Doctor-Patient Communication
An open line of communication between a patient and his or her physician is vital when dealing with a serious disease such as mesothelioma. There will be many questions regarding treatment, whether palliative or aggressive, choices to deal with, and life issues to confront. Being informed and proactive in your care will give you a sense of empowerment.

Although most physicians have limited time to spend with each patient at appointments, it is important to address issues as they occur and resolve them to the satisfaction of all parties involved. Initially, this may mean going to your appointment with a list of symptoms or concerns, or questions regarding specific tests that are recommended. Once mesothelioma has been diagnosed, you may have questions regarding treatment options.

Most questions from patients stem from an initial diagnosis of mesothelioma and subsequent treatment options. Following are some frequently asked questions regarding these two important issues.

What Is My Diagnosis?
There are three types of mesothelioma. Pleural mesothelioma is a cancer of the lining of the lung (pleura), peritoneal mesothelioma is a cancer of the lining of the abdominal cavity (peritoneum), and pericardial mesothelioma is a cancer of the lining surrounding the heart (pericardium). Sub-types (or cell types) of mesothelioma are epithelioid (the most common, and considered the most amenable to treatment), sarcomatous (a much more aggressive form), and biphasic or mixed (a combination of both of the other cell types).

The structural appearance of cells under the microscope determine the cell or sub-type of mesothelioma. Epithelioid is the least aggressive; sarcomatoid, the most aggressive. The biphasic or mixed cell type shows structural elements of both of the other two.

Epithelioid
mesothelioma tissue
Sarcomatoid
mesothelioma tissue
Biphasic
mesothelioma tissue

MESOTHELIOMA STAGES
Treatment options are often determined by the stage of mesothelioma a patient is in. There are three staging systems currently in use for pleural mesothelioma and each one measures somewhat different variables; peritoneal mesothelioma is not staged.

The oldest staging system and the one most often used is the Butchart System which is based mainly on the extent of primary tumor mass and divides mesotheliomas into four stages. The more recent TNM system considers variables of tumor in mass and spread, lymph node involvement/, and metastasis. The Brigham System is the latest system and stages mesothelioma according to resectability (the ability to surgically remove) and lymph node involvement.

Butchart System – extent of primary tumor mass

Stage I: Mesothelioma is present in the right or left pleura and may also involve the diaphragm on the same side.
Stage II: Mesothelioma invades the chest wall or involves the esophagus, heart, or pleura on both sides. Lymph nodes in the chest may also be involved.
Stage III: Mesothelioma has penetrated through the diaphragm into the lining of the abdominal cavity or peritoneum. Lymph nodes beyond those in the chest may also be involved.
Stage IV: There is evidence of metastasis or spread through the bloodstream to other organs.
TNM System — variables of T (tumor), N (lymph nodes), M (metastasis)

Stage I: Mesothelioma involves right or left pleura and may also have spread to the lung, pericardium, or diaphragm on the same side. Lymph nodes are not involved.
Stage II: Mesothelioma has spread from the pleura on one side to nearby lymph nodes next to the lung on the same side. It may also have spread into the lung, pericardium, or diaphragm on the same side.
Stage III: Mesothelioma is now in the chest wall, muscle, ribs, heart, esophagus, or other organs in the chest on the same side with or without spread to lymph nodes on the same side as the primary tumor.
Stage IV: Mesothelioma has spread into the lymph nodes in the chest on the side opposite the primary tumor, or extends to the pleura or lung on the opposite side, or directly extends into organs in the abdominal cavity or neck. Any distant metastases is included in this stage.
Brigham System: (variables of tumor resectability and nodal status)

Stage I: Resectable mesothelioma and no lymph node involvement
Stage II: Resectable mesothelioma but with lymph node involvement
Stage III: Unresectable mesothelioma extending into chest wall, heart, or through diaphragm, peritoneum; with or without extrathoracic lymph node involvement
Stage IV: Distant metastatic disease

How Was This Diagnosis Determined, and How Accurate Were the Tests?
Although you probably took many different tests leading up to your diagnosis, a tissue biopsy is normally the final determining factor. Following are some tests your doctor may recommend, and what may or may not be concluded from these tests.

X-rays, CT scans, and MRIs - See the imaging section for more on these techniques. On conventional x-ray film, mesothelioma appears as a markedly thickened, nodular, irregular pleural-based mass which covers the pleural surface. The tumor often encompasses the involved lung, but is only rarely seen bilaterally. Chest wall, diaphragmatic, and mediastinal invasion may be seen in advanced cases. Moderate to large pleural effusion is often noted on the affected side. On CT scan, pleural thickening greater than 1 cm can be identified in over 90% of cases; thickening which extends into the interlobular fissure is seen in 85% of cases. Absence of pleural thickening does not preclude mesothelioma, and at times, the only CT finding is that of pleural effusion.

Cytology - Testing of the pleural fluid for malignant cells is considered to have limited value in diagnosing mesothelioma. Negative or inconclusive readings account for nearly 85% of all fluid tested. Even with a positive fluid report, many doctors prefer to perform a confirming tissue biopsy as long as it does not compromise the patient’s health.

Needle Biopsy - In this test, done under local anesthetic, a large hollow needle is inserted through the skin and into the chest cavity. The needle is then rotated, and as it is taken out, tissue samples are collected. Because of the small sample size of the tissue, this type of biopsy is considered to be only 25-60% accurate in diagnosing mesothelioma. Because tumor seeding may occur along the needle tract in approximately 20% of patients, local radiation therapy may be used in conjunction with this test.

Open biopsy - This type of biopsy is considered to be the most accurate for mesothelioma diagnosis, and is the procedure of choice because it affords the pathologist a larger tissue sample.. It is done in a hospital under general anesthetic. As with a needle biopsy, local radiation may be used because of the possibility of tumor seeding.

Can I Be Treated by the Doctor Who Diagnosed My Mesothelioma?
If the doctor who diagnosed your mesothelioma is your primary physician, he will most likely refer you to a local oncologist for treatment. The oncologist may offer what he or she feels are the best treatment options, or, if their knowledge of this disease is limited, may suggest you seek out a doctor who specializes in mesothelioma. Most often these physicians are located at larger, teaching hospitals such as those listed in the Comprehensive Cancer Center Section. These facilities are ranked as state-of-the-art cancer centers, and are highly respected for their patient care and innovative cancer treatments. If your choice of treatment involves a radical surgical procedure or a clinical trial involving new, as yet unproven drugs, these facilities may be best for you. If your treatment involves an already-approved, standard form of chemotherapy, this can be carried out locally.

What Treatment Options Will I Be Offered?
Treatment options may vary according to the age and over-all health of the patient, and the extent of the disease. It is important to be informed of all available options for your particular case, so that you can make decision on the option you feel most comfortable with. Surgery, chemotherapy, and clinical trials, as well as new approaches such as photodynamic therapy, immunotherapy, and gene therapy may be offered. Speak openly with your doctor regarding suggested procedures. Questions may include:

Why is this procedure best for me?
What does the procedure entail?
What are the advantages/disadvantages of this treatment (i.e, will this procedure limit my eligibility for other treatments)?
What are the possible risks or adverse side effects?
What are the response, survival, and mortality rates associated with this procedure?
Is Palliative Treatment an Option?
In some circumstances, age, contributing health problems, or advanced disease may make aggressive treatment impossible. In these cases, palliative care (that which treats the symptoms, but not the disease itself) may be appropriate. If you opt for palliative care, it is doubly important to communicate fully with your doctor. Many symptoms of mesothelioma can be alleviated or substantially lessened if you are completely open with your doctor. Each time you have an appointment, tell your doctor how you feel, what discomfort you are experiencing, and your level of pain. A good doctor should be willing to address your questions and concerns.

How is mesothelioma diagnosed?
A diagnosis of mesothelioma is most often obtained with careful assessment of clinical and radiological findings in addition to a confirming tissue biopsy. (Learn about typical mesothelioma symptoms.) A review of the patient’s medical history, including history of asbestos exposure is taken, followed by a complete physical examination, x-rays of the chest or abdomen, and lung function tests. A CT scan or MRI may also be done at this time. If any of these preliminary tests prove suspicious for mesothelioma; a biopsy is necessary to confirm this diagnosis.

Imaging Techniques and Their Value in Diagnosing and Assessing Mesothelioma
There are several imaging techniques which may prove useful when mesothelioma is suspected due to the presence of pleural effusion combined with a history of occupational or secondary asbestos exposure. While these imaging techniques can be valuable in assessing the possibility of the cancer, definitive diagnosis is still most often established through fluid diagnosis or tissue biopsy.

Some of the most commonly used imaging methods include:

• X-ray

A chest x-ray can reveal pleural effusion (fluid build-up) which is confined to either the right (60%) or left (40%) lung. On occasion, a mass may be seen. Signs of prior non-cancerous asbestos disease, such as pleural plaques or pleural calcification, or scarring due to asbestosis may also be noted.

• Computed Tomography (CT)

CT scans are also able to define pleural effusion, as well as pleural thickening, pleural calcification, thickening of interlobular fissures, or possible chest wall invasion. CT, however, is not able to differentiate between changes associated with benign asbestos disease (pleural disease), or differentiate between adenocarcinoma of the lung which may have spread to the pleura verses mesothelioma. CT scans may also be valuable in guiding fine needle aspiration of pleural masses for tissue diagnosis.

• Magnetic Resonance Imaging (MRI)

MRI scans are most often used to determine the extent of tumor prior to aggressive treatment. Because they provide images in multiple planes, they are better able to identify tumors as opposed to normal structures. They are also more accurate than CT scans in assessing enlargement of the mediastinal lymph nodes (those lymph nodes which lie between the two lungs), as well as a clear diaphragmatic surface, both of which play an important role in surgical candidacy.

• Positron Emission Tomography (PET)

PET imaging is now becoming an important part of the diagnosis and evaluation of mesothelioma. While PET scans are more expensive than other types of imaging, and are not always covered under insurance, they are now considered to be the most diagnostic of tumor sites, as well as the most superior in determining the staging of mesothelioma. Further explanation of PET scans.

• CT/PET

For patients who may be candidates for aggressive multimodality treatment (surgery, chemotherapy and radiation), accurate clinical staging is extremely important. Integrated CT/PET imaging provides a relatively new tool in this respect, and has become the imaging technique of choice for determining surgical eligibility. By combining the benefits of CT and PET (anatomic and metabolic information) into a single scan, this technology can more accurately determine the stage of the cancer, and can help identify the best treatment option for the patient. Read about a study of CT-PET imaging in preoperative evaluation of patients with malignant pleural mesothelioma.

A needle biopsy of the mass, or the removal and examination of the fluid surrounding the lung, may be used for diagnosis, however, because these samples are sometimes inadequate as far as determining cell type (epithelial, sarcomatous, or mixed) or because of the unreliability of fluid diagnosis, open pleural biopsy may be recommended. In a pleural biopsy procedure, a surgeon will make a small incision through the chest wall and insert a thin, lighted tube called a thoracoscope into the chest between two ribs. He will then remove a sample of tissue to be reviewed under a microscope by a pathologist. In a peritoneal biopsy, the doctor makes a small incision in the abdomen and inserts a peritoneoscope into the abdominal cavity.

Once mesothelioma is suspected through imaging tests, it is confirmed by pathological examination. Tissue is removed, put under the microscope, and a pathologist makes a definitive diagnosis, and issues a pathology report. This is the end of a process that usually begins with symptoms that send most people to the doctor: a fluid build-up or pleural effusions, shortness of breath, pain in the chest, or pain or swelling in the abdomen. The doctor may order an x-ray or CT scan of the chest or abdomen. If further examination is warranted, the following tests may be done:

Video-Assisted Thoracoscopic Surgery (VATS)
Over the past decade, the use of video-assisted thoracic surgery (VATS) has become one of the most widely used tools in the diagnosis of mesothelioma. Biopsies of the pleural lining, nodules, masses and pleural fluid can now easily be obtained using this minimally invasive procedure, and other therapies such as pleurodesis (talc) for pleural effusions can be done concurrently.While the patient is under general anesthesia, several small incisions or “ports” are made through the chest wall. The surgeon then inserts a small camera, via a scope, into one incision, and other surgical instruments used to retrieve tissue samples into the other incisions. By looking at a video screen showing the camera images, the surgeon is able to complete whatever procedures are necessary

In many cases, this video-assisted technique is able to replace thoracotomy, which requires a much larger incision to gain access to the chest cavity, and because it is minimally invasive, the patient most often has less post-operative pain and a potentially shorter recovery period.

Thoracoscopy
For pleural mesothelioma the doctor may look inside the chest cavity with a special instrument called a thoracoscope. A cut will be made through the chest wall and the thoracoscope will be put into the chest between two ribs. This test is usually done in a hospital with a local anesthetic or painkiller.

If fluid has collected in your chest, your doctor may drain the fluid out of your body by putting a needle into your chest and use gentle suction to remove the fluid. This is called thoracentesis.

Peritoneoscopy
For peritoneal mesothelioma the doctor may also look inside the abdomen with a special tool called a peritoneoscope. The peritoneoscope is put into an opening made in the abdomen. This test is usually done in the hospital under a local anesthetic.

If fluid has collected in your abdomen, your doctor may drain the fluid out of your body by putting a needle into your abdomen and using gentle suction to remove the fluid. This process is called paracentesis.

Biopsy
If abnormal tissue is found, the doctor will need to cut out a small piece and have it looked at under a microscope. This is usually done during the thoracoscopy or peritoneoscopy, but can be done during surgery. More on needle biopsies.

Pathology and The Role of Pathologists in the Diagnostic Process

Pathology, or the scientific study of cells, tissue, or fluid taken from the body is an integral part of a mesothelioma diagnosis. Most hospitals have their own pathology labs staffed by board-certified pathologists and licensed technologists. The importance of pathological diagnosis can not be underestimated, since the course of treatment is dependent upon an accurate diagnosis.

To make a diagnosis, pathologists examine tissue under a microscope, and based on established criteria, make a determination of benign vs. malignant cells. Subsequently, the type of cancer is determined. Although most pathologists have a general expertise of various diseases, a small number acquire training in a subspecialty, such as mesothelioma. These are physicians who have received world-wide recognition as premier experts, and have achieved high acclaim for their research, published articles and abstracts, and teaching. For a list of expert pathologists in the field of mesothelioma diagnosis, please call the MW toll free at 1-877-367-6376 or fill in the form at the bottom of this page specifying your request.

Knowing the stage is a factor in helping the doctor form a treatment plan. Mesothelioma is considered localized if the cancer is confined to the pleura, or advanced if it has spread beyond the pleura to other parts of the body such as the lungs, chest wall, abdominal cavity, or lymph nodes.

The early symptoms of mesothelioma are generally non-specific, and may lead to a delay in diagnosis. Sometimes resembling viral pneumonia, pleural mesothelioma patients may present with shortness of breath, chest pain and/or persistent cough; some patients show no symptoms at all. A chest x-ray may show a build-up of fluid or pleural effusion (discussed below). The right lung is affected 60% of the time, with involvement of both lungs being seen in approximately 5% of patients at the time of diagnosis. Less common symptoms of pleural mesothelioma include fever, night sweats and weight loss. Symptoms of peritoneal mesothelioma may include pain or swelling in the abdomen due to a build-up of fluid, nausea, weight loss, bowel obstruction, anemia or swelling of the feet.

PLEASE KEEP IN MIND THAT THESE SYMPTOMS MAY BE CAUSED BY MESOTHELIOMA OR BY OTHER LESS SERIOUS CONDITIONS. ONLY A DOCTOR CAN MAKE A DEFINITIVE DIAGNOSIS.

Pleural Effusion
One of the most common symptoms of mesothelioma is a pleural effusion, or an accumulation of fluid between the parietal pleura (the pleura covering the chest wall and diaphragm) and the visceral pleura (the pleura covering the lungs). Both of these membranes are covered with mesothelial cells which, under normal conditions, produce a small amount of fluid that acts as a lubricant between the chest wall and the lung. Any excess fluid is absorbed by blood and lymph vessels maintaining a balance. When too much fluid forms, the result is an effusion.

Types
Pleural effusion is broken down into two categories, transudates and exudates. A transudate is a clear fluid that forms not because the pleural surfaces are diseased, but because of an imbalance between the normal production and removal of the fluid. The most common cause of transudative fluid is congestive heart failure. An exudate, which is often cloudy and contains many cells and proteins, results from disease of the pleura itself, and is common to mesothelioma. To determine whether a fluid is a transudate or exudate, a diagnostic thoracentesis, in which a needle or catheter is used to obtain a fluid sample, may be conducted.

Symptoms
As the volume of fluid increases, shortness of breath, known as “dyspnea”, and sometimes pain, ranging from mild to stabbing, may occur. Some patients may experience a dry cough. When the doctor listens to the patient’s chest with a stethoscope, normal breath sounds are muted, and tapping on the chest will reveal dull rather than hollow sounds.

Diagnosis
Diagnosis of pleural effusion is usually accomplished with a simple chest x-ray, although CT scans or ultrasound may also be used. A special x-ray technique, called a lateral decubitus film, may be used to detect smaller effusions or to enable the physician to estimate of the amount of fluid present. If the underlying cause of the effusion is readily apparent (such as in the case of severe congestive heart failure), sampling of the fluid may not be necessary, however, because pleural effusion may be symptomatic of a number of disease processes from benign to malignant, a fluid sample is generally taken. Diagnostic thoracentesis, in which cells are extracted from the pleural cavity, is commonly done when the possibility of mesothelioma exists, however, in up to 85% of cases, the fluid tests negative or inconclusive even though cancer is present. It is ultimately a needle biopsy of the pleura (lining of the lung) or an open surgical biopsy which confirms a mesothelioma diagnosis.

Treatment
Pleural effusion caused by heart failure or infection can usually be resolved by directing treatment at the cause, however, when testing has realized no diagnosis, and fluid continues to build or recur, doctors may recommend chest tube drainage and chemical pleurodesis. Chemical pleurodesis is a technique in which a sclerosing agent is used to abrade the pleural surfaces producing an adhesion between the parietal and visceral pleurae. This will prevent further effusion by eliminating the pleural space. Talc appears to be the most effective agent for pleurodesis, with a success rate of nearly 95%. It is highly effective when administered by either poudrage or slurry. Poudrage is the most widely used method of instilling talc into the pleural space. Before spraying the talc, the medical team removes all pleural fluid to completely collapse the lung. After the talc is administered, they inspect the pleural cavity to be sure the talc has been evenly distributed over the pleural surface. Some doctors prefer to use talc mixed with saline solution which forms a wet slurry that can roll around the pleural cavity.

At some point in our lives, nearly all of us have been exposed to asbestos in the air we breathe and the water we drink; from natural deposits in the earth, and from the deterioration of asbestos products around us. Most of us, however, do not become ill as a result of our exposure. More commonly, those who at some point are diagnosed with asbestos disease, have worked in jobs where more substantial exposure occurred over longer periods of time. Nevertheless, cases of mesothelioma have been documented as the result of lesser exposure, affecting family members of workers who came into contact with asbestos and brought it home on their clothing, skin or hair, or affecting those who lived in close proximity to asbestos manufacturing facilities. Symptoms of asbestos disease usually are not be apparent until decades after exposure.

Asbestos was used commercially in North America as early as the late 1800s, but its use increased dramatically during the World War II era when shipyards produced massive numbers of ships for the war effort. Since that time, asbestos-containing products were used by the construction and building trades, the automotive industry and the manufacturing industry. All told, more than 5,000 products contained asbestos.

For more than 50 years, products containing asbestos remained unregulated, and the manufacturers of those products continued to prosper, knowing full well that many of the millions of workers who came into contact with their products would ultimately suffer as the result of their actions. Finally, in the late 1970s, the Consumer Products Safety Commission banned the use of asbestos in wallboard patching compounds and artificial ash for gas fireplaces because the fiber could easily be released during use. In 1989, the Environmental Protection Agency banned all new use of asbestos, but uses established prior to that time were still allowed. Although awareness of the dangers of asbestos and public concern over the issue have led to a decline in domestic consumption over the years, a total ban on asbestos has not come to fruition. Asbestos is still imported, still used and still dangerous.

Although it is suggested that the number of mesothelioma cases in the U.S. has reached its peak and has begun to drop, a forecast released by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER), in April, 2003, projected the total number of American male mesothelioma cases from 2003-2054 to be approximately 71,000. This number, however, does not take into consideration events such as the World Trade Center disaster on September 11, 2001, when millions of New Yorkers were potentially exposed to air filled with carcinogenic asbestos particles. When the latency period for asbestos disease is factored in, cases of mesothelioma will continue to be diagnosed for years to come.

What is Mesothelioma?
The National Cancer Institute states that: “Malignant mesothelioma, a rare form of cancer, is a disease in which cancer (malignant) cells are found in the sac lining the chest (the pleura), the lining of the abdominal cavity (the peritoneum) or the lining around the heart (the pericardium).”

What is peritoneal mesothelioma?
Peritoneal mesothelioma is a cancer of the lining of the abdominal cavity. This form of cancer makes up approximately one-fifth to one-third of the total number of mesothelioma cases diagnosed. More on peritoneal mesothelioma.

How do you get Mesothelioma?
Most people with malignant mesothelioma have worked on jobs where they breathed asbestos. Others have been exposed to asbestos in a household environment, often without knowing it. More about the different ways in which people have been exposed to asbestos.

How much exposure does it take to get the disease?
An exposure of as little as one or two months can result in mesothelioma 30 or 40 years later. Mesothelioma cause.

How long does it take after exposure for the disease to show up?
People exposed in the 1940s, 50s, 60s, and 70s are now being diagnosed with mesothelioma because of the long latency period of asbestos disease.

What is the prognosis for mesothelioma?
Like most cancers, the prognosis for this disease often depends on how early it is diagnosed and how aggressively it is treated. Click on Treatment Options to find out more about traditional and new approaches.

Is there any promising research or are there promising drugs for mesothelioma?
Research is being conducted at various cancer centers all over the United States as well as by pharmaceutical companies. To find more about these studies, click on Clinical Trials. To read abstracts of the latest journal articles on mesothelioma research and to access these articles, click on Medical Journal Articles; or Mesothelioma News for news articles. A recent study of Alimta showed patients living much longer with Alitma than other chemotherapy drugs.

Where can I find information on living with mesothelioma?
Mesothelioma Aid is a good website for resource for families dealing with mesothelioma. It includes advice and referrals to other resources for coping with cancer, caregiving, financial challenges, and support groups. Alternatively, contact us here at Mesothelioma Web for help finding resouces for living with this disease.

What kinds of other resources are available for people with mesothelioma?
There are numerous cancer web sites, some specific to mesothelioma. Because they are often difficult to locate, we have listed some relevant medical sites under Leading Cancer Links. We are always on the lookout for more so check our site often.

What Is Mesothelioma?

Mesothelioma is a cancer of the smooth lining of the chest, lungs, heart, and abdomen. This skin layer is made up of mesothelial cells, hence the name mesothelioma. Mesothelioma is a diffuse but solid tumor that begins as a result of insult to the tissues caused by asbestos particles. These have penetrated into the pleural cavity of the chest or into the abdomen. Mesothelioma is either called pleural mesothelioma or peritoneal mesothelioma based on where it appears.

In its early stages mesothelioma has few symptoms, but given sufficient time it will grow thicker. Eventually it forms bumps and nodules which coalesce into a crust that compresses the organs of the space within which it grows. Over time, pleural mesothelioma may penetrate through the pleura into the chest wall or through the diaphragm into the abdomen. In Peritoneal mesothelioma it may attach itself onto the omentum or penetrate the abdominal wall. In either case it may begin to invade organs like the lungs, heart, stomach, and liver as it spreads. It may even attach itself to key blood vessels, the esophagus or bowels, making it hard or even impossible to remove surgically.

Figure E: Right Pleural Epithelial Mesothelioma on chest wall and lung. Click here. for enlargement. Photo courtesy K. Brauch

For the vast majority of patients, as the tumor mass grows, once subtle symptoms will give way to weight loss, cough, respiratory infections, fatigue, shortness of breath, digestive and bowel problems and pain in the chest or belly, depending upon whether it is pleural or peritoneal. It may begin to weep fluid into the intracavitary space. For pleural patients this is called an effusion and it fills the space where the lobes of the lung reside, next to the lining of the chest cavity. In peritoneal patients it is called ascites and it fills the abdomen with fluid that surrounds the visceral organs.

Figure F: Epithelial mesothelioma on the diaphragm. Click here. for enlargement. Photo courtesy K. Brauch.

The symptoms gradually become more noticeable until the patient seeks medical help. By this time the progression of the disease may already be too advanced since the tumor may have spread to the lymph nodes and/or begun to metastasize to remote organs of the body like the brain, spleen, liver or kidneys. Metastatic mesothelioma is considered late stage and incurable, given the current state of treatments.

Mesothelioma, What Causes Meso, History of Meso, Path of Exposure, Immune Response, Genetic Damage, Molecular Details, Methylation and Cancer, Simian Virus, Types of Meso, Rare Cancers, Who Gets Meso, Mesothelioma Symptoms, Disease Progression, Diagnosis, Staging
What Causes Meso?

The exact method by which asbestos causes mesothelioma isn’t known with certainty. Animal models have provided some understanding of the type of damage that asbestos fibers can do, but the exact mechanism hasn’t been found yet. After asbestos became a commercially successful product, it was soon apparent that asbestos workers were an at-risk population.

Starting at the turn of the century, British investigators discovered a relationship between exposure to high levels of asbestos and respiratory disease. These early studies were often suppressed by government at the request of the asbestos industry. (k) By the mid 50’s American medical researchers had joined the chorus of concerned professionals identifying asbestos as hazardous. Much of their work was never published or was suppressed and/or disputed by scientists in the pay of the asbestos lobby.

Figure G: Amphiboles Protruding, Brook T. Mossman, UVM College of Medicine.

Asbestos fibers have been detected in many resected surgical specimens from mesothelioma patients. In pleural mesothelioma, asbestos fibers are found trapped in the tissues from the lower parts of the lung and they are sometimes concentrated into nodules or spots on the parietal pleura, the primary location for mesothelioma in the thoracic cavity. Although smoking while exposed to asbestos is known to significantly increase lung cancer risks, smoking does not appear to be implicated in the formation of mesothelioma.

Genetic susceptibility may also contribute to the cause of malignant mesothelioma. Two population of two small villages located in Turkey has been environmentally exposed to a rare asbestos-like fiber called erionite for generations. (Please see erionite on the Understanding Asbestos page for more information.)

In an initial study, 50% of the men in one village contracted malignant mesothelioma while the other village had only one case. This was a woman who was originally from the first village. Further research into the residents of these two communities has confirmed an inheritable genetic predisposition to malignant mesothelioma in the presence of asbestos-like fibers.

Current research has repeatedly found abnormalities in mesothelioma cases where deletions of chromosome regions 1p, 3p, 9p, and 6p, and the loss of chromosome 22 have been observed. It is believed that these deletions affect tumor suppressor genes, allowing for the development of mesothelioma. The mechanism for genetic suppression of tumor development is discussed below.

Mesothelioma, What Causes Meso, History of Meso, Path of Exposure, Immune Response, Genetic Damage, Molecular Details, Methylation and Cancer, Simian Virus, Types of Meso, Rare Cancers, Who Gets Meso, Mesothelioma Symptoms, Disease Progression, Diagnosis, Staging
A History of Meso

The history of the acceptance of mesothelioma as a primary malignancy of the pleura is one of more than 100 years of confusion and frustration. The disease was rare enough that its appearance was only intermittently identified in the medical literature. With less than one case in a thousand being identified as pleural or peritoneal carcinomas, it is little wonder that physicians at first were reluctant to assign it the status of a primary tumor. The medical establishment of the 1800’s was convinced that pleural tumors had to be metastatic cancers from some other primary tumor, regardless of the lack of evidence for this.

In the late 1800’s it was noted that mesothelioma could be found in the lymph nodes and the theory developed that the cancer began in the lymphatic system and spread to the lungs or abdomen. Not until 1891 was consideration given to the opposite theory. As always, research into the nature of mesothelioma was hampered by the lack of a sufficiently large body of evidence. Patients, thankfully, were still few and far between and reaching a consensus with so little clinical data was difficult.

The early 20th century finally brought acceptance that some pleural sarcomas could arise even without a primary cancer elsewhere in the body. From this humble beginning, the realization that the tumor developed from the mesoderm hit home and the term mesothelioma came to be accepted in 1921. Through the ‘30’s and ‘40’s further research and an increasing number of patients established the description of the tumor and began to identify the link to asbestos exposure.

Because of the confusion over whether mesothelioma truly was a separate clinical entity, five different views about causation took hold:

1. The endothelial lining of the lymph nodes was the cause, hence the name endothelioma.
2. Aberrant lung tissue became malignant within the lining of the pleura.
3. The tumor arose in the pleural capillary endothelium.
4. Tumors of epithelial origin always arose from a primary tumor elsewhere. The primary tumors were felt to be too small to be detected in autopsy.
5. The tumor arose from the mesothelial lining of the pleura and peritoneum.

It was Wedler in 1943 who reported a connection too high to be coincidental between asbestosis and pleural malignancy in a population of German asbestos workers. The analysis, which factually reported the connection but made no attempt to stamp the disease with a label, was widely accepted in Germany and ignored in the rest of the world. It wasn’t until the early 1950’s that additional evidence rescued the observations of Wedler and began to build an irrefutable connection between asbestos exposure and mesothelial cancer.

Mesothelioma, What Causes Meso, History of Meso, Path of Exposure, Immune Response, Genetic Damage, Molecular Details, Methylation and Cancer, Simian Virus, Types of Meso, Rare Cancers, Who Gets Meso, Mesothelioma Symptoms, Disease Progression, Diagnosis, Staging
Inhalation- The Primary Path of Exposure:

The primary access path for asbestos fibers is the respiratory system. Fibers released into the air are inhaled by the subjects where they are carried into the deepest recesses of the lungs. Asbestos fibers that are locked into heavier particles of plaster, concrete or paint are often expelled through coughing and rarely reach deeply enough into the lungs. From studies conducted in the early to mid-20th century, most of which were post-mortem examinations, it became apparent that pleural asbestos disease tended to accumulate near the bottom lobes of the lungs, in the gutter of the thoracic cavity and on the surface of the diaphragm.

Microscopic examination of biopsy or autopsy tissue samples revealed that in many cases the asbestos fibers were no longer located in the alveoli of the lungs but rather in the intrapleural space or within the mesothelial lining of that space. This was described by many physicians as a “clearing” of the lungs, but despite the benign sounding label, this process held serious and potentially fatal implications for the subject.

The clearing of the lungs is directly connected to the two primary theories about how injury is caused by asbestos. The first theory postulates that the asbestos fibers pierce the tissue walls of the pleural space (and sometimes the peritoneal space via the stomach or the diaphragm) and cause tissue damage which creates an inflammatory immune response. The second theory states that the asbestos fibers are so small that they begin to interact with mesothelial cells at a molecular level, interrupting cell replication and/or damaging the cellular DNA during mitosis, or cell division.

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Inflammatory Immune Response

The migration of the asbestos fibers out of the alveoli is a function of the small size of the fibers. This allows them to pierce the cell walls and migrate between cell boundaries into the mesothelial lining of the pleural cavity or even into the intrapleural space. There, they sometimes penetrate the diaphragm and make their way into the abdomen or the testes.

Whenever these fibers migrate, they leave a trail of damaged or compromised cells behind. The response to this damage varies by individual and invariably involves the immune system. Evidence for the response is found in the irritation and destruction of cells and the creation of scar tissue at the site of the injury. This process can be quite significant in the case of heavy asbestos exposure and can lead to major impairment of the lungs as a crust or plaque of fibrous scar tissue forms over the affected areas. Microscopic examination of this material has often found asbestos fibers entombed in the nodules and layers of tissue and has been used as prima fascia evidence for the asbestos connection as a cause for the injury.

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Genetic Damage During Cell Division:

All living cells have a limited ability to renew themselves. This ability confers a specific life span that appears to be pre-programmed into their chromosomes. When cells divide, the ends of the DNA molecules get shorter, truncating a section of the chromosome called the telomeres. The DNA strands get shorter and shorter until the cell can no longer replicate itself.

Almost all of the cells in our body, including mesothelial skin cells, will grow old and die. The only exceptions are bone marrow cells (making blood cells) and the sperm producing cells of the testes. These cells are called immortal cells since they never lose the ability to reproduce themselves. They are assisted during cell division by an enzyme called telomerase that allows them to keep dividing endlessly without degrading. Before regular cells get old and die they divide, and new cells, (daughter cells) take their place. This process, called mitosis, can be repeated roughly 60 to 100 times during the human lifespan before the cells lose their ability to divide. Once that happens, our tissues and organs begin to fail and we reach the end of our lifespan.

It is during mitosis of respiratory tissue cells that asbestos fibers are thought to do the damage that eventually leads to mesothelioma. During mitosis, the DNA in the parent cell is split into two haves and each half is drawn towards an opposite end of the cell. There, new amino acids replace the missing halves of the DNA by using the original halves as templates. Assuming nothing goes wrong, the cell now contains two identical sets of DNA and a barrier forms that divides the cell into two identical halves.

During mitosis, asbestos fibers that have penetrated the cell are thought to physically interfere with the replication of the DNA. This may break the DNA chains, causing the cell to fail, or damage the functioning of its genes, making it become cancerous. The majority of cells whose genetic machinery is non-functional will die and be cleaned up by the immune system but not all of them will. Some cells whose genetic machinery wasn’t fatally damaged will continue to live on in a diminished or damaged state. Those malfunctions which cause a regular cell to reproduce endlessly are termed cancer.

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Molecular Details

As cells proceed through mitosis they are monitored by a system of chemical controls that check for DNA damage and look for the inability to perform essential cellular processes. If this system detects damage or errant functions, RNA message molecules are used to cause the cells to stop dividing. These controls cause damaged cells to either repair themselves or self-destruct. The latter process is called apoptosis or programmed cell death.

Recent research has uncovered a protein, called p53, (ad) which identifies chemical messages caused by genetic damage to the cellular DNA. P53 is produced by a gene that oversees tumor suppression. Once activated, p53 then stimulates the production of proteins that stop the DNA replication process. Without this valuable intervention, damage in the genetic machinery of the cell can accumulate unchecked. A direct consequence of failure to produce p53 is that damaged cells progress into a cancerous state. Today, defects in the functioning of p53 are associated with a variety of cancers, including some breast and colon cancers. A more detailed explanation of gene activation and suppression is provided below.

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Cell Methylation and Cancer:

Recent developments in the field of biology have studied the functional processes of genes at the molecular level. Scientists have known for some time that certain sections of the chromosome, called genes, serve essential functions for the health and welfare of the cell and the host organism. There are large areas of the chromosome that were previously regarded as non-functional or “junk” DNA that are now known to have a role in the control of which genes are active (expressed) and which are not. The process of controlling genes through protein molecule messengers is called methylation.

Some genes control the replication of, and also the longevity of the cells that contain them. While we haven’t identified all of these genes, we have learned that, when growth regulating genes are blocked from doing their functions, cells can grow without restraint, causing cancer.

We have now discovered some of the proteins that appear to be responsible for interfering with the balanced and normal functions of a wide variety of regulatory genes. The excessive presence of such proteins in blood or urine (called over-expression) can be used as a measure of the presence of cancer. We still don’t know exactly what causes these proteins to be produced in excessive amounts, nor have we uncovered all the connections between the production of these molecules and the genetic damage caused by asbestos.

However, studies of this area would seem to imply that damage to a cell isn’t automatically a cause for cancer and that other factors come into play.

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Simian Virus SV40

One new and highly contentious issue is the role of simian virus 40 (SV40) in the development of mesothelioma tumors. Animal experiments have established that SV40 is a potent tumor inducing virus, however, clinical studies still have not conclusively linked SV40 to human mesothelioma cases. Many studies and publications have demonstrated the presence of SV40 in human mesothelioma tissue samples.

There is some evidence, however, that the SV40 presence in the samples may be due to pervasive laboratory contamination. The source of this contamination was the original monkey cell cultures used as a medium in which to grow smallpox vaccines. The SV40 remnants were felt to be benign and were therefore ignored by laboratories. it was only later that the tentative connection to cancer was noted.

It is also interesting that the presence of SV40 in pathology samples is statistically indicative of a poor outcome, suggesting that asbestos and SV40 may interact in the spread and aggressiveness of mesothelioma tumors. More research is necessary before we can claim to have a causal link between SV40 and human malignant mesothelioma.

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Types of Mesothelioma

Mesothelioma can be classified into two major groups, benign and malignant. Malignant mesothelioma is organized into four main categories based on the location of the tumor:

pleural – found in the chest cavity, on the surface of the lung and on the diaphragm,
peritoneal – found in the abdomen on the surface of the omentum and visceral organs,
pericardial – growing on the exterior surface of the pericardium, or lining of the heart, and
testicular – noted as a thickening of the ducts and glands in the testes.
While the rarest of the mesos, testicular mesothelioma is the second most common type of testicular cancer after soft tissue tumors.

Each of these categories of mesothelioma is further divided into one of three subtypes, epithelial, sarcomatoid or mixed. Among the total spectrum of asbestos patients there are a smaller number of cases with different cancers, such as lung cancer and metastatic cancer of the liver, kidneys, bones and other organs. (m) In addition, sarcomatous varieties have been judged to be extremely aggressive, and are often associated with intracranial metastases – brain tumors.

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Rare malignancies associated with mesothelioma.

In addition to the above, rare kinds of mesothelioma have been identified such as: small cell mesothelioma and lymphohistiocytoid mesothelioma. (c) Due to their rarity, testicular and pericardial mesothelioma could also be classified in this category. As well, in the peritoneal category, there are mesos such as: benign/low grade proliferations, well differentiated papillary tumors, and peritoneal inclusion cysts. (n)

The human genital tracts have also been found to contain adenomatoid tumors, which were originally thought to be endothelial. Recent research has reclassified these as a benign form of mesothelioma. From time to time, such incidental tumors have been discovered in the pleural cavities during lung resections for other reasons. There source and clinical development of these tumors remains unknown.

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Who Gets Meso/Who is At Risk

As explained above, the process of developing mesothelioma from asbestos exposure is a long one. Furthermore, while the development of mesothelioma correlates with asbestos exposure, such exposure isn’t an absolute indicator of who will get the tumor and who won’t. Since there is no national or international mesothelioma registry, statistics for the disease vary widely, depending upon the source. Nevertheless, there is a valid statistical relationship between the amount of exposure to asbestos and the incidence of mesothelioma.

If we contain this discussion to the subject of pleural mesothelioma, we will find that well over fifty years of published studies have established three primary groups of individuals by virtue of their exposure. These are: -1- individuals with high levels of exposure of a short duration, -2- individuals with high levels of exposure of long duration and -3- individuals with low levels of exposure of long duration. (l)

The majority of studies showed that group -1- exposure sometimes led to gradual impairment of lung function but it didn’t always rise to the level of asbestosis, i.e. there was little evidence of plaque or nodules in the pleural space. Group -1- also had a relatively high incidence of cancer, most of which was later to be called mesothelioma.

The second case, -2-, led to very high levels of impairment with asbestosis and early death from from the effects of the impairment. secondary illnesses with some cases of mesothelioma.

The third case -3- led to gradual impairment with asbestosis and death caused by a broad spectrum of secondary conditions such as pneumonia, emphysema, tuberculosis etc. Asbestosis appeared to greatly reduce the patient’s ability to resist secondary diseases, raising some of these to the level of fatal illnesses. (o)

Mesothelioma was not seen as often in groups two and three. Medical researchers felt that this was because patients either didn’t live long enough to develop cancer or weren’t genetically at risk. Ironically, only after dust abatement practices were mandated into the workplace did the incidence of mesothelioma become a significant health issue in the literature and in the vernacular of the medical community, lending credence to the theory about group two.

Studies also revealed a clear relationship between the amount of dust inhaled over a lifetime and the development of asbestosis. Trades with a history of working with asbestos tend to dominate the population of mesothelioma patients. The greater the former, the more likely it would be that signs of asbestosis would be observed. Conversely, it was discovered that there was no safe level of asbestos exposure with respect to mesothelioma, since even short exposures could create the cancer, with or without asbestosis symptoms.

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Symptoms of Meso

The symptoms of mesothelioma are cruel and painful. As the tumor grows and expands, it often produces fluid that fills the chest or the abdomen, depending upon whether it is pleural or peritoneal mesothelioma. This fluid places pressure on vital organs. In the case of pleural mesothelioma, which represents 80% of cases, the fluid compresses the lung, causing intense pain, shortness of breath and overwhelming fatigue. The mesothelioma sufferer cannot sleep comfortably, loses appetite, and endures excruciating pain as the fluid and the expanding tumor slowly fills up the chest, crushing the lung. Relieving the fluid pressure is only short term symptomatic relief. (p)

Pleural mesothelioma patients in five studies presented by P. Chahinian showed the following symptoms in varying degrees:

Dyspnea (shortness of breath) 6-60% of cases
Chest pain 33-71% of cases
Both dyspnea and pain 19-28% of cases
Cough
3-27%
Hemoptysis (spitting blood or bloody sputum) 1-6%
Hoarseness 1-3%
Dysphagia (difficulty swallowing) 1%
Weight Loss
14-29%
Fever
3-33%
Asymptomatic
3-4%
Pleural effusion (fluid in the chest cavity)
74-84%
Pericardial patients reported different clinical symptoms:

Pericardial effusion (fluid in the pericardial space)
Dyspnea
Pain
Constrictive pericarditis (inflammation of the pericardial sac)
Vascular compression
Cardiac tamponade (bleeding into the pericardium)
Pericardial thickening on scans (12% of patients only)
Peritoneal patients present another set of symptoms again:

Abdominal pain
63%
Abdominal mass
40%
Increased abdominal girth
70%
Ascites (fluid in the abdomen)
66%
Digestive disturbances
33%
Fever
20%
Weight loss
44%
Thrombocytosis (increased platelets in the peripheral blood)
23%
Leukocytosis (elevated white blood cell count)
50%

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Disease Development And Progression

The latency of mesothelioma has been one of its greatest problems and may partly explain why a connection with asbestos exposure took so long to be accepted as the primary cause. Mesothelioma latency isn’t known exactly since exposure to asbestos doesn’t always equate directly or immediately to an insult to the tissues. Consequently, estimates of latency vary widely with mesothelioma patients being reported in age ranges from early teens to octogenarians. The accepted figure falls somewhere between 15 and 50 years from the date of exposure to asbestos although it’s anyone’s guess as to when the asbestos first triggered the cellular damage that translated into mesothelioma.

Since symptoms are often misdiagnosed or even absent during early stage mesothelioma, the rate of progression of the disease is also a guess. The most commonly available figures pertain to median survival time from the date of diagnosis but many mesothelioma experts believe the tumor may be in existence for quite some time before diagnosis.

Even survival times vary widely with no clear consensus emerging. On the low side, survival times of 4 to 8 months are reflected in the information to be gleaned from obituaries and tributes paid to the afflicted. On the high side, 12 to 18 months is considered the norm, although this number is demonstrating some upward movement and tends to become differentiated when mesothelioma types, categories and treatments are considered as part of the assessment.

Of the three subtypes, epithelial, mixed type, or sarcomatous, the latter two have by far the worst prognosis for survival. Patient groups of sarcomatous subtype, or those with lymph node involvement, tend to have no long term survivors. Two year survival rates for these groups are 0% and median survival time is only 5.5 months. Epithelial cases without lymph node involvement, and who are younger than 50, have the best chance for long term survival. Median survival numbers for this group are trending up, and vary based on the type of treatment chosen.

Mesothelioma patients of all subtypes rarely survive long enough for medical science to establish conclusively whether or not mesothelioma actively metastasizes or not. As median survival times lengthen, we may find that mesothelioma is no different from other cancers in this respect.

In pleural mesothelioma, the tumor tends to appear only in one lung, with a right/left preference of 60% to 40%. Pleural mesothelioma occurs about four times more frequently than peritoneal, with peritoneal being on the decline and pleural on the upswing. Men are five times more likely than women to get pleural mesothelioma and both sexes are equally represented with peritoneal.

As of this time, there are no medical procedures that are proven to be curative. Most of the leading treatments (covered under the treatment section of this web site) involve experimental procedures, clinical trials of drugs and novel technologies.

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Diagnosis

Diagnosis of mesothelioma is difficult because the disease often isn’t visible on external scans and the symptoms may be confused with a number of common ailments that misdirect the medical staff and defer more thorough investigations. Once mesothelioma is suspected, a definitive diagnosis requires a tissue biopsy, a complicated, somewhat risky and expensive process.

The process of diagnosis usually begins with some form of radiological investigation. In pleural cases, where respiratory distress is the primary symptom, doctors may fall back on an x-ray to check for pneumonia or shadows on the lung indicative of tuberculosis or lung cancer. It is during this stage that fluid in the pleural cavity is first detected and invasive investigations first begin.

Other external examinations offer greater resolution and accuracy than X-Rays. The primary vehicle for external radiological examination is the Computed Tomography scan or CT examination. Computed tomography involves a series of precisely calibrated X-rays to be taken and received by electronic means rather than photographic film. These images are then reconstructed by computer to offer a highly detailed view of the body in narrow slices, allowing a look inside the body at anatomical details not otherwise visible without surgical examination.

Figure H: PET/CT Fusion showing combined images. The red cross in the human image shows hot spot. The slices show (from left to right) CT scan, PET scan and Combined fusion scan. Click here for enlargement. Photo courtesy K. Brauch.

CT scans are excellent at showing topography but cannot distinguish between scar tissue or tumor. While they can detect pleural or peritoneal thickening, the results aren’t usually definitive enough to allow for a mesothelioma diagnosis with CT scan alone.

Another tool of importance in external exams is the Positron Emission Tomography scanner, or PET. PET is a process where radioactive glucose is injected into the bloodstream, where it is consumed in the greatest proportion by the most active parts of the body. This usually means the brain, heart, sex organs and tumors, if present, will consume the largest amount of this isotope, causing hot spots to appear on a scanned image of the body.

Tumors tend to be extremely active and therefore consume large amounts of the sugar isotope. This will cause hot spots to appear where they normally shouldn’t, allowing the radiologist to identify possible indications of cancer.

Although PET scans can show activity, they are rather indistinct and cannot clearly identify the exact location of the activity. Simply put, CT scans can tell where a growth is located and PET scans can tell if there is excessive biological activity. The latest technology combines both the CT scan and the PET scan into a single computer image. Therefore, taken together, the PET/CT fusion scan produces a much more accurate image of activities inside the body. If an area of thickening is actively consuming sugar it may be cancerous. If the activity level is low or normal, it may simply be inflammatory response to injury, healing or other benign activity.

Figure I: PET/CT slice showing tiny central hot spot and presence of EPP (removed lung) in left of image. For Enlargement click here. Photo courtesy K. Brauch
Magnetic Resonance Imaging (MRI) and Ultrasound are both soft tissue scanning tools that are generally little used in diagnosing mesothelioma. MRI is sometimes used to determine if mesothelioma has penetrated through the diaphragm into the abdomen. In most cases, the images are considered too indistinct to be of much clinical value. Ultrasound simply doesn’t penetrate deeply enough to be a good clinical tool in this setting. Despite the progress, such external tests aren’t yet definitive enough to allow diagnosis without biopsy. Even if a tumor is detected, it must be examined by a pathologist to determine what kind of tumor it is and whether it is mesothelioma or some other type of cancer.

One of the first physical examinations to be conducted is the examination of fluid from the chest or abdomen. Fluid extractions from the chest via needle (thoracentesis) are performed for two reasons, to relieve the buildup of fluid and to provide a sample for a cytological examination. Unfortunately, examinations of the pleural effusion or abdominal ascites are only rarely conclusive. The sample would have to contain discarded tumor cells, something that would take luck to find. A diagnosis of mesothelioma can only be made from pleural fluid in about 33% of cases, so a definitive diagnosis is difficult without invasive surgery and a tissue biopsy.

Needle biopsies are also poor indicators since the mesothelioma tumor can be quite diffuse and thin. Hitting a tumor nodule with the biopsy needle from outside of the chest requires luck as well as skill. The principle means of obtaining a pathology specimen is through surgery and in most cases this involves video assisted surgery. For pleural mesos the surgery itself is called a thoracotomy (chest incision) followed by a thoracoscopy (fiber optic exam of the chest). For abdominal biopsies the surgery is called a laparotomy and laparoscopy (fiber optic exam of the abdomen). These procedures are in themselves difficult surgeries that are only offered in the event a serious illness is suspected. Since the symptoms of mesothelioma are often confused with other, more benign, illnesses, many people either don’t receive them or receive them only after long delays, affecting the prognosis of their cancer.

In an attempt to improve diagnosis of lymph node involvement, some institutions will require a mediastinoscopy to biopsy the lymph nodes in the chest. This procedure is day surgery and a finding of positive lymph nodes might influence a decision not to offer surgery since the surgical staging would be at least stage 3.

Diagnostic examinations may or may not involve rudimentary treatment attempts. In pleural cases, many surgeons opt to perform a pleurodesis (scraping of the tumor) procedure and the injection of abrasive material, like talc, for example. The purpose of this is to irritate the site and stimulate the formation of scar tissue which will enclose the tumor and prevent further weeping of fluid into the body cavity. If the fluid accumulation isn’t stopped, it leads to secondary problems such as compression of the lung, compression of key blood vessels and arteries. Untreated, the fluid accumulation may lead to serious and life threatening complications long before the tumor itself is fatal.

After the thoracotomy, the surgeon will temporarily install a tube, placed in the opening and sewn air-tight to the skin, to allow the remaining fluid and blood from the surgery to drain. This tube may also be used longer term in patients who are receiving chemotherapy and require long term management of the effusion as an alternative to repeated thoracentesis procedures.

In late 2004, a serum test for mesothelioma was released by Fujirebio Diagnostics in Australia and Europe called Mesomarkâ„¢. This blood test checks for elevated levels of a blood serum marker called Serum Mesothelin Related Protein (SMRP) and with further validation and refinement, this test may prove to be a viable alternative method for identifying the presence of mesothelioma. SMRP was the subject of a Meso Foundation grant to investigate its validity in a study of the residents of Libby Montana. (See Meso Foundation press release and press release about European distribution of the test.) Mesomark is not yet available in the United States or Canada.

In the spring of 2005, a research article in the New England Journal of Medicine touted the discovery of another possible mesothelioma serum marker called Osteopontin. Researcher Dr. Harvey Pass felt that the two markers might be complementary to each other and assist with the future diagnosis of mesothelioma. Serum tests will be valuable for allowing non-intrusive tracking of residual tumor or monitoring for recurrence in patients who have been treated for the disease.

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Staging And Outcomes

Assuming a diagnosis of mesothelioma is confirmed, staging of the disease remains extremely difficult and is an obstacle to effective treatment. Staging techniques require knowledge about where the tumor is located, how extensive it is and whether it is still locally contained or whether it has metastasized to organs or adjacent tissues.

Since staging is essential to selecting the appropriate treatment, much effort has been invested in developing an accurate pre-operative staging technique. Because of the difficulty of imaging the extent of mesothelioma and its presence or absence in the lymph nodes, staging pre-operatively remains a fairly imprecise process. Several recent attempts have been made to establish a standard process. (t)

Both the International Mesothelioma Interest Group and Brigham & Women’s Hospital have developed staging systems based upon a common set of variables. These are:

T or tumor staging - what is the size and location of the tumor in relation to nearby organs and structures?
N or nodal staging - are lymph nodes positive or negative for meso?
M or metastatic staging - is there evidence of metastasis?
Each variable above is expressed as a number and the final combination is compared to a table to establish staging. Negative nodes and metastasis is represented as N0 and M0 Regardless of the staging system used, patients with stage 3 or higher disease are almost always only considered for chemotherapy. This is because stage 3 implies that the tumor is no longer locally contained and cannot be removed (resected) by surgical means.

Recent studies with genomics have added an additional set of considerations to outcome. An assay of the markers of genetic damage in a population of patients seems to co-relate certain genotypes to a better prognosis or outcome. While most of this material is just now being published, it may soon be possible to examine mesothelioma cells for DNA markers that can forecast whether the patient would benefit from aggressive surgical treatment or not.

Stage 1 and 2 patients tend to be surgical candidates, while stage 3 and stage 4 patients are generally offered chemotherapy in combination therapies. (q) (r) (s) Radiation is rarely offered as a primary treatment since it has little effect on its own. Staging, therefore, has a pivotal role in choosing treatment options and determining the prognosis for mesothelioma patients. Treatment options and outcomes are discussed in detail under the treatment section of this web site.

In the twentieth century, asbestos was called the “miracle fiber” (b) and found its way into thousands of household and industrial products.

Figure A: Chrysotile Asbestos, The most common form. Photo: New York State department of Environmental Conservation

Such widespread exposure to the natural material has injured generations of workers and created a mountain of litigation that has driven numerous American companies to seek refuge in Chapter 11 bankruptcy. The media has only recently begun to cover the subject of asbestos and its medical as well as economic impact. The 2005 indictments of W.R. Grace Executives, for failing to protect their workers and the general public from exposure to asbestos-tainted vermiculite, has succeeded in making asbestos poisoning prime time news.

What Is Asbestos, History of Asbestos Use, Asbestos Hazards, Who Is Exposed?

What is asbestos?

Asbestos is usually thought of as a single mineral, or at least a family of mineralsthat is well defined and universally recognized. This is false. In fact, “asbestos” was a label created by the need to describe a group of six commercially available mineral fibers, namely actinolite, amosite, anthophyllite, chrysotile, crocidolite and tremolite (z) in litigation.

Figure B: Amosite Asbestos, The second most common type. Photo: New York State department of Environmental Conservation

The need for the catch-all “asbestos” became apparent when exposure to the fiber and its many products proved hazardous. Lawsuits by the first wave of injured workers led to the creation of an “approved list” of mineral specimens by the EPA, negotiated by the government, asbestos manufacturers, and lawyers representing the injured. It was and it remains an economic and political term, not a scientific one. (e)

Figure C: Tremolite Asbestos, Photo: New York State department of Environmental Conservation

As a result, the term asbestos doesn’t include all the possible fibrous mineral forms of impure magnesium silicate that behave like asbestos. Many of these could be considered just as carcinogenic, if not more so. Examples abound; there are Taconite mines in the United States, and while Taconite isn’t on the asbestos list, its carcinogenic track record certainly qualifies it as a health hazard.

Erionite is another fiber that is missing from the list and was recently identified as a particularly toxic asbestiform fiber. Erionite was found in the home building materials used in Turkish villages of Karain and Tuzkoy. It has been implicated in the deaths of hundreds of villagers over the years. (f) It is no longer disputed that Erionite causes mesothelioma and belongs on the registry of asbestos-like minerals. (ac) Deposits of Erionite have been found in San Bernardino County, California and it may well be found elsewhere in the world.

There are two basic forms of asbestos fibers: amphiboles, which are straight needle-like fibers, and serpentine asbestos, which consists of curled and more pliable fibers. Early studies seemed to indicate that only amphiboles caused cancer and there was a vigorous debate concerning conflicting studies as to whether Chrysotile asbestos was carcinogenic.
Recent research has proven that Chrysotile fibers do cause mesothelioma but but that Tremolite and Crocidolite are even more potent.

Figure D: Crocidolite Asbestos, Photo: New York State department of Environmental Conservation

The list of cancer-causing mineral fibers that should be classified as asbestos is still growing. Banning just those fibers known today as asbestos would resolve only a fraction of the problem. The continuing issue of exposure to asbestos-like materials and their health hazards is unlikely to go away in the foreseeable future.

What Is Asbestos, History of Asbestos Use, Asbestos Hazards, Who Is Exposed?

History of Asbestos Use

Marco Polo encountered asbestos in China where it was called salamander’s wool. The ancients had many names for asbestos, calling it “mountain leather,” “incombustible linen,” “rock floss,” and “lapis asbestos”. Defined by its uses, the strange material could be braided into rope or used as insulation. The use of oil lamps for illumination was a major application before the invention of the incandescent light bulb. Once braided, asbestos could be turned into a wick that was both indestructible and cheap. Charlemagne had a napkin made from asbestos that he would purify by throwing into a fire.

At the dawning of the industrial age, machinery, steam, and fire became catalysts for the more widespread use of asbestos. By the 1860’s asbestos began appearing as insulation in the United States and Canada. Thousands of different uses appeared by the middle of the 20th century. These included fire retardant coatings, concrete, bricks, pipes and fireplace cement, heat, fire, and acid resistant gaskets, pipe insulation, ceiling insulation, fireproof drywall, flooring, roofing, lawn furniture, drywall joint compound and on and on. Its widespread use caused an avalanche of mesothelioma cases that continues to this day.
(y)

What Is Asbestos, History of Asbestos Use, Asbestos Hazards, Who Is Exposed?

The Hazards of Asbestos

For all its wonderful properties, asbestos was also recognized early on as the cause of respiratory diseases. The Roman historian Pliny the Elder noted that the slaves who worked in the asbestos mines were less healthy than other slaves. (g) He recommended that such slaves not be purchased since they would “die young”.

Pliny the Elder wasn’t the only sage to notice that asbestos wasn’t mother’s milk. Strabo, a 1st century geographer, also observed the rise of health problems among asbestos workers. Since it was noted that asbestos exposure caused primarily a respiratory disease, Pliny the Elder suggested the use of a respirator made of transparent bladder skin to protect workers from asbestos dust. (i)

Modern medicine first documented an asbestos-related death in 1906. Insurance companies began to cut their coverage of asbestos workers. Soon, medical reports began to identify a mystery tumor. The term mesothelioma entered the medical literature in 1931 when it was identified Klemperer and Rabin, and by the 1940’s it was being associated with asbestos exposure. Still, at the urging of industry, public authorities and the medical establishment continued to resist recognizing the connection between mesothelioma and asbestos. Finally, the link became incontrovertible with a 1960 article published in Lancet entitled “Primary Malignant Mesothelioma of the Pleura.”

During this time, the growing awareness of the connection between asbestos exposure and asbestosis and mesothelioma eventually brought some government regulation. (Contrary to popular belief, to this day asbestos has not been banned in the U.S., though it has in numerous other countries.) It also brought litigation. During trial discovery proceedings it became clear that the asbestos industry had known about the hazards of the product for decades. Moreover, they had conspired to hide the facts from both their workers and the consumers of their products. This disregard for the health and safety of both employees and consumers led to thousands of successful lawsuits and settlements against asbestos vendors. Over time this led to over sixty companies seeking refuge in Chapter 11 bankruptcy protection.

What Is Asbestos, History of Asbestos Use, Asbestos Hazards, Who Is Exposed?

Who Is Exposed?

Exposure to asbestos is much more common than believed. However, certain industries and workers are much more likely to be occupationally exposed to asbestos.

Due to its properties of heat resistance and impermeability, asbestos use tended to focus heavily in the mechanical, construction and ship building industries. The construction business has the largest number of trades involved with past exposure or current exposure to legacy asbestos. These include the following trades: plumbers, electricians, roofers, pipe fitters, sheet metal workers, masons, carpenters, drywallers, painters, tile setters, plasterers, insulators, joiners and common laborers.

The shipbuilding industry and the navy, which used the ships, are where most military personnel were exposed. Trades here include: steamfitters, ironworkers, welders, boilermakers, ship fitters, machinists, electricians, millwrights and operating engineers.

The above is hardly an exhaustive list and effectively illustrates the scale of the problem. Hardest to accept is the fact that no level of exposure is deemed safe when dealing with asbestos and consequently a significant cadre of patients has appeared in the category of secondary or stealth exposure. Examples here are family members of asbestos workers, who were exposed through contact with contaminated clothing or tools brought home from work. The general laborer category fails to adequately identify those casual, summer, or part-time workers who assisted the principal trades. They would be cleaning up work sites, removing debris or doing light, unskilled labor in a contaminated environment. This often took place without adequate or even any protective equipment.

A substantial number of white collar workers who work in contaminated office spaces, schools or businesses have also developed mesothelioma. This group includes teachers and other office workers not associated with industrial or work-related asbestos exposure.

The stealth element comes from the lack of understanding of where and why asbestos was used in construction. Many of the buildings containing asbestos remain standing today. Since 2000, many cases of stealth exposure have been in the news. As an example, school workers in Texas were exposed while re-glazing school windows where asbestos laced putty had been used. In this case, not only the workers but students and teachers using those class rooms were exposed to asbestos dust and debris without any protection whatsoever.

New sources of exposure are being identified constantly, such as environmental exposure. In certain areas of the world, asbestos occurs naturally and can be found on the surface where it is easily disturbed. Examples of problems are the growing expansion of the population and new housing development that has followed. Sometimes this has encroached upon heavily asbestos contaminated soils, potentially exposing the future residents to long term, low level amounts of asbestos.

The tainted vermiculite problem is another issue where millions of homes have been insulated with vermiculite filler that will release asbestos when disturbed. Home renovations, new wiring or furnace repairs may all cause unwitting workers to release clouds of asbestos dust that will expose both themselves and the building occupants to danger.

In summary, not only blue collar trades are at risk from asbestos induced mesothelioma. Many people in “safe” occupations and individuals who do not believe themselves to be at risk may well be on track to developing this tumor in the future. Even once asbestos is someday banned in the U.S., all the individuals who have already been exposed, and all those who will continue to be exposed to the asbestos already present in our environment, will remain at risk for mesothelioma’s suffering and death unless effective treatments are developed now.

Groups representing international labor are making a global asbestos ban atop priority of this year’s activities on International Workers’ Memorial Day (April 28). The Building and Wood Workers International (BWI) are mobilizing their members throughout the world to “engage in peaceful demonstrations and petitions at Canadian Embassies and Consulates to convince the Canadian government to call a halt to its aggressive marketing and promotion of asbestos in developing countries such as India, Zimbabwe and Brazil.” In a recent press release, BWI General Secretary Anita Normark said:

“Today’s exposures guarantee an epidemic lasting at least another generation, with the asbestos graveyards shifting from the developed to the developing world.”

This is the most recent action taken by the BWI, a body which has long been committed to a global asbestos ban. Activities by other groups representing labor will help raise awareness of the global asbestos scandal and increase the pressure on the International Labor Organization, the World Health Organization and United Nations to ban its use. Last year, the International Confederation of Free Trade Unions (ICFTU) and the International Metalworkers’ Federation launched major ban asbestos campaigns. On December 10, 2005, the ICFTU’s Executive Board passed a resolution entitled Global Asbestos Ban which called on:

governments and social partners to support “national bans and a global ban of asbestos and the promotion of alternatives…”

the International Labour Organisation to “adopt health-based policies in favour of the elimination of the use of all forms of asbestos and asbestos-containing materials.”

Public Services International (PSI) a global federation with 650 affiliated public sector trade unions representing 20 million workers in 150 countries, is also broadcasting the ban asbestos message at its April 28 events. The United Network International, the International Union of Food, Agricultural, Hotel, Restaurant, Catering, Tobacco & Allied Workers Association and the International Federation of Journalists are also backing the pro-ban campaign.

Support from other sectors of the international community for a worldwide asbestos ban will be forthcoming on April 28. The publication of a petition by Parliamentarians, being circulated by Belgian Senator Alain Destexhe, will be timed to coincide with the day of action. As of now, 100 politicians from Europe, Africa, Asia, Latin America, North America and the Middle East have signed up to the document which states:

“In the spirit of humanity and equality, we declare that each human being has the right to live and work in a healthy environment. It is not acceptable that a substance which is too harmful to be used in the European Union is used in Asia, Africa and Latin America; it is not acceptable for an industrialized country to dump asbestos-contaminated ships in a developing country. A global asbestos ban is the first step in the campaign to rid humanity of the threat it faces from asbestos. As Parliamentarians we will endeavour to lobby national governments, regional and international bodies and work with international labor, NGOs, groups representing asbestos victims and others to secure a global ban. The time for action is now!”

To provide a vehicle for the expression of public outrage at the continuing trade in this deadly substance, another petition is being circulated; it is hoped that asbestos victims, campaigners, medical professionals and concerned individuals will endorse this petition by logging onto the website:

http://www.thepetitionsite.com/takeaction/878671812

I have seen another ADAO video and I really commend their efforts to prevent asbestos exposure, help with treatment, and raise awareness in general.

ADAO Press Release –> Click Here
read testimony at http://help.senate.gov/Hearings/2007_03_01/2007_03_01.html

2007 ASBESTOS AWARENESS DAY

GLOBAL MISSION : The Asbestos Disease Awareness Organization’s 3rd Annual Asbestos Awareness Day Conference will be held on March 31st and April 1st 2007, under the auspices of the Drexel University of Public Health. This conference is made possible with the support and collaborative efforts from the Drexel University of Public Health and the International Ban Asbestos Secretariat (IBAS).

This international conference will provide education and outreach to affected families, employers, employees and scientists throughout the world in as part of the ADAO’s continuing efforts to educate the public about the dangers of asbestos, ban its use and encourage research efforts to improve treatment options. Prominent physicians, scientists, safety and health directors professionals and persons interested in asbestos will present current and up-to-date information regarding the status of asbestos in the United States, Canada and worldwide.

Sessions include:
· Preventing Asbestos Exposure in Homes, Schools, Hospitals and Workplaces;
· Detecting and Treating Asbestos - Related Diseases;
· Asbestos Victim and Family Psychosocial Support.

Visit the new Johns Hopkins Melanoma Program Website

Brittany Lietz of Edgewater, Md., just wanted to look tan for her senior prom. She didn’t count on a life-altering brush with skin cancer. Now Lietz, winner of the 2006 Miss Maryland competition on July 1, is doing everything she can to raise awareness of skin cancer.

When Lietz, 21, was in high school, she bought a white prom dress. To make her fair skin look healthier, she started going to tanning salons “pretty rigorously,” gradually increasing the length of her sessions from eight minutes to 25 minutes. Soon she was “addicted” to tanning, going to the salon four times a week, in addition to lying outside in the sun without using sunscreen.

Within a year, a small mole on her back, located by her bra strap, had started growing.

“My mom really started bugging me about it, saying it didn’t look normal,” says Lietz, who continued to tan. Then “one day I removed the bra and it started to bleed. That’s when I knew it wasn’t normal.”

On April 24, 2005, Lietz visited a local doctor’s office. She was first evaluated by a nurse practitioner and “within five minutes I was scheduled for a biopsy.” The results showed that the brownish-red mole, about three-quarters of an inch in diameter, was borderline stage II melanoma – a form of deadly skin cancer that had spread to the inner layers of the skin.

On May 13, she underwent surgery at Johns Hopkins Kimmel Cancer Center to remove the mole and six lymph nodes in her right arm, leaving a 14-inch scar across her back. Since then, she has had about 20 additional surgeries to remove other precancerous or atypical lesions all over her body, and now sports small scars on the front of her chest, stomach, hips, one knee and her inner thigh near the groin.

“I attribute almost all of it to the tanning beds,” Lietz says, noting that the lesions found on her inner thigh were located “in an area that the sun doesn’t reach unless you’re in a tanning bed with no clothes on.”

The experience changed Lietz’s outlook on life. She is now a nursing student at the University of Maryland who is pursuing a career in pediatric oncology. She goes for regular skin checks at her dermatologist’s office and Johns Hopkins, and participates in a melanoma patient advocacy group at Hopkins. And, as a contestant in the upcoming Miss Maryland competition, she is using skin cancer awareness as her platform.

“I realized there is not a single person out there telling kids about (melanoma),” says Lietz, who is currently Miss Tidewater. When she was younger, she heard warnings from doctors and nurses, but “unfortunately, teenagers don’t listen unless they hear from someone their own age.”

To that end, she has been traveling to high schools around Maryland, speaking to health classes about skin cancer prevention, and the dangers of tanning beds. She tells them about statistics, that one person dies every hour from melanoma, and how it’s the leading cause of death by cancer in people ages 20 to 29. She also goes over common myths.

“Teenagers think (tanning salons) are healthy because if they tan at a tanning bed, they won’t get burned when they go outside, but 30 minutes in a tanning bed is equivalent to 12 and a half hours of sun exposure,” Lietz says.

Some people think it’s genetic, though Lietz says in her family, only her grandmother was affected, with only one mole. And though her fair skin, blond hair and blue eyes put her at “pretty much the highest risk you can be” for melanoma, she makes sure to tell students that people of all skin colors can get cancer.

“I’ve had a very positive response,” she says of her talks. “Some students say they had no idea how horrible the disease is. Some tell me they’re never setting foot in a tanning salon again.”

In late July, Lietz also plans to join the Skin Cancer Foundation at the Pentagon, where organization representatives will screen soldiers returning from Iraq.

The most common type of cancer on the list is non-melanoma skin cancer, with more than 1,000,000 new cases expected in the United States in 2007. Non-melanoma skin cancers represent about half of all cancers diagnosed in this country.

The cancer on the list with the lowest incidence is thyroid cancer. The estimated number of new cases of thyroid cancer for 2007 is 33,550.

Because colon and rectal cancers are often referred to as “colorectal cancers,” these two cancer types were combined for the list. For 2007, the estimated number of new cases of colon cancer is 112,340, and the estimated number of new cases of rectal cancer is 41,420.

Kidney cancers can be divided into two major groups, renal parenchyma cancers and renal pelvis cancers. Approximately 85 percent of kidney cancers develop in the renal parenchyma,2 and nearly all of these cancers are renal cell cancers. The estimated number of new cases of renal cell cancer for 2007 is 43,512.

Leukemia as a cancer type includes acute lymphoblastic (or lymphoid) leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myelogenous (or myeloid) leukemia, and other forms of leukemia. It is estimated that more than 44,000 new cases of leukemia will be diagnosed in the United States in 2007, with chronic lymphocytic leukemia being the most common type (approximately 15,000 new cases).

The following table gives the estimated numbers of new cases and deaths for each common cancer type:

Cancer Type Estimated New Cases Estimated Deaths
Bladder 67,160 13,750
Breast (Female — Male) 178,480 — 2,030 40,460 — 450
Colon and Rectal (Combined) 153,760 52,180
Endometrial 39,080 7,400
Kidney (Renal Cell) Cancer 43,512 10,957
Leukemia (All) 44,240 21,790
Lung (Including Bronchus) 213,380 160,390
Melanoma 59,940 8,110
Non-Hodgkin’s Lymphoma 63,190 18,660
Pancreatic 37,170 33,370
Prostate 218,890 27,050
Skin (Non-melanoma) >1,000,000

Staging is the process of finding out how widespread a cancer is. The stage of a liver cancer is the most important factor in considering treatment options. A staging system is a standardized way for the cancer care team to summarize information about how far a cancer has spread.

The American Joint Committee on Cancer (AJCC) TNM System

A major system used to describe the stages of liver cancer is the American Joint Committee on Cancer (AJCC) TNM system. There are several other systems, however, none is universally accepted

T stands for tumor (its size, whether it is growing into nearby blood vessels, and how far it has spread within the liver and to nearby organs).
N stands for spread to lymph nodes (bean-sized collections of immune system cells that help fight infections and cancers).
M is for metastasis (spread to distant organs).
Using the TNM staging system, information about the tumor, lymph nodes, and metastasis is combined to assign a stage. This process is called stage grouping. The stage is described in Roman numerals from I to IV.

T Stages

T staging takes into account the number of tumors, the size of the tumors, whether the tumors invade blood vessels (vascular invasion), and whether the tumors invade nearby organs.

T1 Single tumor (any size) without vascular invasion (invasion into blood vessels)
T2 Single tumor (any size) with vascular invasion, OR
Multiple tumors where none are greater than 5 cm (about 2 inches) in diameter
T3 Multiple tumors that are greater than 5 cm (about 2 inches) in diameter, OR
A tumor involving a major branch of the portal or hepatic vein(s)
T4 Tumor invading a nearby organ (other than the gallbladder), OR
Tumor invading the visceral peritoneum (covering surrounding the liver)

N Stages

N staging describes whether the cancer has invaded regional (nearby) lymph nodes.

NX Regional lymph nodes cannot be assessed.
N0 The cancer has not spread to the regional lymph nodes.
N1 The cancer has spread to the regional lymph nodes.
M Stages

M staging describes whether the cancer has metastasized (spread) to distant lymph nodes or to other organs in the body. The most common sites of liver cancer spread are the lungs and bones.

Mx Distant spread cannot be assessed.
M0 The cancer has not spread to distant lymph nodes or other organs.
M1 The cancer has spread to distant lymph nodes or other organs.
Stage Grouping

Summary of AJCC Stages

Stage I: T1, N0, M0: The tumor is any size but does not invade blood vessels.

Stage II: T2, N0, M0: There is a single tumor (any size) that does invade blood vessels; or there are several tumors, and all are less than 5 cm (2 inches) in diameter.

Stage IIIA: T3, N0, M0: There are several tumors, and at least one is larger than 5 cm (2 inches) in diameter; or a tumor invades a branch of the major liver blood vessels (portal vein or hepatic vein).

Stage IIIB: T4, N0, M0:A tumor invades a nearby organ (other than the gallbladder); or A tumor has penetrated the outer covering of the liver.

Stage IIIC: Any T, N1, M0: The cancer has invaded nearby lymph nodes. (Tumors can be any size or number.)

Stage IV: Any T, Any N, M1: The cancer has spread to other parts of the body. (Tumors can be any size or number, and nearby lymph nodes may or may not be involved.)

Localized Resectable, Localized Unresectable, and Advanced Liver Cancer

Doctors often classify liver cancers by whether they can or cannot be entirely cut out (resectable) Resectable is the medical term meaning “able to be removed by surgery.” The 5 year survival for patients with resectable early stage cancer is above 50%. This percentage drops for more advanced cancers or with more severe liver disease. Unfortunately, survival continues to drop after diagnosis and treatment so that by 10 years it is half of what it was at 5 years. Part of this may be due to the liver cirrhosis, not the cancer.

Cancers that have not spread beyond the liver but cannot be completely removed by surgery are classified as localized unresectable. There are several reasons that it might not be possible to safely remove a localized liver cancer. If the non-cancerous part of your liver is not healthy (due to cirrhosis, for example), surgery might not leave enough liver tissue behind for it to function properly. Also, curative surgery may not be possible if your cancer is close to the area where the liver meets the main arteries, veins, and bile ducts.

Cancers that have spread throughout most of the liver and/or have spread to lymph nodes or other organs are classified as advanced. Most advanced liver cancers cannot be treated with surgery.

Cirrhosis staging system: Because people with liver cancer often have 2 diseases, cancer and cirrhosis, doctors treating liver cancer need to know the severity of the cirrhosis. To determine this, they use a system called the Child-Pugh score. This system measures several substances in your blood and grades the results as A, B, or C.

One substance is called bilirubin. People with severe liver disease may have high bilirubin levels that cause their skin and the white area of their eyes to turn yellow.

Albumin is another blood protein that is important in evaluating people with cirrhosis. Albumin is made in the liver. A low albumin level suggests that the liver may be very damaged, although there are other medical conditions that can also affect this substance.

The other blood measurement is the prothrombin time. This measures how well the liver is making blood clotting factors. Other considerations in this system are whether there is fluid in the abdomen and whether your mind is functioning normally.

If all these factors are normal, then you are considered class A. Mild abnormalities are considered class B, and severe abnormalities are considered class C. People with liver cancer and class C cirrhosis are generally too sick for any treatment and usually die in a few months.

Signs and Symptoms of Liver Cancer

Although signs and symptoms are usually not present until the late stages of liver cancer, sometimes they may show up early and lead to an early diagnosis. Many signs and symptoms of liver cancer are relatively nonspecific – that is, they can be caused by other cancers or by non-cancerous diseases. Still, if you have any of the following problems, please see a doctor right away:

unexplained, unintentional weight loss
anorexia (persistent lack of appetite)
early satiety (feeling very full after a small meal)
liver enlargement or a mass that can be felt in the area of the liver (the upper right side of the abdomen)
persistent abdominal (stomach area) pain
increasing abdominal swelling
jaundice (yellow-green coloration of the skin and eyes)
deterioration in your condition if you have chronic hepatitis or cirrhosis
Some liver tumors produce hormones that act on organs other than the liver. These hormones may cause hypercalcemia (high blood calcium levels), hypoglycemia (low blood sugar levels), or gynecomastia (enlargement of the breasts in men). High calcium levels can lead to weakness, and low blood sugar levels can cause fainting and even coma. These unusual findings may cause doctors to suspect a disease of the nervous system or an endocrine (hormone-producing) gland, rather than a liver cancer.

If you have one or more of these symptoms, doctors will use further methods to find out if the disease is really present or to determine if there may be another cause.

History and Physical Exam

The doctor will take your complete medical history (medical interview) to check for risk factors and symptoms. Then the doctor will examine you to look for signs of liver cancer and other health problems. He or she will pay special attention to your abdomen.

Imaging Tests

Ultrasound: This is described in the section Can Liver Cancer Be found Early?

Computed tomography (CT): The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture as does a conventional x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine will take pictures of multiple slices of the part of your body that is being studied. This test is very useful in identifying many types of liver tumors. Often after the first set of pictures is taken you will receive an intravenous injection of a radiocontrast agent, or special dye that helps better outline structures in your body. A second set of pictures will then be taken. The injection can cause some flushing. Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Please be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays and you need to lie still on a table while they are being done. You might feel a bit confined by the machine you have to lie in while the pictures are being taken. But just like other computerized devices, they are getting faster, and your stay might be pleasantly short.

Magnetic resonance imaging (MRI): MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the tissues of the body and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. A contrast material might be injected just as with CT scans. MRI scans are very helpful in looking at liver cancers. Sometimes they can tell a benign tumor from a malignant one.

MRI scans may be a little more uncomfortable than CT scans. First, they take longer – often up to an hour. Also, you may be placed inside a large cylindrical tube, which is confining and can upset people with a fear of enclosed spaces. Finally, the machine makes a thumping noise that you may find disturbing. Some places will provide headphones with music to block this out. Importantly, the benefit of the test outweighs any discomfort.

Angiography: Angiography is an x-ray procedure for examining blood vessels. Contrast medium, or dye, is injected into an artery before x-ray images are taken. The contrast medium outlines the blood vessels on x-ray pictures. Angiography is useful in showing the arteries that supply blood to a liver cancer. This information can help surgeons decide whether a cancer can be removed and if so provides help in planning the operation. Digital subtraction angiography uses computers to produce more detailed images of blood vessels. Dynamic sequential CT scanning combines CT scanning and angiography. It is not routinely used but is sometimes helpful in planning surgery.

This can be an uncomfortable procedure because the radiologist who performs the procedure has to put a tiny catheter into the artery leading to the liver. Usually the catheter is put into an artery in your groin and threaded up into the liver artery. Then the dye is injected quickly to outline all the vessels while the x-rays are being taken. Usually, a local anesthetic is used.

For more information on these imaging procedures, see the American Cancer Society document “Imaging (Radiology) Tests.”

Other Procedures

Laparoscopy: This procedure uses a thin, lighted tube connected to a video monitor which allows a doctor to look at the liver and other internal organs. The tube is inserted through a small incision in the front of the abdomen. Laparoscopy provides a view of organs, which can help in planning surgery or other treatments. Doctors can also use small instruments through this tube to remove small tissue samples to examine under the microscope.

Laparoscopy is usually done at an outpatient center but it is like an operation. You will be sedated (made sleepy), just as for any operation. Because the surgeon only makes a small incision to insert the tubes, there is not much pain after surgery. You should be able to go home after you recover from the anesthesia.

Biopsy: In most cases, the only way to be certain that liver cancer is present is to take a biopsy (sample of the tumor tissue) and examine it under a microscope. However, if imaging studies (CT or MRI) show a tumor mass that is likely cancerous and a blood test reveals the AFP level is very high, a biopsy may not be necessary.

There are several biopsy methods used to take samples of liver tissue. An incisional biopsy (removing a piece of the tumor) or an excisional biopsy (removing the entire tumor with a margin of surrounding normal liver tissue) can be done during a surgical operation. However, since doctors usually prefer to know the exact type of tumor before surgery, other types of biopsy methods are often used.

If the tumor is very large or has spread throughout the liver, a needle can be placed through the skin in the abdomen and anywhere into the liver. Tumor cells can then be sucked into the needle with a syringe. If the tumor is smaller, the doctor will use ultrasonography or CT scanning to guide the needle. With this approach, the doctor slowly advances the needle while its position is checked by one of these imaging tests. When the images show that the needle is in the tumor, a sample is removed and sent to the lab to be looked at under a microscope.

When a biopsy is done, the skin where the needle is placed is first numbed with local anesthesia. The only hard part of this procedure is lying still while the needle is advanced.

Biopsy specimens can also be taken during laparoscopy. This allows the doctor to see the surface of the liver and take samples of abnormal-appearing areas.

Alpha-fetoprotein (AFP) blood test: This is described in the section Can Liver Cancer be Found Early?.

Other blood tests: Because liver cancer often develops in damaged livers, doctors need to know the condition of your liver before proceeding with treatment. A series of tests can be done on your blood. These liver function tests (LFTs) can evaluate the condition of your liver tissue not affected by the cancer. Since the doctor may need to remove a good part of your liver, you may not be able to have curative surgery if your liver is not healthy. This is a common problem in people with liver cancer.

The liver also makes proteins that help blood to clot when you are bleeding. A damaged liver may not make enough of these clotting factors, which could increase your risk of bleeding. Your doctor may order blood tests, such as a prothrombin time (PT), to assess this risk.

If liver cancer has not yet been diagnosed, your doctor may also order other blood tests, such as tests for hepatitis B and C. Results indicating you have been infected with either of these viruses may make it more likely that liver cancer is present.

Because signs and symptoms do not usually appear until the cancer is in its later stages, liver cancer is seldom diagnosed early. Small liver tumors are hard to detect by physical examination because most of the liver is covered by the right rib cage. By the time a tumor can be felt, it may already be quite large. But if a person is known to have cirrhosis, whatever the cause, most doctors recommend screening every 6 months with tests of alpha-fetoprotein and ultrasound. However, there are no studies showing that this will result in a higher cure rate.

Alpha-fetoprotein (AFP) is a protein that is normally present in high concentrations in the blood of fetuses but disappears shortly after birth. If it is found in the blood of adults it suggests they may have liver cancer. AFP is also found in certain other cancers such as testicular and gestation trophoblastic neoplasms. It can be found in the blood of pregnant women if the placenta has become damaged.

Tests for AFP are used to look for early tumors in people at high risk for liver cancer. However, the AFP blood test is not recommended for routine screening for liver cancer in people at average risk because, unfortunately, there are potential problems with using it:

Some tumors do not produce much of this protein. Often by the time AFP is elevated, the tumor is too large to be removed or it has spread outside the liver. Some noncancerous liver diseases can also raise AFP levels.

In areas where hepatocellular cancer is very common, use of the AFP blood test for hepatocellular cancer screening has resulted in the detection of many tumors at an earlier stage. Still, many experts feel that AFP testing isn’t sensitive enough for people living in the United States and Europe, and recommend ultrasound (see below) as the main test, although the AFP level may also be measured.

Many patients who develop liver cancer have long-standing cirrhosis (scar tissue formation due to liver cell damage). If a patient with cirrhosis gets worse for no apparent reason, doctors should suspect that liver cancer may be the cause and do appropriate tests.

Ultrasonography (ultrasound) is a test that uses sound waves and their echoes to produce a picture of internal organs or masses. A small instrument called a transducer emits sound waves and picks up the echoes as they bounce off the organs. The sound wave echoes are converted by a computer into an image that is displayed on a computer screen.

This is a very easy procedure. It uses no radiation which is why it is often used to look at developing fetuses. When you have an ultrasound examination, you simply lie on a table and a technician moves the transducer over the part of your body being examined. Usually, the skin is first lubricated with oil. This test may be done before a biopsy to see if the lump is a cyst and is probably benign or is solid and more likely a tumor. This test is also used in people with certain hepatocellular cancer risk factors to help find cancers earlier. Many experts recommend that the test be done every 6 months. But no one knows for certain what the right screening interval should be.

Who should be screened? There are widely accepted rules. People infected with hepatitis B or C and who have cirrhosis is one group. Usually screening will begin at between the ages of 40 and 50. If a person has HIV infection, along with hepatitis B or C, the risk of cancer is higher and he or she should be screened. Another group is people with cirrhosis from other causes. In particular, if a person’s cirrhosis is so severe that he or she is waiting to receive a liver transplant, he or she should be screened. Otherwise a cancer may develop during the wait and become so advanced that it is incurable. The development of a cancer will also move the person up on the transplant waiting list.

Many liver cancers can be prevented by public health measures that reduce exposure to known risk factors for this disease.

Worldwide, the most significant risk factor is infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). A vaccine can prevent hepatitis B infection. All children, as well as adults at high risk (health care workers, those whose behaviors may put them at risk, etc.), should be vaccinated against hepatitis B virus to prevent this infection and to reduce the risk of liver cancer and liver damage from hepatitis.

There is no vaccine for hepatitis C. Therefore, preventing HCV infection and HBV infection in people who have not been immunized is based on understanding the ways these viruses spread. These viruses are spread through blood transfusions, by contaminated needles of intravenous drug abusers, and by unprotected sexual intercourse. Also, mothers who are hepatitis virus carriers can pass the virus to their children at birth or in early infancy. Blood banks in the United States routinely perform tests to identify donated blood infected with these viruses. All infected blood is discarded. People at high risk for hepatitis C should be tested to see if they have this infection so they can be carefully watched for the development of liver disease.

New drugs have been developed to treat hepatitis B and C. In the past, the drug most commonly used was interferon. Doctors have found that interferon may prevent the development of liver cancer in people who have hepatitis C infection. Recently, interferon has been combined with a drug called ribavirin to treat people with hepatitis C. Because this combination (known as Rebetron) is more successful in slowing the infection than interferon alone, it may be even more successful in preventing the development of liver cancer, although it is too early to know. Also, a new form of interferon called peginterferon seems to be even more effective. One problem is that interferon in either form carries side effects such as severe fatigue and depression and can be difficult to take.

It is not certain whether interferon is as helpful in people with hepatitis B infection. But a new drug called lamivudine (Epivir-HBV) has proven successful in treating people with hepatitis B. Not only does it stop the worsening of liver function, it also reduces the risk of liver cancer. A newer drug, adefovir dipivoxil (Hepsera), is also used to treat chronic hepatitis B. It appears as least as effective as lamivudine and may be used first or if lamivudine doesnÂ’t work. Although it has been shown to reduce liver damage, its effect on the risk of liver cancer is unknown at this time.

If you have hepatitis B or C you should talk to your doctor about these treatments.

In the US, alcohol abuse remains a major cause of the cirrhosis that can lead to liver cancer. However, prevention of liver cancers associated with alcohol abuse remains a challenge. Quitting smoking may also slightly lower the risk of liver cancer, as well as lowering the risk for many other life-threatening diseases.

Changing the way certain grains are stored in tropical and subtropical countries could reduce exposure to cancer-causing substances such as aflatoxins. Many industrialized countries already have regulations to prevent and monitor grain contamination.

Most industrialized countries have regulations to protect consumers and workers from known carcinogens (cancer-causing chemicals). These regulations have essentially eliminated certain chemicals as a cause of liver cancer. The US Environmental Protection Agency (EPA) recently lowered the allowable level of arsenic in drinking water in the United States, which should help to reduce exposure. But this may continue to be a problem in areas of the world where naturally occurring arsenic commonly gets into drinking water.

Certain inherited diseases can cause cirrhosis of the liver, increasing the risk of liver cancer. Finding and treating these diseases early could lower this risk. For example, all children in families where there is hemochromatosis are screened for the disease and treated if they have it. Treatment consists of lowering their iron intake and removing small amounts of blood to use up the bodyÂ’s supply of iron.

Although several risk factors for hepatocellular cancer are known, the exact way in which these factors cause normal liver cells to become cancerous is only partially understood. Scientists believe that cancers first develop when damage to the DNA of the cells occurs. DNA contains the instructions for nearly every chemical process in our bodies. Some of these instructions help cells to grow at a proper rate. If these instructions are altered, the cells may grow out of control and form a tumor. Fortunately, our cells have the ability to repair our DNA, so most DNA damage does not cause cancer.

Certain chemicals that cause liver cancer, such as aflatoxins, are known to damage the DNA in liver cells. Recent studies have shown that aflatoxins can damage the p53 gene, which normally works to prevent cells from growing too much. Damage to p53 DNA can lead to increased growth of abnormal cells and formation of cancers.

Infection of liver cells with hepatitis viruses can also cause DNA damage. These viruses have their own DNA, which carries instructions on how to infect cells and produce more viruses. In some patients this viral DNA can insert itself into a liver cell’s DNA, where it may affect the cellÂ’s genes. But scientists still donÂ’t know exactly how this leads to cancer.

Although scientists are beginning to understand this process, much more must be learned. It is hoped that a more complete understanding will help develop ways to better prevent and treat liver cancers.

A risk factor is anything that increases your chance of getting a disease, such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers in several organs. But having a risk factor, or even several risk factors, does not mean that you will get the disease. Scientists have found several risk factors that make a person more likely to develop hepatocellular carcinoma.

Gender

Hepatocellular carcinoma is about 3 times more common in males than in females, although much of this is likely due to differences in behaviors affecting the risk factors described below. Fibrolamellar HCC occurs in about equal numbers in both sexes.

Certain Types of Chronic Viral Hepatitis

Chronic (long-term) infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is an important liver cancer risk factor. These infections lead to cirrhosis of the liver (see below) and are responsible for making liver cancer the most common cancer in many parts of the world. In the United States, infection with hepatitis C is the most common cause of hepatocellular cancer, while in Asia and developing countries, hepatitis B is more common. People infected with both viruses have a very high risk of developing chronic hepatitis, cirrhosis and liver cancer. In the United States, hepatitis C infection is responsible for about 50% to 60% of all liver cancers. Hepatitis B is responsible for another 20% and alcoholic cirrhosis also causes another 10% to 20% of liver cancers.

Both of these viruses are transmitted through the blood. Most often this occurs as the result of needle sharing in intravenous drug users. Transmission through blood transfusion is extremely rare in the United States. Another source of infection is having unprotected sex with an infected person. In developing countries, children contract hepatitis B infection from prolonged contact with family members who are infected. These viruses can also be transmitted from mother to fetus.

People with hepatitis A infection do not develop chronic hepatitis, do not develop cirrhosis, and have no increased risk of liver cancer.

Cirrhosis

Cirrhosis is the result of scar tissue formation in the liver. This can lead to cancer. Most liver cirrhosis in the United States occurs in people who abuse alcohol. Hepatitis B and C are also major causes of cirrhosis. But people with hepatitis B can develop liver cancer even if they don’t develop cirrhosis. There is also a disease called biliary cirrhosis that increases the risk of liver cancer.

Having too much iron in the liver also can lead to cirrhosis. This happens most often in the United States in people with a hereditary disease (called hemochromatosis) that causes them to absorb too much iron from the food they eat.

Tobacco Use

Several studies have found a link between smoking and liver cancer, although the extent of this link is not known. The association may be stronger among those who also abuse alcohol.

Inherited Metabolic Diseases

Certain inherited metabolic diseases can also lead to cirrhosis. People with hemochromatosis, as mentioned above, absorb too much iron from their food. They are more likely to develop cirrhosis because of the high levels of iron in their liver. Other rare diseases that increase the risk of liver cancer include tyrosinemia, alpha1-antitrypsin deficiency, porphyria cutanea tarda, and WilsonÂ’s disease.

Diabetes

Diabetes can also increase the risk of liver cancer, usually in patients who have other risk factors such as heavy alcohol consumption and/or chronic hepatitis.

Obesity

Obesity increases the risk of developing liver cancer, probably because it can result in fatty liver disease and cirrhosis.

Aflatoxins

These carcinogenic (cancer-causing) substances are produced by a fungus that contaminates peanuts, wheat, soybeans, ground nuts, corn, and rice. Storage in a moist warm environment can lead to the growth of this fungus. Although this can occur almost anywhere in the world it is more common in warmer and tropical countries. Developed countries such as the United States and those in Europe regulate the content of aflatoxins in foods through testing. Long-term exposure to these substances is a major risk factor for hepatocellular carcinoma. The risk is increased even further in people with hepatitis B or C infection.

Vinyl Chloride and Thorium Dioxide (Thorotrast)

These chemicals are risk factors for angiosarcoma of the liver (see the section “What Is Liver Cancer?”). They also increase the risk of developing cholangiocarcinoma and hepatocellular cancer, but to a far lesser degree. They have become much less important because Thorotrast is no longer used and exposure of workers to vinyl chloride is strictly regulated.

Anabolic Steroids

Anabolic steroids are male hormones that are used by some athletes to increase their strength. Long-term anabolic steroid use can slightly increase the risk of hepatocellular cancer. Cortisone-like steroids, such as hydrocortisone and dexamethasone, do not carry this same risk.

Arsenic

Chronic exposure to drinking water contaminated with naturally occurring arsenic, such as that obtained from some wells, increases the risk of hepatocellular cancer. This is more common in parts of East Asia but may be a concern in areas of the United States also.

Birth Control Pills

The section “What Is Liver Cancer?” mentions birth control pills, also known as oral contraceptives, as a cause of benign tumors called hepatic adenomas. Oral contraceptives may also slightly increase the risk of hepatocellular cancer. Most of the studies linking oral contraceptives and hepatocellular cancer involve types of oral contraceptives that are no longer used. Current oral contraceptives use different types of estrogens, different estrogen doses, and different combinations of estrogens with other hormones. It is not known if the newer oral contraceptives significantly increase hepatocellular cancer risk.

The American Cancer Society estimates that 19,160 new cases (13,650 in men and 5,510 in women) of primary liver cancer and intrahepatic bile duct cancer will be diagnosed in the United States during 2007. About 16,780 people (11,280 men and 5,500 women) will die of these cancers in the United States during 2007. In contrast to many other cancers, the rate of people developing liver cancer had been increasing up to 1999. This is no longer true and the rate seems to be stable. The actual number keeps increasing, of course, because the United States population is increasing.

About 85% of people diagnosed with liver cancer are between 45 and 85 years of age. About 4% are between 35 and 44 years of age and only 2.4% are below 35.

This cancer is many times more common in developing countries in Africa and East Asia than in the United States. In many of these countries it is the most common type of cancer. Over 500,000 people are diagnosed with this cancer each year throughout the world.

Since symptoms of liver cancer often do not appear until the disease is advanced, only a small number of liver cancers are found in the early stages and can be removed with surgery. Less than 30% of the patients having explorative surgery are able to have their cancer completely removed by surgery. The overall 5-year relative survival rate from liver cancer is about 10.5%. One reason for this low survival rate is that most patients with liver cancer also have cirrhosis of the liver, which itself can be fatal.

The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Five-year rates are used to produce a standard way of discussing prognosis. Of course, many people live much longer than 5 years. Five-year relative survival rates exclude patients dying of other diseases. This means that anyone who died of another cause, such as heart disease, is not counted in this statistic.

About the Liver

The liver is the largest internal organ. It lies under your right ribs just beneath your right lung and diaphragm. If you were to poke your fingers up under your right ribs, you would almost be touching it.

It is shaped like a pyramid and divided into right and left lobes. The lobes are further divided into segments. The liver, unlike most of the other organs, receives blood from 2 sources: the hepatic artery supplies the liver with blood from the heart that is rich in oxygen and the portal vein carries nutrient-rich blood from the intestines.

You cannot live without your liver. It performs several important functions:

It processes and stores many of the nutrients absorbed from the intestine that are necessary for the body to function. Some nutrients must be chemically changed (metabolized) in the liver before they can be used by the rest of the body for energy or to build and repair body tissues.
It produces most of the clotting factors that keep you from bleeding too much when you are cut or injured.
It secretes bile into the intestine to help absorb nutrients (especially fats).
It plays an important role in removing toxic wastes from the body.
The liver is made of several different types of cells. This is why there are several types of malignant (cancerous) and benign (non-cancerous) tumors that can form in the liver. These tumors have different causes, are treated differently, and have a different prognosis (outlook for health or recovery).

Benign Tumors

Hemangioma, the most common type of benign liver tumor, starts in blood vessels. Because most hemangiomas of the liver cause no symptoms, they do not need treatment. Some, however, may bleed and need to be surgically removed.

Hepatic adenomas are benign tumors that start from hepatocytes (the main type of liver cell). Most cause no symptoms and do not need treatment. However, some eventually cause symptoms, such as abdominal (stomach area) pain, a mass in the abdomen, or blood loss. Because there is a risk that the tumor could rupture (leading to severe blood loss) and a small risk that it could eventually develop into liver cancer, most experts usually recommend surgical removal if possible. Women have a much higher chance of having one of these tumors if they take birth control pills, although this is a rare complication. Stopping the pills can sometimes cause the tumor to shrink. Men who use anabolic steroids (”steroids”) may also develop these tumors. They can also shrink when the drugs are stopped.

Focal nodular hyperplasia (FNH) is a tumor-like growth of several cell types (hepatocytes, bile duct cells, and connective tissue). Although FNH tumors are benign, it can be difficult to tell them apart from true liver cancers, and doctors sometimes surgically remove them when the diagnosis is unclear. If you have symptoms from an FNH tumor, it can be surgically removed and you can be cured.

Both focal nodular hyperplasia and hepatic adenomas are more common in women than in men.

Malignant Tumors

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in adults. It is sometimes called hepatoma because it comes from the hepatocytes (the main type of liver cell). It accounts for about 75% of primary liver cancers.

Hepatocellular cancers can have different growth patterns:

Some begin as a single tumor that grows larger. Only late in the disease does it spread to other parts of the liver.

A second type of liver cancer develops as many smaller cancer nodules throughout the liver almost from the beginning and is not confined to a single tumor. This is seen most often in people with cirrhosis (chronic liver damage) and is the most common pattern seen in the United States.

Under the microscope, doctors can distinguish several subtypes of hepatocellular cancer. Of these subtypes, fibrolamellar, is the most important to recognize. Patients with this rare (less than 1%) type are usually younger (below age 35) than those with other subtypes, and the rest of their non-cancerous liver tissue is not diseased. This subtype has a much better prognosis (outlook) than other forms of hepatocellular cancer.

Cholangiocarcinomas account for about 10% to 20% of primary liver cancers. They are also called intrahepatic (starting within the liver) cholangiocarcinomas. These cancers start in the small bile ducts (tubes that carry bile to the gallbladder) within the liver.

You have a higher risk of developing this cancer if you have gallstones or gallbladder inflammation, chronic ulcerative colitis (a long-standing inflammation of the large bowel), or chronic infection with certain types of parasitic worms, such as Clonorchis sinensis or Opisthorchis viverrini. Although the rest of this document discusses hepatocellular cancers, cholangiocarcinomas are often treated the same way.

For more information on this type of cancer, see the American Cancer Society document “Bile Duct (Cholangiocarcinoma) Cancers.”

Angiosarcomas and hemangiosarcomas are rare cancers that begin in blood vessels of the liver. People who have been exposed to vinyl chloride or to thorium dioxide (Thorotrast) are more likely to develop these cancers. Vinyl chloride is a chemical used in manufacturing some kinds of plastics. Thorotrast is a chemical that in the past was injected into some patients as part of certain x-ray tests. Once the cancer-causing properties of these chemicals were recognized, steps were taken to eliminate them or minimize exposure to them. Workers’ exposure to vinyl chloride is now strictly regulated, and plastics manufacturing processes have been changed. Medical use of Thorotrast was stopped about 50 years ago.

Other cases are thought to be due to exposure to arsenic or radium, or to an inherited condition known as hemochromatosis. In about half of all cases, however, no likely cause can be identified.

Angiosarcomas grow rapidly and are usually too widespread to be removed surgically by the time they are found. Chemotherapy and radiation therapy may not help much. Many patients live less than 6 months after the diagnosis.

Hepatoblastoma is a very rare kind of cancer that develops in children, usually younger than 4 years old. The cells of hepatoblastoma are similar to fetal liver cells. About 70% of children with this disease are treated successfully with surgery and chemotherapy, and the survival rate is greater than 90% for early-stage hepatoblastomas.

Secondary Liver Cancer

Most of the time when cancer is found in the liver it did not start there but spread, or metastasized, from a cancer that started somewhere else in the body. These secondary liver tumors begin in other organs, such as the pancreas, colon, stomach, breast, or lung, and metastasize (spread) to the liver. These tumors are named after their primary site of occurrence (where they started) and are called metastatic. For example, cancer that started in the lung and spread to the liver is called metastatic lung cancer with spread to the liver. In the United States and Europe, secondary (or metastatic) liver tumors are more common than primary liver cancer. The opposite is true for many areas of Asia and Africa

For more information on liver metastases from different types of cancer, refer to the American Cancer Society documents on these cancer types, and to our document on “Advanced Cancer.”

Most of the remaining sections of this document refer only to hepatocellular cancer.

Cancer develops when cells in a part of the body begin to grow out of control. Although there are many kinds of cancer, they all start because of out-of-control growth of abnormal cells.

Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person’s life, normal cells divide more rapidly until the person becomes an adult. After that, cells in most parts of the body divide only to replace worn-out or dying cells and to repair injuries.

Because cancer cells continue to grow and divide, they are different from normal cells. Instead of dying, they outlive normal cells and continue to form new abnormal cells.

Cancer cells develop because of damage to DNA. This substance is in every cell and directs all activities. Most of the time when DNA becomes damaged the body is able to repair it. In cancer cells, the damaged DNA is not repaired. People can inherit damaged DNA, which accounts for inherited cancers. More often, though, a person’s DNA becomes damaged by exposure to something in the environment, like smoking.

Cancer usually forms as a tumor. Some cancers, like leukemia, do not form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow.

Often, cancer cells travel to other parts of the body where they begin to grow and replace normal tissue. This process is called metastasis. Regardless of where a cancer may spread, however, it is always named for the place it began. For instance, breast cancer that spreads to the liver is still called breast cancer, not liver cancer.

Not all tumors are cancerous. Benign (noncancerous) tumors do not spread (metastasize) to other parts of the body and, with very rare exceptions, are not life threatening.

Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

Cancer is the second leading cause of death in the United States. Half of all men and one third of all women in the United States will develop cancer during their lifetimes. Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person’s lifestyle, for example, by quitting smoking and eating a better diet. The sooner a cancer is found and treatment begins, the better are the chances for living for many years.