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Urinary bladder cancer

About Urinary bladder
Urinary bladder is a muscular sac organ located in the pelvis, just above and behind the pubic bone. It is slightly lower in the female than in the male. Bladder collects urine from kidneys through ureters and stores temporary before disposal through urination process. Normally bladder can carry from 300-500Ml of urine.

Structure of urinary bladder
Bladder is a muscular hollow organ that is situated at the base of pelvis. Urinary bladder is made up of smooth muscles fibers called detrusor muscles that gives bladder ability to stretch and contract easily during storing and empting urine.
In men urinary bladder lies in front of rectum with a space between them and in women it lies in front of uterus.
Urinary bladder has sympathetic and parasympathetic nerve supply that play role in micturition process (empting of bladder) as sensation from bladder is transmitted from these nerve fibers to central nervous system through general visceral afferent fibers.

Bladder cancer
Bladder cancer is the disease that develops in the lining of urinary bladder when normal cells change and start to grow and divide in uncontrollably. Urinary bladder is made of several layers made of different cells. Bladder cancer commonly originate from the innermost layer of bladder which is made of cells that forms type of tissue called transitional epithelium (urothelium). When cancer starts from this layer it may grow into or through other layers of bladder and as it gets more advanced it may start invading nearby organs. Statistics shows that in Tanzania Bladder cancer affects more men than women and majority being those above 40 years old and number increases as age increases too.

Types of urinary bladder cancer
There are three common types of bladder cancer as explained below,
1. Urothelial carcinoma, also known as transitional cell carcinoma. This is the common type of bladder cancer that develop from the innermost layer of the bladder called transitional epithelium. It is divided into two types basing on the extent of its spread.
2. Non invasive transitional cell carcinoma, which is the one still in the inner layer of epithelium and it has not spread through other layers of bladder wall.
3. Invasive transitional cell carcinoma, this has already (spread) penetrated through other layers of bladder wall.
4. Squamous cell carcinoma. A squamous cell is another type of tissue found in moist, skin like tissues covering body organs. This type of bladder cancer start from these cells forming this lining in the bladder.
5. Adenocarcinoma. This is rare type of bladder cancer that starts from the mucus producing cells found in the bladder wall.

RISK FACTORS FOR BLADDER CANCER
When it comes to cancer, anything that increases your probability of developing cancer is called a risk factor. Risk factors only influence development of cancer but it does not directly cause cancer. Sometimes people with risk factors do not develop the disease while those with no risk factors do develop the disease. Knowing risk factors will help you live your life making some better healthy choices to reduce the risk. Risk factors for urinary bladder cancer include the following
• Smoking. Smoking is one of the important risk factors for bladder cancer, as smokers are at high risk of developing bladder cancers compared to non smokers. Smoking increase risk of leading to bladder cancer due to the fact that in chemicals found in that smoke have potential of causing DNA destruction and lead to develop cancer.
When these chemicals enter our body through smoke diffuses into our bloodstream.They are then filtered out of the blood by the kidneys and end up in the urine. When the urine is stored in the bladder, these chemicals are in contact with the bladder lining which may lead to the destruction of those cells in the lining.
• Age. Older people are at more risk of developing bladder cancer compared to young once. People with the age of above 50 years are at higher risk of developing this cancer compared to those below 40 years old.
• Exposure at work. There are certain chemicals like aromatic amines which include benzene products and aniline dyes have been linked to bladder cancer, so people working in environment with these chemicals are at higher risk of suffering from this cancer due to long term exposure and the risk increase as they don`t use protective gear when at work. This group include those working in dye industries, textile industries, paint productions industries, painters, hair dressers (likely due to long term exposure to hair dye) and long term drivers (likely due to long term exposure to diesel fumes).
• Chronic infections and irritations. Squamous cell carcinoma of bladder has been highly associated by some chronic urinary tract infections, untreated bladder stones and long term use of catheters (which is common to those who are paralyzed waist down hence require the use of urinary catheters)
• Gender.Just by being a man your risk of developing bladder cancer has increased as statistics shows that men are at higher risk of developing this cancer compared to women.
• Arsenic in drinking water. Arsenic in drinking water has been linked with bladder cancer in some parts of the world as arsenic substance is said to be carcinogenic when someone is exposed in high dose, hence drinking water with this chemical it increases risk of developing bladder cancer.
• Not drinking enough fluid.Those people drinking enough fluid each day like water have slightly lower risk of developing bladder cancer as they empty their bladder more often than those who don`t drink fluid as their bladder stay with urine for long time which increase even time their bladder wall is in contact with possible cancer causing chemicals that may be in urine.
• Personal history of the disease. For a person who previously suffered cancer at any site of urinary tract such as lining of ureter, urethra or even kidney have a higher risk of developing cancer either at the same place or nearby organs including bladder, so those who had cancer in those sites before, needs close follow up.
• Family history and genetic factors. Some people may develop bladder cancer because they inherited some genes from their parents that influence them to develop bladder cancer. This include inheriting genes like GST and NAT that causes bodies to be unable to remove (break) certain toxins and some of them are potential carcinogens that may influence bladder cancer.

PREVENTION OF BLADDER CANCER
Although there is no way to prevent cancer, there are ways that can help to reduce the risk of developing bladder cancer. Among those ways include, avoiding and reducing cigarette smoking, limit exposure to chemicals at a work place, eating lots of fruits and vegetables, drinking plenty of fluids and treating bladder infections and irritations.

EARLY DETECTION AND SCREENING
Detecting the disease early increases the chance of cure. This is simply because the disease will have not spread to other parts of the body. Early detection in most cases is achieved through the process called screening.
Screening: screening is the process of doing examination tests to people with no symptoms of the disease. The tests are done in order to find if a person has disease or not although there are no symptoms shown. Currently there are no organization recommending routine tests for bladder cancer to the public because there are no tests that have shown to lower the risk of dying from bladder cancer to those at average risk.
For those at very high risk like; those who had bladder cancer before, those with family history of the disease and those with birth defects, the following tests are recommended.
• Urinalysis: urinalysis is simply analysis of urine by physical, chemical and microscopic to detect diseases. Though this, professionals can check presence of blood in the urine which is one of the signs of bladder cancer.
• Urine cytology: this is the test based on checking cells in the urine by using microscope. Although this test can show cancer cells, it is not recommended to use this alone as the only and conclusive test.

SIGNS AND SYMPTOMS
People with urinary bladder cancer can experience some of the following signs and symptoms. Sometimes people with this disease do not show any of those signs and symptoms and it is possible also for those signs and symptoms to be associated with other health conditions, so the only possible way to find the truth is through examinations in hospital. Those signs and symptoms include
• Blood in the urine (hematuria): This is one of the common symptoms of bladder cancer whereby some blood will be seen in the urine.It is normally not painful and blood may come and go.
• Changes in bladder habits: These changes include burning feeling during urination, the need to pee more often or urgently, not being able to urinate when you feel the urge andsometimes feeling pain while urinating.
• Lower back pain
• Weight loss
• Loss of appetite
• Swollen legs
• Bone pain

DIAGNOSIS
cancer diagnosis
Medical diagnosis simply means identification of nature of an illness by elimination of the symptoms. Normally people don`t go to hospital knowing they have cancer but during diagnostic procedures is when doctors detect the disease.
Following suspicion of the disease, doctors normally run combination of tests to determine whether there are cancerous cells in the body or not and if there are cancer cells, how far have they spread. Along with thorough medical history and physical examination, doctors normally use combination of the following tests to diagnose cancer.
Laboratory tests. Laboratory tests are important in ruling out other conditions and confirming diagnosis. For cancer diagnosis laboratory tests normally include blood tests, urine tests, tumor markers and other body fluids tests.
• Blood tests. Blood tests help to reveal level of different substances in the blood which will help doctors to know if there is anything wrong in the body. From blood tests doctors can see complete blood count which indicates number, size and maturity of blood cells. Also from the blood tests doctors can analyze if kidney and liver are working properly.
• Urine tests. Urine tests (urinalysis) involve laboratory examination of urine to check presence of blood, proteins, and other substances such as drugs. For instance, blood in the urine may be an indication of benign condition, infection or other health problem.
• Tumor markers. These are biomarkers (proteins) that can be produced by both cancer cells and normal body cells in response to cancer. Tumor markers are released into the blood or urine. Although studies are still conducted to determine role of these markers in diagnosing cancer because sometimes people with benign condition will have elevated level of these proteins. Also not all tumors have their markers and some markers are not specific to one type of tumor.
• Other body fluids. Despite being rarely used, sometimes body fluids can be tested in the lab during diagnosis of cancer. For instance, the use of cerebral spinal fluid (CSF) and pleural fluid. CSF is used in diagnosis of brain tumors while pleural fluid for lung cancer.

Diagnostic imaging
Diagnostic imagings involve tests that create pictures of inside the body that help the doctor to see if there is tumor or not. There are several imaging tests used in cancer diagnosis depending on the type and location of cancer suspected. These imaging tests include;
• Computed tomography (CT) scan. CT scan machine is a donut-shaped scanner that uses x-rays to create series of pictures of body organs from different angles. This machine is linked to a computer where those series of pictures taken will be combined to create a 3D- image of inside the body. During the scanning process patient will lie still on the table which will slide into the scanner. In order to get a clear image, sometimes the doctor will inject the patient with a contrast material before scanning. From the images the doctor will be able to differentiate between healthy and unhealthy tissues.
• Magnetic resonance imaging (MRI). MRI is an imaging technique that uses powerful magnet and radio waves to take series of pictures of body organs and create a 3D image in a computer linked to a machine. Just like in CT, during MRI procedure the patient will lie on a table that will slide into a long round chamber. Also during this procedure, the doctor may inject the patient with a contrast material for clear image view.
• X-ray. This is an imaging technique that is uses low dose of radiation to create pictures of inside your body. Technician will position the patient and direct the x-ray beam to the intended part of the body.
• Ultrasound. Ultrasound is a diagnostic imaging procedure that uses high energy sound waves to produce images of organs inside the body. During the examination, a patient will lie on the table while the technician will slowly move a device called transducer on the skin over the part of the body that is being examined.
• PET scan. Positron emission tomography (PET) scan is an imaging test that uses radioactive glucose to create 3-D images of areas inside the body. Radioactive glucose is used for this test because cancer cells tend to absorb more glucose than normal body cells, so the scan will show which areas of the body has more glucose than others. Before the scan, doctor will inject the patient with tracer called radioactive glucose then during imaging the patient will be asked to lie on the table that will be moving back and forth through the scanner.
• Bone scan. Bone scan is used to examine bones. When it comes to cancer, bone scan is used for diagnosis of bone cancer or cancer that has metastasized into the bones. Before the test, patient will be injected with small amount of radioactive material that tends to collect more on abnormal parts of the bones. Then pictures that will be taken by a scan will indicate the distribution of those radioactive materials in the bones throughout the body.

Biopsy
Biopsy is a diagnostic procedure that involves removing a tissue sample from the body and examines it under microscope in the laboratory. Examination in the laboratory is normally done by a pathologist who will check if the cells in the tissue are cancerous or not. In most cancer cases, biopsy is considered to be the confirmatory test. Depending on the location and type of cancer, biopsy can be obtained in different ways. Some of them include;
• Using needle. By using a thin needle, doctors can draw same tissue or fluid for examination under microscope. This method can be used to draw some fluid (spinal tap), bone marrow (bone marrow aspiration), blood or small amount of tumor from the suspected organ such as liver and breast (fine needle aspiration).
• Surgery. Abnormal tissue samples are obtained while the doctor is performing the surgery. Tissues are then sent to the lab for examination during the surgery. If the surgeon removes just a portion of abnormal area, it is called incisional biopsy while when the entire tumor (abnormal site) is removed it is called excisional biopsy.
• Using endoscope. Endoscope is a thin, lighted tube with a camera (focusing telescope) at the end. It is used for viewing inside the body through natural openings like mouth and anus. During an examination if the doctor sees any abnormal tissue, then endoscope can also be used to take sample for that tissue. There are different kinds of endoscopy exams depending on the site of the body being examined. Some of the exams include colonoscopy (for rectum and colon), bronchoscopy (for trachea, bronchi and lungs) and esophagogastroduodenoscopy EGD (for esophagus, stomach and duodenum)
In addition to medical history and physical examination diagnosis of urinary bladder cancer normally involves the use of ultrasound, CT scan, MRI scan, cystoscopy, biopsy, urinalysis, urine cytology and urine tumor markers which involve evaluating the level of BTA (bladder-tumor associated antigen), NMP22 (nuclear matrix protein number 22) and immunocyt (which include mucin and carcinoembryonic antigen, CEA)

STAGES OF BLADDER CANCER
Staging is a standard way used by cancer care team to explain how far the cancer has grown or spread. Staging also enables the oncology team to decide on the suitable treatment option. In this process of staging doctors normally use systems in order to describe the stage of cancer. In staging bladder cancer, TNM system is commonly used, where these letters are described as follows;
• Tumor. Tumor explains size (how large is the tumor?) and its location.
• Node. This explain lymph nodes involved
• Metastasis. Metastasis explains how far has disease spread?
In this system, those letters are assigned with numbers so as to show the stage of the disease, and there are five stages starting with stage 0 and stage 1 to stage 4 (I-IV), so those letter will be assigned with those numbers. More details on description of the system is as shown below,
Tumor (T)
TX:The primary tumor cannot be evaluated.
T0:There is no evidence of a primary tumor in the bladder.
Ta: Non-invasive papillary carcinoma. Tumor is only found on the surface of the inner
lining of the bladder.
Tis:Carcinoma in situ (CIS).Meaning tumor is only
on or near surface of bladder. It is also called non-muscle invasive bladder cancer.
T1:The tumor has invaded the sub epithelial connective tissue but does not involve the bladder
Wall muscles.
T2: The tumor has invaded the muscle of the bladder wall.
T3: The tumor has invaded the fatty tissue surrounding the bladder (pervesical tissue).
T4:Tumor may have invaded the abdominal wall, the pelvic wall, Prostate, seminal vesicle, uterus
or vagina
T4a: Tumor has invaded prostate, uterus, or vagina.
T4b: Tumor has invaded the pelvic wall or the abdominal wall.
Node (N)
NX: The regional lymph nodes cannot be evaluated.
N0: No regional lymph nodes involvement.
N1: Only single regional lymph node is involved.
N2: More than 2 regional lymph node are involved.
N3: The cancer has spread to the common iliac lymph nodes.
Metastasis (M)
M0: The disease has not metastasized.
M1: There is distant metastasis.

Stages
• Stage 0a (Ta, N0, M0):Non-invasive papillary urothelial carcinoma with no reginal lymph nodes involvement or distant metastasis.
• Stage 0is (Tis, N0, M0): Carcinoma insitu (CIS) with no reginal lymph nodes involvement or distant metastasis.
• Stage I (T1, N0, M0): Tumor has invaded the inner lining of the bladder into the lamina propria but has not reached the bladder walls. There is no reginal lymph nodes involvement or distant metastasis
• Stage II (T2, N0, M0): The cancer has invaded the muscle wall of the bladde but there is no reginal lymph node involvement or distant metastasis. • Stage III(T3 or T4a, N0, M0): Tumor may have invaded the fatty layer of tissue surrounding the bladder. Also it may have invaded the prostate, uterus or vagina. There is no reginal lymph nodes involvement or distant metastasis.
• Stage IV (T4b, N0, M0): The tumor has invaded the pelvic wall or the abdominal wall but there is no lymph node involvement or distant metastasis.
(Any T, N1–3, M0): The tumor is of any size and location but there is 1 or more regional
lymph nodes involvement. There is no distant metastasis
(Any T, any N, M1):Tumor is of any size with any lymph node involvement but there is
distant metastasis.

TREATMENT
Following cancer diagnosis, the doctor will break the news and it is normally not very easy to accept that it is cancer. The doctor will be there to help the patient process the news and to help the patient in taking the next steps.
After the patient receives and processes the news that he/she has cancer, one of the most important steps that will follow is decision making. The doctor will present to the patient (relatives/parents/guardians) with all the possible treatment options and explain what they mean. Then with the help of the doctor, the patient (relatives/parents/guardian) will have to choose which treatment option is good depending on benefits of such option.
Despite all the information given by the doctor, sometimes the patient may still be unsatisfied with what he/she has been told. In such situation, the patient is free and advised to seek a second opinion. Second opinion is the opinion that the patient may seek from another specialist (doctor) regarding his/her health problem and in this case it is cancer. Second opinion may include confirmation of the diagnosis, more clarification on your primary doctor recommendations or even reassurances that all the options have been explored.
In addition to standard care treatment options, sometimes there are those new treatments or drugs or combination of treatments that have not been approved yet to be used as standard care treatments for a particular cancer (disease) but have shown some promising results that they may help. These type of treatments are called clinical trials.
If there are some clinical trials for your case, the doctor may present to the patient or the patient may ask if there are any clinical trials for the particular cancer case. Over the years, have improved treatments and led to better outcomes to people diagnosed with various diseases including cancer. If you have decided to take part in clinical trial, you can also withdraw at any time

Treatment options
Treatment of urinary bladder cancer requires a team of doctors and other health care professionals. This team work together and it is called multidisciplinary team. Team may vary depending on the treatment option for a particular case. But normally multidisciplinary team for treatment of urinary bladder cancer includes surgical oncologist, medical oncologist, radiation oncologist, radiation therapist, pathologist and other health care professionals like oncology nurses, physiotherapist and palliative care team. Treatment options include the following;

Surgery
Surgery is the treatment option that involves removal of tumor and surrounding tissue through operation. This is treatment option is done by a doctor called surgical oncologist. There are various kinds of surgery for treatment of urinary bladder cancer. Among surgical options to treat urinary bladder cancer include the following:
• Transurethral bladder tumor resection (TURBT). this involve removing the tumor from the bladder by using a scope with specialized cutting instrument. During the procedure, the surgeon will insert the cystoscope through the urethra while the patient is under anesthesia to prevent the pain during the operation..
• Cystectomy. This option involves removing the whole bladder or part of it and possibly nearby tissues and organs. Normally nearby lymph nodes are also removed during the operation. This procedure may sometimes involve removing prostate and seminal vesicle for men while to women it may include removing fallopian tube, ovaries, uterus or part of vagina.
This type of treatment option can be done in two different ways depending on the extent of the disease but in either option general anesthesia is used to put the patient under deep sleep.
1. Partial cystectomy
This procedure is applied when cancer has invaded the muscle layer of the bladder wall but is not very large and only in one place, it can sometimes be removed along with part of the bladder wall without taking out the whole bladder. Nearby lymph nodes are also removed and tested to check if the disease has spread.
2. Radical cystectomy
If the cancer is larger or is in more than one part of the bladder, a radical cystectomy will be needed. This operation removes the entire bladder andnearby lymph nodes. In men, the prostate and seminal vesicles are also removed. Inwomen, the ovaries, fallopian tubes (tubes that connect the ovaries and uterus), theuterus (womb), cervix, and a small portion of the vagina are often removed along withthe bladder.

Reconstructive surgery after surgery
This is not one of the treatment options, but it is one of the management after radical cystectomy as after removing the whole bladder you will need another way of temporary storing and removing urine. In this there are different types of reconstructive surgery that can be done depending on your medical condition and personal preference. Among those options include these below;
• Urostomy: This is sometimes called an ileal conduit. Piece of ileum is used to create a passageway (conduit) through which urine will be drained into the bag attached outside the abdomen.
• Neobladder: This involves making a pouch that works in the same way as bladder. Normally the surgeon uses piece of small bowel (45-75cm) to create the new bladder (neobladder). Ureters will be stitched into the top area of the neobladder (chimney) hence urine will drain from the kidneys through the ureters into the neobladder. And after the procedure, special nurse will assist you to learn how to empty your neobladder.
• Continent urinary diversion: In this procedure, a doctor will use small part of your small intestine to create a pouch with a valve which will be collecting and storing urine for a certain period of time before being removed through stoma. With this option you don`t have to wear bag over stoma all the time but bag will be used only during empting of urine from the pouch through catheter (draining tube) which you will insert into pouch trough stoma.

Side effects of surgery
Side effects of surgery to patients with bladder cancer depend on the procedure. For those who had TURBT side effects include blood in urine and bladder infections. Blood in urine usually may last for up to two weeks after surgery. For bladder infections, doctor may prescribe a course of antibiotics.
For those who had partial cystectomy may experience need to urinate more often than normal because their bladder is now small due to surgery.
Total removal 0f bladder together with nearby organs will affect the way your body works. In men nerves that are responsible for erection are most likely to be affected so their sex life will be affected. For women, the removal of reproductive organs will force them to go through menopause if they have not already.

Chemotherapy
Chemotherapy is the use of medicines (drugs) to treat cancer. Those drugs taken will stop growth and division of cancer cells. Usually these drugs are given in cycles at a certain period of time where a patient may be given one drug at a time or may receive combination of different drugs at a time depending on recommendations of their doctor.
For treatment of urinary bladder, there are mainly two ways of delivering chemotherapy depending on the stage of the disease. These include the following;
• Systemic chemotherapy: systemic simply means whole body, so it is called systemic chemotherapy because drugs given and mainly by injecting through veins (intravenous) enter into bloodstream and travel throughout the body. This type of chemotherapy is mainly used for muscle invasive bladder cancer because the disease has started to spread to near organs. So the drug is mainly for killing cancer cells while doing the least possible damage to healthy cells. This type of therapy is given by medical oncologist
• Intravesical chemotherapy: with this type of chemotherapy, drugs are injected direct to the bladder through catheter inserted into bladder through urethra. This type of chemotherapy is given to those with non-muscle invasive bladder cancer (stage 0) and those with minimum invasive bladder cancer (stage 1) because the disease has not spread to near organs hence drugs will affect cancer cells most with no or minimal effect to healthy cells. This type of chemotherapy is given by urologist.

Side effects of chemotherapy
Side effects of chemotherapy depends on the dose and individual but normally may includes fatigue, vomiting, diarrhea, loss of hair, loss of appetite and sometimes infections. These side effects most commonly disappear after completion of treatments.

Radiotherapy
Radiotherapy (radiation therapy) is one of the treatment options of bladder cancer that uses high energy radiations (x-rays or other particles) to kill cancer cells while spearing normal (healthy) tissues as much as possible. Radiation therapy is given by a specialized doctor known as radiation oncologist. Radiotherapy is divided into two types, external beam radiation therapy and internal radiation therapy. External-beam radiation therapy is the one given from the source (machine) positioned outside the body while internal radiation therapy (brachytherapy) the source is placed inside the body.
Normally radiotherapy is not given alone as primary treatment for bladder cancer but it is given in combination with chemotherapy. But for those who cannot receive chemotherapy due to other medical reasons can be given radiotherapy alone.

Side effects of radiotherapy
Side effects of radiotherapy include, fatigue, loss of appetite, mild skin reactions, burning when passing urine and soreness around anus. These radiotherapy side effects commonly disappear following completion of treatments.

Immunotherapy
Immunotherapy is the treatment aims in stimulating and strengthening body immune system to fight of cancer. For bladder cancer it is normally given intravesically (directly into the bladder through the use of catheter) or intravenously (injected into veins). One of the most common drug used for bladder cancer is called bacillus calmette-guerin (BCG).
BCG is normally used for those at early stage and it is given intravesically. When this drug is inside bladder it attaches to the lining of bladder stimulating immune system to destroy cancer cells.
For those at later stage, there is a drug which is used as checkpoint inhibitorwhich enables immune system destroy cancer cells. Checkpoint are molecules on immune cells that are to be turned on or off for immune response to happen, so cancer cells sometimes uses the checkpoints to avoid being destroyed by turning these off.

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