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Carcinoma of the bladder is the second most frequent cancer of the urogenital tract in men, after prostate cancer. It is also the fourth most frequent type of cancer in men, after those of the prostate, lung and colon, while it is the 8th most frequent type in females. The male to female ratio is about 3/1. The frequency of the disease shows a clear upward trend, which among other things is due to the increase of the average human life, as cancer of the bladder (just like most cancers) affects mainly older people.

 

The average age of onset is 69 years in men and 71 in women, but the disease can occur at any age, even in children. Bladder cancer accounts for 2.6% of all cancer deaths in men and 1.4% in women. The mortality rate of women is considered disproportionately large, especially when compared to other parameters of the disease.

 

Reasoning
Chemical carcinogens
Occupational exposure to chemical carcinogens estimated to account for about 20% of bladder cancers. Increased risk for cancer of the bladder are the workers of the oil, rubber, leather, chemicals and dyes industry, but there are studies that indicate an increased risk to car drivers, plumbers or even telephone operators. The latency period between exposure to a carcinogen and appearance of the disease can be very large (even 30-50 years), suggesting that the etiological agent acts cumulatively to induce the onset of the disease.


On the other hand, there are nutrients such as vitamin A and beta-carotene that are considered protective against bladder cancer. Individuals who consume food containing only small quantities of such nutrients, are at an increased risk of developing the disease. It has also been experimentally shown that vitamin A may prevent the development of cancer induced by chemical carcinogens.



Smoking
The strong relationship between smoking and cancer of the bladder has been fully confirmed. It is estimated that smoking accounts for 25-60% of bladder cancer cases. Smokers are at four times the risk of developing carcinoma from non-smokers, and the risk seems to be related to the number of cigarettes, smoking duration and smoke inhalation extent.


Quitting smoking seems to have the effect of reducing the incidence of bladder cancer, a reduction which seems to be progressive and long-lasting. It is estimated that it takes at least 20 years of smoking abstinence so that the relative risk may be reduced to nonsmoker levels and this period is much greater than that of lung cancer and cardiovascular diseases.

 

Tea and coffee
The consumption of coffee and tea have previously been implicated as a causative factor of bladder cancer. Nevertheless, subsequent experimental studies have failed to show that caffeine can initiate or maintain or even enhance a tumorigenic process in the bladder. Therefore, we must accept that the consumption of coffee and tea is not a causative agent of urothelial cancer.



Abuse of analgesics
Consuming large quantities of analgesics has been associated with increased risk of developing transitional cell carcinoma of the bladder and of the renal pelvis.



Chronic cystitis and other infections
It is generally accepted that chronic inflammation of the bladder, microbial or not, can cause cancer.

Specifically:
Patients with permanent catheters have an increased risk of carcinoma of the bladder.
Recurrent urinary tract infections have been implicated as a causative factor in the development of bladder cancer, especially in women. Urinary tract infection can lead to carcinogenesis, while stones (calculi) that remain in the urinary tract for a long time can also cause cancer of the bladder, possibly because they cause injury to the urothelium.
The exact relationship between different viruses and bladder cancer remains unclear, although occasionally different viruses (HPV, retroviruses, papillomaviruses, viruses of the group of herpes simplex, adenoviruses) have been considered as causative factors of the disease.

Radiation of the pelvis
Women undergoing radiotherapy for cervical cancer are 2-4 times at a higher risk of developing cancer of the bladder of a low modulation and locally extensive.

Inheritance
Although "familial" cases of bladder cancer have been reported, there is no epidemiological evidence of the disease's heritability.

Clinical picture
The most common symptom by which neoplasm of the bladder appears is painless hematuria, which is observed in 85% of patients. Hematuria can be either macroscopic or microscopic. Frequent urination, nocturia and urinary urgency may also be present while rarer manifestations of the disease are lumbar pain (due to retroperitoneal lymph node metastases, or even ureteral obstruction), swelling of the lower limbs and presence of a palpable mass (in a locally advanced disease). Weight loss characterizes the late stages of the disease.

Laboratory examination
Ultrasound
The role of ultrasound in the diagnosis of bladder cancer is very important, since all patients with macroscopic or microscopic hematuria are initially subjected to ultrasound testing.

Intravenous urography
It is an irreplaceable examination in assessing a patient with hematuria. Its value lies mainly in the study of the upper urinary tract, which can reveal an obstruction or a contrast deficit which may be due to a tumor.

Cytological urine test
It is a useful diagnostic method for detecting bladder tumors with high malignancy which are not detected by cystoscopy.

Cystoscopy
It is the final test by which the diagnosis is confirmed. Typically, superficial tumors are recognized as mischotes, papillary estuaries of the bladder wall, as opposed to the invasive ones which in their majority are solid tumors with a wide base. However, it should be noted, that the macroscopic characteristics of a tumor can not accurately be distinguished between these two types of bladder tumor.

Computed tomography (CT SCAN)
The CT scan is used both for estimationg the local extension of the disease and the detection of possible metastases. Infiltrated lymph nodes are detected by CT only when their size is larger than 1 cm, whereas liver metastases are detected only when they have a size larger than 2 cm.

Magnetic resonance imaging (MRI)
With the exception of bone metastases, MRI does not seem to have an advantage over CT in the diagnosis and development of the bladder carcinoma, while it also has the disadvantage of increased costs.

Βone scintigraphy
Ιt is usually not used for investigating metastases of bladder cancer, unless the patient is symptomatic or the alkaline phosphatase of the serum looks increased.

Treatment
Patients with a superficial (non-invasive) tumor initially undergo transurethral removal of the tumor (TURT) and then, depending on the stage or degree of malignancy, they are submitted to a systematic monitoring program or alternatively undergo supplementary intravesical therapy. Patients with T2 or T3 invasive tumors are candidates for radical cystectomy which may follow systemic chemotherapy depending on the pathoanatomical findings. Locally extensive tumors or unresectable ones (T4) can be initially treated with systemic chemotherapy in an effort to reduce tumor mass followed by radiotherapy or surgery, depending on the response. Finally, patients with metastatic disease are treated with chemotherapy.