BLADDER CANCER

The bladder is composed of several layers:

• the urothelium which is the mucosal lining on the inside of the bladder
• the lamina propria, a layer of loose connective tissue
• the detrusor or bladder muscle layer
• an outer serosal covering layer.

Tumours can be benign or malignant. Benign tumours are not cancerous and do not spread. Malignant tumours are cancer. Bladder cancer is the most common cancer affecting the urinary tract and mainly begins in the urothelium (bladder lining).

The most common of these urothelial cancers is known as transitional cell cancer (TCC) which may occur anywhere in the urinary tract, but is most frequently found in the bladder.  This form of cancer can develop in many different ways. Some TCC bladder cancers grow like warts on the surface of the bladder lining, known as papillary tumours, while others may grow into large tumours and penetrate the different layers of the wall of the bladder.

A small percentage of urothelial tumours are squamous cell cancers (SCCs) or adenocarcinomas. These may occur as a result of infections such as schistosomiasis and are commonly found in parts of the world where this disease is rife.

Carcinoma in situ (CIS) is a rarer form of flat bladder cancer that spreads over the surface of the bladder. Eventually it can progress into a more invasive form of cancer as above. Since when viewed during cystoscopy, CIS may appear indistinguishable from Hunner’s ulcer, biopsy is essential.
If a bladder cancer only affects the inner lining of the bladder, it is known as a superficial cancer. If it has spread into the muscle wall of the bladder, it is called an invasive cancer. This type of cancer can pentrate not only the bladder wall but also spread into the abdomen, the reproductive organs in the female or to the prostate gland in the male. Metastatic cancer includes tumours which have spread to sites in the body other than the bladder (e.g. lymph nodes, bone, lungs).
The most common symptoms are:

• blood in the urine (haematuria)
• pain during urination
• frequent urination
• thin urine flow
• pelvic pain

Bladder cancer may not produce any symptoms in the early stages. The first indication may be blood in the urine.

The symptoms of bladder cancer can therefore sometimes closely resemble those of other non-cancerous disorders such as urinary tract infections, prostatitis, painful bladder syndrome/interstitial cystitis and stones and benign tumours.

Diagnosis
Diagnosis of bladder cancer includes urological tests (urine cytology) and imaging.
The radiological imaging tests (X-rays) may include an intravenous pyelogram (IVP) in which a dye or contrast agent is injected into a vein. The dye collects in the urine and gives a clear picture of the urinary tract including the bladder. Other imaging tests include computerised tomography (CT) scan, magnetic resonance imaging (MRI), bone scan and ultrasound.
Cystoscopy may be performed under anaesthesia. At the same time, the urologist may remove small samples of tissue. This is known as a biopsy. The tissue samples will be examined under a microscope by a pathologist to see if any cancerous cells are present.
The cancer is then graded and staged. The staging level depends on the degree of penetration of the different layers of the bladder. It is important for the doctor to know if the cancer has spread and if so to which parts of the body.

Treatment
Treatment may consist of surgery, radiation therapy, chemotherapy or immunotherapy (also sometimes called biological therapy) or a combination of these.

These therapies can sometimes cause PBS/IC-type symptoms in the bladder.

The type and extent of the surgery will depend on the type and stage of the cancer. This can include: transurethral resection (TUR) when the cancerous area is burnt away in a process known as fulguration, segmental cystectomy when part of the bladder is removed, radical cystectomy where the entire bladder is removed and replaced by a stoma (with either a continent internal pouch or a pouch worn on the outside of the body).

Further patient information on bladder cancer:

http://www.cancer.gov/cancertopics/types/bladder

http://www.urologyhealth.org/adult/index.cfm?cat=03&topic=37

CHEMICAL / DRUG-INDUCED CYSTITIS

In cancer patients, cystitis may be caused by treatment with chemotherapy drugs (e.g. cyclophosphamide and ifosfamide). These drugs are broken down in the body, leading to formation of metabolites. These are removed from the body in the urine and irritate the lining of the bladder. Other cancer drugs may be administered intravesically and also have the side-effect of irritating the bladder.

Symptoms may include:

• urinary urgency/frequency
• pain or burning when urinating
• abdominal pain
• partial urinary retention
• blood in the urine
• incontinence
• irritation of the perineum or vulva

Tiaprofenic acid, a non-steroidal anti-inflammatory drug, is also known to cause cystitis and is often misdiagnosed as interstitial cystitis. Indomethacin, another NSAID, has also been reported as causing IC-like changes in the bladder in animal experiments.

CHEMICAL IRRITANTS

Chemical irritants such as deodorants and intimate sprays in the genital area, perfumed bubble baths, perfumed soap, perfumed condoms or contraceptive creams may also give rise to symptoms of cystitis.

ENDOMETRIOSIS

Endometriosis is an enigmatic and debilitating disease affecting females in their reproductive years. The cause of endometriosis is unknown. Genetic, environmental and immunologic risk factors have been suggested in studies. All urine cultures are negative and the symptoms do not respond to antibiotic treatment.

The name comes from the term “endometrium” which is the normal layer of tissue that lines the uterus. Each month in the menstrual cycle it builds up and is shed, responding to the rise and fall of estrogen and progesterone produced by the ovaries during the reproductive cycle.
In endometriosis, endometrial tissue is found in other parts of the body, in places where it is not supposed to grow.

Most endometriosis is found in the pelvic cavity:

• on or under the ovaries
• behind the uterus
• on the tissues that hold the uterus in place
• on the intestines or bladder

In very rare cases, endometrial tissue can grow in the lungs or other parts of the body. If it occurs on the ovaries, it may cause cysts to form: so-called ‘chocolate cysts’.

Since symptoms of endometriosis can also closely resemble those of painful bladder syndrome/interstitial cystitis, it is important to avoid the wrong diagnosis.

Symptoms

Endometriosis can cause:

• pelvic pain
• debilitating fatigue
• pain with sexual intercourse
• infertility
• pain before and during menstrual periods
• diarrhoea and/or constipation
• nausea

Bladder endometriosis can cause:

• painful urination
• bladder pain
• blood in the urine
• urgent, frequent need to urinate

Many patients with endometriosis also experience a range of associated disorders such as: allergies, asthma, eczema and certain autoimmune diseases.

There is no known cure for endometriosis: treatment is aimed at alleviating symptoms and may comprise medication (hormonal, pain therapy) or surgery. Oral contraceptives may relieve the symptoms. Symptoms may lessen, however, after the menopause.
Severe cases of bladder endometriosis may necessitate cystectomy (surgical removal of the bladder).

Further patient information:

http://www.nichd.nih.gov/publications/pubs/endometriosis/sub2.htm#what

http://hcd2.bupa.co.uk/fact_sheets/html/endometriosis.html

http://www.endometriosisassn.org

http://www.endo.org.uk/

and see also further reading and references below.

EOSINOPHILIC CYSTITIS

Eosinophilic Cystitis (EC) is a rare inflammatory bladder disorder of unknown cause characterised by “transmural” inflammation (= inflammation through all layers of the bladder wall) and numerous eosinophils. Urine cultures are usually negative. EC can mimic many other urological conditions.

What are eosinophils?
Eosinophils - or eosinophilic granulocytes to give them their correct name - are white blood cells that are active and accumulate in allergic diseases, parasitic infections and other disorders including allergic reactions to medication, autoimmune diseases, asthma, hay fever. The name eosinophil comes from the fact that these cells readily absorb the red dye eosin when examined microscopically.
A study in 2004 reported eosinophilic cystitic induced by an allergy to pencillin.

Symptoms of eosinophilic cystitis may include:

• frequent urination
• blood in the urine
• painful urination
• urinary retention
• nocturia (frequent urination at night)
• suprapubic pain
• bladder lesions
• oedema of the bladder wall
• fibrotic, shrunken bladder
• upper urinary tract dilatation

EC is equally distributed between adult men and women, but in children more boys appear to be affected than girls.
Tests include urinalysis, urine culture, eosinophil count, cystoscopy, biopsy and ultrasound of the bladder and upper urinary tract. Ultrasound may reveal irregular thickening of the bladder wall and tumour-like masses. Cystoscopy and biopsy are essential diagnostic investigations to distinguish EC from cancer. Cystoscopy may show red lesions and swelling, but it may be difficult to tell the difference between eosinophilic cystitis and painful bladder syndrome/interstitial cystitis, tuberculous cystitis, carcinoma in situ (CIS) and other malignancies. Some other conditions can cause secondary eosinophilia (increased eosinophils) in the bladder wall such as tumours, injury and parasitic infections. Deep biopsy is therefore vital to establish a diagnosis of EC.

Treatment includes oral medication (corticosteroids, antihistaminics, NSAIDs), intravesical treatment, avoidance of the suspected antigen, surgical transurethral resection (TUR) or fulguration of bladder lesions and partial cystectomy. Recurrence is common.
Radical cystectomy (removal of the bladder) is reserved for patients for whom all other therapies have failed

RADIATION CYSTITIS

Radiation is used to treat cancer because it damages cancer cells more than the normal cells of the body. However, radiotherapy for pelvic cancer can have the side effect of radiation cystitis or radiation-induced haemorrhagic cystitis in either an acute or delayed form. Symptoms may occur immediately after treatment or may take up to ten years to appear. Radiation cystitis presents a range of symptoms similar to infectious cystitis or PBS/IC:

• bladder inflammation
• pain
• minor to very severe, life-threatening bleeding
• a frequent and urgent need to urinate.

Hyaluronic acid (HA) is being used with some success for both treatment and prevention of radiation cystitis. A study in 2003 showed that intravesical treatment with HA during radiotherapy reduced radiation-induced toxicity in the bladder in some patients.
Studies have also shown hyperbaric oxygen therapy to be potentially useful for radiation cystitis.

STONES IN THE URINARY TRACT

Stones, known as calculi, can form in any part of the urinary tract. They may cause pain, bleeding, obstruction or infection in the kidneys, ureters or bladder. Urolithiasis is the medical term used to describe stones in the urinary tract. Stones form in the kidneys. They may stay in the kidneys, but may move and cause problems anywhere in the urinary tract.
There are different types of kidney stones, formed from different combinations of chemical and minerals:
Calcium stones: may combine with oxalate or calcium phosphate to form stones;
Uric acid stone: formed by people with too much acid in the urine;
Struvite stones: may form following an infection in the urinary tract and contain magnesium and ammonia;
Cystine stones: this is a rare inherited disorder.
Stones in the bladder will be seen during cystoscopy.

Symptoms include:

• extreme pain in the back or side, spreading to the groin
• fever and chills
• blood in the urine
• abdominal distension
• nausea and/or vomiting
• cloudy urine or urine that smells bad
• a burning feeling when urinating

As a stone grows or moves, blood may appear in the urine. If a patient is feverish, this may indicate that the stone has caused an infection. If the stone starts moving but is too large to pass, severe pain may occur. As the stone moves down the urinary tract towards the bladder, there may be frequent need to urinate with a burning sensation during urination. Stones in the bladder can cause irritation of the bladder lining or may form an obstruction making it difficult to urinate or causing an interrupted flow or complete retention. By contrast, stones can also be a cause of incontinence.

Some stones are very small and are simply passed through the urethra. Drinking plenty of fluids will increase fluid production and flush out some stones. For others, drugs may be prescribed. Uric acid stones are sometimes gradually dissolved by making the urine more alkaline. The most commonly used treatment today is Extracorporeal Shockwave Lithotripsy (ESWL). This shock wave therapy breaks up the stones into fine grains that can easily pass through the urinary tract. Surgical treatment is reserved for cases where other options have failed. This includes percutaneous nephrolithotomy for stones in the kidneys or ureteroscopic stone removal for mid and lower ureter stones. Some stones may need to be removed by means of open surgery.

Tips

• To help prevent the formation of stones drink plenty of liquid, preferably water.
• Diets may be recommended for people with a tendency to form specific types of stone.

Further detailed information on kidney stones:

http://kidney.niddk.nih.gov/kudiseases/pubs/stonesadults/

TRAUMA (INJURY)

Trauma following accidents to the bladder, urethra or penis may also be a cause of painful bladder and/or urethra, painful urination, incontinence or overactive bladder.
Trauma may include penetrating instruments (gunshot or stab wounds), car accidents with pelvic injury, falls, blows causing bladder perforation, rupture. Obstetric trauma includes forceps delivery, prolonged labour or Caesarian deliveries. The bladder may be perforated in biopsies or through surgery. Sexual assault can cause urogenital damage. Trauma following vigorous or prolonged “normal” sexual intercourse can cause minor damage, inflammation, bruising and cystitis-like symptoms (as in Honeymoon cystitis). Women with the problem of a dry vagina should use a lubricant to prevent vulvovaginal damage from friction.

Localised vulvodynia (vulvar vestibulitis)
Vulvar vestibulitis is pain or burning sensation caused by something touching the vestibule. Pain is caused by sexual intercourse, insertion of tampons, riding a bicycle, gynaecological examination, tight clothes, any situation where the vestibule is touched. There is usually no pain if the area is not touched. Vulvar vestibulitis is diagnosed by touching the vestibule with a Q-tip. Even light pressure such as this can cause pain.

Generalised (dysesthetic) vulvodynia
Generalised or dysesthetic vulvodynia is pain, burning, stinging or rawness on or around the vulva, labia, vestibule, clitoris or perineum most of the time, whatever they are doing. It is not dependent upon touch or pressure but this can nevertheless exacerbate the symptoms. Urination may cause pain and burning. Sexual activity is sometimes so painful as to be impossible, while at other times there may be little or no pain. Generalised vulvodynia is diagnosed when there is a history of constant pain with no visible cause or other identifiable disorder.

Although treatment is available (local anaesthetic ointments, antidepressants, anticonvulsants), vulvodynia can sometimes be difficult to treat. Studies are looking into new treatments.