CANCER (the disease of diseases)

CANCER

2011-06-21T08:43:00.000-07:00

Cancer is a type of disease in which cells divide abnormally without control and may overrun other tissues. Through blood and other lymph system these cell spread all over the body. Cancer result in spread of cells which can not be controlled.

General information about cancer:The technical term for Cancer is malignant neoplasm, a class of diseases in which a group of cells displays uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). What differentiates these three malignant properties of cancers from benign tumors is that benign tumors are self-limited, and do not invade or metastasize. Although most cancers form a tumor some, like leukemia, do not. There is a specific branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer called oncology.

Cancer is very insidious and may affect people at all ages, even fetuses, but the risk for most varieties increases as a person’s cells age. It is a known fact that cancer causes about 13% of all human deaths. According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007. In fact, cancers can affect all animals.

Almost every cancer known is caused by abnormalities in the genetic material of the transformed cells. There are many possibilities from which these abnormalities may arise. They may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. There are other cancer-promoting genetic abnormalities which may be randomly acquired through errors in DNA replication, or they are inherited, and thus present in all cells from birth. The inheritability of cancers is usually affected by complex interactions between the carcinogens and host's genome. As the field of cancer is studied and new discoveries are made through the human genome, new aspects of the genetics of cancer pathogenesis, such as DNA methylation, and micro-RNAs are increasingly recognized as important.

Two general classes of genes are typically affected by genetic abnormalities found in cancer: Cancer-promoting oncogenes, which are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes then become disactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

A cancer diagnosis usually requires the histologic (the minute structure of animal and plant tissues as discernible with the microscope) examination of a tissue biopsy specimen by a pathologist, even though there may be initial indication of malignancy, which can be symptoms or radiographic imaging abnormalities. Depending on the specific type, location, and stage, most cancers can be treated and some even cured. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. Treatments are becoming more specific for different varieties of cancer as research and knowledge develop.

On another front, there has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Symptoms of cancerTypes The main types of cancer are sarcoma, carcinoma, lymphoma and myeloma, leukemia, central nervous system cancers.

•Sarcoma begins in muscle blood, vessels, cartilage, fat, bone, or any other connective or supportive tissue.
•Carcinoma begins in skin or tissues which cover internal organs.
•Lymphoma and myeloma begins in immune system cells.
•Leukemia starts in blood forming tissue as bone marrow, producing numerous abnormal blood cells and then they enter to blood.
•Central nervous system cancer begins into spinal cords and brain.
origin Cancer has its origin in cell which is basic unit of human body. Body cells raise and divide within limit to keep body healthy. When they become old, they are replaced with new cells. Occasionally change or damage in the DNA material of cell results in mutation production. It affects division and growth of cell. At this stage death of old cells stop but formation of new ones goes on. As a result extra cells produce a tumor, a mass of the tissues. In leukemia tumor is not formed. All tumors are not cancerous some of them are malignant and some of them are benign. Benign tumors are not cancerous and they can be removed. They often do not come back. The cells from these tumors do not spread in body. Malignant tumors are cancerous tumors .These cells can spread in to other parts of body. These cells increase suddenly. Metastasis means spreading cancer from one part to other one. Caners are named after their origin into a specific organ.e.g. Cancer beginning in the mouth is known as the oral cancer.

Risk factors of cancer
External factors causing cancer are:

•Tobacco
•Infectious organisms
•Radiation
•Chemicals
Internal factors causing cancer are:

•Hormone
•Inherited mutations
•Immune conditions
•Mutations that occur from metabolism
If you are exposed to external factor and you are caught by the disease then ten or more years pass till cancer is detected.

Treatment of cancerSurgery,chemotherapy or radiation, biological therapy, hormone therapy,and the target therapy treat cancer.

The treatment provides you options. You have to decide that if you want to cure and control your disease or only get comfort. In early diagnosis cure is possible in middle stage control is achieved and at the last stage the person just wants to live comfortably. Your health in general, financial costs of treatment, reactions of the treatment, effect of treatment can be checked and then after consulting with your surgeon treatment is decided.

Prevention of Cancer
If cancer causes by heavy alcohol intake, or cigarette smoking then it can be prevented. The cancers related to physical inactivity, obesity, nutrition could be prevented. The cancers associated to infectious agents as human papillomavirous (HPV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and others can be prevented through vaccines, behavioral changes, or antibodies. The sun ray protection can prevent various skin cancers.

CANCER (key facts)

2011-06-21T08:35:00.000-07:00

Key facts

Cancer is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008. 1
Tobacco use is a major risk factor for cancer. Harmful alcohol use, poor diet and physical inactivity are other main risk factors.
Certain infections cause up to 20% of cancer deaths in low- and middle-income countries and 9% of cancer deaths in high-income countries.
More than 30% of cancer deaths can be prevented.
Cancer arises from a change in one single cell. The change may be started by external agents and inherited genetic factors.
Deaths from cancer worldwide are projected to continue to rise to over 11 million in 2030.

Cancer is a generic term for a large group of diseases that can affect any part of the body. Other terms used are malignant tumours and neoplasms. One defining feature of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs. This process is referred to as metastasis. Metastases are the major cause of death from cancer.
The problem

Cancer is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008. The main types of cancer are:

lung (1.4 million deaths)
stomach (740 000 deaths)
liver (700 000 deaths)
colorectal (610 000 deaths)
breast (460 000 deaths).

More than 70% of all cancer deaths occurred in low- and middle-income countries. Deaths from cancer worldwide are projected to continue to rise to over 11 million in 2030.
What causes cancer?

Cancer arises from one single cell. The transformation from a normal cell into a tumour cell is a multistage process, typically a progression from a pre-cancerous lesion to malignant tumours. These changes are the result of the interaction between a person's genetic factors and three categories of external agents, including:

physical carcinogens, such as ultraviolet and ionizing radiation;
chemical carcinogens, such as asbestos, components of tobacco smoke, aflatoxin (a food contaminant) and arsenic (a drinking water contaminant); and
biological carcinogens, such as infections from certain viruses, bacteria or parasites.

Ageing is another fundamental factor for the development of cancer. The incidence of cancer rises dramatically with age, most likely due to a build up of risks for specific cancers that increase with age. The overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less effective as a person grows older.
Risk factors for cancers

Tobacco use, alcohol use, unhealthy diet, and chronic infections from hepatitis B (HBV), hepatitis C virus (HCV) and some types of Human Papilloma Virus (HPV) are leading risk factors for cancer in low- and middle-income countries. Cervical cancer, which is caused by HPV, is a leading cause of cancer death among women in low-income countries.
How can the burden of cancer be reduced?

Knowledge about the causes of cancer, and interventions to prevent and manage the disease is extensive. Cancer can be reduced and controlled by implementing evidence-based strategies for cancer prevention, early detection of cancer and management of patients with cancer.
Modifying and avoiding risk factors

More than 30% of cancer could be prevented by modifying or avoiding key risk factors, including:

tobacco use
being overweight or obese
low fruit and vegetable intake
physical inactivity
alcohol use
sexually transmitted HPV-infection
urban air pollution
indoor smoke from household use of solid fuels.

Prevention strategies

Increase avoidance of the risk factors listed above.
Vaccinate against human papilloma virus (HPV) and hepatitis B virus (HBV).
Control occupational hazards.
Reduce exposure to sunlight.

Early detection

Cancer mortality can be reduced if cases are detected and treated early. There are two components of early detection efforts:
Early diagnosis

The awareness of early signs and symptoms (such as cervical, breast and oral cancers) in order to facilitate diagnosis and treatment before the disease becomes advanced. Early diagnosis programmes are particularly relevant in low-resource settings where the majority of patients are diagnosed in very late stages.
Screening

The systematic application of a screening test in an asymptomatic population. It aims to identify individuals with abnormalities suggestive of a specific cancer or pre-cancer and refer them promptly for diagnosis and treatment. Screening programmes are especially effective for frequent cancer types that have a screening test that is cost-effective, affordable, acceptable and accessible to the majority of the population at risk.

Examples of screening methods are:

visual inspection with acetic acid (VIA) for cervical cancer in low-resource settings;
PAP test for cervical cancer in middle- and high-income settings;
mammography screening for breast cancer in high-income settings.

Treatment

Treatment is the series of interventions, including psychosocial support, surgery, radiotherapy, chemotherapy that is aimed at curing the disease or considerably prolonging life while improving the patient's quality of life.
Treatment of early detectable cancers

Some of the most common cancer types, such as breast cancer, cervical cancer, oral cancer and colorectal cancer have higher cure rates when detected early and treated according to best practices.
Treatment of other cancers with potential for cure

Some cancer types, even though disseminated, such as leukemias and lymphomas in children, and testicular seminoma, have high cure rates if appropriate treatment is provided.
Palliative care

Palliative care is treatment to relieve, rather than cure, symptoms caused by cancer. Palliative care can help people live more comfortably; it is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. It is particularly needed in places with a high proportion of patients in advanced stages where there is little chance of cure.

Relief from physical, psychosocial and spiritual problems can be achieved in over 90% of advanced cancer patients through palliative care.
Palliative care strategies

Effective public health strategies, comprising of community- and home-based care are essential to provide pain relief and palliative care for patients and their families in low-resource settings.

Improved access to oral morphine is mandatory for the treatment of moderate to severe cancer pain, suffered by over 80% of cancer patients in terminal phase.

WHO response

In 2008, WHO launched its Noncommunicable Diseases Action Plan.

WHO and the International Agency for Research on Cancer, the specialized cancer agency of WHO, collaborate with other United Nations organizations and partners in the areas of international cancer prevention and control to:

increase political commitment for cancer prevention and control;
generate new knowledge, and disseminate existing knowledge to facilitate the delivery of evidence-based approaches to cancer control;
develop standards and tools to guide the planning and implementation of interventions for prevention, early detection, treatment and care;
facilitate broad networks of cancer control partners at global, regional and national levels;
strengthen health systems at national and local levels;
provide technical assistance for rapid, effective transfer of best practice interventions to developing countries; and
coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and develop scientific strategies for cancer prevention and control.

THYROID CANCER

2011-06-21T08:30:00.000-07:00

Thyroid cancer is a cancerous growth of the thyroid gland.
Causes, incidence, and risk factors

Thyroid cancer can occur in all age groups.

People who have had radiation therapy to the neck are at higher risk. Radiation therapy was commonly used in the 1950s to treat enlarged thymus glands, adenoids and tonsils, and skin disorders. People who received radiation therapy as children are at increased risk for developing thyroid cancer.

Other risk factors are a family history of thyroid cancer and chronic goiter.

There are several types of thyroid cancer:

Anaplastic carcinoma (also called giant and spindle cell cancer) is the most dangerous form of thyroid cancer. It is rare, and does not respond to radioiodine therapy. Anaplastic carcinoma spreads quickly and invades nearby structures such as the windpipe (trachea), causing breathing difficulties.

Follicular carcinoma accounts for about 10% of all cases and is more likely to come back and spread.

Medullary carcinoma is a cancer of nonthyroid cells that are normally present in the thyroid gland. This form of the thyroid cancer tends to occur in families. It requires different treatment than other types of thyroid cancer.

Papillary carcinoma is the most common type, and usually affects women of childbearing age. It spreads slowly and is the least dangerous type of thyroid cancer.

Symptoms

Cough

Difficulty swallowing

Enlargement of the thyroid gland

Hoarseness or changing voice

Neck swelling

Thyroid lump (nodule)

Note: Symptoms may vary depending on the type of thyroid cancer
Signs and tests

A physical examination can reveal a thyroid mass or nodule (usually in the lower part of the front of the neck), or enlarged lymph nodes in the neck.

Tests for thyroid cancer:

Elevated serum calcitonin (for medullary cancer) or serum thyroglobulin (for papillary or follicular cancer)

Laryngoscopy showing paralyzed vocal cords

Thyroid biopsy showing anaplastic, follicular, medullary, or papillary cancer cells

Thyroid scan showing a nodule that does not light up on the scan (cold nodule)

Ultrasound of the thyroid showing a nodule

This disease may also affect the results of the following thyroid function tests:

T3

T4

TSH

Treatment

Treatment varies significantly, depending on the type of tumor.

Surgery is usually the treatment of choice, and the entire thyroid gland is usually removed. If the doctor suspects that the cancer has spread to lymph nodes in the neck, these will also be removed during surgery.

Radiation therapy may be performed using external beam (x-ray) radiation or by taking radioactive iodine by mouth. It may be done with or without surgery.

After treatment, you need to take thyroid hormone to replace what your glands used to make. The dose is usually a little higher than what your body needs, which helps keep the cancer from coming back.

If the cancer does not respond to surgery or radiation and has spread to other parts of the body, chemotherapy may be used, but this is only effective for a small number of patients.
Support Groups

You can ease the stress of illness by joining a support group made up of people who share common experiences and problems. See: Cancer - support group
Expectations (prognosis)

Anaplastic carcinoma has the worst outcome of all the types of thyroid cancer. It is usually fatal despite aggressive treatment.

Follicular carcinomas are often fast growing and may invade other tissues, but the outlook is still good -- most patients are cured.

The outcome with medullary carcinoma varies. Women under age 40 have a better chance of a good outcome.

Papillary carcinomas are usually slower growing. Most people are cured and have a normal life expectancy.

Patients who have treatment for thyroid cancer must take thyroid hormone pills for the rest of their lives.
Complications

Injury to the voice box or nerve, and hoarseness after surgery

Low calcium levels from accidental removal of the parathyroid glands during surgery

Spread of the cancer to the lungs, bones, or other parts of the body

Calling your health care provider

Call your health care provider if you notice a lump in your neck.

Also call if your symptoms get worse during treatment.
Prevention

There is no known prevention. Awareness of risk (such as previous radiation therapy to the neck) can allow earlier diagnosis and treatment.
References

Ladenson P, Kim M. Thyroid. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 244.
National Comprehensive Cancer Network. NCCN Guidelines in Oncology 2010: Thyroid Cancer. Version 1.2010.

Review Date: 3/2/2010.

Reviewed by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine and Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

PROSTATE CANCER

2011-06-21T08:05:00.000-07:00

Prostate cancer
Cancer - prostate; Biopsy - prostate; Prostate biopsy; Gleason score

Last reviewed: September 23, 2010.

Prostate cancer is cancer that starts in the prostate gland. The prostate is a small, walnut-sized structure that makes up part of a man's reproductive system. It wraps around the urethra, the tube that carries urine out of the body.
Causes, incidence, and risk factors

Prostate cancer is the third most common cause of death from cancer in men of all ages and is the most common cause of death from cancer in men over age 75. Prostate cancer is rarely found in men younger than 40.

People who are at higher risk include:

African-American men, who are also likely to develop cancer at every age

Men who are older than 60

Men who have a father or brother with prostate cancer

Other people at risk include:

Men exposed to agent orange exposure

Men who abuse alcohol

Farmers

Men who eat a diet high in fat, especially animal fat

Tire plant workers

Painters

Men who have been exposed to cadmium

The lowest number of cases occurs in Japanese men living in Japan (this benefit is lost after one generation of living in the U.S.) and those who do not eat meat (vegetarians).

A common problem in almost all men as they grow older is an enlarged prostate (benign prostatic hyperplasia, or BPH). This problem does not raise your risk of prostate cancer.
Symptoms

The PSA blood test is often done to screen men for prostate cancer. Because of PSA testing, most prostate cancers are now found before they cause any symptoms.

The symptoms listed below can occur with prostate cancer (Most of the time these symptoms are caused by other prostate problems that are not cancer):

Delayed or slowed start of urinary stream

Dribbling or leakage of urine, most often after urinating

Slow urinary stream

Straining when urinating, or not being able to empty out all of the urine

Blood in the urine or semen

Bone pain or tenderness, most often in the lower back and pelvic bones (only when the cancer has spread)

Signs and tests

Prostate biopsy is the only test that can confirm the diagnosis. Tissue from the prostate is viewed underneath a microscope. Biopsy results are reported using something called a Gleason grade and a Gleason score.

The Gleason grade is how aggressive the prostate cancer might be. It grades tumors on a scale of 1 - 5, based on how different from normal tissue the cells are.

Often, more than one Gleason grade is present within the same tissue sample. The Gleason grade is therefore used to create a Gleason score by adding the two most predominant grades together (a scale of 2 - 10). The higher the Gleason score, the more likely the cancer is to have spread beyond the prostate gland:

Scores 2 - 4: Low-grade cancer

Scores 5 - 7: Intermediate- (or in the middle-) grade cancer. Most prostate cancers fall into this category.

Scores 8 - 10: High-grade cancer (poorly-differentiated cells)

There are two reasons your doctor may perform a prostate biopsy:

Your PSA blood test is high.

A rectal exam may show a large prostate or a hard, irregular surface. Because of PSA testing, prostate cancer is diagnosed during a rectal exam much less often.

The PSA blood test will also be used to monitor your cancer after treatment. Often, PSA levels will begin to rise before there are any symptoms. An abnormal digital rectal exam may be the only sign of prostate cancer (even if the PSA is normal).

The following tests may be done to determine whether the cancer has spread:

CT scan

Bone scan

Treatment

The best treatment for your prostate cancer may not always be clear. Sometimes, your doctor may recommend one treatment because of what is known about your type of cancer and your risk factors. Other times, your doctor will talk with you about two or more treatments that could be good for your cancer.

In the early stages, talk to your doctor about several options, including surgery and radiation therapy. In older patients, simply monitoring the cancer with PSA tests and biopsies may be an option.

Prostate cancer that has spread may be treated with drugs to reduce testosterone levels, surgery to remove the testes, or chemotherapy.

Surgery, radiation therapy, and hormonal therapy can interfere with sexual desire or performance. Problems with urine control are common after surgery and radiation therapy. These problems may either improve over time or get worse, depending on the treatment. Discuss your concerns with your health care provider.

SURGERY

Surgery is usually only recommended after a thorough evaluation and discussion of the benefits and risks of the procedure.

Surgery to remove the prostate and some of the tissue around it is an option when the cancer has not spread beyond the prostate gland. This surgery is called radical prostatectomy. It can also be done with robotic surgery.

Possible problems after the surgeries include difficulty controlling urine or bowel movements and erection problems.

RADIATION THERAPY

Radiation therapy uses high-powered x-rays or radioactive seeds to kill cancer cells.

Radiation therapy works best to treat prostate cancer that has not spread outside of the prostate. It may also be used after surgery, if there is a risk that prostate cancer cells may still be present. Radiation is sometimes used for pain relief when cancer has spread to the bone.

External beam radiation therapy uses high-powered x-rays pointed at the prostate gland.

It is done in a radiation oncology center usually connected to a hospital. You will come to the center from home 5 days a week for the treatments. The therapy lasts for 6 -8 weeks.

Before treatment, a therapist will mark the part of the body that is to be treated with a special pen.

The radiation is delivered to the prostate gland using a device that looks like a normal x-ray machine. The treatment itself is generally painless.

Side effects may include impotence, incontinence, appetite loss, fatigue, skin reactions, rectal burning or injury, diarrhea, bladder urgency, and blood in urine.

Prostate brachytherapy involves placing radioactive seeds inside the prostate gland.

A surgeon inserts small needles through the skin behind your scrotum to inject the seeds. The seeds are so small that you don't feel them. They can be temporary or permanent.

Brachytherapy is often used for men with smaller prostate cancer that is found early and is slow-growing.

It also may be given with external beam radiation therapy for some patients with more advanced cancer.

Side effects may include pain, swelling or bruising in your penis or scrotum, red-brown urine or semen, impotence, incontinence, and diarrhea.

Proton therapy is another kind of radiation used to treat prostate cancer. Doctors aim proton beams onto a tumor, so there is less damage to the surrounding tissue.

HORMONE THERAPY

Testosterone is the body's main male hormone. Prostate tumors need testosterone to grow. Hormonal therapy is any treatment that decreases the effect of testosterone on prostate cancer. These treatments can prevent further growth and spread of cancer.

Hormone therapy is mainly used in men whose cancer has spread to help relieve symptoms. There are two types of drugs used for hormone therapy.

The primary type is called a luteinizing hormone-releasing hormones (LH-RH) agonist:

These medicines block the body from making testosterone. The drugs must be given by injection, usually every 3 - 6 months.

They include leuprolide, goserelin, nafarelin, triptorelin, histrelin, buserelin, and degarelix.

Possible side effects include nausea and vomiting, hot flashes, anemia, lethargy, osteoporosis, reduced sexual desire, decreased muscle mass, weight gain, and impotence.

The other medications used are called androgen-blocking drugs.

They are often given along with the above drugs.

They include flutamide, bicalutamide, and nilutamide.

Possible side effects include erectile dysfunction, loss of sexual desire, liver problems, diarrhea, and enlarged breasts.

Much of the body's testosterone is made by the testes. As a result, removal of the testes (called orchiectomy) can also be used as a hormonal treatment. This surgery is not done very often.

Chemotherapy and immunotherapy are used to treat prostate cancers that no longer respond to hormone treatment. An oncology specialist will usually recommend a single drug or a combination of drugs.

MONITORING

After treatment for prostate cancer, you will be closely watched to make sure the cancer does not spread. This involves routine doctor check-ups, including serial PSA blood tests (usually every 3 months to 1 year).
Support Groups

You can ease the stress of illness by joining a support group whose members share common experiences and problems. See: Support group - prostate cancer
Expectations (prognosis)

The outcome varies greatly. It is mostly affected by whether the cancer has spread outside the prostate gland and how abnormal the cancer cells are (the Gleason score) when you are diagnosed.

Many patients with prostate cancer that has not spread can be cured, as well as some patients whose cancer has not spread very much outside the prostate gland.

Even for patients who cannot be cured, hormone treatment can extend their life by many years.
Complications

The complications of prostate cancer are mostly due to different treatments.
Calling your health care provider

Discuss the advantages and disadvantages to PSA screening with your health care provider.
Prevention

Following a vegetarian, low-fat diet or one that is similar to the traditional Japanese diet may lower your risk. This would include foods high in omega-3 fatty acids.

Finasteride (Proscar, generic) and dutasteride (Avodart) are drugs used to treat benign prostatic hyperplasia (BPH).

The American Society of Clinical Oncology (ASCO) and the American Urological Association (AUA) recommend that doctors discuss the pros and cons of these drugs with men who:

Have a PSA score of 3.0 or below

Are being screened yearly for prostate cancer

Do not yet show signs of prostate cancer

Not all experts agree with this recommendation.

Acute myeloid leukemia (AML)

2011-06-21T08:00:00.000-07:00

By Kottapurath Kunjumoideen MD

Introduction
Acute myeloid leukemia (AML) is a type of leukemia (increased production of abnormal white blood cells due to bone marrow dysfunction). AML is diagnosed in approximately 3.6 per 100,000 individuals in the United States annually. The median age at diagnosis is 65 years, with the incidence of AML rising from 1.8 per 100,000 individuals below age 65 years to 16.3 per 100,000 individuals at age 65 years and over.

What causes acute myeloid leukemia?
Most cases of acute myeloid leukemia (AML) are the result of genetic mutations (alteration in normal gene) that occur in stem cells in the bone marrow. It also seems that the majority of these mutations are acquired during an individual's lifetime, as opposed to being inherited. Environmental factors like chemicals (benzene etc.), drugs (alkylator chemotherapy), radiation etc. have been implicated as a causative factors for AML in many cases. Genetic mutations result in two type of gene anomalies i.e translocations or deletions. Translocations result when two chromosome exchange genetic materials and deletions occur when a chromosome lose genetic material. Translocations are found in less than 10% of patients over the age of 60 years with de novo acute myeloid leukemia (AML). In contrast, genetic deletions seem to be more characteristic of older AML patients.

Symptoms and Signs of acute myeloid leukemia

Common symptoms of acute myeloid leukemia (AML) include unexplained fever, weakness and fatigue, bleeding (gums, skin bruising etc.), lymph node swelling over neck, armpits or groin and gum swelling. This is due to bone marrow dysfunction leading to decreased normal white blood cells (causes infection & fever), decreased platelets (causing bleeding) and anemia (causing fatigue).

How do you diagnose acute myeloid leukemia?
Acute myeloid leukemia is initially suspected on a complete blood count done in patients who have the above symptoms. Diagnosis is further confirmed by bone marrow biopsy and specialized tests on the bone marrow biopsy specimen namely immunohistochemistry with cytogenetic analysis are mandatory (analysis of chromosomal abnormalities). Additional tests to evaluate the extent of the disease may include renal and liver function tests. Imaging tests include a chest roentgenogram and ultrasound of abdomen and pelvis.

Classification and Prognostic factors of AML
Treatment of acute myeloid leukemia (AML) depends upon the exact sub-type of leukemia. Acute myeloid leukemia (AML) is classified into seven subtypes M1 to M7 by the French American British (FAB) classification system. Out of these M3 has got the best prognosis as a targeted therapy called ATRA (all-trans retinoic acid) is available for its treatment. The prognosis in all other AML is based on the cytogenetic analysis with most favorable outcome in translocations (8;21) and (16;16). Patients with deletion in chromosome 5, 7 or 3 have worst prognosis. In general, patients with AML whose cells have translocations seem to fare better than those whose cells have deletions. The poor prognosis associated with increased age may be related to the higher incidence of genetic deletions. Also drug and chemical induced AML have worse prognosis.

Traditional Treatment for Newly Diagnosed AML
The standard treatment of AML is systemic chemotherapy and consists of two phases: The intensive induction phase during which the majority of leukemic stem cells are killed and the consolidation phase during which the minimal residual disease left behind is attempted to be eradicated.

1. Induction chemotherapy : This comprises a seven day course of two drugs, cytosar arabinoside for seven days and anthracycline for three days (the 7+3 regimen). This is followed by a period of prolonged bone marrow suppression for around three weeks during which the patient is monitored for life threatening infections and bleeding.

2. Consolidation Phase: This comprises of intensified chemotherapy high dose cytosar arabinoside (HDAC) for 3-4 cycles over next 4 months in cases of favorable cytogenetics or an allogenic stem cell transplant (transplantation with stem cells obtained from a donor) if a suitable sibling donor is available with an HLA matched bone marrow, in cases of unfavorable cytogenetics. If no suitable donor is available for SCT, then unfavorable cytogenetic patients are also treated with 3-4 cycles of HDAC.

Monoclonal Antibody Therapy in Acute myeloid leukemia (AML)
One of the more innovative approaches to treatment of malignancy within the last decade has been the development of monoclonal antibody (MAb) therapy. By targeting features unique to malignant cells, these treatments conceptually allow for eradication of malignant clones while sparing normal tissue. Anti CD-33 antiobody Gemtuzumab is currently investigational in US. Gemtuzumab ozogamicin (Mylotarg; Wyeth-Ayerst Laboratories; Madison, New Jersey) has been approved by the FDA for relapsed/refractory CD33-positive AML in patients aged 60 years or older who are not considered candidates for other types of cytotoxic chemotherapy.

Role of Supportive Care in AML
Besides the cytotoxic chemotherapy AML patients require intensive supportive care preferably in intensive care units (ICU) with blood components, empirical antibiotics, growth factors (controversial) and good nutritional support.

Conclusions
The treatment of AML is advancing rapidly, and, like therapy in other malignant states, is favoring treatment strategies "tailored" to specific leukemia subtypes. As more becomes known about the genetic and molecular characteristics of leukemia cells, and the pathways of leukemogenesis are further elucidated, it is hoped that future therapies will be directed specifically toward the least toxic clonal malignant cells. The use of more supportive measures to allow for more intensive therapies may begin to change the disappointing outcomes now seen in older patients.

SKIN CANCER (MELANOMA)

2011-06-21T07:50:00.001-07:00

Melanoma is a disease in which cancer cells originate in the skin cells called melanocytes. Melanocytes are found throughout the lower part of the epidermis. They produce melanin, the pigment that gives skin its natural color. When skin is exposed to the sun, melanocytes produce more pigment, causing the skin to tan, or darken. The skin is the body's largest organ. It protects against heat, sunlight, injury, and infection. The skin has 2 main layers: the epidermis (upper or outer layer) and the dermis (lower or inner layer). When melanoma starts in the skin, the disease is called cutaneous melanoma. description summary is about cutaneous (skin) melanoma. Melanoma may also occur in the eye and is called intraocular or ocular melanoma.

There are 3 basic types of skin cancers

Melanoma
Basal cell skin cancer
Squamous cell skin cancer

Melanoma is most aggressive of all these three types of skin cancers. Melanoma can occur anywhere on the body. In men, melanoma is often found on the trunk (the area from the shoulders to the hips) or the head and neck. In women, melanoma often develops on the arms and legs. Melanoma usually occurs in adults, but it is sometimes found in children and adolescents. Unusual moles, exposure to sunlight, and health history can affect the risk of developing melanoma.

Risk factors for melanoma include the following:

Unusual moles
Exposure to natural sunlight
Exposure to artificial ultraviolet light (tanning booth)
Family or personal history of melanoma
Being white and older than 20 years
Red or blond hair
White or light-colored skin and freckles
Blue eyes

The following may be an early or late evidence of melanoma. If you notice any of the following changes in mole a doctor should be consulted.

Changes in size, shape, or color
Irregular edges or borders
More than 1 color
Asymmetrical (if the mole is divided in half, the 2 halves are different in size or shape)
itches
Oozes, bleeds, or is ulcerated (a hole forms in the skin when the top layer of cells breaks down and the underlying tissue shows through)
Change in color
Satellite moles (new moles that grow near an existing mole

A suspicious mole can be examined by a physician or nurse and may perform the following tests.

Skin examination: A doctor or nurse examines the skin to look for moles, birthmarks, or other pigmented areas that look abnormal in color, size, shape, or texture.
Biopsy: A local excision is done to remove as much of the suspicious mole or lesion as possible. A pathologist then looks at the tissue under a microscope to check for cancer cells. Because melanoma can be hard to diagnose, patients should consider having their biopsy sample checked by a second pathologist.

The prognosis (chance of recovery) and treatment options depend on the following:

The stage of melanoma (whether cancer is found in the outer layer of skin only, or has spread to the lymph nodes, or to other places in the body.
Whether there was bleeding or ulceration at the primary site.
The location and size of the tumor.
The patientâ€™s general health.

Ref: National cancer Institute (http://www.nci.nih.gov/)

OVARIAN CANCER

2010-05-29T08:46:00.000-07:00

Ovarian cancer is a common malignancy in women in the United States, with about 21,650 new cases diagnosed each year.[1] The ovaries are small female reproductive organs that reside in the pelvis. The ovary makes female hormones and stores all of the egg cells, which are released once a month during ovulation. There are two ovaries, one on each side of the uterus, or womb. Egg cells are delivered from the ovaries to the uterus by hollow organs called fallopian tubes.
Some ovarian tumors are benign (not cancerous). Malignant (cancerous) ovarian tumors can originate from the surface epithelium (cells covering or lining the ovaries), germ cells (cells that are destined to form eggs), or sex cord-stromal cells (cells that secrete hormones and connect the different structures of the ovaries). The majority of ovarian cancers develop from cells in the lining of the ovary. These are referred to collectively as epithelial ovarian cancers. In this treatment overview, the term ovarian cancer refers to epithelial ovarian cancer. Benign ovarian tumors and ovarian germ cell tumors are not further discussed in this section.
Common Epithelial Tumors: Common epithelial cancers that start in the surface epithelium account for the majority of ovarian cancers and include the following types:

Serous: This is the most common type of ovarian cancer and accounts for about 40% of common epithelial cancers. It occurs most often in women between the ages of 40 and 60.
Endometrioid: This type of ovarian cancer accounts for about 20% of common epithelial cancers and is associated with endometriosis in 5% and endometrial carcinoma (cancer of the womb) in 20% of cases. It occurs most often in women between the ages of 50 and 70.
Mucinous: Mucinous cancers account for 6-10% of common epithelial ovarian cancer and most often affect women between 30 to 50 years of age.
Clear Cell Carcinoma: Clear cell carcinomas account for about 5% of common epithelial tumors and most often affect women between age 40 and 80.
Undifferentiated Cancers: The remaining 15% of common epithelial cancers are referred to as undifferentiated tumors because their exact cell of origin cannot be determined under a microscope.
Borderline Ovarian Tumors: These ovarian tumors of low malignant potential are a subgroup of common epithelial tumors that occur in 10-15% of cases. These tumors are between cancerous and non-cancerous in nature. They originate on the surface of the ovary, but do not invade deeper tissues of the ovary. They have a better prognosis (prediction about the possible outcome of a disease) and cure rate than invasive ovarian tumors.

Because epithelial ovarian cancers begin deep in the pelvis, they often do not cause any symptoms until they are at an advanced stage. Furthermore, many of the symptoms of ovarian cancer are hard to differentiate from symptoms experienced by women who do not have ovarian cancer, such as back pain, fatigue, abdominal bloating, constipation, vague abdominal pain, and urinary symptoms. Because of the lack of specificity of early ovarian cancer symptoms,[2] the majority of women (roughly 70%) already have advanced cancer at the time of diagnosis.[3] Ovarian cancer is often originally suspected in women when their physician finds an abnormal pelvic growth during an internal pelvic examination. Ovarian cancer may spread to the lining of the abdominal cavity and lead to the buildup of fluid inside the abdomen, called ascites. Ovarian cancer may cause symptoms such as swelling of the abdomen, pain, irregular bowel movements or difficulty breathing when fluid places pressure on the lungs.
The optimal treatment of ovarian cancer requires a combination of surgery, chemotherapy and, in some rare cases, radiation therapy. When ovarian cancer is suspected because of pelvic growth, additional evaluation is necessary. Ovarian cancers may spread to other organs in the pelvis, local or regional lymph nodes, the surface of the abdominal contents, or through the blood to other locations in the body, most frequently to the bowel, bladder, uterus, lungs, and liver.[4] In order to effectively plan treatment, it is important to first determine the extent of the spread or the stage of the cancer. In order to gain the most information prior to surgery, a number of tests are performed. These may include an ultrasound of the abdomen and pelvis and several blood tests, including a CA-125 level.
Elevated levels of the protein CA-125 in the blood have been associated with ovarian cancer. However, the presence of elevated levels of CA-125 in the blood does not always indicate the presence of ovarian cancer because CA-125 levels can be elevated in a number of other conditions. The normal level of CA-125 is less than 35 units per milliliter in the blood. In general, the higher the level of CA-125 found, the greater the chance of having ovarian cancer, especially for women past menopause. Once a diagnosis of ovarian cancer has been established, the level of CA-125 in the blood is a useful indicator of cancer growth during or after treatment.
Accurate surgical evaluation of ovarian cancer is necessary for nearly all patients and can only be accomplished during a laparotomy to determine the stage of the cancer and to remove as much cancer as possible. Patients who have already undergone surgery for ovarian cancer and know their stage of cancer may select from the options below. Patients who have not yet undergone surgery can select Surgical Management of Ovarian Cancer.
Following surgical removal and staging of ovarian cancer, a final stage will be given. A Roman numeral from I to IV describes the stage and a letter from "A" to "C" describes a sub-stage. All new treatment information concerning ovarian cancer is categorized and discussed by the stage. In order to learn more about the most recent information available concerning the treatment of ovarian cancer, click on the stage for which you are interested.
Stage I: Cancer is found only in one or both of the ovaries. Cancer cells may also be found in abdominal fluid, or ascites.
Stage II: Cancer is found in the ovaries and has spread to the uterus (womb), the fallopian tubes, or other areas within the pelvis. Cancer cells may also be found in abdominal fluid, or ascites.
Stage III: Cancer is found in the ovaries and has spread to other body locations within the abdomen, such as the surface of the liver, intestine or lymph nodes.
Stage IV: Cancer is found in the ovaries and has spread outside the abdomen or inside of the liver.
Recurrent or Refractory: Recurrent disease means that the cancer has returned (recurred) after it has been treated. Refractory disease means the cancer is no longer responding to treatment.

References:

[1] American Cancer Society. Cancer Facts & Figures 2008. Available at: http://www.cancer.org/docroot/STT/stt_0.asp (Accessed September 29, 2008).

[2] Chobanian N, Dietrich CS. Ovarian Cancer. Surgical Clinics of North America. 2008; 88: 285-99, vi.

[3] Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site, 2008.

[4] Armstrong, D. Ovaries and fallopian tubes. In: Abeloff MD ed. Abeloff's Clinical Oncology, 4^th ed. Philadelphia: Churchill Livingstone, 2008: 1827-50.

FEW SUN SCREENS WIN GREEN RATING

2010-05-29T08:32:00.001-07:00

EWG’s fourth annual Sunscreen Guide gives low marks to the current crop of sunscreen products, with a few notable exceptions. EWG researchers recommend only 39 – 8 percent – of 500 beach and sport sunscreens for this season.
The reason? A surge in exaggerated SPF claims above 50 and new disclosures about potentially hazardous ingredients, in particular recently developed government data linking the common sunscreen ingredient vitamin A to accelerated development of skin tumors and lesions.
Industry’s lackluster performance and the federal Food and Drug Administration’s failure to issue regulations for sunscreens lead EWG to warn consumers not to depend on any sunscreen for primary protection from the sun’s harmful ultraviolet rays. Hats, clothing and shade are still the most reliable sun protection.
Products with high SPF ratings sell a false sense of security because most people using them stay out in the sun longer, still get burned (which increases risk of skin cancer) and subject their skin to large amounts of UVA radiation, the type of sunlight that does not burn but is believed responsible for considerable skin damage and cancer. High SPF products, which protect against sunburn, often provide very little protection against UVA radiation.
Few people use enough sunscreen to benefit from the SPF protection promised on the label. Studies show that people typically use about a quarter of the recommended amount. Because sunscreen effectiveness drops off precipitously when under-applied, in everyday practice a product labeled SPF 100 actually performs like SPF 3.2, an SPF 30 rating equates to a 2.3 and SPF 15 translates to 2. Moreover, FDA scientists say SPF claims above 50 cannot be reliably substantiated.
This year, new concerns have arisen about a form of vitamin A called retinyl palmitate, found in 41 percent of sunscreens. The FDA is investigating whether this compound may accelerate skin damage and elevate skin cancer risk when applied to skin exposed to sunlight. FDA data suggest that vitamin A may be photocarcinogenic, meaning that in the presence of the sun’s ultraviolet rays, the compound and skin undergo complex biochemical changes resulting in cancer. The evidence against vitamin A is far from conclusive, but as long as it is suspect, EWG recommends that consumers choose vitamin A-free sunscreens.
EWG has again flagged products with oxybenzone, a hormone-disrupting compound found in about 60 percent of the 500 beach and sport sunscreens analyzed. The chemical penetrates the skin and enters the bloodstream: biomonitoring surveys conducted by the federal Centers for Disease Control and Prevention have detected oxybenzone in the bodies of 97 percent of Americans tested.
In all, EWG researchers assessed about 1,400 products with SPF, including beach and sports lotions, sprays and creams, moisturizers, make-up and lip balms. The 39 beach and sports products that earned EWG’s coveted “green” rating for safety and efficacy all contain the minerals zinc or titanium. We could find no non-mineral sunscreens that scored better than “yellow.”
Some of the blame falls on the FDA, which has yet to finalize regulations for sunscreens promised since 1978. FDA officials estimate that the regulations may be issued next October – but even then, they expect to give manufacturers at least a year, and possibly longer, to comply with the new rules. That means the first federally regulated sunscreens won’t go on store shelves before the summer of 2012.

SURVIVORS OF SOME CHILDHOOD CANCERS MAY FACE COGNITIVE IMPAIRMENT

2010-05-29T08:26:00.000-07:00

Survivors of non-central nervous system (CNS) childhood cancers reported a statistically and clinically significantly higher rate of neurocognitive impairment than their cancer-free siblings, according to the results of a study published in the Journal of the National Cancer Institute.1
The survival rate for childhood cancer is high, with 80% of children and adolescents surviving five or more years. One potential late effect for these survivors is neurocognitive impairment, which can affect quality of life and overall daily functioning. Children who survive CNS cancers face impaired neurocognitive functioning due to the location of their tumors as well as the treatment directed at the cranial area; however, some research indicates that even survivors of non-CNS cancers are faced with impaired cognitive functioning.
A retrospective analysis involved 5,937 adult survivors of non-CNS cancers and 382 siblings. Participants completed neuropsychological assessments and were then compared. The data indicated that survivors of childhood cancers were 50% more likely than their cancer-free siblings to face cognitive impairment.

13% of survivors experienced impairment in task efficiency compared with 7.3% of siblings.
12.5% of survivors experienced impaired memory compared with 7.6% of siblings.
21.2% of survivors experienced impaired emotional regulation compared with 14.4% of siblings.

Survivors of acute lymphoblastic leukemia who received cranial radiation therapy, myeloid leukemia who received cranial therapy, and non-Hodgkin’s lymphoma were most likely to have impaired task efficiency. The factors most often associated with impairment were being diagnosed before the age of six, being female, undergoing cranial radiation therapy, and being hearing impaired.
The researchers concluded that survivors of non-CNS childhood cancers had a statistically and clinically significantly higher risk of cognitive impairment than their siblings. They recommend diligent monitoring in this population in order to identify learning difficulties and provide appropriate intervention.
Reference:

1 Kadan-Lottick NS, Zeltzer LK, Liu Q, et al. Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers. Journal of the National Cancer Institute [early online publication]. May 10, 2010.

DEPRESSION MAY PERSIST WITH METASTATIC CANCER

2010-05-29T08:22:00.001-07:00

A substantial number of patients with metastatic cancer may suffer from depression which tends to persist and grow more severe toward the end of life, according to the results of a study published early online in the Journal of Clinical Oncology.[1]
While cancer and other serious illnesses are risk factors for depression, little research has been performed to evaluate the severity and duration of depression among patients with advanced cancer. In an effort to establish the risk factors and progression of depressive symptoms in this group, researchers from Canada conducted a study among 365 patients with metastatic gastrointestinal or lung cancer.
At the beginning of the study, patients were evaluated in terms of physical distress, self-esteem, attachment security, spiritual wellbeing, social support, hopelessness, and depression. Then, at two-month intervals, patients were reevaluated in terms of physical distress, social support, hopelessness, and depression. T
hirty-five percent of patients reported at least mild depressive symptoms and 16% experienced moderate to severe depression. This depression persisted in up to one-third of subjects. Moderate to severe depression was three times more common in the final three months of life than it was at least one year prior to death.
Risk factors for depression included younger age; pre-existing antidepressant use; lower self-esteem and spiritual wellbeing; and a higher degree of attachment anxiety, hopelessness, and physical burden of illness. The researchers commented that “the combination of greater physical suffering and psychosocial vulnerability put individuals at greatest risk for depression.”
The researchers concluded that depression is relatively common among patients with advanced cancer and grows stronger with closer proximity to death. They recommend an integrated approach that addresses the emotional and physical distress in this patient population.
Reference:

[1] Lo C, Zimmermann C, Rydall A, et al. Longitudinal study of depressive symptoms in patients with metastatic gastrointestinal and lung cancer. Journal of Clinical Oncology. Published early online: May 17, 2010.

LUNG CANCER RISK AND TRAFFIC RELATED AIR POLLUTION

2010-05-29T08:19:00.001-07:00

Researchers report a modest association between air pollution resulting from traffic and risk of lung cancer. These findings were recently published in the journal Cancer Epidemiology, Biomarkers & Prevention.[1]
Although the relationship between lung cancer and air pollution has not been clearly defined, some research indicates that exposure to certain air pollutants may be associated with lung cancer. These air pollutants include byproducts of fossil fuel combustion, exhaust from motor vehicles and diesel engines, and emissions from power plants and industrial centers.
This Danish study evaluated lung cancer risk in relation to levels of traffic-related air pollution as measured by concentrations of nitrogen oxides. The study involved 679 people with lung cancer and 3,481 people without lung cancer. Average exposure to nitrogen oxides was estimated based on residential address. The analysis accounted for other known or potential lung cancer risk factors such as smoking, educational level, body mass index, and alcohol consumption.
The researchers reported a modest association between traffic-related air pollution and lung cancer risk (37% increase in risk for every100 μg/m3 increase in nitrogen oxides).
Research is ongoing to determine the causes of lung cancer and find ways to prevent it. Avoiding environmental risk factors may help to prevent lung cancer.
Reference:
[1] Raaschou-Nielsen O, Bak H, Sørensen M, et al. Air Pollution from Traffic and Risk for Lung Cancer in Three Danish Cohorts. Cancer Epidemiology, Biomarkers & Prevention. 2010; 19(5):1284-91.

PROSTATE CANCER TREATMENT MAY LEAVE LASTING IMPACT ON THE QUALITY OF LIFE

2010-05-29T08:18:00.000-07:00

Prostate cancer treatment may have lasting effects on quality-of-life issues related to sexual function and urinary problems, but it doesn’t seem to strongly impact overall quality of life, according to a study published in the Journal of Urology.¹
Depending on the stage and extent of prostate cancer, the disease can be treated in several ways: radical prostatectomy (surgical removal of the prostate gland), interstitial brachytherapy (implantation of radioactive “seeds” in the prostate gland), externally delivered radiation therapy, and hormonal therapy. Treatment for prostate cancer can cause erectile dysfunction and urinary incontinence—leading researchers to wonder about long-term impact on quality of life.
In a study that included data from 1,269 men who underwent treatment for prostate cancer, men completed follow-up questionnaires for four years following treatment. Most of the men in the study (60%) underwent prostatectomy; 17% had brachytherapy; 12% received external radiation; 6% received a combination of the radiation therapies; and 5% received hormonal therapy.
Men who underwent surgery or any form of radiation experienced urinary incontinence that grew worse throughout the first year following treatment and then improved during the second year; however, they reported that their urinary-related quality of life never returned to pre-treatment standards. Men who underwent surgery experienced the most problems. In contrast, men who underwent hormone therapy reported that their urinary function gradually grew worse over the four-year period.
All treatment groups reported declines in sexual function during the first year, with surgery patients seeing the biggest problems; however, surgery patients also experienced an improvement during the second year, while the other groups did not.
In terms of overall quality of life, prostate cancer did not seem to have a substantial impact. Thus, the researchers concluded that prostate cancer treatment adversely impacts urinary and sexual function, but does not appear to significantly impact overall quality of life.
Reference: Huang GJ, Sadetsky N, Penson DF. Health related quality of life for men treated for localized prostate cancer with long-term followup. Journal of Urology. 2010; 83(6):2206-12.

LIVER CANCER INCIDENCE IS ON THE RISE IN THE UNITED STATES

2010-05-29T08:15:00.000-07:00

From 2001 to 2006, the incidence of hepatocellular carcinoma (HCC) increased significantly with an average increase of 3.5% annually. This analysis was recently reported in the Centers for Disease Control and Prevention’s (CDC) Morbidity and Mortality Weekly Report.[1]
The liver is the largest organ in the body and is responsible for over 500 functions, including the secretion of glucose, proteins, vitamins, and fats; the production of bile; the processing of hemoglobin; and detoxification of numerous substances. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer (cancer that begins in the liver). Factors that increase the risk of developing HCC include long-term, heavy alcohol use and chronic infection with hepatitis B or C viruses.
Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Historically, the rates of HCC have been lower in the United States than in other countries; however, the disease is on the rise. The incidence of liver cancer in the United States tripled between 1975 and 2005, but survival rates are improving, according to the results of a study published in the Journal of Clinical Oncology.[2]
To evaluate the most current data on HCC incidence, researchers analyzed HCC cases from 2001-2006 from the CDC’s National Program of Cancer Registries as well as from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) system. In 2001, the average annual incidence rate of HCC was 2.7 per 100,000 people and increased to 3.2 in 2006. The researchers also reported that HCC incidence was three times higher for males than females. When the researchers looked at incidence of HCC by race or age, the largest increases in incidence from 2001 to 2006 were among whites, blacks, and individuals between 50 and 59 years old. The researchers also reported that the lowest incidence of HCC is in the state of South Dakota and the highest is in Hawaii.
The incidence of HCC increased from 2001 to 2006 in the United States. Results from other studies suggest that diabetes prevention as well as avoidance of heavy alcohol use and hepatitis B and C virus infections could make an important contribution to HCC prevention in the United States.
References:

[1] O’Connor S, Ward JW, Watson M, Momin B, and Richardson LC. Hepatocellular Carcinoma- United States 2001-2006. MMWR. 2010;59:517-520.
[2] Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. Journal of Clinical Oncology. 2009; 27: 1485-1491.

YOGA IMPROVES SLEEP AND QUALITY OF LIFE

2010-05-29T08:14:00.000-07:00

A four-week yoga program that included breathing, meditation, postures, and other techniques improved sleep and quality of life among cancer survivors. The results of this study will be presented at the 2010 annual meeting of the American Society of Clinical Oncology.
Sleep problems and fatigue are among the most common problems experienced by cancer survivors, and can have a profound impact on quality of life. Sleep problems are very common during cancer treatment, but can persist even after treatment ends.
To evaluate the impact of a yoga program on sleep and fatigue, researchers at the University of Rochester conducted a study among 410 survivors of early-stage cancers who reported sleeping problems after completion of cancer treatment. Three-quarters of the study participants were breast cancer survivors.
Study participants were assigned to receive either usual care or usual care plus a four-week, twice-weekly YOCAS® (Yoga for Cancer Survivors) program. The YOCAS program consisted of mindfulness exercises such as breathing, meditation, visualization, and poses in standing, seated, and lying-down positions.
Compared with patients who received usual care alone, patients in the yoga program reported greater sleep quality, less use of drugs for sleep, less fatigue, and better quality of life. Patients in the yoga program reported a 42% reduction in fatigue, compared with a 12% reduction in fatigue among patients who received usual care alone.
These results suggest that a structured yoga program can improve sleep, reduce fatigue, and improve quality of life among cancer survivors.
Reference: Mustian KM, Palesh O, Sprod L et al. Effect of YOCAS yoga on sleep, fatigue, and quality of life: A URCC CCOP randomized, controlled clinical trial among 410 cancer survivors. To be presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 9013.

DEBATE OVER CELL PHONE USE AND CANCER RISK....

2010-05-28T09:45:00.000-07:00

Results from a major international study released Monday do not establish a definitive link between cell phone use and cancer, but they don’t rule one out, either. In fact, the Interphone study, coordinated by the International Agency for Research on Cancer (IARC), may have raised more questions than it answered.
The largest study to date to investigate the relationship between cell phone use and cancer, the Interphone study tracked nearly 13,000 cell phone users in 13 countries over the course of 10 years. Participating countries included Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom. The study focused on adults aged 30-59 – the largest group of cell phone users at the start of the decade -- and looked at the relationship between use and an increased risk of gliomas, a type of brain cancer, and benign brain tumors. It included over 2000 brain cancer patients.
Cell phone safety has been debated for years, and most research has been contradictory or inconclusive. Public health experts hoped this study would provide clearer guidance on the issue. However, the results do not give a definitive answer.
"This is the largest study of mobile phone use in relation to brain tumors. While the findings are predominantly negative, they are highly unlikely to end the controversy about whether cell phone use affects cancer risk,” said Michael J. Thun, MD, American Cancer Society vice president emeritus, Epidemiology & Surveillance Research.
What the Interphone study found
Overall, researchers found no direct relationship between cell phone use and an increased risk of brain cancer or benign brain tumors. In fact, people who used their cell phones the most were less likely than never-users to get brain cancer or benign brain tumors. However, in a completely contradictory finding, among cell phone users who used their phones the most, researchers found an increased risk for gliomas compared to other groups in the study.
The study also could not address certain issues.
For one, the authors acknowledge, even the heaviest cell phone users in the study wouldn’t be considered heavy users by today’s standards.
Thun echoes that concern: “The majority of participants in this study were not heavy cell phone users compared to today's practices; those who used cell phones for about one half hour per day ranked in the top 10 percent of use, and almost no one in the study had used cell phones for more than 20 years.”
Another issue is the lack of data on the risk to children, many of whom start using cell phones early in life. The heavy use of cell phones by young children is of particular concern because the radiofrequency (RF) waves from cell phones reach more brain tissue in children than in adults.
Further, the authors explain the seemingly protective effect of cell phone use by citing flaws in the study design and data collection. Error may also have adversely affected the data suggesting high-volume users are at an increased risk, the study authors concluded.
What does this mean for you?
“It is important that these issues continue to be studied in children, with longer term use, and through prospective studies," says Thun.
The Centre for Research in Environmental Epidemiology (CREAL) is currently investigating cell phone use and cancer risk in children and adolescents through the MobiKids program, funded by the European Union. Other studies assessing cell phone use and cancer risk currently are underway.
In the meantime, the American Cancer Society recommends that people who are concerned take simple steps to reduce their exposure:

Use a speaker phone or other hands-free device.
Purchase a cell phone model with lower SAR (specific absorption rate) ratings. SAR is a measure of how much radiofrequency (RF) is absorbed by the body. Cell phones do not emit ionizing radiation, but there is some concern that RF may indirectly affect tumor growth.
Parents may wish to limit their children's use of cell phones.

people who use tanning bed are more likely to melanoma.....

2010-05-28T09:38:00.000-07:00

People who use tanning beds are more likely to develop melanoma, the deadliest form of skin cancer, than never users, according to a new study from the University of Minnesota. The more regularly a person frequents tanning salons, the greater the risk, the study shows.
In July 2009, after a comprehensive review of the available research, the International Agency for Research on Cancer (IARC) elevated tanning devices to its highest cancer risk category – "carcinogenic to humans" (Group 1). Despite this risk, approximately 30 million Americans still visit indoor tanning salons each year. That may be at least in part because the tanning industry has pointed to limitations in previous studies and continues to tout the purported health benefits of tanning, including vitamin D production.
The new study, funded by the National Cancer Institute and the American Cancer Society, was designed to help answer more definitively whether tanning bed use is linked to skin cancer.
“Most reports were not able to adjust for sun exposure, confirm a dose-response, or examine specific tanning devices,” said study author DeAnn Lazovich, PhD, professor of epidemiology, University of Minnesota School of Publish and co-leader of the Masonic Cancer Center’s Prevention and Etiology Research Program. “Our population-based, case-control study was conducted to address these limitations.”
What this study found
The researchers, led by Lazovich, collected detailed information on the tanning habits of more than 1,100 Minnesotans aged 25 to 59 who had been diagnosed with melanoma between July 2004 and December 2007, as well as a matched group of more than 1,100 people without melanoma.
The researchers gathered data on tanning bed use, including years of use, age at which use began, and the specific devices used, as well as other factors such as age, sunscreen use, and family history of melanoma.
According to their findings, people who had ever used an indoor tanning device were about 75% more likely to have developed melanoma. Frequent users – defined as using a tanning device for at least 50 hours, at least 100 sessions, or at least 10 years – were 2.5 to 3 times more likely to develop melanoma than those who had never used them. The risk went up with increasing tanning bed use, the study showed, and was elevated regardless of the type of device.
“We found that it didn’t matter the type of tanning device used; there was no safe tanning device,” Lazovich said. “We also found – and this is new data – that the risk of getting melanoma is associated more with how much a person tans and not the age at which a person starts using tanning devices. Risk rises with frequency of use, regardless of age, gender, or device.”
Lazovich and her team’s findings are published in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.
Melanoma on the rise
The number of new cases of melanoma in the United States has been increasing for at least 30 years. The American Cancer Society estimates that about 68,720 new melanomas will be diagnosed in the United States during 2009. Melanoma is 10 times more common in whites than in African Americans. It is slightly more common in men than in women.
More than 2 million skin cancers are diagnosed each year in the United States. That's more than cancers of the prostate, breast, lung, colon, uterus, ovaries, and pancreas combined.
Most skin cancers are caused by too much exposure to ultraviolet (UV) rays. Much of this exposure comes from the sun, but it also comes from manmade sources, such as tanning beds.
Because of the popularity of tanning among young people, both the World Health Organization and the International Commission on Non-ionizing Radiation Protection recommend that the use of indoor tanning should be restricted in anyone under the age of 18.
The American Cancer Society recommends people avoid tanning beds altogether.

BLOCKING GENES BOOSTS RADIO THERAPY

2010-05-25T10:44:00.000-07:00

A gene which hinders the ability of radiotherapy to kill cancer cells has been detected by UK researchers.
The team found that if they blocked the POLQ gene - which has a role in repairing damaged DNA - radiotherapy was more effective.
It is hoped that the discovery, which came about after a trawl through 200 candidate genes, could lead to new drugs to boost radiotherapy.
The findings are published in the journal Cancer Research.
Many thousands of cancer patients will have some form of radiotherapy as part of their treatment, and it is estimated to contribute to 40% of cases where cancer is eliminated.
The researchers from the University of Oxford said tumours can differ widely in the way they respond to radiotherapy - but the reasons for these differences are largely unknown.
In order to find a potential target for increasing the chances that radiotherapy would work, they looked specifically at genes involved in repairing DNA damage.
After pinpointing the POLQ gene, they found that blocking it in several different types of cancer cell in the laboratory, including laryngeal and pancreatic tumours, rendered the cells more vulnerable to the effects of radiation.
Selective
Previous research had shown that the POLQ gene is not particularly active in normal healthy tissue.
Doing the same experiment in healthy cells, the team found that blocking the gene did not have any effect on the sensitivity of normal tissue to radiation.
The researchers said the fact that the POLQ seemed to more abundant in cancer cells than normal cells made it a good target for boosting the effects of radiotherapy.
Study leader Dr Geoff Higgins, a Cancer Research UK scientist at the Gray Institute for Radiation Oncology and Biology, said: "We've sieved through a vast pool of promising genetic information and identified a gene that could potentially be targeted by drugs to improve the effectiveness of radiotherapy.
"Blocking the activity of this gene resulted in a greater number of tumour cells dying after radiotherapy and provides new avenues for research."
Professor Gillies McKenna, director of the institute, added: "The next stage is to translate this discovery into a treatment that will benefit patients."

WE SHOULD USE MULTI VITAMIN OR NOT.....

2010-05-25T10:42:00.000-07:00

To take the multivitamin or to not take the multivitamin: That is the question researchers are still trying to answer.
New research on vitamins has offered conclusions that weren't crystal clear. But researchers generally recommend getting vitamins from foods, not supplements, to boost your health.
Vitamin supplements and cancer
A study done on women in Puerto Rico, presented Sunday at the American Association for Cancer Research, found that multivitamin and calcium supplements have a protective effect against breast cancer. But a large Swedish study in the American Journal of Clinical Nutrition found that taking multivitamin supplements may increase the risk of breast cancer.
The Puerto Rican study, which was not published in a peer-reviewed journal, looked at the capacity of DNA to repair itself in the face of damage. A low DNA repair capacity has previously been linked to cancer risk, said Jaime Matta at the Ponce School of Medicine. Researchers surveyed 268 breast cancer patients and 457 healthy controls and took samples from them to analyze their DNA repair capacity.
They found that participants who took multivitamin supplements reduced the odds of having breast cancer by 30 percent, and those who took calcium had a 40 percent decreased risk. Statistical analysis suggested that the calcium effect could be explained by the DNA repair capacity, but the vitamin effect was independent. Taking supplements of individual vitamins such as A, C and E had no effect, Matta said.
The Swedish study, which looked at more than 35,000 Swedish women, found that those who reported taking multivitamins were 19 percent more likely to develop breast cancer than those who said they didn't take them.
Both studies should be looked at in the broader context of research on the subject, which has consistently found no association between multivitamins and cancer, said Joanne Dorgan, epidemiologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania.
A 2009 study of more than 160,000 women in the U.S. Women's Health Initiative found no link between multivitamin use and the likelihood of developing cancer or cardiovascular disease, or of dying. Other large-scale studies similarly have not found connections between breast cancer and multivitamin use.
The Swedish study, which also has a large sample, should be followed up, Dorgan said.
Although the Puerto Rican study is small, it generates a useful hypothesis about DNA repair capacity that should be looked into also, said Dr. Banu Arun, professor of medicine at University of Texas M. D. Anderson Cancer Center. It is important to explore why some people may benefit from vitamin intake more than others, and DNA repair capacity is a possible factor in that, she said.
Arun's bottom line: "Don't take all of these multivitamins with the intention that it will decrease breast cancer risk. Getting the vitamins and minerals from natural sources -- food source -- is the best." Those with deficiencies because of genetics or chronic illnesses should compensate with supplements, she said.
Vitamins in diet and the heart
Getting nutrients from foods gets more support from a large Japanese study published in the Journal of the American Heart Association.
Researchers looked at more than 23,000 men and 35,000 women, ages 40 to 79. They used questionnaires to assess how much folate, vitamin B-6 and vitamin B-12 participants had in their diets.
They found that greater intake of folate and vitamin B-6 was linked to fewer deaths from heart failure in men. These nutrients were also linked to fewer deaths from stroke, heart disease and overall cardiovascular diseases in women.
When researchers controlled for cardiovascular risk factors and took out the participants who used supplements, the folate and vitamin B-6 continued to show these benefits.
Previous research has found that higher levels of homocysteine, an amino acid in the blood, may be related to blood clots and artery lining damage. B vitamins such as folic acid help break down homocysteine, but this study does not prove a direct cause.
The study represents a substantial source of data to further evaluate or expand upon dietary recommendations, said Linda Van Horn, nutrition researcher at Northwestern University Feinberg School of Medicine, who was not involved in the study.
The large sample size and the standardized food frequency questionnaire give credence to the study, Van Horn said.
"These particular nutrients -- there's no reason to think they wouldn't be as important in an American population as they are in a Japanese population," she said.
Still, the findings may not be entirely generalizable to the United States, as the Japanese dietary intake is different, and the country's population is less obese as a whole. There should be a similar assessment in the United States to determine if the findings can be applied there, researchers said.
The message is to eat foods that contain B-vitamins, Van Horn said. These include dark green leafy vegetables such as spinach, broccoli, dried beans, peas, lentils and kidney beans, and chickpeas. Many cereals are also fortified with the vitamins.

BONE DRUGS LOWERS BREAST CANCER RISK....

2010-05-25T10:35:00.000-07:00

A common osteoporosis drug, raloxifene, reduces breast cancer risk by 38% in women at high risk for the disease, without causing the serious side effects of similar drugs, a new study shows.
That suggests more high-risk women should consider taking raloxifene, also known as Evista, says Victor Vogel, main author of the study presented Monday at the American Association for Cancer Research meeting in Washington.
"It's not a cure ... but it's an important protection for women who are at very high risk," says Vogel, who followed nearly 20,000 high-risk, postmenopausal women for almost seven years.
Both raloxifene and another drug, tamoxifen, are approved to prevent breast cancer in women at high risk. Few women take them for prevention, however, because of concerns about side effects.
Tamoxifen reduces breast cancer by 50% but can also cause hot flashes and other symptoms. So about half of breast cancer patients, who often take it to prevent a relapse, stop the drug early, says study co-author Lawrence Wickerham of Allegheny General Hospital.
Tamoxifen also doubles the risk of endometrial cancer, from about one in 1,000 women to about two in 1,000, according to the National Cancer Institute, so many doctors are cautious about prescribing it.
Given these concerns, no more than 5% of high-risk women today "even consider taking" either drug, says Gabriel Hortobagyi of Houston's M.D. Anderson Cancer Center, who wasn't involved with the study but will participate in a panel discussion at the conference. "The impact of these drugs is huge," he says. "The only thing that reduces the risk as much is a bilateral mastectomy."
The new study — which shows that raloxifene doesn't substantially increase the risk of endometrial cancer — should put those concerns to rest, says co-author Patricia Ganz, who runs a clinic for high-risk women at the University of California-Los Angeles.
"We have two very effective agents for breast cancer prevention," Ganz says. "If women were not so risk-averse, we might actually be able to reduce the risk of breast cancer in high-risk women."
A typical American woman has about a 12% chance of getting breast cancer in her lifetime. That risk rises to about 18% for a woman whose mother or sister has had the disease, and to 30% for a woman with a breast lesion called atypical hyperplasia, Ganz says.

OLDER DRUGS CUTS BREAST CANCER RISK MORE..

2010-05-25T10:32:00.000-07:00

WASHINGTON—A long-term study comparing two popular drugs that help to prevent breast cancer suggests the older one is significantly more effective over time.

But both tamoxifen and Eli Lilly & Co.'s newer Evista cut high-risk women's risk of developing breast cancer, according to results presented Monday at a meeting here of the American Association for Cancer Research. Tamoxifen, while more effective, also brought increased risk of side effects.
The federally funded study followed 19,490 women for almost seven years during and after their treatment with tamoxifen, an off-patent drug used to treat cancer, and Evista, which was developed as an osteoporosis drug and is generically known as raloxifene.
The drugs are used to fend off breast cancer in post-menopausal women at high risk of the disease. Only 5% to 20% of the tens of thousands who could benefit from the medicines use them, according to researchers.
In 2006, earlier published results of the study, known as STAR, found that both drugs cut the risk of breast cancer by 50% in high-risk, postmenopausal women. In those results, women taking tamoxifen had increased risk of certain side effects, such as blood clots.
Monday's findings suggest tamoxifen is significantly better than raloxifene at preventing breast cancer several years after treatment, which generally lasts about five years. Over the longer time period, tamoxifen cut the risk of invasive breast cancer by 50%, while raloxifene's effectiveness dropped to 38%. Raloxifene did match tamoxifen in preventing noninvasive breast cancer.
Raloxifene users continued to have significantly fewer side effects, including blood clots and uterine cancer, compared with those who took tamoxifen.
"Tamoxifen is still a little bit better," said D. Lawrence Wickerham, who presented the data and helps leads a federally funded research network on breast and colorectal cancer. But "raloxifene remains an effective way to prevent breast cancer and does it with far less toxicity," said Dr. Wickerham, who serves as a consultant to Eli Lilly.
Unless women have a known risk for blood clots or uterine cancer, they can consider both drugs as breast-cancer prevention options, according to Dr. Wickerham. Raloxifene may be particularly beneficial for those post-menopausal women with fragile bones because it offers them a "two-for-one benefit," he said.
But not all experts agree that raloxifene is just as good an option as tamoxifen.
"Tamoxifen is more protective than raloxifene," said Mary Daly, chairwoman of clinical genetics Fox Chase Cancer Center site in Philadelphia, who ran the study at that site. "Raloxifene is falling behind. The longer we follow these women, the more that divide will grow."
These drugs work by acting like the hormone estrogen in some organs and by blocking the effect of estrogen in others. In the breast, both block estrogen's action, which prevents the progress of breast cancer or pre-malignant changes in the breast.
However, in the lining of the uterus, tamoxifen acts like estrogen. This may be the reason women taking it experience higher rates of endometrial cancer.
Tamoxifen stays in the body much longer than does raloxifene, which might be the reason for the difference in the drugs' effectiveness, said researchers.
Patricia Ganz, another study investigator and director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, said she would incorporate the new findings into her practice by leaning toward tamoxifen for preventing breast cancer in high-risk women, those with a family history of the disease or who have had a biopsy to look at abnormally growing cells, or those with no uterus.
But if a woman had an elevated risk of blood clots or couldn't tolerate the side effects of tamoxifen, Dr. Ganz said she would suggest raloxifene.
"The updated results of the STAR trial provide important information to help guide patients and health care professionals in weighing the risks and benefits of medications available to reduce the risk of invasive breast cancer," said Teeresa Shewman, a spokeswoman for Eli Lilly. "Lilly stands behind the safety profile and efficacy of Evista."
Eric Winer, director of the breast oncology center at Dana-Farber Cancer Institute in Boston, who wasn't involved in the study, agrees that there are more women in the U.S. who could benefit from these treatments than currently use them if they understood more about them.
"It doesn't mean that everyone should take it," said Dr. Winer. But, women "deserve to hear more."
WALLSTREET JOURNAL

MESOTHELIOMA: THE BASICS 3

2009-12-15T06:51:00.000-08:00

How is mesothelioma diagnosed and staged?

Patients who present with symptoms worrisome for mesothelioma may have a chest x-ray done, indicating a build-up of fluid in the lining of the lung. These patients would then undergo CT scan to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan is obtained to visualize the anatomy in the abdomen.
Patients would then undergo a biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs, to obtain a sample of the tissue. A peritoneoscope is used to enter the abdomen to obtain a tissue sample in abdominal mesothelioma.
Staging refers to determining the extent of the disease, and the stage dictates the treatment. Physicians use the TNM system (also called tumor - node - metastasis system). This describes the size of the tumor (T), if the lymph nodes are involved (N), and if it has spread to other areas of the body (M). This is then interpreted as a stage somewhere from one to four. Patients with earlier stage tumors tend to live longer and respond better to available treatments.

What are the treatments for mesothelioma?

Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age, and his or her state of health at the time. Younger, healthy patients with early stage disease may be candidates for surgery that removes the mesothelial tissue around the tumor. This surgery is extensive, and it is not well understood how much benefit it provides the patient.
Traditional radiation therapy is used in some cases after surgery, but this can cause damage to the healthy lung tissue in the process of treating the cancer and may result in toxicity that outweighs any benefit. Research is investigating ways of giving radiation directly to the tumor, using implants or UV light therapy.
Chemotherapy has often been used to treat patients with mesothelioma, but until recently the benefit was not clear. We now know that chemotherapy can provide significant relief of symptoms. Agents that are used, either alone or in combination, include cisplatin, carboplatin, mitomycin, vinblastine, gemcitabine and anthracycline agents (doxorubicin and others). These medications have had responses in 10 to 20 percent of patients.
A more recent trial randomized patients to receive either cisplatin alone or cisplatin in combination with pemetrexed (Alimta). Patients who received the combination of drugs had increased response rates, survived longer, and had fewer side effects. In addition, researchers found that giving folic acid and vitamin B12 along with the combination resulted in less toxicity and no decrease in the therapy’s effectiveness. This regimen is now considered standard of care for mesothelioma that is not treatable with surgery.
Researchers are conducting studies that administer the chemotherapy directly into the pleural space. So far, the results of these studies have been disappointing.
Because the current therapies have limited effectiveness, researchers are continuing to look for new ways to treat mesothelioma. Some of the treatments being investigated include interleukin-2 (a biologic therapy), lovastatin (a cholesterol-lowering drug), immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), and Photodynamic Therapy (PDT-a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer). Patients should talk with their physicians about current clinical trials for mesothelioma.
One problem that patients may encounter is the recurring build-up of fluid in the pleural space. This fluid can be removed with a chest tube (a tube that is put into the chest wall and left in for a period of time to allow drainage) or a procedure called thoracentesis (a small needle is put through the chest wall, into the pleural space, the fluid is drained, and the needle removed). In many cases, this will be followed by a procedure called pleurodesis, in which a medication (talc, bleomycin) is injected into the lung to create scar tissue in the hopes of decreasing future fluid from developing. In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained.
If this is a chronic problem, patients may have a catheter placed in the chest semi-permanently, allowing them to drain the fluid themselves at home as needed. Removal of the fluid alleviates the difficulty in breathing and the chest pain that are caused by the build-up.

Follow-up testing?

The physician will follow the patient with physical examinations, chest x-rays, and CT scans.

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MESOTHELIOMA: THE BASICS 2

2009-12-15T06:49:00.001-08:00

How can I prevent mesothelioma?

By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures.

What screening tests are available?

There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur.

What are the signs of mesothelioma?

The symptoms of mesothelioma are caused by a build-up of tumor tissue surrounding the lung and fluid in the pleural space that prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. In the abdomen, this fluid and tumor tissue causes abdominal swelling, pain and weight loss.

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MESOTHELIOMA: THE BASICS

2009-12-15T06:47:00.000-08:00

What is mesothelial tissue?

The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. The area between the two layers is often called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, lungs, testes and heart.

What is mesothelioma?

Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in the unwanted encasement of organs within a thick rind of tumor tissue and excess fluid build up, ultimately causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.
The majority of mesotheliomas are found in the lining of the lung (65-70%). About 20-30% percent of cases are found in the abdominal cavity lining, and even more rarely, mesothelioma is found in the lining of the heart (1-2%) or testicles.

Am I at risk for mesothelioma?

Mesothelioma is a rare cancer, with approximately 2,000 cases diagnosed each year in the United States. It is eight times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 70 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970's, the U.S. Occupational Safety and Health Administration (OSHA) has set limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma.
Eighty percent of cases of pleural mesothelioma occur in individuals who have had known asbestos exposure, yet only 10% of people with a history of heavy exposure develop the disease. This suggests that additional exposures or factors are involved to actually develop the disease. Even more puzzling is the fact that only 50% of people with peritoneal mesothelioma have a history of asbestos exposure.
It takes 20 to 40 years from the time of asbestos exposure until mesothelioma is detected. This exposure was usually over a period of time, but has been reported to be as little as one or two months of exposure. Smoking does not seem to increase the risk of developing the disease.
The incidence of mesothelioma varies in different areas of the world, depending on when asbestos was widely used in that area. Rates are higher in the United Kingdom, where about 1800 cases per year are diagnosed. The incidence takes into consideration the number of cases and the size of the population. This is because asbestos use in Western Europe remained high until 1980, whereas maximum exposure in the U.S. was from the 1930s to 1960s. Australia was one of the world’s largest producers of asbestos, leading to the country having the highest rates worldwide (based on the size of the population). Rates in the U.S. are beginning to decline, whereas rates in Europe and Australia are expected to plateau in the next 10-15 years before declining.
Following the ban of asbestos in many countries, asbestos producers started to promote the sale of their product to developing countries, such as Asia and Latin America. Experts fear that the peak rates in these areas are yet to come, and will mimic what has been seen in the U.S. and Europe.

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MELANOMA :THE BASICS 3

2009-12-13T01:09:00.000-08:00

HOW IS MELANOMA DIAGNOSED AND STAGED?

When melanoma is suspected, an excisional biopsy should be performed. This biopsy removes the lesion and the layers beneath it, allowing the depth of the lesion to be accurately determined. The depth of the lesion determines prognosis and treatment, so it is important for this to be accurate. This depth is described in two ways: Breslow thickness, which is the depth of invasion in millimeters, and Clark's level, which describes depth of invasion by the tissue it invades (levels I-V). Clark's Level I involves the epidermis only. Clark's Level II involves the epidermis and the layer of skin immediately below, the papillary dermis. Clark's Level III goes one layer deeper into the reticular dermis. Clark's Level IV involves the deep dermis. Clark's Level V invades beyond the skin layers into the subcutaneous fat. Clark's levels are often confused with the staging of melanoma, but Clark's level is an indication of the depth of penetration of the melanoma only, not the stage of disease.
The staging is based on these measurements, and is classified as follows:

Melanoma in-situ - the melanoma is present only in the epidermis; a Breslow thickness and Clark's level are not determined for this early stage lesion
Stage I - less than 1 mm thick
Stage II - greater than 1 mm thick or Clark's level IV-V (invasion into reticular dermis or subcutaneous tissue)
Stage III - has spread to local lymph nodes (may or may not have known of a primary lesion) or Clark's level V (invades subcutaneous tissue)
Stage IV - presents with distant metastasis (most commonly liver, lung, and brain)

There are additional elements identified on the pathology report from a biopsy that contain important information about prognosis.
Depending on the stage of the melanoma, patients will have a chest x-ray and liver function studies to assess for metastases. In patients with stages II-IV, further evaluation for metastases is needed; this may include cat scans, PET scans, and lymph node dissection (with or without sentinel node biopsy).

WHAT ARE TREATMENTS FOR MELANOMA?

Surgery is the mainstay of treatment for melanoma. After a melanoma is diagnosed by a biopsy, the next step is to have a "wide excision". This surgical procedure removes an area of normal tissue around where the lesion was located. The amount of tissue removed is based on the depth of the melanoma. This area of normal skin is referred to as the "margins".
If the melanoma is deeper than 1mm or invades to Clark's level IV or greater, a sentinel lymph node biopsy may be performed. In a sentinel lymph node biopsy, a blue dye with a radioactive tracer is injected into the site of the original tumor. The dye spreads to the "sentinel node" (the first node that to which the cancer would spread). These blue lymph nodes are removed, examined under a microscope and tested for cancer. If any of these lymph nodes are positive, the remaining lymph nodes in the region are removed, a procedure known as a lymph node dissection. If the sentinel nodes do not contain melanoma, a completion lymph node dissection can be avoided.
Patients with early stage melanoma and negative lymph nodes are monitored regularly with skin examinations, chest x-rays, and liver function tests for the development of any recurrence or a second melanoma. These patients have a good prognosis, with 95 percent of patients alive 5 years after diagnosis. However, having one melanoma in a patient's lifetime places him/her at higher risk for developing a second melanoma and follow up with a dermatologist is a mainstay of on-going treatment.
Patients with lymph node involvement are considered to have Stage III disease. Theoretically, in Stage III melanoma, the cancer has been removed by the surgery and lymph node dissection. Unfortunately, there are often tumor cells circulating in the body that we cannot see. For this reason, the patient may be offered treatment with radiation therapy, immunotherapy, chemotherapy (DTIC, cisplatin), vaccine therapies, and/or a clinical trial to destroy any remaining cancer cells and prevent further spread of the cancer. Radiation therapy can be used to treat a local area thought to be at risk for recurrence of the melanoma . An immunotherapy agent (interferon, interleukin-2, GM-CSF, Bacille Calmette-Guerin (BCG) bacteria) can be used to stimulate the patient's own immune system against cancer. Chemotherapy can be used to kill any rapidly dividing cells, such as melanoma cells. Clinical trials may be testing new treatment modalities or new monitoring techniques.
Melanoma can also spread into the region between the original site and the lymph nodes. These lesions are called "in-transit metastases." These may often be treated with the treatment modalities used in Stage III disease. One technique being used in patients with tumors confined to one limb is isolated limb perfusion. This involves temporarily cutting off circulation to the affected limb and administering high doses of chemotherapy to the limb, sparing the rest of the body of the medication's toxicities.
When the cancer has spread beyond the regional lymph nodes, into another organ, it is considered Stage IV melanoma. Stage IV disease has a poorer prognosis. In some instances, patients with isolated areas of metastasis are able to have these surgically removed. Chemotherapy, immunotherapy, and/or participation in a clinical trial are treatment options often used to treat Stage IV melanoma.
Clinical trials are testing many new agents for the treatment of melanoma. These may include: vaccines, which can be made from the patient's own tumor cells or parts of the melanoma cells; varying combinations of chemotherapy; immunotherapy agents; and surgical techniques. One technique being tested in patients with tumors confined to one limb is isolated limb perfusion. This involves temporarily cutting off circulation to the affected limb and administering high doses of chemotherapy to the limb, sparing the rest of the body of the medication's toxicities. New medications and techniques are continually being tested to find more effective therapies for this disease.

Follow-up testing

About 5 percent of patients will develop a second melanoma in their lifetime, while others may develop metastases from the original tumor, and therefore all patients require follow-up. Patients should be evaluated every 3 to 6 months for the first 3 years after diagnosis, then every 6 to 12 months for 2 years, and then annually. Chest x-ray and liver function tests may be done each year, and CT scans, if appropriate, for a particular case.
This article is meant to give you a better understanding of melanoma. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information.

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MELANOMA :THE BASICS 2

2009-12-13T01:05:00.000-08:00

HOW CAN I PREVENT MELANOMA?

The best way to prevent melanoma is to protect the skin from sun exposure (both natural and artificial). Avoid sun exposure between 10am and 4pm, wear protective clothing (including a hat) when in the sun, and use sunscreen with a sun protection factor (SPF) of 15 or greater everyday, even in the winter! Sunscreen use is especially important for children due to the fact that sunburns during childhood greatly increase the risk of melanoma in adulthood. Consistent use of sunscreen has even shown the ability to reduce further skin damage in people with a history of extensive sun exposure.
You should examine your own skin regularly. Be aware of the shapes and coloring of any moles you have. Melanoma often develops from an existing mole, causing its appearance to change. Examine your skin routinely in a mirror, including your back, bottom of your feet, nail beds, and scalp. Look for changes in existing moles, or the development of new ones. Concerning moles are ones that have the "ABCDE" characteristics. "A" is for asymmetry. If an asymmetric mole were divided in half, one side would not look like the other. "B" is for border irregularity. The border of the mole may appear blurry and uneven. "C" is for color. This can be a change in the color the mole has always been, the development of a black mole, or color variation within a mole, meaning that a single mole may have red, brown, and black colors within it. "D" is for diameter. You should have a mole that has changed in size or color, particularly those greater than 6mm in diameter, checked by a physician. “E” is for evolution meaning that a mole has changed in appearance over time, color, shape, or elevation. These rules are not set in stone, which is why you should be aware of your own moles, and report any changes in moles to a physician.

WHAT SCREENING TESTS ARE AVAILABLE ?

The best screening is a skin examination. Your physician should examine your skin during routine physicals, but you should also examine your skin routinely at home. Because you see your skin everyday, you are most likely to notice any changes early on. Prognosis is best when lesions are found early, making skin examination very important

WHAT ARE THE SIGNS?

Melanoma usually presents as an irregular mole, with the "ABCDE" characteristics described above. This can be a preexisting mole that has changed or a newly developed mole. More advanced lesions may have inflammation, oozing, crusting, itching, ulceration or bleeding.

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MELANOMA :THE BASICS

2009-12-13T00:58:00.000-08:00

AM I AT RISK FOR MELANOMA?

Risk factors for cutaneous melanoma, or melanoma that arises in the skin, include fair skin or complexion, a history of sunburns and/or prolonged exposure to ultraviolet light (both sun and artificial UV light), multiple moles, older age, a personal or family history of non-melanoma skin cancer and a personal or family history of melanoma.
As we age, our years of sun exposure increase, and therefore the risk of melanoma increases.
Researchers have found that the risk of melanoma is 2.24 times higher in people with a first-degree relative with the diagnosis; therefore it is important to be aware of your family history. If you have been diagnosed with melanoma, it is important to share this information with your relatives so that they can undergo appropriate screening. Certain types of moles, called dysplastic nevi, are associated with a higher incidence of melanoma. These moles are typically large (>5mm in diameter) and have uneven pigmentation and borders. A single dysplastic nevi is associated with a 2-fold increased risk, while 10 or more nevi indicate a 12- fold increased risk of developing melanoma.
People with fair skin, light eyes, or those who have a tendency to freckle or burn easily are all at higher risk. Melanoma rates are 20 times higher in Caucasians than in Blacks. The melanin in dark-skinned people has been found to have a natural sun protection factor (SPF) and can filter twice as much ultraviolet light as that of a light-skinned person. This protection, however, is not complete, and melanoma can develop in dark-skinned people. Melanoma is more commonly found on soles, palms, or nail beds in dark-skinned people.
A history of 3 or more sunburns, particularly blistering sunburns, before age 20 greatly increases risk. A history of severe sunburns in childhood and adolescence may actually double the risk of melanoma in adulthood. For many years, the tanning industry has promoted tanning salons as a safe alternative to natural sun, or a way to prevent sunburn. This is because the tanning machines were said to produce only UVA rays, without producing UVB rays, which are responsible for most sunburns. Researchers have since learned that tanning beds do produce UVB rays in varying amounts, depending on the machine. They have also learned that UVA is not as safe as once thought. Despite the fact that UVA is less likely to cause sunburn, it has many biologic effects that can cause long-term damage. As for using tanning beds to prevent sunburn on a vacation, this is also untrue. A visit to a tanning bed, followed by natural sun exposure, causes a cumulative effect on skin cells and can cause an unexpected burn. Bottom line: Tanned skin is not healthy and actually indicates that the skin has been damaged.

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Medulloblastoma:Overview 3

2009-12-04T02:29:00.000-08:00

How is medulloblastoma treated?

Surgery

Surgery is typically the first component of therapy, although it is no longer acceptable as the only component. Long-term results of medulloblastoma patients treated as far back as the 1930's have taught us that surgery alone does not cure this tumor.

It is, however, very important to perform as maximal and complete a surgery as possible, with the goal being removal of all visible tumor while sparing as much surrounding brain tissue as possible. This is then confirmed after surgery with a post-operative MRI scan of the brain to look for any leftover, or residual tumor. Based on what the MRI shows, the surgery is classified as one of the following:

•Gross total resection = No evidence of any tumor left behind either at time of surgery or on post-surgery MRI

•Near-total resection = More than 90% of original tumor removed by surgery

•Subtotal resection = Anywhere from 51-90% of original tumor removed by surgery

•Partial resection = Anywhere from 10-50% of original tumor removed by surgery

•Any surgery that removed less than 10% of the original tumor is basically considered just a biopsy, or sampling, of the tumor.

So the ideal situation is a gross total resection, but this is not always possible. For example, sometimes the tumor is invading into or stuck onto other parts of the brain, making safe surgery very difficult. Nonetheless, the overall goal is to take as much of the tumor out as possible without risking severe brain deficits, as the long-term survival of medulloblastoma patients is directly influenced by the degree of surgery. In other words, the more complete the surgery, the better the long-term outcome.

Radiation Therapy

After surgery, external radiation to the entire CNS (craniospinal irradiation, or CSI) is recommended to prevent the tumor from coming back in this area (recurrence, or relapse). Even if complete surgery is performed, low-dose radiation to the brain and spine is very important for local control, local meaning within the CNS. This is the region that is most at-risk for the tumor returning.

Data from old clinical studies of medulloblastoma patients clearly shows that as many as 60-70% of children who got good surgery and no other treatment had recurrence of the tumor. In contrast, patients who got good surgery followed by CSI had lower rates of tumor recurrence. The long-term disease-free survival (patient living without tumor) with the modern radiotherapy techniques of today is as high as 60-65%.

After radiation of the entire cranium and spine to a lower dose of radiation, the area of the original tumor, including where the surgeon operated, continues to receive radiation to a higher final dose (so-called radiation "boost"). This is because the region in the brain where the tumor first started is the most likely place to still have some lingering, unseen, microscopic tumor cells. Historically, the entire cerebellum has been boosted to this higher radiation dose, putting normal structures including the inner ear at risk for radiation damage. In recent studies, only the tumor bed has been boosted with apparently similar success, which allows for protection of normal tissues.

Much attention has understandably been paid to the possible long-term complications of radiation therapy to the brain and spine of a growing child. These can include deficits in memory, learning, and social/emotional adjustment, hearing, and growth problems. The development of such side effects depends on many factors, including extent of pre-radiation surgery, amount and location of brain that is treated, and how much radiation dose is given, among others.

However, modern radiotherapy techniques and proper attention to minimizing radiation dose to important brain structures whenever feasible can allow for safe and effective treatment, even in younger children. While no therapy is without its side effects, radiation therapy can be planned and delivered in such a way as to minimize potential long-term side-effects. This is best accomplished at a major radiation oncology center where physicians and staff are familiar with pediatric patients and technologically capable of treating childhood cancers.

Proton Radiotherapy

Even though the actual craniospinal volume that is irradiated is small, a large volume of normal tissue is also with photon radiotherapy, including the heart, lung, bowel, gonads, and vertebral bodies. Proton radiotherapy offers a major potential advantage over photons for the radiation of the spinal canal, as the lack of exit dose can prevent treatment of tissue deep to the spine. Proton therapy also can prevent radiation dose to normal tissues for the cranial boost, especially for sensitive structures such as middle ear.

At Loma Linda, three children with medulloblastoma were treated with craniospinal proton irradiation to a dose of 36 CGE (Cobalt Gray Equivalents, the accepted unit of proton radiation that equates to 1 Gray of photon radiation) with an 18 CGE posterior fossa boost. No clinically significant blood count depression was seen, and only Grade 2 dermatitis was observed. One child was followed for 3 years and did not show any evidence of scoliosis. More patients and longer follow-up will be needed to fully realize the relative benefit PRT in medulloblastoma.

Chemotherapy

At the present time, the role of chemotherapy in medulloblastoma is primarily as an additional treatment following surgery and radiation to help increase long-term disease-free survival. Clinical trials document disease-free survival at 5 years from diagnosis of about 85%, which is very good. However, these high rates were achieved with chemotherapy drugs such as cisplatin, vincristine, and CCNU, all of which have associated side effects. Furthermore, the addition of chemotherapy to the previous standard of surgery and postoperative radiation has not resulted in overall survival benefits, which are obviously a very important endpoint in pediatric cancer trials. Nonetheless, the use of chemotherapy after surgery, CSI and boost radiation is considered the current standard of care.

Importantly, studies are ongoing looking at the use of chemotherapy not only for disease control, but as a possible means to lower craniospinal radiation doses in particularly young children without compromising local tumor control.In light of the potentially severe long-term side effects of radiation to the CNS of a very young child, this is certainly a worthwhile research endeavor, and results of such studies may be incorporated in future treatment of medulloblastomas. Other novel agents, such as cholesterol lowering drugs ("statins") and cyclopamine (an inhibitor of the Sonic hedgehog signaling pathway) have been studied in the laboratory and may be promising less toxic agents for the treatment of medulloblastoma

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Medulloblastoma:Overview 2

2009-12-04T02:24:00.000-08:00

What are the signs of medulloblastoma?

The most common symptom of this tumor is frequent, severe vomiting. Less commonly seen are headache, nausea, and visual changes, such as double vision. Typically, children with medulloblastoma come to the attention of parents and teachers because of unsteady walking and clumsiness with holding things. All of these symptoms are consistent with a problem in the cerebellar region. For example, the constant vomiting results from excessive pressure in the brain due to tumor blockage of important pathways for cerebrospinal fluid flow.

Please note that the symptoms mentioned here do not necessarily or automatically mean a child has a brain tumor, but further medical evaluation is required to rule out the possibility of a cerebellar tumor, such as medulloblastoma.

How is medulloblastoma diagnosed?

A magnetic resonance imaging (MRI) scan of the brain with gadolinium contrast-enhancement is the gold standard for detecting medulloblastoma. It has a very characteristic appearance on MRI scan: a well-defined, solid-looking mass located in the cerebellum, with fairly uniform contrast enhancement.

Medulloblastoma is a tumor type that is classically associated with spread from the brain to the spine and/or cerebrospinal fluid (CSF) bathing the CNS. Thus, part of the diagnostic workup should also include a gadolinium-enhanced MRI of the spine. The search for disease spread to the spine can be supplemented with a lumbar puncture. This is a procedure in which a thin needle is inserted into the lower back in order to obtain a sample of the cerebrospinal fluid, looking for floating tumor cells (cytology).

Of course, the only way to know the diagnosis of a suspicious mass is to biopsy it, meaning to "cut out a piece of the mass". Although performing a biopsy on the brain may sound like a bad idea, it is actually pretty easy to do for tumors located towards the front or the top of the brain using modern neurosurgical techniques.

However, medulloblastomas, as mentioned before, occur in the cerebellar region, which is technically rather difficult to access for simple biopsy. Thus, diagnosis is typically made from radiology studies +/- lumbar puncture cytology, and surgery is undertaken with the goal of complete mass removal (gross total resection), rather than just biopsy. This is further explained below.

How is medulloblastoma staged?

As mentioned earlier, staging is a way of grouping cancer patients with similar diagnoses and similar extent of disease. Most CNS tumors remain where they started, (ie: in the brain or in the spine), often referred to as "localized disease". However, medulloblastomas are notorious for spreading from the cerebellum down to the spine, or "metastasizing". They typically invade the surrounding lining tissues (meninges) before gaining access to the cerebrospinal fluid (CSF) which bathes both the brain and the spine. Once there, tumor cells can travel through the CSF and deposit themselves, or "seed", in any part of the spine, resulting in "metastatic disease". Rarely, these tumor cells can gain access outside of the CNS and metastasize to distant bone or bone marrow.

For medulloblastoma, a modified version of the Chang staging system is commonly used. The original Chang system was devised in the late 1960's, before the widespread use of radiology scans, and so it relies primarily on information about tumor size and spread that is obtained during actual surgery, with the naked eye. Based on what the surgeon sees at the time of the surgery, the actual tumor is placed in one of the following categories (T referring to tumor):

•T1 Tumor <3 cm in diameter

•T2 Tumor >3 cm in diameter

•T3a Tumor >3 cm in diameter with spread

•T3b Tumor >3 cm in diameter with definite spread into the brain stem (part of brain that controls breathing, hearing, seeing, and other important functions)

•T4 Tumor >3 cm in diameter with extension up past the aqueduct of Sylvius and/or down past the foramen magnum

In addition to "T" staging, medulloblastoma staging has been modified by including "M" staging, where the "M" stands for metastasis. Remember, this is a word that describes how far the tumor cells have spread from the original location, if at all. The M stage is determined not only by the surgeon's observations, but also in combination with MRI scans and lumbar cytology, and consists of 5 possible groups:

•M0 No evidence of metastasis

•M1 Tumor cells found in cerebrospinal fluid (by lumbar puncture and cytology study)

•M2 Tumor beyond primary site but still in brain

•M3 Tumor deposits ("seeds") in spine area that are easily seen on MRI

•M4 Tumor spread to areas outside the CNS (outside both brain and spine)

Each patient is assigned a combination of one T stage and one M stage. As mentioned in the introduction, one of the reasons staging is important is that it helps predict how a patient might do in the long run, or how "curable" their cancer is, in a way. For medulloblastomas, the M stage is considered far more important in determining ultimate patient outcome and survival than the T stage. In other words, regardless of what the T stage may be, children who are in the M0 group do far better than those in M1, who tend to fare better than M2 kids, who in turn do better than M3 or M4 children.

Of course, each case of medulloblastoma is different, and while staging tries to group patients together, any one individual patient may not follow the rules, so to speak.

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Medulloblastoma: Overview

2009-12-04T02:21:00.000-08:00

Some Background

Almost 20% of all childhood cancers start in the central nervous system (CNS), which consists of the brain, the spinal cord, and the surrounding fluid (cerebrospinal fluid, or CSF), lining tissues (meninges) and bone (cranium and vertebrae).

In the past several years, the incidence of pediatric CNS tumors has been increasing. This increase is partially explained by medical advances that have led to earlier detection and diagnosis of brain tumors.

There are many different types of pediatric CNS cancers, all of which have long and rather complicated names. The diagnosis typically depends on two things: 1) where in the CNS the tumor starts, or the location , and 2) how the tumor looks under a microscope, also known as the histology . Primary brain tumors are tumors that arise in the brain, while primary spinal tumors grow in the spinal cord. However, some brain tumors can spread to involve parts of the spine, and vice versa. On occasion, certain types of tumors can even spread to areas outside of the CNS, such as distant bones or bone marrow.

This is where the concept of "staging" the tumor comes in, and each tumor type has its own specific staging system. The purpose of assigning a cancer stage is to help predict outcome, as well as to guide treatment by appropriately applying the data acquired from clinical pediatric cancer trials. Of course, ultimately, every cancer treatment plan is individualized for every patient, and takes into account not only the stage and the clinical data, but also the goals and desires of the patient and his or her family.

What is medulloblastoma?

Medulloblastoma is a type of brain tumor that occurs in infants and young children. It represents about 20% of all pediatric CNS cancers. By definition, medulloblastomas occur in the cerebellum, which is the back part of the brain that controls walking, balance and fine motor coordination, among other things.

Medulloblastoma is a long name made up of three smaller words: medulla = Latin for marrow, meaning inner substance or core; blastos = Greek word for germ, meaning young, primitive, not fully developed; and oma = Greek for tumor. In other words, this is a tumor of primitive, undeveloped cells located inside the cerebellum.

Who gets this tumor, and how?

Medulloblastoma almost always occurs in children less than 15 years old, and most commonly between the ages of 5-6 years. About 20% of the cases occur in infants less than two years old. This disease appears to be more common in boys than girls.

No clear or definitive causes of medulloblastoma have been identified. It does not appear to "run in families" or to be directly inherited from the parents. However, medulloblastoma is associated with certain chromosomal abnormalities that probably occur at some point during a child's development. This includes not only development after birth, but also the prenatal period before a baby is born, while it is still a growing embryo or fetus. One possible cause that has been suggested is exposure of the fetus to certain causative viruses or environmental agents, but this theory remains under investigation.

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LUNG CANCER:THE BASICS 3

2009-12-04T02:10:00.000-08:00

How is lung cancer diagnosed and staged?

When a patient at risk for lung cancer has symptoms suggestive of a lung tumor, they will usually first be referred for a chest x-ray. If the chest x-ray looks abnormal, then they will be referred for a CT scan (a 3-D x-ray) to better characterize the lesion. The other thing that your doctor may do is called sputum cytology, which means examining your phlegm for cancer cells.

Depending on the results of the sputum cytology, chest x-rays, and/or CT scans, your doctors may recommend that you have a biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to see your cells under a microscope. There are different ways that a biopsy may be done. Your doctors may want to do fiberoptic bronchoscopy, which means putting a thin, lighted tube down your nose or mouth and into your lung to look at the tumor and take samples of it. Another way to get a biopsy sample is to do a needle biopsy, which means placing a needle through the skin into the tumor to get cells. Sometimes, tumors cells can get into the fluid around your lungs, and your doctor may want to drain off some fluid (called a thoracentesis) and examine it under a microscope.

Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from and what subtype of lung cancer it is, how abnormal it looks (known as the grade), and whether or not it is invading surrounding tissues.

In order to guide treatment and offer some insight into prognosis, lung cancer is staged into different groups. The staging system is different for the two main types of lung cancer: small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC). This staging is done in a limited fashion before surgery taking into account the size of the tumor on CT scan, where it is, and any evidence of spread to other organs that is picked up with imaging modalities; and it is done definitively after a surgical procedure that removes lymph nodes and allows a pathologist to examine them for signs of cancer. Sometimes, surgeons will do procedures just for staging. One such procedure is called a mediastinoscopy. A mediastinoscopy is a procedure in which a surgeon uses a scope to sample the lymph nodes near the trachea (the windpipe) so that the pathologist can examine them for signs of cancer. Often, your doctors will want to know the exact stage of your cancer before treatment is planned, because the stage of the cancer drastically affects how it is treated. The staging system is somewhat complex, but here is a simplified version of it:

Small Cell Lung Cancer - divided into two stages

1.Limited Stage - means the cancer is on only one side of the chest (lung and/or lymph nodes), so it could be reasonably treated with a radiation field

2.Extended Stage - means the cancer is on both sides of the chest (spread to both lungs and/or lymph nodes on both sides of the body) or spread outside of the chest to other areas of the body, so it could not be reasonably treated with a radiation field

Non Small Cell Lung Cancer - divided into four main stages

1.Stage IA- the tumor is less than 3 cm, isn't in a main bronchus, and hasn't spread to any lymph nodes

Stage IB - the tumor doesn't invade any organs, isn't too close to the trachea if it is in the main bronchus, doesn't cause obstruction of the lung, and hasn't spread to any lymph nodes

2.Stage IIA- the tumor is less than 3 cm, isn't in a main bronchus and has spread to lymph nodes on the same side as the tumor

Stage IIB - the tumor doesn't invade any organs, isn't too close to the trachea if it is in the main bronchus, doesn't cause obstruction of the entire lung but has spread to hilar lymph nodes on the same side as the tumor.

3.Stage IIIA - the tumor can have spread to different types of lymph nodes than Stage II (called mediastinal or subcarinal), but they are still on the same side as the tumor and it hasn't invaded any vital organs

Stage IIIB - the tumor has either invaded vital adjacent organs and/or spread to lymph nodes on the other side of the mediastinum as the tumor, or specific lymph nodes called scalenes or supraclavicular. Also, the patient may have tumor spread to the fluid surrounding the lung

4.Stage IV- the tumor has spread (metastasized) to other organs in the body outside the lungs (like the bones, brain or liver)

Stage IIIB and stage IV non small cell lung cancers are generally considered inoperable, so it is very important to know if the cancer has spread to lymph nodes on the opposite side of the chest as the tumor. Part of your workup to look for spread of the tumor (metastasis) will probably also entail CT scans of the liver and adrenals, a CT scan or MRI (a different sort of scan which uses magnets) of your brain, and a PET scan. If you are having particular symptoms, then your doctor may want different or more specific exams. Often times, if there is a plan for surgery, your doctor will order tests called PFT's (pulmonary function tests) to assess your lung capacity. Overall, your doctors will want to know as much about your particular tumor as possible so that they can plan the best available treatments.

What are the treatments for lung cancer?

Surgery

For patients with non small cell lung cancer, surgery is often employed in cancers up to and including stage IIIA. The purpose of the surgery is to remove all of the cancer if possible. If the tumor is small and in a favorable location, or the patient has limited lung function, the surgeon may choose to remove the tumor with a small section of lung; this is called a wedge resection. Most times the surgeon will choose to remove the entire lobe of the involved lung; this is known as a lobectomy. On occasion, the surgeon must remove the entire lung affected by the cancer; and this is known a pneumonectomy. Not every patient can tolerate these surgeries. Patients with diminished lung function due to other diseases may not be able to survive after such a surgery, or they may be severely limited in their activities. Preoperative pulmonary function tests (PFT's) are used to help predict who is a good candidate for surgery. Sometimes a quantified ventilation perfusion scan will be ordered which shows the amount that each area of lung is currently working. These tests may help the surgeon to predict how much lung function will be lost based on the amount of lung that will need to be removed, and how well the patient will feel after surgery. Surgery is not generally recommended for small cell lung cancer of any stage. Small cell lung cancer is usually treated with chemotherapy and radiation therapy. There have been some studies on the use of surgery in small cell lung cancer for very early stage lesions; however, this is not generally considered a standard option for patients with small cell lung cancer.

Another potential use for surgery with lung cancer lies in treating solitary brain or spinal metastases. If a patient has a solitary lesion in the brain or spine, a neurosurgeon may elect to remove them surgically. Talk with your doctor about the different ways to approach treatment of your particular disease.

Chemotherapy

Despite the fact that the tumors are often removed by surgery, there is always a risk of recurrence because there may be microscopic cancer cells left that the surgeon cannot remove. Also, some patients are not candidates for surgery or choose not to have surgery. Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein or as pills by mouth. Chemotherapy is recommended after surgery for some stage I and stage II non-small cell lung cancer patients. Because current treatment of advanced stage non-small cell lung cancers (stage III) is often a combination of radiation and/or chemotherapy and/or surgery, the timing and use of chemotherapy may vary depending on the specifics of the case. It may be given at the same time as radiation, or before or after radiation. Chemotherapy is offered to many patients with stage IV disease.

Small cell lung cancer is very responsive to chemotherapy, and most patients with small cell lung cancer will be offered chemotherapy. Again, depending on the specifics of an individual case, it may be given during radiation, or before or after radiation is complete.

There are many different chemotherapy drugs, and they are often given in combinations. Patients will usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Different chemotherapy regimens are used for different purposes. Some of the drugs used in lung cancer chemotherapy include: Etoposide (and Teniposide), Cisplatin (and Carboplatin), Ifosfamide, Cyclophosphamide, Vincristine, Doxorubicin, Paclitaxel, Docetaxel, Gemcitabine (Gemzar ®) and Vinorelbine (Navelbine). There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle.

Targeted Therapies/Biologic Therapies

Targeted (also called "biologic") therapies are a new class of medications that have been specifically designed to combat precise pathways in various cancers. Cancers have abnormal genetic pathways and receptors, and recent research has helped characterize the particular molecular pathways that make cells cancerous and resistant to treatment with chemotherapy and radiation. Sophisticated laboratory research and pharmaceutical design have created a new class of medications, known as targeted therapies. These medications often produce less significant side effects than standard chemotherapy drugs. They can be given both though a vein or as pills by mouth. They can also be given in combination with standard chemotherapy. Benefits in stage IV lung cancer patients have been recently reported using two different targeted therapies: "Bevacizumab (Avastin)" and "Erlotinib (Tarceva)". Clinical trials are ongoing to determine the benefit of other targeted therapies in this disease. For more information on targeted therapies see the Targeted Therapy Basics and Types of Targeted Therapies sections of Oncolink and talk to your doctor.

Radiotherapy

Lung cancer patients commonly are treated with radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for up to 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Radiation therapy is often combined with surgery and is important in the treatment of all types of lung cancer. It may be recommended before surgery to shrink a tumor to make it easier for the surgeon to remove. Radiation may be used after surgery if there are worrisome risk factors that make it likely for a tumor to come back in the chest. Sometimes radiation is used instead of surgery if a surgery is felt to be too dangerous for the patient, or if a tumor is too extensive to be removed with surgery.

Radiation is often used in the setting of metastatic disease (cancer cells that have spread to other regions of the body). Radiation can be used to reduce pain from metastatic disease, or reduce the risk of problems from cancer that may have spread to the brain.

In small cell lung cancer, brain radiation is sometimes used even if a patient does not have known cancer in the brain. This is called prophylactic cranial radiation. Clinical trials have shown that patients with small cell lung cancer may live longer if they have radiation to the brain; this is likely because cancer cells have spread to the brain, but tumor regions are too small to be seen with CT or MRI scans. Prophylactic cranial radiation can be used to kill these cells before they cause the patient problems.

Photodynamic Therapy

Photodynamic therapy (PDT) involves injecting a patient with a drug that preferentially gets taken up in cancer cells and then makes them sensitive to a particular kind of light. When the light is shone on the tumor, the drug is activated, and cancer cells are killed. Photodynamic therapy is occasionally used in the treatment of lung cancer for lesions in the airway. There are also clinical trials ongoing at the Hospital of the University of Pennsylvania to treat cancers with PDT that have spread to the fluid surrounding the lung cavity. Please visit the OncoLink/Emergingmed Clinical Trials Resource Center to see if you qualify for any of these studies.

Follow-up testing

Once a patient has been treated for lung cancer, he or she needs to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up chest x-rays, CT scans, or other tests. Lung cancer is generally considered an aggressive tumor that often comes back after treatment; thus it is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments. Finally, if you haven't yet done it, you need to quit smoking. Remember, it is never too late to get the health benefits of smoking cessation.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of lung cancer. You may find this knowledge useful when meeting with your physician, making treatment decisions, and continuing your search for information.

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LUNG CANCER:THE BASICS 2

2009-12-04T02:05:00.000-08:00

How can I prevent lung cancer?

The best way to prevent lung cancer is to quit smoking, or to never start in the first place. You should try and avoid being around people who are smoking; and also avoid pipes, cigars, and marijuana. If you live in an area with radon, you should make sure there is adequate ventilation in your basement to get rid of it. Use a detector to make sure the radon levels are low. If you work in an industry where you are exposed to substances known to cause lung cancer, make sure to use all the proper protective equipment and attire made available by your employer.

There has been some suggestion that a diet high in fruits and vegetables may decrease your risk of lung cancer. This has yet to be definitively proven. Many substances, including antioxidants like vitamin A, vitamin E, and beta-carotene, have been suggested to decrease your risk of lung cancer. None of these has been shown to be beneficial in randomized controlled trials and cannot be recommended for this purpose. In fact, large clinical trials have shown and increased risk of lung cancer in patients that take increased quantities of vitamin E, vitamin A, and beta-carotene.

The future of lung cancer prevention will rely on sophisticated analysis of patients' genes and molecular markers for lung cancer risk; this coupled with "smart drug" design and novel imaging techniques may one day help decrease the risk of developing lung cancer.

What screening tests are available?

It is generally held that there are no good screening tests available for lung cancer. In all of the studies conducted to date, comparing people who are screened with chest x- rays and/or sputum samples, there has never been a documented decrease in deaths from lung cancer due to screening. However, this is an issue that is hotly debated because some studies have shown that cancers can be picked up in earlier stages if patients are screened with chest x-rays. The problem is that picking up the cancers earlier hasn't translated to a decrease in deaths because of the screening. Some doctors may choose to screen high risk patients (usually those patients over 50 years old with a significant smoking history) with annual chest x-rays in an effort to find cancers earlier, however, no professional society has endorsed this practice. Currently, there is debate about the utility of screening people with CT scans (3-D x-rays that are more sensitive than standard chest x-rays). The debate is the same as with chest x-rays; no one has demonstrated a decreased mortality in patients screened with CT scans thus far. As more data is collected and more sophisticated imaging techniques are developed, perhaps one day there will be a good screening test for lung cancer. In the absence of a good screening tool, the best way we can decrease the number of lung cancer deaths is to help people to quit smoking.

What are the signs of lung cancer?

Unfortunately, the early stages of lung cancer may not have any symptoms. As the tumor grows in size, it can produce a variety of symptoms including:

•cough (especially one that doesn't go away or gets worse in character)

•chest pain

•shortness of breath

•coughing up blood or bloody phlegm

•new onset hoarseness or wheezing

•recurrent problems with pneumonia or bronchitis

•weight loss

•loss of appetite

•fatigue

•bone pain

•dizziness or double vision

•numbness or tingling in your arms or legs

•turning yellow (jaundice)

•seizures

Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. Most patients (85%-90%) who are diagnosed with lung cancer have symptoms that prompt a doctor to order tests to look for a problem. A cough is the most common presenting symptom of lung cancer; however, many long term smokers have a chronic cough, so it is especially important for someone with a chronic cough to see their doctor if their cough changes in character or severity

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Lung Cancer: The Basics

2009-12-04T02:00:00.000-08:00

What are the lungs?

The lungs are two spongy organs found in the chest. They are responsible for delivering oxygen to the bloodstream. When you take a breath in, air moves into the lungs causing them to expand. The air can then come very close to blood that is traveling in small vessels called capillaries. When you breathe out, you exhale substances that you don't need like carbon dioxide. The lungs are specially designed to place blood in close contact with as much air as possible, so their tissues are very delicate. The right lung has three sections called lobes. The left lung has only two lobes. Air comes in through your mouth and nose and then travels down a tube to the lungs called the trachea. The trachea divides into smaller branches called bronchi, and the bronchi keep dividing and dividing like branches on a tree. As the branches get smaller, they are called bronchioles. At the end of the branches, there are little sacs of air called alveoli. The air comes into contact with blood in the alveoli. The lungs are exposed to whatever you breathe in, so any toxic chemicals or pollutants in the air you breathe can get into your body through your lungs.

What is lung cancer?

Lung cancer happens when cells in the lung begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of cancer cells are called tumors. Cells in any of the tissues in the lung can develop cancer; but most commonly, lung cancer comes from the lining of the bronchi. Lung cancer is not really thought of as a single disease, but rather a collection of several diseases that are characterized by the cell type that makes them up, how they behave, and how they are treated. Lung cancer is divided into two main categories:

•Small cell lung cancer (SCLC) - the rarer of the two types (about 20% of all lung cancers), small cell lung cancer is more aggressive than non small cell lung cancer because is grows more quickly and is more likely to spread to other organs

•Non small cell lung cancer (NSCLC) - the more common of the two types (80% of all lung cancers), non small cell lung cancer is generally slower growing than small cell lung cancer and is divided into three different types based on how the cells look that make it up - adenocarcinoma, large cell carcinoma, and squamous cell carcinoma

Am I at risk for lung cancer?

Lung cancer is the most common cause of cancer death in the world for both men and women. In the United States alone, it is estimated that 163,510 people will die from lung cancer in 2005. In comparison, 127,500 people are expected to die from colon, breast and prostate cancer combined in 2005 (the 2nd, 3rd, and 4th most common cancers in the U.S.). In the U.S., there has been a striking increase in the number of women getting lung cancer; in the 1990s, lung cancer overtook breast cancer as the most common cause of cancer death amongst women. This probably reflects increase incidence of smoking among women.

Every smoker is at risk for lung cancer. It is estimated that 87% of all cases of lung cancer are caused by cigarette smoking. The major risk factor for lung cancer is cigarette smoking. Your risk of getting lung cancer from cigarette smoking increases the longer you smoke, the more you smoke, and the deeper you inhale. Smoking low tar cigarettes does not prevent you from getting lung cancer. Importantly, if you quit smoking, your risk of getting lung cancer declines. The longer you go without smoking, the greater your risk declines. It is never too late to quit because your risk declines somewhat no matter how long you have been smoking. Even patients who have been diagnosed with lung cancer have been demonstrated to respond to treatment better and live longer if they quit smoking at the time of their diagnosis.

Smoking also has an affect on people around you. Second-hand smoke, or smoke inhaled when you are near someone smoking, is another risk factor for lung cancer. It is estimated that 17% of cases of lung cancer in non-smokers are caused by second-hand smoke exposure in childhood and adolescence. Non-smoking spouses of smokers are 30% more likely than spouses of non-smokers to get lung cancer. Even though many people don't inhale them, smoking pipes and cigars is a risk factor for lung cancer as well. The more pipes or cigars you smoke, the more likely you are to get lung cancer. Although it is not as well established as cigarette smoking, smoking marijuana is also a risk factor for getting lung cancer. Both the magnitude and duration of marijuana use seems to be related to your overall risk.

Although smoking cigarettes is by far the most common and important risk factor for getting lung cancer, there are some environmental exposures that increase your risk for lung cancer as well. People who work with asbestos are more likely to get lung cancer; and if they smoke cigarettes too, their risk rises even higher. Asbestos is found in industries like shipbuilding, brake manufacture, insulation/fireproofing, and asbestos mining and production. Other workers who may have a higher risk of lung cancer are those exposed to arsenic, chromium, nickel, vinyl chloride, hard metal dusts, talc, uranium, and gasoline and diesel exhaust fumes.

Radon is an invisible, odorless gas that exists naturally in areas where there is a lot of uranium in the ground. Radon can collect in both uranium mines and peoples' houses. Exposure to radon has been associated with a slightly increased risk of lung cancer. You can check for radon with detectors available at a hardware store, and getting rid of it is usually as easy as opening a basement window.

People who have already had lung cancer are at risk for getting it again. A history of interstitial lung disease or tuberculosis (TB) also increases your risk of getting lung cancer. However, it should be stressed that cigarette smoking is far and away the most important and dangerous risk factor for developing lung cancer.

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Laryngeal Cancer: The Basics 4

2009-08-16T05:23:00.001-07:00

Supraglottis

Many of the issues for early stage supraglottic cancers are the same as those for early stage glottic lesions. As far as treatment of the primary tumor in the throat, cure can often be achieved with radiation therapy alone or with voice-preserving surgery, such as the supraglottic laryngectomy, a specialized surgical procedure that removes the tumor but leaves much of the vocal cords intact.

A major difference between early stage glottic cancer and early stage supraglottic cancer is the chance of spread to the lymph nodes. As stated before, glottic cancer has very little risk of spread to the lymph nodes while a patient with a supraglottic cancer has a significant chance of having spread of tumor to the lymph nodes. Therefore, treatment of the neck must also be a concern. This is done in one of two ways: Either by using radiation therapy delivered to the entire neck, or through a surgical procedure called a neck dissection. Either modality can likely be used, and often it depends on which treatment is being used to treat the primary tumor. If radiation therapy is being used to treat the tumor in the throat, then radiation will likely be recommended as treatment to the neck. The same goes for surgery. Some patients who have surgery may also need radiation to the neck, if many lymph nodes are found to be involved with tumor or other features of the tumor warrant additional treatment.

Advanced larynx cancer

Many times, cancer of the larynx grows too large to consider a minor surgical procedure for cure. For patients with more advanced tumors, radiation therapy alone is also unlikely to achieve cure. In the past, all of these patients would be required to have a total laryngectomy, a surgical procedure that removes the entire voice box. This leaves the patient with a hole in the neck to breathe through and without the ability to speak normally. This is still a very acceptable treatment, and the only treatment available in patients with very advanced tumors in their throat. Obviously, it leaves the patient with functional disabilities, but is efficacious in treating the cancer itself.

Some centers are currently making use of investigational robotic surgical procedures, referred to as “transoral robotic surgery” (TORS). These procedures allow surgeons to access the supraglottic and glottic regions by way of the mouth, to reduce surgical morbidity. They may also allow surgeons to perform more limited surgical procedures than total laryngectomy; however, the indications for robotic surgery are still dependent on in the individual patient and individual tumor.

Many physicians have investigated "organ-sparing" treatment for advanced laryngeal cancers. The organ preservation approach makes use radiation in combination with chemotherapy to attempt to cure the patient of his or her cancer without requiring a total laryngectomy. This type of treatment was first investigated by a large study conducted by the Veterans Affairs Medical Center. In this study, patients with advanced laryngeal cancer were randomized to one of two treatments – total laryngectomy or chemotherapy followed by radiation therapy. Patients in the two groups had similar cure rates and survival, but the rate of voice preservation was higher for group who had chemotherapy and radiation therapy. Recently, a large study was presented in which patients who had chemotherapy and radiation therapy at the same time had an even higher rate of keeping their larynx. Therefore, this is what many physicians offer their patients who desire to attempt to keep their larynx intact.

Organ preservation treatment, usually consisting of use of radiation and chemotherapy together, should not be undertaken lightly. The combined use of chemotherapy and radiation therapy can have severe side effects, both during treatment and after. Most patients who undergo this treatment will have severe pain with swallowing during their radiation therapy. The pain may be severe enough to cause malnutrition, so many patients require a feeding tube during the treatment. Symptoms of pain get better after the treatment is completed, and feeding tubes can usually be removed in the months after radiation therapy is complete.

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Laryngeal Cancer: The Basics 3

2009-08-16T05:22:00.000-07:00

How is larynx cancer diagnosed and staged?

Staging

The staging of a cancer basically describes how much it is grown before the diagnosis has been made, documenting the extent of disease. Glottic cancer often produces hoarseness early, causing it to be diagnosed earlier. Unfortunately, supraglottic and subglottic laryngeal cancer often present as a more advanced disease because of lack of early diagnosis, due mainly to the lack of specific symptoms that are associated with it. Before the staging systems are introduced, we will first discuss some background on how cancers grow and spread:.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way larynx cancers can spread is by local extension to invade through the normal structures in the throat and into adjacent structures in the neck. These include the vocal cords themselves, the structures controlling voice and swallowing, the epiglottis (which is needed to prevent choking when swallowing), and even the cartilage and muscles surrounding the larynx. All cancers can spread via local extension, though this method of spread is particularly important in larynx cancer and other cancers of the throat. Tumor growth by local extension in the larynx can cause a patient's airway to be compromised or the swallowing function to be interrupted (which leads to problems eating and subsequent malnutrition), as well as causing the loss of the protection of the airway during swallowing which leads to choking and infection. Keep in mind that larynx cancers, when spreading via local extension, often spread from one subsite to the other (i.e.-glottis cancers can spread locally to involve the supraglottis). Sometimes, if cancers are locally advanced, it can be difficult to tell from which part of the larynx they originally grew.

Larynx cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Larynx cancers differ in their propensity to spread, again based on the site of the larynx that the tumor involves. Supraglottic cancers have spread to the lymph nodes in over 50% of patients by the time a diagnosis has been made. This is in contrast to a pure glottic cancer (one that has not spread to the supraglottis or other sites within the throat by local extension) which spreads to the lymph nodes in less than 5% of patients upon diagnosis. However, keep in mind that once a cancer spreads from the glottis (the true vocal cords) to another subsite, it can spread to lymph nodes just as much as a cancer that originated in that other subsite. The first lymph nodes that cancer cells spread to are the "jugular chain" of lymph nodes which are found along the side of the neck. They can be found in front of the large muscles on either side of the neck that contract when the head is turned from side to side. Tumor cells that spread to the jugular lymph nodes can then spread to the "supraclavicular" lymph nodes (found behind the collar bone) and to other lymph nodes in the neck.

Larynx cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from this travel to other organs are called metastases. Cancers of the larynx generally spread locally or to lymph nodes before spreading distantly through the bloodstream. Hence, the incidence of distant metastases is generally thought to be 10% or less. However, as more patients are being cured of their local and lymph node disease, this incidence of distant metastases may climb. Although it increases with extent of disease in the throat and neck and is more common with supraglottic (and subglottic) tumors, distant metastases are still found in only a small number of patients diagnosed with laryngeal cancer (15% or less). If spread through the bloodstream does occur, the lungs are the most common site followed by the bones as the next most common site.

The staging system used in larynx cancer is designed to describe the extent of disease in both the throat itself and the neck (with spread to the lymph nodes). Both are important for treatment and need to be considered somewhat separately, as will be noted in the treatment section. The staging system used to describe laryngeal tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the throat itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases). Since the different subsites of the larynx have different structures, the "T" portion (or local extent of disease) is described separately for each.

The "T" stage is as follows:

Glottis:

T1-tumor limited to the vocal cords

T1a-tumor limited to one vocal cord
T1b-tumor involves both vocal cords

T2-tumor extends to the supraglottis and/or subglottis and/or causes impaired vocal cord mobility
T3-tumor with vocal cord fixation (a cord cannot move at all)
T4-tumor invades outside of the larynx (trachea, soft tissues of the neck, etc.)

Supraglottis:

T1-tumor limited to one subsite of the supraglottis with normal vocal cord mobility
T2-tumor invades one adjacent site of the supraglottis or glottis or one region outside of the supraglottis without fixation of the vocal cords
T3-tumor limited to the larynx with vocal cord fixation or invasion into the area behind the larynx or in front of the larynx
T4- tumor invades outside of the larynx (trachea, soft tissues of the neck, etc.)

Subglottis:

T1-tumor limited to the subglottis
T2-tumor extends to vocal cord(s) with normal or impaired mobility.
T3-tumor limited to the larynx with vocal cord fixation.
T4- tumor invades outside of the larynx (trachea, soft tissues of the neck).

The "N" stage is as follows for any subsite:

N0-no spread to lymph nodes
N1-tumor spread to one lymph node on the same side as the tumor in the throat. Lymph node must be <>
N2a-tumor spread to one lymph node on the same side as the tumor in the throat. Lymph node is between 3 and 6 cm
N2b-tumor spread to more than one lymph nodes on the same side as the tumor in the throat, with none being >6 cm N2c-tumor spread to lymph nodes on both sides of the neck, with none being >6 cm

N3-tumor spread to a lymph node when the lymph node is > 6 cm

The "M" stage is as follows:

M0-no tumor spread to other organs
M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters:

Stage I-T1N0M0
Stage II-T2N0M0
Stage III-T1-3N1M0 or T3N0M0
Stage IVA-T4N0-1M0 or Any T, N2M0
Stage IVB-Any T, N3M0
Stage IV-any M1

Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through various tests done as the diagnosis and work-up of the cancer is being performed.

Diagnosis

Clinical evaluation of a laryngeal cancer must include an evaluation of the throat. This can be done with a mirror, though it is more commonly done using a fiberoptic scope called a nasopharyngolaryngoscope. This is a camera attached to a long fiberoptic endoscope that is inserted into the patient's nose to view the throat. Medicine designed to numb the inside of a patient's nose is sprayed into the nostrils before the procedure to maintain comfort during the short exam during which the patient is awake. The entire throat down to the level of the vocal cords is evaluated with special attention to the surfaces of the throat and the movement of the vocal cords. This is followed by a direct laryngoscopy, which is done in the operating room under anesthesia. Since the patient is sleeping during this examination, a more thorough exam can be done with biopsies being done at that time. A careful examination of the neck is also required to detect spread of tumor to the lymph nodes.

Other procedures are needed to determine the stage of the tumor in a patient. CT scans ("CAT scans") or sometimes MRIs of the neck are done to further determine the extent of the disease, both in the throat and in the neck. A chest x-ray is also often ordered to rule out spread of tumor to the lungs. Other, more routine, tests done before treatment include blood screening tests, to insure that overall blood counts are within normal limits, and that a patient's liver, kidneys, and overall health are normal.

What are the treatments for laryngeal cancer?

The treatment of laryngeal cancer has undergone changes in the past 10 years or so, mainly to reflect the desire to preserve a patient's voice box. In keeping with other aspects of laryngeal cancer, treatment can also differ greatly depending on subsite. In addition, there are different treatments available for early stage diseases that would not be used in someone with more advanced disease. Finally, treatment of larynx cancer should be thought of in two parts: Treatment of the throat itself (the primary tumor) and treatment of the neck (from spread to the lymph nodes). Your physician will need to address these somewhat separately, with a constant concern about spread through the bloodstream, or distant metastatic disease.

Glottic Cancer

As stated above, glottic cancer (cancer of the true vocal cords) produces symptoms early. Therefore, patients can present with early lesions, or even pre-cancerous lesions (cancer-in-situ, or cancer that has not invaded into tissues). Cancer-in-situ of the vocal cords is highly curable and can be treated by microexcision, laser vaporization, or radiation therapy. Though all treatments produce sufficient cure rates, the treatment of choice is usually microexcision, with radiation therapy being reserved for more diffuse lesions.

As noted above, in patients with early glottic tumors (T1 or early T2-those without significant spread outside of the vocal cords), have very little chance of spread to the lymph nodes of the neck (<5%).>

The management of T2 glottic cancers is similar to that of smaller tumors (T1). However, it is more complicated because a T2 glottic cancer can mean anything from a small tumor just outside the vocal cords to a larger tumor that causes some decreased movement in the vocal cord. Because it probably offers the best rate of vocal preservation, radiation is an excellent choice in early T2 lesions. For larger tumors, or if vocal cord movement is impaired by a tumor, a surgery called a hemilaryngectomy is often needed. A hemilaryngectomy removes a portion of the vocal cords, yet still leaves enough of the vocal cord behind to maintain a hoarse, but acceptable voice.

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Laryngeal Cancer: The Basics 2

2009-08-16T05:21:00.000-07:00

How can I prevent laryngeal cancer?

Smoking is by far the strongest risk factor associated with the development of laryngeal cancer. Since it is fairly uncommon for a non-smoker to be diagnosed with laryngeal cancer, smoking cessation is the best way to prevent laryngeal cancer. In fact, not using tobacco of any kind, by either smoking or smokeless, is the healthiest thing anyone can do, both in terms of preventing laryngeal cancer, as well as the prevention of other throat cancers, lung cancers, and many other serious health problems.

Reducing alcohol intake may also be helpful in the prevention of laryngeal cancer, especially for people who smoke. Reducing other risk factors, such as chronic vocal irritation and gastroesophageal reflux may also be beneficial. A healthcare professional should be consulted for chronic health problems such as laryngitis or chronic heartburn.

Trials have been performed in the past investigating 13-cis-retinoic acid (found in vitamin A) for the prevention of second cancers after patients were cured of their first cancer. There was a large decrease in the incidence of these second cancers in patients who used 13-cis-retinoic acid. However, this has not yet been substantiated and is currently being tested in patients without a history of cancers. Regardless of the outcome, taking 13-cis-retinoic acid is by no means a substitute for smoking cessation.

What screening tests are available?

Cancer of the larynx affects about 15,000 people per year, which is many fewer than breast cancer, lung cancer, and prostate cancer. Therefore, it is not large enough of a health problem to warrant screening of the general population. Some physicians have advocated screening in high-risk patients (heavy smokers), though screening program have not been proven to be beneficial, even in this population.

Hoarseness is often an early sign of laryngeal cancer; especially in cancer of the true vocal cords. Therefore, physicians should regularly screen their patients for complaints of hoarseness or changes in their voice quality and patients should bring the attention of their physicians to these symptoms. In these cases, patients should be referred to an otolaryngologist (an ear-nose-throat doctor) for evaluation. The laryngeal cancer detection rate in these situations is usually between 3-5%.

What are the signs of laryngeal cancer?

Signs or symptoms of larynx cancer are somewhat dependent on where the cancer is growing (supraglottis, glottis, subglottis). Patients with glottic cancer, or cancer that grows on the true vocal cords, often present with the early sign of hoarseness. This occurs because even a slight interference with the vibrating function of the vocal cords can produce voice changes. Hence, any long-standing hoarseness or voice changes should prompt a laryngeal examination. If hoarseness is ignored or if advanced disease occurs, airway obstruction, pain, or difficulty swallowing can result.

Supraglottic cancers usually do not produce early signs or symptoms, so supraglottic cancers are more often in advanced stage upon diagnosis. Hoarseness can also occur with supraglottic cancer, though usually later in the disease state. Also, in patients with supraglottic cancer, voice changes referred to as "hot potato voice" can occur. This can be described as the type of voice someone would speak in if they had a piece of hot food (potato) in their mouth. In addition to voice changes, patients can also present with pain, problems swallowing, or even ear pain, which can result from the involvement of nerves in the throat by the tumor. Supraglottic cancers often spread to lymph nodes in the neck, and many patients notice a lump in the neck as the first sign of cancer. Any lump or bump in the neck that does not go away within a few days should be evaluated by a physician.

Subglottic cancers are fairly rare, though they also fail to produce early symptoms. Therefore, they also present in more advanced stages and patients can have signs of disease similar to that of supraglottic cancers.

Again, these signs and symptoms are nonspecific and could represent a variety of different conditions-both benign and malignant. However, if you have any of these symptoms, especially if they are longstanding or if you are a smoker, you should see your physician.

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Laryngeal Cancer: The Basics

2009-08-16T05:20:00.000-07:00

Ryan P. Smith, MD and Christine Hill-Kayser, MD
Affiliation: The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 26, 2008

What is the Larynx?

The larynx, or voice box, is an area in the throat that contains an intricate mixture of cartilage and muscles. Not only is it responsible for producing our voice, but also performs other complex functions such as protecting our airway during swallowing. The larynx is divided into three separate regions: the supraglottic larynx, the glottis, and the subglottic larynx. The glottis is the region that contains the true vocal cords, thin strips of cartilage that vibrate together to produce sound. It is protected in the front by the large thyroid cartilage, which can be felt as the "Adam's apple" in our neck. When you feel for your Adam's apple, directly under that large piece of firm cartilage is the voice box, or the glottic portion of the larynx where the true vocal cords are located. Directly above the actual voice box is the supraglottic larynx, or supraglottis. This area contains some of the lining of the throat, cartilage and muscles that control the movement of the vocal cords, and the epiglottis, which is a flap of cartilage that closes over the voice box to protect our airway during swallowing. Below the vocal cords is the subglottic larynx, or subglottis. This area is the area of the throat and airway below the vocal cords but above the trachea. All three of these areas together are considered the larynx.

What is laryngeal cancer?

Cancers are described by the types of cells from which they arise. Over 95% of laryngeal cancers arise from the lining of the throat (not from the actual muscle or cartilage cells) and are called squamous cell carcinomas. Approximately 5% of these are called verrucous carcinoma, which have a wart-like appearance to them and are often less aggressive and slow-growing. Although there are other cancers that can arise in the larynx (salivary gland tumors-from minor salivary glands contained in the larynx, lymphomas of the larynx, and sarcomas-from muscle and cartilage cells), the vast majority are squamous cell carcinomas. Hence, these are the most commonly studied.

In addition to invasive cancers, patients are sometimes diagnosed with precancerous lesions, called carcinoma-in-situ. These most commonly occur in the glottis itself (where the true vocals cords are), as this area is more likely to produce early signs of disease. Carcinoma-in-situ occurs when the lining of the throat undergoes changes similar to cancerous changes without any invasion into the deeper tissues. Hence, while the cells themselves have cancer-like qualities, there is no risk of spread, as no invasion has occurred.

Am I at risk for laryngeal cancer?

Laryngeal cancer occurs in approximately 12,000 Americans per year, causing about 4,200 deaths. It makes up one quarter to one third of all cancers of the throat. It has classically been thought of as a disease that affects older men. Most patients are diagnosed when they are in their fifties or sixties, and it only rarely occurs in younger people. In America, blacks have a significantly higher incidence of laryngeal cancer than do whites. In the 1950s and 1960s, 15 men had laryngeal cancer for every one woman. However, this ratio is decreasing, and in more recent studies, about five to six men are diagnosed with laryngeal cancer for every one woman. This almost certainly reflects the long-term effects of women starting to smoke as much as men.

Many risk factors have been implicated in the development of laryngeal cancer. These include chronic irritation from laryngitis or voice abuse, chronic gastric reflux, and exposure to certain chemicals, such as wood dust, nitrogen mustard, and asbestos. However, far and away the largest risk factor for the development of laryngeal cancer is smoking. Pipe smoking, cigar smoking, and cigarette smoking have all been strongly associated with the development of larynx cancer. There is also an association between heavy alcohol intake and laryngeal cancer. Although it has classically been thought of as a co-risk factor that only increases the risk of smoking, some more recent studies have shown that heavy alcohol use can increase the risk of laryngeal cancer by itself. It is estimated that heavy drinking increases the risk of laryngeal cancer by 2-6 times, while smoking increases the risk between 5-25 times, depending on how much one smokes. In a person who both smokes and drinks, the risk is increased to up to 40 times the risk of someone who neither smokes nor drinks. National public health measures have been implemented in the United States to attempt to decrease the abuse of tobacco and alcohol. Although no specific decrease has been seen yet, there is hope that these measures will lead to a decrease in the incidence of laryngeal cancers over the next 15 years.

Though there is some improvement in the smoking rates in younger people in the United States, there is still a large proportion using smokeless tobacco. This puts them at a higher risk of oral cavity, tongue, and lip cancer. People who use smokeless tobacco may also be at increased risk for developing cancer of the supraglottic larynx, although this risk is probably not as high as it is for people who smoke cigarettes, cigars, or a pipe.

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Kidney Cancer: The Basics 4

2009-08-16T05:17:00.001-07:00

What are signs of kidney cancer?

Kidney cancer presents as signs and symptoms of either the local tumor in the kidney or as signs and symptoms resulting from spread of disease to other locations in the body (metastatic disease). Symptoms resulting from local tumor extension include hematuria (blood in the urine), abdominal pain, and a flank mass. Hematuria is the most common symptom and present as either gross hematuria, where the blood is visible in the urine, or as microscopic hematuria, where the blood is only detected by laboratory testing. Therefore, any presence of blood in the urine that is detected in a urine sample should be investigated. In medical textbooks, patients present with the "classic triad" of all three symptoms, though only about 10% of patients actually have all three symptoms at diagnosis.

Symptoms caused by metastatic disease include fever, weight loss, and night sweats (drenching sweats that require changing of clothes or bedsheets). Other symptoms include hypertension, increased calcium in the blood, and liver problems. These more unique symptoms are thought to be caused by chemical signals released by the tumor cells into the bloodstream and the body's reaction to them.
How is kidney cancer diagnosed and staged?
Diagnosis

Work up of a kidney cancer usually starts after the patient develops symptoms, with the exception of those cancers that are found incidentally. The point of all of the tests done prior to treatment of kidney cancer is to determine the extent of disease that is present so that treatment can be adjusted accordingly. This includes documenting the extent of disease both locally, in the tissues and lymph nodes surrounding the kidney, as well as ensuring there is no spread distantly, outside the area of the kidney (called metastases). The most sensitive test to document local disease is the CT scan, which has been shown to predict the tumor extent 90% of patients. MRI scans have been used to ensure the tumor has not involved any of the large blood vessels that are in the vicinity of the kidney. Other tests, including basic laboratory blood tests and analysis of the urinemay be used to evaluate general health and the extend of the cancer. In addition, chest x-ray and bone scan are usually done, to ensure that metastatic spread to the lungs and bones, respectively, has not occurred. To obtain a diagnosis of any cancer, tissue or cells must be examined by a pathologist. Therefore, to obtain a diagnosis of kidney cancer, a biopsy is often obtained by inserting a needle into the presumed tumor mass during a CT scan. However, there are also times that the CT scan and/or MRI is so convincing that the mass is a tumor, that the initial biopsy is done during an open surgical procedure, which is done to ultimately remove the kidney as treatment for the kidney cancer. The most appropriate surgical approach must be determined on an individual basis.
Staging

After all of these tests are performed, the stage of the cancer is known. The staging of a cancer basically describes how much it has grown before the diagnosis has been made, documenting the extent of disease. This is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, we will first describe some of the ways that cancers may grow and spread.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way kidney cancer can spread is by local extension to invade through the normal structures. This initially includes the kidney, hence causing hematuria, a mass, and abdominal pain. If more growth occurs, cancer can grow to involve the main vein that leaves the kidney (the renal vein), the large vein that returns blood from the bottom half of the body to the heart (the inferior vena cava), or into other organs-most commonly the adrenal glands which sit atop the kidneys.

Kidney cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Kidney cancer can spread, at times, into the lymph nodes surrounding the kidney, called the perirenal lymph nodes.

Kidney cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and cause distant metastases. Cancers of the kidney generally spread locally into the fat surrounding the kidney, the adrenal glands, or the veins prior to spreading via the lymphatic system or the bloodstream. However, tumors, especially larger tumors, can access the bloodstream and spread to the lungs and bones, most commonly. Kidney tumors have also been known to spread to the testis and ovaries through the testicular or ovarian veins that are in close proximity to the kidney.

The staging system used today in kidney cancer is designed to describe the extent of disease within the area of the kidney, in the surrounding lymph nodes, and distantly. The staging system most commonly used today to describe kidney tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the kidney itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

The "T" stage is as follows:

For kidney (cortex) tumors:

* T1-tumor size of 7 cm or less and confined to the kidney
* T2-tumor size more than 7 cm, but still confined to the kidney
* T3a-tumor invading into the adrenal gland or just outside of the kidney
* T3b-tumor invading into the renal vein or inferior vena cava, but contained below the diaphragm
* T3c- tumor invading into the renal vein or inferior vena cava, and extending above the diaphragm
* T4-tumor invades outside of these areas

For medullary tumors:

* T1-tumor contained within the collecting system
* T2-tumor invades into the muscular layer of the wall of the collecting system
* T3-tumor invades into the fat surrounding the collecting system
* T4-tumor invades into other organs

The "N" stage is as follows for any subsite:

* N0-no spread to lymph nodes
* N1-tumor spread to a single lymph node
* N2-tumor spread to multiple lymph nodes or for collecting system tumors, lymph node spread that is between 2 and 5 cm
* N3-for collecting system tumors only, those lymph nodes that are >5 cm

The "M" stage is as follows:

* M0-no tumor spread to other organs
* M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters:

For kidney cortex tumors

* Stage I: T1N0M0
* Stage II: T2N0M0
* Stage III:
o T1-2N1M0
o T3N0-1M0
* Stage IV: and T4, any N2 or M1

For collecting system tumors

* Stage I: T1N0M0
* Stage II: T2N0M0
* Stage III: T3N0M0
* Stage IV: any T4, any N1-3, any M1

Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.
What are the treatments for kidney cancer?

Surgical resection (removal) is the only known curative treatment for kidney cancer. The procedure that is most often done in the case of kidney cancer is called a nephrectomy. This procedure includes the removal of the entire kidney that is involved with tumor The surgical procedure also usually includes removing at least some of the lymph nodes surrounding the kidney, which has shown to increase survival in patients with kidney cancer. So-called partial nephrectomies (where only a part of the kidney is removed) may be utilized in some patients with small tumors. This should only be attempted in patients with tumors <4cm. If the tumor can be completely removed, the risk of the tumor coming back in the remaining part of the kidney is about 5%. Therefore, this treatment is very effective. For larger tumors that require total nephrectomy, the adrenal gland and the fat surrounding the kidney and adrenal gland may need to be removed in order for the entire tumor to be removed. Even if the kidney cancer has spread to a single different part of the body, a nephrectomy may be recommended, as it has been shown to improve survival. If there are many sites of disease, however, nephrectomy has not been shown to be useful. Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our bodies can repair radiation damage much more quickly than tumor cells can, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. Radiation therapy, however, is not routinely used in the initial treatment of kidney cancer.. Radiation may be considered for patients whose tumors are too large to be completely removed; after as much surgical removal as possible is performed, radiation may be useful in treating tumor that remains. This treatment is experimental and should be done only as part of a clinical trial. Radiation may also be used as a method for pain relief in patients who have pain from kidney cancer that has spread to other regions of the body. Chemotherapies are drugs that are used to kill tumor cells. Up to this point, there is no chemotherapy regimen that has been consistently shown to be efficacious in the treatment of curative or metastatic kidney cancer. New modalities are constantly being investigated, including interferon, anti-angiogenesis agents (which inhibit the tumor from growing more blood vessels), and molecular agents that target specific genes that may be essential for the tumor cells' survivals.

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Kidney Cancer : The Basics 3

2009-08-16T05:17:00.000-07:00

What are signs of kidney cancer?

Kidney cancer presents as signs and symptoms of either the local tumor in the kidney or as signs and symptoms resulting from spread of disease to other locations in the body (metastatic disease). Symptoms resulting from local tumor extension include hematuria (blood in the urine), abdominal pain, and a flank mass. Hematuria is the most common symptom and present as either gross hematuria, where the blood is visible in the urine, or as microscopic hematuria, where the blood is only detected by laboratory testing. Therefore, any presence of blood in the urine that is detected in a urine sample should be investigated. In medical textbooks, patients present with the "classic triad" of all three symptoms, though only about 10% of patients actually have all three symptoms at diagnosis.

Symptoms caused by metastatic disease include fever, weight loss, and night sweats (drenching sweats that require changing of clothes or bedsheets). Other symptoms include hypertension, increased calcium in the blood, and liver problems. These more unique symptoms are thought to be caused by chemical signals released by the tumor cells into the bloodstream and the body's reaction to them.
How is kidney cancer diagnosed and staged?
Diagnosis

Work up of a kidney cancer usually starts after the patient develops symptoms, with the exception of those cancers that are found incidentally. The point of all of the tests done prior to treatment of kidney cancer is to determine the extent of disease that is present so that treatment can be adjusted accordingly. This includes documenting the extent of disease both locally, in the tissues and lymph nodes surrounding the kidney, as well as ensuring there is no spread distantly, outside the area of the kidney (called metastases). The most sensitive test to document local disease is the CT scan, which has been shown to predict the tumor extent 90% of patients. MRI scans have been used to ensure the tumor has not involved any of the large blood vessels that are in the vicinity of the kidney. Other tests, including basic laboratory blood tests and analysis of the urinemay be used to evaluate general health and the extend of the cancer. In addition, chest x-ray and bone scan are usually done, to ensure that metastatic spread to the lungs and bones, respectively, has not occurred. To obtain a diagnosis of any cancer, tissue or cells must be examined by a pathologist. Therefore, to obtain a diagnosis of kidney cancer, a biopsy is often obtained by inserting a needle into the presumed tumor mass during a CT scan. However, there are also times that the CT scan and/or MRI is so convincing that the mass is a tumor, that the initial biopsy is done during an open surgical procedure, which is done to ultimately remove the kidney as treatment for the kidney cancer. The most appropriate surgical approach must be determined on an individual basis.
Staging

After all of these tests are performed, the stage of the cancer is known. The staging of a cancer basically describes how much it has grown before the diagnosis has been made, documenting the extent of disease. This is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, we will first describe some of the ways that cancers may grow and spread.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way kidney cancer can spread is by local extension to invade through the normal structures. This initially includes the kidney, hence causing hematuria, a mass, and abdominal pain. If more growth occurs, cancer can grow to involve the main vein that leaves the kidney (the renal vein), the large vein that returns blood from the bottom half of the body to the heart (the inferior vena cava), or into other organs-most commonly the adrenal glands which sit atop the kidneys.

Kidney cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Kidney cancer can spread, at times, into the lymph nodes surrounding the kidney, called the perirenal lymph nodes.

Kidney cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and cause distant metastases. Cancers of the kidney generally spread locally into the fat surrounding the kidney, the adrenal glands, or the veins prior to spreading via the lymphatic system or the bloodstream. However, tumors, especially larger tumors, can access the bloodstream and spread to the lungs and bones, most commonly. Kidney tumors have also been known to spread to the testis and ovaries through the testicular or ovarian veins that are in close proximity to the kidney.

The staging system used today in kidney cancer is designed to describe the extent of disease within the area of the kidney, in the surrounding lymph nodes, and distantly. The staging system most commonly used today to describe kidney tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the kidney itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

The "T" stage is as follows:

For kidney (cortex) tumors:

* T1-tumor size of 7 cm or less and confined to the kidney
* T2-tumor size more than 7 cm, but still confined to the kidney
* T3a-tumor invading into the adrenal gland or just outside of the kidney
* T3b-tumor invading into the renal vein or inferior vena cava, but contained below the diaphragm
* T3c- tumor invading into the renal vein or inferior vena cava, and extending above the diaphragm
* T4-tumor invades outside of these areas

For medullary tumors:

* T1-tumor contained within the collecting system
* T2-tumor invades into the muscular layer of the wall of the collecting system
* T3-tumor invades into the fat surrounding the collecting system
* T4-tumor invades into other organs

The "N" stage is as follows for any subsite:

* N0-no spread to lymph nodes
* N1-tumor spread to a single lymph node
* N2-tumor spread to multiple lymph nodes or for collecting system tumors, lymph node spread that is between 2 and 5 cm
* N3-for collecting system tumors only, those lymph nodes that are >5 cm

The "M" stage is as follows:

* M0-no tumor spread to other organs
* M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters:

For kidney cortex tumors

* Stage I: T1N0M0
* Stage II: T2N0M0
* Stage III:
o T1-2N1M0
o T3N0-1M0
* Stage IV: and T4, any N2 or M1

For collecting system tumors

* Stage I: T1N0M0
* Stage II: T2N0M0
* Stage III: T3N0M0
* Stage IV: any T4, any N1-3, any M1

Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.
What are the treatments for kidney cancer?

Surgical resection (removal) is the only known curative treatment for kidney cancer. The procedure that is most often done in the case of kidney cancer is called a nephrectomy. This procedure includes the removal of the entire kidney that is involved with tumor The surgical procedure also usually includes removing at least some of the lymph nodes surrounding the kidney, which has shown to increase survival in patients with kidney cancer. So-called partial nephrectomies (where only a part of the kidney is removed) may be utilized in some patients with small tumors. This should only be attempted in patients with tumors <4cm. If the tumor can be completely removed, the risk of the tumor coming back in the remaining part of the kidney is about 5%. Therefore, this treatment is very effective.For larger tumors that require total nephrectomy, the adrenal gland and the fat surrounding the kidney and adrenal gland may need to be removed in order for the entire tumor to be removed.Even if the kidney cancer has spread to a single different part of the body, a nephrectomy may be recommended, as it has been shown to improve survival. If there are many sites of disease, however, nephrectomy has not been shown to be useful.Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our bodies can repair radiation damage much more quickly than tumor cells can, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. Radiation therapy, however, is not routinely used in the initial treatment of kidney cancer.. Radiation may be considered for patients whose tumors are too large to be completely removed; after as much surgical removal as possible is performed, radiation may be useful in treating tumor that remains. This treatment is experimental and should be done only as part of a clinical trial.Radiation may also be used as a method for pain relief in patients who have pain from kidney cancer that has spread to other regions of the body.Chemotherapies are drugs that are used to kill tumor cells. Up to this point, there is no chemotherapy regimen that has been consistently shown to be efficacious in the treatment of curative or metastatic kidney cancer. New modalities are constantly being investigated, including interferon, anti-angiogenesis agents (which inhibit the tumor from growing more blood vessels), and molecular agents that target specific genes that may be essential for the tumor cells' survivals.

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Kidney Cancer: The Basics 2

2009-08-16T05:16:00.001-07:00

Am I at risk for kidney cancer?

Kidney cancer occurs in approximately 31,000 Americans per year and cancers of the renal pelvis will occur in approximately 3,000 Americans per year. Most patients are diagnosed between the ages of 50 and 70. Kidney cancer is more common in men than women, with an equal preponderance in whites and blacks. A number of risk factors are associated with an increased probability of renal cell cancer: The most prominent risk is cigarette smoking. Persons who smoke have twice the risk of developing kidney cancer as people who don’t smoke, and smoking is directly responsible for up to one out of every three cancers. The risk for kidney cancer also increases fourfold in persons with a first-degree relative who had kidney cancer. Other, less-proven risk factors include obesity (especially in women), analgesic abuse, high blood pressure, and several uncommon hereditary diseases, including von Hippel-Lindau disease and polycystic kidney disease.

How can I prevent kidney cancer?

As cigarette smoking doubles the risk of kidney cancer, the best way to decrease your risk of developing kidney cancer is to discontinue smoking. Other than smoking, the only substantial risk factors for the development of kidney cancer are related to family history. Obviously, no one can change the family they are born into, so the risk factor of having someone in the family with a history of kidney cancer, or rare genetic diseases such as von Hippel Lindau and polycystic disease cannot be prevented.

What screening tests are available?

There are no screening tests for kidney cancer that are akin to mammography for breast cancer or colonoscopy for colorectal cancer. However, the use of CT scans and ultrasounds have enhanced the early detection of kidney cancer once signs or symptoms have developed (see below). Intravenous pyelograms (IVP) are used to assess kidney function. IVPs are done by injecting dye into a patient's arm and then taking x-rays of the abdomen to see that dye subsequently excreted by the kidneys as urine. Cytology is simply looking at urine under a microscope and looking for cancerous cells within the urine. Because they may cause early symptoms that lead to testing, kidney cancers that develop in the area of the collecting system may be detected earlier than those in other regions.

With the advent of CT scans and ultrasounds, 25-40% of kidney cancers are now detected incidentally during the work up of a different problem. These tumors are more likely to be smaller (hence causing no symptoms), and hence more likely to result in a cure.

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Kidney Cancer: The Basics

2009-08-16T05:13:00.000-07:00

What is the Kidney?

The kidneys are two bean-shaped organs that are located in the back of the abdomen, and that have many important functions essential for life. Among the most important are filtrating the blood, removing waste products from the blood and ensuring that the electrolytes within the blood are correctly balanced. In addition, the kidneys produce erythropoietin, a hormone responsible for the production of (the oxygen carrying) red blood cells. Each of the kidneys can be divided into two main functional parts. The outer region of the kidney is called the cortex The cortex consists of a series of tubes (called collecting tubules) and is responsible for the filtration of blood.. The inner region of the kidney is called the renal pelvis. The renal pelvis contains medullary pyramids that collect the filtrate (urine) from collecting tubules in the cortex and send it through the ureters to the urinary bladder. Different types of cancers develop from the two different regions of the kidneys.
The kidneys are located in the posterior aspect of the abdomen, directly in front of where the lowest ribs can be felt on a person's back. A physician can palpate them in the abdomen at times, though often only if the kidney is enlarged or has a mass on it.

What is kidney cancer?

The definition of a tumor is a mass of abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any ability to spread to distant parts of the body. A tumor is called malignant, or cancer, if tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, kidney cancer occurs when cells in either the cortex of the kidney or cells in the renal pelvis grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.
Cancers are described by the types of cells from which they arise. Again, when discussing kidney cancer, the cortex and the renal pelvis must be discussed separately. In the kidney cortex, the vast majority of cancers arise from the cells that line the collecting tubules, more specifically, the proximal tubules. Cancers that develop from lining such as this are called carcinomas. In this case, they are called renal cell carcinomas. Over 75% of renal cell carcinomas are called clear cell carcinomas, named after the characteristics they display when looking at them under the microscope. Other classifications, in decreasing order of prevalence, include chromophilic, chromophobic, oncocytic, and collecting duct cancers. However, it does not appear that these various types of renal cell carcinoma differ in presentation or prognosis.
Cancers of the renal pelvis, or medulla, are uncommon. Over 90% of cancers that develop in the renal pelvis are called transitional cell carcinomas. They are so named because they develop from cells that line the renal pelvis and upper ureters.

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Gastric Cancer: The Basics 3

2009-08-16T05:12:00.000-07:00

How is gastric cancer diagnosed and staged?

Diagnosis

Upper endoscopy, as described above, is routinely used for the initial diagnosis and staging of patients with gastric cancer. Using endoscopy, the diagnosis can be obtained in over 95% of cases. Many times, ultrasound during endoscopy is used to attempt to identify how deep into the wall of the stomach the cancer has penetrated. In addition, ultrasound can identify spread to lymph nodes in many cases. Depth of wall invasion and presence of lymph node spread are two very important components of treatment, as the surgeon uses this information to determine if he or she can operate.

Other procedures are needed to determine the stage of the disease. CT scans ("CAT scans") of the abdomen and chest are done, not only to rule out spread to distant organs, like the liver and lungs, but also to determine the spread to lymph nodes close to the stomach that could not be identified by ultrasound. Other tests to rule out abdominal spread of disease outside of the stomach itself are PET scans, which use radioactive solutions to identify tumors, and laparoscopy. Laparoscopy is a surgical procedure that involves puncturing the abdominal cavity with a fiber optic camera and directly viewing the organs and tissues in the stomach's area and the entire abdominal cavity. Although PET scans and laparoscopy are fairly new introductions to the staging of gastric cancer, CT scans, endoscopy, and ultrasound are more generally accepted as required in order to properly identify the extent of disease, and all will likely be done in a patient diagnosed with gastric cancer.

Other, more routine tests done before treatment include blood screening tests, to insure that overall blood counts are within normal limits, and that a patient's liver, kidneys, and overall health are normal.

All of these test are important to determine the extent of the disease which allows the disease to be staged. The stage provides a guideline for the optimal treatment of the gastric cancer as well as the prognosis.

Staging

The staging of a cancer basically describes how much it has grown before the diagnosis has been made, documenting the extent of disease. Unfortunately, gastric cancer often presents as a more advanced disease because of lack of early diagnosis, due mainly to the lack of specific associated symptoms. Before the staging systems are introduced, here’s some background on how cancers grow and spread, and therefore become more advanced in stage.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way gastric cancer can spread is by local extension to invade through the stomach wall and into adjacent structures. These surrounding structures include the soft tissues and fat surrounding the stomach as well as other organs such as the spleen, pancreas, large intestine, small intestine, liver, and large blood vessels.

Gastric cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Gastric cancers have a propensity to undergo lymphatic spread because there are many small lymphatic vessels contained within the stomach wall. The first lymph nodes that cancer cells spread to are the "perigastric" nodes along the sides of the stomach itself. They can then spread to lymph nodes adjacent to the liver, spleen, pancreas, and aorta.

Gastric cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from these cells are called metastases. Because of the stomach's blood supply, the most common organ it spreads to is the liver, though tumors can also spread to the lung or other organs less commonly.

A fourth way gastric cancer can spread is throughout the entire abdomen, the so-called peritoneal cavity. Although rare, once cancer cells grow outside of the stomach itself, there is nothing stopping cells from spreading to any surface in the entire abdominal cavity.

There are two accepted staging systems in gastric cancer. They both detail the extent of disease by describing the growth of tumor in the stomach itself as well as the presence and extent of spread to the lymph nodes. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the stomach itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

The "T" stage is as follows:

Tis-"in-situ cancer"-very superficial tumor, without invasion of the stomach wall
T1-tumor invades into only the superficial portions of the stomach wall
T2-tumor invades into the deeper layers of the stomach wall
T3-tumor extends through the stomach wall into the fat outside of the stomach
T4-tumor extends outside the stomach wall and invades into other organs

The "N" stage is as follows:

N0-no spread to lymph nodes
N1-tumor spread to 1-6 lymph nodes
N2-tumor spread to 7-15 lymph nodes
N3-tumor spread to more than 15 lymph nodes

The "M" stage is as follows:

M0-no tumor spread to other organs
M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters:

Stage IA-T1N0M0
Stage IB-T1N1M0 or T2N0M0
Stage II-T1N2M0 or T2N1M0 or T3N0M0
Stage IIIA-T2N2M0 or T3N1M0 or T4N0M0
Stage IIIB-T3N2M0 or
Stage IV-T4N2M0 or T1-3N3M0 or T4N1-3M0 or any M1

Though complicated, this staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through various tests done as the diagnosis and work-up of the cancer is being performed.

What are the treatments for gastric cancer?

Currently, all curative treatments for gastric cancer involve surgery (surgical resection of all of the cancer). The smallest amount of surgery that is possible while still taking out all of the cancer is what is normally performed. Generally, tumors which are localized to the part of the stomach closest to the esophagus (proximal stomach) are treated with a gastrectomy (removal of the entire stomach). A partial gastrectomy is the removal of only a portion of the stomach, in contrast to a total gastrectomy, which is done when the tumor is larger. Partial gastrectomies may be appropriate for those tumors located further from the esophagus, in the distal portion of the stomach. For partial gastrectomy, the surgical margin around the gastric cancer needs to be 5 cm, i.e., there needs to be 5 cm of normal stomach tissue around the tumor in the portion of the stomach removed. Diffuse disease involving the stomach is also an indication for a total gastrectomy. Also, the surgeon performs a complete dissection of the lymph nodes, removing as many as possible. How extensive of a lymph node dissection to perform is controversial, with contradictory data from the United States compared with Japan. However, it is import that an experienced surgeon perform the dissection as it is a difficult surgery. Obviously, when the stomach or a portion of the stomach is removed, the two ends must be rejoined. This is done by various procedures, all attempting to eliminate as many of the side effects of the surgery as possible, such as inability to eat larger meals and the so-called "dumping syndrome". Dumping syndrome results from the stomach being removed and the result of the small intestine filling too rapidly with undigested food. Symptoms include nausea, vomiting, bloating, diarrhea, and even shortness of breath. These symptoms can usually be managed with dietary modifications.

Although surgery is always required for curative treatment, it is often not enough to achieve cure in many cases. The majority of cases of early gastric cancer are cured by surgery alone. However, in most patients with more advanced cases of gastric cancer, such as those with positive lymph nodes or tumors which have invaded the deep layers of the stomach or beyond, the cancer will come back if only surgery is done. Up to two-thirds of these patients recur, with cancer coming back in their lymph nodes or other organs. To combat this, radiation therapy and chemotherapy are recommended in many patients. It is felt that any patient with stage IB or higher gastric cancer (involvement of deeper portions of the stomach wall or any lymph nodes involved with cancer) will benefit from additional therapy with concurrent radiation and chemotherapy.

Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our body can repair radiation damage much quicker than tumor cells, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. After radiation oncologists set up the radiation fields ("radiation fields" are the areas of the body that will be treated by radiation), treatment is begun. Radiation is given 5 days a week for approximately 5 weeks at a radiation treatment center. The treatment takes just a few minutes each day and is completely painless. The typical radiation field used in the treatment of gastric cancer includes portions of the upper abdomen. In other words, it is designed to kill tumor cells in the area that the surgery was performed. Typical side effects include nausea and vomiting (though this should be less of a problems since the stomach has already been removed) and diarrhea.

Chemotherapy is defined as drugs that are used to kill tumor cells. The large advantage in using chemotherapy is that, since it is a medicine, is travels through the entire body. Hence, if some tumor cells have spread outside of what surgery or radiation can treat, they can potentially be killed by chemotherapy. Similar to radiation, some normal cells are damaged during treatment, resulting in side effects. The standard chemotherapy used in the treatment of gastric cancer is called 5-FU, coupled with another drug called leucovorin. This type of chemotherapy is delivered through the vein. Side effects from 5-FU and leucovorin include nausea, diarrhea, skin changes, and sores of the mouth. Although other chemotherapy drugs (cisplatin, oxaloplatin, epirubicin) are being investigated for the treatment of gastric cancer, 5-FU plus leucovorin remains the standard. Sometimes chemotherapy and radiation are used prior to surgery, but a large trial has demonstrated that surgery follow by radiation with chemotherapy appears to be the best current treatment. The value of radiation and chemotherapy was demonstrated in a large study just reported in 2001 by MacDonald et al. These authors reported a much better outcome in patients with Stage IB or greater gastric cancer who were treated with radiation and chemotherapy after potentially curable surgery. This study has established the “standard of care” in the United States, and is detailed as follows:

Surgery- to remove all of the cancer, as well as removal of the lymph nodes in the area of the stomach
Radiation- to the area of the upper abdomen, 5 days per week for 5 weeks;usually starts 4-6 weeks after surgery, to allow for recovery from surgery, but may be delayed by a few weeks if chemotherapy is started first, prior to combining the two treatments.
Chemotherapy- using 5-FU and leucovorin combination therapy, given during the radiation and also after the radiation is completed; can sometimes be started for a few weeks prior to the start of radiation therapy, to allow for local healing if needed

There has also been a study which has demonstrated the benefit of postoperative chemotherapy alone in people who may not tolerate radiation with chemotherapy. The type of chemotherapy advised in this setting is epirubicin, cisplatin and 5-fluorouracil (ECF).

Follow-up testing for gastric cancer

Once someone completes treatment for gastric cancer (including surgery +/- radiation and chemotherapy), he or she needs to be closely followed by his or her cancer physicians. This close follow-up is required for a couple of reasons. First, it needs to be insured that the patient recovers from the cancer treatment itself. This includes ensuring that the patient has no vomiting or diarrhea and has healed from surgery. Also, symptoms of "dumping syndrome" need to be addressed with dietary modifications. In addition, because of the removal of the stomach or a portion of the stomach, gastric cancer patients are prone to a certain type of anemia, resulting from not having enough vitamin B-12. This will be monitored for the patient's entire life, as this anemia does not usually occur until years after the surgery.

The other major reason a patient needs to be followed closely is to make sure their cancer does not recur. Recurrence can be detected using physical exam, repeat, periodic endoscopies, and CT scans. At first, patients will have follow-up visits and tests fairly often. The longer the patient is free of disease, the less often he or she will have to go for check-ups.

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Gastric Cancer: The Basics 2

2009-08-16T05:11:00.000-07:00

How can I prevent gastric cancer?

Because there is no one risk factor directly associated with gastric cancer, there is no strict lifestyle change that can greatly decrease a person's risk of developing gastric cancer. However, eating a "Western" type diet, without heavily smoked or salted foods and rich in fruits and vegetables will likely decrease a person's risk. Also, smoking cessation will likely decrease gastric cancer risk (though smoking should be stopped for numerous other health reasons). Some have advocated the consumption of foods with high level of antioxidants and vitamin C to prevent gastric cancers, though this has not been definitively proven. Since H. pylori infections have been linked to the development of gastric cancers, the quick treatment of H. pylori infections may decrease the numbers of gastric cancers, though whether treating H. Pylori actually reduces the risk ofgastic cancer remains controversial. The decision to treat H. pylori should be discussed with your physician.

What screening tests are available?

There are no established programs for primary prevention of gastric cancer in the United States. There are no plans to initiate a screening program in the United States, simply because the incidence of gastric cancer is fairly low, and thus the yield from gastric cancer screening would be far too low to approach cost-effectiveness. A few populations may be exceptions (e.g.-patients with known atrophic gastritis), but overall screening for gastric cancer in the United States would likely cause more problems than it would solve (i.e. a lot of false positives, or false alarms). Currently, screening for H. Pylori is not recommended for areas with a relatively low incidence of gastric cancer, such as in the United States.

In some Japanese centers, where gastric cancer is much more prevalent, screening has been more successful. A variety of tests have been used in these screening programs, with the ability to accurately identify gastric cancers in over 90% of patients who actually have it. These tests include double-contrast barium radiographs (so-call "upper GIs" or "barium swallows") and upper endoscopies. An upper endoscopy (or an "EGD") is a test done using a camera at the end of a long tube that is placed down the patient's throat to the stomach itself. The physician performing the EGD is able to directly visualize the stomach. Many abnormalities can be detected with an EGD-most importantly, ulcers and cancers. Patients are sedated during the procedure, so discomfort is kept to a minimum.

More recently, studies have verified the use of a newer blood test that could be used for screening for gastric cancer. This analyzes the presence of enzymes in the blood called the serum pepsinogen I/II ratio, which is low in patients at risk for atrophic gastritis and gastric cancer. However, this is still in the earlier stage of testing and needs to be verified.

What are the signs of gastric cancer?

The symptoms of gastric cancer are often nonspecific, and the majority of people will unfortunately present with advanced disease. The vast majority of gastric cancer patients present with vague complaints such as upper abdominal discomfort or indigestion, loss of appetite, occasional vomiting, belching, or decreased ability to eat a large meal. Unfortunately, these symptoms are often the exact symptoms that patients experience when they have peptic ulcer disease or gastritis. Therefore, patients can be treated for benign diseases, such as ulcers, without the diagnosis of gastric cancers being made. This is not incorrect management, as gastritis and peptic ulcer disease are much more common than gastric cancer. However, if symptoms persist or do not respond to treatment, further investigations should follow.

Up to 25% of people with gastric cancer will have a history of gastric ulcers. Other symptoms, such as vomiting blood or problems with swallowing, are less common, but should be investigated without delay. Additional symptoms that generally apply to cancer patients are unexplained weight loss as well as fatigue and weakness, with or without anemia. Again, these symptoms are, unfortunately, nondescript, and do not necessarily apply to cancer in general or gastric cancer specifically.. Advanced disease can present with lymph node involvement with masses in the area of the belly button, the underarms, or the clavicle. People with advanced disease may also present with abdominal swelling.

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Gastric Cancer: The Basics

2009-08-16T05:10:00.000-07:00

Ryan P. Smith, MD and Eric Shinohara, MD, MSCI
Affiliation: Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 23, 2008

What is the stomach?

Gastric cancer is cancer of the stomach. The stomach is the organ that holds and stores food. It is located just underneath (deep to) the lower portion of the rib cage on the left side. It is connected to the mouth and throat by the esophagus. The stomach contains acid and is quite muscular. Due to the motion of the stomach and the acid, quite a bit of digestion takes place in the stomach. The partially digested food is then emptied into the small intestine so that absorption of the nutrients from food can take place. Although the stomach obviously cannot be directly visualized, it can be seen via an endoscopy procedure using a fiber-optic camera (see below).

What is gastric cancer?

The definition of a tumor is a mass of quickly and abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any spread. A malignant tumor is called cancer when these tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, gastric cancer occurs when cells in the lining of the stomach grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. Over 90% of gastric cancers arise from the lining of the stomach. Since this lining has glands, the cancer that comes from it is called adenocarcinoma. Although there are other cancers that can arise in the stomach (lymphomas-from lymph tissue, leiomyosarcoma-from muscle tissue, squamous cell carcinoma-from lining without glands), the vast majority are adenocarcinomas. Hence, these are the most commonly studied.

Am I at risk for gastric cancer?

In the United States, there are about 22,000 gastric cancers annually, with about 11,00 deaths attributed to this disease each year Interestingly, its incidence has drastically decreased since 1930. Although it is presumed that this is due to some sort of dietary or environmental factor(s), the exact reason behind this decrease is not known. One theory is that the advent of refrigeration led to decreased use of nitrites, “smoking” of foods, and other such forms of food preservation. It also decreased food contamination. Gastric cancer is approximately twice as common in men and more common in Blacks than Caucasians. It is rare to see gastric cancer before the age of 40, and its incidence increases with age thereafter. There are two types of gastric cancer, the intestinal type and the diffuse type; the latter carries a worse prognosis.

Although gastric cancer has greatly decreased in the United States, on a worldwide scale its incidence is still high, and it is the second leading cause of cancer death worldwide, behind lung cancer. Its highest incidence is in East Asia (e.g.-Japan, China), presumably because of a diet consisting of heavily smoked, salted, and pickled foods. Interestingly, first generation immigrants from these countries have a decreased incidence of stomach cancer after moving to the United States, but it is still higher than the general American population. However, the incidence greatly declines in second and third generation Japanese and Chinese immigrants to the United States, pointing to the fact that there does not appear to be an inherently genetic component in Eastern Asians’ preponderance to gastric cancer, but rather an environmental component.

As mentioned above, diets heavily salted, smoked, or pickled are associated with an increased risk of disease, while diets rich in fruits, vegetables, and dietary fiber are associated with a decreased risk of cancer. The incidence of gastric cancers also increases with decreasing socioeconomic status, likely due to a number of social, occupational, and cultural factors. Tobacco use has also been associated with an increase in gastric cancers. There does not appear to be a link with alcohol consumption.

There does appear to be a genetic link in some cases of gastric cancer, and there are some genetic diseases such as hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and Peutz Jeghers syndrome which all predispose to gastric cancer. It also appears that people with blood type A are at increased risk for gastric caner for an unknown reason.

Studies have also linked infection with Helicobacter pylori with gastric cancer. H. pylori is associated with gastric ulcers and chronic atrophic gastritis, which may explain the high incidence of gastric cancer in patients infected with H. pylori. However, the exact role of H. pylori in the development of gastric cancer remains unclear. It is theorized that H. pylori causes a gastritis or inflammation of the stomach, which can lead to a loss of secretory cells in the stomach, also known as strophic gastritis. It is believed that this process of atrophy can lead to gastric cancer. H. pylori has also been linked to lymphomas of the stomach.

Pernicious anemia, an autoimmune disease where the stomach does not produce stomach acid, has also been linked to gastric cancer. Drugs which cause a decrease in stomach acid production have not been linked to an increased risk of gastric cancer.

It should be noted that, although these risk factors are listed above, the majority of gastric cancers develop without any one obvious predisposing cause. In other words, there is no extremely strong cause effect relationship with any risk factor, in contrast, for example, to that between smoking and lung cancer.

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Gallbladder Cancer: The Basics 4

2009-08-16T05:09:00.000-07:00

What are the outcomes of treatment?

Disease stage at presentation is the most important prognostic factor.

Stage I patients can have very good 5-year survival rates, on the order of 70-85% after a complete surgery. Perioperative mortality rates range from 0-21%, depending upon the extent of liver resection required or the need for pancreas and small bowel removal (pancreaticoduodenectomy).

5-year survival rates

stage I – 70-85%
stage II – 25%
stage III – 12%
stage IV – 1-2%

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Gallbladder Cancer: The Basics 3

2009-08-16T05:08:00.002-07:00

How is gallbladder cancer diagnosed?

First and foremost, a HCP should always perform a thorough history and physical examination. Laboratory work should include metabolic chemistry and liver function panels to look for abnormal levels of various substances in the blood that are suggestive of general hepatobiliary disease. A urinalysis is usually done to evaluate urinary levels of some of these substances as well.

*The role of tumor markers, [carbohydrate antigen 19-9 (CA 19-9), cancer antigen 125 (CA125), and carcinoembryonic antigen (CEA)] has not been established in gallbladder cancer.

Ultrasonography ( US) is the standard study done first in patients presenting with right upper quadrant pain. It allows HCPs to make a diagnosis of gallbladder cancer in about half of patients, and can also detect disease spread into the liver or bile ducts about half of the time. This is an important test, as it can help differentiate people who are having pain from gallstones from those who have gallbladder cancer. Endoscopic ultrasound, where a camera is inserted down through the mouth (while under sedation) allows the ultrasound probe to be placed closer to the gallbladder and appears to be more accurate than the traditional ultrasound which is placed against the abdominal wall. Endoscopic ultrasound may also better detect nodes and whether the tumor has spread beyond the gallbladder.

Computed tomography (CT) scans can also be helpful in patients with upper abdominal pain. They are better than US for detecting tumor invasion out of the gallbladder and disease spread to other sites in the abdomen or pelvis. About 70-80% of cases will have some degree of liver invasion, and so the combination of CT and US provides more accurate information.

Magnetic resonance imaging (MRI) has been useful in examining this region for disease spread into the liver or other tissues. This technology is particularly good for planning surgery, by evaluating surrounding blood vessels [magnetic resonance angiogram (MRA)] and bile duct passages [magnetic resonance cholangiogram (MRC)].

Cholangiography, either through the skin or the stomach, is a technique that allows HCPs to not only establish a diagnosis, but to locate the blockage and place a stent through the blockage to help alleviate the blockage.

Routine blood work may also help your physician determine whether there is a blockage in the bile ducts and how well the liver is functioning. There are tumor markers which can be tested for in the blood, such as CEA and CA 19-9. These markers can be elevated in cancer of the gallbladder, but are not good for diagnosis as they are non-specific and other conditions can cause them to be elevated.

How is gallbladder cancer staged?

The American Joint Committee on Cancer uses the TNM system to stage gallbladder cancer as follows: (Adapted from AJCC 6 th edition, 2002)

Primary tumor (T)

TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ
T1 - Tumor invades mucosa or muscle layer
T2 - Tumor invades perimuscular connective tissue
T3 - Tumor invades/perforates the serosa and/or directly invades the liver and/or one other adjacent organ or structure
T4 - Tumor invades main portal vein or hepatic artery or >2 adjacent organs

Regional lymph node (N)

NX - Regional lymph nodes cannot be assessed
N0 - No metastases in regional lymph nodes
N1 – Regional lymph node metastases

Metastases (M)

MX - Presence of metastases cannot be assessed
M0 - No distant metastases
M1 - Distant metastases

TNM Groupings by Stage

Stage	T	N	M
Stage 0	Tis	N0	M0
Stage IA	T1	N0	M0
Stage IB	T2	N0	M0
Stage IIA	T3	N0	M0
Stage IIB	T1 T2 T3	N1 N1 N1	M0 M0 M0
Stage III	T4	Any N	M0
Stage IV	Any T	Any N	M1

How is gallbladder cancer treated?

As with many tumor types, management is often a multidisciplinary approach involving a variety of treatments.

For early stage disease (Stage I), surgery alone can be considered. In patients who have a gallbladder cancer found during a cholecystectomy, reexcision is recommended if the disease is stage II or higher. In stage I disease, the need for reexcision is more controversial. Total surgical removal of all known tumor is the only truly “curative” treatment. Unfortunately, only about 25% of patients with gallbladder cancer are able to undergo definitive surgery. Furthermore, such a procedure is typically quite extensive, and involves removal of the gallbladder, regional lymph nodes, and a portion of liver if there is concern of invasion. As you might expect, such a surgery carries a high risk of serious operative injury. Even when surgery is possible, the surgeon is usually unable to take very large resection margins around the tumor, meaning that cancer cells may exist at, or very close to, the tissue edges where the surgeon cut. Even with improving surgical techniques, the risk of recurrence is high. In such cases, external beam radiation therapy can be used in hopes of eradicating any microscopic cancer remaining in the surgical area and surrounding at-risk regions. Median survival in patients with advanced but operable disease treated with surgery alone is cited as roughly 6-7 months. This can sometimes be improved to over 16 months with postoperative radiation therapy. Adjuvant chemotherapy after surgery can also be considered, most commonly with 5-FU.

For patients who are unable to undergo surgery, either because the disease is too advanced or because of other serious medical conditions, HCPs can use radiation therapy with or without concurrent chemotherapy in order to improve symptoms, and in some cases maybe even increase survival. At present, there are several trials investigating various combinations of chemotherapy with 5-FU, as a clearly superior regimen has not yet been demonstrated. Research is ongoing.

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Gallbladder Cancer: The Basics 2

2009-08-16T05:08:00.001-07:00

Who gets gallbladder cancer?

Gallbladder cancer is most often seen in older patients, with a median age at diagnosis of 62-66 years. It occurs more often in females, with a female-to-male ratio of about 3:1. The highest rates of gallbladder cancer occur among US Native Americans, as well as in Mexico, South America, Israel, and China. In fact, Israel has the highest worldwide incidence, with 7.5 cases per 100,000 men and 13.8 cases per 100,000 women. Gallbladder cancer is the fifth most common GI cancer in the United States. However, it is the most common GI malignancy in Mexican Americans and Southwest Native Americans. Low rates are seen in India, Nigeria, and Singapore.

What causes gallbladder cancer? What are the risk factors?

The cause of gallbladder cancer is unknown, although it has been associated with gallstones, high estrogen levels, cigarette smoking, alcohol, obesity, and the female gender. Approximately 70-90 percent of people with gallbladder cancer have gallstones. However, the opposite is not true, as most people with gallstones do not develop gallbladder cancers, and it is unclear how big of a risk gallstones pose. It has been suggested that infection with salmonella may also increase the risk of gallbladder cancers. Also, patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are 10 times more likely to develop cancer of the extrahepatic biliary tract.

What are the signs and symptoms of gallbladder cancer?

Unfortunately, there are no specific, surefire symptoms that suggest a diagnosis of gallbladder cancer. Usually, patients present with problems resulting from blockage of the bile ducts, such as jaundice, loss of appetite and weight loss. There may be a mass and/or pain in the abdomen, especially on the right under the ribcage. However, people often have no symptoms, or their symptoms closely mimic those of gallstones. The most common way gallbladder tumors are diagnosed is incidentally, during surgery performed to remove the gallbladder (cholecystectomy) for some other reason. About 1-2% cholecystectomies reveal a cancer of the gallbladder.

On patient examination, a healthcare provider (HCP) may detect jaundice of skin or the whites of the eyes, a mass in the right upper abdominal quadrant or around the belly button (periumbilical).

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Gallbladder Cancer: The Basics

2009-08-16T05:06:00.000-07:00

Neha Vapiwala, MD
Affiliation: The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 23, 2008

What is the gallbladder, and what does it do?

It is a small pear-shaped organ that stores and concentrates a substance called bile. Bile is a greenish liquid substance produced by the cells of the liver (hepatocytes) that aids in the digestion of fats. It emulsifies fats, causing the fats to accumulate into droplets which can be easily absorbed in the small intestine. It also aids in the absorption of so-called “fat soluble vitamins, such as vitamins A, D, E and K. Bile is also the way the body disposes of hemoglobin from old red blood cells which are no longer functional. This is what makes bile green and stool brown. Once hepatocytes have produced bile, it is transported to the duodenum(the segment of small intestine right after the stomach), where it is secreted through a small opening known as the Ampulla of Vater. It can then form droplets together with fat particles exiting the stomach. The bile also goes to the gallbladder where it can be stored. The gallbladder and liver are connected by the hepatic duct.

When you eat fatty food, the food passes from the stomach into the small intestine, and triggers the lining of the small bowel to release a hormone called CCK (cholecystokinin). CCK is then carried in the bloodstream to the gallbladder, where it causes the gallbladder to contract and send bile through the common bile duct and into the small bowel duodenum. Gallstones form when the substances contained in bile crystallize into small, hard rocks.

How common is gallbladder cancer?

Primary cancer of the gallbladder is very rare and affects about 5000 adults in the US each year.

What are the types of gallbladder cancer?

The majority of these cancers are "adenocarcinomas", with subtypes such as papillary, nodular, and tubular, depending on the appearance of the tumor cells under the microscope. Less common subtypes include: squamous cell, signet ring cell, and adenosquamous (adenoacanthoma).

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Fallopian Tube Cancer: The Basics 4

2009-08-16T05:05:00.000-07:00

Once it is diagnosed, how is fallopian tube cancer staged?

The following is adapted from the Federation of Gynecology and Obstetrics ( FIGO) staging system for fallopian tube carcinoma.

Stage 0	Carcinoma in situ (limited to tubal mucosa)
Stage I	Growth limited to the fallopian tubes
Stage IA	Growth limited to one tube with extension into submucosa and/or muscularis but not penetrating the serosal surface, no ascites. Ascites refers to a build-up of abdominal fluid that may occur as a result of cancer or other illness.
Stage IB	Growth limited to both tubes with extension into submucosa and/or muscularis but not penetrating the serosal surface, no ascites
Stage 1C	Tumor either stage 1A or 1B with tumor extension through or onto the tubal serosa OR with ascites containing malignant cells OR with positive peritoneal washings. Peritoneal washings are performed by instilling fluid into the abdominal cavity and withdrawing it to assess for the presence of tumor cells in the abdominal cavity.
Stage II	Growth involving one or both fallopian tubes with pelvic extension
Stage IIA	Extension and/or metastasis to the uterus and/or ovaries
Stage IIB	Extension to other pelvic tissues
Stage IIC	Tumor either stage IIA or IIB AND with ascites containing malignant cells OR with positive peritoneal washing.
Stage III	Tumor involving one or both fallopian tubes with peritoneal implants outside of the pelvis, involvement of the small bowel, omentum, or liver surface, and/or positive retroperitoneal or inguinal nodes. Peritoneal implants are studs of tumors implanted on the abdominal wall.
Stage IIIA	Tumor grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces (small bowel, omentum, or liver surface).
Stage IIIB	Tumor involving one or both tubes with histologically confirmed implants visualized on the abdominal peritoneal surfaces (small bowel, omentum, liver surface), none exceeding 2 cm in diameter. Lymph nodes negative for tumor.
Stage IIIC	Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes
Stage IV	Growth invading one or both fallopian tubes with distant metastases, including parenchymal liver metastases. Parenchymal liver disease refers to cancer in the inside of the liver; it differs from disease on the liver surface, which may qualify as stage III disease. Fluid on the lungs (pleural effusion) may classify as stage IV disease, but only if cancer cells are found to be present in the fluid.

How is fallopian tube cancer treated?

As always, the optimal treatment regimen should ultimately be individualized as much as possible. It should take into account the patient's stage of disease, other medical history, and personal preference, among other things.

Surgery

As mentioned earlier, fallopian tube cancer is typically diagnosed with surgery. The new FIGO staging system requires an extensive surgical procedure very similar to the one used for ovarian cancer. It includes sampling of pelvic fluid, pelvic and abdominal washings, transabdominal removal of uterus (hysterectomy), removal of both ovaries and fallopian tubes (bilateral salpingoo-ophorectomy), removal of some connective tissue folds (omentectomy), selective removal of pelvic lymph nodes (lymphadenectomy), and selective biopsies of the lining of the abdominal walls and organs (peritoneum).

In cases of very advanced disease, the goal of surgery is primarily to remove as much tumor bulk as safely possible (cytoreduction). Some surgeons also advocate performing a "second-look" surgery, in which a repeat abdominal surgery is done to look for residual or recurrent disease at a later time.

Radiation Therapy

According to a national retrospective study that compared postoperative chemotherapy to postoperative whole abdomen-pelvis radiation therapy in patients with early stage disease, there was no significant difference in survival between the two treatment groups. However, this is not a randomized study, and so the ability to make conclusions from this data is limited. Unfortunately, there are no randomized trials comparing the efficacy of abdominopelvic radiotherapy and cisplatin-containing chemotherapy in the postoperative setting; given the rarity of this cancer, randomized data may never be available. Treatment after surgery should be determined by the patient and physicians together, based on location of any remaining disease, as well as the patient’s lifestyle and overall health..

Chemotherapy

Fallopian tube cancer is fairly responsive to multi-drug regimens containing the agent cisplatin, as compared to non-cisplatin single agents or multi-drug regimens. Again, an individual chemotherapeutic regimen should be developed by the oncologist with the patient’s specific needs in mind.

Hormonal Therapy

The role of hormonal treatment for fallopian tube cancer is not clear, although both medroxyprogesterone acetate and megestrol acetate have been used together with chemotherapy with varying degrees of success.

Combined Modality

The latest in combined modality approaches for advanced disease consists of cytoreductive surgery, post-surgical chemotherapy to reduce remaining tumor burden to microscopic levels, and possible radiation to the abdomen and pelvis following chemotherapy.

What is the prognosis?

Outcome is strongly dependent on stage, extent of postoperative residual disease, and treatment.

Fallopian tube carcinoma is a very rare form of gynecologic cancer and therefore, there are few patients to develop a general prognosis. A recent population based study (a way of combining all known cases to have larger numbers) found the 5-year survival (the percentage of patients alive 5 years after their diagnosis) to be 95% for patients with Stage I disease, 75% for stage II, 69% for stage III, and 45% for stage IV. In general, patients with fallopian tube cancer have a slightly better prognosis than those with ovarian cancer.

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Fallopian Tube Cancer: The Basics 3

2009-08-16T05:04:00.001-07:00

What are the risk factors for fallopian tube cancer?

Given its rarity, the causes and risk factors for developing primary fallopian tube cancer are not clearly defined. There has been some association of the cancer with chronic infection and/or inflammation of the fallopian tubes (due to untreated sexually transmitted diseases, for example), although a cause-effect relationship has not been definitively established.

What are the symptoms of fallopian tube cancer?

The most common symptoms are vaginal bleeding, vaginal discharge, and/or pelvic pain. As a general rule, any vaginal bleeding in a postmenopausal women should be quickly and carefully evaluated. Blood tinged vaginal discharge that does not respond to antibiotic treatment may signify the presence of cancer. Finally, pelvic pain may occur because of trapped fluid blocking and distending the fallopian tube.

There is a syndrome called "hydrops tubae profluens" which consists of: 1) a pelvic mass, 2) profuse watery or honey-colored vaginal discharge, and 3) pelvic pain that essentially goes away upon sudden disappearance of the mass. Although this triad is rarely found in practice, it a classic diagnostic syndrome for fallopian tube disease.

How is fallopian tube cancer diagnosed?

Both in light of its rarity and the difficulty of seeing something abnormal growing on the inside of a tube, fallopian tube cancer can be a difficult diagnosis to make.

One of the most important steps in evaluating any patient with a gynecologic complaint is a proper pelvic examination. The healthcare provider (HCP) should examine the uterus, ovaries, fallopian tubes, and vagina. A pelvic mass is the most common physical finding, seen in about two-thirds of patients. Pelvic fluid (ascites) together with a mass is not as common, occurring in only about 15%.

Having said this, fallopian tube cancers are so rare that the finding of a pelvic mass is not enough to make a diagnosis of fallopian tube cancer. Radiologic studies of the genitourinary and gastrointestinal tracts are also not very helpful in making the diagnosis..

Microscopic analysis (as is done to look for cervical cancer, for example) of cervical and/or vaginal fluid has not in itself been a very reliable technique, with reports of only 40 - 60% of women with fallopian tube cancer having abnormal smears. A stronger tool is the combination of finding adenocarcinoma cells in cervical/vaginal fluid samples together with a negative in-depth exam and biopsy of the uterus (aka "dilatation and curettage").

Over the past 10 years or so, there has been increasing use of ultrasound, looking for the typical finding of a sausage-shaped mass with growths inside the fluid-filled center of the tube (so-called "cogwheel" appearance). The use of both transvaginal color and pulsed Doppler ultrasound seems to be an especially promising strategy.

Ultimately, most physicians feel that the diagnosis requires surgery to evaluate the tubes and obtain definitive tissue specimens.

Serum levels of a marker called CA-125 can be abnormally high in patients with gynecologic diseases, both cancer and non-cancer types (ie: pelvic inflammatory disease, endometriosis, early pregnancy). Although CA-125 is nonspecific, and may be elevated due to many problems that are not cancer, checking a preoperative level is often recommended in a postmenopausal woman with a pelvic mass, if for no other reason than to establish a baseline value for later comparison and assessment of response to therapy.

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Fallopian Tube Cancer: The Basics 2

2009-08-16T05:03:00.000-07:00

What are the different types of fallopian tube cancer?

The vast majority (>95%) of fallopian tube cancers are papillary serous adenocarcinomas. These cancers grow from cells that line the fallopian tubes that have become abnormal. When the cells begin to divide abnormally and gain the ability to invade other organs or spread to other parts of the body, tumors may form. Very occasionally, tumors can form from smooth muscle in the fallopian tubes, in which case they are called sarcomas (leiomyosarcomas), or from other cells that line the fallopian tubes, in which case they are called transitional cell carcinomas.

How common is fallopian tube cancer?

Primary fallopian tube cancer is the rarest (only about 1%) of all gynecologic cancers. The annual incidence of is about 3.6 per million women per year.

Who gets fallopian tube cancer?

The peak incidence is in women who are 60 - 64 years of age, but can continue to occur in women who are in their early- to mid- 80's. The diagnosis is more common in Caucasian women than in Black women, although the cause for this is not well understood.

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Fallopian Tube Cancer: The Basics

2009-08-16T05:00:00.000-07:00

What are the fallopian tube(s)?

The fallopian tubes are a pair of skinny ducts that transport a woman's eggs (ova) from her ovaries (where they are housed) to her uterus (aka "womb") where they are either fertilized by male sperm or discarded during menstruation. Typically, an egg is released from one of the ovaries into the adjacent fallopian tube once each month during ovulation, which occurs in reproductive-age women. The tube helps to move the egg along its journey to the uterus with small hair-like projections called cilia that line the tube's insides.
The tubes are named after a famous Italian physician named Gabriele Fallopio (1523–1562), who first described them.
What is cancer of the fallopian tube(s)?

Cancer of the fallopian tubes is an abnormal growth of malignant cells (neoplasm, tumor) in one or both of a woman's fallopian tubes.

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Endometrial Cancer: The Basics 3

2009-08-11T00:55:00.000-07:00

How is endometrial cancer diagnosed and staged?

When a post-menopausal woman has new onset vaginal bleeding, or any woman has symptoms that suggest a possibility of endometrial cancer, their doctors will want to get a sample of their endometrium called an endometrial biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from and what subtype of cancer it is, how abnormal it looks (known as the grade), and whether or not it is invading surrounding tissues.

The least invasive method to get a biopsy is to do it in your doctor's office. A thin flexible tube is passed through a woman's vagina and cervix and then into her uterus. A small amount of endometrium is removed; this can be somewhat uncomfortable and sometimes anti-inflammatory medications can help with the pain. Occasionally, your doctor will not be able to get enough endometrial tissue with an office biopsy. In this case, you will need to have a dilation and curettage (D & C). D&Cs are done in the hospital, in the operating room under anesthesia. Your doctor dilates the opening to your uterus and then scrapes endometrial tissue from the inside of the uterus, which can then be sent to a pathologist to be studied under a microscope.. The D & C is often done with the aid of a thin scope, known as a hysteroscope, so your doctors can see the inside of the uterus and specifically sample areas that appear abnormal.

Another technique that can help make the diagnosis of endometrial cancer is called transvaginal ultrasound. Ultrasound is an imaging modality that uses sound waves that bounce off of tissues and provide a picture of whatever is being investigated. By inserting an ultrasound probe into a woman's vagina, doctors can get a pretty good look at the thickness of her endometrium. This technique can help differentiate benign (non-cancerous causes of bleeding) from malignant causes of bleeding. If the endometrium appears too thick, then biopsies can be taken. However, it may be more difficult to determine if the thickening is due to cancer in premenopausal women, as they normally have a thicker endometrial stripe. Another type of ultrasound known as a sonohysterography involves placing fluid in the uterus to get a better view of the endometrial stripe.

Endometrial cancer is a type of cancer that needs to be staged during a surgery; it is usually staged and treated during the same operation. In order to guide treatment and offer some insight into prognosis, endometrial cancer is staged into four different groups at the time of the surgery. Surgeons who specialize in gynecologic malignancies go through a careful inspection and sampling of a woman's pelvis during this procedure, and biopsy specimens are sent to a pathologist while the surgeon is still working. The staging system used for endometrial cancer is the FIGO system (International Federation of Gynecologists and Obstetricians). The staging system is somewhat complex, but here is a simplified version of it:

Stage I -- endometrial cancer confined to the body of the uterus (no cervical spread)

Stage II - endometrial cancer which has spread to the cervix (but not outside the uterus)

Stage III -- endometrial cancer outside the uterus, but confined to the pelvis (but not in the bladder or rectum), cancer may have spread to pelvic lymph nodes, the vagina, or within the fluid of the abdominal cavity

Stage IV - endometrial cancer which has spread to the bladder or rectum, or has distant metastasis (spread) to other organs

Generally, the higher the stage, the more serious the cancer is. Although surgery is required for staging, your physicians may want to order some other tests to better characterize the mass/masses and look for distant spread. Tests like CT (CAT) scans (a 3-D x-ray) or MRIs (like a CT scan but done with magnets) can examine the pelvis and localized lymph nodes. A chest X-ray is also sometimes used to determine if there is spread of disease to the chest. You may get also get a colonoscopy, which uses a lighted scope to examine your rectum and colon, or a barium enema in which dye is inserted into your rectum and an x-ray is taken. These tests are to look for spread of the tumor to your colon and rectum. Your doctor may order a blood test called a CA-125, which if positive, predicts that there is spread of the cancer outside of your uterus. Each patient is an individual so the specific tests people get will vary; but overall, your doctors want to know as much about your particular tumor as possible so that they can plan the best available treatments.

What are the treatments for endometrial cancer?

Surgery

Almost all women with endometrial cancer will have some type of surgery in the course of their treatment. The purpose of surgery is first to stage the cancer, and then to remove as much of the cancer as possible. In early stage cancers (stage I and II), surgeons can often remove all of the visible cancer. Generally, women with endometrial cancer will have a hysterectomy (removal of the uterus) and bilateral salpingo-ooporectomy (removal of both ovaries and fallopian tubes) as part of their operation. This is because there is always a risk of microscopic disease in both of the ovaries and the uterus. This surgery is usually done with an abdominal incision but there have been studies examining the use of laproscopic surgery, Laproscopic surgery uses a small camera, and smaller incision to insert small instruments into the abdomen. There are ongoing studies to determine if this method is as effective as the surgery with the abdominal incision. The abdominal cavity is carefully inspected and fluid is collected from the abdominal cavity during the surgery. Biopsies from other area of the abdomen to look for malignant cells may also be collected. Rarely, it may be recommended that the ovaries be preserved in younger women with a low risk of ovarian involvement. This strategy requires an indepth discussion with your surgeon. The only circumstance in which a woman may not have an operation is if she has a very early stage cancer (IA) that looks favorable under the microscope (grade 1). If a woman's tumor has these characteristics and she desires to maintain the ability to have children, then she can be treated by other modalities. Then after she is done having children, she will need to have her uterus, tubes and ovaries removed. With any other stage or grade of tumor, or in patients finished with childbearing, the entire operation should be performed in order to provide the best possible chance for a cure. Depending on the particulars of your case, your surgeon may also remove pelvic lymph nodes during the operation to look for possible cancer spread.

Women who have more advanced disease (stage III or IV) will often have debulking surgeries, which means that their surgeon will attempt to remove as much disease as possible. Data collected in many studies has demonstrated that the more tumor that it debulked, the better the long term outcome for the patient. Operations for endometrial cancer should be performed by surgeons who are trained in dealing with gynecologic malignancies because there are special skills and techniques necessary to deal with these tumors. In patients with very advanced cancers, surgery may be used for palliation- meaning that patients are operated on with the intent of easing their pain or symptoms, rather than trying to cure their disease. Talk to your surgeons about exactly type of operation you are going to undergo.

Radiotherapy

Endometrial cancer commonly receives Radiation therapy radiation therapy as well as surgery, and radiation has proven very effective in management. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation is usually offered after an operation as an adjuvant therapy to the surgery. Radiation is generally used in all but the most favorable cases (very early stages with low grades, and little invasion). Radiation is used to decrease the chances that the cancer will come back. Radiation can also be used in place of surgery in patients who are too ill to risk having anesthesia, but the best results come from the combination of both surgery and radiation.

Radiation therapy for endometrial cancer either comes from an external source (external beam radiation) or an internal source (brachytherapy). External beam radiation therapy requires patients to come in 5 days a week for up 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and is painless. Usually, patients will also be offered internal brachytherapy. Brachytherapy (also called intracavitary irradiation) allows your radiation oncologist to "boost" the radiation dose to the tumor bed. This provides an added impact while sparing your normal tissues. This is done by inserting a hollow tube into your vagina. Then a small radioactive source is placed in the tube. A computer has calculated how long the source needs to be there, but usually for what is called low dose rate (LDR) brachytherapy, you will need to have the source in for a few days. This procedure is done in the hospital, because for those few days you have to remain in bed. Another type of brachytherapy, called high dose rate (HDR) brachytherapy, uses more powerful sources that only stay in for a few minutes. Although this option usually sounds better to patients, not all institutions offer it. Talk to your radiation oncologist about your options and their opinion as to HDR versus LDR for endometrial cancer treatment in your case. Your radiation oncologist may recommend brachytherapy alone, external beam radiation alone, or may recommend a combination of both, depending on your situation. Radiation can cause bowel irritation with diarrhea and bladder irritation which can cause frequent urination. Additionally, the vagina can form scar tissue which can make intercourse painful. The use of a dilator to prevent scar tissue formation can stop this from happening.

Chemotherapy

Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Chemotherapy is not as important as surgery and radiation for treating endometrial cancer. It is usually used in endometrial cancers that are very advanced, or which have recurred after definitive treatment with surgery and radiation. There are many different chemotherapy drugs, and they are often given in combinations. Patients will usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Different chemotherapy regimens are used for different purposes. Some of the drugs used in endometrial cancer chemotherapy include: Cisplatin, Carboplatin, Doxorubicin, and Paclitaxel. There are advantages and disadvantages to each of the different regimens that your medical oncologist can discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle.

Hormonal Therapy

When the pathologist examines your tumor specimen, he or she finds out if the tumor is expressing estrogen and progesterone receptors. Patients whose tumors express progesterone receptors are candidates for therapy with progesterone like agents such as hydroxyprogesterone and medroxyprogesterone. These medications are usually used in patients with very advanced or recurrent endometrial cancers when they are not healthy enough to undergo surgery or radiation.

Follow-up testing

Once a patient has been treated for endometrial cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The highest chance for a recurrence is in the first 3 years after diagnosis. Not surprisingly, the highest risk of recurrence is in those women who had high risk disease. In women with low risk disease, there tends to be a very small risk of recurrence (less than 5%). About 40% of recurrences are local (near where the tumor was) and 60% are distant (to other organs). The majority of recurrences (70%) cause symptoms such as vaginal bleeding, abdominal pain, or weight loss, and should be reported to one’s physician immediately if they occur. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up visits, pelvic ultrasounds, CA-125 levels and/or CT scans depending on your case. Your doctors will also perform pelvic examinations during each of your office visits. During these pelvic exams, your doctors may get samples of your vaginal cells to look for recurrent cancer. Generally, it is recommended that you follow up with your physician every three to six months after being treated for the first two years then annually, if everything appears normal. It is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of endometrial cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about endometrial cancer on OncoLink through the related links to the left.

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Endometrial Cancer: The Basics 2

2009-08-11T00:53:00.000-07:00

How can I prevent endometrial cancer?

Unfortunately, there aren't very good screening methods for endometrial cancer, so preventing it is a particularly important challenge. If you are a woman without a family history/genetic syndrome, there are some things which are under your control and which can reduce the risk of endometrial cancer Birth control (like OCPs - oral contraceptive pills, or depo-provera) that stop ovulation/menstruation can reduce the risk of developing both endometrial and ovarian cancer. Multiple studies have demonstrated that OCPs reduce a woman's risk for developing endometrial cancer; the longer a woman takes them, the more they help in this regard. Combined hormone replacement therapy with both an estrogen and a progesterone component also appears to decrease the risk of endometrial cancer. However, both birth control and combined hormone replacement have several side effects so consult with your physician to see if they are right for your specific situation. Exercise also appears to reduce the risk of developing endometrial cancer.

While a diet high in animal fats has been implicated in endometrial cancer, a diet rich in fruits and vegetables may have a small preventive effect. It has been suggested that diets high in naturally occurring phytoestrogens (which are prevalent in soy products) and fatty fishes may decrease your risk, but further studies need to be performed before these particular nutritional recommendations can be made regarding endometrial cancer prevention.

Women who are carriers of Lynch Syndrome, the above mentioned genetic syndrome, face different decisions. They generally need to have more rigorous screening done for endometrial cancer, and some of them may elect to have their uterus's removed when they are still healthy (called a prophylactic hysterectomy). This should only be done when a woman is finished having children, and it can eliminate the possibility that a woman will contract endometrial cancer. Before a woman decides to do this, she should have genetic testing and a significant amount of counseling from a physician who has experience with genetic diseases. Another time that some women will be offered a prophylactic hysterectomy is if they are done having children, have already gone through menopause, and are taking estrogens as a part of hormone replacement therapy. Discuss your options with your doctors to best sort out the different methods of preventing endometrial cancer in your particular case.

What screening tests are available?

Patients who are diagnosed with early endometrial cancers tend to respond to treatment better than patients with more advanced cancers, so it is beneficial to detect endometrial cancers as early as possible. Luckily, many endometrial cancers are found at early stages, because early endometrial cancers often cause vaginal bleeding (which is very abnormal in post-menopausal women). When post-menopausal women experience vaginal bleeding, they are often worried enough to see their physicians who can then use more invasive tests to look for endometrial cancers. Remember, all postmenopausal vaginal bleeding should be brought to a physician’s attention as soon as possible. The amount of bleeding does not correlate with the risk of cancer, so even a small amount of bleeding should be investigated. Additionally, pre-menopausal woman, who have risk factors for endometrial cancer (such as tamoxifen or estrogen replacement therapy use,) who have bleeding between menstruations, should also be evaluated by a physician.

Right now, there aren't any endometrial cancer screening recommendations for the general population (women without hereditary cancer syndromes) because there aren't any effective screening tests available. Women should get annual pelvic exams for cervical and ovarian cancer screening, but endometrial cancer is not routinely screened for in the general population.

Women with a strong family history and many risk factors or who have a proven hereditary cancer syndrome may need to get rigorous screening for endometrial cancer. Currently, the American Cancer Society recommends that women, who have Lynch Syndrome (HNPCC) or, who have a family member with Lynch Syndrome, or, who have a strong family history of colon cancer (even with negative genetic testing), get annual endometrial biopsies starting at age 35. Endometrial biopsies can be done in your doctor's office. They are often the first step a doctor takes when a post-menopausal patient has vaginal bleeding. However, only women with a very high risk for getting endometrial cancer, (like patients with a genetic syndrome), should be screened in this manner. Talk to your doctor about your endometrial cancer risk, and whether or not you need to be screened.

What are the signs of endometrial cancer?

Luckily, the early stages of endometrial cancer can cause symptoms. When a post-menopausal woman has vaginal bleeding (present in 90% of women at the time of diagnosis with endometrial cancer), the first thing that needs to be looked into is the possibility of endometrial cancer. However, some of the other symptoms are occasionally non-specific, and don't always point toward a diagnosis of endometrial cancer. As a tumor grows in size, it can produce a variety of problems including:

vaginal bleeding (in a post-menopausal woman)
abnormal bleeding (including bleeding in between periods, or heavier/longer lasting menstrual bleeding)
abnormal vaginal discharge (may be foul smelling)
pelvic or back pain
pain on urination
pain on sexual intercourse
blood in the stool or urine

All of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you develop any of these problems.

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Endometrial Cancer: The Basics

2009-08-11T00:29:00.000-07:00

Christopher Dolinsky, MD

Affiliation: The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 29, 2008

What is the endometrium?

The endometrium is the inner layer lining the uterus. The uterus is an organ that only women have, and it is where a baby grows and develops when a woman is pregnant. During pregnancy, the uterus undergoes an enormous increase in size. When a woman is not pregnant, the uterus is a small, pear-shaped organ that sits between a woman's rectum and her bladder. The cervix is the name for the lowest part of the uterus, and serves as the entrance to the uterus. There are two layers to the uterus: the myometrium, which is the outer, muscular layer, and the endometrium, the inner lining.. Every month that a woman is fertile and not pregnant, her ovaries release an egg that travels into her uterus and has the potential to become fertilized. During the few weeks leading up to an ovulation, a woman's endometrium thickens to provide a place for a fertilized embryo to grow and develop. If the egg is not fertilized, the endometrial lining is shed and together with the unneeded blood supply is passed through the birth canal (the woman's vagina). This is called menstruation. Two very important hormones, estrogen and progesterone, help regulate a woman's menstrual cycle and cause the endometrium to grow and thicken each month.

What is endometrial cancer?

Endometrial cancer develops when cells in the endometrium begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of this “out of control” tissue are called tumors. However, some tumors are not true cancers because they cannot spread or threaten someone's life. These are called benign tumors. The tumors that can spread throughout the body or invade nearby tissues are considered true cancers and are generally called malignant tumors. The distinction between benign and malignant tumors is very important in uterine cancer because there are many benign processes which affect the uterusand may get confused for cancers. Fibroids are very common benign tumors of the muscle of the uterus (myometrium), which are not cancerous. They can occasionally cause increased vaginal bleeding, vaginal discharge, or pain. Your doctor may suggest that you have your fibroids removed if they are becoming bothersome.

Cancers are characterized by the normal cells from which they form. The most common type of endometrial cancer is called endometrioid adenocarcinoma; it comes from cells that form glands in the endometrium, and it has a characteristic appearance under the microscope. Endometrioid endometrial cancer compromises about 75-80% of all endometrial cancers. The second most common form is papillary serous adenocarcinoma (about 10% of all endometrial cancers), and yet another form is clear cell adenocarcinoma (about 4-5% of all endometrial carcinomas). Both papillary serous and clear cell adenocarcinomas tend to be more aggressive than endometrioid adenocarcinomas, and are often detected at advanced stages. Sometimes an endometrial cancer has features of more than one subtype; this is called a mixed adenocarcinoma and they make up about 10% of all endometrial cancers. There are a few other rare types like mucinous adenocarcinoma and squamous cell adenocarcinoma that each compromise less than 1% of endometrial cancers.

Am I at risk for endometrial cancer?

Endometrial cancer is the most common gynecological malignancy in the United States. There were approximately 39,000 new cases diagnosed and 7,400 deaths attributed to endometrial cancer in 2007. There is a 2.6% chance of a woman developing endometrial cancer during her lifetime and it causes approximately 6% of all cancers in women.

The majority of women diagnosed with endometrial cancer have already gone through menopause, although it can occur in younger women as well. The average age of diagnosis isaround 60 years of age.Endometrial cancer is uncommon in women less than 40 years of age (5-10% of cases). It appears to be slightly more common in Caucasian women, but women of other races tend to present with more advanced disease.

Although there are several known risk factors for getting endometrial cancer, no one knows exactly why one woman gets it and another doesn't. One of the risk factors for developing endometrial cancer is age; the older a woman becomes, the higher her chances are of getting it. There appear to be two types of endometrial cancers: type I, which is estrogen-related and is more common (80% of cases), and type II, which does not appear to be estrogen-related and tends to present with more aggressive disease. For women with type I endometrial cancer, it appears that the amount of estrogen that a woman is exposed to in her lifetime influences her chances of contracting endometrial cancer. Women who are exposed to more estrogen, either naturally or from outside sources, are more likely to develop endometrial cancer. Thus, any factor that causes a woman to have high levels of estrogen is also a risk factor for endometrial cancer. The more menstrual cycles a woman has in her lifetime, the more estrogen to which her endometrium is exposed. Women who started menstruating early, go through menopause late, don't have any children, don't breastfeed, or don't use a form of birth control that stops ovulation (like birth control pills) are all potentially more likely to develop endometrial cancer. Another condition that increases estrogen in a woman's body is obesity. Fat tissue converts other hormones into estrogens, so extremely overweight people have higher levels of estrogen than thin people. This means that obesity is also a risk factor for endometrial cancer. Diabetes and high blood pressure (hypertension) (which also tends to occur in obese people) appear to be arisk factors for endometrial cancer as wellWomen who take hormone replacement therapy (HRT) after menopause are at a slightly increased risk for endometrial cancer. Tamoxifen is a drug that is used in women with breast cancer to decrease their risk of a cancer recurrence. Because it has estrogen-like properties, the use of tamoxifen is linked to higher rates of endometrial cancer. However, the danger is relatively small and tamoxifen is prescribed because the relative benefits of taking it (in terms of breast cancer prevention) outweigh the apparently minor increased risk of developing endometrial cancer.

Another risk factor for endometrial cancer is a family history of endometrial cancer. The greatest risk appears to be in first degree relatives (direct family members). A small percentage of women who get endometrial cancer carry a genetic mutation that causes a syndrome that increases their risk. The Lynch Syndrome is associated with colon and endometrial cancers (it is also called hereditary nonpolyposis colorectal cancer syndrome - HNPCC), Women can inherit a mutation from their parents and it may be worth testing for mutations if a woman has a particularly strong family history of endometrial or colon cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get the disease). Having a mutation doesn't necessarily mean a woman is going to get the disease, but it does greatly increase her chances above the general population. Family members may elect to get tested to see if they carry mutations as well. If a woman does have the mutation, she can get more rigorous screening or even undergo a prophylactic hysterectomy (preventive removal of your uterus) to decrease her chances of contracting cancer. The decision to get tested is a highly personal one that should be discussed with a doctor who is trained in counseling patients about genetic testing. People with a history of breast cancer may also be at increased risk for endometrial cancer, but this is difficult to determine as many of the risk factors for breast and endometrial cancer overlap. As of yet, there has not been any association found between genes associated with breast cancer, such as the BRCA1 gene, and endometrial cancer, though studies are ongoing,

It has been demonstrated that a diet high in animal fats and low in fruits and vegetables can increase your risk for endometrial cancer Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get endometrial cancer. Talk to your doctor about your risk factors for endometrial cancer to understand his/her recommendations for screening and prevention.

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ESOPHAGEAL CANCER DIAGNOSIS

2009-08-04T21:57:00.000-07:00

How is esophageal cancer diagnosed and staged?
Diagnosis
Work up of an esophageal cancer usually starts after the patient presents with symptoms. In the case of esophageal cancer, this usually means problems with swallowing. The first step is to establish the diagnosis of esophageal cancer. Initial tests sometimes include a barium swallow, where the person swallows barium to permit visualization of the contours of the esophagus on x-rays. Generally, the esophagus is smooth, and if there is a defect in the smooth contour of the esophagus, this may suggest a cancer. An endoscopy is commonly done when people first present with symptoms. Using endoscopy, the area of concern in the esophagus can be viewed directly with the fiber-optic camera, and the location of the abnormality, the presence or absence of bleeding, and the amount of obstruction can all be seen. Endoscopy also allows a biopsy to be performed. Once a biopsy is performed, the pathologist can determine if there is esophageal cancer, and whether it is adenocarcinoma or squamous cell carcinoma. Once the diagnosis has been established, it is important to determine how much cancer is present in the esophagus, as well as whether it has spread to any other parts of the body (metastasis). This is known as cancer staging and plays an important role in selecting the optimal treatment for the cancer. If your doctor suspects that the tumor may have grown into the trachea a bronchoscopy may be ordered, which allows the airways to be visualized. The standard of care today would also include performing an ultrasound during the endoscopy, called an endoscopic ultrasound examination (EUS). This allows for the prediction of how much of the esophageal wall is involved by tumor with over 90% accuracy and the presence of any lymph nodes that are involved with spread of tumor with over 75% accuracy. A CT ("CAT") scan is also usually done to determine the amount of disease in the chest, though it is seemingly less accurate than the EUS. The CT scan should include imaging through the upper abdomen such that the liver liver and lymph nodes in the area of the stomach can be visualized. Other, more routine tests done before treatment include blood screening tests, to insure that overall blood counts are within normal limits, and that a patient's liver, kidneys, and overall health are normal. Other tests may also be included, as symptoms require. Granted, that is a lot of tests, though all are important to offer the best individual treatment for every person.

Staging
After all of these tests are performed, the stage of the cancer is known. The staging of a cancer describes how much cancer has grown within the esophagus as well as whether it has spread This is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, first some background on how cancers grow and spread, and therefore advance in stage.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way esophageal cancer can spread is by local extension to invade through the normal structures in the chest and into adjacent structures. These include the trachea, the diaphragm, and even into the large veins and arteries emanating from the heart. All cancers can spread via local extension, and it is very common for esophageal cancer to spread quite extensively locally before diagnosis is obtained. This is what causes the many symptoms of esophageal cancer, including difficulties with swallowing, cough, bleeding, and subsequent fatigue and weight loss due to malnutrition.

Esophageal cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Within the wall of the esophagus, there is an extensive network of lymphatic channels, hence a large proportion of patients present with lymph nodes already involved with cancer.

The first lymph nodes that cancer cells spread to are the lymph nodes found just along the side of the esophagus (peri-esophageal lymph nodes. Cancer can then spread into the middle of the chest (mediastinal lymph nodes) and into the areas of the neck above the collar bone (supraclavicular lymph nodes) or into the abdomen (peri-gastric and celiac lymph nodes), depending where the primary esophageal cancer is located.

Esophageal cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that arise from cells' travel to other organs are called metastases. Cancers of the esophagus generally spread locally or to lymph nodes before spreading distantly through the bloodstream. Hence, the incidence of distant metastases upon diagnosis is fairly low. It was previously thought that esophageal cancer almost never spread distantly. However, as more and more patients are cured of their local disease with advancements in therapy, this is unfortunately now known not to be the case.

The staging system used in esophageal cancer is designed to describe the extent of disease within the esophagus, in the surrounding lymph nodes, and distantly. The staging system used to describe esophageal tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the esophagus itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases). The staging system for esophageal cancer his complex, particularly regarding lymph node spread, where the location of the esophageal cancer with in the esophagus affects the staging.

The "T" stage is as follows:

•Tis-carcinoma in situ
•T1-tumor confined to the inner layer of the esophageal wall (submucosa or lamina propria)
•T2-tumor invades into the muscular layer of the wall
•T3-tumor invades into the outer layer of the wall (adventitia)
•T4-tumor invades into other structures or organs
The "N" stage is as follows for any subsite:

•N0-no spread to lymph nodes
•N1-tumor spread to regional lymph nodes
◦lymph nodes outside the chest are considered "M1"
The "M" stage is as follows:

•M0-no tumor spread to other organs
•M1-tumor spread to other organs
This is also broken down by site of the primary tumor within the esophagus:

Tumors of the lower esophagus:

•M1a-cancer spread to the lymph nodes in the abdomen (called celiac nodes).
•M1b-cancer has spread to other parts of the body.
Tumors of the upper esophagus:

•M1a-cancer spread to the lymph nodes in the neck (called cervical or supraclavicular nodes).
•M1b-cancer has spread to other parts of the body.
The overall stage is based on a combination of these T, N, and M parameters:

Stage 0: Cancer in situ.

Stage I: Cancer in the two inside layers of the esophagus (T1N0M0)

Stage IIA: Cancer in any of the four layers of the esophagus (T2-3N0M0)

Stage IIB: Cancer in any layer of the esophagus, with spread to lymph nodes near the tumor (T1-2N1M0)

Stage III: Cancer is in the outside layer of the esophagus, or through the wall. Cancer is also in the lymph nodes (T3-4N1M0)

Stage IVA: Cancer spread to the lymph nodes of the abdomen or neck (T1-4N0-1M1a)

Stage IVB: Cancer has spread to other parts of the body (T1-4N0-1M1b)

Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.

What are the treatments for esophageal cancer?
The treatment chosen for a person with esophageal cancer is greatly dependent on two main factors: the extent of the cancer and the general health state of the person. In people who have very early stage disease where it has not spread to lymph nodes or deep into the esophagus, surgery alone may be appropriate. However, commonly people present with more advanced stage disease because symptoms often develop only after the tumor has grown to a large size or has spread. Therefore, there is often a large amount of tumor present before cancer treatment can even begin. There are a number of different modalities that can be used to treat esophageal cancer including surgery, radiation, and chemotherapy. However, in people who can tolerate it, combined modality treatment with surgery, radiation and chemotherapy is preferred.

Surgery (removing the esophagus-an esophagectomy-and exploration of the regional lymph nodes) is a very aggressive procedure that is often not attempted on patients who are not in fairly good health. There are several different surgical procedures remove the esophagus however, generally the esophagus is removed either with the incision through the ribs and abdomen or the neck and abdomen. When the esophagus is removed, the stomach is pulled up into the chest to keep the passageway for food intact. Not only is there a risk of infection and bleeding from the surgery itself, but the recovery period after surgery can be difficult. Additionally, there is the risk of a leak forming at the new connection that is formed between the stomach and the remaining portion of the esophagus (known as an anastamosis), which can then require further surgery and potentially lead to fatal complications. In advanced esophageal cancer, there is still a high failure rate with surgery alone. These failures occur both locally (in the region of the primary tumor or regional lymph nodes) or distantly (from metastatic spread of cancer through the bloodstream). Many studies have looked into adding chemotherapy and radiation therapy to esophagectomy to attempt to add to the cure rate. Though the results of these studies are somewhat mixed, it is thought that both radiation and chemotherapy add a benefit. Therefore, radiation therapy (for local tumor control) and chemotherapy (for distant control as well as to potentiate the effectiveness of radiation therapy) is almost always recommended either before or after the surgery.

Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our body can repair radiation damage much quicker than tumor cells, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. After radiation oncologists set up the radiation fields ("radiation fields" are the areas of the body that will be treated by radiation), treatment is begun. Radiation is given 5 days a week for approximately 5-7 weeks at a radiation treatment center. The treatment takes just a few minutes each day and is completely painless. It is designed to kill tumor cells in the area that is at risk to contain cancer cells, whether it is in the esophagus or the regional lymph nodes. Typical side effects mainly include a sore throat, skin irritation (resembling a sunburn), and fatigue.

Chemotherapy is defined as drugs that are used to kill tumor cells. The large advantage in using chemotherapy is that, since it is a medicine, is travels throughout the entire body. Hence, if some tumor cells have spread outside of what surgery or radiation can treat, they can potentially be killed by chemotherapy. The additional important benefit from chemotherapy in the treatment of esophageal cancer is that it works with radiation, resulting in more killing of cancer cells. Similar to radiation, some normal cells are damaged during treatment, resulting in side effects. The exact side effects depend on which type of chemotherapy is used, though fatigue, some nausea, skin chapping, and a decrease in blood counts can result from any chemotherapy.

There is some debate as to the optimal order in which to deliver these treatments to the esophagus. Different institutions may vary the order in which they use these three modalities in the attempt to cure esophageal cancer. Many will use radiation therapy combined with chemotherapy pre-operatively. The advantage of this method is that it often results in the decrease in the amount of tumor that needs to be removed and is able to be given in a patient who has not already had to undergo an extensive procedure. This allows for easier tolerance of the radiation and chemotherapy and also decreases the size of the radiation field required which reduces this toxicity from surgery. However, the toxicity from combining radiation with chemotherapy is worse than either alone. It is very important for the people to maintain their nutrition such that they can heal well in anticipation of surgery. Surgery after chemotherapy and radiation appears to improve the local control further. However, some centers recommend post-operative treatment. The main advantage of this method is that surgery can be performed in an unirradiated field, allowing for a better surgical technique. Since the surgical removal of the entire tumor is the crucial step in therapy, this consideration often trumps any other.

In some cases, the person is too sick to undergo surgery, or may choose not to undergo surgery. In these cases, a combined, concurrent use of chemotherapy with radiation therapy is usually employed. This method has been proven better than radiation alone, and some think it can reach cure rates comparable to surgery, however this is still being studied. The combined use of radiation therapy and chemotherapy has toxicities as well-mainly irritation of the esophagus making it extremely painful and hence difficult to swallow towards the end of treatment. Some people are too sick to tolerate combined treatment and are treated with radiation or chemotherapy alone.

Alternatively, people can be treated with techniques to open the esophagus in the event that they are too sick to undergo radiation or chemotherapy. Advanced esophageal cancer that is incurable often leaves the patient with difficulty swallowing or unable to swallow at all. Chest pain and bleeding are other common symptoms that can require palliation. Radiation therapy is often used to achieve palliation, with varying success-especially with obstruction, though studies have reported palliation of the obstruction of swallowing in approximately 80% of patients. Actual mechanical stents can also be placed in this scenario or laser removal of tumor can be attempted. These can achieve symptom relief quicker, though they are invasive procedures with their own inherent risks and are also only temporary measures. Hence, these are usually followed by radiation therapy.

As different treatments may be effective in treating a patient's cancer, the more well-informed the better. Regardless of the treatment chosen, it is very important to work with the physicians involved as well as specialists (nutritionists, speech pathologists, etc.) to maximize chance of cure and function after treatment. Obviously the best treatment for cancer is prevention of ever developing cancer. By far, the best prevention is not smoking or immediate smoking and alcohol cessation.
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Esophageal Cancer: The Basics page 2

2009-08-04T21:56:00.000-07:00

85%) of the esophageal cancers diagnosed were squamous cell cancers that occurred in the upper esophagus. Risk factors for this type of cancer include smoking and alcohol use. Although both are thought to be independent risk factors (with smoking being the stronger), there seems to be a synergistic effect between the two for the development of esophageal cancer. In other words, people that both smoke and drink heavily are at an exceptionally high risk to develop esophageal cancer when compared to non-smokers and non-drinkers. Other potential carcinogens for the development of squamous cell carcinoma of the esophagus are nitrosamines, asbestos fibers, and petroleum products.

However, in recent years adenocarcinomas have been on the rise, and are now the most common type of esophageal cancer seen. In contrast with squamous cell carcinomas of the esophagus, adenocarcinomas of the esophagus tend to involve the lower part of the esophagus. Adenocarcinoma is thought to almost always arise in the setting of Barrett's esophagus, which is a condition in which the normal lining of the esophagus is replaced by lining normally found in the stomach. Barrett's esophagus is diagnosed by endoscopy, which is a procedure that uses a fiberoptic camera to look down into the esophagus. This is usually performed by a gastroenterologist, and if any suspicious lesions are seen they can be biopsied during the endoscopy.. Adenocarcinoma of the esophagus is thought to develop from Barrett's esophagus due to further carcinogenic changes in the abnormal lining. Barrett's esophagus is thought to be caused by chronic irritation due to stomach acid. This happens due to a defect in the sphincter, discussed above, which separates the stomach from the esophagus. This sphincter is located at approximately the level of the diaphragm. When it is dysfunctional, acid can reflux, or pass from the stomach into the esophagus. This condition is commonly known as gastroesophageal reflux disease or GERD. This can result in heartburn, bloating, loss of appetite, and stomach pain. Additionally, some people complain of chronic cough from the reflux due to irritation of the voice box from the acid reflux. Patients with chronic GERD are at risk for developing Barrett's esophagus and hence are at higher risk for developing adenocarcinoma of the esophagus. It is not clear if GERD outside the setting of Barrett's esophagus increases the risk of esophageal cancer, though it appears a long or severe history of reflux may increase the risk of esophageal cancer. There are several conditions which can cause or worsen GERD, including a condition known as a hiatal hernia, where portions of the stomach herniate or improperly move through the diaphragm into the chest, causing sphincter dysfunction and resulting reflux. Additionally, obesity, smoking, and certain foods such as coffee and chocolate may potentially worsen reflux.

How can I prevent esophageal cancer?There is not a clear link between a family medical history of esophageal cancer and an individual’s risk of developing esophageal cancer. Smoking is by far the strongest risk factor associated with the development of squamous cell cancer of the esophagus, with alcohol likely playing a supporting role. Therefore, smoking cessation and decreasing alcohol intake are by far the best methods of decreasing the risk of developing squamous cell carcinoma of the esophagus. There also been several dietary factors which have been linked with squamous cell carcinoma of the esophagus, predominantly foods containing N-nitroso compounds, as seen in pickled, dried or smoked foods. Pre-existing esophageal conditions may also increase the risk of developing squamous cell carcinoma of the esophagus. Conditions like achalasia, which is a condition where there is ineffective peristalsis in the esophagus, as well as caustic esophageal injury, say from lye ingestion, can increase the risk of esophageal cancer.

Adenocarcinomas of the esophagus tend to be more common in Caucasian males. As it is thought that the majority of adenocarcinomas develop from Barrett's esophagus, the best prevention of adenocarcinoma would be decreasing the risk of chronic GERD, the cause of Barrett's esophagus in the first place. Smoking, particularly in the setting of Barrett's esophagus, may increase the risk of developing adenocarcinomas of the esophagus. As previously mentioned, obesity may also increase the risk of developing adenocarcinoma of the esophagus. Additionally, decreasing caffeine intake may decrease the risk of adenocarcinoma of the esophagus. Decreasing alcohol intake may also reduce the risk of esophageal adenocarcinoma, but this is controversial.,, Certain genetic conditions which cause increased acid secretion, such as Zollinger-Ellison syndrome, may increase the risk of adenocarcinomas of the esophagus. Although pharmaceutical agents for the prevention of acid secretion (histamine blockers, proton pump inhibitors) can be effective for the prevention of GERD symptoms, there is no proof that they decrease the incidence of Barrett's esophagus. In fact, many think that it increases the risk, as it decreases the pressure of the sphincter between the esophagus and the stomach, making it easier for acid to reach the esophagus. More research into this is required before the answer is known. Once Barrett's esophagus has developed, there is also little evidence that symptomatic medical treatments (histamine blockers and proton pump inhibitors) prevent the development of cancer. Some believe that proton pump inhibitors may cause Barrett's esophagus to regress and hence not develop into cancer. Again, this is mainly unproven. Surgical manipulation of the aforementioned esophageal sphincter, making it more difficult for acid to reach the esophagus, may lead to regression, though again, this is unproven. The most important recommendation for someone with Barrett's esophagus is persistent surveillance, which will be discussed below [under screening].

What screening tests are available?
There are no mass screening recommendations for the general public per se, and there is no specific screening test that exists for squamous cell carcinoma of the esophagus. This makes it even more important to reduce the risk factors for squamous cell cancer-mainly smoking and heavy alcohol use. However, screening and surveillance is very important in patients with Barrett's esophagus, to insure that it does not progress to adenocarcinoma. It has been estimated that there is approximately a 0.2%-2% risk annually of someone with Barrett's esophagus developing esophageal cancer. As above, various medical or surgical procedures can be done to attempt to reverse Barrett's esophagus, but the effect of these is unsubstantiated. Therefore, the best way to insure that Barrett's esophagus causes no problems is repeat evaluations through biopsy via endoscopy. The primary goal of endoscopy is to detect dysplasia early. Although Barrett's esophagus, by definition, is when the lining of the esophagus is abnormal, there can be varied levels of “abnormal”. This is graded in terms of dysplasia, which is a term that refers to how likely the Barrett's esophagus is to progress to cancer. In patients without dysplasia, but just simple replacement of normal esophageal lining with stomach lining, endoscopy is recommended every two to three years. In patients with mild or low grade dysplasia, at least two endoscopies should be done six months apart, then yearly if those are OK. Patients with Barrett's esophagus with high grade dysplasia should be followed by endoscopy every 3 months or actually undergo treatment, as these are considered premalignant changes that have a high likelihood of progressing to cancer. Areas of dysplasia can be treated during endoscopy. Ablative techniques exist, such as with a laser. Photodynamic therapy can be used to treat high-grade lesions using a compound to sensitize tumors to a specific wavelength of light, followed by light exposure to the tumor. Surgical resection of an involved portion of mucosa can also be used.

What are signs of esophageal cancer?
Over 90% of people with esophageal cancer present with problems swallowing, often leading to a significant amount of weight loss prior to the actual diagnosis. Equal often complain of a sensation that food "gets stuck" somewhere in the chest, where the growing of the cancer precludes the passage of food. Problems usually start with food, though eventually even liquids could "get stuck" if the cancer progresses and continues to grow into the hollow tube that the esophagus is. This is similar to a bathroom drain being clogged-if something is in the pipe preventing water from draining, it backs up and is not allowed to pass. People with esophageal cancer often have pain with swallowing as well. Though these are the most common symptoms, others could exist, especially if the tumor grows through the esophageal wall or into other organs. Chest pain can occur in patients who have esophageal spasm, again from irritation from the tumor. A larger tumor can erode the wall to the point where it causes bleeding. This can cause patients to cough up blood, or vomits blood. Additionally, if the blood is swallowed, one may notice blood in the stool or black tarry stools also known as melena. The trachea (windpipe) is located directly in front of the esophagus, and it is possible for an esophageal cancer to erode the entire way through the esophageal wall and into the trachea, creating what is called a tracheoesophageal (respiratory) fistula. This causes cough, an irritating sensation with breathing (especially with deep breaths), and hoarseness.

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Esophageal Cancer: The Basics

2009-08-04T21:52:00.000-07:00

Ryan P. Smith, MD and Eric T. Shinohara, MD
Affiliation: The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 21, 2008

What is the esophagus?
The esophagus is a muscular tube which connects the mouth to the stomach. The wall of the esophagus is composed of a series of muscles that are responsible for peristalsis, or the muscular motion that eases the delivery of food into the stomach. The esophagus is lined with two layers of tissue known as the mucosa and submucosa, which are where most cancers of the esophagus develop. The esophagus is a long tube, with an average length of 25 cm. The throat (or pharynx) is continuous with the esophagus, and although the two are indistinguishable, the esophagus is thought to start a few centimeters below the thyroid cartilage (Adam's apple). The esophagus travels down through the chest, between the lungs. It then passes through a hole in the diaphragm to connect with the stomach. There is a ring of muscle, also known as the lower esophageal sphincter, between the stomach and esophagus which prevents food in stomach acid from going back up into the esophagus.

What is esophageal cancer?
The definition of a tumor is a mass of quickly and abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any spread. A malignant tumor is called cancer when these tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, esophageal cancer occurs when cells in the lining of the esophagus grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. The vast majority of esophageal cancers develop from the inner lining (mucosa) of the esophagus and not from the muscle or cartilage cells that make up the rest of the esophagus. The lining of the esophagus is somewhat unique as it changes as it goes from the throat to the stomach. In the upper (proximal) esophagus, the lining of the esophagus resembles the lining of the throat, made up of squamous cells. Hence, when cancers develop in this region, they are usually squamous cell carcinomas. In the lower (distal) esophagus, the more common type of cancer is called adenocarcinoma, which is what the cancer is called when it develops from a lining that contains glands.

In addition to invasive cancers, patients are sometimes diagnosed with precancerous lesions, called carcinoma-in-situ. These precancerous lesions can be seen prior to the development of either squamous cell carcinoma or adenocarcinoma. Carcinoma-in-situ occurs when the lining of the esophagus undergoes changes similar to cancerous changes without any invasion into the deeper tissues. Hence, while the cells themselves have cancer-like qualities, there is no risk of spread, as no invasion has occurred. Another type of lesion that is considered to be a precursor to cancer itself is called Barrett's esophagus, which is explained in depth below.

Am I at risk for esophageal cancer?
Esophageal cancer occurs in approximately 13,500 Americans per year, causing about 12,500 deaths. Most patients are diagnosed in their 50s or 60s, with approximately four times as many men diagnosed than women. This being said, there is a dichotomy of patients who develop esophageal cancer. In the past, the vast majority (

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colon cancer page 4

2009-07-29T22:15:00.000-07:00

Follow-Up Testing
Once a patient has completed chemotherapy, they must be followed closely for recurrence. The guidelines for follow-up surveillance, written by the National Comprehensive Cancer Network are: physical exam (including digital rectal exam) every 3 months for 2 years, then every 6 months for 3 years; CEA level (if elevated preoperatively) checked every 3 months for 2 years, then every 6 months for 3 years; and colonoscopy in 1 year, with a repeat in 1 year if abnormal, or every 2-3 years if no polyps are found. There is not enough evidence to support or refute the use of chest x-ray or CT scan for surveillance at this time, so this varies from physician to physician and is more likely used in higher risk cases.

Clinical trials have played and continue to play an important role in the treatment of colon cancer. In the past 20 years, considerable improvements have been made in colon cancer therapy, with overall survival rates increasing from 45 to 75 percent. The treatments we have today were refined through clinical trials, and many new avenues continue to be explored. Talk with your physician about current clinical trials for colon cancer in your area or visit our clinical trials matching service.

This article is meant to give you a better understanding of colon cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about colon cancer on OncoLink through the related links on the left.

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colon cancer page 3

2009-07-29T22:14:00.000-07:00

How is Colon Cancer Diagnosed and Staged?
After a cancer has been found, the stage must be determined to decide on appropriate treatment. The stage tells how far the tumor has invaded into the colon wall, and if it has spread to other parts of the body.

•Stage 0 (also called carcinoma in situ) - the cancer is confined to the outermost portion of the colon wall.
•Stage I - the cancer has spread to the second and third layer of the colon wall, but not to the outer colon wall or beyond. This is also called Dukes' A colon cancer.
•Stage II - the cancer has spread through the colon wall, but has not invaded any lymph nodes (these are small structures that help in fighting infection and disease). This is also called Dukes' B colon cancer.
•Stage III - the cancer has spread through the colon wall and into lymph nodes, but has not spread to other areas of the body. This is also called Dukes' C colon cancer.
•Stage IV - the cancer has spread to other areas of the body (i.e. liver and lungs). This is also called Dukes' D colon cancer.
After the tumor and lymph nodes are removed by a surgeon, they are examined by a pathologist, who determines how much of the colon wall and lymph nodes have been invaded by tumor. See Understanding Your Pathology Report for more information. Patients with invasive cancer (stages II, III, and IV) require a staging workup, including full colonoscopy, carcinoembryonic antigen (CEA) level (a marker for colon cancer found in the blood), chest x-ray, and CT scan of the abdomen and pelvis, to determine if the cancer has spread.

What are the Treatments for Colon Cancer?
Surgery
Surgery is the most common treatment for colon cancer. If the cancer is limited to a polyp, the patient can undergo a polypectomy (removal of the polyp), or a local excision, where a small amount of surrounding tissue is also removed. If the tumor invades the bowel wall or surrounding tissues, the patient will require a partial resection (removal of the cancer and a portion of the bowel) and removal of local lymph nodes to determine if the cancer has spread into them. After the tumor is removed, the two ends of the remaining colon are reconnected, allowing normal bowel function. In some situations, it may not be possible to reconnect the colon, and a colostomy (an opening in the abdominal wall to allow passage of stool) is needed, which may be temporary or permanent.

Chemotherapy
Despite the fact that a majority of patients have the entire tumor removed by surgery, as many as 50 to 60% will develop a recurrence without further treatment. Chemotherapy is given to reduce this chance of recurrence. There is some controversy over whether or not patients with stage II disease should receive chemotherapy. Studies have not consistently shown a benefit in treating these patients or have shown only a very small benefit. Generally, patients with stage II disease who present with a bowel perforation or obstruction, or who have large or poorly differentiated tumors (determined by a pathologist looking at the tumor under a microscope), are considered at higher risk for recurrence and are treated with 6 months of fluorouracil (5-FU) chemotherapy, leucovorin (LV) and in some protocols, either oxaliplatin or irinotecan chemotherapy. Other patients with stage II disease are followed closely, but receive no chemotherapy.

Patients who present with stage III colon cancer are treated with a regimen of chemotherapy, including some combination of fluorouracil (5-FU) and leucovorin, oxaliplatin, irinotecan and capecitabine for 6 months, resulting in improved survival rates when compared with surgery alone. After completion of this therapy, they are monitored for recurrence of the disease.

Forty to fifty percent of patients have metastatic disease (cancer that has spread to other organs, also called stage IV) at the time of diagnosis, or have a recurrence of the disease after therapy. Unfortunately, stage IV disease is not considered cureable, but patients can have improved quality of life and longer survival with chemotherapy treatment. The standard therapy for patients with advanced disease is some combination of fluorouracil, leucovorin, irinotecan (CPT-11 or Camptosar), oxaliplatin (Eloxitin) and capecitabine. Regimens adding either irinotecan or oxaliplatin to fluorouracil and leucovorin were found to be more effective than using the fluorouracil and leucovorin alone. With this therapy, an average of 39% of patients have a response, but the average survival is still only 20 months.

Targeted therapies are drug treatments that target a specific abnormality found in the cancer cells. The following are targeted therapies that are commonly used in the treatment of colon cancer.

Bevacizumab (Avastin) is a type of treatment called anti-angiogenic therapy. Tumors need nutrients to survive and are able to get these nutrients by growing new blood vessels. This medication works by attacking the new blood vessels the tumor has formed -- in other words, by cutting off its food source. Bevacizumab is used in combination with chemotherapy.

Cetuximab (Erbitux) and panitumumab (Vectibix) are types of monoclonal antibodies that target cancer cells specifically, sparing the normal cells and therefore causing fewer side effects. Cetuximab causes the patient's immune system to recognize the cancer cells as foreign and attack them and is given either alone or in conjunction with chemotherapy agents.

Epidermal growth factor receptor (EGFR) is abnormally over expressed in many cancers (including those of the colon and rectum), so inhibition of EGFR can result in a decrease in tumor cell growth and decreased production of other factors responsible for metastasis (tumor spread). Panitumumab exerts its cancer fighting properties by competitively inhibiting the binding of epidermal growth factor to EGFR, which prevents epidermal growth factor from working and hence not allowing cancer growth to occur.

Capecitabine (Xeloda), an oral form of fluorouracil, is also used in the treatment of colon cancers when the patient cannot tolerate or has progressed on the above therapies.

Patients and their physicians must weigh the benefits of therapy versus the side effects of the treatment. Patients who are younger and/or in better physical shape are more likely to tolerate therapy, but elderly patients should not be excluded from chemotherapy based on age alone.

Radiotherapy
Colon cancer is not typically treated with radiation therapy. If the cancer has invaded another organ, or attached itself to the abdominal wall, radiation therapy may be a treatment option. One reason for the limited role of radiation is that it is a local treatment typically aimed at a "target". Once the colon cancer has been surgically resected, the "target" or high-risk area for disease recurrence is not very easy to define. Furthermore, if the cancer has spread to other organs, chemotherapy (rather than radiation therapy) is able to reach all the distant areas of tumor cells.

Interventional Radiology
Interventional radiologists are specialists who use radiology techniques, such as CT scan, to access areas of the body and treat diseases without traditional surgery. These techniques are sometimes called “minimally invasive”. In some cases, these physicians are able to help patients with colon cancer that has metastasized to the liver or lung. The techniques currently being used by these specialists include: CT directed biopsies, chemoembolization, radiofrequency ablation and radioembolization. By entering a patient’s blood vessels, the physician can thread a catheter all the way to the liver and give treatment directly to the tumor.

Radiofrequency ablation (RFA) is a local treatment that kills the tumor cells with heat, while sparing healthy liver tissue. When the tumor is too large or in a location not amenable to RFA, embolization may be used to cut off the blood supply to the tumor, deliver radiation to a tumor (radioembolization), or combine this technique with chemotherapy to deliver the cancer drug directly to the tumor (chemoembolization). These therapies are not considered curative, but can provide improved quality of life and extend survival.

Some patients may benefit from having an infusion pump inserted to infuse chemotherapy directly into the liver. IR physicians can also perform palliative procedures, such as inserting a stent to relieve an obstruction, treating certain types of pain, inserting central catheters or treating blood clots.

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Colon Cancer: The Basics page 2

2009-07-29T22:12:00.000-07:00

How Can I Prevent Colon Cancer?
Given the things that put a person at higher risk, a low-fat diet high in fruits and vegetables and low in red meat, together with regular exercise and maintaining a healthy body weight, may aide in prevention. The term chemoprevention can be defined as 'the use of a chemical compound to prevent, inhibit, or reverse the formation of the cancer'. There are ongoing studies looking at vitamins A, E, D, and C, folic acid, calcium, selenium, aspirin, cox-2 inhibitors, statin medications (traditionally used to lower cholesterol) and hormone replacement therapy as potential chemopreventive agents that may prevent or reverse the formation of polyps and colon cancer. Thus far, these studies have been inconclusive, so no specific recommendations can be made for the general population. Some of these agents continue to be evaluated in clinical trials.

What Screening Tests are Available?
Some tumors and polyps may bleed intermittently, and this blood can be detected in stool samples by a test called fecal occult blood testing (FOBT). By itself, FOBT only finds about 24% of cancers. It is recommended by the American Cancer Society that FOBT be done annually, in conjunction with a flexible sigmoidoscopy every 5 years after age 50. This combination of tests detects about 76% of colon tumors. The sigmoidoscope is a slender, flexible tube that has the ability to view about 1/3 of the colon. If a polyp or tumor is detected with this test, the patient must be referred for a full colonoscopy to have the polyp removed and tested for cancer.

The colonoscope is similar to the sigmoidoscope, but is longer and thus can view the entire colon. If a polyp is found, the physician can remove it and send it to a pathology lab to determine if it is adenomatous (cancerous). As a screening method, the American Cancer Society ( ACS ) recommends that a colonoscopy be done every 10 years after age 50. Patients with a family or personal history should have more frequent screenings, beginning at an earlier age than their relative was when he or she was diagnosed. Patients with a history of ulcerative colitis are also at increased risk and should have more frequent screening than the general public. Patients should talk with their physicians about which screening method is best for them, and how often it should be performed. You can learn more about screening by reading Basic Information about Colorectal Cancer and Colorectal Cancer Screening. You can learn about two new tests still in development, virtual colonoscopy and DNA stool testing.

Despite the effectiveness of screening tests for colon cancer, one study found that only 44% of adults who are age 50 and older had undergone testing. Recent media focus, including Katie Couric's efforts and ACS commercials, has helped to raise public awareness of this cancer, but more education is needed.

What are the Signs of Colon Cancer?
Unfortunately, the early stages of colon cancer may not have any symptoms. This is why it is important to have screening tests done even though you may feel well. As the polyp grows into a tumor, it may bleed or obstruct the colon, causing symptoms. These symptoms include:

•Bleeding from the rectum
•Blood in the stool or toilet after a bowel movement
•A change in the shape of the stool (i.e. thinning)
•Cramping pain in the abdomen
•Feeling the need to have a bowel movement when you don't actually have to
As you can see, these symptoms can also be caused by conditions other than cancer. If you experience these symptoms, you should be checked by a doctor.

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Colon Cancer: The Basics

2009-07-29T22:02:00.000-07:00

Carolyn Vachani, RN, MSN, AOCN
Affiliation: The Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 1, 2008

What is the colon?
The colon is the longest portion of the large intestine, also known as the large bowel. The large intestine is the last part of the digestive tract. It is a tube that is about 5 to 6 feet in length; the first 5 feet make up the colon, which then connects to about 6 inches of rectum, and finally ends with the anus. By the time food reaches the colon (about 3 to 8 hours after eating), the nutrients have been absorbed and the remainder is liquid waste product. The colon's function is to change this liquid waste into solid stool. The stool can spend anywhere from 10 hours to several days in the colon before being expelled through the anus. It has been suggested that the longer stool remains in the colon, the higher the risk for colon cancer, but this has not been proven.

What is colon cancer?
Colon cancer is malignant tissue that grows in the wall of the colon. The majority of tumors begin when normal tissue in the colon wall forms an adenomatous polyp, or pre-cancerous growth projecting from the colon wall. As this polyp grows larger, the tumor is formed. This process can take many years, which allows time for early detection with screening tests.

Am I at Risk for Colon Cancer?
Colon cancer is the third most common type of cancer, in both males and females, in the Western world. The incidence is highest in African Americans, who are also more likely to die of the disease. Certain factors put people at higher risk, but with about 108,000 new cases each year in the United States, we must all be aware of this deadly disease. The risk of colon cancer rises substantially after age 50, but every year there are numerous cases reported in younger people. Individuals with a personal or family history of colon cancer, polyps, or inherited colon cancer syndromes (i.e., FAP and HNPCC), as well as patients with ulcerative colitis or Crohn's disease, are all at higher risk and may require screening at an earlier age than the general population. A person with one first degree relative (parent, sibling or child) with colon cancer is 2 to 3 times as likely to develop the cancer as someone who does not have an affected relative.

However, this does not mean that people without a family history are not at risk. In fact, about 80% of new colon cancer cases are diagnosed in people who would not be identified as "high risk". Studies of colon cancer cases found that lifestyle factors may put a person at higher risk. These factors include: a diet high in fat and red meat but low in fruits and vegetables, high caloric intake, low levels of physical activity, and obesity. In addition, smoking and excessive alcohol intake may play a role in colon cancer development. Despite avoiding all of these factors, some people will still develop colon cancer. With screening and early detection, these patients can be effectively treated in a majority of the cases.

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Chronic Myeloid Leukemia (CML): The Basics PAGE 3

2009-07-28T22:04:00.000-07:00

How is CML treated?
In 2001, the U.S. Food and Drug Administration approved Imatinib (Gleevec) for the treatment of CML, and it has become the standard of care for newly diagnosed CML patients. Imatinib is a tyrosine kinase inhibitor; tyrosine kinase is a type of protein called an enzyme. The specific enzyme of interest in CML is abnormal because it is produced by an abnormal gene associated with CML called the bcr-abl gene, also known as the Philadelphia chromosome. By blocking the function of the tyrosine kinase protein, the drug effectively reduces the abnormal effects of this “bad” bcr-abl gene, (i.e. the Philadelphia chromosome). In addition, the drug can also cause direct death of the bcr-abl -expressing cells to die (a process known as apoptosis).

Patients can continue to take imatinib for as long as the disease continues to respond and as long as they are able to tolerate any side effects, which are generally mild. In many patients, the Philadelphia chromosome becomes undetectable by current testing methods, but studies have shown that the abnormality will return quickly if the drug is stopped. Patients must have the presence and amount of Philadelphia chromosome monitored every 3-4 months while on the drug.

Dasatinib and Nilotinib are newer tyrosine kinase inhibitors that are effective in some patients whose CML has grown resistant to imatinib. These drugs may be used before proceeding to transplant, or in patients not able to undergo transplant (due to age, health issues or lack of a donor). Unfortunately, the three available tyrosine kinase inhibitors work best in chronic phase CML, and their efficacy decreases for accelerated and blast phases. In addition, some patients have an abnormality (called a T315I mutation) against which these drugs are not effective.

Prior to the discovery of imatinib, patients with CML were often offered allogeneic stem cell transplant, which remains the only known cure for CML. However, the procedure itself carries a 10-20% risk of death, making it a difficult treatment to choose when the patient has no symptoms and feels well. Transplant is now reserved for patients who do not respond to imatinib or who develop resistance to the medication.

Interferon alfa was also commonly used before imatinib and was effective in 30-55% of patients, but few had the Philadelphia chromosome eliminated (the necessary step to cure). This therapy may be used in patients who are not able to undergo transplant. Hommoharringtonine, chemotherapy developed from a Chinese evergreen tree, has been studied in the past with some success and is being looked at again. Arsenic trioxide had also been previously studied, but newer, safer versions of the drug have renewed interest in this medication. Researchers continue to look for ways to improve the tyrosine kinase inhibitors or to target the disease from other angles with the hope of achieving a cure for all patients.

What is Blast Phase?
CML eventually progresses, or speeds up, and transforms to an acute form of leukemia, which most often resembles AML (acute myeloid leukemia). This may also be referred to as “blast phase” or “blast crisis”. Patients may be treated with imatinib or with chemotherapy drugs similar to those used in AML. This phase of the disease is particularly difficult to treat and prognosis is poor.

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Chronic Myeloid Leukemia (CML): The Basics PAGE 2

2009-07-28T22:03:00.000-07:00

What causes CML?
In most cases, the cause of CML is not known. Exposure to high doses of radiation (such as those after an atomic bomb or older radiation treatment methods for cancer) raises the risk for getting the disease. Chemical exposure has not been shown to cause CML, nor is there a hereditary link.

How is CML “staged”?
CML is not staged like other cancers, but rather is broken down into three phases: chronic, accelerated, and blast. The phases are identified by the number of immature white blood cells (called blasts) that are present in the blood stream. This is also a sign of how aggressive the disease is at that point. Chronic phase is defined as less than 10% blast cells in the blood and is the least aggressive of the phases, accelerated phase is defined as 10-19% blast cells in the blood and blast phase is defined as 20% or more blast cells seen in the blood and is the most aggressive phase of the disease.

How do people with CML present?
Chronic phase is also called the stable phase, and about 90% of people will be diagnosed in this phase. Almost half of newly diagnosed chronic phase patients will have no symptoms, and the disease will be detected by an elevated white blood cell count on a routine blood test. The most common symptoms (regardless of stage) are a result of a low red blood cell count (anemia) and an enlarged spleen (splenomegaly). Anemia leads to fatigue, shortness of breath with activity and a pale appearance. Splenomegaly causes abdominal fullness or discomfort, feeling full early when eating (the spleen is pressing on the stomach) and weight loss.

If CML is suspected, blood and bone marrow samples will be sent to a lab to check for the Philadelphia chromosome or Bcr-Abl gene.

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Chronic Myeloid Leukemia (CML): The Basics

2009-07-28T21:59:00.000-07:00

The discovery of CML
CML is a chronic blood cancer that starts with a defect in two chromosomes and results in an overgrowth of white blood cells. Each person has 23 chromosomes, which contain DNA and a person's genetic makeup (genes). While CML has been recognized since the late 1800's, it was the discovery of the Philadelphia chromosome in 1960 that changed the face of CML.

Drs. Peter Nowell and David Hungerford, two Philadelphia researchers, were experimenting with cells from various types of leukemia when one noticed a smaller-than-normal chromosome number 22 on the cancer cells of 2 individuals with CML. With the far less sophisticated techniques of the time, they were unable to tell what happened to the material missing from the small chromosome.

Nowell and Hungerford published their research in 1960, describing the abnormality that had then been found in 9 out of 10 CML patients they studied. The findings were confirmed by a group in the United Kingdom, and the abnormality was subsequently named the Philadelphia Chromosome, for the city in which it was discovered. Nowell and Hungerford had demonstrated that this genetic change was required for the development of CML a novel and often unaccepted concept at that time.

It would be 1972 before another researcher; Janet Rowley, MD, would discover the missing piece of chromosome number 22 attached to chromosome number 9, thereby identifying the first known chromosomal translocation. The 9;22 translocation is found on the leukemic cells of more than 95% of patients with CML. As the field of genetics grew, it was discovered that the gene abl (pronounced “able”), normally located on chromosome 9, had attached itself to the gene bcr (pronounced “b-c-r”) on chromosome 22. The bcr-abl gene causes the cell to release an abnormal protein (called tyrosine kinase), resulting in too many stem cells developing into white blood cells, leaving a shortage of other cell types. This genetic change to bcr-abl occurs during a person's lifetime and is not passed on to future generations or inherited from parents.

You may wonder why all of this is important. Well, these discoveries led to the development of a drug, called Gleevec, which changed the lives of people with CML, which we will discuss later.

The facts about CML
CML accounts for about 15% of all leukemia cases in the United States, with an estimated 4,570 new cases to be diagnosed in 2007. The Leukemia & Lymphoma Society estimates that over 21,500 people are living with CML. It can occur at any age, but most often occurs in people over age 50. Only 10% of people diagnosed with CML are under the age of 20.

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Chronic Lymphocytic Leukemia (CLL) page 3

2009-07-28T21:45:00.000-07:00

What precautions do people with CLL need to take?
CLL affects a person's ability to fight infection and precautions must be taken to prevent infection. The number one way to prevent infection is through hand washing, both the patient and those they come into contact with. Avoiding large crowds, like a shopping mall the day before Christmas! The lack of a properly functioning immune system means that the common cold, flu or pneumonia can spell real trouble, and can even be life threatening, for a person with CLL. Unfortunately, the same dysfunction in the immune system makes vaccines, such as the flu vaccine, much less effective in people with CLL. Patients should discuss the need for vaccines and when to receive them (in relation to treatments) with their healthcare team. Some studies have shown that giving the pneumococcal vaccine (protects against the most common type of pneumonia) early in CLL may improve its effectiveness.

People with low hemoglobin counts (also called anemia) can experience fatigue, shortness of breath or appear pale. Talk with your healthcare team about ways to treat anemia. Low platelet count (also called thrombocytopenia) can lead to bleeding. This can be as small as gums bleeding when brushing the teeth or a nosebleed to dangerous bleeding, such as a stroke. Patients should avoid contact sports, shaving (electric razor is okay), or any activities that increase the risk of bleeding or bruising. Patients should always inform their healthcare team if they have symptoms of anemia or thrombocytopenia.

What is Richter's Syndrome?
In 3-15% of patients, CLL "transforms" into an aggressive form of lymphoma, which is called Richter's syndrome. There is no way to predict which patients this will occur in, but the prognosis with transformation is very poor. Patients with Richter's syndrome will have increasing swelling of the lymph nodes, spleen and liver; develop fever, abdominal pain and weight loss. Blood counts typically worsen, with anemia, thrombocytopenia and a rapid increase in the lymphocyte count. A lymph node biopsy can diagnose the lymphoma.

Are there other types of CLL?
Yes, there are two other types of B cell leukemias called prolymphocytic leukemia and hairy cell leukemia. T cell leukemias are quite rare, accounting for only 2% of all CLL cases. These include: mycosis fungoides, T-PLL, adult T-cell leukemia, NK (natural killer) cell leukemia (NK cells are a part of the immune system) and large granular lymphocytosis.

Prolymphocytic leukemia (PLL) tends to occur in older persons and most are diagnosed with advanced stage disease. While PLL also affects B cells, they are less mature than those affected in CLL. PLL tends to respond poorly to chemotherapy and the median survival is about 3 years (median means this is the time when half of the patients have died, but half are still living; it is not the same as an average).

Hairy cell leukemia (HCL) occurs in about 600-800 people each year in the United States and is more common in men, by a rate of 4 to 1. It is named for the "hairy" appearance of the B cells under the microscope. Patients most commonly present with recurrent infections, fatigue, enlarged spleen (splenomegaly) or liver (hepatomegaly), low blood counts and the presence of "hairy" cells in the blood stream.

Many patients with HCL will not require treatment, which is only initiated if the disease progresses. When treatment is necessary, cladribine and pentostatin are chemotherapy agents, which can achieve remission in 90% of patients. Other medications used to treat HCL include interferon alpha and Rituxan. Patients with HCL were often treated by removal of the spleen (splenectomy) until the early 1980's, when it was determined that this did not change the course of the disease. Splenectomy may still be performed in patients who do not respond to other therapy.

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Chronic Lymphocytic Leukemia (CLL) page 2

2009-07-28T21:44:00.000-07:00

How do people with CLL present?
The majority of people will not have any symptoms of the disease. If present, symptoms can include: repeated infections, fatigue (due to anemia or low red blood count), bleeding (due to low platelet count), and enlarged lymph nodes. A healthcare practitioner may find enlargement of the spleen (splenomegaly) or liver (hepatomegaly) and/or enlarged lymph nodes or abnormalities in the white blood cell count on a routine blood test.

Once suspected, a blood sample will be sent for a test called "flow cytometry", which detects "markers" on the surface of the cancer cells, confirming the diagnosis. Markers seen on CLL cells include: CD5, CD19, CD23 and CD20.

How is CLL staged?
Some patients with CLL will have aggressive disease, which requires treatment and has a poor prognosis of 2-3 years, while others have a very slow growing disease and can live for 10 to 20 years. About half of all patients are in between these two extremes. Researchers have developed the Rai system to stage the disease, assess prognosis and the need for treatment. Originally Rai assigned stages of 0-IV, but it was determined that there were only three groups for the purposes of prognosis, so the system was modified to include low, intermediate and high risk. (See table below)

Rai Classification System

Simplified System
Stage
Clinical Features
Median survival in years

Low risk
0
Elevated lymphocyte count (lymphocytosis) greater than 5000/mm 3 (in blood and bone marrow)
>10

Intermediate risk
I

II
Lymphocytosis with enlarged lymph nodes

Lymphocytosis with enlarged spleen and/or liver (may or may not have enlarged lymph nodes)
7

High risk
III

IV
Lymphocytosis with anemia (hemoglobin<11g/dl)>How is CLL treated?
The decision to treat or not is an important one. People with early stage or less aggressive disease can actually have better outcomes if treatment is not started until disease related symptoms or rapid doubling time occur. For years, clinicians thought that patients would experience significant psychological distress from "watching and waiting", but this did not prove true in studies.

Once a decision to treat has been reached, there are no set in stone regimens. A chemotherapy drug called fludarabine is considered standard first line therapy, but several studies have shown decreased disease progression when it is combined with another agent such as cyclophosphamide, so combination therapy is often used. Chlorambucil is an oral chemotherapy that was considered the standard before fludarabine and is still a good choice for first or second line therapy. Despite the many clinical trials of various drugs, none has clearly shown longer survival time over the others (they have shown less disease progression, but this may not translate to longer life).

Monoclonal antibodies (alemtuzumab, rituximab) are a group of medications that are designed to target a specific type of cell (in this case, B-cell leukemia) and are being studied in CLL. Antibodies, which are normally found in the body, are developed by the immune system to destroy foreign things (such as a germ). These medications are antibodies that are made in a laboratory, with the goal of stimulating the patient's immune system to attack the leukemia cells.

Other medications used to treat CLL include: cladribine (2-CDA), pentostatin, and prednisone.

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Chronic Lymphocytic Leukemia (CLL) page 1

2009-07-28T21:36:00.000-07:00

What is CLL?
CLL is a chronic blood cancer that affects the lymphocytes, of which there are two types, B and T lymphocytes. These white blood cells are an important component of the immune system, helping to fight infection. More than 90% of CLL cases affect the B cells. In acute leukemia, one cell begins rapidly reproducing, leaving little room for healthy cells, causing symptoms to quickly develop. In CLL, the abnormal B cells accumulate over time, but the rate they are reproducing is not abnormal. Rather than overgrowth, CLL is caused by a loss of apoptosis, or programmed cell death. The B cells should die once they reach a certain number, but cancerous B cells have lost the ability to self destruct in this situation.

CLL accounts for a little over 30% of all adult leukemia cases in the United States, with an estimated 15,340 new cases diagnosed in 2007. The Leukemia & Lymphoma Society estimates that over 95,000 people are living with CLL. The average age at diagnosis is 55-60 and it is more common as age increases, but can develop as early as age 18. It is more common in men and much less common in Asian populations, compared with U.S. or European populations.

What causes CLL?
No one really knows what causes CLL. Exposure to radiation and a chemical called benzene can lead to other types of leukemia, but this is not a cause of CLL. The Veteran's Administration has concluded that exposure to Agent Orange is associated with CLL. In rare cases, more than one person in a family may have CLL, but in the large majority of cases it is not familial in nature.

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cervical cancer page 3

2009-07-28T21:28:00.001-07:00

How is cervical cancer diagnosed and staged?
The most common reason for your doctor to pursue the diagnosis of cervical cancer is if you have an abnormal Pap test. Pap tests exist to find pre-cancerous lesions in your cervix. A pre-cancerous lesion means that there are abnormal appearing cancer cells, but they haven't invaded past a tissue barrier in your cervix; thus a pre-cancerous lesion cannot spread or harm you. However, if left untreated, a pre-cancerous lesion can evolve to an invasive cancer. Pap tests are reported as no abnormal cells, abnormal cells of undetermined significance, low risk abnormal cells or high risk abnormal cells. Depending on your specific case, your doctor will decide how to proceed.

A report of no abnormal cells equates to a negative test, meaning you simply need to follow-up in one year. The abnormal cells of undetermined significance can be handled in three different ways. Women can either get a repeat Pap test in 4-6 months, they can get HPV testing, or they can be referred for colposcopy. Colposcopy is a procedure done during a pelvic exam with the aide of a colposcope, which is like a microscope. By using acetic acid on the cervix and examining it with a colposcope, your doctor can look for abnormal areas of your cervix. Then, the most abnormal areas can be biopsied. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. Once the tissue is removed, a doctor known as a pathologist will review the specimen. Colposcopy is uncomfortable, but not painful, and can be done in your gynecologist's office. Your doctor will decide how to proceed with the workup of a Pap test showing abnormal cells of undetermined significance depending on the details of your case. If repeat Pap tests are not normal, then you will be referred for colposcopy. If you test positive for HPV, you will be referred for colposcopy. Generally, most patients with low risk abnormal cells, or high risk abnormal cells will be immediately referred for colposcopy. If you are pregnant, an adolescent, HIV positive, or post-menopausal, your doctor may have slightly different recommendations. Also, sometimes your Pap test will show cells that look abnormal but could have come from higher in your uterus. There is a chance that if this happens, you will need to have your uterine lining sampled. Talk to your doctor about your Pap test results, and what you need to do next after an abnormal Pap smear.

If you are having symptoms (bleeding/discharge) from a cervical cancer, then it can probably be visualized during a pelvic exam. Any time your doctor can see a cervical tumor on pelvic exam, it will be immediately biopsied. When abnormal appearing tissue is noticed during a colposcopy, then it needs to be biopsied as well. There are a few different ways to do a biopsy. A punch biopsy may be used to remove a small section of the cervix. A LEEP (loop electrosurgical excision procedure) is another method to do a biopsy where a thin slice of the cervix is removed. Finally, a conization or cone biopsy may be performed. A cone biopsy removes a thicker section of the cervix, and allows the pathologist to see if malignant cells have invaded underneath the surface. The cone biopsy has the added value of sometimes being able to cure a pre-cancerous lesion that is localized to a small area. Treatments for cervical cancer and pre-cancerous lesions will be discussed further in the next section.

In order to guide treatment and offer some insight into prognosis, cervical cancer is staged into different groups. There are a few different staging systems, but the most popular one for cervical cancer is the FIGO system (International Federation of Gynecologists and Obstetricians). The FIGO system is a clinical staging system which means that the cancer is staged by a doctor's physical examination and the results of a biopsy. The FIGO staging system is for invasive cervical cancers, not pre-cancerous lesions. A simplified version of the FIGO staging system is:

•Stage IA - microscopic cancer confined to the cervix
•Stage IB - cancer visible by the naked eye confined to the cervix
•Stage II - cervical cancer invading beyond the uterus but not to the pelvic wall or lower 1/3 of the vagina
•Stage III - cervical cancer invading to the pelvic wall and/or lower 1/3 of the vagina and/or causing a non-functioning kidney
•Stage IVA - cervical cancer that invades the bladder or rectum, or extends beyond the pelvis
•Stage IVB - distant metastases
Because the physical exam is so important for staging a cervical cancer, your doctors may want to do the most thorough examination while you are under anesthesia. Another important test is called intravenous pyelography (IVP), which takes an x-ray of your kidneys after you receive a dye given by vein to allow evaluation of your kidney function. Other times, your doctors will want the results of other radiologic tests to better characterize your specific cancer. Tests like CAT scans (3-D x-rays) or MRIs (like a CAT scans but done with magnets) can examine the cervix and localized lymph nodes. X-rays may be taken of your bones and/or chest. Sometimes, your doctors may want to have a look in your bladder and do a cystoscopy, in which a lighted scope is inserted through your urethra into your bladder. You may get also get a proctosigmoidoscopy, which uses a lighted scope to examine your rectum and colon. Each patient is an individual so the specific tests people get will vary; but overall, your doctors want to know as much about your particular tumor as possible so that they can plan the best available treatments.

What are the treatments for cervical cancer?
Pre-cancerous lesions
Women who have pre-cancerous lesions demonstrated on biopsy after colposcopy have a few different options how to proceed. A woman may decide on a specific option depending on whether or not she plans to have children in the future, her current health status and life expectancy, and her concerns about the future and the possibility of having a cancer come back. You should talk to your doctor about you fears, concerns and preferences. Sometimes, women with low grade lesions may choose to not have any further treatment, especially if the biopsy removed the entire lesion. If you decide to do this, you will need frequent pelvic exams and Pap tests. There are several; different ways to remove pre-cancerous lesions without removing the entire uterus (and thus preserving a woman's ability to have a baby in the future). Women can have cryosurgery (freezing off the abnormal lesion), a LEEP (the same type of electrosurgical procedure used for biopsies), a conization (the thicker type of biopsy that gets tissue under the surface), or have the cells removed with a laser. Your doctor can discuss the benefits and drawbacks of each of these modalities. Women who do not have any plans to have children in the future and are particularly worried about their chances of getting an invasive cancer may elect to have a hysterectomy (a surgery that removes your uterus and cervix). This procedure is much more invasive than any of the previous treatment modalities, but can provide peace of mind to women finished with childbearing.

Surgery
Surgery is generally only employed in early stage cervical cancers. The purpose of surgery is to remove as much disease as possible, but it usually isn't used unless all of the cancer can be removed at the time of surgery. Cancers that have a high chance of already being in the lymph nodes are not treated with surgery (lymph nodes are small, pea-sized pieces of tissue that filter and clean lymph, a liquid waste product). There are a few different types of surgeries that can be performed. The earliest stage IA tumors can sometimes be treated with only a hysterectomy (removal of the uterus and cervix). Bigger stage IA, stage IB, and occasionally stage IIA tumors can be treated with more extensive hysterectomies coupled with lymphadenectomies (procedures that remove lymph nodes in the pelvis). Depending on the amount of disease, your surgeon may have to remove tissues around the uterus, as well as part of the vagina and the fallopian tubes. One of the benefits of surgery in young women is that sometimes their ovaries can be left, so that they do not go through menopause at an early age. Higher stage disease is usually treated with radiation and chemotherapy, but sometimes surgery is employed if cervical cancer comes back after it has already been treated. A pelvic exenteration is reserved for recurrent cervical cancers. A pelvic exenteration is a major surgery in which the uterus, cervix, fallopian tubes, ovaries, vagina, bladder, rectum and part of the colon are removed. This surgery is not commonly employed, but is occasionally used for recurrent cancers.

Radiotherapy
Radiation therapy has proven very effective in treating cervical cancer. Radiation therapy uses high energy x-rays to kill cancer cells. Radiation therapy is another option besides surgery for early stage cervical cancer; and when advanced stage cervical cancer needs to be treated, it is usually done with radiation therapy. Surgery and radiation have been shown to be equivalent treatments for early stage cervical cancers, and radiation helps avoid surgery in patients who are too ill to risk having anesthesia. Radiation has the benefit of being able to treat all of the disease in the radiation field; thus lymph nodes can be treated as well as the primary tumor in the course of the same treatment.

Radiation therapy for cervical cancer either comes from an external source (outside of the patient, known as external beam radiation) or an internal sourc (inside the patient, known as brachytherapy). External beam radiation therapy requires patients to come in 5 days a week for up 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. With all cervical cancers above stage IB, the standard approach with radiotherapy is to use external beam radiation coupled with internal brachytherapy. Brachytherapy (also called intracavitary irradiation) allows your radiation oncologist to "boost" the radiation dose to the tumor site. This provides an added impact to the tumor, while sparing your normal tissues. This is done by inserting a hollow, metal tube with two egg shaped cartridges into your vagina. Then a small radioactive source is placed in the tube and cartridges. A computer has calculated how long the source needs to be there, but usually for what is called low dose rate (LDR) brachytherapy, you will need to have the source in for a few days. This procedure is done in the hospital, because for those few days you have to remain in bed. Another type of brachytherapy, called high dose rate (HDR) brachytherapy, uses more powerful sources that only stay in for a few minutes. Although this option usually sounds more appealing to patients, there is debate as to which type is more effective and some institutions favor one over the other. Talk to your radiation oncologist about your options and your doctor’s opinions as to HDR versus LDR for cervical cancer treatment.

Another use of radiation is for palliation - meaning that patients with very advanced cases of cervical cancer are treated with the intent of easing their pain or symptoms, rather than trying to cure their disease.

Sometimes, women with early stage are treated with surgery, but after the results of the surgery, it becomes clear that they will need radiation as well. In any setting, radiation is often combined with chemotherapy, and, depending on your case, your doctor will decide on the best possible treatment arrangement for your lifestyle and wishes.

Chemotherapy
Despite the fact that tumors are removed by surgery or treated with radiation, there is always a risk of recurrence because there may be microscopic cancer cells left in the body. In order to decrease a patient's risk of a recurrence, she may be offered chemotherapy. Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Practically all patients who are in good medical condition and receiving radiation for stage IIA or higher cervical cancer will be offered chemotherapy in addition to their radiation. It may even be offered for earlier stage cases depending individual aspects of the patient and her disease. There have been many studies that demonstrate the usefulness of adding chemotherapy to radiation in terms of decreasing mortality from cervical cancer.

There are many different chemotherapy drugs, and they are often given in combinations for a series of months. Depending on the type of chemotherapy regimen you receive, you may get medication every week or few weeks; and you usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. The most commonly employed regimens use a drug called Cisplatin, but other drugs like 5-FU, Hydroxyurea, Ifosfamide, and Paclitaxel may also be employed. There are advantages and disadvantages to each of the different regimens that your gynecologic oncologist or medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your lifestyle.

Follow-up testing
Once a patient has been treated for cervix cancer, she needs to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up visits, Pap tests, and x-rays or scans depending on your case. Your doctor will also do pelvic exams regularly during your office visits. It is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.

Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of cervical cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about cervical cancer on OncoLink through the related links to the left.

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cervical cancer page 2

2009-07-28T21:26:00.000-07:00

How can I prevent cervical cancer?
Fortunately, there are several actions that women can take to decrease the risk of dying from cervix cancer. The first of these is undergoing regular Pap testing. Pap tests will be discussed further in the next section, but the reason that women have had such a drastic drop in cervical cancer cases and deaths in this country has been because of the Pap test and annual screening.

Recently, a vaccine called Gardasil has been developed. It has been demonstrated to be effective against cervical cancer when given before a female person is exposed to HPV. For this reason, Gardasil is recommended and approved in girls and young women ages 11 – 26 years. Gardasil represents the first commercially available cancer vaccine, and should be discussed with any female patient in the appropriate age range. The use of Gardasil in boys and men is currently being investigated.

For further prevention, women should try to reduce risk factors as much as possible. Don't start smoking, and if you are already a smoker, it is time to quit. Women can limit their numbers of sexual partners, and delay the onset of sexual activity. Unfortunately, condoms do not protect you from developing HPV, so even though they can protect you from other sexually transmitted diseases and HIV, they cannot help lower your risk for developing cervical cancer.

Many people are interested in preventing cervical cancer with vitamins or diets. Studies looking at beta-carotene and folic acid for preventing cervical cancer have shown no benefit. Some people think that anti-oxidants (like vitamin A and vitamin E) may play a role in cervical cancer prevention, but there is currently no convincing data that would suggest so. Further studies need to be performed before any nutritional recommendations can be made regarding cervix cancer prevention.

What screening tests are available?
Cervical cancer is considered a preventable disease. It usually takes a very long time for pre-cancerous lesions to progress to invasive cancers and we have effective screening methods that can detect pre-cancerous lesions that can generally be cured without serious side effects. Effective screening programs in the United States have led to the drastic decline in the numbers of cervical cancer deaths in the last 50 years. For women who do end up with cervical cancer in developed nations, 60% of them either have never been screened or haven't been screened in the last five years. The importance of regular cervical cancer screening cannot be overstated.

The current hallmark of cervical cancer screening is the Pap test. Pap is short for Papanicolaou, the inventor of the test, who published a breakthrough paper back in 1941. A Pap test is easily performed in your doctor's office. During a pelvic examination, your doctor uses a wooden spatula and/or a brush to get samples of cervical cells. These cells are placed on a slide, fixed, and sent to a laboratory where an expert in examining cells under a microscope can look for cancerous changes. Many women find the exam uncomfortable, but rarely painful. Depending on the results of the test, your doctor may need to perform further examinations.

Although the Pap test is highly effective, it isn't a perfect test. Sometimes, the test may miss cells that have potential to become an invasive cancer. The test shouldn't be performed when you are menstruating; and if collection goes perfectly, even the best laboratories can miss abnormal cells. This is why women need to have the tests performed on a regular basis - it may miss abnormal cells one year, but it is unlikely to miss anything two years in a row.

Women should begin having yearly Pap tests done at the onset of sexual activity, or the age 18 - whichever comes first. Most women should continue to have Pap tests done on a yearly basis; however, there is a subset of women who could get testing done every two or even every three years with the agreement of their physician. Women in low risk groups (monogamous with monogamous partners) who have had three normal Pap tests may want to discuss the option of getting the tests done every two or three years. However, after having a new sexual partner, these women need to go back to yearly Pap testing. Women who have had a hysterectomy still need to be examined with a Pap test. Women who have had a "subtotal or supracervical" hysterectomy still have a cervix, and need to continue Pap testing annually. Women who have had a total hysterectomy need to have the tissue in their vaginas examined by a Pap test every 3 to 5 years. Women who are post-menopausal still need Pap exams, but the frequency will depend on their physician's understanding of their particular health needs.

A new screening modality for cervical cancer that may become important in the future is HPV testing. HPV testing can theoretically find the vast majority of women who are at risk for developing cervical cancer. With modern DNA analysis, we have the ability to tell which subtype, or strain, of HPV a person is infected with. The subtype of HPV predicts how likely it is to lead to a cervical cancer. Some of the advantages of HPV testing are that it can be done at home, in private, by a woman collecting a sample herself and sending it to a laboratory via the mail. Also, there is less technical expertise required to correctly run an HPV test than a Pap test. This cuts down on errors and cost. However, the test isn't perfect because the majority of women with HPV will not go on to have cervical cancer, and a positive test result creates the need for expensive and often unnecessary follow-up testing. Although this test is not in current use by itself for cervical cancer screening, in the future, HPV testing may one day replace Pap testing for primary cervical cancer screening. Another possible benefit of HPV testing comes coupling the Pap test with an HPV test, to pick up even more cases of pre-cancerous lesions. Talk to your doctor about your options and the availability of HPV testing in your area.

What are the signs of cervical cancer?
Unfortunately, the early stages of cervical cancer usually do not have any symptoms. This is why it is important to have screening Pap tests. As a tumor grows in size, it can produce a variety of symptoms including:

•abnormal bleeding (including bleeding after sexual intercourse, in between periods, heavier/longer lasting menstrual bleeding, or bleeding after menopause)
•abnormal vaginal discharge (may be foul smelling)
•pelvic or back pain
•pain on urination
•blood in the stool or urine
Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems.

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cervical cancer the basics page 1

2009-07-28T21:25:00.000-07:00

Cervical Cancer: The Basics

Christopher Dolinsky, MD and Christine Hill-Kayser, MD
Affiliation: Abramson Cancer Center of the University of Pennsylvania
Last Modified: April 17, 2009

What is the cervix?
The cervix is the name for the lowest part of the uterus. The uterus is an organ that only women have, and it is where a baby grows and develops when a woman is pregnant. During pregnancy, the uterus has an enormous increase in size. When a woman is not pregnant, the uterus is a small, pear-shaped organ that sits between a woman's rectum and her bladder. The cervix connects the uterus with the birth canal (the vagina). The cervix can both be visualized and sampled by your doctor during a routine pelvic examination in his or her office.

What is cervical cancer?
Cervical cancer develops when cells in the cervix begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of cells that grow abnormally are called tumors. Some tumors are not cancer, because they cannot spread or threaten someone's life. These are called benign tumors. The tumors that can spread throughout the body or invade nearby tissues are considered cancer and are called malignant tumors. Usually, cervix cancer is very slow growing, although in certain circumstances it can grow and spread quickly.

Cancers are characterized by the cells that they originally form from. The most common type of cervical cancer is called squamous cell carcinoma; it comes from cells that lie on the surface of the cervix known as squamous cells. Squamous cell cervical cancer compromises about 80% of all cervical cancers. The second most common form is adenocarcinoma; it comes from cells that make up glands in the cervix. The percentage of cervical cancers that are adenocarcinomas has risen since the 1970s, although no one knows exactly why. About 3% to 5% of cervical cancers have characteristics of both squamous and adenocarcinomas and are called adenosquamous carcinomas. There are a few other very rare types like small cell and neuroendocrine carcinoma that are so infrequent that they will not be discussed further here.

Am I at risk for cervical cancer?
Cervical cancer is vastly more common in developing nations than it is in developed nations, and it is fairly rare inthe United States. In the U.S., it is expected that 13,000 women will develop cervical cancer in 2002; and 4100 women will die of cervical cancer in 2002. This puts cervical cancer as the 12th most common cancer that women develop, and the 14th most common cause of cancer death for women in the U.S. However, cervical cancer is the 2nd most common cause of cancer death in developing nations, with about 370,000 new cases annually having a 50% mortality rate. There has been a 75% decrease in incidence and mortality from cervical cancer in developed nations over the past 50 years. Most of this decrease is attributed to the effective institution of cervical cancer screening programs in the wealthier nations.

Although there are several known risk factors for getting cervical cancer, no one knows exactly why one woman gets it and another doesn't. One of the most important risk factors for cervical cancer is infection with a virus called HPV (human papillomavirus). HPV is a sexually transmitted disease that is incredibly common in the population; most college-aged men and women have been exposed to HPV. HPV is the virus that causes genital warts, but having genital warts doesn't necessarily mean you are going to get cervical cancer. There are different subtypes, or strains, of HPV. Only certain subtypes are likely to cause cervical cancer, and the subtypes that cause warts are unlikely to cause a cancer. Often, infection with HPV causes no symptoms at all, until a woman develops a pre-cancerous lesion of the cervix. It should be stressed that only a very small percentage of women who have HPV will develop cervical cancer; so simply having HPV doesn't mean that you will get sick. However, almost all cervical cancers have evidence of HPV virus in them, so infection is a major risk factor for developing it.

Because infection with a sexually transmitted disease is a risk factor for cervical cancer, any risk factors for developing sexually transmitted diseases are also risk factors for developing cervical cancer. Women who have had multiple male sexual partners, began having sexual intercourse at an early age, or have had male sexual partners who are considered high risk (meaning that they have had many sexual partners and/or began having sexual intercourse at an early age) are at a higher risk for developing cervical cancer. Also, contracting any other sexually transmitted diseases (like herpes, gonorrhea, syphilis, or Chlamydia) increases a woman's risk. HIV infection is another risk factor for cervical cancer, but it may be so for a slightly different reason. It seems that any condition that weakens your immune system also increases your risk for developing cervical cancer. Conditions that weaken your immune system include HIV, having had an organ transplantation, and Hodgkin's disease. Another important risk factor for developing cervical cancer is smoking. Smokers are at least twice as likely as non-smokers to develop cervix tumors. Smoking may also increase the importance of the other risk factors for cancer. Finally, being in a low socioeconomic group seems to increase the likelihood for developing and dying from cervical cancer. This may be because of increased smoking rates, or perhaps because there are more barriers to getting annual screening exams. Cervical cancer is one of the few cancers that affects young women (in their twenties and even their teens), so no one who is sexually active is really too young to begin screening. Additionally, the risk for cervical cancer doesn't ever decline, so no one is too old to continue screening. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get cervical cancer. Proper screening and early detection are our best weapons in reducing the mortality associated with this disease.

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brain tumors page 4

2009-07-28T21:19:00.001-07:00

What are the treatments for brain tumors?
There are a number of different treatments for brain tumors. Most brain tumors are treated with a combination of multiple different types of therapy. The exact location and type of brain tumor will dictate which treatments are recommended.

Surgery
Surgical resection is recommended for the majority of brain tumors. It is rare that a primary brain tumor can be cured without a surgical resection. However, the location of the brain tumor will dictate whether or not surgery is an option. Some tumors are seated in places in the brain that are just too dangerous to operate on, and surgery cannot be employed. The risks to the patient from surgery depend on the location and size of the tumor. Talk to your neurosurgeon about the specific risks of your planned surgery.

Chemotherapy
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein or with pills by mouth. One of the special challenges in treating brain tumors with chemotherapy is that there is a natural barrier between the brain and the blood, which blocks many medications from entering the brain. Only certain chemotherapy drugs can cross this blood-brain barrier to treat disease in the nervous system. One of the new ways that chemotherapy can be delivered for brain tumors is by implantation on a biodegradable wafer that is inserted by the neurosurgeon into the space left behind after surgery (called the tumor bed ). The chemotherapy wafer can then deliver high doses of chemotherapy to a localized area. Chemotherapy wafers are only approved for certain brain tumors, although future research may prove this approach useful for more diseases.

For advanced brain tumors (Stage IV also known as Glioblastoma Multiforme) the most commonly used chemotherapy is known as Temozolamide, an alkylating chemotherapy. It has been shown to be effective when used with radiation after surgery. Additional temozolamide is given about four weeks after completing radiation and chemotherapy, usually for 6 months.

There are many other different chemotherapy drugs used for brain tumors, and your medical oncologist can explain why he or she recommends one particular regimen over another in your case.

Radiation
Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation can come from an external source (called external beam radiation therapy ), and it requires patients to come in 5 days a week for up to 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. External beam radiation therapy is often employed for brain tumors, both as primary treatment for unresectable tumors and in addition to surgery.

Radiation therapy can also be given to a very focused area of the brain using a technique called stereotactic radiosurgery. Stereotactic radiosurgery requires a patient to have a head frame attached, so that a precise map can be made of the patient's head. Radiation is then focused from a variety of different angles to deliver a large radiation dose to the tumor or tumor bed. This can be performed using the same machine that delivers external beam radiation or by a special machine called a gamma knife.

Radiation can also be given internally by implanting high strength radioactive sources in the vicinity of the tumor or the tumor bed. This is called brachytherapy. This can be done with radioactive seeds which are placed directly into the tumor bed or by using a balloon like device, known as a GliaSite, which can be placed into the cavity left after the surgery. The balloon is connected to a small “button” (also known as a port) which is placed under the skin of the scalp. Your physician can then perform a brain CT and determine how much radiation is needed to treat the tumor bed. The port can be accessed with a needle through the skin, which allows the physician to inject a radioactive liquid into the balloon, which can then treat the tumor bed. After injecting the radioactive liquid, you usually need to stay in the hospital while the radiation is working (usually about 5 days). The radioactive liquid is then removed and, often times, the balloon is then removed surgically.

Occasionally, your physician may recommend a type of radiation known as Intensity Modulated Radiation Therapy (IMRT) for treatment. If the brain tumor is close to critical structures within the brain which are more sensitive to radiation damage, such as the nerves of the eyes or the brainstem, IMRT can be used to avoid these structures. IMRT is not beneficial in ever case and your physician can discuss this treatment option with you further.

Your radiation oncologist can answer questions about the utility, process, and side effects of any of the above mentioned types of radiation and can recommend the best type of radiation therapy in your particular case.

Follow-up testing
Once a patient has been treated for a brain tumor, he or she needs to be closely followed for a recurrence. At first, the patient will have follow-up visits fairly often. The longer he or she is free of disease, the less often he or she will have to go for checkups with examinations. The doctor will decide when to obtain follow-up MRI scans or PET scans.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of brain tumors. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about other brain tumors on OncoLink through the related links to the left.

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brain tumors the basics page 3

2009-07-28T21:18:00.000-07:00

What screening tests are available?
Primary brain tumors are rare enough that they are not screened for with any specific tests. The best way to pick up a diagnosis of a brain tumor early is to see your doctor regularly for a thorough physical examination and to report any new, worrisome symptoms promptly. People with genetic disorders that predispose them for the development of primary brain tumors will often get periodic imaging studies of their brains to look for any evidence of abnormalities.

What are the signs of brain tumors?
Unfortunately, the very early stages of brain tumors may not cause any symptoms. As the tumor grows in size, it can produce a variety of symptoms, including:

•headache
•nausea
•vomiting
•loss of appetite
•seizures
•memory loss
•weakness
•visual changes
•problems with speech and language
•personality changes
•thought processing problems
Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. Because the brain controls so many different functions, the symptoms caused by brain tumors can be extremely variable. Headache is the most common symptom for patients with brain tumors, occurring in about 50% of cases.

How are brain tumors diagnosed and staged?
When a patient presents with symptoms suggestive of a brain tumor, the physician will perform a thorough history and physical examination. After that, the key to making the diagnosis is appropriate imaging.

Imaging can be performed with either a CT scan or MRI scan. A CT scan is a three dimensional x-ray, and patients will often be injected with a contrast agent to help visualize any abnormalities. CT scans are good tests because they are quick and easy to obtain, and will often be used as the first step towards making a diagnosis. However, an MRI scan is a better test for evaluating abnormalities in the brain. MRI scans utilize powerful magnets to make a three-dimensional picture. An MRI picks up finer detail than a CT scan, and is the study of choice to make the diagnosis of a brain tumor. MRI scans are usually obtained with the use of an injectable contrast agent as well.

There are some further imaging studies that may be used to determine if a mass in the brain is a tumor (as opposed to other causes, such as infection) and if it is a tumor, what type it is. There is a special type of MRI, known as MR spectroscopy or MRS, which allows your physician to learn more about the contents of the mass and helps them determine what the mass is. A functional MRI is another special type of MRI that can help define areas of the brain, which activate when a person moves or speaks. This allows the doctor to “map the brain” and helps the doctor know which areas to avoid during surgery if the tumor is close to a portion of the brain, which is critical for movement or speech. PET scans can also sometimes be used to determine how active the mass is to help determine if it is really a cancer. It can also sometimes be used to map functional parts of the brain like functional MRI.

For many types of brain tumors, the imaging characteristics are distinctive enough to give physicians a pretty good idea of the diagnosis. The primary management of most brain tumors is surgery. If imaging reveals that a mass suspicious for a brain tumor is in a surgically accessible spot, the patient is generally scheduled for surgery without any further diagnostic testing. After surgery, the specimen can be examined under the microscope by a pathologist, and a final diagnosis can be made. However, sometimes, tumors are not in a safe location for surgery. In those cases, in order to make a diagnosis, patients will often need a biopsy. A biopsy is a procedure where a small piece of the tumor is obtained using a needle under image guidance. The biopsy is usually done as a stereotactic biopsy, where the head is immobilized with a frame that is attached to the skull with pins. A scan of the brain is then done with the frame in place. With the same immobilization device on, the person is taken to surgery and the surgeon can use the scan to guide them precisely to the tumor.

Occasionally, your physician may need to examine the fluid that baths the brain (cerebrospinal fluid or CSF for short) to see if there are any cancer cells that have spread to this liquid. This can be done with a procedure known as a lumbar tap, or an LP for short. A need is inserted between the vertebral bodies (bones of the spinal cord) and into the sack which holds the spinal cord. Some of the CSF is then taken out and a pathologist can examine it and determine if there are cancer cells in the CSF.

Usually, if it is thought that the brain tumor is a metastasis, imaging of the body will also be performed to determine if there is a cancer somewhere else in the body which could be causing the metastasis to the brain. This can be done with an X-ray or a CT scan. Your physician may also order other laboratory tests to determine if cancer is affecting other organs.

Primary brain tumors do not have a classic staging system the way most other cancers do. This is because the size of a brain tumor is less important than its location and the type of brain cell that makes it up. The likelihood of curing a brain tumor has to do with its location, the cell that makes it up, and how the tumor cells look under a microscope. Your doctor will give you a sense of how dangerous your tumor is and how it should be treated after weighing these factors.

Brain metastases are considered within the staging system of the cancer from which they originated. Thus, the presence of brain metastases automatically makes the primary tumor a stage IV cancer, because stage IV means the presence of any metastasis.

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