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About Bladder Cancer

Bladder cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in... more

Bladder cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called urothelial cell or transitional cell carcinoma (UCC or TCC).

Risk factors

Exposure to environmental carcinogens of various types is responsible for the development of most bladder cancers. Tobacco abuse (specifically cigarette smoking) is thought to cause 50% of bladder cancers discovered in male patients and 30% of those found in female patients. Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. Certain drugs such as cyclophosphamide and phenacetin are known to predispose to bladder TCC. Chronic bladder irritation (infection, bladder stones, catheters, bilharzia) predisposes to squamous cell carcinoma of the bladder. Approximately 20% of bladder cancers occur in patients without predisposing risk factors. Bladder cancer is not currently believed to be heritable (i.e., does not "run in families" as a consequence of a specific genetic abnormality).

Signs and symptoms

Bladder cancer characteristically causes blood in the urine, this may be visible to the naked eye (frank haematuria) or detectable only be microscope (microscopic haematuria). Other possible symptoms include pain during urination, frequent urination or feeling the need to urinate without results. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate infections and cystitis.

Pathological Classification

90% of bladder cancer are transitional cell carcinomas (TCC) that arise from the inner lining of the bladder called the urothelium. The other 10% of tumours are squamous cell carcinoma, adenocarcinoma, sarcoma, small cell carcinoma and secondary deposits from cancers elsewhere in the body.

TCCs are often multifocal, with 30-40% of patients having a more than one tumour at diagnosis.

The pattern of growth of TCCs can be papillary, sessile (flat)or carcinoma-in-situ (CIS).

The 1973 WHO grading system for TCCs (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO [1] grading (papillary neoplasm of low malignant potential (PNLMP), low grade and high grade papillary carcinoma.

CIS invariably consists of cytologically high grade tumour cells.

Bladder TCC is staged according to the 1997 TNM system:

* Ta Non-invasive papillary tumour
* T1 Invasive but not as far as the muscular bladder layer
* T2 Invasive into the muscular layer
* T3 Invasive beyobd the muscle into the fat outside the bladder
* T4 Invasive into surrounding structures like the prostate, uterus or pelvic wall

Treatment

The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope. Immunotherapy in the form of BCG instillation is also used to treat and prevent the recurrence of superficial tumors. BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy into the bladder can also be used to treat superficial disease.

Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.

A combination of radiation and chemotherapy can also be used to treat invasive disease, and, in many cases, it is not yet known which is the better treatment - radiotherapy or radical ablative surgery.

There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statins is associated with failure of BCG immunotherapy.

Epidemiology

In the United States, bladder cancer is the fourth most common type of cancer in men and the ninth most common cancer in women. More than 47,000 men and 16,000 women are diagnosed with bladder cancer each year. One reason for its higher incidence in men is that a molecular receptor or protein that is much more active in men than women plays a role in the development of the disease.

Genetics

Bladder cancer is not linked to specific genes; however some which are more prominently studied include the FGFR3, HRAS, RB1 and TP53 genes. As with most cancers, the exact causes of bladder cancer are not known; however, many risk factors are associated with this disease. Chief among them are smoking, followed by exposure to certain chemicals. Mutations in the gene that arise in the bladder are another important risk factor for developing bladder cancer. Several genes have been identified which play a role in regulating the cycle of cell division, preventing cells from dividing too rapidly or in an uncontrolled way. Alterations in these genes may help explain why some bladder cancers grow and spread more rapidly than others.

Bladder cancer is generally not inherited; tumors usually result from genetic mutations that occur in certain bladder cells during a person's lifetime. These noninherited genetic changes are called somatic mutations. A family history of bladder cancer is, however, a risk factor for the disease. Along these lines, some people appear to inherit a reduced ability to break down certain chemicals, which makes them more sensitive to the cancer-causing effects of tobacco smoke and certain industrial chemicals.

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