Horner Syndrome http://emedicine.medscape.

com/article/279394overview#showall

Background
Horner syndrome results from an interruption of the sympathetic nerve supply to the eye and is characterized by the classic triad of miosis (ie, constricted pupil), partial ptosis, and loss of hemifacial sweating (ie, anhidrosis).

Origin of Term
Franois Pourfour du Petit (1664-1741) first described the condition in 1727 in animal experiments; du Petit cut the intercostal nerves in the neck of dogs and noted that disturbances occurred in the eyes and face on the same side, which disproved earlier views of the cerebral origin of the intercostal nerves.[1] In 1838, the British physician Edward Selleck Hare (1812-1838) gave a description of the condition in a man with a tumor in the cervical region. It was more thoroughly described by Claude Bernard in 1852.[2] A clinical report of the syndrome in a man shot through the throat was rendered in 1864 by 3 American army physicians, Silas Weir Mitchell (1829-1914), William Keen, Jr. (1837-1932), and George Read Morehouse (1829-1905).[3] Later, in 1869, Horner wrote an account of a 40year-old woman who developed the classic manifestations of the syndrome.[4] In 1958, DG Durham documented a family in which 5 persons in 2 generations were affected.[5] This rare genetic form is probably an autosomal dominant trait. The term Horner syndrome is commonly used in English-speaking countries, whereas the term Bernard-Horner syndrome is common in France. Von Passow syndrome is an association of Horner syndrome with heterochromia iridis.[6]

Pathophysiology
Sympathetic innervation to the eye consists of a 3-neuron arc. First-order fibers descend from the ipsilateral hypothalamus through the brain stem and cervical cord to T1/T2. These fibers synapse on ipsilateral preganglionic sympathetic fibers, exit the cord, travel to the sympathetic chain as second-order neurons to the superior cervical ganglion, and then synapse on postganglionic sympathetic fibers. The third-order neurons travel via the internal carotid artery to the orbit and innervate the (dilator) radial smooth muscle of the iris. Postganglionic sympathetic fibers also innervate the muscle of Mueller within the eyelid. This muscle is responsible for initiating eyelid retraction during eyelid opening. Postganglionic sympathetic fibers responsible for facial sweating follow the external carotid

artery to the sweat glands of the face. Interruption at any location along this pathway results in ipsilateral Horner syndrome. Horner syndrome may result from the following conditions:

A lesion of the primary neuron Brainstem stroke or tumor or syrinx of the preganglionic neuron (In one study, 33% of patients with brainstem lesions demonstrated Horner syndrome.[7] ) Trauma to the brachial plexus Tumors (eg, Pancoast) or infection of the lung apex (See Lung Cancer.) A lesion of the postganglionic neuron Dissecting carotid aneurysm (In one study, 44% (65/146) of patients with internal extracranial carotid artery dissections had painful Horner syndrome, which remained isolated in half the cases (32/65).[8] ) Carotid artery ischemia Migraine Middle cranial fossa neoplasm

Epidemiology
Frequency
United States Horner syndrome is uncommon.

Mortality/Morbidity
The implications of disease depend on the underlying cause.

Race
No known racial predilection exists.

Sex
No known sexual predilection exists.

Age
No known age predilection exists.

Mesothelioma
http://emedicine.medscape.com/article/280367-overview#showall

Background
Malignancies involving mesothelial cells that normally line the body cavities, including the pleura, peritoneum, pericardium, and testis, are known as malignant mesothelioma, which may be localized or diffuse. Most, but not all, cases of pleural malignant mesothelioma (MM [lung cancer]) are associated with asbestos exposure.[1] Of patients with pleural malignant mesothelioma, 77% have been exposed to asbestos in the past. Diagnosis is difficult because the results from fluid analysis of the effusion from the tumor are not usually diagnostic. Mesothelioma is more common in males than in females and it occurs most commonly in the fifth through seventh decades of life. Most cases (~90%) of malignant mesothelioma occur in the pleura.

Pathophysiology
The 3 major histological types of mesothelioma are sarcomatous, epithelial, and mixed. Pleural mesothelioma usually begins as discrete plaques and nodules that coalesce to produce a sheetlike neoplasm. Tumor growth usually begins at the lower part of the chest. The tumor may invade the diaphragm and encase the surface of the lung and interlobar fissures. The tumor may also grow along drainage and thoracotomy tracts. As the disease progresses, it often extends into the pulmonary parenchyma, chest wall, and mediastinum. Pleural mesothelioma may extend into the esophagus, ribs, vertebra, brachial plexus, and superior vena cava. Asbestos, amphibole asbestos, asbestos-crocidolite, and amosite asbestos in particular, is the principal carcinogen implicated in the pathogenesis. Exposure to chrysotile asbestos is associated with a lower incidence of mesothelioma. The industries associated with asbestos exposure include mining, ship building involving the use of asbestos, asbestos cement manufacture, ceramics, paper milling, auto parts (asbestos brake lining), railroad repair, and insulation. In Turkey, the use of the fibrous substance erionite (similar to amphibole asbestos) in building construction has led to an epidemic of pulmonary mesothelioma. Environmental exposure to asbestos in areas polluted by the substance may increase the incidence of mesothelioma. Most malignant mesotheliomas have complex karyotypes, with extensive aneuploidy and rearrangement of many chromosomes. A loss of a single copy on chromosome 22 is the most common abnormality.

Epidemiology

Frequency
United States Approximately 2500-3000 cases are diagnosed per year. In the absence of occupational exposure to asbestos, the incidence is 0.1-0.2 per 100,000 population in both sexes. The risk is increased in polluted areas by 2- to 10-fold compared to nonpolluted areas. Of patients with malignant mesothelioma in the United States, 80% have been exposed to asbestos. International Incidence is 0.9 cases per 100,000 persons per year. Marked variability exists in the incidence of malignant mesothelioma in different countries. In some countries, the incidence is low even though asbestos exposure is high. The reasons for these differences are not known.

Mortality/Morbidity

Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal. Median survival based on histologic type is 9.4 months for sarcomatous, 12.5 months for epithelial, and 11 months for mixed. Approximately 15% of patients have an indolent course. In a recent review of 64 patients undergoing pleurectomy the overall survival rate was 43%, 28%, and 10% at 1, 2, and 3 years, respectively. The overall median survival with epithelial histology was 21.7 months (n=56 patients), 5.8 months for sarcomatous or mixed type (n=28 patients, P=.0001). The causes of morbidity include atrial fibrillation, wound infection, prolonged intubation, pulmonary emboli, myocardial infarction, respiratory failure, deep vein thrombosis, and postoperative bleeding. Asbestos exposure is linked to at least 50% of patients developing malignant mesothelioma. Approximately 8 million people in the United States have been exposed to asbestos in the workplace. Family members are also exposed to asbestos embedded in the worker's clothing. Alcohol use, dietary factors, and smoking tobacco have no effect on the incidence of pleural mesothelioma.

Race

Mesothelioma has no racial predilection. Asbestos exposure is the most important factor. Race is not a factor.

Sex

Malignant mesothelioma is more common in men, with a male-to-female ratio of 3:1. It can also occur in children; however, these cases are not thought to be associated with asbestos exposure. o For women with mesothelioma, a 1996 case series by Ascoli et al showed 86% of tumors arising from the pleura, of which most were the epithelial type. Of the patients in this series, 75% had a history of exposure to asbestos and more than half developed the malignancy secondary to household contact with a worker exposed to asbestos.[2]

For men with mesothelioma, the same case series demonstrated 45.5% with a history of exposure to asbestos and 53% with occupational exposure to asbestos. Most who were involved were construction workers, railroad workers, naval mechanics, bakers, explosive workers, and automobile mechanics.[2]

Age

Malignant mesothelioma has a peak incidence 35-45 years after asbestos exposure. Two-thirds of cases of malignant mesothelioma develop in the fifth to seventh decade of life.

Non-Small Cell Lung Cancer

http://emedicine.medscape.com/article/279960-overview#showall

Background
Lung cancer was a rare entity in the early 1900s but has since become far more prevalent. The prevalence of lung cancer is second only to that of prostate cancer in men and breast cancer in women. By the end of the 1900s, lung cancer had become the leading cause of preventable death in the United States,[1] and recently, it surpassed heart disease as the leading cause of smoking-related mortality. Lung cancers are generally divided into 2 main categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all lung cancers. NSCLC is divided further into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma histologies. (See Pathophysiology.) Lung cancer is the leading cause of cancer-related mortality in both men and women not only in the United States but also throughout the world. In 2006, the disease caused more than 158,000 deaths in the United Statesmore than colorectal, breast, and prostate cancers combined.[2] The type of lung cancer in the United States, as well as in many other countries, have also changed in the past few decades: the frequency of adenocarcinoma has risen, and that of SCC has declined. (See Epidemiology.) Most lung carcinomas are diagnosed at an advanced stage, conferring a poor prognosis. The need to diagnose lung cancer at an early and potentially curable stage is thus obvious. (See Prognosis.) In addition, most patients who develop lung cancer have been smokers and have smoking-related damage to the heart and lungs, making aggressive surgical or multimodality therapies less viable options. Lung cancer is often insidious, and it may produce no symptoms until the disease is well advanced. Approximately 7-10% of patients with lung cancer are asymptomatic, and their cancers are diagnosed incidentally after a chest radiograph performed for other reasons.

Systemic findings may include unexplained weight loss and low-grade fever. Numerous signs may be associated with NSCLC. (See Clinical Presentation.) Because of the importance of stage on the therapeutic decision-making process, all patients with non-small cell lung cancer (NSCLC) must be staged adequately. A complete staging workup for NSCLC should be carried out to evaluate the extent of disease. (See Workup.) Treatment primarily involves surgery, chemotherapy, or radiation therapy. Because most lung cancers cannot be cured with currently available therapeutic modalities, the appropriate application of skilled palliative care is an important part of the treatment of patients with NSCLC. (See Treatment and Management.) Go to Small Cell Lung Cancer for complete information on this topic.

Pathophysiology
Both exposure (environmental or occupational) to particular agents and an individuals susceptibility to these agents are thought to contribute to ones risk of developing lung cancer. In the United States, active smoking is responsible for 90% of lung cancer cases. Occupational exposures to carcinogens account for approximately 9-15% of lung cancer cases.

Exposure to carcinogens
Tobacco smoke contains more than 300 harmful substances with at least 40 known potent carcinogens. Poly-aromatic hydrocarbons and the nitrosamine-NNK are known to cause DNA damage by forming DNA adducts in animal models. Benzo-A-pyrine also appears to induce molecular signaling such as AKT, as well as inducing mutations in p53 and other tumor suppressor genes. The most common occupational risk factor for lung cancer is exposure to asbestos. Studies have shown radon exposure to be associated with 10% of lung cancer cases, while outdoor air pollution accounts for perhaps 1-2%.[3] In addition, preexisting nonmalignant lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and tuberculosis have all been shown to be associated with increased lung cancer rates. The current multiple hit theory suggests that a series of toxic cellular insults disrupts orderly genetic reproduction. Symptoms ultimately develop from the uncontrolled disorganized growth that interferes with local or distant anatomy or physiologic processes.[3] A study by Ito et al assessed the shift in histologic types of lung cancer in Japan and the United States in relation to the shift from nonfiltered to filtered cigarettes.[4] The study determined that the shift in cigarette types only altered the most frequent type of lung cancer, shifting from SCC to adenocarcinoma.

Genetic susceptibility
Recently, advanced molecular techniques have identified amplification of oncogenes and inactivation of tumor suppressor genes in NSCLC. The most important abnormalities

detected are mutations involving the ras family of oncogenes. The ras oncogene family has 3 members: H-ras, K-ras, and N-ras. These genes encode a protein on the inner surface of the cell membrane with GTPase activity and may be involved in signal transduction. Studies performed on mice suggest the involvement of ras mutations in the molecular pathogenesis of NSCLC. Studies in humans suggest that ras activation contributes to tumor progression in persons with lung cancer. The ras gene mutations occur almost exclusively in adenocarcinoma and are found in 30% of such cases. These mutations were not identified in adenocarcinomas that developed in persons who do not smoke. The K-ras mutation appears to be an independent prognostic factor. Studies are ongoing to develop management plans according to the presence or absence of ras gene mutations. Other molecular abnormalities found in NSCLC include mutations in c-myc and c-raf among oncogenes and retinoblastoma (Rb) and p53 among tumor suppressor genes.

Classification of lung cancer

Lung cancers are generally divided into 2 main categories: SCLC and NSCLC. NSCLC accounts for approximately 85% of all lung cancers. NSCLC is divided further into adenocarcinoma, SCC, and large cell carcinoma histologies. All share similar treatment approaches and prognoses but have distinct histologic and clinical characteristics. Adenocarcinoma, arising from the bronchial mucosal glands, is the most frequent non-small cell lung cancer in the United States, representing 35-40% of all lung cancers. It usually occurs in a peripheral location within the lung. Adenocarcinoma is the most common histologic subtype, and may manifest as a scar carcinoma. This is the subtype observed most commonly in persons who do not smoke. This type may manifest as multifocal tumors in a bronchoalveolar form. Bronchoalveolar carcinoma is a distinct subtype of adenocarcinoma with a classic manifestation as an interstitial lung disease on chest radiograph. Bronchoalveolar carcinoma arises from type II pneumocytes and grows along alveolar septa. This subtype may manifest as a solitary peripheral nodule, multifocal disease, or a rapidly progressing pneumonic form. A characteristic finding in persons with advanced disease is voluminous watery sputum. SCC accounts for 25-30% of all lung cancers. Whereas adenocarcinoma tumors are peripheral in origin, SCC is found in the central parts of the lung (see the image below). The classic manifestation is a cavitary lesion in a proximal bronchus. This type is characterized histologically by the presence of keratin pearls and can be detected with cytologic studies because it has a tendency to exfoliate. It is the type most often associated with hypercalcemia.

Nonsmall cell lung cancer. A cavitating right lower lobe squamous cell carcinoma. Large cell carcinoma accounts for 10-15% of lung cancers, typically manifesting as a large peripheral mass on chest radiograph; it appears to be decreasing in incidence because of improved diagnostic techniques.[5] Histologically, this type has sheets of highly atypical cells with focal necrosis, with no evidence of keratinization (typical of SCC) or gland formation (typical of adenocarcinomas). Improved histopathologic procedures and the use of electron microscopy allow for most large cell tumors to be identified as undifferentiated adenocarcinomas and less frequently as SCCs. Large cell undifferentiated cancers have the same prognosis as do adenocarcinomas and are combined with them in clinical trials. SCLC is also divided into several types, including pure small cell, mixed small cell, and combined small cell. SCLC is usually more aggressive than NSCLC and presents as a central lesion with hilar and mediastinal invasion along with regional adenopathy. It is not uncommon for patients with SCLC to already have metastatic disease at initial diagnosis. The most common sites of metastasis of lung cancer are the bones, liver, adrenal glands, pericardium, brain, and spinal cord.[6]

Etiology
Causes of lung cancer include the following:

Smoking (78% in men, 90% in women) Asbestos exposure Radon exposure Halogen ether exposure Chronic interstitial pneumonitis Inorganic arsenic exposure Radioisotope exposure, ionizing radiation Atmospheric pollution Chromium, nickel exposure Vinyl chloride

Unlike many other malignancies, whose causes are largely unknown, lung cancer is known to be caused by tobacco smoking in as many as 90% of patients.

Because not all smokers develop lung cancer and not all lung cancer patients have a history of smoking, other factors (eg, genetic susceptibility see Pathophysiology, arsenic exposure, radiation exposure, and other environmental carcinogens[7] ) also play a causative role, either independently or in conjunction with smoking. Genetic factors probably contribute in all populations, but the contribution of other factors is population-specific.

Smoking
Smoking prevalence in the United States has gradually declined over last 4 decades. In 2008, there were an estimated 46 million active smokers in the United States, with highest prevalence among Native Americans and lowest prevalence among Hispanic and Asian Americans. Overall, the prevalence was highest in adults aged 25 years or older with low educational attainment.[8] Worldwide, the incidence of smoking in developing countries is on the rise, with almost 320 million smokers in China alone. The development of lung cancer is directly related to number of cigarettes smoked, length of smoking history, and the tar and nicotine content of the cigarettes. Risk is highest among current smokers and lowest among nonsmokers. A large trial showed that persistent smokers had a 16-fold elevated lung cancer risk, which was further doubled in those who started smoking when younger than 16 years.[9] The age-adjusted incidence rates range from 4.8-20.8 per 100,000 among nonsmokers to 140-362 among active smokers. Although tobacco smoking is the major cause of lung cancer, it is now believed that males and females may differ in their susceptibility to carcinogenic effects of tobacco smoke. This difference may be due to differences in DNA repair mechanisms. Although still considered controversial, it is well known that women are more likely to develop adenocarcinomas and that, stage for stage, women live longer. In addition, differences in response to certain biologic therapies (eg, epidermal growth factor [EGF] inhibitors) and antiangiogenic agents have been observed between sexes. The risk of lung cancer declines slowly after smoking cessation. Long-term follow-up studies show that the relative risk remains high in the first 10 years after cessation and gradually declines to 2-fold approximately 30 years after cessation. This long-term risk explains the development of almost 50% of United States lung cancer cases in past smokers. A minority of lung cancers develop in those who have never smoked. These lung cancers are genetically distinct from smoking-related NSCLC, and this distinction may have therapeutic implications. The observed genetic differences include a lower frequency of K-ras and a higher frequency of mutations in EGF receptor and likely are responsible for the higher efficacy of EGF receptor inhibitors in this patient population. Cigarette smoke containing the carcinogenic N -nitrosamines and aromatic polycyclic hydrocarbons can be inhaled passively by nonsmokers (secondhand smoke); urinary levels of these carcinogens are 1-5% of those found in active smokers. As many as 25% of the lung cancers in persons who do not smoke are believed to be caused by secondhand smoke.[10] The US Environmental Protection Agency has recognized passive smoking as a potential carcinogen. About 3000 cases of lung cancer appear to be related to passive exposure. This awareness has led to local ordinances restricting smoking in enclosed public places, including restaurants and government buildings.

Asbestos exposure
The silicate type of asbestos fiber is an important carcinogen. Asbestos exposure has been shown to be strongly associated with the causation of lung cancer, malignant pleural mesothelioma, and pulmonary fibrosis. It increases the risk of developing lung cancer by as much as 5 times. Tobacco smoke and asbestos exposure act synergistically, and the risk of developing lung cancer for persons who currently smoke tobacco and have a history of asbestos exposure approaches 80-90 times that of control populations.

Radon exposure
Radon is an inert gas produced as a result of uranium decay. Radon exposure is a wellestablished risk factor for lung cancer in uranium miners. Approximately 2-3% of lung cancers annually are estimated to be caused by radon exposure. Household exposure to radon, however, has never been clearly shown to cause lung cancer. The US National Research Councils report of the Sixth Committee on Biological Effects of Ionizing Radiation has estimated that radon exposure causes 2100 new lung cancers each year, while it contributes to lung cancer causation in approximately 9100 persons who smoke.

HIV infection
A recent report from the State of Texas Health Department suggested a 6.5-fold increase in lung cancer in patients infected with HIV.[11] Other large series do not support an increased prevalence of lung cancers in subjects with HIV infection.[12]

Other environmental agents

Beryllium, nickel, copper, chromium, and cadmium have all been implicated in causing lung cancer. Dietary fiber and vegetables have been suggested as protective from lung cancer. Although diets rich in fruits and vegetables appear to be associated with lower rates of lung cancer, trials of supplemental beta-carotene, alone or in combination with vitamin E or retinyl palmitate, in persons at high risk for lung cancer found that this supplementation actually increased the incidence of lung cancers.

Epidemiology
United States statistics
In the United States, lung cancer is the second most common cancer in women, and it is second only to prostate cancer in men. In 2008, 215,000 lung cancer cases occurred and 161,000 deaths were expected.[13] The American Cancer Society projected that 219,440 cancers of the lung and bronchus would be diagnosed in the United States in 2009, with 116,090 cases in males and 103,350 cases in females.[14]

From 1991-2005, the incidence of lung cancer in men has decreased each year by 1.8%; however, the incidence has increased by 0.5% per year for women over that same period. Lung cancer death rates for US women are among the highest in the world. Although in the United States death rates among males are higher than among females, rates for US men are still lower than rates among men in several other countries.[15] These trends in US death rates parallel trends in smoking prevalence over the past 50 years. Overall, the prevalence of smoking is approximately 21.6% in the United States and has remained unchanged over the past 15 years.

International statistics
Lung cancer is the most commonly diagnosed cancer worldwide,[16] and its incidence continues to grow. In 2007, an estimated 1.5 million new cases of lung cancer were diagnosed globally, accounting for approximately 12% of the global cancer burden. An estimated 1.35 million lung cancer deaths occurred in 2007. Among all cancers, lung cancer now has the highest mortality rate in most countries, with industrialized regions such as North America and Europe having the highest rates. Several differences exist in lung cancer incidence according to geographic area. The highest incidence occurs in the United Kingdom and Poland (>100 cases per 100,000 population per year). The lowest incidence rate occurs in Senegal and Nigeria (< 1 case per 100,000 population per year). With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India. Generally, global lung cancer trends have followed the trends in smoking, with a lag time of several decades. Lung cancer incidence has been declining in several countries, including the United States, Canada, the United Kingdom, and Australia, following the decreasing rate of smoking. Lung cancer incidence among women, however, continues to increase in several parts of the globe, although it has begun to plateau in the United States. Notably, despite a very low rate of smoking, Chinese females have a higher incidence of lung cancer than European females.

Age distribution for NSCLC

Lung cancer occurs predominately in persons aged 50-70 years. The probability of developing lung cancer remains very low until age 39 years in both sexes. It then slowly starts to rise and peaks among those older than 70 years. The risk of developing lung cancer remains higher among men in all age groups after age 40 years.

Sex distribution for NSCLC

Lung cancer is more common in men than in women. In the United States, Northern Europe, and Western Europe, the prevalence of lung cancer has been decreasing in men. In Eastern and Southern European countries, the incidence of lung cancer has been rapidly increasing. Most Western countries have encountered a disturbing trend of increasing prevalence in women and younger patients. Women have a higher incidence of localized disease at presentation and of adenocarcinoma and typically are younger when they present with symptoms.

In the United States, the probability of developing lung cancer remains equal in both sexes until age 39 years (0.03% or approximately 1 in 3,000). It then starts to increase among men compared with women, reaching a maximum in those older than 70 years (6.74% vs 4.61% or 1 in 15 vs 1 in 22, among men and women respectively).

Prevalence of NSCLC by race

Whereas lung cancer incidence rates are similar among African American and white women, lung cancer occurrence is approximately 45% higher among African American men than among white men.[15] This increased incidence has been attributed to differences in smoking habits; however, recent evidence suggests a slight difference in susceptibility. From 1995-2001, the 5-year relative survival rate was 13% lower in African Americans compared with white individuals.[15] This racial gap persisted within each stage at diagnosis for both men and women. Trends in 5-year survival rates in lung cancer from 1975-2003 revealed that while modest gains occurred in 5-year survival rates among whites, survival rates remained unchanged in the African American population. Current 5-year survival rates are estimated to be 16% among whites and 13% among non-whites.

Prognosis
Lung cancer is highly lethal. Data compiled by the American Cancer Society show lung cancer to be, by far, the most common fatal cancer in men (31%) and in women (26%). The American Cancer Society projected that deaths related to lung cancer would total 159,390 (88,900 in males and 70,490 in females) in the United States in 2009, accounting for 28% of all cancer-related deaths.[2] Worldwide, an estimated 1,351,000 deaths due to lung cancer occurred in 2007 (975,000 in men and 376,000 in females). In Europe, the 5-year overall survival rate is 8%, similar to that of the developing world. The highest recorded 5-year patient survival rates are observed in the United States. US data collected from 1995-2001 indicate that the 5-year relative survival rate for lung cancer was 15.7%, reflecting a steady but slow improvement from 12.5% in 1975.[15] However, the 5-year relative survival rate varies markedly, depending on how advanced the disease is at diagnosis:

49% for local disease 16% for regional disease 2% for distant stage disease

Estimated 5-year survival rates for specific stages of disease are as follows:

Stage IA - 75% Stage IB - 55% Stage IIA - 50% Stage IIB - 40% Stage IIIA - 10-35% Stage IIIB - Less than 5% Stage IV - Less than 5%

Prognostic factors for NSCLC are summarized in the image below.

Nonsmall cell lung cancer. Prognostic factors for lung cancer. A retrospective Surveillance, Epidemiology, and End Results (SEER) data analysis suggests that the number of nodes with cancer may be predictive of survival.[17] Patients with in situ and stage I lung cancer may respond to surgery. Their prognosis is far better than that of patients with more advanced disease. In patients with radiologically occult lung neoplasms, the 5-year survival rate is 24-26%; in those with abnormal chest radiographic findings, the rate is 12%. If the cancer is nonresectable, the prognosis is poor, with a mean survival rate of 8-14 months. Mostertz et al found that in some patient populations, the oncogenic pathway activation profile of the tumor can have prognostic significance.[18] Retrospective analysis of 787 patients with predominantly early-stage NSCLC, using gene expression profiling, showed the following:

In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src and tumor necrosis factor (TNF) pathways. In women, high-risk patients demonstrated increased activation of the invasiveness and signal transducer and activator of transcription 3 (STAT3) pathways. Multivariate analyses confirmed the independent clinical relevance of the pathwaybased subphenotypes in women and patients younger than 70 years.

A meta-analysis by Parsons et al suggests that smoking cessation after diagnosis of earlystage lung cancer may improve prognosis, probably by reducing cancer progression. Life table modelling on the basis of data from 9 studies gave an estimated 5-year survival rate of 33% in 65-year-old patients with early-stage NSCLC who continued to smoke compared with 70% in those who quit smoking.[19] Secondary analyses of the Womens Health Initiative (WHI) randomized, placebo-controlled trial, performed on patients taking daily conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg), found that women diagnosed with NSCLC who take estrogen-progestin had an increased mortality compared with women who have NSCLC and do not take hormone therapy.[20] The analyses included 16,608 multiethnic postmenopausal women aged 50-79 years and assessed the association of hormone therapy on lung cancer incidence and mortality. Confirmation of lung cancers was completed by medical record review. Results showed that the use of CEE plus MPA for more than 5 years increased a womans risk for NSCLC. This

area deserves more attention and study to determine the risks and benefits of hormone therapy for postmenopausal women who smoke. A review of 8 trials by Rothwell et al found that allocation to aspirin reduced death caused by cancer. Individual patient data were available from 7 of the 8 trials. Benefit was apparent after 5 years of follow-up. The 20-year risk of cancer death was also lower in the aspirin group for all solid cancers. A latent period of 5 years was observed before risk of death was decreased for esophageal, pancreatic, brain, and lung cancers. A more delayed latent period was observed for stomach, colorectal, and prostate cancer. Benefit was only seen for adenocarcinomas in lung and esophageal cancers. The overall effect on 20-year risk of cancer death was greatest for adenocarcinomas.[21] A study by Bouchardy et al found that patients who had received antiestrogen treatment for breast cancer had a lower lung cancer mortality rate.[22]

Patient Education
Advise patients that, among all measures, smoking cessation is most important. Smoking cessation by others who share the patients home, car, or both is also important. According to published data, the use of nicotine alternatives (eg, gum, patch, spray) instead of cigarettes reduces the incidence of lung cancer. However, it does not affect the incidence of ischemic heart disease. Advise the patient to avoid asbestos exposure. Consider prophylactic administration of retinoids, such as beta-carotene. For patient education information, see the Cancer and Tumors Center, as well as Lung Cancer, Bronchoscopy, and Understanding Lung Cancer Medications.