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Sunday, 21 September 2008

7 Steps How to Determine if You Have Mesothelioma

Mesothelioma diagnosis is very important as far as an early treatment is considered. It helps with better pain management. Mesothelioma diagnosis is confusing as the symptoms mimic many lung infections.

Here are the 7 Steps :

1. Don't sit there and keep guessing. Consult your physician.
2. Get Mesothelioma tests done. An early initiation of treatment will help reduce the cancer pain considerably.
- Valuable Imaging techniques used in Mesothelioma tests are X Ray, CT (Computerized tomography), MRI (Magnetic Resonance Imaging) and PET (Positive Electron Tomography)
- Invasive procedures for Tissue and fluid samples are also done. Usually invasive procedures {which invade the body} are required to make a final confirmed Mesothelioma Diagnosis (Thoracoscopy, Peritoneoscopy and Biopsy)
- Recently the first ever Blood test for Mesothelioma have been devised as reported by Pacific North-West Research Institute. This is basedon the fact that [ cells release tumor markers called SMR (Soluble mesothelin-related) proteins

3.Two important questions you should answer before you go ahead with the Mesothelioma diagnosis are: Have you been exposed to asbestos? (Although not all the Mesothelioma cases are direct results of asbestos exposure there is a strong association between the two.) Do you experience Mesothelioma symptoms?

4. Asbestosis mesothelioma, sometimes called mesothelioma lung cancer, most often occurs in the thin membrane lining (or mesothelium) of cavities that house the lungs, chest, abdomen, and (sometimes) heart. The immune system identifies the "foreign" matter in the body and focus on the asbestos fiber, trying to dissolve it. The acids that the body excrete, starts to irritate the surrounding healthy body cells. Mesothelioma cancer commence when the healthy body cells mutate due to the acidic irritation. In stead of dying off... their cell membranes harden, and they start to multiply. The cancerous growth creates a localised pain that increases over time until it becomes unbarable.[1]

5. You may have been at a place or environment with asbestos risk at any time during your lifetime. It could have been in the home where your grew up, your school, your current home or work environment, or even a specific geographical location.[2]

6. Mesothelioma is difficult to treat, largely due to the fact that it remains latent in the body for up to five decades and is usually not diagnosed until its late stages. Also, diagnosis may be difficult due to the non-specific nature of most mesothelioma symptoms, which often resemble symptoms of less serious diseases.

7. The process for diagnosis usually begins with a compilation of the patient's full medical and work history including any exposure to asbestos. A medical examination is performed and if a problem is suspected, one or more diagnostic tests are ordered. These typically include medical imaging tests such as x-ray or CT and MRI scans, as well as biopsy procedures that test samples of fluid and tissue for the presence of cancer cells. Diagnostic tests are also used to determine how far the cancer has advanced, and whether it has spread to other locations in the body.



Source : www.wikihow.com


Pathophysiology of Mesothelioma

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 fibers 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.

Source : www.wikipedia.com

Screening and Staging of Mesothelioma

A. Screening

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.

B. Staging

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.

Source : www.wikipedia.com

Friday, 19 September 2008

Diagnosis Mesothelioma

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.

Typical immunohistochemistry results
PositiveNegative
EMA (epithelial membrane antigen) in a membranous distributionCEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1)B72.3
CalretininMOC-3 1
Mesothelin-1CD15
Cytokeratin 5/6Ber-EP4
HBME-1 (human mesothelial cell 1)TTF-1 (thyroid transcription factor-1)




Source : www.wikipedia.com

Signs and symptoms Mesothelioma

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 (hemoptysis)

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:

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.



Source : www.wikipedia.com




Mesothelioma

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 internal chest wall), but it may also occur in the peritoneum (the lining of the abdominal cavity), the pericardium (a sac that surrounds the heart) or tunica vaginalis.

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they 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. Unlike lung cancer, there is no association between mesothelioma and smoking.[1] Compensation via asbestos funds or lawsuits is an important issue in mesothelioma (see asbestos and the law).

The symptoms of mesothelioma include shortness of breath due to pleural effusion (fluid between the lung and the chest wall) or chest wall pain, and general symptoms such as weight loss. The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy (tissue sample) and microscopic examination. A thoracoscopy (inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc to obliterate the pleural space (called pleurodesis), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis. Research about screening tests for the early detection of mesothelioma is ongoing.


Source : www.wikipedia.com