Anatomy and Physiology of the Bladder
The bladder is a sac-like organ in the pelvis that stores the urine produced by the kidneys. There are two tubular structures called ureters (one from each kidney) that drain the urine into the bladder. The urethra is the outflow tract of the bladder and connects the bladder to the exterior.
Anatomically, the bladder is the most anterior (closest to the front) organ in the pelvis, located just behind the pelvic bone. Organs closest to the bladder include the rectum (the last part of the colon), which is the most posterior (closest to the back) organ in the pelvis, the prostate gland and seminal vesicles (in males), and the uterus, ovaries and fallopian tubes (in females). In males, the prostate gland and seminal vesicles (organs that contribute secretions in semen) are situated below the bladder and in front of the rectum. In females, the uterus (the womb), ovaries and fallopian tubes are located posterior the bladder and anterior to the rectum.
The bladder itself is made up of four layers. These layers are important landmarks in determining how deeply the tumor has invaded and the ultimate stage of the cancer.
1. Epithelium: The epithelium, which lines the bladder and is in contact with the urine, is referred as transitional epithelium or urothelium. Most bladder cancers originate from the cells of this transitional epithelium. The urethra, ureters and the pelvis of the kidney are also lined by this transitional epithelium, therefore, the same types of cancers seen in the bladder can also occur in these sites.
2. Lamina propria: Under the epithelium is the lamina propria, a layer of connective tissue and blood vessels. Within the lamina propria, there is a thin and often discontinuous layer of smooth muscle called the muscularis mucosae. This superficial layer of smooth muscle is not to be confused with the true muscular layer of the bladder called the muscularis propria or detrusor muscle.
3. Muscularis propria or detrusor muscle: This deep muscle layer consists of thick smooth muscle bundles that form the wall of the bladder. For purposes of staging bladder cancer, the muscularis propria has been divided into a superficial (inner) half and a deep (outer) half.
4. Perivesical soft tissue: This outermost layer consists of fat, fibrous tissue and blood vessels. When the tumor reaches this layer, it is considered out of the bladder.
There are several types of bladder cancers: the major type is urotheloal (transitional cell) carcinoma (>90%); other types include squamous cell carcinoma (2%); and adenocarcinoma (1%).
Grade and Stage describe the bladder tumor, helping to provide
guidance for the urologist in choosing the best treatment option(s). Staging
is a careful attempt to find out the extent of the cancer. Staging will define
whether the cancer has invaded into or through the bladder wall, whether
the disease has spread, and if so, to what parts of the body. The higher the
stage the further the cancer has grown away from its original site on the
surface of the bladder.
The following are the stages for bladder tumors: (Figure 5)
T0: No tumor
Ta: Papillary tumor involves the urothelium without invasion
into the bladder wall
TIS (CIS): Carcinoma in situ (non-invasive flat high grade cancer)
T1: Tumor invades the lamina propria
T2: Tumor invades the muscle layer
T3: Tumor grows through the bladder wall into the
surrounding fat layer
T4 Tumor invades other organs near the bladder
(i.e., prostate, uterus, vagina, pelvic wall)
Grade refers to what the cancer cells look like, and how many cells are multiplying. Grade is separated into low and high grade. High grade cancers are more aggressive.
The tumor can grow into the surrounding organs (uterus and vagina in women and prostate in men) and that is called locally advanced disease. It can also spread to the lymph nodes and/or to the liver, bones, or lungs and that is called distant metastasis. Rarely bladder cancer spreads to other parts of the body.
- Bladder cancer is nearly three times more common in men in the United States than in women, but women have more than a 30% higher chance of dying of bladder cancer, if they develop it, than men do.
- Bladder cancer is rare in persos younger than the age of 50, with median ages at diagnosis of around 70 years for each gender. Incidence of and mortality from the disease increase further with age.
- Bladder cancer occurs roughly half as often in African Americans as in whites ut is nearly twice as likely to be lethal in African Americans as in whites.
- In Hispanic Americans, bladder cancer also occurs about half as often as in whites but Hispanics are less likely to die of bladder cancer, if they develop it, than whis are.
For most people, the first symptom of bladder cancer is hematuria, or blood in the urine. Sometimes the blood can be seen (known as gross hematuria)_ when the patient urinates and occasionally blood clots will also be seen. At other times the urine looks clear but a “urinalysis” shows microscopic traces of blood (known as microscopic hematuria).
Other symptoms that might mean bladder cancer include:
- Frequent urination, or feeling the need to urinate without being able to do so
- Pain during urination
- Lower back pain
- Signs and symptoms of a blocked kidney such as flank pain, or imbalances in the chemicals in the blood having to do with the kidney
Bladder cancer has various risk factors. These include:
- Using tobacco, especially smoking cigarettes. (This is by far the greatest risk factor in the USA). increased risk (fourfold compared with people who never smoked) only declining slowly after smoking is discontinued. patients with bladder cancer who are smokers are strongly encouraged to start a smoking cessation program, to help people overcome their habit. Research has shown that quitting smoking will reduce the likelihood of developing a recurrence of bladder cancer.
- Being exposed to certain substances, such as soot from coal, or chemicals used to make rubber, certain dyes, paint, hairdressing supplies or textiles.
- Working as a dry cleaner or in places where paper, rope, twine, or clothing is made.
- Taking A. fangchi, a Chinese herb.
- Past treatment with certain anticancer drugs (esp cycylophosphamide) or radiation therapy to the pelvis.
- Having a kidney transplant.
- Having an inherited disorder called hereditary non-polypopsis colon cancer (HNPCC; Lynch syndrome).
Risk factors for squamous cell carcinoma
- Long-term use of urinary catheters.
- Having an infection caused by a certain parasite.
Diagnosis of bladder cancer can be made using the following tests:
- Cystoscopy: A urologist is able to examine the bladder using a small hollow lighted instrument inserted through the urethra into the bladder. Tissue samples (biopsies) may be taken through the scope for analysis
- Urine tests: Usually this is a so-called urine cytology; that is, an examination of urine under a microscope to check for abnormal cells. Sometimes sophisticated molecular tests are used in addition or instead of a cytology test
- CT scan or MRI of abdomen and pelvis. Preferably given with contrast if kidney function is adequate.
Once bladder cancer is discovered, the urologist must biopsy or resect the cancer in order for the stage and grade to be determined. This is usually done with the patient under anesthesia as an outpatient procedure. The urologist will perform a TRANSURETHRAL RESECTION OF BLADDER TUMOR (TURBT) which is done through the urethra similar to how cystoscopy is performed. Attached to this scope is a small, electrified loop of wire which is moved back and forth through the tumor to cut and remove the tissue
Your urologist may suggest instilling chemotherapy into the bladder at the time of TURBT to help prevent tumor recurrence.
The most common risks of the TURBT are bleeding, pain, and burning when urinating. If the bladder tumor is large, the urologist may choose to leave a urinary catheter for a few days two to minimize problems occurring from bleeding, clot formation in the bladder or expansion of the bladder due to possible storage of excess urine or blood. Even if the tumor is small, a catheter may be inserted to rinse the bladder out if the bleeding persists.
All the specimens from the TURBT will be sent to the pathologist for review. Whether further treatment is necessary will depend on the pathologist’s findings.
Low grade Ta (non-invasive) tumors
If the tumor is low-grade and non-invasive (Ta), the urologist will often choose to follow the patient with cystoscopy and/or cytology (urinalysis) on a regular basis. There will be life-long monitoring that will require diligence and compliance on the part of the patient.
High grade Ta/T1 tumors and/or CIS
These types of tumors are more aggressive with a higher risk of progression to muscle invasive disease. As a result, these tumors usually require additional treatment than just surveillance alone. Your urologist may choose to have you go back to the operating room to “reresect” the site of the initial tumor and take additional biopsies of the bladder. This is done to make sure that the tumor is accurately staged and helps to determine whether CIS is present or not.
There are tools to help your urologist determine what the risk of recurrence and progression are for those with non-muscle invasive tumors. One calculator is available on line at http://www.eortc.be/tools/bladdercalculator/. These tools can be helpful for you and your urologist. Usually, these tumors are treated with intravesical immunotherapy or chemotherapy, although in select cases, the decision is made to remove the bladder (cystectomy) because of a high risk of future disease progression.
Intravesical treatments are given in the urology clinic. The treatment is instilled through a temporary urinary catheter. You will receive 6 treatments over 6 weeks (induction treatment). Your urologist may then want to take repeat biopsies after 6-8 more weeks. You will then be placed on a surveillance schedule with periodic cystoscopy and urine cytology testing. Often, a “maintenance” schedule of intravesical treatment will be suggested to be given Weekly for three weeks given at 3, 6, 12, 18, 24, 30, and 36 months after the initiation of induction therapy.
General instructions for patients receiving intravesical therapy
· Patients should be instructed not to drink any fluid in the twelve hours prior to instillation.
· Once the instillation has been completed, the patients should be rotated a quarter turn every fifteen minutes.
· The treatment should be retained in the bladder for 1 hour.
· The patient should be instructed to void at the end of the treatment hour
There are several different agents for intravesical instillation. However, the primary agents are mitomycin C (MMC) and BCG.
Mitomycin C is an intravesical chemotherapy drug that has been
shown to be effective after the TURBT in reducing the number of
recurrences of bladder tumors by as much as 50%. An advantage of
Mitomycin C is that it is not easily absorbed through the lining of the
bladder and into the blood and, thus is less risky than chemotherapy
given intravenously (into the veins). Side effects from the drug can be
painful urination and/or “chemical cystitis,” an irritation of the lining
of the bladder which can feel like a urinary tract infection.
Bacille Calmette-Guerin or BCG is intravesical immunotherapy which
causes an immune or allergic reaction that has been shown to kill cancer
cells on the lining of the bladder. Bacillus Calmette-Guerin (BCG), which is an inactivated form of the bacterium Mycobacterium tuberculosis. BCG is preferred for high risk tumors. Dysuria (pain or difficulty upon urination) and urinary frequency are expected as a consequence of the inflammatory response, and cystitis is the most frequent adverse reaction-occurring in up to 90% of cases. Blood in the urine may occur with cystitis and is seen in one-third of patients. Side effects of BCG are cumulatory, and generally increase with successive treatments.6 Some people complain of flu like symptoms including fatigue, joint pain and muscle ache. 7 If you experience a high fever after BCG treatment, contact your doctor immediately. Because BCG is an inactivated for of tuberculosis, in very rare circumstances a person may require treatment for tuberculosis.
Tumors that recur during or after intravesical treatment may be treated in different ways, including
· Retreatment with the same intravsical agent
· Treatment with a different intravesical agent
· Radical cystectomy (removal of the bladder)
muscle-invasive bladder cancers are not treated with intravesical therapy. Instead, these tumors are usually treated with radical cystectomy (removal of the bladder) . In rare cases, a partial cystectomy may be performed.
In a radical Cystectomy, The bladder is removed by the urologist together with the surrounding lymph nodes. In a man the prostate is also removed., In women most often the urterus and ovaries are also removed; sometimes part of the vagina must be removed also.
After removal of the bladder, the urologist uses a segment of your intestines (usually the small bowel) to drain your urine. There are different options for urinary reconstruction. Each has advantages and disadvantages. The decision on urinary diversion requires consideration of several factors, including physician and patient preference, extent of disease, an individuals anatomy and other medical conditions (e.g., kidney function, overall health, age). The three options are:
1. Ileal conduit (ileal loop)
3. Continent cutaneous urinary reservoir (CUR)
An Ileal Conduit is the easiest and most common reconstruction
performed by the urologist. A small portion of the ileum or small
intestine is disconnected. One side of the piece of ileum is attached to
a skin opening on the right side and a small stoma or mouth is created.
A plastic appliance or ostomy bag is placed over the stoma to collect
the urine. The ureters are sewn or re-implanted near the other end of
the ileum. Because the nerves and the blood supply are preserved, the
conduit is able to propel the urine into the appliance.
A continent cutaneous pouch is an internal storage “container” for
urine. Using a combination of small and large intestine, the urologist
reconstructs the tubular shape of the intestine and creates a sphere
or pouch. This pouch is connected to the skin on the abdomen by a
small stoma creating a type of continent urinary reservoir; no external
bag is necessary. The patient drains the pouch periodically by inserting
a catheter (a thin tube) through the small stoma and then removing
the catheter and, in some cases, covering the stoma with a bandage.
A neobladder creates an internal storage “container” for urine. Using a
portion of small intestine, the urologist reconstructs the tubular shape of
the intestine and creates a sphere. The ureters are connected at the top
of the sphere, while the urethra is attached at the bottom (Figure 11).
By tensing the abdominal muscles, relaxing the sphincter muscle, the
patient is able to push the urine through the urethra.
In many situations, chemotherapy may be recommended prior to cystectomy (termed neoadjuvant chemotherapy). clinical trials have shown that the use of intravenous chemotherapy before radical cystectomy improves survival for
patients with invasive bladder cancer. It appears that this type of initial chemotherapy shrinks the tumor within the bladder and may also kill small metastatic deposits of disease that have spread beyond the bladder.
However, not all patients are candidates for chemotherapy and several factors are considered when determinging whether or not chemotherapy is right for you. In addition to discussing with your urologist, you may meet with a medical oncologist to discuss neoadjuvant chemotherapy further.
After surgery, chemotherapy may be recommended depending on the extent of disease and whether or not the cancer had spread to the lymph nodes. Chemotherapy after surgery is called adjuvant chemotherapy.
Another alternative for muscle invasive bladder cancer treatment is a combination of chemotherapy and radiation as bladder preservation treatment.
To ensure the success of bladder preservation therapy, there are at least
Four requirements which should be met: 1) a “complete” resection of the
tumor(s) by TURBT; 2) no obstruction of one or both kidneys as a result
of the bladder tumor; 3) no T3/4 bladder tumors, and 4) no CIS.
If the tumors do not respond to an initial course of chemotherapy
and radiation, it may be reasonable to perform, if medically possible, a