Scandinavian journal of urology and nephrology. Supplementum最新文献

A major challenge for molecular diagnosis of bladder cancer is the subdivision of tumors beyond histological classifications into clinical relevant molecular subgroups. The evolution of molecular high-throughput techniques assessing a large number of molecular features at the same time has made comprehensive investigation of these subgroups possible. Molecular signatures for disease stage, grade, progression, carcinoma in situ, presence of metastases, and treatment response have been reported. Some of these molecular signatures are now being tested in multicenter studies with the purpose of introducing these into the clinic, for planning of follow-up and treatment selection. In this review, we define the clinical relevant subgroups and give an overview of recent advances in marker identification in the field of non-muscle invasive and invasive bladder cancer. Furthermore, we stress the methods and materials needed to translate such molecular profiles into clinically useful tests.

Bladder cancer is a major health concern for older males in Western populations. About 30 years ago there was a suggestion that nutrition may have a role in the aetiology of the disease. Although the literature has been accumulating since then, owing to heterogeneity between studies results have often been inconsistent and unclear. The aim of this paper was to present an updated summary of the scientific evidence on the association between nutrition, total fluid intake and bladder cancer. A search of computerized databases, PubMed, ISI, Embase and Cochrane Library, was conducted to identify all epidemiological studies published between 1966 and October 2007. The level of scientific evidence for the various nutritional factors and total fluid intake was ranked according to the number of studies reporting a statistically significant association and the existence of mechanistic evidence. The levels of association were based on a ranking of statistically significant relative risks. Fruit and yellow-orange vegetables, particularly carrots and selenium, are probably associated with a moderately reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were also identified as having a possible protective effect. Possible risk factors are salted and barbecued meat, pork, total fat, pickled vegetables, salt, soy products, spices and artificial sweeteners. No clear association could be determined for beef, eggs, processed meats and total fluid intake. In conclusion, specific fruit and vegetables may act to reduce the risk of bladder cancer. Future studies on bladder cancer should investigate the effect of food categorization, amount and gender.

To date, many epidemiological studies have been conducted to examine the association between occupation and bladder cancer incidence. However, results from these studies often have been inconsistent, and significant associations have rarely been found, possibly owing to the lack of adequate statistical power in these studies. This meta-analysis summarizes the relevant literature regarding occupation and bladder cancer incidence to increase the statistical power to detect associations. The Medline and Embase databases were searched to retrieve epidemiological studies published up until May 2008. Individual risk estimates for subjects with an employment history in the occupation of interest were extracted from each included publication. For each occupation, a summary relative risk (SRR) was calculated by means of a random effects model. Significantly increased risks with an SRR greater than 1.20 were identified for miners [SRR=1.31, 95% confidence interval (CI) 1.09-1.57], bus drivers (SRR=1.29, 95% CI 1.08-1.53), rubber workers (SRR=1.29, 95% CI 1.06-1.58), motor mechanics (SRR=1.27, 95% CI 1.10-1.46), leather workers (SRR=1.27, 95% CI 1.07-1.49), blacksmiths (SRR=1.27, 95% CI 1.02-1.58), machine setters (SRR=1.24, 95% CI 1.09-1.42), hairdressers (SRR=1.23, 95% CI 1.11-1.37) and mechanics (SRR=1.21, 95% CI 1.12-1.31). In conclusion, the studies reviewed provide consistent support for a small but significant increased risk of bladder cancer among workers in these nine occupations. Although the relative risk of bladder cancer associated with these occupations is small, the public health impact may be significant, considering the substantial number of people who were and are employed in these occupations.

Patients with non-muscle-invasive bladder cancer are treated by transurethral resection. About 60-70% of these patients will develop recurrences and in 11% of these cases progression to a muscle-invasive tumour occurs. Surveillance of patients by cystoscopy is therefore carried out every 3-4 months in the first 2 years and yearly thereafter. Several biomarkers have been developed that potentially can detect recurrent bladder cancer in voided urine samples and may present an alternative for the invasive cystoscopy procedure. Recently, van Rhijn reviewed the performance of several of these biomarkers regarding detection of recurrent disease in patients under surveillance. In general, sensitivities were much lower when only patients under surveillance were taken into account than when the patient cohorts included patients with primary disease or patients with high-grade tumours. In this article recent new data on those markers that displayed a sensitivity and specificity of at least 70% as mentioned in the review by van Rhijn are reviewed. The literature selected was limited to those papers in which the performance of makers was assayed only on urine samples of patients under surveillance. The markers with sensitivity and specificity over 70% that were selected from the previous study are Lewis X, NMP22, microsatellite analysis (MA), CYFRA 21.1, cytokeratin 20 and the UroVysion fluorescence in situ hybridization (FISH) test. Recent new developments such as the use of FGFR3 mutation analysis and methylation detection are also discussed. In conclusion, tests such as the UroVysion FISH test and MA are able to detect most concomitant recurrences and to predict recurrent disease. In general, lesions that are missed are pTa and low grade. With MA several upper tract recurrences were identified that were missed by cystoscopy. The value of the most promising urine tests needs to be established in longitudinal studies and exclusively on patients under surveillance for recurrent disease. A longitudinal setting allows subsequent urine samples to be tested and this increases sensitivity because a negative test outcome sometimes occurs between positive ones. Stratification of patients according to the genetic status of their primary tumours and smoking habits should be investigated. Decision models should be developed that recommend at which points in time cystoscopy or urine testing should be performed.

The use of molecular markers and gene expression profiling provides a promising approach for improving the predictive accuracy of current prognostic indices for predicting which patients with non-muscle-invasive bladder cancer will progress to muscle-invasive disease. There are many statistical pitfalls in establishing the benefit of a multigene expression classifier during its development. First, there are issues related to the identification of the individual genes and the false discovery rate, the instability of the genes identified and their combination into a classifier. Secondly, the classifier should be validated, preferably on an independent data set, to show its reproducibility. Next, it is necessary to show that adding the classifier to an existing model based on the most important clinical and pathological factors improves the predictive accuracy of the model. This cannot be determined based on the classifier's hazard ratio or p-value in a multivariate model, but should be assessed based on an improvement in statistics such as the area under the curve and the concordance index. Finally, nomograms are superior to stage and risk group classifications for predicting outcome, but the model predicting the outcome must be well calibrated. It is important for investigators to be aware of these pitfalls in order to develop statistically valid classifiers that will truly improve our ability to predict a patient's risk of progression.

Bladder tumours represent a heterogeneous group of cancers. The natural history of these bladder cancers is that of recurrence of disease and progression to higher grade and stage disease. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumour characteristics, mainly tumour grade and stage. The most recent World Health Organization (WHO) classification of tumours of the urinary system includes urothelial flat lesions: flat hyperplasia, dysplasia and carcinoma in situ. The papillary lesions are broadly subdivided into benign (papilloma and inverted papilloma), papillary urothelial neoplasia of low malignant potential (PUNLMP) and non-invasive papillary carcinoma (low or high grade). The initial proposal of the 2004 WHO has been achieved, with most reports supporting that categories are better defined than in previous classifications. An additional important issue is that PUNLMP, the most controversial proposal of the WHO in 2004, has lower malignant behaviour than low-grade carcinoma. Whether PUNLMP remains a clinically useful category, or whether this category should be expanded to include all low-grade, stage Ta lesions (PUNLMP and low-grade papillary carcinoma) as a wider category of less aggressive tumours not labelled as cancer, needs to be discussed in the near future. This article summarizes the recent literature concerning important issues in the pathology and the clinical management of patients with bladder urothelial carcinoma. Emphasis is placed on clinical presentation, the significance of haematuria, macroscopic appearance (papillary, solid or mixed, single or multiple) and synchronous or metachronous presentation (field disease vs monoclonal disease with seeding), classification and microscopic variations of bladder cancer with clinical significance, TNM distribution and the pathological grading according to the 2004 WHO proposal.