MESOTHELIOMA
Dr.sreechithra.H
Mesotheleoma is a malignant form of cancer arising from the mesothelium, a protective lining that covers most of the body’s internal organs. It is common among people who have worked on jobs were they have inhaled asbestos particles, or have been exposed to asbestos dust and fibers in other ways.
COMMEN SITES OF MELANOMA
- Pleura (outer lining of lung and internal chest wall)
- Peritoneum(the lining of abdominal cavity)
- Pericardium(sac that surrounds the heart)
- Tunica vaginalis
WHAT IS ASBESTOS?
Asbestos is a group of minerals that occur naturally as strong flexible fibers. It is widely used in many industrial products, including cement, brake linings, and insulation. During their manufacturing procedure tiny asbestos floats in air, its inhalation or swallowing causes serious health hazard , which apart from mesothelioma includes lung cancer, asbestosis(a non cancerous lung disease),other cancers of kidney, trachea etc.
Many building material still uses asbestosis both in public and domestic buildings even prior to their banning.
CARSINOGENIC PROPERTIES OF ASBESTOS
- Analysis of the interaction between asbestos and DNA suggest that the asbestos fiber after entangled to chromosome can induce complex abnormality, which include monosomy of chromosome 22. This can induce deletion of tumor suppressor gene resulting in the development of a tumor.
- Inactivation of tumor suppressor genes.
- Activation of oncogenes.
- Activation of proto oncogenes
- Activation of DNA repairs enzymes, which may prone to error.
- Activation of telomerase.(it is an enzyme that adds specific DNA sequence repeats (TTAGGG in all vertebrates)to the 3ed end of DNA strands in the telomere region. It has direct relation to the development of carcinoma and with diseases like Werner’s syndrome, ataxia telangiectasia, bloom syndrome, fanconi’s anemia, nijmeg en breakage syndrome etc).
- Prevention of apoptosis(is the process of programmed cell death(PCD) or natural cell death. This will leads to the prevention of cell death among CA cells)
- Asbestos fibers alter the function and secretary properties of macrophages, which in turn secrete large amount of hydroxyl radicle, which are known for their clastogenic function. This will trigger the ongogenic activation by interacting with DNA.
- Asbestos have immunosuppressive properties.
EPIDAMOLOGY
INCIDENCE
Although the incidence rates have increased in the past 20 years, it is still a relatively rare form of cancer.
- The incidence rate is 1:1,000,000. The highest incidence is found in Brittan, Australia, and Belgium- 7-40: I, 000.000.
- Mesothelioma occurs more in men than in women and the risk increases with age, although it is susceptible to any age and sex.
- Around 3000 deaths occur in USA alone annually due to this carcinoma.
RISK FACTOR
- Working with asbestos is one of the major risk factor( it is officially recognized since 1900)
- Radiation
- Intrapleural thorium dioxide(Thorotrast)
- Inhalation of other fibrous silicate such as Erionite
- Although smoking has no relation to the development of mesothelioma it gradually increases the risk of formation of other asbestos induced carcinoma.
- Environmental exposure to asbestos.
- Para occupational secondary exposure (family members living with asbestos workers has increased risk of mesothelioma due to asbestos dust brought in their clothes and hair.
PATHOPHYSIOLOGY
Mesothelium consists of a single layer of flattened or cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities.
Inhalation of the asbestos fumes will leads to the deposition of those particles in the parenchyma of the lung tissue. It will later result in the penetration of the visceral pleura from where it is carried to the pleural surface, were it gradually develop to form mesothelial plaques. From lung it is transported to the abdomen and other organs through lymphatic system, and also by ingestion of contaminated sputum.(Long thin asbestos fibers (blue asbestos)are more potent carcinogen than the feathery once(white fibers).more over small particle is more dangerous than the large once as it easily penetrate the lung parenchyma.).
Deposition of asbestos in the mesothelium will attract significant number of macrophages and other cells of immune system, to form a localized lesion. This in turn will continue to attract and accumulate macrophages, and as the disease progress cellular changes within the lesion culminate into a morphologically malignant tumor. Also this fiber will interact with DNA, causing mutation, which will also help in triggering the oncogenic activity.
SINGS AND SYMPTOMS
Sings and symptom may not appear until 20-50 years after the exposure to asbestos. This carcinoma does not usually spread to bones, brain and adrenal glands.
Sings of peritoneal mesothelioma
- Weight loss
- Cachexia
- Abdominal swelling and pain due to acitis
- Mass in abdomen
- Bowel obstruction
- Blood clotting anomalies
- Anemia
- Fever
If the CA has spread beyond the mesothelium symptoms like pain, trouble swallowing, swelling of neck and face can also be seen.
Sings of pleural mesothelioma
Unlike lung cancer it is usually found only on one side of lung
- Shortness of breath
- Cough
- Pain in chest wall(due to accumulation of fluid between the pleural space)
- Pleural effusion
- Fatigue or anemia
- Wheezing, hoarseness or cough
- Blood in sputum or hemopytisis
In severe cases the person may have many tumors mass. The individual may develop pneumo thorax or even collapse of lung.
In severe case
- Bloods clots in veins, which can cause thrombophlebitis.
- Disseminated intra vascular coagulation causing severe bleeding in the internal organs
- Jaundice
- Decreased blood sugar level
- Plural effusion
- Pulmonary emboli
- Severe ascitis
STAGING
Staging is based on the recommendation of the international mesothelioma interest group. Mesothelioma is staged from 1a- 1V based on the TNM status
T- Size of tumor
N- Involment of lymph node
M- Metastasis
- T(1-4)- size of tumor or direct extension of primary tumor
- N(0-3)- No- no nodular involvement
N1- regional involvement
N2- moderate distant involvement
N3grave involvement of distal nodes
- M(0/1)- Mo- no metastasis
M1- metastasis present
DIAGNOSIS
Diagnosis is often very difficult as it is very similar to many other diseases especially to that of bronchogenic carcinoma of lung.
- Diagnosis often begin with the review on the patients medical history for any asbestos exposure
- Physical examination
- Chest X ray will reveal any plural tumor or thickening
- CT or MRI
- Cytology- fluid aspired from plural or abdominal cavity can detect any malignant cells
- Biopsy – done by thorascopy or laparoscopy to find any abnormal cell
SCREENING
Screening is usually done in people who are exposed to asbestos, for the early detection of the disease
- It is done by ascertaining the level of serum osteopontin
- Serum level of soluble mesothelin related protein
- Measuring the level of mesothelin related protein(SMRP) released by diseased mesothelial protein
PROGNOSIS
Despite treatment by surgery, radiation and by other methods, mesothelioma gives a very poor prognosis
TREATMENT
Treatment is based on the staging and development of tumors. Usually combination of radiation and chemotherapy is done up to stage 1 or 11.
- Surgery
Surgery by its self has proven to be very disappointing. so it is combined with radiation and chemotherapy.. Usually during the surgery the lining of the lung is removed. In a less common method lung, lining inside the chest, hemi diaphragm and the pericardium is removed
- Radiation
For patients with localized disease and who can tolerate radiation is given in combination with chemotherapy as a post operative consol dative treatment.
- Chemotherapy
It is the only treatment for mesothelioma that has proven to improve the surveillance rate.
- Immunotherapy
It is the process to boost the immune response artificially. but mesothelioma cells pose resistant to this therapy, and also it is associated wit major side effects
- Heated intra operative intra peritoneal chemotherapy
Here the surgeon removes as much of the tumor possible followed by the direct administration of the chemotherapy agent, heated between 40- 48 degree centigrade. This is per fused for about 60- 120 mts and then drained.
NOTABLE PEOPLE DIED FROM MESOTHELIOMA
- Hamilton Jordan- chief of staff for president Jimmy Cartor, and a life long cancer activist died on 2008
- Bernie Banton- an Australian worker’s activist succumbed to this disease after a long fight for compensation from the company responsible.
- Rock an roll musician and song writer Warren Zevon scum to this disease after a long period of untreated illness and pain
LEGAL ISSUES
The first law suit against asbestos manufacturer was bought in at 1929. In 1960 an article published by Wagner el al first officially establish mesothelioma as a disease arising due to the exposure of asbestos. in 1965 an article in British journal of industrial medicine establish that people who lived in the neibourhood of asbestos and mines has contracted mesothelioma.
After 1929 many law suits have been filled against asbestos manufacturer for neglecting to implement safety measurements after the links between asbestos, mesothelioma, asbestosis etc become known. However, to date, the government has not stepped in and there are no federal laws governing asbestos compensation. Despite the warning many of the building products still process this silent killer ASBESTOS
Dr.sreechithra.H
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