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Urologic Oncology

Jump to: Adrenal Cancer | Bladder Cancer

Adrenal Cancer

Adrenal cancer is a rare disease that originates in the adrenal glands. The adrenal glands are located on top of the kidneys and consist of two parts that function separately: the outer layer (cortex) and the inner area (medulla).

The cortex produces three major hormones: cortisol (a glucocorticoid), aldosterone (a mineralocorticoid), and dehydroepiandrosterone (DHEA; an androgen). The medulla produces epinephrine (adrenaline), norepinephrine, and dopamine.

Adrenal tumors can increase hormone production (called functioning tumors). Adrenal tumors that do not produce hormones are called nonfunctioning. Symptoms of adrenal cancer and treatment for the condition depend on whether the tumor is functioning or nonfunctioning, and on which hormone is being overproduced.

Types

Most (99%) adrenal tumors are noncancerous (i.e., benign) adrenal cortical adenomas and do not require treatment. These tumors usually do not cause symptoms, are small, and are found incidentally during diagnostic imaging. The most common type of adrenal cancer develops in the adrenal cortex and is called adrenocortical carcinoma. Functioning adrenocortical carcinomas may produce symptoms related to increased hormone production.

Nonfunctioning tumors may cause pain from pressure on abdominal organs and a mass in the abdomen that is able to be felt with the fingers (palpable).
Cancers that develop in the adrenal medulla include neuroblastoma (originates in undeveloped nerve cells) and pheochromocytoma (originates in cells that produce epinephrine and norephinephrine). Neuroblastoma usually occurs in infants and children and pheochromocytoma more commonly occurs in people who are in their 30s and 40s.

Other types of cancer (e.g., breast, lung) may spread (metastasize) to the adrenal glands.

Incidence and Prevalence

Worldwide, about 1 out of 1 million people develop adrenal cancer each year. Prevalence of the condition is slightly higher in men in their 40s and 50s and in children younger than 5 years old.

Causes and Risk Factors

The cause of adrenal cancer is unknown and most cases do not have identifiable risk factors. In some cases, heredity plays a role in the development of the disease. Li-Fraumeni syndrome and type 1 multiple endocrine neoplasia (MEN1) are genetic mutations in tumor suppressor genes that increase the risk for several types of cancer, including adrenal cancer.

Genetic testing may be recommended in families with a high incidence of suspected tumor suppressor gene mutation. Other familial syndromes associated with adrenal cancer include:
• Gardner syndrome
• Carney triad
• Cowden syndrome
• Familial polyposis
• Turcot syndrome
• Signs and Symptoms

Adrenal cancer does not always produce symptoms. Both nonfunctioning adrenocortical carcinomas and large functioning tumors may cause the following:
• Fever
• Palpable (able to be felt with the fingers) abdominal mass
• Persistent abdominal pain
• Sensation of abdominal "fullness"
• Weight loss
• Additional symptoms of functioning adrenocortical carcinoma depend on which hormones are overproduced. Overproduction of androgens (e.g., dehydroepiandrosterone, estrogen) usually does not produce symptoms in men because the testicles produce testosterone, which is a more potent androgen. Rarely, abnormal breast enlargement (gynecomastia) occurs in men. Excess androgens may cause early puberty in children and masculinization (i.e., abnormal facial and body hair, deepening voice) in women and children.

Complications

• A functioning adrenocortical tumor that produces excess cortisol may result in Cushing's syndrome. Approximately 30–40% of patients with Cushing's syndrome and an adrenal mass are diagnosed with adrenal cancer.
• Symptoms of Cushing's syndrome include the following:
• Absence of menstruation (amenorrhea)
• Bruising easily
• Excessive growth of facial and body hair in women (hirsutism)
• Flushing (reddish complexion)
• High blood pressure (hypertension)
• Increased blood sugar, diabetes (hyperglycemia)
• Increased body fat (adiposity) in the face, neck, and abdomen
• Loss of bone mass (osteoporosis); may cause spinal curvature
• Severe acne
• Slowed growth rate in children
• Stretch marks (abdominal striae)
• Weakness and muscle wasting
• Conn's syndrome is caused by increased aldosterone production and may result from a functioning tumor in the adrenal cortex. Symptoms of Conn's syndrome include the following:
• Chronic excessive thirst (polydipsia)
• Excessive urination (polyuria)
• High blood pressure (hypertension)
• Low level of potassium in the blood (hypokalemia)

The hallmark of pheochromocytoma is sudden or sustained high blood pressure that is often resistant to treatment. Other symptoms include severe headaches, sweating, heart palpitations (rapid pulse), and nausea. Symptoms of neuroblastoma include abdominal pain and bone pain resulting from metastatic disease.

Diagnosis

Diagnosis of adrenal cancer involves taking a medical history and performing a physical examination, blood and urine tests, imaging tests, and a biopsy. Medical history includes family history of adrenal cancer, menstrual (in women) and sexual history, and the patient's history of symptoms. Physical examination includes palpating (feeling with the fingers) the abdomen for evidence of an adrenal mass.

Blood and Urine Tests
Blood and urine tests are used to detect elevated levels of hormones (e.g., cortisol, aldosterone) and other substances (e.g., potassium). The patient's symptoms determine which tests are performed.

Imaging Tests
Computed tomography (CT scan) and magnetic resonance imaging (MRI scan) are the imaging studies of choice used to produce images of the adrenal gland and identify abnormal enlargement or tumors. CT scan uses x-rays to produce detailed images of the adrenal glands, other abdominal organs, and lymph nodes. In some cases, a contrast agent (dye) is used to detect metastasis.

MRI uses magnetic fields to produce a cross-sectional image that detects abnormal enlargement of the adrenal gland. This test may be used to help determine if adrenal tumors are benign or cancerous (malignant).

Biopsy
Biopsy is the surgical removal of cells or tissue for microscopic evaluation. This procedure may be used to evaluate an adrenal mass for cancer cells. During biopsy, ultrasound or CT scan is used to guide a needle into the tumor to remove cells (called a fine needle aspirate) or a larger amount of tissue (called core tissue biopsy). The cells are then examined under a microscope and if cancerous cells are found, the cancer

Treatment

Treatment for adrenal cancer depends on the stage of the disease at diagnosis. Options include surgery, chemotherapy, and radiation. Treatment for patients with functioning tumors usually involves using medications to manage symptoms. Pheochromocytomas require treatment before surgery (neoadjuvant treatment) for high blood pressure, which often includes alpha-blockers (e.g., phenoxybenzamine, prazosin) followed by beta-blockers (e.g., propranolol), and metyrosine.

Surgery
Surgical removal of the adrenal gland (called adrenalectomy) is the only cure for adrenal cancer. It is important to determine if the cancer has spread before surgery, because metastases to lymph nodes or other organs (e.g., liver, lungs, and kidneys) often require extensive surgery. Adrenal tumors that have not spread are sometimes removed using laparoscopic adrenalectomy, which is performed through a smaller incision.

Chemotherapy
Chemotherapy is a treatment that travels throughout the body via the bloodstream (called a systemic treatment) that often uses a combination of drugs to destroy cancer cells. It is used as a palliative treatment for metastatic adrenal cancer and may also be used in addition to surgery (adjuvant therapy). Drugs may be administered orally or through a vein (intravenously).

Mitotane (Lysodren®) suppresses adrenal gland function and is the drug of choice to treat inoperable adrenal cancer. Approximately 20% of adrenal cancer patients respond to treatment with mitotane. Side effects include gastrointestinal disturbances (e.g., loss of appetite, nausea, vomiting, and diarrhea) and neurological disturbances (e.g., depression, lethargy, sleepiness).

When mitotane therapy fails, cisplatin (Platinol®) may be tried, alone or combined with other agents. Drug combinations used include the following:
Cyclophosphamide (Cytoxin®, Neosar®), doxorubicin (Adriamycin®), cisplatin Fluorouracil (Adrucil®, Efudex®), doxorubicin, cisplatin
Cisplatin with VP-16 Neuroblastoma may be treated with chemotherapy in addition to surgery (adjuvant therapy) using carboplatin (Paraplatin®), cyclophosphamide, doxorubicin, and etoposide (Vepesid®).

Side effects of chemotherapy are often severe and include gastrointestinal disturbances, low blood count (anemia), skin disorders, and neurological disorders.

Radiation Therapy
Radiation therapy uses high energy x-rays to destroy cancer cells. Radiation is not used as a primary treatment for adrenal cancer. It is sometimes used as a pain relieving (palliative) treatment for metastatic adrenal cancer.

Medical Management of Functioning Tumors
Treatment for patients with functioning tumors includes managing symptoms caused by increased hormone production.
Increased cortisol production (Cushing's syndrome) is often treated with aminoglutethimide or ketoconazole (Nizoral®) to inhibit cortisol build-up (synthesis). They may be used alone, or in combination with chemotherapy. Side effects include nausea, vomiting, and abdominal pain.
Excess aldosterone production ( Conn's syndrome) is usually treated using spironolactone (Aldactone®). Spironolactone is an aldosterone antagonist (i.e., counteracts the action of aldosterone). Side effects include ulcers, abnormal breast enlargement in men (gynecomastia), fever, and headache.
Aromatase inhibitors such as anastrozole (Arimidex®) and anti-androgens such as bicalutamide (Casodex®) may be used to treat excessive androgen production.

Prognosis

The prognosis for adrenal cancer depends on the stage of the disease. Metastatic tumors have a poor prognosis. The 5-year survival rate when surgical removal of the cancer is achieved is approximately 40%. About 80% of cases recur within 10 years after treatment.

Prevention

Adrenal cancer cannot be prevented.

Bladder Cancer

Overview

Bladder cancer is the second most common urologic cancer after prostate cancer accounting for approximately 54,000 cases per year. The actual causes of bladder cancer are unknown although it is associated with exposure to tobacco and certain chemicals.

Risk Factors and Warning Signs

The risk of developing bladder cancer is greater for individuals who have:

  • Tobacco Use: According to the American Cancer Society, smoking is responsible for approximately 47 percent of bladder cancer deaths among men and 37 percent among women
  • Industrial Chemicals and Dyes Exposure

The most common warning sign of bladder cancer is blood in the urine (hematuria), which does not necessarily change the color of the urine as it is very often microscopic (not visible to the naked eye).

Other symptoms may include:

  • Change in bladder habits, including having to urinate more often: 
  • Difficulty initiating or stopping urine flow 
  • Weak or interrupted urine flow 
  • Painful urination

Early Detection and Screening

Screening tests (which are also used diagnostically) may include:
• Urine Cytology: In this test, the urine is examined under a microscope to look for any cancerous or precancerous cells.
• Cystoscopy: Using a cystoscope - an instrument consisting of a slender tube with a lens and light that is placed into the bladder through the urethra - the physician can check the bladder and urethra for possible cancers. Suspicious tissue can be removed during this procedure so that they may be checked under a microscopic for signs of cancer.

Diagnosis 

If bladder cancer is suspected, there are several methods to confirm the diagnosis as well as to determine the stage (spread) of the disease. Staging of the bladder cancer is necessary to determine the most effective therapy. This takes into account the size of the tumor, the extent of disease as to whether it has metastasized or spread to other organs.

superficial bladder cancer
Superficial bladder cancer
invasive bladder cancer
Invasive bladder cancer
In Stage 0, the tumor cells remain confined within the bladder and have not invaded the muscle or connective tissue of the bladder wall. Stage I disease means the cancer has spread to the layer of connective or supporting tissue under the lining layer of the bladder, but it has not spread to the thick layer of muscle in the bladder wall, the lymph nodes or to any other organs. In Stage II disease, the tumor has invaded the thick muscle layer of the bladder wall, but has not reached the fatty tissue that surrounds the bladder or beyond. Stage III and IV indicate more serious disease with invasion of the cancer into nearby organs, such as the prostate, uterus or vagina, or in Stage IV, to the lymph nodes and more distant organs, such as bones, liver or lungs. The lower the number of the stage, the less the cancer has spread.

To make the diagnosis and to assess the extent of the tumor the following are often necessary:
• Biopsy: Suspicious tissue can be removed during a cystoscope procedure so that it can be analyzed under a microscopic for signs of cancer.
• CT Scan: If it is suspected that bladder cancer has spread, a CT scan of the pelvis provides information about the extent to which it has spread.
• MRI Scan: Like the CT scan, an MRI may be recommended to determine if cancer has spread beyond the bladder into adjacent tissues, nearby lymph nodes or to distant organs.

Treatment

Surgery
• TRANSURETHRAL SURGERY: This procedure is indicated for bladder cancer in the early stages. It is performed through a cystoscope like instrument to scrape out the tumor within the bladder when it has not penetrated the bladder wall. Since there is a propensity for recurrence, close follow-up treatment is indicated to ensure early detection of future cancers.
• CYSTECTOMY: For cancer that is more invasive, a cystectomy may be indicated in which part of the bladder (partial cystectomy) or the entire bladder and nearby lymph nodes and adjacent organs (radical or total cystectomy) may be indicated.
• RECONSTRUCTIVE SURGERY: If the bladder needs to be removed, reconstructive surgery can be performed to create an alternative for storage and removal of urine. Please see “Urinary Diversion”.

Radiation Therapy
Radiation therapy is usually advised to eliminate any remaining abnormal cells following transurethral surgery. The treatment uses high-energy rays that are applied externally or small pellets of radioactive material placed directly into the cancer. Radiation therapy may also be used to shrink the tumor prior to surgery to make the procedure easier. External beam radiation therapy administered in conjunction with chemotherapy following local removal of a bladder tumor can allow for bladder preservation without compromising loco-regional tumor control.

Immunotherapy
In this treatment, an immunotherapeutic agent (BCG) is delivered directly to the bladder (intravesical) through a catheter to treat low-stage bladder cancer.

Chemotherapy
Chemotherapy uses drugs to destroy cancer cells and is an important treatment for bladder cancer and can be delivered directly into the bladder (intravesical), by mouth or via injection. When given directly into the bladder, the chemotherapy will not reach cancer cells that have invaded the bladder wall or spread to other organs. Therefore this treatment is used for only non-invasive or minimally invasive bladder cancer. For more advanced disease, chemotherapy should be given by mouth or by injection so that it can reach cancer cells that have spread beyond the bladder to lymph nodes and other organs.

Prevention

It is recommended to abstain from smoking - a significant risk factor for developing this disease, and to use appropriate precautions to limit occupational exposure to certain dyes (particularly aniline dyes), rubber and leather, which have been shown to increase the risk of bladder cancer.