It is the second most common tumor among urogenital system tumors. It is seen four times more in men than in women. It usually occurs over the age of 50. It has been definitively shown that aromatic amines of the aniline group, used in the paint and adhesive industry, enter the body through respiration, ingestion, and skin, and irritate the urinary system, especially the bladder mucosa, for many years, causing bladder cancer. These aromatic amines, 2-Naphthylamin, Benzidine, and 4-Aminodiphenyl, do not have a direct bladder cancer-causing effect. Their metabolites formed in the body are carcinogenic. After entering the body, these substances are metabolized in the liver by conjugation with sulfate and glucuronic acid, converting them to neutral carcinogenic orthoaminophenols. These are filtered by the kidneys and excreted in the urine, where they are activated by the enzyme beta glucuronidase to convert them to active carcinogenic orthophenols. These active carcinogenic orthophenols affect (stimulate) the urinary tract mucosa for years, causing stratified transitional epithelial cancer (transitional cell carcinoma) most commonly in the bladder and, to a lesser extent, in the mucosa of the ureter and renal collecting systems and pools. The reason they occur more frequently in the bladder is that urine is stored there and exposed to the effects of carcinogens for a longer period of time. In other parts of the urinary tract, urine flows into the bladder without delay.
Bladder cancer is also seen in cows that eat ferns in the Eastern Black Sea region. Bladder cancer can also occur in people who drink the milk of these cows. Perhaps this is the reason why bladder cancer is more common in the Eastern Black Sea region compared to other regions. Veterinarian Prof. Pamukçu conducted research in this region and found that shikimic acid found in ferns causes bladder cancer in cows.
Kynurenine, kynurenic acid, 3-hydroxykynurenine, and acetylkynurenine, metabolites of the amino acid tryptophan normally found in the human body, are metabolized in the liver and converted to neutral carcinogenic orthoaminophenols through the effects of sulfate and glucuronic acid. These, in turn, interact with the enzyme beta-glucuronidase in the urine and are converted to active carcinogenic orthophenols. These, in turn, irritate the urinary tract mucosa over many years, causing bladder cancer.
Bladder cancer is three times more common in smokers than in non-smokers. Smoking disrupts normal endogenous tryptophan metabolism, leading to bladder cancer.
Excessive use of phenacetin and similar analgesics (painkillers), as well as artificial sweeteners, can cause bladder cancer due to metabolites of the benzene ring in their structures.
In diseases that cause incomplete bladder emptying, such as prostate enlargement and urethral stricture, residual carcinogens in urine that remain in the bladder may cause bladder cancer, even though they would not cause harm if they were not retained in the bladder. Because urine remains in bladder pockets (bladder diverticula) and cannot be excreted, it can still lead to cancer.
Long-term irritation from bladder and kidney stones and infections can cause the urinary mucosa to transform into stratified squamous epithelium, which can then develop into stratified squamous epithelial cancer.
Schihistomia hematobium bilharzi, worms 1 cm or smaller that live in human bladder veins, penetrate the bladder wall and lay their eggs under the mucosa. These larvae hatch, tear the bladder mucosa, and are excreted in the urine, causing bleeding in the urine, infection, and stratified epithelial metaplasia (change) in the mucosa. Squamous cell bladder cancer develops from these sites. This disease, which is particularly common in Egypt and some Arab countries today, has been eradicated for 70-80 years in and around Mardin. Hopefully, it will not reoccur due to Syrians seeking refuge in Türkiye.
Radiation therapy to the abdominal area and the drug cyclophosphamide, used for chemotherapy in general cancer treatment, can affect the DNA of bladder cells, leading to hyperchromasia and the development of cancer.
These causes of bladder cancer indicate the possibility. Not every shoemaker who takes painkillers, artificial sweeteners, smokes cigarettes, eats dyed foods, or constantly uses adhesives will necessarily develop bladder cancer.
94% of bladder cancers are transitional cell carcinomas (stratified transitional epithelial cancer), 5% are squamous cell carcinomas (epidermoid cancer), and 1% are adenocarcinomas that develop from embryonic remnants in the bladder (like gastrointestinal cancer cells).
Bladder tumors are most common at the base of the bladder, where the urinary openings (ureteral orifices) open, and on the sides and back.It settles in the walls. If it grows too large, it can block the urinary tract, causing the patient's kidneys to enlarge (hydroureteronephrosis), increase urea levels, and, if it blocks the bladder outlet, cause an inability to urinate, similar to a prostate.
Bladder tumors generally grow into the bladder lumen like polyps. If left untreated, these small polyps grow and deepen into the bladder wall, taking on a cauliflower-like appearance. If it's delayed, they can spread to surrounding tissues, including the intestines, prostate, testicles, uterus, and vagina. It can also spread to the intra-abdominal lymph nodes. While initially treated with laparoscopic surgery, open surgery is often necessary to remove the entire bladder and even surrounding organs. Additionally, radiotherapy and chemotherapy are added to the treatment when appropriate. Of course, this spread is also related to the tumor's cellular grade. Grade I bladder tumors, with their cells, are more superficial, less prone to recurrence, and have more intact cells. Grade II In Grade III tumors, the cells are slightly more deformed and atypical. These are low-grade papillary cancers. The tumor is larger, the papillae are shortened, and they have invaded slightly deeper into the bladder wall, into the bladder wall muscle. In Grade III tumors, the cells are thoroughly deformed, the papillae are very shortened, and none remain, spreading deeper into the bladder wall. These are high-grade, invasive bladder cancers. Spread to surrounding organs and lymph nodes has usually occurred. Carcinoma in situ (CIS), a tumor that does not protrude into the bladder, is highly malignant. It appears as velvety red areas in the bladder.
In bladder cancer, the patient complains of painless, clotted, and visible (macroscopic) hematuria (blood in the urine). The blood in the urine is intermittent, appearing for a few days and then disappearing for a week. The patient should not assume they are cured. Even if the urine appears clear to the eye, microscopically, blood cells are always present. Clots are irregular and red in color. Clots are always present. Patients should not be alarmed immediately when blood is seen in the urine. Many urological conditions cause blood in the urine. However, it is advisable to see a urologist immediately for a diagnosis.
If the tumor obstructs the bladder outlet or ulcerates, complaints of dysuria (burning sensation during urination), pollakiuria (frequent urination during the day), and nocturia (waking up at night to urinate) may occur. Urgency (urgency to urinate) may occur. If the tumor obstructs the ureteral orifices at the base of the bladder, anuria (absence of urine production) and high urea levels may occur.
Complications related to that organ may be observed depending on metastases (spreading).
The patient's examination is usually normal. Abdominal examination and rectal digital examination are usually unremarkable. However, urinalysis always reveals blood. If an infection is present, leukocytes are also present in the urine. Because of the constant, gradual blood loss, the patient is anemia. Sometimes, the patient's urea level may be high.
Diagnosis used to be made through an IVF (renal x-ray) and cystography (a cystogram) performed after filling the bladder with a catheter. However, today, diagnosis is made through a simpler and easier abdominal ultrasound. Abdominal CT and MRI also confirm the diagnosis and indicate the extent of the disease.
However, a definitive diagnosis is made through cystoscopy (observing the bladder with an optical instrument) and a biopsy and pathological analysis.
Academic tests such as urine cytology and urine NMP22 testing are unnecessary routine tests.
LDH (lactic dehydrogenase), CEA (carcinoembryonic antigen), IgG, and IgA may be elevated in urine and blood. However, since they are not specific tumor markers, they are not significant.
The treatment for bladder tumors is surgery. Early-stage and low-grade tumors are resected using a closed-dose technique using a special optical instrument and an electrical system that visualizes the bladder interior (Transurethral bladder tumor resection-TURB). This treatment is sufficient for 60-70% of patients presenting early. However, it should be remembered that bladder cancers are prone to recurrence. These patients who undergo surgery should quit smoking, avoid colored foods and beverages, avoid artificial sweeteners and painkillers, and avoid touching or sniffing adhesives. They should also drink plenty of water to produce 2 liters of urine per day to reduce the concentration of carcinogens that may be present in their urine. These patients undergo follow-up ultrasounds and cystoscopy every 3 months for one year, every 6 months for the second year, and annually after the third year. If there is no recurrence after 5 years, the patient is considered fully recovered. If recurrence occurs in 30-40% of patients, a repeat TURB is performed. The follow-up period begins anew. These patients, as well as those who have undergone TURB for tumors in several foci, are also treated with TURB.10-15 days after surgery (when no blood is seen in the urine), attenuated tuberculosis vaccine (imminocyst) or chemotherapeutic agents (thiotepa, mitomycin) are administered into the bladder through a catheter once a week for six weeks. The patient lies on their back. They change positions every half hour, lying on their right side, left side, or stomach, and urinate after a total of two hours. Patients who have only been given the tuberculosis vaccine are advised to urinate two or three times into the toilet bowl, flush the toilet immediately, and soap their genital area after urinating, as they carry live microbes. Rarely, tuberculous cystitis and ovarian inflammation can develop. These patients are treated with two anti-tuberculosis drugs for three months. Those receiving intracavitary chemotherapy should have their blood counts checked weekly, and their white blood cells may decrease.
Laser treatment can also be performed on patients with superficial tumors of the same type. However, TUR-Tm is more suitable.
Partial cystectomy (removal of the tumor along with the entire bladder wall) can be performed for larger tumors located on the anterior, lateral, and apex of the bladder.
For larger or multiple tumors that have not spread beyond the bladder, the entire bladder is removed (total radical cystectomy). To maintain urinary continuity, the ureters can be connected to the abdominal skin (ureterocutaneostomy), the ureters can be connected to a segment of intestine within the abdomen, and the other end of the intestine can be opened to the abdominal skin (ileal loop surgery), or the ureters can be connected directly to the sigmoid, the last section of the large intestine (ureterosigmoidostomy surgery).
Radiation therapy and chemotherapy can be applied in advanced disease.
Permanent nephrostomy (a permanent tube inserted through the skin into the kidney) can be placed in patients with advanced disease who cannot undergo surgery, have blocked urethra, and are unable to pass urine (anuria).
We wish you healthy days.
Prof. Dr. İbrahim Bozkırlı
Private Mersin System Surgical Medical Center