Screening for familial and hereditary prostate cancer.

Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies.

A practical approach to difficult urinary catheterizations.

Routine placement of transurethral catheters can be challenging in some situations, such as urethral strictures, severe phimosis and false passages. Intravaginal retraction of the urethral meatus can complicate Foley placement in postmenopausal females. In men, blind urethral procedures with mechanical or metal sounds without visual guidance or guidewire assistance are now discouraged due to the increased risk of urethral trauma and false passages. Newer techniques of urethral catheterization including guidewires, directed hydrophilic mechanical dilators, urethral balloon dilation, and direct vision endoscopic catheter systems are discussed, along with the new standardized protocol for difficult transurethral catheter insertions. Suprapubic catheter placement techniques, including percutaneous trocars and the use of the curved Lowsley tractor for initial suprapubic catheter insertion, are reviewed. Prevention and management of common catheter-related problems such as encrustation, leakage, Foley malposition, balloon cuffing and frequent blockages are discussed.

Calcium nephrolithiasis: effect of water hardness on urinary electrolytes.

OBJECTIVES: To analyze the impact of water hardness from public water supplies on calcium stone incidence and 24-hour urine chemistries in patients with known calcium urinary stone formation. Patients are frequently concerned that their public water supply may contribute to urinary stone disease. Investigators have documented an inverse relationship between water hardness and calcium lithogenesis. Others have found no such association. METHODS: Patients who form calcium stones (n = 4833) were identified geographically by their zip code. Water hardness information from distinct geographic public water supplies was obtained, and patient 24-hour urine chemistries were evaluated. Drinking water hardness was divided into decile rankings on the basis of the public water supply information obtained from the Environmental Protection Agency. These data were compared with patient questionnaires and 24-hour urine chemistries. The calcium and magnesium levels in the drinking water were analyzed as independent variables. RESULTS: The number of total lifetime stone episodes was similar between patients residing in areas with soft public water and hard public water. Patients consuming the softest water decile formed 3.4 lifetime stones and those who consumed the hardest water developed 3.0 lifetime stones (P = 0.0017). The 24-hour urine calcium, magnesium, and citrate levels increased directly with drinking water hardness, and no significant change was found in urinary oxalate, uric acid, pH, or volume. CONCLUSIONS: The impact of water hardness on urinary stone formation remains unclear, despite a weak correlation between water hardness and urinary calcium, magnesium, and citrate excretion. Tap water, however, can change urinary electrolytes in patients who form calcium stones.

The impact of cystinuria on renal function.

PURPOSE: Patients with cystinuria frequently have recurrent renal calculi and may subsequently require multiple stone removing procedures during their lifetime which could have an impact on overall renal function. We determined the potential impact of cystinuria and cystine stone formation on the level of renal function compared to calcium oxalate stone formers. MATERIALS AND METHODS: Clinical data on 40 cystinuric patients followed at 2 medical centers and 45 such individuals in a large stone population data base were analyzed. These results were compared to data on 3,964 calcium oxalate stone formers enrolled in this data base. RESULTS: Mean serum creatinine plus or minus standard deviation for stone forming cystinuric patients was significantly higher than that of the calcium oxalate cohort (1.13 +/- 0.28 versus 1.01 +/- 0.28 mg./100 ml., p = 0.0001). A significantly greater percentage of cystinuric patients (5.8%) had an abnormally increased serum creatinine compared to the calcium oxalate stone formers (2.2%, p = 0.046). Male gender, increasing number of open surgical stone removing procedures and nephrectomy were significant variables associated with an increased serum creatinine (p = 0.0010, p = 0.0038, p = 0.0133, respectively). An increasing number of open surgical stone removing procedures had a significant positive correlation with performance of nephrectomy in the cystinuric population (p = 0.0166). A significantly greater percentage of cystinuric patients compared to the calcium oxalate cohort were subjected to nephrectomy (14.1% versus 2.9%, p = 0.007). CONCLUSIONS: Cystinuric patients have higher serum creatinine levels than calcium oxalate stone formers and they are at more risk for renal loss. When stone removal is required, a minimally invasive approach is preferred.