Mesothelioma Cancer

Radiation therapy, also called radiotherapy, treats cancer by using penetrating beams of high energy or streams of particles called radiation. In treating mesothelioma, radiation may be used aggressively in combination with surgery, or palliatively to control symptoms.

In an aggressive combined modality approach, radiation is used to attack microscopic or residual disease remaining in the chest cavity after extrapleural pnuemonectomy. An example of this is Intensity Modulated Radiation Therapy (IMRT), which uses x-rays of varying intensities in conjunction with computer generated images to deliver targeted radiation directly to cancer cells while reducing the amount of radiation to surrounding healthy tissue. More on Intensity Modulated Radiation Therapy (IMRT).

Used palliatively, radiation can help control metastases (spread) of the tumor along tracks left by invasive procedures such as thoracoscopy, needle biopsy and chest tube drainage, or to control disease symptoms, such as pain or shortness of breath.

An exciting new development in radiation oncology is tomotherapy. A brief description of steps in the helical tomotherapy process.

Labels: Radiation

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Chemotherapy is defined as the treatment of cancer using chemical substances. When cancer occurs, abnormal cells continue to divide uncontrolled. Anticancer, or chemotherapy drugs, work to destroy cancer cells by preventing them from multiplying. Read more on types of chemotherapy medicines.

Purposes of Chemotherapy

Chemotherapy may be used to achieve different goals, depending on the stage of the cancer at the time of diagnosis and the age and health of the patient. Since chemotherapy for mesothelioma is not considered "curative", the goal is:

* To control the cancer by stopping its spread or slowing its growth.
* To shrink tumors prior to other treatments, such as surgery. This is called neoadjuvant chemotherapy.
* To destroy microscopic disease which may remain after surgery. This is called adjuvant chemotherapy.
* To relieve symptoms, such as pain. This is called palliative chemotherapy, and is given in cases when a drastic reduction in the tumor is not expected.

The most common use for chemotherapy in mesothelioma patients, is as an option for those who are not surgical candidates, however, various cancer centers are now conducting trials using the neoadjuvant approach. Alimta (pemetrexed) is a new drug recently approved by the Food and Drug Administration (FDA) for use with Cisplatin in the treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are not candidates for curative surgery. Alimta is the first drug approval specific to mesothelioma.

The Alimta/Cisplatin chemotherapy regimen is the first Food and Drug Administration (FDA) approved treatment specifically for malignant pleural mesothelioma. This is currently considered the most effective first-line treatment for mesothelioma patients who are not surgical candidates. A multi-targeted antifolate drug, Alimta works by blocking the enzymes necessary for DNA copying and cell division. During the clinical trial process, Alimta/Cisplatin improved median survival for pleural mesothelioma patients by approximately three months over treatment with Cisplatin as a single agent. Eli Lilly's information on treatment with Alimta.

As with any medical treatment, it is important to discuss the use of Alimta with your doctor. This conversation should include all pertinent information regarding effectiveness, administration and possible side effects of the drug combination. It is also important to begin vitamin supplementation of B12 by injection during the week prior to treatment (to be repeated every 9 weeks), and folic acid by mouth daily (to be continued until 21 days after the last cycle of Alimta). Additionally, you will be given an oral steroid medication to minimize the risk of skin rash or other possible side effects. Your doctor will have information on the correct dosages of each medication. Be sure to tell your doctor of any other medications you are taking (including non-prescription drugs) so he may be aware of any adverse interactions.

Alimta/Cisplatin is administered to patients on an outpatient basis every 21 days. This cycle of treatment involves a 10-minute IV infusion of Alimta followed by a 2 hour infusion of Cisplatin. How many cycles of treatment you receive will be dependent on your response rate to the drug (regression of the tumor or halt to progression of the disease) and the side effects you might experience.

Side effects of Alimta/Cisplatin are mild to moderate for most mesothelioma patients, i.e., nausea, vomiting and fatigue, and can usually be managed by your doctor. For some patients, however, side effects may be debilitating, and may require a decrease in dosage or removal from the program. All potential side effects should be mentioned to your doctor. Never assume any complaint is minor.

Administration of Chemotherapy

The most common way to administer chemotherapy is intravenously, or through a vein. A thin needle is inserted into a vein in the hand or in the lower arm. Intravenous administration of drugs allows for rapid entry into the blood stream. Drugs may also be delivered via catheters and/or ports.

* Catheters are soft, thin, flexible tubes placed into a large vein in the body. They remain in place for as long as they are needed.
* The catheter may sometimes be attached to a port, a small round plastic or metal disc placed under the skin on the chest. Ports also remain in place for as long as necessary.

Intraperitoneal chemotherapy may also be delivered through a catheter or a port. The catheter is inserted through the abdominal wall. Chemotherapy drugs can then be infused directly into the abdominal cavity. Ports may also be placed under the skin of the abdominal wall and the catheter tunneled between the skin and muscle into the peritoneum.

Side Effects of Chemotherapy

Cancer cells grow and divide more rapidly than normal cells, but some normal cells also multiply quickly, particularly those in the digestive tract, reproduction system, and hair follicles. It is the damage done to normal cells that causes side effects. The type of side effects you might experience and how severe they are, depend on the type of chemotherapy you are receiving, the dosage given and how your own body reacts. Before beginning any chemotherapy treatment, you will be asked to sign a consent form. Before signing the form, be sure your doctor informs you of all the facts regarding the treatment he/she will be administering, including information about the particular drug or combination of drugs to be used, the possible risks or side effects, the number of treatments you will receive and how often, and whether it will be given during a hospital stay or on an outpatient basis. More on anti-nausea treatment for chemotherapy patients.

Click here if you are interested in learning more about chemotherapy for mesothelioma and the types of questions you should ask your doctor.

Retrieved from http://www.mesotheliomaweb.org/treat.htm#surgery on May 5/16/07

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Diagnostic Procedures

As previously mentioned in the "Symptoms" section of this website, a diagnosis of mesothelioma from fluid is many times inconclusive. Given this fact, diagnostic surgery becomes a necessary next step in confirming and staging mesothelioma.

Thoracoscopy enables a physician to evaluate the pleural cavity and to conduct multiple tissue biopsies under direct vision. In up to 98% of cases, a definitive diagnosis can be obtained. Often, chemical pleurodesis aimed at relieving the accumulation of fluid in the intrapleural space, can be accomplished during the same procedure. It is also possible to gauge the extent of the tumor, and make a determination of surgical resectability. While less invasive than an open biopsy, it can only be performed on patients where tumor has not obliterated the pleural space.

VATS, or video-assisted thoracic surgery is an alternative to thoracoscopy, although because of its more invasive nature, concerns of tumor seeding increase. By utilizing small incisions, the physician can view the pleural space with the assistance of a camera, and obtain sufficient tissue samples for analysis by a pathologist. Extent of the tumor (i.e., pleural involvement, chest wall invasion) may also determined, and recommendation as to the type of debulking procedure necessary can be made at this time.

Mediastinoscopy is sometimes used as an aid in staging extent of disease when enlarged nodes are seen using imaging techniques.

Laproscopy is used in mesothelioma patients in cases where imaging techniques suggest possible invasion of the tumor through the diaphragm. This information can be important in evaluating a patient for potential pleurectomy or extrapleural pneumonectomy.

Palliative Procedures

Palliative surgical procedures are those which treat a symptom of mesothelioma, without aggressively treating the disease itself.

Chest Tube Drainage and Pleurodesis is considered the most common of palliative treatments. Fluid build-up, or pleural effusion, is most often the first symptom which will prompt mesothelioma patients to seek medical attention. Once this effusion has occurred, it is many times persistent, returning rapidly after initial thoracentesis (draining of the fluid). In order to eliminate this problem, the pleural space must be closed. This is accomplished by use of a talc slurry or other sclerosing agent which produces an adhesion.

Thoracoscopy and Pleurodesis is done in conjunction with VATS using a powdered form of talc versus talc slurry. Both this and chest tube drainage and pleurodesis will be only effective if there is no tumor encasing the lung which restricts its expansion.

Pleuroperitoneal Shunt plays a limited role in palliation for several reasons. It involves placement of a catheter run under the skin from the pleural to the peritoneal cavity. Obstruction of the catheter and possible seeding of the tumor into the abdominal cavity may be concerns.

Pleurectomy, used as a palliative procedure, may be performed where more extensive surgery is not an option. In these cases, it is understood that all visible or gross tumor will not be removed. It is considered the most effective means of controlling pleural effusion in cases where the lung's expansion is restricted by disease.

Potentially Curative Procedures

These procedures are performed with "curative intent". Their goal is removal of all gross disease, with the knowledge that microscopic disease will most likely remain. Adjuvant therapy (another form of treatment in addition to the primary therapy) is typically aimed at eliminating residual disease.
For Pleural Mesothelioma:

* Pleurectomy/Decortication is usually performed on patients with early stage disease (Stage I and selected Stage II), and attempts to remove all gross tumor. If it is found that all tumor can not be removed without removing the lung, this may be done at the same time and is called pneumonectomy.

* Extrapleural Pneumonectomy is considerably more radical than other surgical approaches, and should be carried out by surgeons with great expertise in evaluating patients and performing the procedure itself. (See Finding Specialists.) Because in the past surgery alone has failed to effect a cure, or even to help prolong life for any extended period of time, it is currently being combined with traditional chemotherapy and/or radiation, or other new approaches such as gene therapy, immunotherapy or photodynamic therapy.

For Peritoneal Mesothelioma:

* Cytoreductive Surgery is aimed at removing all or nearly all of the gross or visible tumor in the peritoneal cavity. In order to treat any remaining cancer cells, Intra-Peritoneal Hyperthermic (heated) Chemotherapy (IPHC) is then delivered to the abdominal cavity. The type of chemotherapy drug used may vary according to the physician’s preference. Click here for more on treatment of peritoneal mesothelioma.

Retrieved from http://www.mesotheliomaweb.org/treat.htm#surgery on May 5/16/07

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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.

Retrieved from http://www.mesotheliomaweb.org/cause.htm on May 16, 2007

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1. What is the mesothelium?

The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

The mesothelium has different names, depending on its location in the body. The peritoneum is the mesothelial tissue that covers most of the organs in the abdominal cavity. The pleura is the membrane that surrounds the lungs and lines the wall of the chest cavity. The pericardium covers and protects the heart. The mesothelial tissue surrounding the male internal reproductive organs is called the tunica vaginalis testis. The tunica serosa uteri covers the internal reproductive organs in women.

2. What is mesothelioma?

Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.

3. How common is mesothelioma?

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age.

4. What are the risk factors for mesothelioma?

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person’s risk of developing cancer of the air passageways in the lung.

5. Who is at increased risk for developing mesothelioma?

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.

There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

6. What are the symptoms of mesothelioma?

Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

7. How is mesothelioma diagnosed?

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. If the cancer is in the abdomen, the doctor may perform a peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

8. How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient’s age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

* Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.

* Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).

* Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).

To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

9. Are new treatments for mesothelioma being studied?

Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.

People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the Cancer Information Service (CIS) (see below) at 1–800–4–CANCER. Information specialists at the CIS use PDQ®, NCI’s cancer information database, to identify and provide detailed information about specific ongoing clinical trials. Patients also have the option of searching for clinical trials on their own. The clinical trials page on the NCI’s Cancer.gov Web site, located at http://www.cancer.gov/clinical_trials on the Internet, provides general information about clinical trials and links to PDQ.

People considering clinical trials may be interested in the NCI booklet Taking Part in Clinical Trials: What Cancer Patients Need To Know. This booklet describes how research studies are carried out and explains their possible benefits and risks. The booklet is available by calling the CIS, or from the NCI Publications Locator Web site at http://www.cancer.gov/publications on the Internet.

# # #

National Cancer Institute (NCI) Resources

Cancer Information Service (toll-free)
Telephone: 1–800–4–CANCER (1–800–422–6237)
TTY: 1–800–332–8615

Online
NCI’s Web site: http://www.cancer.gov
LiveHelp, NCI’s live online assistance:
https://cissecure.nci.nih.gov/livehelp/welcome.asp

Labels: Mesothelioma

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Treatment of MM using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.

Surgery

Surgery, either by itself or used in combination with pre- and post-operative adjuvant therapies has proved disappointing with a 5 year survival rate of less than 10%. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. It is not possible to remove the entire mesothelium without killing the patient.

Radiation

For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston. [7] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.

Chemotherapy

In February 2004, the Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed.

Immunotherapy

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.

Heated Intraoperative Intraperitoneal Chemotherapy

A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[7] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.

This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.

"Mesothelioma." Wikipedia, The Free Encyclopedia. 16 May 2007, 21:39 UTC. Wikimedia Foundation, Inc. 17 May 2007 .

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Posted by Mike Seever at 5:08 PM | Permalink | Comments

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.

Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[4] However, there is now evidence that smaller particles may be more dangerous than the larger fibers.[1][2] They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[3]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.

Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:

* Neurofibromatosis type 2 at 22q12
* P16INK4A
* P14ARF

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

* Inactivation of tumor suppressor genes
* Activation of oncogenes
* Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
* Activation of DNA repair enzymes, which may be prone to error
* Activation of telomerase
* Prevention of apoptosis

Asbestos fibres have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.

"Mesothelioma." Wikipedia, The Free Encyclopedia. 16 May 2007, 21:39 UTC. Wikimedia Foundation, Inc. 17 May 2007 .

Labels: Mesothelioma

Posted by Mike Seever at 5:07 PM | Permalink | Comments

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).

If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.

If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.


"Mesothelioma." Wikipedia, The Free Encyclopedia. 16 May 2007, 21:39 UTC. Wikimedia Foundation, Inc. 17 May 2007 .

Labels: Mesothelioma

Posted by Mike Seever at 5:07 PM | Permalink | Comments

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

* chest wall pain
* pleural effusion, or fluid surrounding the lung
* shortness of breath
* fatigue or anemia
* wheezing, hoarseness, or cough
* blood in the sputum (fluid) coughed up

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

* abdominal pain
* ascites, or an abnormal buildup of fluid in the abdomen
* a mass in the abdomen
* problems with bowel function
* weight loss

In severe cases of the disease, the following signs and symptoms may be present:

* blood clots in the veins, which may cause thrombophlebitis
* jaundice, or yellowing of the eyes and skin
* low blood sugar level
* pleural effusion
* pulmonary emboli, or blood clots in the arteries of the lungs
* severe ascites

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.


"Mesothelioma." Wikipedia, The Free Encyclopedia. 16 May 2007, 21:39 UTC. Wikimedia Foundation, Inc. 17 May 2007 .

Labels: Mesothelioma

Posted by Mike Seever at 5:06 PM | Permalink | Comments

Mesothelioma is a form of cancer that is almost always caused by previous exposure to asbestos.In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. Unlike lung cancer, there is no association between mesothelioma and smoking.

"Mesothelioma." Wikipedia, The Free Encyclopedia. 16 May 2007, 21:39 UTC. Wikimedia Foundation, Inc. 17 May 2007 .

Labels: Mesothelioma

Posted by Mike Seever at 5:05 PM | Permalink | Comments