Scandinavian journal of urology and nephrology. Supplementum最新文献

Anogenital human papillomavirus (HPV) infection is a sexually transmitted disease (STD) that typically follows a self-limiting transient course for both sexes. The HPV incidences and prevalences vary greatly, because they reflect the sexual activity of the individuals studied and of the population they are in contact with. Higher prevalences are seen in young, sexually active groups and in high-risk areas for cervical and penile cancer, e.g. in Colombia. There has also been an increasing trend with time in Western Europe, paralleling the spread of other STDs and changes in sexual behavior. Penile intraepithelial neoplasia is usually positive for high-risk HPV DNA, mostly of type 16, whereas only approximately 50% of invasive penile cancers are positive for HPV DNA. This is similar to the role of high-risk HPV in vulvar carcinoma, where the attributable proportion is also approximately 40-50%. Moreover, in both sites similar histologic types of squamous cell carcinoma, i.e. the basoloid and basaloid/warty types, are mainly associated with high-risk HPV types. The studies performed so far have indicated that HPV has an etiological role in penile cancer, although the attributable proportion may be only approximately 40-50%.

Objective: To review the epidemiology of invasive cancer of the penis based on scientific publications identified by a Medline search from 1966-2000 for the keywords penis/penile, cancer/carcinoma and risk as well as the cited references in the identified papers.

Results: Strong risk factors (OR >10) identified by case-control studies included phimosis, chronic inflammatory conditions such as balanopostitis and lichen sclerosus et atrophicus and treatment with psoralen and ultraviolet A photochemotheraphy (PUVA). A consistent association was found between penile cancer and smoking that was dose-dependent and not explained by investigated confounding factors such as sexual history. Sexual history and self-reported history of condyloma were associated with a 3-5-fold increased penile cancer risk. Cervical cancer in the wife was not consistently associated with cancer of the penis in the husband. Circumcision was associated with penile cancer risk in ecological studies. In a case-control study, circumcision neonatally, but not after the neonatal period, was associated with a 3-fold decreased risk, albeit 20% of penile cancer patients had been circumcised neonatally. In a large number of case series, human papillomavirus (HPV) DNA was identified in penile neoplastic tissue. In penile intraepithelial neoplasia, between 70 and 100% of lesions were HPV DNA positive, whereas invasive penile cancer was positive in only 40-50% of cases. A few serological case-control studies and one prospective study also identified an association between HPV type 16 and penile cancer risk. An association between penile cancer risk and HPV prevalence in the population was also suggested by ecological studies.

Conclusion: The evidence on risk factors for penile cancer suggests that preventive measures that could be considered include prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and prophylactic prevention of HPV infection.

Bladder neoplasms are common around the world. Incidences are particularly high in the Nile River Valley secondary to schistosomiasis, which is frequently associated with the development of squamous cell carcinoma similar to that of other chronic inflammatory processes of the lower urinary tract. However, elsewhere, most bladder tumors are of the urothelial (transitional) cell type. There is a marked male predominance and there are extensive racial differences. It is predominantly a neoplasm that occurs in patients aged >50 years. Urothelial carcinomas comprise two distinct diseases both biologically and molecularly: a low-grade papillary tumor which frequently recurs; and a high-grade malignancy which can present as dysplasia or carcinoma in situ, but frequently presents as invasive disease. However, epidemiological investigations of urothelial malignancies have generally not distinguished between preneoplastic and invasive neoplasms or between these two types of urothelial neoplasms. It is recommended that future studies should distinguish between these entities. The most common etiologic factor of urothelial malignancies besides schistosomiasis is cigarette smoking. In addition, numerous specific chemicals have been identified as bladder carcinogens in humans, some relating to specific occupational exposures. Bladder carcinogens include aromatic amines and amides, such as 4-aminobiphenyl, benzidine, 2-naphthylamine and phenacetin-containing analgesics, and certain cancer chemotherapeutic agents, such as phosphoramide mustards. More recently, occupational exposure to various combustion gases, such as diesel exhaust, has been related to an increased risk of developing bladder neoplasms. Also, exposure to chlorination by-products in drinking water and to arsenic has been suggested as increasing the risk of bladder neoplasia. As numerous specific chemicals appear to be related to the development of bladder tumors, various polymorphisms of enzymes involved in their metabolism have been suggested as affecting the susceptibility to their carcinogenicity. This has been particularly true with respect to the role of acetyltransferases in relation to aromatic amine carcinogenesis. Dietary influences have also been suggested as affecting bladder neoplasia susceptibility. Various heterocyclic amines generated by pyrolysis of food have been suggested as potential dietary factors increasing the risk of bladder cancer, particularly in relation to the ingestion of red meat. Despite the existence of several identifiable factors that increase or decrease the risk of bladder cancer, many patients have no known carcinogens or risk factors.

Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant metastases. Because of the variation in the clinical course it has also been suggested that different forms of cancer develop along different molecular pathways leading to tumor presentations of various malignant potential. Today we treat and prognosticate bladder cancer on the basis of clinical and histologic findings that are insufficient to assess all the biologic potential of these tumors. Understanding the pathogenesis of bladder cancer might lead to a more precise identification of particular tumors with regard to clinical aggressiveness, resulting in individualized strategies for treatment and prophylaxis. Bladder cancer is seldom diagnosed in its preclinical stage, it is instead detected at cystoscopy and virtually never recognized as an incidental finding on autopsy. Therefore its "natural history" largely reflects that of "treated" disease. The true incidence of premalignant and malignant epithelial changes is not known. Incidences of hyperplasia and dysplasia of approximately 10% and approximately 5%, respectively and only occasional findings of cancer itself were reported in two autopsy series. Urothelial dysplasia is generally believed to be premalignant and a putative precursor of invasive cancer but unfortunately there has been a lack of standardization in terms of terminology and diagnosis. There is also a need for an agreed definition of the boundary between premalignancy, i.e. urothelial changes that have some but not all the features of carcinoma in situ, and malignancy, especially when considering potentially harmful treatments to prevent this transition. Most new diagnostic tools available and being tested today compare new detection techniques with traditional methods such as cytology or conventional histology of malignant rather than premalignant changes. There is probably also a short preclinical latency, as implied by the incidental findings of bladder cancer at autopsy, which makes it necessary to define how and when to promote early detection and treatment. Future studies therefore have to concentrate on methods for early detection of disease as well as characterization of host susceptibility, evaluation of exposure to carcinogens and potential effects of preventive measures. It is also likely that the improved tools of molecular prognostication will allow us to design trials more precisely in order to tailor therapeutic strategies.

Urological pathologists representing the World Health Organization and the International Society of Urological Pathology have reached a new consensus on the definitions of flat, non-invasive lesions of the urothelium. Lesions are classified as: (1) carcinoma in situ (CIS); (2) dysplasia; (3) atypia of unknown significance; and (4) reactive atypia. These terms are intended to describe a histological spectrum of architectural and cytological abnormalities ranging from the unequivocally malignant (CIS) through the probably neoplastic (dysplasia) to the benign (atypia). The biological potential of these lesions in individual patients cannot be accurately predicted, although the degree of risk for an adverse outcome is very likely to be proportional to the degree of architectural and cytological anaplasia. It is likely that each phenotype has two biological potentials: dynamic and effete. It should be emphasized that most of our knowledge concerning these lesions in humans has been obtained from studies of groups of patients who have already developed a papillary or nodular, invasive or non-invasive urothelial carcinoma, as descriptions of primary CIS, dysplasia, and atypia are uncommon. Future knowledge in this area might be enhanced by attention to the following: better definitions of terms and more accurate application of words such as bladder cancer, early lesion, tumor progression, precursor, and premalignant; increased understanding of the biological processes underlying phenotypic changes; development of models (probably computer-based) with the capacity to factor in the complexities of human carcinogenesis in an ongoing fashion, as new information becomes available.

Prostate cancer lends itself ideally to chemoprevention due to a number of specific features of the disease. These include a high prevalence, long latency time, hormone dependency, the availability of an ideal marker (prostate serum antigen) and, last but not least, the availability of a defined precursor lesion (prostatic intraepithelial neoplasia) among the pathways leading to clinical disease. The large variability in the incidence of the tumor in different geographical regions suggests the possibility of nutritional influences regarding the stimulation and/or inhibition of clinical cancer, as there is a similar prevalence worldwide of the precursor lesion. A great number of publications have dealt with a number of nutritional factors, including fat, phytoestrogens, vitamins (especially vitamin E) and minerals such as selenium and calcium. These are among the most reported substances with a possible influence on disease development; however, unfortunately there are no conclusive results or study outcomes at present which satisfy accepted standards of evidence. Ongoing studies on nutrition and prostate cancer may bring the required evidence to support what is still only an hypothesis at present.

The molecular genetic changes reported in bladder tumors can be classified as primary and secondary aberrations. Primary molecular alterations may be defined as those directly related to the genesis of cancer. These are frequently found as the sole abnormality and are often associated with particular tumors. There are characteristic primary abnormalities involved in th production of low-grade/well-differentiated neoplasms, which destabilize cellular proliferation but have little effect on cellula "social" interactions or differentiation, as well as the rate of cell death or apoptosis. Other molecular events lead to high-grad neoplasms which disrupt growth control, including the cell cycle and apoptosis, and which have a major impact on biological behavior. A primary target leading to low-grade papillary superficial bladder tumors resides on chromosome 9, while p53 gene alterations are commonly seen in flat carcinoma in situ. Other molecular alterations must be elucidated, as many non-invasive neoplasms have neither chromosome 9 nor p53 alterations. Novel approaches utilizing tissue microdissection techniques an molecular genetic assays are needed to shed further light on this subject. Secondary genetic or epigenetic abnormalities may be fortuitous, or may determine the biological behavior of the tumor. Multiple molecular abnormalities are identified in most human cancers studied, including bladder neoplasms. The accumulation, rather than the order, of these genetic alterations may be the critical factor that grants synergistic activity. In this regard, it is noteworthy that many of the genes that are altered act upon the two recognized critical growth and senescenc pathways, TP53 and RB. These particular molecular aberrations may be especially important to evaluate for their use in the management of bladder cancer because of their commonality in progressive forms of the disease. Thus, clinical trials are underway to explore their use in specific situations, particularly in the surgical management of locally advanced disease, and to determine whether adjuvant chemotherapy in such patients may be of benefit. The use of molecular alterations in the management of non-invasive bladder neoplasms remains to be firmly established. Our knowledge of molecular alterations important in bladder cancer progression is far from complete, and further study is necessary to further elucidate cruci pathways involved in progression and therapeutic response. As per preneoplastic conditions, difficulties in identifying and interpreting the significance of phenotypic changes have imposed certain limitations, as has an evolving nomenclature and issues of reproducibility in interpreting morphologica criteria. Nevertheless, molecular alterations involving chromosome 9q and the INK4A locus in papillary superficial tumors vs changes in chromosomes 14q and 8q, p53 and RB in flat carcinoma in situ lesions may indicate a molecular basis for early events that lead to varyi

There is a heterogenous spectrum of abnormalities and atypical lesions in the penile epithelium. The terminology used to designate precursor lesions is variable but squamous intraepithelial lesions of low and high grade or penile intraepithelial neoplasia I, II and III are the recommended terms. Other probable precursor lesions are squamous hyperplasia and bowenoid papulosis. Low- and high-grade squamous intraepithelial lesions may be classified into squamous or simplex, the most frequent types, or warty (condylomatous) and basaloid. There is a striking morphological correspondence between precancerous lesions of the penis and their respective invasive lesions. The presence of two groups of lesions in the precancerous as well as invasive carcinomas, the squamous typical and the warty basaloid, is consistent with the bimodal hypothesis of the existence of non-HPV (the typical squamous) and HPV-related (warty or basaloid) tumors.