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.
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 heart,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 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. Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases the risk of other asbestos-induced cancers. 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.
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.
Cause
Working with asbestos is the major risk factor for mesothelioma.In the United States, asbestos is the major cause of malignant mesothelioma and has been considered "indisputably" 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. 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.
Asbestos was known in antiquity, but it wasn't mined and widely used commercially until 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 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. 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. There appears to be a linear, dose-response relationship, with increasing dose producing increasing disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.Again, there is no known safe level of asbestos 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. 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. In a review of occupationally related mesothelioma cases, the median latency was 32 years.Based upon the data from Peto et al, the risk of mesothelioma appears to increase to the third or fourth power from first exposure.
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, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition. 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.
Occupational
Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 1900s. 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.
Paraoccupational secondary exposure
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 fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
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.
Diagnosis
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 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.
Staging
Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group 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.
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.
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 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.
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. 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:
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.
Treatment
The prognosis for malignant mesothelioma remains disappointing, although there have been some modest improvements in prognosis from newer chemotherapies and multimodality treatments.[27] 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.
Surgery
Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.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.
Radiation
Wikibooks has a book on the topic of
Radiation Oncology/Lung/Mesothelioma
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.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
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. 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 combination pemetrexed group in patients who 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.
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.
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. 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.
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.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).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.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. 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.
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.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. 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. 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.
Society and culture
Famous victims
Mesothelioma, though rare, has had a number of notable patients.
Malcolm McLaren, former manager of New York Dolls and Sex Pistols, died on 8 April 2010.
Hamilton Jordan, Chief of Staff for U.S. President Jimmy Carter and lifelong cancer activist, died in 2008.
Richard J. Herrnstein, psychologist and co-author of The Bell Curve, died in 1994.
Australian anti-racism activist Bob Bellear died in 2005.
British science fiction writer Michael G. Coney, responsible for nearly 100 works, also died in 2005.
American film and television actor Paul Gleason, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast Club, died in 2006.
Mickie Most, an English record producer, died of mesothelioma in 2003.
Paul Rudolph, American architect, died in 1997.
Bernie Banton, an Australian workers' rights activist, fought a long battle for compensation from James Hardie after he contracted mesothelioma after working for that company. He claimed James Hardie knew of the dangers of asbestos before he began work with the substance making insulation for power stations. Mesothelioma eventually took his life along with his brothers and hundreds of James Hardie workers. James Hardie made an undisclosed settlement with Banton only when his mesothelioma had reached its final stages and he was expected to have no more than 48 hours to live. Australian Prime Minister Kevin Rudd mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian federal election.
Actor Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen subsequently sought alternative treatments at clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or from its use as an insulating material in automobile racing suits (McQueen was an avid racing driver and fan).
United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder award is given yearly by his wife at the MARF Symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.
Rock and roll musician and songwriter Warren Zevon, after a long period of untreated illness and pain, was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments that he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind, including the song "Keep Me in Your Heart," which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.
Christie Hennessy, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death.Hennessy's mesothelioma has been attributed to his younger years spent working on building sites in London.
Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation, died of mesothelioma in 1994.
Scottish Labour MP John William MacDougall died of mesothelioma on August 13, 2008, after fighting the disease for two years.
Australian journalist and news presenter Peter Leonard of Canberra succumbed to the condition on September 23, 2008.
Terrence McCann, Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006, at his home in Dana Point, California.
Merlin Olsen, Pro Football Hall of Famer and television actor, died on March 10, 2010, from mesothelioma that had been diagnosed in 2009.
Notable people who have lived for some time with mesothelioma
Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message" for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma. Author Paul Kraus was diagnosed with peritoneal mesothelioma in July 1997. He was given a prognosis of less than a year to live and used a variety of complementary modalities. He continues to outlive his prognosis and wrote a book about his experience "Surviving Mesothelioma and Other Cancers: A Patient's Guide" in which he presented his philosophy about healing and the decision making that led him to use integrative medicine.
Legal issues
The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.
History
The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos.The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Prior to the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer.In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.
In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.
Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.
By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.
In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.
viernes, 20 de agosto de 2010
Lung Cancer(this can happen to you if u smoke)
Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer, the most common cause of cancer-related death in men and women, is responsible for 1.3 million deaths worldwide annually, as of 2004. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss.
The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation.The most common cause of lung cancer is long-term exposure to tobacco smokeThe occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases,is often attributed to a combination of genetic factorsradon gas, asbestos, and air pollution[including secondhand smoke.
Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Depending on the stage and treatment, the five-year survival rate is 14%
Classification
Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. The two most prevalent histological types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell and small-cell lung carcinoma. The non-small cell type is the most prevalent by far (see accompanying table).
Frequency of histological types of lung cancer Histological type Frequency (%)
Non-small cell lung carcinoma 80.4
Small cell lung carcinoma 16.8
Carcinoid 0.8
Sarcoma 0.1
Unspecified lung cancer 1.9
Non-small cell lung carcinoma (NSCLC)
Micrograph of squamous carcinoma, a type of non-small cell carcinoma. FNA specimen. Pap stain.The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma.
Sub-types of non-small cell lung cancer in
smokers and never-smokers Histological sub-type Frequency of non-small cell lung cancers (%)
Smokers Never-smokers
Squamous cell lung carcinoma 42 33
Adenocarcinoma Adenocarcinoma (not otherwise specified) 39 35
Bronchioloalveolar carcinoma 4 10
Carcinoid 7 16
Other 8 6
Accounting for 25% of lung cancers,squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.
Adenocarcinoma accounts for 40% of non-small cell lung cancers. It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.
Small cell lung carcinoma (SCLC)
Small cell lung carcinoma (microscopic view of a core needle biopsy).Small cell lung carcinoma is less common. It was formerly referred to as "oat cell" carcinoma.Most cases arise in the larger airways (primary and secondary bronchi) and grow rapidly, becoming quite largeThe small cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association. While initially more sensitive to chemotherapy and radiation, it is often metastatic at presentation, and ultimately carries a worse prognosis. Small cell lung cancers have long been dichotomously staged into limited and extensive stage disease. This type of lung cancer is strongly associated with smoking.
Others
Lung cancers are highly heterogeneous malignancies, with tumors containing more than one subtype being very common.
Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer. It recognizes numerous other distinct histopathological entities of non-small cell lung carcinoma, organized into several additional subtypes, including sarcomatoid carcinoma, salivary gland tumors, carcinoid tumor, and adenosquamous carcinoma. The latter subtype includes tumors containing at least 10% each of adenocarcinoma and squamous cell carcinoma. When a tumor is found to contain a mixture of both small cell carcinoma and non-small cell carcinoma, it is classified as a variant of small cell carcinoma and called a combined small cell carcinoma. Combined small cell carcinoma is the only currently recognized variant of small cell carcinoma.
In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.
Secondary cancers
Micrograph of a lung lymph node biopsy showing metastatic colorectal adenocarcinoma. Field stain.The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer. Metastases often have a characteristic round appearance on chest radiograph. Solitary round lung nodules are not infrequently of an uncertain etiology and may prompt a lung biopsy.
In children, the majority of lung cancers are secondary.
Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.
Staging
Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis). Small cell lung carcinoma is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field; otherwise, it is extensive stage.
Signs and symptoms
Symptoms that suggest lung cancer include:
dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic coughing or change in regular coughing pattern
wheezing
chest pain or pain in the abdomen
cachexia (weight loss), fatigue, and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails (uncommon)
dysphagia (difficulty swallowing).
If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.
Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus.
Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph
Causes
The main causes of any cancer include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.
Smoking
NIH graph showing the correlation and time-lag between tobacco smoking and lung cancer rate in the U.S. male population.Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, almost 90% of lung cancer deaths are caused by smoking] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.
Women who smoke (former smokers and current smokers) and take hormone therapy are at a much higher risk of dying of lung cancer. In a study by Chlebowski et al. published in 2009, the women taking hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for never smokers. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo.
The time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.[] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.
Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S.,Europe,the UK, and Australiahave consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.
10–15% of lung cancer patients have never smoked. That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.
Radon gas
Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking with the risk increasing by 8% to 16% for every 100 Bq/m^3 increase in radonincrease in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³).Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.
Asbestos
Ferruginous bodies the histopathologic find associated with asbestosis. H&E stain.Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer. In the UK, asbestos accounts for 2–3% of male lung cancer deathsAsbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
Viruses
Viruses are known to cause lung cancer in animals,and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus JC virus, simian virus 40 (SV40), BK virus, and cytomegalovirus. These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.
Particulate matter
Studies of the American Cancer Society cohort directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%. Further, it has been established that particle size matters, as ultrafine particles penetrate further into the lungs
Pathogenesis
Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.Mutations and amplification of EGFR are common in non-small cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently. Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases. Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.
Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,cytochrome P450, apoptosis promoters such as caspase-8,and DNA repair molecules such as XRCC1. People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.
A recent study suggested that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.
Diagnosis
Chest radiograph showing a cancerous tumor in the left lung.Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.
Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer
CT scan showing a cancerous tumor in the left lung.The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason.
Pathologic
The definitive diagnosis of lung cancer and its classification (described above) is based on examination of the suspicious tissue under the microscope.
Prevention
Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens has been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process Of utmost importance are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.
Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005. In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008.
Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.
The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer
The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.
Screening
Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph or computed tomography (CT). As of December 2009, screening programs for lung cancer have not demonstrated any benefit.
Treatment
Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.
Surgery
Main article: Lung cancer surgery
Gross appearance of the cut surface of a pneumonectomy specimen containing a lung cancer, here a squamous cell carcinoma (the whitish tumor near the bronchi).If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.
Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated.
Surgery itself has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors. Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.
Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.
Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.
Chemotherapy
Small cell lung carcinoma is treated primarily with chemotherapy and radiation, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung carcinoma.
The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.In small cell lung carcinoma, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. In extensive-stage small-cell lung cancer celecoxib may safely be combined with etoposide, this combination showed improve outcomes.
Adjuvant chemotherapy for NSCLC
Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%. Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).
Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[96][97] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung carcinoma have been inconclusive
Radiotherapy
Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.For small cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.
For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer.
Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.It is used when inoperable lung cancer causes blockage of a large airway.
Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis. More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.
Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.
Interventional radiology
Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.
Targeted therapy
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib
Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma, specifically those with specific mutations in EGFR.
The angiogenesis inhibitor bevacizumab, (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma. However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.
Advances in cytotoxic drugs, pharmacogenetics and targeted drug design show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitorsthe apoptosis promoter exisulind, proteasome inhibitors, bexarotene, the epidermal growth factor receptor inhibitor cetuximab, and vaccines. Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement.In a story that was on NBCs Today Show in mid April 2010 called "Discovery of a New Approach For Identifying Smokers at Highest Risk For Developing Lung Cancer", researchers from the Boston University School of Medicine found a novel gene-expression based approach to define oncogenic pathway signatures, in collaboration with Dr. Andrea Bild at the University of Utar. They have now discovered that the expression of genes belonging to one specific cancer-related pathway P13K, are activated in the cells that line the airway of smokers with Lung Cancer. This gene expression activity in normal cells of the proximal airway, precedes the development of Lung Cancer and may be reversed with a specific chemopreventive agent Myo-Inositol. Myo-Inositol targets this pathway.
Prognosis
Prognostic factors in non-small cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.
For non-small cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57% The five-year survival rate of patients with stage IV NSCLC is about 1%.
For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.
According to data provided by the National Cancer Institute, the median age of death for cases of lung cancer in the United States is 70 years, and the median age is 71 years.
Epidemiology
Age-standardized death from tracheal, bronchial, and lung cancers per 100,000 inhabitants in 2004.
Lung cancer distribution in the United StatesWorldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.35 million new cases per year and 1.18 million deaths), with the highest rates in Europe and North America The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising for over the last decades, and are just recently beginning to stabilize. The evolution of "Big Tobacco" plays a significant role in the smoking culture. Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes . Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women.
Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.
Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. Lung cancer incidence is currently less common in developing countries. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India.
Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventive effect of vitamin D (which is produced in the skin on exposure to sunlight).
From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancerThis is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.However, in some developing countries like India, there has been little change in the epidemiology with squamous cell carcinoma continuing to be the predominant histological type.An absence of change in the type of tobacco smoking or the pattern of tobacco consumption in the population could be one of the possible reasons.
History
Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign.The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.
The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.
The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery. In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.
With small cell lung carcinoma, initial attempts in the 1960s at surgical resectionand radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed
The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. This distinction is important, because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with surgery, while small cell lung carcinoma (SCLC) usually responds better to chemotherapy and radiation.The most common cause of lung cancer is long-term exposure to tobacco smokeThe occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases,is often attributed to a combination of genetic factorsradon gas, asbestos, and air pollution[including secondhand smoke.
Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Depending on the stage and treatment, the five-year survival rate is 14%
Classification
Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. The two most prevalent histological types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell and small-cell lung carcinoma. The non-small cell type is the most prevalent by far (see accompanying table).
Frequency of histological types of lung cancer Histological type Frequency (%)
Non-small cell lung carcinoma 80.4
Small cell lung carcinoma 16.8
Carcinoid 0.8
Sarcoma 0.1
Unspecified lung cancer 1.9
Non-small cell lung carcinoma (NSCLC)
Micrograph of squamous carcinoma, a type of non-small cell carcinoma. FNA specimen. Pap stain.The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large cell lung carcinoma.
Sub-types of non-small cell lung cancer in
smokers and never-smokers Histological sub-type Frequency of non-small cell lung cancers (%)
Smokers Never-smokers
Squamous cell lung carcinoma 42 33
Adenocarcinoma Adenocarcinoma (not otherwise specified) 39 35
Bronchioloalveolar carcinoma 4 10
Carcinoid 7 16
Other 8 6
Accounting for 25% of lung cancers,squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.
Adenocarcinoma accounts for 40% of non-small cell lung cancers. It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.
Small cell lung carcinoma (SCLC)
Small cell lung carcinoma (microscopic view of a core needle biopsy).Small cell lung carcinoma is less common. It was formerly referred to as "oat cell" carcinoma.Most cases arise in the larger airways (primary and secondary bronchi) and grow rapidly, becoming quite largeThe small cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association. While initially more sensitive to chemotherapy and radiation, it is often metastatic at presentation, and ultimately carries a worse prognosis. Small cell lung cancers have long been dichotomously staged into limited and extensive stage disease. This type of lung cancer is strongly associated with smoking.
Others
Lung cancers are highly heterogeneous malignancies, with tumors containing more than one subtype being very common.
Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer. It recognizes numerous other distinct histopathological entities of non-small cell lung carcinoma, organized into several additional subtypes, including sarcomatoid carcinoma, salivary gland tumors, carcinoid tumor, and adenosquamous carcinoma. The latter subtype includes tumors containing at least 10% each of adenocarcinoma and squamous cell carcinoma. When a tumor is found to contain a mixture of both small cell carcinoma and non-small cell carcinoma, it is classified as a variant of small cell carcinoma and called a combined small cell carcinoma. Combined small cell carcinoma is the only currently recognized variant of small cell carcinoma.
In infants and children, the most common primary lung cancers are pleuropulmonary blastoma and carcinoid tumor.
Secondary cancers
Micrograph of a lung lymph node biopsy showing metastatic colorectal adenocarcinoma. Field stain.The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer. Metastases often have a characteristic round appearance on chest radiograph. Solitary round lung nodules are not infrequently of an uncertain etiology and may prompt a lung biopsy.
In children, the majority of lung cancers are secondary.
Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.
Staging
Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis). Small cell lung carcinoma is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field; otherwise, it is extensive stage.
Signs and symptoms
Symptoms that suggest lung cancer include:
dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic coughing or change in regular coughing pattern
wheezing
chest pain or pain in the abdomen
cachexia (weight loss), fatigue, and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails (uncommon)
dysphagia (difficulty swallowing).
If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.
Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus.
Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph
Causes
The main causes of any cancer include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.
Smoking
NIH graph showing the correlation and time-lag between tobacco smoking and lung cancer rate in the U.S. male population.Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, almost 90% of lung cancer deaths are caused by smoking] In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women.
Women who smoke (former smokers and current smokers) and take hormone therapy are at a much higher risk of dying of lung cancer. In a study by Chlebowski et al. published in 2009, the women taking hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for never smokers. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo.
The time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.[] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[] and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit.
Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S.,Europe,the UK, and Australiahave consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation.
10–15% of lung cancer patients have never smoked. That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS.
Radon gas
Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking with the risk increasing by 8% to 16% for every 100 Bq/m^3 increase in radonincrease in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³).Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L.
Asbestos
Ferruginous bodies the histopathologic find associated with asbestosis. H&E stain.Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer. In the UK, asbestos accounts for 2–3% of male lung cancer deathsAsbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
Viruses
Viruses are known to cause lung cancer in animals,and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus JC virus, simian virus 40 (SV40), BK virus, and cytomegalovirus. These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.
Particulate matter
Studies of the American Cancer Society cohort directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%. Further, it has been established that particle size matters, as ultrafine particles penetrate further into the lungs
Pathogenesis
Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.Mutations and amplification of EGFR are common in non-small cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently. Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases. Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.
Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1,cytochrome P450, apoptosis promoters such as caspase-8,and DNA repair molecules such as XRCC1. People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.
A recent study suggested that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.
Diagnosis
Chest radiograph showing a cancerous tumor in the left lung.Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type.
Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer
CT scan showing a cancerous tumor in the left lung.The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[3] Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason.
Pathologic
The definitive diagnosis of lung cancer and its classification (described above) is based on examination of the suspicious tissue under the microscope.
Prevention
Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens has been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process Of utmost importance are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies.Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts.
Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005. In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking at public places on Oct 2 2008.
Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling, and the risk that such a ban cannot be enforced.
The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer
The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted.
Screening
Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph or computed tomography (CT). As of December 2009, screening programs for lung cancer have not demonstrated any benefit.
Treatment
Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.
Surgery
Main article: Lung cancer surgery
Gross appearance of the cut surface of a pneumonectomy specimen containing a lung cancer, here a squamous cell carcinoma (the whitish tumor near the bronchi).If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.
Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated.
Surgery itself has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors. Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed.
Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.
Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs.
Chemotherapy
Small cell lung carcinoma is treated primarily with chemotherapy and radiation, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung carcinoma.
The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine.In small cell lung carcinoma, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. In extensive-stage small-cell lung cancer celecoxib may safely be combined with etoposide, this combination showed improve outcomes.
Adjuvant chemotherapy for NSCLC
Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%. Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).
Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[96][97] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung carcinoma have been inconclusive
Radiotherapy
Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.For small cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes.
For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer.
Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.It is used when inoperable lung cancer causes blockage of a large airway.
Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis. More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.
Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.
Interventional radiology
Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.
Targeted therapy
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib
Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma, specifically those with specific mutations in EGFR.
The angiogenesis inhibitor bevacizumab, (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma. However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.
Advances in cytotoxic drugs, pharmacogenetics and targeted drug design show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitorsthe apoptosis promoter exisulind, proteasome inhibitors, bexarotene, the epidermal growth factor receptor inhibitor cetuximab, and vaccines. Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement.In a story that was on NBCs Today Show in mid April 2010 called "Discovery of a New Approach For Identifying Smokers at Highest Risk For Developing Lung Cancer", researchers from the Boston University School of Medicine found a novel gene-expression based approach to define oncogenic pathway signatures, in collaboration with Dr. Andrea Bild at the University of Utar. They have now discovered that the expression of genes belonging to one specific cancer-related pathway P13K, are activated in the cells that line the airway of smokers with Lung Cancer. This gene expression activity in normal cells of the proximal airway, precedes the development of Lung Cancer and may be reversed with a specific chemopreventive agent Myo-Inositol. Myo-Inositol targets this pathway.
Prognosis
Prognostic factors in non-small cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.
For non-small cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57% The five-year survival rate of patients with stage IV NSCLC is about 1%.
For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.
According to data provided by the National Cancer Institute, the median age of death for cases of lung cancer in the United States is 70 years, and the median age is 71 years.
Epidemiology
Age-standardized death from tracheal, bronchial, and lung cancers per 100,000 inhabitants in 2004.
Lung cancer distribution in the United StatesWorldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.35 million new cases per year and 1.18 million deaths), with the highest rates in Europe and North America The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising for over the last decades, and are just recently beginning to stabilize. The evolution of "Big Tobacco" plays a significant role in the smoking culture. Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes . Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women.
Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks.
Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. Lung cancer incidence is currently less common in developing countries. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India.
Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventive effect of vitamin D (which is produced in the skin on exposure to sunlight).
From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancerThis is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution.However, in some developing countries like India, there has been little change in the epidemiology with squamous cell carcinoma continuing to be the predominant histological type.An absence of change in the type of tobacco smoking or the pattern of tobacco consumption in the population could be one of the possible reasons.
History
Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign.The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.
The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.
The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery. In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.
With small cell lung carcinoma, initial attempts in the 1960s at surgical resectionand radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed
Arthritis(this has nothing to do with the bklog but its something important i wanted to write about since a family member suffers from this)
Arthritis (from Greek arthro-, joint + -itis, inflammation; plural: arthritides) is a group of conditions involving damage to the joints of the body.
There are over 100 different forms of arthritisThe most common form, osteoarthritis (degenerative joint disease) is a result of trauma to the joint, infection of the joint, or age. Other arthritis forms are rheumatoid arthritis, psoriatic arthritis, and autoimmune diseases in which the body attacks itself. Septic arthritis is caused by joint infection.
The major complaint by individuals who have arthritis is pain. Pain is often a constant and daily feature of the disease. The pain may be localized to the back, neck, hip, knee or feet. The pain from arthritis occurs due to inflammation that occurs around the joint, damage to the joint from disease, daily wear and tear of joint, muscles strains caused by forceful movements against stiff, painful joints and fatigue. The most important factor in treatment is to understand the disorder and find ways to overcome the obstacles which prevent physical exercise.
Classification
Primary forms of arthritis:
Osteoarthritis
Rheumatoid arthritis
Septic arthritis
Gout and pseudo-gout
Juvenile idiopathic arthritis
Still's disease
Ankylosing spondylitis
Secondary to other diseases:
Ehlers-Danlos Syndrome
Sarcoidosis
Henoch-Schönlein purpura
Psoriatic arthritis
Reactive arthritis
Haemochromatosis
Hepatitis
Wegener's granulomatosis (and many other vasculitis syndromes)
Lyme disease
Familial Mediterranean fever
Hyperimmunoglobulinemia D with recurrent fever
TNF receptor associated periodic syndrome
Inflammatory bowel disease (Including Crohn's Disease and Ulcerative Colitis)
Diseases that can mimic arthritis include:
Hypertrophic osteoarthropathy
Multiple myeloma
Osteoporosis
Fifth disease (parvovirus infection)
Rheumatoid Arthritis
Rheumatoid arthritis is a disorder where, for some unknown reason, the body's own immune system starts to attack body tissues. The attack is not only directed at the joint but to many other parts of the body. In rheumatoid arthritis, most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones. Rheumatoid arthritis affects joints in the fingers, wrists, knees and elbows. The disease is symmetrical and can lead to severe deformity in a few years if not treated. Rheumatoid arthritis occurs mostly in people aged 20 and above. In children, the disorder can present with a skin rash, fever, pain, disability, and limitations in daily activities. No one knows why rheumatoid arthritis occurs and all treatments are focused on easing the symptoms. With earlier diagnosis and aggressive treatment, many individuals can lead a decent quality of life. The drugs to treat rheumatoid arthritis range from corticosteroids to monoclonal antibodies given intravenously. The latest drugs like Remicade can significantly improve quality of life in the short term. In rare cases, surgery may be required to replace joints but there is no cure for the illness
Rheumatic fever has now seen resurgence in America primarily because of mass immigration of people from developing countriesThe disorder can present with a migratory nature of arthritis with many other features like heart problems, skin rash, gait abnormality and skin nodules.
Osteoarthritis
Unlike rheumatoid arthritis, osteoarthritis can affect both the larger and the smaller joints of the body, including the hands, feet, back, hip or knee. The disease is essentially one acquired from daily wear and tear of the joint. Osteoarthritis begins in the cartilage and eventually leads to the two opposing bones eroding into each other. Initially, the condition starts with minor pain while walking but soon the pain can be continuous and even occur at night. The pain can be debilitating and prevent one from doing any type of activity. Osteoarthritis typically affects the weight bearing joints like the back, spine and pelvis. Unlike rheumatoid arthritis, osteoarthritis is a disease of the elderly. More than 30 percent of females have some degree of osteoarthritis by age 65.
Risk factors for osteoarthritis:
Prior joint trauma
Obesity
Repetitive joint use
Sedentary lifestyle
Osteoarthritis, like rheumatoid arthritis, cannot be cured but one can prevent the condition from worsening. Weight loss is the key to improving symptoms and preventing progression. Physical therapy to strengthen muscles and joints is very helpful. Pain medications are widely required by individuals with osteoarthritis. When the disease is far advanced and the pain is continuous, surgery may be an option. Unlike rheumatoid arthritis, joint replacement does help many individuals with osteoarthritis.
Lupus
This is a common collagen vascular disorder that can be present with severe arthritis. Other features of lupus include a skin rash, extreme photosensitivity, hair loss, kidney problems, emotional lability, lung fibrosis and constant joint pain.
Gout
It is caused by deposition of uric acid crystals in the joint, causing inflammation. There is also an uncommon form of gout caused by the formation of rhomboid crystals of calcium pyrophosphate. This gout is known as pseudogout. In the early stages, the gouty arthritis usually occur in one joint, but with time, it can occur in many joints and be quite crippling. The joints in gout can often become swollen and lose function.
Other
Infectious arthritis is another severe form of arthritis. It presents with sudden onset of chills, fever and joint pain. The condition is caused by bacteria elsewhere in the body. Infectious arthritis must be rapidly diagnosed and treated promptly to prevent irreversible and permanent joint damage.
Psoriasis is another type of arthritis. With psoriasis, most individuals develop the skin problem first and then the arthritis. The typical features are of continuous joint pains, stiffness and swelling. The disease does recur with periods of remission but there is no cure for the disorder. A small percentage develop a severe painful and destructive form of arthritis which destroys the small joint in the hands and can lead to permanent disability and loss of hand function
Signs and symptoms
Irrespective of the type of arthritis, the common symptoms for all arthritis disorders include varied levels of pain, swelling, joint stiffness and sometimes a constant ache around the joint(s). Arthritic disorders like lupus and rheumatoid can also affect other organs in the body with a variety of symptoms.
Inability to use the hand or walk
Malaise and a feeling of tiredness
Fever
Weight loss
Poor sleep
Muscle aches and pains
Tenderness
Difficulty moving the joint
It is common in advanced arthritis for significant secondary changes to occur. For example, in someone who has limited their physical activity:
Muscle weakness
Loss of flexibility
Decreased aerobic fitness
These changes can also impact on life and social roles, such as community involvement.
Disability
Arthritis is the most common cause of disability in the USA. More than 20 million individuals with arthritis have severe limitations in function on a daily basis. Absenteeism and frequent visits to the physician are common in individuals who have arthritis. Arthritis makes it very difficult for individuals to be physically active and soon become home bound.
It is estimated that the total cost of arthritis cases is close to $100 billion of which nearly 50% accounts from lost earnings. Each year, arthritis results in nearly 1 million hospitalizations and close to 45 million outpatient visits to health care centers.
Arthritis makes it very difficult for the individual to remain physically active. Many individuals who have arthritis also suffer from obesity, high cholesterol or have heart disease. Individuals with arthritis also become depressed and have fear of worsening symptoms.
Diagnosis
Diagnosis is made by clinical examination from an appropriate health professional, and may be supported by other tests such as radiology and blood tests, depending on the type of suspected arthritis. All arthritides potentially feature pain. Pain patterns may differ depending on the arthritides and the location. Rheumatoid arthritis is generally worse in the morning and associated with stiffness; in the early stages, patients often have no symptoms after a morning shower. Osteoarthritis, on the other hand, tends to be worse after exercise. In the aged and children, pain might not be the main presenting feature; the aged patient simply moves less, the infantile patient refuses to use the affected limb.
Elements of the history of the disorder guide diagnosis. Important features are speed and time of onset, pattern of joint involvement, symmetry of symptoms, early morning stiffness, tenderness, gelling or locking with inactivity, aggravating and relieving factors, and other systemic symptoms. Physical examination may confirm the diagnosis, or may indicate systemic disease. Radiographs are often used to follow progression or help assess severity.
Prevention
While neither Rheumatoid arthritis nor osteoarthritis can be completely prevented, one can reduce the risks by becoming physically active, participating in physical therapy, losing weight and eating healthily. All individuals who have pain in the joints should seek early diagnosis because the earlier the treatment is started, the better is the prognosis.
Treatment
Once the diagnosis of arthritis is made, treatments are available for a variety of symptoms. There is no cure for either rheumatoid or osteoarthritis.
Treatment options vary depending on the type of arthritis and include physical therapy, lifestyle changes (including exercise and weight control), orthopedic bracing, medications, and dietary supplements (symptomatic or targeted at the disease process causing the arthritis). Arthroplasty (joint replacement surgery) may be required in eroding forms of arthritis. Medications can help reduce inflammation in the joint which decreases pain. Moreover, by decreasing inflammation, the joint damage is slowed.
In general, studies have shown that physical exercise of the affected joint can have noticeable improvement in terms of long-term pain relief. Furthermore, exercise of the arthritic joint is encouraged to maintain the health of the particular joint and the overall body of the person.
Physical Therapy
Individuals with arthritis can definitely benefit from both physical and occupational therapy. In arthritis the joints become stiff and the range of movement can be limited. Physical therapy has been shown to significantly improve function, decrease pain, and delay need for surgical intervention in advanced cases Exercise prescribed by a physical therapist has been shown to be more effective than medications in treating osteoarthritis of the knee. Exercise often focusses on improving muscle strength, endurance and flexibility. In some cases, exercises may be designed to train balance. Occupational therapy can teach you how to reduce stress on your joint from daily living activities. Occupation therapy can also teach you how to modify your home and work environment so that you do reduce movements that may worsen your arthritis. There are also assist devices available that can help you drive, getting a bath, dressing and also in housekeeping labors.
As well as exercise, physical therapy may include education about modifying activities, and other self-management skills such as using ice or heat, and ultrasound. Physical therapists will routinely educate patients to manage their problems related to arthritis themselves. Other aspects of physical therapy means learning how to maintain good posture, conserving energy by allowing rest before and after activity.
Occupational therapy can help you do everyday activities without worsening pain or causing joint damage. The techniques can help you distribute pressures to minimize stress on any one joint. Ways to accomplish daily living tasks are made easier.
Medications
Physicians usually start with drugs which have the fewest side effects and shift to stronger medications as the disease progresses.
Non-steroidal anti-inflammatory drugs (NSAIDs) are usually the drugs of first choice. These drugs help decrease inflammation and reduce pain. Over the counter medications like Ibuprofen or Aleve do help but most people require stronger prescription painkillers like Celebrex or tramadol. While these drugs are effective, they are also associated with a variety of side effects like abdominal pain, bleeding, ulcers, liver and kidney damage. Non steroidal anti inflammatory drugs should not be used for prolonged periods without proper physician supervision.
Corticosteroids are frequently prescribed for individuals with arthritis. These potent drugs can help reduce inflammation and slow down joint damage. However, corticosteroids have potent side effects which range from ulcer, skin bruising, weight gain, cataracts, bone thinning, diabetes and hypertension. Corticosteroids are usually given for a short time to help reduce acute symptoms.
Disease-modifying antirheumatic drugs (DMARDs) can help slow down progression of rheumatoid arthritis and joint damage. The most common DMARDs include methotrexate (Rheumatrex, Trexall), leflunomide (Arava), hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine) and minocycline (Dynacin, Minocin). All these drugs have side effects which include liver damage, bone marrow suppression and possibility of opportunistic infections.
Immunosuppressants like cyclosporine and cyclophosphamide suppress potent cells of the body and help decrease the inflammation. These medications do help treat severe arthritis but also make one prone to infections.
Tumor necrosis factor inhibitors have been shown to reduce inflammation, pain, morning stiffness and swelling of joints. Drugs like etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) can significantly improve quality of life. The most common side effects from these drugs include pain at site of injection, heart failure and increased risk of infection.
Epidemiology
Arthritis is predominantly a disease of the elderly, but children can also be affected by the disease. More than 70% of individuals in North America affected by arthritis are over the age of 65. Arthritis is more common in women than men at all ages and affects all races, ethnic groups and cultures. An estimated 46 million individuals in USA have arthritis and the numbers continue to increase each year. Close to one million individuals are admitted to hospitals each year because of their arthritis.
History
While evidence of primary ankle (kaki) osteoarthritis has been discovered in dinosaurs, the first known traces of human arthritis date back as far as 4500 BC. In early reports, arthritis was frequently referred to as the most common ailment of prehistoric peoples. It was noted in skeletal remains of Native Americans found in Tennessee and parts of what
There are over 100 different forms of arthritisThe most common form, osteoarthritis (degenerative joint disease) is a result of trauma to the joint, infection of the joint, or age. Other arthritis forms are rheumatoid arthritis, psoriatic arthritis, and autoimmune diseases in which the body attacks itself. Septic arthritis is caused by joint infection.
The major complaint by individuals who have arthritis is pain. Pain is often a constant and daily feature of the disease. The pain may be localized to the back, neck, hip, knee or feet. The pain from arthritis occurs due to inflammation that occurs around the joint, damage to the joint from disease, daily wear and tear of joint, muscles strains caused by forceful movements against stiff, painful joints and fatigue. The most important factor in treatment is to understand the disorder and find ways to overcome the obstacles which prevent physical exercise.
Classification
Primary forms of arthritis:
Osteoarthritis
Rheumatoid arthritis
Septic arthritis
Gout and pseudo-gout
Juvenile idiopathic arthritis
Still's disease
Ankylosing spondylitis
Secondary to other diseases:
Ehlers-Danlos Syndrome
Sarcoidosis
Henoch-Schönlein purpura
Psoriatic arthritis
Reactive arthritis
Haemochromatosis
Hepatitis
Wegener's granulomatosis (and many other vasculitis syndromes)
Lyme disease
Familial Mediterranean fever
Hyperimmunoglobulinemia D with recurrent fever
TNF receptor associated periodic syndrome
Inflammatory bowel disease (Including Crohn's Disease and Ulcerative Colitis)
Diseases that can mimic arthritis include:
Hypertrophic osteoarthropathy
Multiple myeloma
Osteoporosis
Fifth disease (parvovirus infection)
Rheumatoid Arthritis
Rheumatoid arthritis is a disorder where, for some unknown reason, the body's own immune system starts to attack body tissues. The attack is not only directed at the joint but to many other parts of the body. In rheumatoid arthritis, most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones. Rheumatoid arthritis affects joints in the fingers, wrists, knees and elbows. The disease is symmetrical and can lead to severe deformity in a few years if not treated. Rheumatoid arthritis occurs mostly in people aged 20 and above. In children, the disorder can present with a skin rash, fever, pain, disability, and limitations in daily activities. No one knows why rheumatoid arthritis occurs and all treatments are focused on easing the symptoms. With earlier diagnosis and aggressive treatment, many individuals can lead a decent quality of life. The drugs to treat rheumatoid arthritis range from corticosteroids to monoclonal antibodies given intravenously. The latest drugs like Remicade can significantly improve quality of life in the short term. In rare cases, surgery may be required to replace joints but there is no cure for the illness
Rheumatic fever has now seen resurgence in America primarily because of mass immigration of people from developing countriesThe disorder can present with a migratory nature of arthritis with many other features like heart problems, skin rash, gait abnormality and skin nodules.
Osteoarthritis
Unlike rheumatoid arthritis, osteoarthritis can affect both the larger and the smaller joints of the body, including the hands, feet, back, hip or knee. The disease is essentially one acquired from daily wear and tear of the joint. Osteoarthritis begins in the cartilage and eventually leads to the two opposing bones eroding into each other. Initially, the condition starts with minor pain while walking but soon the pain can be continuous and even occur at night. The pain can be debilitating and prevent one from doing any type of activity. Osteoarthritis typically affects the weight bearing joints like the back, spine and pelvis. Unlike rheumatoid arthritis, osteoarthritis is a disease of the elderly. More than 30 percent of females have some degree of osteoarthritis by age 65.
Risk factors for osteoarthritis:
Prior joint trauma
Obesity
Repetitive joint use
Sedentary lifestyle
Osteoarthritis, like rheumatoid arthritis, cannot be cured but one can prevent the condition from worsening. Weight loss is the key to improving symptoms and preventing progression. Physical therapy to strengthen muscles and joints is very helpful. Pain medications are widely required by individuals with osteoarthritis. When the disease is far advanced and the pain is continuous, surgery may be an option. Unlike rheumatoid arthritis, joint replacement does help many individuals with osteoarthritis.
Lupus
This is a common collagen vascular disorder that can be present with severe arthritis. Other features of lupus include a skin rash, extreme photosensitivity, hair loss, kidney problems, emotional lability, lung fibrosis and constant joint pain.
Gout
It is caused by deposition of uric acid crystals in the joint, causing inflammation. There is also an uncommon form of gout caused by the formation of rhomboid crystals of calcium pyrophosphate. This gout is known as pseudogout. In the early stages, the gouty arthritis usually occur in one joint, but with time, it can occur in many joints and be quite crippling. The joints in gout can often become swollen and lose function.
Other
Infectious arthritis is another severe form of arthritis. It presents with sudden onset of chills, fever and joint pain. The condition is caused by bacteria elsewhere in the body. Infectious arthritis must be rapidly diagnosed and treated promptly to prevent irreversible and permanent joint damage.
Psoriasis is another type of arthritis. With psoriasis, most individuals develop the skin problem first and then the arthritis. The typical features are of continuous joint pains, stiffness and swelling. The disease does recur with periods of remission but there is no cure for the disorder. A small percentage develop a severe painful and destructive form of arthritis which destroys the small joint in the hands and can lead to permanent disability and loss of hand function
Signs and symptoms
Irrespective of the type of arthritis, the common symptoms for all arthritis disorders include varied levels of pain, swelling, joint stiffness and sometimes a constant ache around the joint(s). Arthritic disorders like lupus and rheumatoid can also affect other organs in the body with a variety of symptoms.
Inability to use the hand or walk
Malaise and a feeling of tiredness
Fever
Weight loss
Poor sleep
Muscle aches and pains
Tenderness
Difficulty moving the joint
It is common in advanced arthritis for significant secondary changes to occur. For example, in someone who has limited their physical activity:
Muscle weakness
Loss of flexibility
Decreased aerobic fitness
These changes can also impact on life and social roles, such as community involvement.
Disability
Arthritis is the most common cause of disability in the USA. More than 20 million individuals with arthritis have severe limitations in function on a daily basis. Absenteeism and frequent visits to the physician are common in individuals who have arthritis. Arthritis makes it very difficult for individuals to be physically active and soon become home bound.
It is estimated that the total cost of arthritis cases is close to $100 billion of which nearly 50% accounts from lost earnings. Each year, arthritis results in nearly 1 million hospitalizations and close to 45 million outpatient visits to health care centers.
Arthritis makes it very difficult for the individual to remain physically active. Many individuals who have arthritis also suffer from obesity, high cholesterol or have heart disease. Individuals with arthritis also become depressed and have fear of worsening symptoms.
Diagnosis
Diagnosis is made by clinical examination from an appropriate health professional, and may be supported by other tests such as radiology and blood tests, depending on the type of suspected arthritis. All arthritides potentially feature pain. Pain patterns may differ depending on the arthritides and the location. Rheumatoid arthritis is generally worse in the morning and associated with stiffness; in the early stages, patients often have no symptoms after a morning shower. Osteoarthritis, on the other hand, tends to be worse after exercise. In the aged and children, pain might not be the main presenting feature; the aged patient simply moves less, the infantile patient refuses to use the affected limb.
Elements of the history of the disorder guide diagnosis. Important features are speed and time of onset, pattern of joint involvement, symmetry of symptoms, early morning stiffness, tenderness, gelling or locking with inactivity, aggravating and relieving factors, and other systemic symptoms. Physical examination may confirm the diagnosis, or may indicate systemic disease. Radiographs are often used to follow progression or help assess severity.
Prevention
While neither Rheumatoid arthritis nor osteoarthritis can be completely prevented, one can reduce the risks by becoming physically active, participating in physical therapy, losing weight and eating healthily. All individuals who have pain in the joints should seek early diagnosis because the earlier the treatment is started, the better is the prognosis.
Treatment
Once the diagnosis of arthritis is made, treatments are available for a variety of symptoms. There is no cure for either rheumatoid or osteoarthritis.
Treatment options vary depending on the type of arthritis and include physical therapy, lifestyle changes (including exercise and weight control), orthopedic bracing, medications, and dietary supplements (symptomatic or targeted at the disease process causing the arthritis). Arthroplasty (joint replacement surgery) may be required in eroding forms of arthritis. Medications can help reduce inflammation in the joint which decreases pain. Moreover, by decreasing inflammation, the joint damage is slowed.
In general, studies have shown that physical exercise of the affected joint can have noticeable improvement in terms of long-term pain relief. Furthermore, exercise of the arthritic joint is encouraged to maintain the health of the particular joint and the overall body of the person.
Physical Therapy
Individuals with arthritis can definitely benefit from both physical and occupational therapy. In arthritis the joints become stiff and the range of movement can be limited. Physical therapy has been shown to significantly improve function, decrease pain, and delay need for surgical intervention in advanced cases Exercise prescribed by a physical therapist has been shown to be more effective than medications in treating osteoarthritis of the knee. Exercise often focusses on improving muscle strength, endurance and flexibility. In some cases, exercises may be designed to train balance. Occupational therapy can teach you how to reduce stress on your joint from daily living activities. Occupation therapy can also teach you how to modify your home and work environment so that you do reduce movements that may worsen your arthritis. There are also assist devices available that can help you drive, getting a bath, dressing and also in housekeeping labors.
As well as exercise, physical therapy may include education about modifying activities, and other self-management skills such as using ice or heat, and ultrasound. Physical therapists will routinely educate patients to manage their problems related to arthritis themselves. Other aspects of physical therapy means learning how to maintain good posture, conserving energy by allowing rest before and after activity.
Occupational therapy can help you do everyday activities without worsening pain or causing joint damage. The techniques can help you distribute pressures to minimize stress on any one joint. Ways to accomplish daily living tasks are made easier.
Medications
Physicians usually start with drugs which have the fewest side effects and shift to stronger medications as the disease progresses.
Non-steroidal anti-inflammatory drugs (NSAIDs) are usually the drugs of first choice. These drugs help decrease inflammation and reduce pain. Over the counter medications like Ibuprofen or Aleve do help but most people require stronger prescription painkillers like Celebrex or tramadol. While these drugs are effective, they are also associated with a variety of side effects like abdominal pain, bleeding, ulcers, liver and kidney damage. Non steroidal anti inflammatory drugs should not be used for prolonged periods without proper physician supervision.
Corticosteroids are frequently prescribed for individuals with arthritis. These potent drugs can help reduce inflammation and slow down joint damage. However, corticosteroids have potent side effects which range from ulcer, skin bruising, weight gain, cataracts, bone thinning, diabetes and hypertension. Corticosteroids are usually given for a short time to help reduce acute symptoms.
Disease-modifying antirheumatic drugs (DMARDs) can help slow down progression of rheumatoid arthritis and joint damage. The most common DMARDs include methotrexate (Rheumatrex, Trexall), leflunomide (Arava), hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine) and minocycline (Dynacin, Minocin). All these drugs have side effects which include liver damage, bone marrow suppression and possibility of opportunistic infections.
Immunosuppressants like cyclosporine and cyclophosphamide suppress potent cells of the body and help decrease the inflammation. These medications do help treat severe arthritis but also make one prone to infections.
Tumor necrosis factor inhibitors have been shown to reduce inflammation, pain, morning stiffness and swelling of joints. Drugs like etanercept (Enbrel), infliximab (Remicade) and adalimumab (Humira) can significantly improve quality of life. The most common side effects from these drugs include pain at site of injection, heart failure and increased risk of infection.
Epidemiology
Arthritis is predominantly a disease of the elderly, but children can also be affected by the disease. More than 70% of individuals in North America affected by arthritis are over the age of 65. Arthritis is more common in women than men at all ages and affects all races, ethnic groups and cultures. An estimated 46 million individuals in USA have arthritis and the numbers continue to increase each year. Close to one million individuals are admitted to hospitals each year because of their arthritis.
History
While evidence of primary ankle (kaki) osteoarthritis has been discovered in dinosaurs, the first known traces of human arthritis date back as far as 4500 BC. In early reports, arthritis was frequently referred to as the most common ailment of prehistoric peoples. It was noted in skeletal remains of Native Americans found in Tennessee and parts of what
miércoles, 18 de agosto de 2010
Evidence
Religious texts
Proponents cite ancient mythologies to support their viewpoints based on the idea that ancient creation myths of gods who descend from the heavens to Earth to create or instruct humanity are actually representations of alien visitors, whose superior technology accounts for their reception as gods. Proponents attempt to draw an analogy to occurrences in modern times when isolated cultures are exposed to Western technology, such as when, in the early 20th century, "cargo cults" were discovered in the South Pacific: cultures who believed various Western ships and their cargo to be sent from the gods as fulfillment of prophecies concerning their return.
Flying machines are sometimes mentioned in ancient texts; one example is the Vimanas, flying machines found in the Hindu epics. These tales range from fantastic aerial battles employing various weaponry, to the mundane relating simple technical information, flight procedure, and flights of fancy.
Ezekiel
In the Biblical Old Testament, the Book of Ezekiel tells of a flying object seen as a fiery whirlwind which when descended to the ground gave the appearance of being made of metal. It is described among other things as a wheel within a wheel containing four occupants, "living creatures", whose likeness was that of man. The passage goes on to say that wherever the wheels went the creatures went, and when the living creatures were lifted up the wheels were lifted up.[20] In chapter 4 of Chariots of the Gods?, entitled, “Was God an Astronaut?” von Däniken refers to the vision of Ezekiel, suggesting Ezekiel had seen a spaceship, a comparison Morris Jessup had made in 1956.
Genesis
In the Book of Genesis, Genesis 6:1-4 states that "When men began to multiply on the face of the ground, and daughters were born to them, the sons of God saw that the daughters of men were fair; and they took to wife such of them as they chose... The Nephilim were on the earth in those days, and also afterward, when the sons of God came in to the daughters of men, and they bore children to them." In the King James Version they are identified as "giants".
The Nephilim are perhaps children of the fallen angels, although scholars are uncertain.Erich von Däniken sees an extraterrestrial connection in this passage, and suggests that here “we have the sons of God, who interbreed with human beings.”
Chuck Missler and Mark Eastman argue that UFOs carry the fallen angels, or offspring of fallen angels, the Nephilim of Genesis, who have now returned. They believe it was this interbreeding between the angels and humans that led to what they call “the gene pool problem.” Noah was perfect in his “generations,” that is “Noah’s genealogy was not tarnished by the intrusion of fallen angels. It seems that this adulteration of the human gene pool was a major problem on the planet earth.”
Von Däniken also suggests that the two angels who visited Lot in Genesis 19 were not angels, but ancient astronauts. They may have used atomic weapons to destroy the city of Sodom. In any case, the other worldly beings acted as if there was a time set for Sodom’s destruction. Von Däniken questioned why God would work on a timetable and why an "infinitely good Father" would give "preference to ‘favorite children,’ such as Lot’s family, over countless others."
Other Old Testament passages
In several chapters of the Old Testament God is depicted as traveling as a column of smoke and/or fire and making the sound of a trumpet. These descriptions also describe Yahweh as having a physical presence, rather than an abstraction. Yahweh is described raining lightning and stones down upon the enemies of the Hebrews. However, descriptions of the Hebrew God have also featured protecting wings and outstretched arms in the Psalms, features which may be considered contrary to theories of mechanical manifestations of God.
Additionally, the characteristics of the Ark of the Covenant and the Urim and Thummim are identified as suggesting high technology, perhaps from alien origins.
Apocryphal writings
The apocryphal Book of Enoch tells of similar flying objects and beings called "the Watchers" who have mutinied from "heaven" and descended to earth, but goes further in that Enoch is taken on journeys to various corners of the Earth in the object and at one point even travels to the heavens.
Artifacts and artwork
Alleged physical evidence includes the discovery of artifacts in Egypt (the Saqqara Bird) and Colombia-Ecuador, which are claimed to be similar to modern planes and gliders, although these have been interpreted by archaeologists as stylized representations of birds and insects.
"The Baptism of Christ", 1710, by Aert de GelderMore support of this theory draws upon what are claimed to be representations of flying saucers in medieval and renaissance art.This is used to support the ancient astronaut theory by attempting to show that the creators of humanity return to check up on their creation throughout time.
Other artistic support for the ancient astronaut theory has been sought in Palaeolithic cave paintings. Wondjina in Australia and Val Camonica in Italy (seen above) are claimed to bear a resemblance to present day astronauts. Supporters of the ancient astronaut theory sometimes claim that similarities such as dome shaped heads, interpreted as beings wearing space helmets, prove that early man was visited by an extraterrestrial race.
Nazca Lines
The ancient Nazca Lines comprise hundreds of enormous ground drawings etched into the high desert landscape of Peru, which consist primarily of geometric shapes, but also include depictions of a variety of animals and at least one human figure. Many believers in ancient astronauts cite the Nazca lines as evidence because the figures created by the lines are most clearly depicted or only able to be seen when viewed from the air. Writing professor Joe Nickell of the University of Kentucky, using only technology he believed to be available to people of the time, was able to recreate one of the larger figures with a reasonable degree of accuracy.
Monumental architecture
Evidence for ancient astronauts is claimed to include the existence of ancient monuments and megalithic ruins such as the Giza pyramids of Egypt, Machu Picchu in Peru, or Baalbek in Lebanon, and the Moai of Easter Island. Supporters contend these stone structures could not have been built with the technical abilities and tools of the people of the time and further argue that many could not be duplicated even today. They suggest that the large size of the building stones, the precision with which they were laid, and the distances many were transported leaves the question open as to who constructed these sites. These contentions are categorically rejected by mainstream archeology. Some mainstream archeologists have participated in experiments to move large megaliths. These experiments have succeeded in moving megaliths up to at least 40 tons, and they have speculated that with a larger workforce larger megaliths could be towed with ancient technology.Such allegations are not unique in history, however, as similar reasoning lay behind the wonder of the Cyclopean masonry walling at Mycenaean cities in the eyes of Greeks of the following "Dark Age," who believed that the giant Cyclopes had built the walls.
Proponents cite ancient mythologies to support their viewpoints based on the idea that ancient creation myths of gods who descend from the heavens to Earth to create or instruct humanity are actually representations of alien visitors, whose superior technology accounts for their reception as gods. Proponents attempt to draw an analogy to occurrences in modern times when isolated cultures are exposed to Western technology, such as when, in the early 20th century, "cargo cults" were discovered in the South Pacific: cultures who believed various Western ships and their cargo to be sent from the gods as fulfillment of prophecies concerning their return.
Flying machines are sometimes mentioned in ancient texts; one example is the Vimanas, flying machines found in the Hindu epics. These tales range from fantastic aerial battles employing various weaponry, to the mundane relating simple technical information, flight procedure, and flights of fancy.
Ezekiel
In the Biblical Old Testament, the Book of Ezekiel tells of a flying object seen as a fiery whirlwind which when descended to the ground gave the appearance of being made of metal. It is described among other things as a wheel within a wheel containing four occupants, "living creatures", whose likeness was that of man. The passage goes on to say that wherever the wheels went the creatures went, and when the living creatures were lifted up the wheels were lifted up.[20] In chapter 4 of Chariots of the Gods?, entitled, “Was God an Astronaut?” von Däniken refers to the vision of Ezekiel, suggesting Ezekiel had seen a spaceship, a comparison Morris Jessup had made in 1956.
Genesis
In the Book of Genesis, Genesis 6:1-4 states that "When men began to multiply on the face of the ground, and daughters were born to them, the sons of God saw that the daughters of men were fair; and they took to wife such of them as they chose... The Nephilim were on the earth in those days, and also afterward, when the sons of God came in to the daughters of men, and they bore children to them." In the King James Version they are identified as "giants".
The Nephilim are perhaps children of the fallen angels, although scholars are uncertain.Erich von Däniken sees an extraterrestrial connection in this passage, and suggests that here “we have the sons of God, who interbreed with human beings.”
Chuck Missler and Mark Eastman argue that UFOs carry the fallen angels, or offspring of fallen angels, the Nephilim of Genesis, who have now returned. They believe it was this interbreeding between the angels and humans that led to what they call “the gene pool problem.” Noah was perfect in his “generations,” that is “Noah’s genealogy was not tarnished by the intrusion of fallen angels. It seems that this adulteration of the human gene pool was a major problem on the planet earth.”
Von Däniken also suggests that the two angels who visited Lot in Genesis 19 were not angels, but ancient astronauts. They may have used atomic weapons to destroy the city of Sodom. In any case, the other worldly beings acted as if there was a time set for Sodom’s destruction. Von Däniken questioned why God would work on a timetable and why an "infinitely good Father" would give "preference to ‘favorite children,’ such as Lot’s family, over countless others."
Other Old Testament passages
In several chapters of the Old Testament God is depicted as traveling as a column of smoke and/or fire and making the sound of a trumpet. These descriptions also describe Yahweh as having a physical presence, rather than an abstraction. Yahweh is described raining lightning and stones down upon the enemies of the Hebrews. However, descriptions of the Hebrew God have also featured protecting wings and outstretched arms in the Psalms, features which may be considered contrary to theories of mechanical manifestations of God.
Additionally, the characteristics of the Ark of the Covenant and the Urim and Thummim are identified as suggesting high technology, perhaps from alien origins.
Apocryphal writings
The apocryphal Book of Enoch tells of similar flying objects and beings called "the Watchers" who have mutinied from "heaven" and descended to earth, but goes further in that Enoch is taken on journeys to various corners of the Earth in the object and at one point even travels to the heavens.
Artifacts and artwork
Alleged physical evidence includes the discovery of artifacts in Egypt (the Saqqara Bird) and Colombia-Ecuador, which are claimed to be similar to modern planes and gliders, although these have been interpreted by archaeologists as stylized representations of birds and insects.
"The Baptism of Christ", 1710, by Aert de GelderMore support of this theory draws upon what are claimed to be representations of flying saucers in medieval and renaissance art.This is used to support the ancient astronaut theory by attempting to show that the creators of humanity return to check up on their creation throughout time.
Other artistic support for the ancient astronaut theory has been sought in Palaeolithic cave paintings. Wondjina in Australia and Val Camonica in Italy (seen above) are claimed to bear a resemblance to present day astronauts. Supporters of the ancient astronaut theory sometimes claim that similarities such as dome shaped heads, interpreted as beings wearing space helmets, prove that early man was visited by an extraterrestrial race.
Nazca Lines
The ancient Nazca Lines comprise hundreds of enormous ground drawings etched into the high desert landscape of Peru, which consist primarily of geometric shapes, but also include depictions of a variety of animals and at least one human figure. Many believers in ancient astronauts cite the Nazca lines as evidence because the figures created by the lines are most clearly depicted or only able to be seen when viewed from the air. Writing professor Joe Nickell of the University of Kentucky, using only technology he believed to be available to people of the time, was able to recreate one of the larger figures with a reasonable degree of accuracy.
Monumental architecture
Evidence for ancient astronauts is claimed to include the existence of ancient monuments and megalithic ruins such as the Giza pyramids of Egypt, Machu Picchu in Peru, or Baalbek in Lebanon, and the Moai of Easter Island. Supporters contend these stone structures could not have been built with the technical abilities and tools of the people of the time and further argue that many could not be duplicated even today. They suggest that the large size of the building stones, the precision with which they were laid, and the distances many were transported leaves the question open as to who constructed these sites. These contentions are categorically rejected by mainstream archeology. Some mainstream archeologists have participated in experiments to move large megaliths. These experiments have succeeded in moving megaliths up to at least 40 tons, and they have speculated that with a larger workforce larger megaliths could be towed with ancient technology.Such allegations are not unique in history, however, as similar reasoning lay behind the wonder of the Cyclopean masonry walling at Mycenaean cities in the eyes of Greeks of the following "Dark Age," who believed that the giant Cyclopes had built the walls.
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