Family Run Online Furniture Businesses Thriving


With the economy still down, some families have started successful furniture eCommerce businesses to help their families, in some cases with great success.

FOR IMMEDIATE RELEASE

PRLog (Press Release) - Jan 20, 2012 - There have been several stories in the media recently about ordinary families who are running very successful online furniture businesses, in many cases from home.  With the general economy still in a state of turmoil, many workers are turning to the internet to make extra money to help support their families. With the barrier to entry in e-commerce much lower than in brick-and-mortar based businesses, some families have even been able to tap into the furniture market, and had outstanding success as a result.

Natalie Cox, a woman from Gilbert, Arizona, in the US, started a thriving business almost by accident, after racking her brains to figure out something she could do to help her family’s financial situation in the down economy. "With the economy down, we were struggling and I just felt like I needed to do something and help out," said Natalie. "I stayed up late one night mentally thinking of things I could do."

Natalie soon came up with the idea of refurnishing furniture and selling it online on classifieds websites like Craigslist. She quickly put the idea into action, only to realise that her plan worked out even better than she had hoped. "They sold a lot faster than I thought they would," said Natalie. "It all took off from there”.

It wasn’t long before Natalie was running a thriving business out of the family garage called “Natty by Design”. Natalie’s business also encompasses a blog, and companies in the industry have started to take notice, with many now advertising on the site.

Another successful family furniture business is run by Dan Mayne, from Ontario, Canada. Dan’s business, Much More Furniture, started as an online furniture store, exporting from ports in the United States and distributing to customers on the island of Bermuda. Dan has since been able to grow his business to service islands right throughout the Caribbean, all the while running his business from his home in Canada.

Not only has Dan been able to rapidly grow the distribution network of his business, he is also now selling the ecommerce platform that he designed to power his company’s website. Several high street businesses have already made a commitment to purchase the system, which enables companies to view, zoom and alter an inventory of 16,000 products.

It is not only overseas-based online furniture businesses that are currently thriving. Here in the UK there is also a family owned furniture businesses that is very prominent online. SofaSofa, a company based in Wales, is owned and run by the Ridgwell family, and now supplies sofas to over 1000 customers each week from right around the UK, and counts previous customers in the millions. The family business was founded in 1981, and now services many customers online from its website, sofasofa.co.uk. While perhaps not so small anymore, the success of SofaSofa demonstrates how far a family run furniture business can come in the booming information age.

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ReadmoreFamily Run Online Furniture Businesses Thriving

Google Presents Snow on Computer Screen

Want to feel the snow? It goes all the way to the poles, you can feel it through the computer screen wherever you are.

That's the new features offered by Google's search engine during this winter. By using the phrase "Let it snow" in the Google search box, you will get the effects of snowfall on the monitor screen.

The hail was initially in the form of digital animation drizzle snow. Eventually the snow will fill your monitor up to white. The longer, the area of ​​snow dew on the screen width and thickness up to close the text or images on the screen.

You can play around on the screen fogged it. As in the glass windows fogged, you can wipe the screen with the mouse pointer to clear the playing dew earlier. To remove all dew all over the screen, click the button at the top right Defrost. The snow was still ongoing, but the dew on the screen will disappear.


Source :   kompas.com
ReadmoreGoogle Presents Snow on Computer Screen

About Angioplasty

Angioplasty

From Wikipedia, the free encyclopedia
Angioplasty
Intervention

Balloon angioplasty.
ICD-9-CM 00.6, 36.0 39.50
MeSH D017130
Angioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size using water pressures some 75 to 500 times normal blood pressure (6 to 20 atmospheres). The balloon crushes the fatty deposits, opening up the blood vessel for improved flow, and the balloon is then deflated and withdrawn.
The word is composed of the medical combining forms of the Greek words ανγειος angeus meaning "vessel" and πλαστός plastus meaning "formed" or "moulded." Angioplasty has come to include all manner of vascular interventions that are typically performed in a minimally invasive or percutaneous method.

Contents

 [hide

[edit] History

Diagram of a balloon catheter.
Angioplasty was initially described by the US interventional radiologist Charles Dotter in 1964.[1] Dr. Dotter pioneered modern medicine with the invention of angioplasty and the catheter-delivered stent, which were first used to treat peripheral arterial disease. On January 16, 1964, Dotter percutaneously dilated a tight, localized stenosis of the superficial femoral artery (SFA) in an 82-year-old woman with painful leg ischemia and gangrene who refused leg amputation. After successful dilation of the stenosis with a guide wire and coaxial Teflon catheters, the circulation returned to her leg. The dilated artery stayed open until her death from pneumonia two and a half years later.[2] Charles Dotter is commonly known as the "Father of Interventional Radiology" and was nominated for the Nobel Prize in medicine in 1978.
The first coronary angioplasty on a waking patient was performed by Swiss cardiologist Andreas Gruentzig in September 1977.[3]

[edit] Causes of Coronary Artery Disease

Blockages in the arteries may be caused by hypertension, diabetes, sedentary lifestyle, smoking, high cholesterol levels, and cardiovascular disease. Removing blockages is done with angioplasty.[4]
Angioplasties are safer than bypass surgery; less than 1% of people die from complications after this procedure.[5] Complications that may occur after or during an angioplasty:
  • Tearing of the artery, resulting in total blockage and possible myocardial infarction; this can usually be repaired with a stent
  • dislodging of a clot, which may cause a stroke in some circumstances (in less than 1% of patients who undergo angioplasties)
  • Bleeding or bruising where the catheters were inserted
  • Kidney problems, especially in people with underlying kidney disease and diabetes. This is caused by the iodine contrast dye used for the X-ray; intravenous fluids and medications can be given before and after the procedure to reduce this risk.
  • Arrhythmia (irregular heartbeat);[6]
  • Allergic reaction to the dye given during the angioplasty
  • Myocardial infarction, which occurs in 3% to 5% of cases
  • The artery closing down instead of opening up. This may necessitate emergency coronary artery bypass grafting during the procedure (2-4% of patients).
  • Restenosis—one of the most common complications of angioplasties, which consists in the gradual re-narrowing of the blood vessels within several weeks or months of the procedure. Some conditions increase the risk of developing this complication, e.g., hypertension, diabetes, angina or kidney disease.
  • Blood clots (in-stent thrombosis) forming within stents hours or months after the procedure. These may cause myocardial infarction.[7]
The risks associated with angioplasty are greater in
  • patients older than 75 years,
  • patients who suffer from diabetes or kidney disease,
  • those who have extensive heart disease or blood clots in the heart arteries
  • people with poor pumping function in their hearts
  • women
Complications such as myocardial infarction, stroke or kidney problems are, however, among the rarest. The death rate among patients who have angioplasty is very small, about 0.1% (compared to 1% to 2% for routine bypass surgery).
In most cases, when the potential benefits and the expected risks are taken into account the choice to perform angioplasty is the right one. (risk-benefit ratio).[8]

[edit] Limited value in stable patients

The value of angioplasty in rescuing someone having a heart attack (by immediately alleviating an obstruction) is clearly defined in multiple studies, but studies have failed to find reduction in hard endpoints for angioplasty vs. medical therapy in stable angina patients. The artery-opening procedure can temporarily alleviate chest pain, but does not contribute to longevity. The "vast majority of heart attacks do not originate with obstructions that narrow arteries".[9]
A more permanent and successful way to prevent heart attacks in patients at high risk is to give up smoking, increase exercise/yoga and take "drugs to get blood pressure under control, drive cholesterol levels down and prevent blood clotting".[9]

[edit] After the procedure

After angioplasty, most of the patients are monitored overnight in the hospital but if there are no complications, the next day, patients are sent home.
The catheter site is checked for bleeding and swelling and the heart rate and blood pressure are monitored. Usually, patients receive medication that will relax them to protect the arteries against spasms. Patients are typically able to walk within two to six hours following the procedure and return to their normal routine by the following week.[10]
Angioplasty recovery consists in avoiding physical activity for several days after the procedure. Patients are advised to avoid any type of lifting, babysitting grandchildren or other strenuous physical activity for a week.[11] Patients will need to avoid physical stress or prolonged sport activities for a maximum of two weeks after a delicate balloon angioplasty.[12]
Patients with stents are usually prescribed an anticoagulant, clopidogrel, which is taken at the same time as acetylsalicylic acid (aspirin). These medicines are intended to prevent blood clots and they are usually taken for at least the first months after the procedure is performed. In most cases, patients are given these medicines for 1 year.
Patients who experience swelling, bleeding or pain at the insertion site, develop fever, feel faint or weak, notice a change in temperature or color in the arm or leg that was used or have shortness of breath or chest pain should immediately seek medical advice.

[edit] Peripheral angioplasty

Peripheral angioplasty refers to the use of a balloon to open a blood vessels outside the coronary arteries. It is commonly done to treat atherosclerotic narrowings of the abdomen, leg and renal arteries. PA can also be done to treat narrowings in veins, etc. Often, peripheral angioplasty is used in conjunction with peripheral stenting and atherectomy.

[edit] Coronary angioplasty

A coronary angiogram (an X-ray with radio-opaque contrast in the coronary arteries) that shows the left coronary circulation. The distal left main coronary artery (LMCA) is in the left upper quadrant of the image. Its main branches (also visible) are the left circumflex artery (LCX), which courses top-to-bottom initially and then toward the centre-bottom, and the left anterior descending (LAD) artery, which courses from left-to-right on the image and then courses down the middle of the image to project underneath the distal LCX. The LAD, as is usual, has two large diagonal branches, which arise at the centre-top of the image and course toward the centre-right of the image.
Percutaneous coronary intervention (PCI), commonly known as coronary angioplasty is a therapeutic procedure to treat the stenotic (narrowed) coronary arteries of the heart found in coronary heart disease. These stenotic segments are due to the build up of cholesterol-laden plaques that form due to atherosclerosis. PCI is usually performed by an interventional cardiologist.
Treatment with PCI for patients with stable coronary artery disease reduces chest pain, but does not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.[13]

[edit] Renal artery angioplasty

Atherosclerotic obstruction of the renal artery can be treated with angioplasty of the renal artery (percutaneous transluminal renal angioplasty, PTRA). Renal artery stenosis can lead to hypertension and loss of renal function.

[edit] Carotid angioplasty

Carotid artery stenosis is treated with angioplasty and stenting for high-risk patients in many hospitals.

[edit] Cerebral arteries angioplasty

In 1983, the Russian neurosurgeon Zubkov and colleagues reported the first use of transluminal balloon angioplasty for vasospasm after aneurysmal SAH.[14][15]

[edit] See also

[edit] References

  1. ^ Dotter, C.T. and M.P. Judkins. Transluminal treatment of arteriosclerotic obstruction. Circulation. November 1964, Volume XXX. Pages 654-670.
  2. ^ Rosch Josef et al. (2003). "The birth, early years, and future of interventional radiology". J Vasc Interv Radiol 14 (7): 841–853. PMID 12847192.
  3. ^ Biographic sketch of Andreas Gruentzig. http://www.ptca.org/archive/bios/gruentzig.html
  4. ^ "Angioplasty". Retrieved 2010-04-06.
  5. ^ "The Facts on Angioplasty". Retrieved 2010-04-06.
  6. ^ "What Are the Risks of Coronary Angioplasty?". Retrieved 2010-04-06.
  7. ^ "Risks And Possible Complications". Retrieved 2010-04-06.
  8. ^ "PTCA or Balloon Angioplasty". Retrieved 2010-04-06.
  9. ^ a b Kolata, Gina. "New Heart Studies Question the Value Of Opening Arteries" The New York Times, March 21, 2004. Retrieved January 29, 2011.
  10. ^ "What should I expect after my procedure?". Retrieved 2010-04-06.
  11. ^ "After the operation". Retrieved 2010-04-06.
  12. ^ "Angioplasty Recovery". Retrieved 2010-04-06.
  13. ^ Boden W. E., O'Rourke R. A. et al. (2007). "Optimal medical therapy with or without PCI for stable coronary disease". N Engl J Med 356 (15): 1503–16. doi:10.1056/NEJMoa070829. PMID 17387127.
  14. ^ Zubkov IuN, Nikiforov BM, Shustin VA (Sep-Oct 1983). "1st attempt at dilating spastic cerebral arteries in the acute stage of rupture of arterial aneurysms". Zh Vopr Neirokhir Im N N Burdenko 5 (5): 17–23. PMID 6228084.
  15. ^ Zubkov YN, Nikiforov BM, Shustin VA (Sep-Oct 1984). "Balloon catheter technique for dilatation of constricted cerebral arteries after aneurysmal SAH". Acta Neurochir (Wien) 70 (1-2): 65–79. doi:10.1007/BF01406044. PMID 6234754.
  16. Source :  http://en.wikipedia.org/wiki/Angioplasty
ReadmoreAbout Angioplasty

About Mesothelioma

Mesothelioma

From Wikipedia, the free encyclopedia
Mesothelioma
Classification and external resources

Left sided mesothelioma with mediastinal node enlargement : CT scan.
ICD-10 C45
ICD-9 163
ICD-O: M9050/3-9055
OMIM 156240
DiseasesDB 8074
MedlinePlus 000115
eMedicine med/1457
MeSH D008654
Mesothelioma, more precisely malignant mesothelioma, is a rare form of cancer that develops from the protective lining that covers many of the body's internal organs, the mesothelium. It is usually caused by exposure to asbestos.[1]
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),[2] or the tunica vaginalis (a sac that surrounds the testis).
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.[3] Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases the risk of other asbestos-induced cancers.[4] Those who have been exposed to asbestos have collected damages for asbestos-related disease, including mesothelioma. Compensation via asbestos funds or lawsuits is an important issue in law practices regarding 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.

Contents

 [hide

[edit] Signs and symptoms

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) 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:
  • Blood clots in the veins, which may cause thrombophlebitis
  • Disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
  • 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.

[edit] Cause

Working with asbestos is the major risk factor for mesothelioma.[5] In the United States, asbestos is the major cause of malignant mesothelioma and has been considered "indisputably"[6] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a “signal” or “sentinel” tumor.[7][8][9][10] A history of asbestos exposure exists in most cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[11]
Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. 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 publicly 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 official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, they are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[12] Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[13] There appears to be a linear, dose-response relationship, with increasing dose producing increasing disease.[14] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[6] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[6] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.
The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 1–3 months of exposure.[15][16] People who work with asbestos wear personal protective equipment to lower their risk of exposure.
Latency, the time from first exposure to manifestation of disease, is prolonged in the case of mesothelioma. It is virtually never less than fifteen years and peaks at 30–40 years.[6] In a review of occupationally related mesothelioma cases, the median latency was 32 years.[17] Based upon the data from Peto et al., the risk of mesothelioma appears to increase to the third or fourth power from first exposure.[14]

[edit] Environmental exposures

Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos. Recently, however, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.[18][19] The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.

[edit] Occupational

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.

[edit] Paraoccupational secondary exposure

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases.[20][21] 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 fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

[edit] Asbestos in buildings

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.

[edit] Diagnosis

CXR demonstrating a mesothelioma
CT scan of a patient with mesothelioma, coronal section (the section follows the plane that divides the body in a front and a back half). The mesothelioma is indicated by yellow arrows, the central pleural effusion (fluid collection) is marked with a yellow star. Red numbers: (1) right lung, (2) spine, (3) left lung, (4) ribs, (5) descending part of the aorta, (6) spleen, (7) left kidney, (8) right kidney, (9) liver.
Micrograph of a pleural fluid cytopathology specimen showing mesothelioma.
Micrographs showing mesothelioma in a core biopsy.

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 cytopathology if this fluid is aspirated with a syringe. For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial[disambiguation needed ] 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). Unfortunately, the diagnosis of malignant mesothelioma by cytology alone is difficult, even with expert pathologists.
Generally, a biopsy is needed to confirm a diagnosis of malignant 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. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision 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.
Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics. There are numerous tests and panels available. No single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant.
Typical immunohistochemistry results
Positive Negative
EMA (epithelial membrane antigen) in a membranous distribution CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1) B72.3
Calretinin MOC-3 1
Mesothelin-1 CD15
Cytokeratin 5/6 Ber-EP4
HBME-1 (human mesothelial cell 1) TTF-1 (thyroid transcription factor-1)
There are three histological types of malignant mesothelioma: (1) Epithelioid; (2) Sarcomatoid; and (3) Biphasic (Mixed). Epithelioid comprises about 50-60% of malignant mesothelioma cases and generally holds a better prognosis than the Sarcomatoid or Biphasic subtypes.[22]

[edit] Staging

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[23] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.[23][24]

[edit] 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.[25] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[26]

[edit] Pathophysiology

Diffuse pleural mesothelioma with extensive involvement of the pericardium.
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 fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber 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 fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.
Pleural contamination with asbestos or other mineral fibers 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).[6] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. 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.[27]
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers 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 localized lesions of accumulated asbestos fibers 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 tumor.
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 fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers 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 fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber 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:
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:
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.

[edit] Treatment

The prognosis for malignant mesothelioma remains disappointing, although there have been some modest improvements in prognosis from newer chemotherapies and multimodality treatments.[28] Treatment of malignant mesothelioma at earlier stages has a better prognosis, but cures are exceedingly rare. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors 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. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.[29]

[edit] Surgery

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.[28] However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008). (For more information on multimodality therapy with surgery, see below). 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.

[edit] 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. 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.

[edit] Chemotherapy

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[30] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[31]
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.

[edit] 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.

[edit] Heated Intraoperative Intraperitoneal Chemotherapy

A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[32] 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.
This technique is also used in patients with malignant pleural mesothelioma.[33]

[edit] Multimodality Therapy

All of the standard approaches to treating solid tumors—radiation, chemotherapy, and surgery—have been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (3–14 years) among patients with favorable prognostic factors.[34] However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years).[28] Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma.[35] Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation.[36] Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.[37]

[edit] Epidemiology

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year.[38] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[39] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. 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. Approximately one fifth to one third of all mesotheliomas are peritoneal.
Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[40] Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.

Source : http://en.wikipedia.org/wiki/Mesothelioma
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