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Lung cancer

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Lung cancer
   Classifications and external resources

   Cross section of a human lung. The white area in the upper lobe is
   cancer; the black areas indicate the patient was a smoker.
     ICD- 10   C 33.- C 34.
     ICD- 9    162
   DiseasesDB  7616
   MedlinePlus 007194
    eMedicine  med/1333  med/1336 emerg/335 radio/807 radio/405 radio/406
      MeSH     D002283

   Lung cancer is a cancer of the lungs characterized by the presence of
   malignant tumours. Most commonly it is bronchogenic carcinoma (about
   90%). Lung cancer is the most lethal of cancers worldwide, causing up
   to 3 million deaths annually. Only one in ten patients diagnosed with
   this disease will survive the following five years. Although lung
   cancer was previously an illness that affected predominately men, the
   lung cancer rate for women has been increasing in the last few decades,
   which has been attributed to the rising ratio of female to male
   smokers. More women die of lung cancer than any other cancer, including
   breast cancer, ovarian cancer and uterine cancers combined.

   Current research indicates that the factor with the greatest impact on
   risk of lung cancer is long-term exposure to inhaled carcinogens. The
   most common means of such exposure is tobacco smoke.

   Treatment and prognosis depend upon the histological type of cancer,
   the stage (degree of spread), and the patient's performance status.
   Treatments include surgery, chemotherapy, and radiotherapy.

Signs and symptoms

   Symptoms that suggest lung cancer include:
     * dyspnea (shortness of breath)
     * hemoptysis (coughing up blood)
     * chronic cough 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)
     * difficulty swallowing

   If the cancer grows into the lumen it may obstruct the airway, 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, this may be
   Lambert-Eaton myasthenic syndrome (muscle weakness due to
   auto-antibodies), hypercalcemia and 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.

   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 bone, such as the spine (causing back
   pain and occasionally spinal cord compression), the liver and the
   brain.

Diagnosis

   Performing a chest X-ray is the first step if a patient reports
   symptoms that may be suggestive of lung cancer. This may reveal an
   obvious mass, widening of the mediastinum (suggestive of spread to
   lymph nodes there), atelectasis (collapse), consolidation ( infection)
   and pleural effusion. If there are no X-ray findings but the suspicion
   is high (e.g. a heavy smoker with blood-stained sputum), bronchoscopy
   and/or a CT scan may provide the necessary information. In any case,
   bronchoscopy or CT-guided biopsy is often necessary to identify the
   tumor type.

   If investigations have confirmed lung cancer, scan results and often
   positron emission tomography (PET) are used to determine whether the
   disease is localised and amenable to surgery or whether it has spread
   to the point it cannot be cured surgically. PET is not useful as
   screening, as not all malignancies are positive on PET scan (such as
   bronchoalveolar carcinoma), and lung infections may be positive on PET
   Scan.

   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 a very poor respiratory reserve, as may occur in
   chronic smokers, surgery may be contraindicated.

Types

   There are two main types of lung cancer categorized by the size and
   appearance of the malignant cells seen by a histopathologist under a
   microscope: non-small cell (80%) and small-cell (roughly 20%) lung
   cancer. This classification although based on simple pathomorphological
   criteria has very important implications for clinical management and
   prognosis of the disease.

Non-small cell lung cancer

   The non-small cell lung cancers (NSCLC) are grouped together because
   their prognosis and management is roughly identical. When it cannot be
   subtyped, it is frequently coded to 8046/3. The subtypes are:
     * ( M 8070/3) Squamous cell carcinoma, accounting for 20% to 25% of
       NSCLC, also starts in the larger breathing tubes but grows slower
       meaning that the size of these tumours varies on diagnosis.
     * ( M 8140/3) Adenocarcinoma is the most common subtype of NSCLC,
       accounting for 50% to 60% of NSCLC. It is a form which starts near
       the gas-exchanging surface of the lung. Most cases of the
       adenocarcinoma are associated with smoking. However, among
       non-smokers and in particular female non-smokers, adenocarcinoma is
       the most common form of lung cancer. A subtype of adenocarcinoma,
       the bronchioalveolar carcinoma, is more common in female
       non-smokers and may have different responses to treatment.
     * Large cell carcinoma is a fast-growing form that grows near the
       surface of the lung. It is primarily a diagnosis of exclusion, and
       when more investigation is done, it is usually reclassified to
       squamous cell carcinoma or adenocarcinoma.

Small cell lung cancer

   Lung small cell carcinoma (microscopic view from a core needle biopsy)
   Enlarge
   Lung small cell carcinoma (microscopic view from a core needle biopsy)
     * ( M 8041/3) Small cell carcinoma (SCLC, also called " oat cell
       carcinoma") is the less common form of lung cancer. It tends to
       start in the larger breathing tubes and grows rapidly becoming
       quite large. The oncogene most commonly involved is L-myc. The
       "oat" cell contains dense neurosecretory granules which give this
       an endocrine/paraneoplastic syndrome association. It is more
       sensitive to chemotherapy, but carries a worse prognosis and is
       often metastatic at presentation. This type of lung cancer is
       strongly associated with smoking.

Other types

     * ( M 8240/3) carcinoid (the main representatives in this group)
     * ( M 8200/3) adenoid cystic carcinoma
     * cylindroma
     * mucoepidermoid carcinoma

Metastatic

   The lung is a common place for metastasis from tumors in other parts of
   the body. These cancers, however, are identified by the site of origin,
   i.e., a breast cancer metastasis to the lung is still known as breast
   cancer. The adrenal glands, liver, brain, and bone are the most common
   sites of metastasis from primary lung cancer itself.

Causes

   Exposure to carcinogens, such as those present in tobacco smoke,
   immediately causes cumulative changes to the tissue lining the bronchi
   of the lungs (the bronchial mucous membrane) and more tissue gets
   damaged until a tumour develops.

   There are four major causes of lung cancer (and cancer in general):
     * Carcinogens such as those in cigarette smoke
     * Radiation exposure
     * Genetic susceptibility
     * Viral infection

The role of smoking

   The incidence of lung cancer is highly correlated with smoking.
   Source:NIH.
   Enlarge
   The incidence of lung cancer is highly correlated with smoking.
   Source:NIH.

   Smoking, particularly of cigarettes, is by far the main contributor to
   lung cancer, which at least in theory makes it one of the easiest
   diseases to prevent. In the United States, smoking is estimated to
   account for 87% of lung cancer cases (90% in men and 79% in women), and
   in the UK for 90%. Cigarette smoke contains 19 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. The length of time a
   person continues to smoke as well as the amount smoked increases the
   person's chances of contracting lung cancer. If a person stops smoking,
   these chances steadily decrease as damage to the lungs is repaired and
   contaminant particles are gradually vacated. More recent work has shown
   that, across the developed world, almost 90% of lung cancer deaths are
   caused by smoking.

   Passive smoking—the inhalation of smoke from another's smoking— is
   claimed to be a cause of lung cancer in non-smokers. Studies from the
   USA (1986, 1992, 1997, 2001, 2003), Europe (1998), the UK (1998,), and
   Australia (1997) have consistently shown a significant increase in
   relative risk among those exposed to passive smoke.

   The EPA in 1993 claimed that about 3,000 lung cancer-related deaths a
   year were caused by passive smoking. However, since this report was
   based on a study that was alleged to be heavily biased and was ruled by
   a federal judge to be "unscientific", the EPA report was declared null
   and void by a federal judge in 1998(,).

   CAPTION: Percentage of lung cancer deaths attributable to smoking in
   the developed world

         35-69 years 70 years+ All ages
    Men  93.9        90.3      92.5
   Women 68.8        68.9      68.8
   Both  88.7        84.3      86.6

   The extensive attempts made by Philip Morris to delay the release of
   the 1997 IARC study, to affect the wording of its conclusions, to
   neutralise its negative results for their business, and to counteract
   its impact on public and policymakers' opinion has been documented by
   Ong & Glantz in The Lancet journal. Their work was based on 32 million
   pages of documents made public as part of the settlement of the 1998
   legal case of State of Minnesota and Blue Cross/Blue Shield of
   Minnesota vs Philip Morris Inc, et al. and available at Philip Morris'
   own website.

   Recent investigation of sidestream smoke suggests it is more dangerous
   than direct smoke inhalation.

Asbestos

   Asbestos can cause a variety of lung diseases. It increases the risk of
   developing lung cancer. There is a synergistic effect between tobacco
   smoking and asbestos in the formation of lung cancer.

   Asbestos can also cause cancer of the pleura, called mesothelioma
   (which is distinct from lung cancer).

Radon gas

   Radon is a colorless and odourless gas generated by the breakdown of
   radioactive radium, which in turn is the decay product of uranium,
   found in the earth's crust. Radon exposure is the second major cause of
   lung cancer after smoking. The radiation ionizes genetic material,
   causing mutations that sometimes turn cancerous. 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. In the
   US, the EPA estimates that one in 15 homes has radon levels above the
   recommended standard.

   Radon causes lung cancer because it causes arbitrary damage to the
   chromosomes and DNA molecules contained in the nucleus of the cell.

Genetics and viruses

   Oncogenes are genes that are believed make people more susceptible to
   cancer. Proto-oncogenes are believed to turn into oncogenes when
   exposed to particular carcinogens. Viruses are also suspected of
   causing cancer in humans, as this link has already been proven in
   animals. Genetic susceptibility and viral infection are not of major
   importance in lung cancer, but they may influence pathogenesis.

Lung cancer staging

   Lung cancer staging is an important part of the assessment of prognosis
   and potential treatment for lung cancer.

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

   Surgery is usually only an option in NSCLC and if the disease is
   limited to one lung and has not spread beyond its confines. This is
   assessed with medical imaging ( computed tomography, positron emission
   tomography). Furthermore, as stated, a sufficient respiratory reserve
   needs to be present to allow for the removal of lung tissue. Procedures
   performed include lobectomy (removal of one lobe), bilobectomy (two
   lobes) or pneumonectomy (removal of a whole lung). Smaller resections
   include wedge excision or segmentectomy (part of a lobe).

   The role of sub lobar resection (extended wedge resection) continues to
   be debated for the primary management of NSCLC. Although overall
   survival appears to be equivalent to that of lobectomy resection, the
   local recurrence rate has been documented to be over three times more
   common (19% compared to 5%). Accordingly, sub lobar resection has
   historically been used as a "compromise resection" approach for the
   management of small (less than 3 centimeters diameter) stage I
   peripheral NSCLC identified in patients with impaired cardiopulmonary
   reserve. Recent reports of the use of intraoperative radioactive iodine
   brachytherapy implants at the margins of sublobar resection suggest
   that local recurrence can be reduced to that of lobectomy when this is
   used as a surgical adjunct to sublobar resection.

   The role of anatomic segmentectomy (a larger sublobar resection) with
   complete lymph node staging has also been found to have potential
   survival benefits similar to lobectomy. Such resections should be
   limited to peripheral small (less than 2 centimeter diameter) stage I
   NSCLC where a margin of resection equivalent to the diameter of the
   tumor can be achieved.

   Five-year prognosis is often as good as 70% following complete
   resection of limited (lesions limited to the lung tissue without lymph
   node spread - stage 1) disease.

   After surgery, adjuvant chemotherapy may be recommended if lymph nodes
   within the lung tissues resected (stage 2) or the mediastinum (lymph
   nodes in the peri-tracheal region -stage 3) are found to be positive
   for cancer spread. Survival may be improved by up to 15% above patients
   receiving only surgical resection in these circumstances. The role of
   adjuvant chemotherapy for patients with large stage 1 NSCLC (tumors
   greater than 3 centimeters diameters without lymph node involvement -
   stage 1b) remains controversial.

   The NCI Canada study JBR.10 treated patients with stage 1B to 2B NSCLC
   with vinorelbine and cisplatin chemotherapy and showed a significant
   survival benefit of 15% over 5 years. However subgroup analysis of
   patients in stage IB showed that chemotherapy did not result in any
   survival gain in them. Similarly, while the Italian ANITA study showed
   a survival benefit of 8% over 5 years with vinorelbine and cisplatin
   chemotherapy in stages 1B to 3A patients, subgroup analysis also showed
   no benefit in the 1B stage.

   The Cancer and Leukemia -Group B (CALGB) study was a randomized study
   which examined the use of carboplatin and paclitaxel chemotherapy in
   patients with stage 1B disease. Unfortunately, although initial
   immature result in 2004 was encouraging, an update at the recent
   American Society of Clinical Oncology meeting (June 2006) reported that
   the findings are now negative with no survival advantage with the use
   of adjuvant chemotherapy in patients with this stage of disease.
   However, exploratory analysis of patients in the CALGB study suggested
   that perhaps those with tumors equal or greater than 4cm in size may
   still benefit.

   At present, it is standard practice to offer patients with resected
   stage 2-3A NSCLC adjuvant 3rd generation platinum based chemotherapy
   (e.g. cisplatin and vinorelbine). Adjuvant chemotherapy for patients
   with stage 1B remains controversial as clinical trials have not clearly
   demonstrated a survival benefit.

Chemotherapy

   Small-cell lung cancer is treated primarily with chemotherapy, as
   surgery has no demonstrable influence on survival. Primary chemotherapy
   is also given in metastatic NSCLC.

   The combination regimen depends on the tumour type:
     * NSCLC: cisplatin or carboplatin, in combination with gemcitabine,
       paclitaxel, docetaxel, etoposide or vinorelbine. In metastatic lung
       cancer, the addition of bevacizumab when added to carboplatin and
       paclitaxel was found to improve survival (though in this study,
       patients with squamous cell lung cancer were excluded because of
       problems with pulmonary hemorrhage in this group in the past).
     * SCLC: cisplatin or carboplatin, in combination etoposide or
       ifosfamide; combinations with gemcitabine, paclitaxel, vinorelbine,
       topotecan and irinotecan are being studied.

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 epidermal growth factor receptor
   (EGF-R) which is expressed in many cases of NSCLC. However despite an
   exciting start it was not shown to increase survival, although females,
   Asians, non-smokers and those with the adenocarcinoma cell type appear
   to be deriving most benefit from gefitinib.

   A newer drug called erlotinib (Tarceva), another EGF-R 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 cancer.[Similar to gefitinib, it appeared to work
   best in females, Asians, non-smokers and those with the adenocarcinoma
   cell type.

   A number of targeted agents are at the early stages of clinical
   research, such as cyclo-oxygenase-2 (COX-2) inhibitors, the pre-apoptic
   inhibitor exisulind, proteasome inhibitors, bexarotene (Targretin) and
   vaccines

   Treatment of non-small cell lung cancer is evolving.

Radiotherapy

   Radiotherapy is often given together with chemotherapy, and may be used
   with curative intent in patients who are not eligible for surgery. A
   radiation dose of 40 or more Gy in many fractions is commonly used with
   curative intent in non-small cell lung cancer; typically in North
   America, the dose prescribed is 60 or 66 Gy in 30 to 33 fractions given
   once daily, 5 days a week, for 6 to 6½ weeks. For small cell lung
   cancer cases that are potentially curable, in addition to chemotherapy,
   chest radiation is often recommended. For these small cell lung cancer
   cases, chest radiation doses of 40 Gy or more in many fractions are
   commonly given; typically in North America, the dose prescribed is 45
   to 50 Gy and can be given in either once daily treatments for 5 weeks
   or twice daily treatments for 3 weeks.

   For both non-small cell lung cancer and small cell lung cancer
   patients, radiation of disease in the chest to smaller doses (typically
   20 Gy in 5 fractions) may be used for symptom control.

Interventional radiology

   Radiofrequency ablation is increasing in popularity for this condition
   as it is nontoxic and causes very little pain. It seems especially
   effective when combined with chemotherapy as it catches the cells
   inside a tumor—the ones difficult to get with chemotherapy due to
   reduced blood supply to the inside of the tumor. It is done by
   inserting a small heat probe into the tumor to cook the tumor cells.
   The body then disposes of the cooked cells through its normal
   eliminative processes.

Epidemiology

   Lung cancer distribution in the United States.
   Enlarge
   Lung cancer distribution in the United States.

   The population segment most likely to develop lung cancer is the
   over-fifties who also 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 for men
   and women. In the US, 175,000 new cases are expected in 2006: 90,700 in
   men and 80,000 in women. Although the rate of men dying from lung
   cancer is declining in western countries, it is actually increasing for
   women due to the increased takeup of smoking by this group. Among
   lifetime non-smokers, men who have never smoked have higher
   age-standardized lung cancer death rates than women. Of the 80,000
   women who are diagnosed with lung cancer in 2006, approximately 70,000
   are expected to die from it.

   The British Doctors Study, published in the 1950s, first offered solid
   evidence on the link between lung cancer and smoking.

   Not all cases of lung cancer are due to smoking, but the role of
   passive smoking is increasingly being recognised as a risk factor for
   lung cancer, leading to policy interventions to decrease undesired
   exposure of non-smokers to others' tobacco smoke.

   In the Second World and Third World, smoking-related lung cancer is
   rising rapidly in incidence. Countries such as China are expected to
   see a marked increase in lung cancer cases as smoking is exceedingly
   common and other causes of death (such as infections) are becoming less
   common, revealing an "iceberg" of pulmonary neoplasms. Cheap tobacco
   products and heavy advertising are seen by health campaigners as a
   major problem in these countries.

Prevention

Primary prevention

   Prevention is the most cost-effective means of fighting lung cancer on
   the national and global scales. While in most countries industrial and
   domestic carcinogens have been identified and banned, tobacco smoking
   is still widespread. Eliminating tobacco smoking is a primary goal in
   the fight to prevent lung cancer, and smoking cessation is the most
   important preventative tool in this process.

   Policy interventions to decrease passive smoking (e.g. in restaurants
   and workplaces) have become more common in various Western countries,
   with California taking a lead in banning smoking in public
   establishments in 1998, Ireland playing a similar role in Europe in
   2004, followed by Italy and Norway in 2005 and Scotland as well as
   several others in 2006. New Zealand has also recently banned smoking in
   public places. (See Smoking ban).

   Only the Asian state of Bhutan has a complete smoking ban (since 2005).
   In many countries pressure groups are campaigning for similar bans.
   Arguments cited against such bans is criminalisation of smoking,
   increased risk of smuggling and the risk that such a ban cannot be
   enforced.

Screening and secondary prevention

   Regular chest radiography and sputum examination programs were not
   effective in reducing mortality from lung cancer. Earlier studies (Mayo
   Lung Project and Czechoslovakia lung cancer screening study, combining
   over 17,000 smokers) showed earlier detection of lung cancer was
   possible but mortality was not improved. Simply detecting a tumor at an
   earlier stage may not necessarily yield improved mortality. For
   example, plain radiography resulted in increased time from diagnosis of
   cancer until death and those cancers being detected by screening tended
   to be earlier stages. However, these patients continued to die at the
   same rate as those who are not screened. At present, no professional or
   specialty organization advocates screening for lung cancer outside of
   clinical trials.

   A computed tomography (CT) scan can uncover tumors not yet visible on
   an X-ray. CT scanning is now being actively evaluated as a screening
   tool for lung cancer in high risk patients, and it is showing promising
   results. The USA-based National Cancer Institute is currently
   completing a randomized trial comparing CT scans with chest
   radiographs. Several single-institution trials are ongoing around the
   world. The International Early Lung Cancer Action Project published the
   results of CT screening on over 31,000 high-risk patients in late 2006
   in the New England Journal of Medicine. In this study 85% of the 484
   detected lung cancers were stage I and thus highly treatable.
   Mathematically these stage I patients would have an expected 10-year
   survival of 88%. However, there was no randomization of patients (all
   received CT scans and there was no comparison group receiving only
   x-rays) and the patients were not actually followed out to 10 years
   post detection (the median followup was 40 months). Other studies are
   underway in this area to see if decreased long-term mortality can be
   directly observed from CT screening.

   It should be noted that screening studies have only been done in high
   risk populations, such as smokers and workers with occupational
   exposure to certain substances. This is important when one considers
   that repeated radiation exposure from screening could actually induce
   carcinogenesis in a small percentage of screened subjects, so this this
   risk should be mitigated by a (relatively) high prevalence of lung
   cancer in the population being screened.
   Retrieved from " http://en.wikipedia.org/wiki/Lung_cancer"
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