Materials and Methods: 1413 patients with bladder and 810 cases with kidney cancer and 4702 controls were genotyped for two PALB2 variants: 509&#95;510delGA and 172&#95;175delTTGT., Results: Two mutations of PALB2 gene were detected in 5 of 1413 (0.35%) unselected bladder cases and in 10 of 4702 controls (odds ratio [OR], 1.7; 95% CI 0.56-4.88; p = 0.52). Among 810 unselected kidney cancer cases two PALB2 mutations were reported in two patients (0,24%) (odds ratio [OR], (OR = 1.2; 95% CI 0.25-5.13; p = 0.84). In cases with mutations in PALB2 gene cancer family history was negative., Conclusion: We found no difference in the prevalence of recurrent PALB2 mutations between cases and healthy controls. The mutations in PALB2 gene seem not to play a major role in bladder and kidney cancer development in Polish patients.

Introduction: Determining the clinical stage of bladder carcinoma before radical cystectomy is characterized by a high inaccuracy rate. The discrepancy in some reports reaches up to 48%. Therefore intraoperative clinical staging of bladder carcinoma is not recommended before radical treatment as it is for prostate cancer. However, the accuracy of clinical assessment of the muscle invasive character of the tumors at the time of transurethral resection has not been studied. In our study we estimate the accuracy of clinical staging during endoscopic treatment., Material and Methods: 332 patients who had undergone transurethral resection of bladder cancer were studied in this retrospective analysis. Data such as age, gender, presence of hydronephrosis, operator, the results of bimanual bladder examination, TURB report and pathologic report, were collected from each patient. Intraoperative prediction of the muscle invasive nature of the tumor was compared with pathological reports. A logistic regression analysis was used to evaluate the influence of particular variables on upstaging and downstaging., Results: Overall accuracy between clinical and histopathology staging was 87.8%. Discrepancy was observed only in 36 patients. Patients with pTa stage were the most numerous group among patients with accurate prediction of the muscle invasiveness character of the tumor. Univariable logistic regression indicated that the presence of a palpable mass in the bimanual examination was a predictor of upstaging, with an OR 11.75 CI95% [2.49-55.32]., Conclusions: The study indicated the high accuracy between clinical and pathological reports. Intraoperative evaluation of tumor character should be an indispensable part of treatment, which can be useful for planning in advance the further stages of treatment., Competing Interests: The authors declare no conflicts of interest.

Background: Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet., Methods: To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls., Results: Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases., Conclusions: BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland., (© 2013 Elsevier B.V. All rights reserved.)