Background: Transrectal ultrasound guided biopsies (TRUSp) are associated with a risk of serious infections. Recently, there has been a rise in incidence of infections after TRUSp and quinolone-resistant bacteria. The most commonly used prophylaxis is ciprofloxacin (CFLX). Objective: To document the incidence and risk factors of post-TRUSp infections and investigate the microbial resistance patterns for the patients presenting with a serious infection after TRUSp. Materials and methods: Data were collected, including age, comorbidity, previous TRUSp, number of biopsies, previously received antibiotics, time between TRUSp and hospitalization, results of microbiological cultivations, antibiotic prophylaxis, and development of infection for all patients at The University Hospital of Southern Denmark, Esbjerg who underwent TRUSp from November 2014 to November 2016. Results: In total, 590 patients were included and 37 (6.1%) patients were hospitalized with symptoms of infection. Of those 37 patients, 21 (56,8%) patients had positive microbiology (blood and/or urine), 18 (48.6%) patients were infected with E. coli and 11 (29.7%) patients had CFLX-resistant E. coli. If patients had previously received antibiotics, they had a significantly higher risk of developing infection after TRUSp (p = 0.01). Conclusion: Patients who have been exposed to antibiotics before TRUSp are at higher risk of developing serious infections as a complication to TRUSp. CFLX-resistant E. coli were a major reason for hospitalization.
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.
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.
Screening is used to detect disease earlier in its course, allow earlier treatment, and presumably decrease morbidities and potential mortality associated with the later expression of more advanced disease and presumably more complex treatments consequently required. Judicious screening in bladder cancer depends on an understanding of how the different forms of bladder cancer express their biological potential, whether the tools available for screening have sufficient sensitivity and specificity to have accurate predictive value in accurately diagnosing and assessing each cancer diathesis earlier in its course, and how this may influence the morbidities and mortality associated with each. The principles of screening, potential biases that can affect their accuracy and the interpretation of outcomes, tools currently available for screening, their efficacies and pitfalls, and lessons learned from studies of the role of screening in prostate cancer will be reviewed to offer an understanding of the potential role that screening may play in the different forms of bladder cancer in the context of their preclinical and treated natural history.
Tobacco smoking is the main known cause of urinary bladder cancer in humans. In most populations, over half of cases in men and a sizeable proportion in women are attributable to this habit. Epidemiological studies conducted in different populations have shown a linear relationship between intensity and duration of smoking and risk. Quitting smoking reduces the risk of bladder cancer. Smoking black (air-cured) cigarettes results in a higher risk than smoking blond (flue-cured) tobacco cigarettes; results on inhalation patterns and use of filter are not consistent. Cigar and pipe smoking also increases the risk of bladder cancer; data on other tobacco products are limited. The evidence for non-transitional bladder carcinoma is limited, but consistent with an increased risk. The available evidence does not point towards a different carcinogenic effect of tobacco smoking in men and women or in whites and blacks. Data on involuntary smoke and use of smokeless tobacco products are limited, but do not suggest an increased risk of bladder cancer.
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.
A few data sets have been used for assessing the risk of radiation-associated bladder cancer. The most important are the Japanese atomic bomb survivors and patients exposed to ionizing radiation for medical purposes. According to a report from the United Nations Commission on the Effect of Ionizing Radiation, there is convincing evidence of a relationship between exposure to ionizing radiation and bladder cancer. In contrast to many other malignancies it is not clear how age at exposure and gender affect the risk of bladder cancer. Furthermore, the potential interaction between smoking and radiation exposure needs to be studied in greater detail.
Several important observations emerge from this 2008 International Consultation "Bladder Cancer from Pathogenesis to Prevention". The following is a brief summary the issues that have been discussed in the articles from the meeting.
"Bladder cancer: From pathogenesis to prevention." Scandinavian Journal of Urology and Nephrology, 42(sup218), pp. 5–6
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.
Bladder cancer is an increasingly important international public health problem. As a multifactorial disease, both environmental and genetic factors are involved in its development and progression. This neoplasm is a paradigm for the participation of low-penetrance genetic variants (GSTM1-null and NAT2-slow) and provides the best established gene – environment interaction in cancer (NAT2-slow * tobacco). Genetic variants in nucleotide excision and double strand break DNA repair pathways have provided promising results, ERCC2-XPD rs238406 being the most consistent variant associated with an increased of bladder cancer risk, by itself and by interacting with tobacco. Variants in other pathways such as cell-cycle control, 1-C metabolism and inflammation have been studied, although the results are inconsistent. Three very large whole genome association studies are being undertaken using the same genotyping platform. Their results will be available soon. Genetic variants have seldom been considered as markers of prognosis or response to therapy in this tumour. The results of these studies are inconclusive. Other issues that need to be addressed are the role of genetic variants in different population subgroups – defined by ethnicity, gender and age, among others – and the association with bladder cancer subphenotypes according to clinical, pathological and molecular characteristics of the tumour. This endeavour can only be achieved by integrating multidisciplinary tools and information. Can this information be applied better to identify high-risk populations? Can the information be used to better assess prognosis or predict response to therapy? These questions require large, well-designed, multicentre studies to be conducted. Funding agencies should be aware of these needs.
The introduction of tissue microarray (TMA) methodology 10 years ago has provided a valuable tool for high-throughput genomic and proteomic analyses. Using this method hundreds of minute tissue samples can be investigated on one microscopic glass slide. Several studies demonstrated that these small tissue areas are representative for the entire tumour block and can provide reliable information on the relation of molecular markers and clinical outcome of the patient. Types of TMA used in bladder cancer research include defined clinical case series, stage-specific series (e.g. pT1), stage progression series, TMAs containing all specimens from clinical trials for specific therapies, flat (pre)neoplastic lesions, cell culture pellets and mouse model TMAs. The TMA technique has frequently been used in bladder cancer research to evaluate immunohistochemical candidate markers for prognosis and to reveal the amplification frequency of candidate oncogenes in regions with copy number alterations detected by comparative genomic hybridization and array-based methods. In addition, multimarker expression studies of several specific biological functions (e.g. apoptosis or cell-cycle proteins) or signal transduction pathways have been performed. TMAs are also used for validation of array-based gene expression studies on the protein level. TMA technology represents a crucial technique for translating new information on molecular changes in bladder cancer into clinical practice.
Bladder cancer results from complex and only partially understood host-environmental interactions. Tobacco smoking is the greatest risk factor for bladder cancer, but the actual risk to an individual reflects not only the amount of exposure to the carcinogens in tobacco smoke but also host susceptibility to these carcinogens and possibly other factors. Lifestyle may have a significant effect on the incidence of this disease. The forms of chemoprevention and their relevance to bladder cancer, the impact of lifestyle and complementary medicine, and the costs of diagnosing and treating bladder cancer are reviewed to provide a base for advances in decreasing the incidence, recurrence and costs of this disease.
First degree relatives of patients with bladder cancer have a two-fold increased risk of bladder cancer but high-risk bladder cancer families are extremely rare. There is no clear Mendelian inheritance pattern that can explain the increased familial risk. This makes classical linkage studies for the mapping of susceptibility genes impossible. The disease is probably caused by a combination of exposure to exogenous carcinogens and a large number of susceptibility genes with modest effects. Genome-wide association studies are better suited to identify these genes. Three such studies are currently underway and are expected to report their results in 2008.
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.
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?
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.
"Bladder cancer: pathogenesis." Scandinavian Journal of Urology and Nephrology, 42(sup218), pp. 93–94
Statistics on the incidence of bladder cancer are particularly hard to interpret, because of changing classification, variations in counting of multiple cancers in the same individual and, most importantly, the variable inclusion of non-invasive cancers in different data sets. Mortality statistics are almost certainly more comparable, but as indirect estimators of disease risk, require some cautious interpretation, because of differing survival between populations, and over time. Cancer of the bladder is estimated to be the ninth most common cause of cancer worldwide (357 000 cases in 2002) and the 13th most numerous cause of death from cancer (145 000 deaths). Rates in males are three to four times those in females. Incidence rates are high in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. The highest estimated mortality is in Egypt, where rates are more than three times greater than the highest rates in Europe and eight times those in the USA. In the USA, the incidence in whites is higher than in blacks. In general, in Western countries, incidence rates have been rising, but the increase has slowed or stopped in many. Mortality rates are, for the most part, decreasing. Trends are more variable in developing countries. To some extent, the geography and time trends are related to prevalence of known risk factors, especially exposure to tobacco (responsible for almost one-third of bladder cancer deaths) and, in some specific areas, schistosomiasis.
