Scandinavian journal of urology and nephrology. Supplementum最新文献

Epidemiological studies on coffee, alcohol and bladder cancer risk published up to 2007 were reviewed. Coffee drinkers have a moderately higher relative risk of bladder cancer compared to non-drinkers. The association may partly be due to residual confounding by smoking or dietary factors, but the interpretation remains open to discussion, although the absence of dose and duration-risk relations weighs against the presence of a causal association. Most studies of alcohol and bladder cancer found no association, with some studies finding a direct and other an inverse one. This again may be due to differential confounding effect of tobacco smoking--the major risk factor for bladder cancer--in various populations. Thus, epidemiological findings on the relation between alcohol drinking and bladder cancer exclude any meaningful association.

This article reviews the literature regarding the possible correlation between infection and occurrence of bladder cancer. The PubMed literature database was searched from inception to January 2008. Keywords of bladder, cancer, parasitic, bacterial, viral and infection, were used. Forty studies were included in the review. Several investigators support the idea that schistosomiasis is aetiologically related to the development of bladder cancer in individuals infected with Schistosoma haematobium. Approximately 70% of those with chronic schistosomiasis who have bladder cancer develop squamous cell rather than transitional cell carcinoma. Several investigators suggest that bacteria may play a role in inducing bladder cancer. Clinically, researchers have linked the development of infection, urinary stones and indwelling catheters with bladder cancer. Nevertheless, to date, no prospective study has examined the association between urinary tract infection and bladder cancer risk. The possibility that infection by human papilloma virus (HPV) is a risk factor contributing to bladder cancer has been investigated but no definite conclusions have been drawn. Thus, the debate remains open as to whether there is any direct link between chronic HPV infection and bladder cancer. Only 15 cases of vesical carcinoma have been reported, to date, in the setting of human immunodeficiency virus (HIV). The rare occurrence of bladder cancer during HIV infection and the lack of correlation with the laboratory markers of HIV disease progression may suggest a trivial association between two unrelated disorders. BK virus is oncogenic in newborn hamsters and can transfer to mammalian cells in vitro, but there is little consistent evidence of a link with human bladder cancer. Studies showed no correlation between herpes simplex virus (HSV) and bladder cancer, but bladder cancer becomes infected with HSV much more easily than non-neoplastic urothelium. In conclusion, with the exception of chronic infection with S. haematobium, the association between the occurrence of bladder cancer and chronic bacterial or viral infections could not be confirmed. Prospective studies with large numbers of patients and controls are required to confirm this issue.

Bladder tumours comprise a heterogeneous group with respect to both histopathology and clinical behaviour. Although many features of bladder tumours have been studied, assessment of risk for recurrence and progression to invasive disease is not precise and response to specific therapies cannot be predicted accurately. It is anticipated that a thorough knowledge of the molecular alterations that are involved in the development and progression of bladder cancer will lead to greater predictive power and the application of novel individualized therapies. This review summarizes the current state of knowledge of genomic alterations found in transitional cell carcinoma and putative precursor lesions.

The current World Health Organization (WHO) 2004 classification of urothelial neoplasms was based on an attempt to reconcile molecular-genetic and pathology findings. This article provides an overview of the more recent molecular-genetic findings in the field and critically appraises their relationship with each of the WHO 2004 disease categories. Most of the WHO 2004 categories were successfully distinguished by means of expression and genome profiling and by distinct genetic alterations. Regarding urothelial papilloma, clinical and limited molecular-genetic data seem to suggest that they may not represent a precursor lesion for bladder cancer. It is more likely that urothelial papilloma is a benign neoplasm sharing mutations in the fibroblast growth factor-3 gene with seborrhoeic keratosis, allegedly its epidermal counterpart. Genetic alterations in papillary urothelial neoplasia of low malignant potential are identical to those found in non-invasive low-grade papillary urothelial carcinoma, implying that they are within a spectrum of the same neoplasm. Expression profiling data corroborate the view that (secondary) carcinoma in situ may act not only as a precursor lesion for invasive non-papillary urothelial carcinoma, but also as a precursor for non-muscle-invasive papillary urothelial carcinoma. Given the significant molecular genetic differences between non-invasive and invasive papillary urothelial carcinomas and their analogy with exophytic neoplastic precursor lesions in other organ systems, an alternative nomenclature is proposed, replacing papillary urothelial carcinoma with papillary intraurothelial neoplasm for the non-invasive (pTa) papillary carcinomas.

A brief overview is given of the disastrous effects of tobacco smoking on health, the environment and the economy. Obstacles for prevention are exemplified by the strong addictive property of nicotine, the ruthlessness and greed of the tobacco industry, and the ambivalence still demonstrated by the political and the health professional community in the fight against tobacco. A successful comprehensive tobacco control strategy is recognized and promoted by the first global health convention, the World Health Organization (WHO) Framework Convention on Tobacco Control. WHO has great expectations of the health community to support the implementation of the convention: who else has a greater responsibility?

The association between exposure to selected chemical carcinogens, occupations or industries and bladder cancer is well established, and it is estimated that 20-27% of bladder cancers are attributable to occupational exposures. The risk of bladder cancer stemming from an occupational exposure depends not only on compound carcinogenicity, exposure intensity and workplace characteristics, but also on individual susceptibility to these cancers. Regulatory controls in industrialized nations have resulted in a decreased burden of exposure to bladder carcinogens in the workplace. Unfortunately, the same is unlikely in many developing countries, where risky technologies may have been transferred from more developed countries, and where enforcement of regulations and worker protection are likely to be less stringent.

Bladder cancer is the fifth most commonly diagnosed non-cutaneous solid malignancy, and the second most commonly diagnosed genitourinary malignancy amongst people living in the United States, where it is estimated that more than 61,000 new cases of bladder cancer will be diagnosed in the year 2008. Approximately 90% of malignant tumors arising in the urinary bladder are of epithelial origin, the majority being transitional cell carcinomas. Early stage bladder tumors have been classified into two groups with distinct behavior and unique molecular profiles: low grade tumors (always papillary and usually superficial), and high-grade tumors (either papillary or non-papillary, and often invasive). Clinically, superficial bladder tumors (stages Ta and Tis) account for 75% to 85% of neoplasms, while the remaining 15% to 25% are invasive (T1, T2-T4) or metastatic lesions at the time of initial presentation. Studies from the author's group and others have revealed that distinct genotypic and phenotypic patterns are associated with early versus late stages of bladder cancer. Most importantly, early superficial diseases appear to segregate into two main pathways. Superficial papillary bladder tumors are characterized by gain-of-function mutations, mainly affecting classical oncogenes such as RAS and FGFR3. Deletions of chromosome 9, mainly allelic losses on the long arm (9q) are also frequent events in these tumors. Such genetic alterations are observed in most if not all superficial papillary non-invasive tumors (Ta), but only in a small subset of invasive bladder neoplasms. Flat carcinoma in situ (Tis) and invasive tumors are characterized by loss-of-function mutations, affecting the prototype tumor suppressor genes, including p53, RB and PTEN. These alterations are absent or very rare in the Ta tumors analyzed, but have been frequently identified in invasive bladder carcinomas. Based on these data, a novel model for bladder tumor progression has been proposed in which two separate genetic pathways characterize the evolution of superficial bladder neoplasms. Numerous individual molecular markers have been identified in the tissue specimens that correlate to some extent with tumor stage, and possibly with prognosis in bladder cancer. However, these molecular prognosticators do not play a role in the clinical routine management of patients with bladder tumors, mainly due to lack of large prospective validation studies. Thus, the need for development of specific tissue and serum tumor markers for prognostic stratification remains. The advent of high-throughput microarrays technologies allows comprehensive discovery of targets relevant in bladder cancer progression, which could be translated into new approaches for drug and biomarker development. Further investigation is warranted to define novel biomarkers specific for bladder cancer patients based on the molecular alterations of tumor progression, and multiplexed strategies for clinical management.