Mesothelioma

Malignant mesothelioma is the most serious of all asbestos-related diseases. Although uncommon, mesothelioma is no longer considered rare. Mesothelioma is a cancer that is particulary difficult for doctors to diagnose and one that does not respond well to therapy.
The chest cavity, abdominal cavity, and the cavity around the heart are surrounded by a a layer of specialized mesothelial cells. Most other internal organs are also covered by these cells. The tissue formed by these cells is called mesothelium.
A special protective lubricating fluid that allows organs to move around is produced by the mesothelium. This protective fluid helps the lungs to move without resistance inside the chest cavity while breathing. The medical name for the mesothelium of the chest is the pleura and the medical name for the mesothelium of the abdomen is the peritoneum. The mesothelium of the "sac-like" space around the heart is called the pericardium.
A malignant (cancerous) tumor of the mesothelium is called a malignant mesothelioma. As most mesothelial tumors are cancerous, malignant mesothelioma is often simply called mesothelioma. Tumors of the mesothelium can also be benign (noncancerous) but benign mesotheliomas are much more rare.
Mesothelioma was recognized as a tumor of the pleura, peritoneum and pericardium in the late 1700's. However it was not until much later, in 1960, that this particular type of tumor was described in more detail and even more importantly, its association with asbestos exposure was recognized. The first report linking mesothelioma to asbestos exposure was written by J.C.Wagner, and described 32 cases of workers in the "Asbestos Hills" in South Africa. Since than the relationship between mesothelioma and asbestos exposure has been confirmed in studies around the world.
The incidence of mesothelioma in the United States remains very low, with 14 cases occurring per million people per year. Despite these numbers the noticed threefold increase in mesothelioma in males between 1970 and 1984, is directly associated with environmental and occupational exposure to asbestos, mostly in areas of asbestos product plants and shipbuilding facilities.
Although the disease is much more commonly seen in 60-year old men, it has been described in women and early childhood as well. The cause of the disease is not so well understood in these latter two groups, but there is some evidence of possible asbestos exposure for some of these cases as well.
Malignant mesotheliomas are divided into three main types. About 50% to 70% of mesotheliomas are the epithelioid type. This type has the best prognosis (outlook for survival). The other two types are the sarcomatoid type (7%-20%), and the mixed/biphasic type (20%-35%). Treatment options for all three types are the same.
About three-fourths of mesotheliomas start in the chest cavity. They are known as pleural mesothelioma. Another 10% to 20% begin in the abdomen. These are called Peritone mesothelioma. Pericardial mesothelioma, starts in the cavity around the heart, and is very rare. The covering layer of the testicles is actually an outpouching of peritoneum into the scrotum. Mesotheliomas that affect this covering of the testicles are quite rare.

Mesothelioma Treatments

Messothelioma Treatemant:

There are several types of treatment available for patients with mesothelioma, some recommended more frequently than others. The most commonly used treatments are surgery, chemotherapy, and radiation therapy. In addition, some experimental treatments are becoming more widely used, or are showing some encouraging results in clinical trials. These treatments include photodynamic therapy, gene therapy, and immunotherapy, among others.

Most of these treatments are not used in isolation. In many cases, treatment may consist of a combination of therapies. For example, surgery to remove as much of the cancer as possible may be followed by radiotherapy or chemotherapy to remove residual cancer cells. This is one of the most common treatment options for mesothelioma among those who are candidates for surgery.

A number of alternative therapies can also be combined with traditional treatment options. Many patients choose to add alternative therapies such as massage, acupuncture, or TENS therapy to their conventional treatment approach in an effort to enhance or compliment the treatment process. A variety of alternative therapies, including aromatherapy, meditation, or yoga, are often added to a treatment regimen to provide pain relief and foster relaxation.

If you or a loved one have been diagnosed with mesothelioma it is likely you’re interested in the various treatment options available. Working with your doctor to create the best treatment plan is an important step. Knowing what the treatment plan will do to help treat the cancer often helps patients and their families understand the process and feel more comfortable. We offer a complimentary informative packet that includes all the information on our Web site and additional information about available treatment options that you may take with you continually educate yourself and those around you about mesothelioma. Click here to receive your packet overnight.



Mesothelioma Cure:

Mesothelioma is regarded as a highly aggressive cancer, as this disease is exceptionally resistant to current treatment methods. Though a number of treatments are available to mesothelioma patients, such as surgery, chemotherapy, and radiation, these options are known to only offer palliative relief - not a cure.
A number of scientific studies and clinical trials have worked tirelessly to find a cure for mesothelioma to no avail. Those versed in the politics of cancer research posit that since mesothelioma is such a rare cancer, little financial funding has been allotted to support the search for a cure. Hence, the hope for a mesothelioma cure is undeniably reliant upon increased funding to support research efforts.

Thankfully, the general public is becoming increasingly aware of mesothelioma. As more people and specific interest groups recognize the critical need to support research for a mesothelioma cure, funding will undoubtedly increase and this cancer may start to receive financial support that contends with the nation's most recognized forms of cancer. Once adequate funding for research becomes available, the hope for a cure will become a more tangible reality to mesothelioma sufferers across the globe.


Mesothelioma Surgery:

Surgical treatments for mesothelioma include three main types - diagnostic surgery, curative surgery, and palliative surgery. Some types of surgery fall into more than one category.


Surgery can only be performed during mesothelioma stages I and II.For example, thoracentesis may be used as a diagnostic procedure, and as a palliative treatment to provide symptomatic relief. Only curative surgery can potentially remove all cancer from a patient with mesothelioma.
However, for curative surgery to be effective, it is particularly important that mesothelioma be diagnosed as early as possible. Unfortunately, mesothelioma is not usually diagnosed until it reaches Stage III or IV, when surgery is not an option.



Chemotheraphy


Most forms of chemotherapy involve the intravenous administration of drugs such as Alimta and Cisplatin. Chemotherapeutic drugs are targeted to kill cells that are rapidly dividing by interfering with processes that occur during cell division.

However, while cancer cells themselves divide rapidly, so do some types of healthy cells, causing some of the unpleasant side effects that are often associated with this form of treatment. Though older chemotherapy medications seemed to do little to fight mesothelioma, newer chemotherapy drugs are showing much promise.
A relatively new form of chemotherapy called heated chemotherapy is an option for patients with peritoneal mesothelioma.
This treatment is carried out following surgery, and involves the perfusion of heated chemotherapeutic medications into the peritoneum.


Radiation:



Radiation therapy, or "ionizing radiation", is used to kill cancer cells and to limit the spread of cancer. For patients with mesothelioma, radiation therapy is most often used in conjunction with surgery.

However, in some cases radiation may be used as a stand-alone treatment to relieve pain and other symptoms associated with mesothelioma. In either case, it is rare for radiation therapy to provide more than short-term symptomatic relief.
Mesothelioma patients may receive one of two types of radiation therapies, depending on whether or not they are suitable candidates for either procedure.
External beam radiation therapy is the traditional type of radiation therapy, where tumors are bombarded with beams of radiation to kill cancer cells. Brachytherapy is a newer type of radiation treatment. It involves tiny radioactive rods which are implanted within a tumor to provide a strong, concentrated dose of radiation to tumors while doing very little damage to surrounding healthy tissue.


PhotoDynamic Theraphy


Photodynamic therapy is a highly specialized and specific form of treatment that is most often used to treat skin cancers, some types of lung cancer, and pleural mesothelioma.

However, this treatment is usually unsuitable for patients with metastasized cancer; it is most effective in patients who have localized disease.
This type of therapy involves the use of light energy to kill cancer cells. In photodynamic therapy treatment, the patient is given an intravenous solution of a medication that makes cancer cells highly sensitive to a particular kind of light.
One to three days after this treatment, the patient is exposed to the light, and cancer cells that have absorbed the medication are killed.


Gene Theraphy:

Gene therapy involves using genetic material to specifically target cancer cells and make them more vulnerable to chemotherapy treatment.

The main type of gene therapy being developed for use in mesothelioma patients is called "suicide gene therapy," because it forces cancer cells to produce substances that cause their death.
When undergoing this type of gene therapy, the patient is treated with a non-infectious virus that has been altered with genetic material that makes them produce a particular protein.
When undergoing this type of gene therapy, the patient is treated with a non-infectious virus that has been altered with genetic material that makes them produce a particular protein
Following this procedure, the patient is then treated with a chemotherapeutic medication that is specially formulated to be toxic only to cancer cells. This type of therapy has produced some promising results for mesothelioma patients, but it is still only available through clinical trials.
Immunotherapy is a type of treatment in which the patient's own immune system is 'tricked' into killing cancer cells. A healthy, normally-functioning immune system does not kill cancer cells, because even though these are diseased cells, the immune system is unable to recognize them as being harmful.
There are two main types of immunotherapy: active and passive. In active immunotherapy, mesothelioma cancer cells are removed from a patient and then treated in a laboratory to turn them into a vaccine. Following this laboratory treatment, the patient is injected with the vaccine and if the treatment is successful, the patient's immune system recognizes the vaccine as a harmful substance, thus recognizing the cancer as being harmful as well.
Passive immunotherapy is somewhat different in that it does not attempt to activate the patient's immune system. Instead, it uses substances such as cytokines (molecules that direct and regulate the immune system) and other agents to help boost the patient's immune response to their cancer

What is Mesothelioma?

Throughout the past decade, the term "mesothelioma" has become more and more recognizable. Once an obscure disease that meant little to the general public, mention of this disease now conjures up thoughts and pictures of factories and mines strewn with asbestos and the unfortunate workers who were employed in those dangerous places.

Thanks to concerned medical professionals, researchers, and watchdog organizations, we're learning more and more about mesothelioma and how it affects the lives of those who are afflicted. However, there's still far to go as both better treatments and a cure for the disease are sought.

About the Disease

Simply put, mesothelioma which is commonly referred to as asbestos cancer, is an aggressive cancer caused primarily by the inhalation of dangerous asbestos fibers. The disease attacks the mesothelium, a protective, two-layered membrane that covers the internal organs of the body including the lungs, heart and abdominal organs. Between these layers, the cells produce fluid, which allows easy movement of the heart and lungs within the chest cavity. The layer that covers the lungs is called the pleura, and the layer that covers the heart is called the pericardium. The peritoneum lines the abdominal cavity. Mesothelium also lines the male and female reproductive organs. Mesothelioma can affect any of these cells, but is usually seen in the pleural or peritoneal mesothelium. The most commonly diagnosed form of this cancer is pleural mesothelioma.

Mesothelioma takes anywhere from 20 to 50 years to develop, which is why older individuals are usually the victims. However, recent cases involving September 11th World Trade Center first responders and clean-up crews show that high concentrations of asbestos can cause the disease to develop much more rapidly. A few WTC workers have already died of the disease.

Effects of the Disease

The invasion of the mesothelium by cancer cells makes it very difficult for the patient to breathe, resulting in the need for oxygen, especially as the disease progresses. Those with the pleural form of mesothelioma may also suffer from pleural effusions. These effusions prevent the smooth movement of the lungs and other organs in the chest. Peritoneal mesothelioma also affects the stomach area and abdominal cavity, causing nausea, vomiting, or loss of appetite, which can result in dangerous weight loss. In addition to breathing difficulties and loss of appetite, mesothelioma victims also complain of excessive coughing, sleeping difficulties, persistent chest pain, fever, and pain in the lower back.

Mesothelioma, in general, is a very painful disease and because it is usually not diagnosed until it's in an advanced stage. For this reason, the symptoms are typically quite serious. Late diagnosis also means that the cancer is more likely to have metastasized, or spread, making successful mesothelioma treatment even more difficult.

Who Gets Mesothelioma?

Statistics show that, because of their work history, the disease most often affects men between the ages of 50 and 70 who were employed in an asbestos-laden environment before asbestos warnings and bans were in place in the 1970s. Though women still have a much lower frequency of the disease, cases of second-hand exposure to asbestos has prompted more diagnoses among women, especially those whose male family members worked with asbestos. The occupations most associated with mesothelioma are shipyard workers, electricians, plumbers, construction industry workers, pipefitters, boilermakers, and anyone subject to heavy exposure to dangerous asbestos and airborne asbestos fibers.

An abundance of cases have also demonstrated that mesothelioma can develop among people who lived in communities where asbestos factories or mines were located. In some instances, entire towns have been adversely affected by the presence of asbestos fibers in the air. For example, in Libby, Montana - site of a former vermiculite asbestos mine - hundreds have already died of mesothelioma.

Though still significantly rarer than other cancers, an estimated 2,000 to 3,000 new cases of mesothelioma are diagnosed each year in the United States. Other countries, notably the United Kingdom and Australia, report a much higher incidence of the disease. Nevertheless, the United States - like many other countries - has seen an increase in asbestos-caused cancer as men who worked in U.S. shipyards in the 1940s and 1950s, at the height of production, are now being diagnosed with mesothelioma.

Dealing with Mesothelioma

Mesothelioma is most often diagnosed in its late stages, and such a diagnosis is devastating to the individual and his/her family. Though research into the disease has been ongoing, there is currently no cure for mesothelioma. Some patients may be candidates for surgery to remove tumors or even an entire lung, but most are better treated with radiation or chemotherapy. More often than not, these treatments are palliative, serving to lessen the severity of the symptoms of the disease rather than offering a cure.

Medical professionals and research scientists, however, are constantly exploring new ways to combat the disease. For example, doctors know that some combinations of chemotherapy drugs work better than others and tests developed to ascertain earlier diagnosis of the disease or to monitor those most at risk have arrived on the scene.

Who's to Blame?

The reason someone develops mesothelioma is usually the lack of proper protection offered to those who worked with asbestos. Though the dangerous properties of asbestos and asbestos products have been evident for decades, many employers neglected to protect their workers from inhaling asbestos while on the job. It wasn't until public awareness of the dangers of the material were revealed in the 1970s that many employers began offering protective clothing such as respirators, gloves, aprons, and other such items to those working with asbestos on a daily basis.

Due to the negligence of employers, many companies who manufacture asbestos or products that contain asbestos have been subject to literally thousands of lawsuits filed by those who've been harmed by the material. Many of those lawsuits have come from individuals suffering from mesothelioma.

Chemotherapy

While the recommended mesothelioma treatment will no doubt vary from patient to patient and doctor to doctor, the form of cancer treatment most widely suggested is chemotherapy.

Dealing with the idea of chemotherapy can be equally as frightening as the initial diagnosis of mesothelioma. Chemo conjures up thoughts of treatments that cause horrible side affects and often leave the patient feeling worse than if they had no treatments at all. However, because advances in chemotherapy drugs and medications to lessen the side affects have decreased some of the unpleasant effects of chemo, patients should remain open to the idea of undergoing this type of treatment and should listen with an open mind.

How Does Chemotherapy Help?

Quite simply, chemotherapy - treatment with a specific cancer drug or combination of drugs - kills cancer cells. Unlike surgery and radiation therapy, which can destroy cancer cells in one particular location, chemotherapy can be used to destroy cells that have metastasized - or spread to other parts of the body.

There are currently about 100 chemotherapy drugs on the market. Though single chemo drugs are sometimes used to treat a particular type of cancer, more often a few of these drugs are used in tandem. This is called combination chemotherapy. Some combinations have proved more helpful than others in fighting mesothelioma and its troublesome symptoms. Because all of these drugs work a bit differently, your oncologist will determine which are best suited to treating your disease. The doctor will also be able to determine the length of your course of treatment as well as the frequency of treatments.

Types of Chemotherapy

Chemotherapy is received either by means of a pill or intravenously via a needle in the vein. Chemotherapy drugs may be administered 1) systemically - which means that the drugs are carried through the blood stream; or 2) intrapleurally - injected directly into the site of the tumor, with in the case of mesothelioma is usually the pleura, the lining of the lung. Doctors have had some success with both methods.

Chemo and Mesothelioma

Mesothelioma is a very aggressive form of cancer, so doctors treat it as aggressively as possible. That includes the use of highly toxic chemo drugs that will, hopefully, help destroy cancer cells while also providing some relief from the bothersome side affects of the disease, such as coughing, shortness of breath, and chest pain.

Years ago, doctors opted for single chemotherapy treatments for the disease. Unfortunately, they yielded little more than approximately a 15% success rate, providing minimal relief to the mesothelioma patient. More recently, oncologists and research scientists have determined that the best way to fight mesothelioma is through combination chemotherapy.

Currently, the drugs of choice are a newer drug, Alimta (pemetrexed), combined with Cisplatin, which has been on the market for some time. As a matter of fact, Alimta, when given with cisplatin, is the first and only chemotherapy drug to be approved by the Food and Drug Administration (FDA) for the treatment of patients with malignant pleural mesothelioma when surgery is not an option.

Other common chemotherapy drugs used to treat mesothelioma include gemcitabine, vinorelbine, and onconase. Researchers continue to experiment with new drugs and new combinations of chemotherapy medications in hopes that they can find the best available to treat the disease and its symptoms.

What to Expect

Chemotherapy is not a miracle drug, especially where mesothelioma is concerned, so it's necessary to be patient when dealing with the treatment. Most patients receiving chemotherapy for the first time will be especially concerned about side effects. Different chemo drugs have different side effects, but your doctor should be able to tell you what to expect.

Because your doctor has experience with specific chemo drugs, he/she may also be able to tell you when to expect the side effects, how long they'll last, and what to do about them. These days, there are many options available to help minimize or avoid these side effects so the chemotherapy of today is much different than that of decades or even years ago. Remember, also, that most of these side effects will disappear when the treatment has ended.

The most common chemotherapy side effects include:

• Nausea
• Vomiting
• Low white blood cell count (which leaves you prone to infection)
• Loss of appetite
• Constipation
• Fatigue
• Fever and chills
• Low platelet count (which may cause problems with clotting)
• Generalized achy-ness
• Tingling hands and feet
• Rash
• Depression

It's important to tell your doctor about any side effects you might experience, even if they are noted as "common" side effects of your chemotherapy. High fever, inability to eat or drink, blood in the stool or urine, and signs of infection should be addressed immediately. Your doctor will inform you about other side effects which he/she considers life-threatening.

Chemotherapy Drugs & Fact Sheets

• Alimta
• Carboplatin
• Cisplatin
• Gemcitabine
• Navelbine
• Onconase

Radiation Therapy

Radiation therapy is one of the oldest and most frequently prescribed treatments for a variety of cancers, including mesothelioma. The American Cancer Society reports that about 60% of all cancer patients receive some form of radiation therapy. Somewhat less frightening than chemotherapy and surgery, radiation may be prescribed for the treatment of the disease itself or to help lessen the troublesome symptoms of a cancer such as pleural mesothelioma.

How Does Radiation Work?

High dose radiation kills cancerous cells that are found in the body of a person suffering from mesothelioma or any other cancer. Technically, the radiation destroys cancer cells at the molecular level and keeps them from reproducing. It is especially adept at killing cells that replicate quickly, such as those associated with mesothelioma.

Unlike chemotherapy, however, radiation therapy is a localized mesothelioma treatment which kills only the cells in the area to which the radiation is applied. It is not helpful in treating cancer which has metastasized - spread to other parts of the body.

Types of Radiation

Traditionally, there have been two types of radiation therapy available to cancer patients.

External radiation

The most common form of radiation therapy, external radiation is achieved by means of an x-ray machine which aims radioactive waves at the tumor or affected portion of the body. The procedure is fairly quick and is accomplished on an outpatient basis. How many radiation treatments a patient requires will depend on individual cases and include factors such as stage of the disease and size and location of the tumor.

Internal radiation

Also known as Brachytherapy, this type of radiation involves planting radioactive material into the cancerous tissue. It allows for the implementation of higher doses in a single treatment or is suggested for patients with tumors that are located deep inside the body and are unable to be reached by traditional external radiation. Patients must be admitted to the hospital for internal radiation, and because exposure to the patient may cause danger to others due to radioactivity, visitors will be limited for the first few days. Implants such as these may be temporary or permanent.

Radiation and Mesothelioma

Some mesothelioma patients are not candidates for radiation therapy while the treatment may be suggested for others. If also may be offered in tandem with other treatments, like surgery or chemotherapy.

While it is impossible for radiation to cure mesothelioma, doctors often suggest it as a palliative measure in order to relieve some of the uncomfortable side effects of the disease. Radiation therapy has proven quite successful in relieving pain as well as reducing instances of shortness of breath in mesothelioma patients.

Oncologists experienced in the treatment of mesothelioma will be able to determine if and how a particular patient might benefit from radiation therapy. If it is prescribed for you or a loved one, it is essential to stick to the schedule so that the patient receives the most benefit from the treatment.

What to Expect

Once your doctor has determined that you are a candidate for external radiation therapy, he/she will suggest an outpatient facility where you can receive the treatment. If internal radiation therapy is in order, you may be sent to a consult with a surgeon before you receive the treatment. He/she will set up a schedule of treatments as well. The schedule may involve days, weeks, or even months of radiation therapy.

While you will suffer the unpleasant side effects of surgery after Brachytherapy as well as some traditional radiation therapy side effects, the side effects of external radiation are quite mild compared to most other cancer therapies. The downside of radiation is that it can also destroy healthy cells along with cancerous cells. However, these cells will eventually begin to repair themselves.

The most common side effects of radiation therapy are:

• Extreme fatigue
• Redness near the treated area
• Nausea
• Vomiting
• Dry mouth
• Loss of appetite
• Diarrhea
• Hair loss (infrequent)
• Decrease in white blood cells (leaving patient prone to infection)

A Mesothelioma Cure

Following the backlash of asbestos-related exposures and illnesses, many people were wondering how scientific research was going to proceed. The response has been encouraging, with cancer specialists and other doctors working each day towards a cure for malignant mesothelioma. While a way to completely eliminate the cancer from the body does not presently exist, there are several successful mesothelioma treatment programs as well as clinical trials that are working towards developing a way to eliminate this unfortunate form of cancer.

Treatments for patients of malignant mesothelioma commonly fall in line with treatment of other lung and lung-related cancers. Curative treatments are those which remove the cancer from the body completely. While there are no cures for mesothelioma, any treatment could theoretically be curative, so long as it is successful in completely removing the cancer from the body. While the treatment may be curative, it is important to remember that curative treatments do not rule out the recurrence of the disease.

While curative treatments may not prevent the disease from recurring, it is important to be aware of current initiatives that are working towards a total cure for the disease. There have been instances of unique treatment programs that have prevented the recurrence of the disease for several years. Paul Krauss was diagnosed with mesothelioma in 1997 and given only a few months to live by his physician. Today, Paul Krauss is still alive and active and has dedicated himself towards spreading awareness of the disease and working with others in developing treatment programs that would be as successful as his has been.

Combination treatments, which integrate two or more different treatment options, such as surgery coupled with radiation, or surgery paired with radiation and chemotherapy have been successful in extending life expectancies. Researchers believe that when the right combination of therapies is found, prognoses will be far longer than anyone could have imagined when the disease first manifested. Technology has also afforded new possibilities to mesothelioma patients. CT (Computer Topography) scans have been able to map three-dimensional images of the body's internal organs for targeted chemotherapy or radiation therapy to be administered.

Another novel technique is being integrated with surgical resections of mesothelioma tumors. Heated chemotherapeutic agents have shown increased proficiency in the elimination of cancer cells. Side effects of chemotherapy have, in the past, prevented physicians from delivering an optimal dosage of the drug. However, a novel procedure known as intracavity heated chemotherapy treatment has integrated these two concepts into a successful program. Heated chemotherapeutic agent is administered directly to the affected area during the surgical removal, destroying any remaining cancer cells in the area and extending prognoses well beyond typical timeframs.

It is through technology and advancements such as these that cancer specialists and physicians are laying the groundwork for a cure.

A Patient's Options

Once an individual has been diagnosed with mesothelioma, the next step is to discuss mesothelioma treatment options with his/her physician. Recent scientific research has produced significant breakthroughs with regard to treatment protocols for mesothelioma patients and more options are now available for managing the disease and supporting improved quality of life. Newly diagnosed patients always have many questions about the treatment options that would be most effective for them, including questions about new treatment therapies like Alimta and Cisplatin and other chemotherapy drugs. In addition to these newer drugs that are being used to treat asbestos cancer, mesothelioma patients also have a number of "conventional" treatment options to consider, including chemotherapy, radiation therapy and surgery. Clinical trials and experimental treatments are still other options that some mesothelioma patients may be eligible to participate in. Our site features a comprehensive mesothelioma cancer treatment section that includes important information for patients and families. We’ve included resources on top mesothelioma doctors such as Dr. Sugarbaker, as well as a comprehensive list of questions that you may wish to discuss with your personal physician when preparing a treatment plan. We are always providing new and informative resources regarding mesothelioma treatment including: Clinical Trials, conventional treatments, experimental therapies, and more. Check back often for the most recent advances in mesothelioma treatments.

Types

What are the different types of mesothelioma?

Pleural Mesothelioma – affects the chest and lungs

Malignant pleural mesothelioma often originates within the chest cavity and can, at times, involve the lung. This particular form of mesothelioma can metastasize to numerous organs in the body – even the brain - and tends to do so more frequently than not.

Pleural mesothelioma is not always easily detectable. Frequently, in the early stages of the disease, symptoms may be mild. Patients usually report pain in one area of the chest that never seems to go away, weight loss and fever. Occasionally, other symptoms are more severe and include problems with breathing due to fluid build up in the chest. A CT Scan of the chest area has proven to be the best test for identifying how far along the disease has progressed.

Frequently serum markers are used to diagnose of various forms of cancer. Mesothelioma cannot be diagnosed using this method as no serum markers currently exist. If high levels of hyaluronic acid are present it may be possible to distinguish mesothelioma from other types of cancer or to determine the effectiveness of a treatment protocol.

The survival rate for patients diagnosed with pleural mesothelioma typically is not high. Patients typically do not live beyond seventeen months from the onset of symptoms. Only 8% of those diagnosed with mesothelioma will live three to five years from the onset of symptoms.

Pericardial Mesothelioma – affects the heart

Pericardial mesothelioma is the least common form of mesothelioma. Pericardial mesothelioma, as the name suggests, involves the heart. This rare type of mesothelioma invades the pericardium, the sac that surrounds the heart. As the cancer progresses, the heart is not able to deliver oxygen as efficiently to the body causing further decline in health at an increasingly rapid rate. The symptoms most commonly associated with pericardial mesothelioma mimic those of a heart attack: nausea, pain in the chest and shortness of breath.

Peritoneal Mesothelioma – affects the abdomen

Peritoneal mesothelioma originates in the abdomen and will frequently spread to other organs in area including the liver, spleen or bowel. Severe abdominal pain is the most common complaint that patients present to their doctor. There may also be a discomfort level with fluid build up in the abdomen as well. Other symptoms of peritoneal mesothelioma may include difficult bowel movements, nausea and vomiting, fever and swollen feet.

The survival rate is even worse for those diagnosed with peritoneal mesothelioma will patients typically surviving only ten months from time that they first started experiencing the symptoms noted above.

Malignant Mesothelioma

Malignant mesothelioma is an uncommon form of cancer and of all asbestos related diseases, the most serious. The symptoms associated with the disease make it difficult for doctors to diagnose. Often, by the time that a proper diagnosis is made, the disease has progressed to a point where patients do not respond well to treatment therapy. Malignant mesothelioma is caused almost exclusively by the inhalation of airborne asbestos particles. Another unique factor associated with the disease is that there can be a long latency period between the time an individual is exposed to asbestos and the actual manifestation of the disease in the form of malignant mesothelioma.

Benign Mesothelioma – affects the peritoneum

Cystic mesothelioma primarily affects women of younger age and affects the peritoneum. This type of mesothelioma is not frequently diagnosed and is also not a malignant form of the disease. It is, however, extremely difficult to identify and requires specialized microscopes and immunologic techniques to aid in diagnosis.

Mesothelioma in Uncommon Sites

A form of cardiac cancer that is rarely seen involves the pericardium. Tumors associated with this type of mesothelioma are not easily detectable and patients presented with this diagnosis tend to have a very low survival rate. There have also been reports of mesothelioma involving ovaries in women and the scrotum in men. Treatment for all of these rare forms of mesothelioma will vary depending on what stage a patient has progressed to but in most all cases the projected outcome is not favorable.

Glossary of Terms

asbestos: combination of several minerals that separate into long, threadlike fibers. Because they do not burn, do not conduct heat or electricity, and are very resistant to chemicals, these minerals are often used for making fireproof materials, electrical insulation, roofing, filters, etc. benign: doing no harm, good incidence: the frequency with which an event occurs (usually in a group at risk) pericardium: a thin membrane surrounding the heart and the roots of the great blood vessels.

peritoneum: a thin membrane that covers the abdominal cavity and partially covers some of the abdominal organs.

pleura: a thin membrane that covers the lungs (visceral pleura) and lines the chest cavity (parietal pleura) malignant: harmful, dangerous (a malignant tumor is a cancer).

median: middle number in a series of numbers (for example: median survival of 10 months means that for that specific group of patients the survival varied from probably 2 months to 30 months).

mesoderm: the middle layer of cells in an embryo, from which the muscular, skeletal, vascular, connective etc. tissues develop.

mesothelioma: a tumor of the mesothelium, that can be benign (localized) or malignant (diffusely spread), and that is most commonly caused by the ingestion of asbestos particles.

mesothelium: the thin layer of mesodermal epithelial cells that forms the pleura, peritoneum, pericardium.

metastases: the spread of tumor cells from one part of the body to another unrelated part of the body by the way of the bloodstream or lymphatics.

prognosis: prediction of the probable course of the disease in an individual. Prognostic factors are factors associated with prognosis.

TNM staging: assigning a stage to the tumor based on size, local versus disseminated growth, lymph node involvement and presence or absence of distant metastases.

tumor: a mass of tissue, a growth independent of its surrounding structures and having no physiological function/ a neoplasm. A tumor can be benign or malignant.

Symptoms

What are the warning signs of mesothelioma?

Mesothelioma is difficult to diagnose because the early signs and symptoms of the disease can be subtle at best. Symptoms are all too frequently ignored or dismissed by people who are inclined to attribute them to common every day ailments. Sometimes patients live with symptoms for up to 6 months before being diagnosed but usually the symptoms are present for two to three months prior to diagnosis.

About 60% of patients diagnosed with pleural mesothelioma experience lower back pain or side chest pain and there are frequent reports of shortness of breath. Lower numbers of people may experience difficulty swallowing, or have a persistent cough, fever, weight loss or fatigue. Symptoms to also consider are muscle weakness, loss of sensory capability, coughing up blood, facial and arm swelling and hoarseness.

Peritoneal mesothelioma originates in the abdomen and as a result, symptoms often include abdominal pain, weight loss, nausea, and vomiting. In the event that there is a hernia present, fluid build up may occur in the abdomen as well.

Anyone previously exposed to asbestos displaying any of these symptoms should seek medical attention right away.

Stages

How is mesothelioma staged?

Staging is the process of finding out how far the cancer has spread. Staging of mesothelioma is based on imaging studies such as x-rays, CT scans, and MRI scans. The treatment and outlook for patients with mesothelioma largely depends on the stage (extent of spread) of their cancer. Since pleural mesothelioma occurs most frequently and has been studied the most, it is the only mesothelioma for which a staging classification exists.

The staging system most often used for mesothelioma is the Butchart system. This system is based mainly on the extent of the primary tumor mass, and divides mesotheliomas into stages I through IV.

Butchart Staging System

• Stage I: Mesothelioma is present within the right or left pleura, and may also involve the lung, pericardium, or diaphragm (the muscle separating the chest from the abdomen) on the same side.
• Stage II: Mesothelioma invades the chest wall or involves the esophagus (food passage connecting the throat to the stomach), heart, or pleura on both sides. The lymph nodes in the chest may also be involved.
• Stage III: Mesothelioma has penetrated through the diaphragm into the peritoneum (lining of the abdominal cavity). Lymph nodes beyond those in the chest may also be involved.
• Stage IV: There is evidence of distant metastases (spread through the bloodstream to other organs).

Another staging system has recently been developed by the American Joint Committee on Cancer (AJCC). This is a TNM system, similar to staging systems used for most other cancers. T stands for tumor (its size and how far it has spread to nearby organs), N stands for spread to lymph nodes and M is for metastasis (spread to distant organs). In TNM staging, information about the tumor, lymph nodes, and metastasis is combined in a process called stage grouping to assign a stage described by Roman numerals from I to IV. Minor differences exist between the AJCC TNM staging system and the Butchart staging system.

TNM Staging System

• Stage I: Mesothelioma involves the right or left pleura. It may also have spread into the lung, pericardium, or diaphragm on the same side. It has not yet spread to the lymph nodes.
• Stage II: Mesothelioma has spread from the pleura on one side to the nearby peribronchial and/or hilar 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 has spread into the chest wall muscle, ribs, heart, esophagus, or other organs in the chest on the same side as the primary tumor, with or without spread to subcarinal and/or mediastinal lymph nodes on the same side as the main tumor. Subcarinal nodes are located at the point where the windpipe branches to the left and right lungs. Mediastinal lymph nodes are located in the space behind the chest bone in front of the heart. Mesotheliomas with the same extent of local spread as in stage II that have also spread to subcarinal and/or mediastinal lymph nodes on the same side are also included in stage III.
• Stage IV: Mesothelioma has spread into the lymph nodes in the chest on the side opposite that of the primary tumor, or directly extends to the pleura or lung on the opposite side, or directly extends into the peritoneum, or directly extends into organs in the abdominal cavity or neck. Any mesothelioma with evidence of distant metastases (spread to other organs through the bloodstream) or spread to organs beyond the chest or abdomen is included in this stage.

Although the recently developed TNM classification is the most detailed and precise, the original Butchart staging system is still used most often to describe the spread of pleural mesotheliomas. Understanding these staging systems for mesothelioma is important both for estimating and better understanding prognosis, and also for assessing therapeutic options.

Prognostic Factors

Because pleural mesothelioma has been better studied than peritoneal mesothelioma we know more about factors associated with prognosis for pleural mesothelioma. Younger age at diagnosis, performance status (functional status) and absence of weight loss are associated with a more favorable prognosis.

Mesotheliomas are usually of three different cell types (histological analysis): 1) epithelial cell type - has the most favorable prognosis; 2) fibrosarcomatous cell type - carries the worst prognosis and 3) mixed cell type - has an intermediate prognosis.

Risk Factors

What are the risk factors for malignant mesothelioma?

There are several risk factors that increase the likelihood that a person will develop mesothelioma. The primary risk factor is asbestos exposure. Exposure to this very harmful substance can significantly enhance the chances of contracting the disease. Other secondary factors include exposure to radiation, zeolite, simian virus 40 (SV40) and tobacco. We discuss each of these risk factors in more detail below.

Asbestos

Exposure to asbestos is the leading risk factor associated with mesothelioma. Asbestos is an insulating material comprised of magnesium-silicate mineral fibers. It was favored by builders and contractors for many years for its low heat conductivity and resistance to melting and burning. Since researchers have identified more and more links between mesothelioma and exposure to asbestos, the material is now less widely used. Prior to this discovery, however, millions of Americans have experienced serious exposure to this harmful substance.

Over 700,000 schools and buildings in the United States today contain asbestos insulation as reported by the US Environmental Protection Agency. Asbestos exposure doesn’t stop there, however. Asbestos is often found in ship yards, manufacturing facilities, railway facilities and construction sites. Blue collar workers are at the highest risk for developing mesothelioma due to occupational exposure and include those who work in mines, factories, shipyards, construction sites, railroads and for insulation manufacturers and gas mask manufacturers. The occupations most widely affected are miners, factory workers, railroad workers, ship builders and construction workers - especially those who install asbestos containing insulation. Sometimes family members related to the workers receive second hand exposure to asbestos from the dust and fibers that were brought home on the workers clothes and also become at risk for contracting mesothelioma.

Serpentine fibers and amphiboles are the 2 primary types of asbestos used. Chrysotile is a form of serpentine fiber and the most frequently used. These fibers tend to be curly and flexible. Amphibole fibers, however, are generally straight and thin and usually comprise one of five types: crocidolite, amosite, anthrophylite, tremolite, and actinolyte. The crocidolite type of Amphiboles is thought to be the leading contributor to cancer caused by asbestos. Serpentine fibers are dangerous as well, however, and have also been linked to mesothelioma.

Some research points to the fact that inhaled asbestos fibers cause a physical irritation resulting in cancer rather than the cancer being caused by a reaction that is more chemical in nature. As fibers are inhaled through the mouth and nose they are cleared from the body by adhering to mucus in the nose, throat and airways and then get expelled by coughing or swallowing. The Amphibole fibers (long and thin) do not clear as easily and it is therefore thought that they can embed into the lining of the lungs and chest and result in mesothelioma.

Asbestosis (scar tissue in the lungs) or lung cancer can also be caused by the inhalation of asbestos fibers. In fact, people exposed to asbestos are seven times more likely to develop lung cancer over the general public. Workers who sustain high levels of asbestos exposure are more likely to die from asbestosis, lung cancer or mesothelioma than any other disease. It is also believed that the action of coughing up and swallowing asbestos could contribute to a form of mesothelioma originating in the abdomen called peritoneal mesothelioma. Mesothelioma has been found to exist in other organs of the body as well such as the larynx, pancreas and colon, but those instances are extremely limited compared to lung cancer incidents.

The chance of developing mesothelioma is in direct proportion to the duration and amount of asbestos exposure that an individual sustains. Those who are exposed to high levels of asbestos at a young age, for long periods of time have a greater risk of being diagnosed with mesothelioma than those who have short, low level exposure. Another important consideration is that Mesothelioma can take a long time to manifest. Often, twenty to forty years can elapse from the time of exposure to diagnosis. Genetic factors can also play a role which explains why not everyone exposed to asbestos develops and asbestos related disease.

Radiation

Thorium dioxide (Thorotrast), a substance used in x-ray tests in the past has reported links to pleural mesothelioma and peritoneal mesothelioma. The use of Thorotrast has been discontinued for many years due to this discovery.

Zeolite

Some mesothelioma cases in the Anatoli region within Turkey have been linked to Zeolite, a silica based mineral with chemical properties similar to asbestos found in the soil there.

Simian Virus 40 (SV40)

Some scientists have found the simian virus 40 (SV30) in mesothelioma cells from humans and have been able to create mesothelioma in animals with the virus. The relationship between this virus and mesothelioma is still unclear, however, and further research is being conducted to gain clarity on this potential link.

Tobacco

Smoking alone is not linked to mesothelioma, but smokers who are exposed to asbestos have a much higher chance of developing lung cancer (as much as fifty to ninety percent higher). Research indicates that lung cancer is the leading cause of death among asbestos workers.

Mesothelioma Information

As with any disease or health condition, mesothelioma researchers have, over time, collected statistical information about mesothelioma. These statistics can help us learn about the proclivities of the disease and its incidence and potentially help future patients as we learn more about mesothelioma.

Incidence of Diagnosis

New cases of mesothelioma are diagnosed in between 2,500 and 3,000 Americans each year. These numbers, while significant, would indicate that mesothelioma is still a relatively rare disease, though incidence is expected to rise in the next decade according to projections.

Age at Diagnosis

The first diagnosis of mesothelioma typically occurs in men and women between the ages of 50 and 70 years. Mesothelioma patients, certainly, have been diagnosed at ages younger than 50 and older than 70, but diagnoses for those age groups are considered statistical anomalies.

Does Mesothelioma Occur in a Particular Sex or Racial Demographic More than Another?

Mesothelioma is much more common in men than women, due mostly to occupational asbestos exposure being more common among men of industrial labor sites. That is not to say, however, that women cannot be diagnosed with mesothelioma. In fact, recent evidence suggests that mesothelioma incidence in women may rise in the coming years as secondary exposures to asbestos can manifest in the form of a positive mesothelioma diagnosis. Also of note is that mesothelioma is much less common among African Americans than white Americans, the reasons for which researchers are still investigating.

What are Typical Patient Survival Rates Following a Mesothelioma Diagnosis?

As mesothelioma is often diagnosed in its advanced stages, the prognosis is sometimes poor with life expectancy being little more than a year following diagnosis. If diagnosed early enough however, patient prognoses increase dramatically. Patient survival rates are often contingent on the treatments available to the particular patient. Early-stage tumors eligible for surgical resection, for instance, will result in improved prognoses over those diagnosed with later-stage disease. As new therapies and treatments are researched and employed in the future, it is realistic to anticipate an improvement in patient survival rates.

Diagnosis

How do medical professionals diagnose mesothelioma?

If you believe that you may have mesothelioma, a qualified medical professional will use a variety of diagnostic tests and methods to confirm the presence of the disease.

Medical history review and exam

The first step that your health professional will take in evaluating you for an asbestos related disease is to obtain a full medical history to determine the level and severity of risk factors and presenting symptoms. This interview will look consider among other things, where you were exposed to asbestos, the length of exposure and the amount of asbestos that you were exposed to.

In addition, he/she will perform a medical exam to look for signs and symptoms of various forms of mesothelioma. For example, if pleural mesothelioma is suspected the doctor will look for fluid in the chest, peritoneal mesothelioma often shows fluid in the abdomen and pericardial mesothelioma presents with fluid in the area of the heart.

Diagnostic imaging tests

Chest x-rays are used to identify abnormalities in the lungs including unusual thickening, mineral deposits and fluid in the chest area. If these conditions are present then it may be evidence that mesothelioma has developed.

Diagnostic image tests like x-rays, CT scans and MRI's are useful in determining more information about the cancer including how far it is progressed. Each method provides another piece of information to your doctor to assist in making an accurate diagnosis. CT scans are capable of providing images of the same location from many different angles. MRI technology uses magnetic fields rather than x-ray to provide additional views.

Testing fluid and tissue samples

If fluid build-up in the chest, abdomen or heart area is present, your doctor may want to obtain a sample. To accomplish this he/she will use a long needle to obtain fluid from the target area. The fluid will then be sent to the lab for analysis.

If fluid build-up in the chest, abdomen or heart area is present, your doctor may want to obtain a sample. To accomplish this he/she will use a long needle to obtain fluid from the target area. The fluid will then be sent to the lab for analysis.

A bronchoscopy procedure may be recommended for patients who are suspected of having pleural mesothelioma. For this medical test, a soft tube illuminates the trachea and bronchi to determine if any masses are present in the airways. If deemed necessary, the technician my take sample of tissue that appears to be abnormal for further testing.

If lymph node involvement is suspected which is common with lung cancer, patients may also undergo a mediastinoscopy. This procedure is similar to a bronchoscopy in that a soft tube enters the body under the chest bone and illuminates the chest area. In this way, the surgeon can examine lymph nodes for abnormalities, check to see how far disease may have progressed and when necessary help diagnose lung cancer vs. mesothelioma.

Diagnosing mesothelioma is never easy. Fluid build up alone in the chest, belly or heart regions is not enough to confirm a diagnosis. Tissue samples obtained from biopsy procedures are also difficult to discern because mesothelioma cancer cells often resemble other types of cancer. For this reason, specialized laboratory procedures are often employed to identify certain chemicals that are known to exist with mesothelioma and high powered laboratory equipment is used to examine the smallest details of cancer cells to confirm that mesothelioma is present.

Experimental Cancer Drug Tarceva

NEW YORK (Reuters Health) - OSI Pharmaceuticals Inc. is more confident than ever of the potential of its experimental cancer drug Tarceva (erlotinib HCl), even after the failure of a similar drug in a major clinical study this summer, OSI Chairman and CEO Dr. Colin Goddard told investors at the UBS Warburg Global Life Sciences conference here on Wednesday.

In August, AstraZeneca Plc. announced that adding its investigational non-small cell lung cancer (NSCLC) drug Iressa to standard therapy did not improve survival in a phase III trial of patients who had failed prior chemotherapy. The news raised concerns about a new class of cancer drugs expected to be effective with fewer side effects than other therapies.

Iressa is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. These kinds of drugs are believed to cause fewer adverse events because they target specific proteins associated only with tumors.

Since Tarceva is also an EGFR inhibitor, many industry watchers began to worry that the drug, which is still being evaluated in a phase III trial of NSCLC patients, might also fail to meet expectations.

But Dr. Goddard dismissed these concerns on Wednesday, noting that while similar, Iressa and Tarceva are structurally different. But more importantly, he said, the companies' approaches in evaluating their respective drugs are very different, as well.

Dr. Goddard told Reuters Health that in its failed trial, AstraZeneca was using doses of Iressa one-third to two-thirds of the maximum tolerable dose. OSI is using the highest tolerated dose of Tarceva.

Interestingly, he said, one of the side effects of Tarceva treatment is rash, and "what we find is when we produce rash, patients tend to do very well. In other words, there's a suggestion that pushing dose has real benefit in terms of survival."

"Hence, our whole rationale and belief is that we will see a differentiation between [Iressa and Tarceva] on the basis of that [dosing] strategy."

The OSI study is expected to complete patient accrual by the end of the year. Dr. Goddard said that OSI expects Tarceva to receive a six-month priority review by the US Food and Drug Administration after it is submitted.

Anti-cancer Drug

Tuesday morning, Alfacell Corp. said that according to the research findings published in National Academy of Sciences Journal, the company's anti-cancer drug Onconase might be one of the most effective methods of treatment for mesothelioma and lung cancer caused by asbestos.

Onconase is a novel anti-cancer drug for the treatment of patients with inoperable malignant mesothelioma. Malignant mesothelioma is an asbestos-related cancer of the inner lining of the chest and abdomen.

The research findings have also identified the molecular mechanism by which asbestos provokes lung cancer that so far has remained difficult to understand.

Asbestos is made of tiny fibres, which are inhaled when one comes in contact with it. This triggers the release of TNF-Alpha, a cytokine, which leads to a series of biochemical events. The release of TNF-Alpha activates NF-KappaB (Nuclear Factor-Kappa B) protein, a transcription factor. This transcription factor protects asbestos-damaged cells against cell death. As a result the damaged cells gets accumulated leading to cancer.

According to the research journal, as Onconase inhibits the same pathways that lead to mesothelial cell malignant transformation and mesothelioma, the drug might show unique promise in preventing and treating mesothelioma and lung cancer.

Alfacell said that Onconase's efficacy in preventing mesothelioma in high-risk cohorts is soon to be tested because of its minimal side effects.

Mesothelioma Subtype Shows Lengthier Projected Longevity: IASLC

SEOUL, Sept. 21 -- Some malignant mesothelioma patients may have a prognosis that's not as grim as once widely believed, said a Nordic collaborative group.

Patients diagnosed with epithelial subtype mesothelioma and treated solely with chemotherapy had a median survival of 15 months, while some patients survived beyond three years. This was reported at the International Association for the Study of Lung Cancer meeting by Gunnar Hillerdal, M.D., of the Karolinska University Hospital in Stockholm and colleagues.

The Nordic group experience contrasts with a clinical perception that mesothelioma patients usually die within a year, the investigators noted. A large multicenter trial based in the U.S. demonstrated a 12 month survival rate when using cisplatin with or without pemetrexed versus nine months with cisplatin alone. Other trials have yielded similar results.

Dr. Hillerdal said, "The Nordic Mesothelioma Group experience is different."

Surgery is used sparingly in treating mesothelioma in the Nordic countries. Dr. Hillerdal said, elsewhere in the world, patients with the most favorable characteristics (such as good performance status and lower-stage disease) often are recommended for surgery, leaving patients with the worst prognosis for chemotherapy treatment.

Data on 147 mesothelioma patients treated with chemotherapy alone and followed until death or for a minimum of 18 months were analyzed by Nordic investigators. All the patients were given gemcitabine, carboplatin, and liposomal doxorubicin.

In analyzing survival by histologic subtype it was seen that the epithelial subtype represented 108 patients (73%), 21 patients (14%) for the mixed subtype, and 18 patients (12%) for the sarcomatous subtype.

44% of epithelial subtype mesothelioma patients survived at least 18 months, 25% survived for two years, 9% lived three years or longer, and two patients remained alive after five years of follow-up. Those diagnosed with epithelial stage IV disease (distant metastases) had a median survival rate of 11 months, two lived for at least two years, and one patient was still living at 61 months.

Dr. Hillerdal remarked, "This is more favorable than stage IV non-small-cell lung cancer".

Patients with mixed subtype mesothelioma or sarcomatous disease had a less favorable outlook. This was demonstrated in a median survival rate of eight months and four months, respectively. There were no patients in either group that lived as long as two years.

"The key message from this study is that the survival rate for people diagnosed with mesothelioma is not as bad as many would believe," said Dr. Hillerdal. "Survival with chemotherapy can be just as good as with surgery or even better with proper patient selection. Patient selection is the important thing to consider. Stage is less important than subtype, and that should be kept in mind when evaluating results of surgical remedies."

A Case Report: Malignant Mesothelioma with Unexpected Contralateral Mediastinal Shift

Case Introduction: An unusual clinical feature of mesothelioma is the presentation of contralateral mediastinal shift due to pleural mesothelioma tissue, rather than a pleural effusion.

Case Summary: A woman, 63 years of age, who had been treated in the past for invasive ductal carcinoma of the breast, presented with chest pain and breathlessness. A radiograph of the chest revealed that she had contralateral mediastinal shift. Her symptoms were relieved after drainage of over 3 litres of pleural fluid.

Further investigations that she underwent revealed pleural mesothelioma rather than metastatic breast cancer which was expected. A few months later she again re-presented with breathlessness and a contralateral mediastinal shift was also again demonstrated in a chest radiograph.

On this occasion, a thoracic ultrasound revealed only a small loculated pleural effusion and, surprisingly, a large amount of malignant tissue which explained what was appearing in the chest radiographs.

Case Conclusion: This case illustrates that the mesothelioma tissue itself caused the mediastinal shift away from the affected side, not a pleural effusion which usually causes contralateral mediastinal shift in mesothelioma cases.

Despite Onconase Trial Results Quintessence Moves Ahead

In an article posted in this column a few weeks ago, it was reported that researchers at Madison-based Quintessence Bioscience were waiting for the results of a Phase IIIb clinical trial from Alfacell Corp., a significant East Coast competitor, on an anti-cancer therapeutic compound, Onconase. QBI-139, Quintessence's lead drug candidate, is very similar to Onconase but has not yet gone through clinical testing.

Upon the release of the Onconase trial results, Ralph Kauten, Quintessence Chairman and CEO commented that he was "disappointed that the Onconase clinical trial results were not reported to be overwhelmingly successful."

In a communication that Quintessence sent to its shareholders about the Alfacell trial, Kauten shared the following:

"Data has been released by Alfacell showing that their first-in-class drug, Onconase, did not meet the primary endpoint in the Phase IIIb confirmatory trial for malignant mesothelioma. The trial involved a comparison of a combination of Onconase plus doxorubicin versus doxorubicin by itself. The intended primary endpoint was an overall increase in patient survival. Initial analysis of Alfacell's data showed no statistically significant improvement for patients evaluated after taking the doxorubicin and Onconase combination."

Alfacell, in other words, tested whether treating mesothelioma patients with a combination of Onconase plus the standard chemotherapy drug, doxorubicin, would increase their survival at a statistically significant rate vs. those treated with doxorubicin alone. Mesothelioma is a very difficult cancer to treat and is generally related to asbestos exposure. Upon analysis of the data, there was no significant difference in survival rates when comparing the two therapeutic approaches which indicates that the patient survival rate was not favorably impacted by adding Onconase.

When the data were examined more closely, however, it became evident that a subset of patients failing the standard chemotherapy approach for treating mesothelioma, showed a small but statistically discernable increase in survival when they were treated using Onconase. It is based on the results of these data that Alfacell intends to submit an application to the FDA that would allow the use of Onconase as a "second-line" therapy for mesothelioma patients who do not respond to traditional chemotherapy. The FDA has not reacted favorably to this type of sub-group analysis of data in the past so it is unclear how they will respond to the application. Traditionally, they have not favored this type of analysis, but because there are emerging indications of a change in that attitude, Alfacell is continuing with the process for getting the new drug approved.

Is there reason to be concerned?

It was asked again if there should be any concern at Quintessence over these less than encouraging results from Alfacell. Despite the results, Quintessence remains committed to moving QBI-139 into clinical trials, most likely sometime this summer. In their communique to shareholders, Quintessence also explained the following:

"Getting Onconase approved is made more challenging because it failed to meet the primary endpoints in the Alfacell Phase IIIb trial. Onconase, however, still has major potential to get approval for use as a second line treatment therapy for malignant mesothelioma. This change would create a smaller market for the drug, but we continue to be of the opinion that the road to general acceptance of RNases as cancer therapeutics will be paved by any successful FDA approval of Onconase."

It was further reported that "Quintessence continues to progress toward filing an IND and starting a Phase I clinical trial for QBI-139. Most of the data that supports the IND has been collected and analyzed and GMP manufacturing is taking place. We are in contract negotiation with the clinical trial site and a contract monitoring group. We look forward to being able to demonstrate the clinical benefit of QBI-139 in patients who have been diagnosed with cancer."

The future of RNase-based therapies that Alfacell and Quintessence are developing hinges on the FDA's response to Alfacell. Unfortunately, if a drug is tested on the wrong disease and fails, it is difficult to try to test it on another, more appropriate, disease. If a drug gets a bad reputation, NIH grant reviewers and investors may not respond enthusiastically.

Testing Onconase on mesothelioma may turn out to be a bad decision on the part of Alfacell, but it was still an interesting strategic decision made by the company. Alfacell chose Mesothelioma for the initial clinical trials because of the stubbornness that Mesothelioma exhibits in response to traditional therapy. As a result, the FDA granted Onconase fast track status and orphan-drug designation and Onconase was able to get into advanced clinical trials much sooner that it would have otherwise.

The results that have been demonstrated by Onconase do not mean that RNase-based therapies will not work on other types of cancers and there is still reason to believe that Quintessence's lead RNase therapy, QBI-139 will be even better than Onconase.

>Q & A with Dr. Sugarbaker

These are questions asked of Dr. Sugarbaker by a patient regarding a mesothelioma surgical procedure in January of 1997.

What exactly will be removed during surgery?

The surgery is called extrapleural pneumonectomy. It is removal of the left lung, the parietal pleura (lining of the lung), the ipsilateral pericardium (left side of the lining of the heart), ipsilateral diaphragm (left side of the diaphragm).

How many surgeries of this type for Mesothelioma have you performed?

250

Of those patients, what is the percentage survival rate?

The median survival rate is 41 months.

Of the patients who survived what was the quality of life?

The quality of life for most patients was fairly normal, some have even returned to work. Patients should not be oxygen dependent. Patients with epithelial cell type without lymph node involvement have a 2-5 year survival rate of 74% to 39% receptively.(Pg. 288 study)

How long of a hospital stay is required with this surgery?

A 5 to 10 day stay provided there are no complications.

How long will it take to recover from the surgery?

Complete recovery time is about a year.

How long after surgery will the chemotherapy and radiation start?

Chemotherapy will start about 4 to 6 weeks after surgery. There will be three cycles of therapy. One cycle of Taxol, one cycle of Carboplatinum and then the final cycle is with both chemo agents followed by 1 month of radiation. Total treatment time is 3 1/2 months and the recovery time.

Based on the test results of the MRI, Echocardiogram and V/Q scan, what stage is the asbestos cancer in?

Stage I because there is no evidence of lymph node involvement.

Based on the prior surgery on November 15, 1996, how long a wait before having surgery again?

The surgery can be performed now. They will use the same incision site.

What are the risks associated with the surgery?

Hemorrhage, respiratory failure, pneumonia, disrupted diaphragmatic patch, perforated duodenal ulcer, empyema (infection), upper gastrointestinal bleed, deep vein thrombosis, death.

Based on the additional tests, is the cancer localized to the left lung?

Yes. There was no evidence of the cancer in the chest wall, right lung, or in the diaphragm.

Sex difference in diffuse malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is rare and in the past has proved an invariably fatal disease. Female patients have been reported to have an improved survival outcome for reasons that are not understood. METHODS: The survival of 34 men and 28 women who underwent cytoreduction and perioperative intraperitoneal chemotherapy for DMPM was compared. Twenty-five clinicopathological variables were subjected to univariate analysis. RESULTS: The women had a 5-year survival rate of 63 per cent and median survival was not reached. The men had a 5-year survival rate of 42 per cent, with a median survival of 32 months (P = 0.045). Women had undergone more extensive previous surgery and had less extensive peritoneal involvement at the time of cytoreduction. Tumours in women more frequently showed a small nuclear size (30 microm or less) and the chromatin pattern was more often granular than clear. CONCLUSION: Women with DMPM had better survival. This observation may be related to the favourable clinical and histopathological features associated with women.

Current Therapy For Mesothelioma

Malignant pleural mesothelioma is locally aggressive, invasive, and almost universally fatal.

INTRODUCTION

Mesotheliomas of the pleural cavity are relatively rare tumors. Generally, two types of pleural tumors can be referred to as mesotheliomas. The less common is the solitary (or localized) fibrous tumor of the pleura, previously known as "benign mesothelioma." This slow-growing, commonly benign, well- circumscribed tumor is pedunculated on a pleural-based pedicle and often is cured by resection. The tumor appears to originate from submesothelial rather than mesothelial or epithelial cells. The more common variety is the diffuse malignant pleural mesothelioma (DMPM), a true mesothelial malignancy that is locally aggressive, invasive, and almost universally fatal. This multicentric tumor infiltrates the pleural space, results in a pleural effusion, and mechanically compresses the surrounding structures. Though distant metastatic lesions may be seen in up to 30% of cases in autopsy series, most patients die of locoregional invasion and compression of vital structures. The median survival for patients with DMPM is between four and 12 months, depending on the stage at presentation.

BACKGROUND*: Diffuse malignant pleural mesotheliomas (DMPMs) are highly lethal tumors that are becoming more common. Standard management approaches have provided limited effectiveness.

METHODS*: The literature on management has been revised, and the authors present their data on outcomes for 120 patients treated with an aggressive trimodality approach.

RESULTS*: An aggressive trimodality approach including extrapleural pneumonectomy followed by chemoradiation produces low mortality and acceptable morbidity. The five-year survival rate in patients with epithelial histology and negative nodes approaches 40%.

CONCLUSIONS: Mesothelioma is increasing in frequency and presents many diagnostic and management challenges. An optimal universal staging system is still awaiting definition and validation. Prognosis is best for patients with localized disease and epithelial histology. Surgical techniques including pleurectomy/decortication and EPP can result in a major debulking of disease, and studies are ongoing to determine if the addition of chemotherapy and radiation has an impact on survival. Several new investigational approaches are now being tested, including intrapleural interferon gamma, photodynamic therapy, immunotherapy, and gene therapy.

Laparoscopy and mesothelioma

Malignant mesothelioma is a well-recognized long-term sequela of chronic asbestos exposure. Asbestos use in the United States began in the 1950s and was widespread until the mid-1970s. Although currently only 2.2 cases per million population per year are diagnosed, disease incidence is increasing because of the long latency of this neoplasm. A latency of 15-50 years means that a higher incidence of this neoplasm can be anticipated in the future. The authors report a patient with peritoneal mesothelioma and no known prior exposure to asbestos. The diagnosis was confirmed by exploratory laparoscopy, which entailed biopsies of the diaphragm and of the peritoneal and abdominal walls, and by cytologic evaluation of 700 ml ascitis fluid. At present, exploratory laparoscopy offers the quickest, safest, and least invasive way to confirm the clinical diagnosis of peritoneal malignant mesothelioma.

Current problems in the diagnosis of malignant pleural mesothelioma.

The diagnosis of malignant pleural mesothelioma (MPM) is challenging although MPM is highly aggressive tumor. The current diagnostic gold standard is principally based on light microscopic examination of hematoxylin-eosin and immunohistochemical stains of large tissue sections. However, pathological diagnosis of MPM and classification of histological findings into 1 of the 3 subtypes (epithelial, sarcomatoid, biphasic) are difficult. We studied correlation between initial and final histological diagnosis retrospectively from the records of 21 cases with MPM from 1989 to 2005. The diagnosis of MPM was confirmed by histopathological examination of pleural tissue samples obtained by closed biopsy under computed tomography (CT) or ultrasonography-guided (5 cases), by biopsy under thoracoscopy with local anesthesia (9), by open biopsy via thoracotomy (2), and by video-assisted thoracoscopic surgery (VATS) [5] . Pleural biopsy under those diagnostic methods led to initial diagnosis of MPM in 15 of 21 cases (71.4%) . In 6 cases (28.6%) , initial diagnosis of MPM were not confirmed because of missing malignant tissue (1 case) and relatively small and sarcomatous element (5). In 2 cases examined by closed biopsy and in 3 examined by thoracoscopy under local anesthesia, initial diagnosis of MPM were not confirmed. To get the accurate diagnosis of MPM, obtaining large tissue samples in the initial examination by less invasive thoracoscopy is recommended.

Managing Your Care

Mesothelioma is a major challenge and keeping up with activities involving your treatment and doctor visits can be overwhelming. The patient, the family, and close friends are faced with new and unfamiliar experiences. A methodological approach to your care can often make life easier for everyone.

The concept of a personal medical file is becoming more popular, and these files can be especially useful for cancer patients who see multiple doctors and receive treatment at more than one location. The personal medical file helps ensure that you always have access to critical data (even when your doctor’s office is closed) and there is a backup of the most important documents. When you visit a new health care provider, you will have comprehensive access to the information they need. More on personal medical files.

Keeping track of the medications you are taking can be a hassle, especially given the amount of prescriptions the typical mesothelioma patient takes. You need to know what medicines you are taking, which doctor prescribed them, what the dosage is and how many pills a day you take. A formal file and notebook organizer can help here. More tips on managing your medications.

Keeping track of your expenses is important. Everyone has different financial resources, insurance coverage, and Medicare eligibility. Many mesothelioma patients can get compensation from the asbestos industry, which can help with medical costs. Whatever the source of your funding, you need to keep track of all bills from hospitals and clinics, bills from drugs stores, and insurance claims and payments. Tips on managing your expenses.

Because mesothelioma is a rare cancer, your doctor may not have much experience dealing with it. There is nothing wrong with getting a second opinion from another physician. Here are some ideas on second opinions. You may wish to look at our list of mesothelioma specialists. Contact us if you are interested in reaching these doctors. Note that the type of doctor that specializes in cancer treatment is called oncologists. However, because mesothelioma is so rare, even most oncologists have seen a limited number of cases. Also you may wish to look into the community clinical oncology program, sponsored by the federal government, which offer access to clinical trials to patients at cancer centers around the country.

Your Health Care Team

A diagnosis of mesothelioma brings with it one of the most difficult challenges you or your loved one will ever face. One of the most important things to remember, however, is that there are resources to help with every aspect of care, and that you or your loved one is at the center of the health care team that will provide help in many different forms. Remember also that in addition to your doctor you can also get a second opinion from another physician.

You, the Patient

Your role as the most important member of the team is to be a good consumer by gathering information and asking questions. Following are some easy ways to make the most of your appointment times with other members of your medical team:

• Once you know the day and time of your appointment, start a list of questions you want to ask that particular team member. These questions could be about mesothelioma itself, about test results or about treatments you are undergoing or considering. It is also a good idea to write down any symptoms you may be experiencing so that they can be addressed at this time. If there is something you don’t completely understand, ask to have it explained in simpler terms. Above all, don’t be embarrassed to ask questions or request clarifications.
• If possible, take along another person who can take notes, ask additional questions or record your appointment for later review. Sometimes it can be helpful to return home and play back what was discussed.
• Ask for written material or brochures that can help in making treatment or care decisions . These might include information on nutrition, pain management, support groups or hospice or home care.

Other than your doctors, who could include your primary care doctor, surgeons, medical oncologists, and/or radiation oncologists, you will probably have the most contact with your nursing staff and your social worker. These medical professionals can be your best source of practical assistance when trying to navigate the waters of a mesothelioma diagnosis.

Nurses

All specialized cancer treatment facilities have nurses who are familiar with implementing the cancer treatment plan initialized by your doctor, and are trained to administer medication, monitor side effects and conduct routine tests. Whether you are a hospital inpatient or outpatient, you can benefit greatly from developing a strong working relationship with your nursing staff.

You may also request home visits by a registered nurse, if necessary. If approved by your doctor, these visits may be covered under insurance. Be sure to check with your individual insurance provider for details.

Social Workers

Social workers are a good starting point for newly diagnosed patients who are overwhelmed by their diagnosis and the many things that have to be accomplished and decided.

Some types of social workers include:

• Oncology social workers specialize in assisting those diagnosed with cancer. Most cancer treatment facilities have certified oncology social workers on staff.
• Clinical social workers specialize in providing services aimed at family therapy and counseling, or counseling for those coping with a serious illness.
• Hospital social workers can help find resources in your local area such as home care, transportation services or support groups, and can also help you understand your diagnosis, your treatments and other care options.

Psychiatrists and Psychologists

Because of the emotional issues surrounding a mesothelioma diagnosis, some patients or their family members may benefit from the help of someone trained to deal with depression, anxiety or inability to cope. Don’t be afraid to ask for this type of help for yourself or your loved one – good emotional health is essential to quality of life.

• Psychiatrists are medical doctors who specialize in providing psychotherapy and other general psychological services to their patients. They are licensed to prescribe medications such as antidepressants and sleep aids. (Related: concerns about drug addition during cancer treatment.)
• Psychologists can provide many of the same services as a psychiatrist such as counseling for depression, anxiety, etc., however, they are not medical doctors. Most have PhD’s in psychology and counseling.

Nutritionists and Dietitians

Nutrition is another area that can greatly affect quality of life. Many patients lose weight because of anxiety associated with the diagnostic process, subsequent treatments or the natural progression of mesothelioma. Working with a nutritionist or dietitian as soon after diagnosis as possible is one of the most important benefits you can obtain from your health care team. These professionals can help you be sure you receive enough calories, vitamins and protein to maintain a healthy weight, as well as tailoring a program for those with concurrent health problems such as diabetes or high cholesterol. They can also suggest ways to minimize the side effects of chemotherapy or other aggressive treatment.

Most local hospitals have registered dietitians on staff, or you can ask your doctor to recommend someone in your area. As with other health care needs, check to see whether these services are covered under your insurance. If they are not, there may be community-based services available in your area at no cost.

Hospice and Home Care

• Hospice care is palliative in nature, and provides comfort care by helping to control a patient’s physical symptoms as well as offering emotional and spiritual support. Although in most cases, care is provided at home, there are also hospice facilities that provide full-time care in a hospital setting. You can discuss the benefits of hospice with your doctor, nurse or social worker.
• Home care provides assistance in the home with daily activities such as bathing, meal preparation or household chores. These services are usually provided by a home health aide, and may or may not be under the supervision of a nurse. Ask your doctor, nurse or social worker for Home Health Care Agencies in your area.