Lung cancer
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- Также приведены классификации рака легкого. Освещены диагностические критерии и подходы при стадировании заболевания.
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MINISTRY OF PUBLIC HEALTH OF UKRAINE KHARKOV STATE MEDICAL UNIVERSITY В.И.Стариков А.Н.Белый
LUNG CANCERРАК ЛЕГКОГО Kharkov KSMU – 2006УДК 616.024-006.6-07 ISBN 966-7152-05-9 Утверждено ученым советом Харьковского государственного медицинского университета Протокол № от АВТОРЫ:
В учебном пособии, изложенном на английском языке, рассмотрены вопросы эпидемиологии, этиологии, патоморфологии, диагностики рака легкого, его осложнений. Подробно описана клиническая картина различных форм заболевания, проводится дифференциальная диагностика с наиболее распространенными заболеваниями легких.Также приведены классификации рака легкого. Освещены диагностические критерии и подходы при стадировании заболевания.В пособии подробно изложены вопросы хирургического, лучевого, химотерапевтического методов лечения и их возможных комбинаций, приведены стандарты диагностики рака легкого, освещены пути дальнейшего развития науки по проблеме рака легкого. Учебное пособие рассчитано на студентов медицинских вузов, обучающихся на английском языке. ISBN 966-7152-05-9 © В.И. Стариков, А.Н. Белый Рак легкого 2004
Lung cancer (LC) is the malignant tumor developing from an epithelium of bronchi mucous or in cicatrix of lung parenchyma. The lung cancer is the group of tumors differing by a biological nature, clinical signs, morphological structure, speed of growth and ability to metastasize. Lung cancer is one of the most important diseases in respiratory medicine. Worldwide, it is the commonest cancer in men, virtually the commonest in women, and has a greater total incidence than that of colorectal, cervical, and breast cancer combined.
Bronchogenic carcinoma remains a major health problem throughout the world. Worldwide it is estimated that 47–52% of men and 10–12% of women smoke. Compared with women, men started smoking younger, smoked more and for a longer duration, inhaled more deeply, and bought cigarettes with a higher tar content. Women took up smoking in the United States and Western Europe during the second World War. Recent case-control studies have shown female smokers to have a higher relative risk of lung cancer than males, after adjusting for age and average daily consumption. While the incidence of almost all other malignancies is falling or remaining stable, the incidence of lung cancer continues to increase dramatically. During 50 years the incidence of LC has grown in 14 times (Fig. 1). In Ukraine the case rate has increased in 2 times for last 20 years, thus the annual gain makes 3,8%. Over the past 20 years, the male preponderance of 5-7 : 1 has fallen to its current level due to the striking increase in lung cancer among women, which began in 1965 (Fig. 1). Presumably, this changing pattern of disease is due to the post-World War II increases in cigarette smoking among the general population, and women in particular, which are only now being felt. The high level of an incidence is marked in England (57,5), Germany (62,7), France (66,2 on 100 thousand population).
At the end of the twentieth century, lung cancer had become one of the world's leading causes of preventable deaths. By 1950, case-control epidemiologic studies showed that cigarettes were strongly associated with the risk of lung cancer. In 1962, the Royal College of Physicians in London intervened in a public health matter for the first time since 1725 and published a compelling document supporting the evidence that smoking caused lung cancer. In 2001, lung cancer will have caused more than 1 million deaths worldwide and this global incidence is rising at 0.5% per annum. The etiology of the great majority of lung cancers has been known for nearly 50 years, but we have failed to make serious inroads into the powerbase of the tobacco industry. The elevation of a LC mortality correlates with increasing of its incidence. In the majority of the countries of the world the LC is conducting reason of deaths among men more than 45 years. Important LC facts (US data):
ETIOLOGY OF THE LUNG CANCER LC is the multifactor disease. There are chemical, physical and genetic theories of a carcinogenesis for today. The role of factors of an environment in a genesis of LC is conventional. The most essential factors are smoking, professional factors, pollution of atmospheric air and air of living rooms. Smoking. The majority of scientists count, that 80 % of all cases of occurrence of a LC are connected with a smoking. There are over 2000 chemicals in cigarette smoke; several of them are either direct carcinogens or cocarcinogens. Worldwide it is estimated that 47–52% of men and 10–12% of women smoke. Compared with women, men started smoking younger, smoked more and for a longer duration, inhaled more deeply, and bought cigarettes with a higher tar content. Women took up smoking in the United States and Western Europe during the second World War. Recent case-control studies have shown female smokers to have a higher relative risk of lung cancer than males, after adjusting for age and average daily consumption. Smoking induces a spectrum of histologic changes in the bronchial epithelium, which are not seen in nonsmokers. These changes include loss of bronchial cilia, basal epithelial hyperplasia, and nuclear abnormalities. The severity of such changes increases in heavy smokers and tends to be most severe in patients dying from lung cancer. Smoking-induced alterations in bronchial mucosa may slowly resolve in individuals who stop smoking. It precisely fixed, that in persons smoking per day more than 1 pack of cigarettes the risk of LC in 30 times greater than in nonsmokers. Results of epidemiological researches specify correlation of a case rate of a LC with amount of smoked cigarettes and duration of smoking (Fig. 2). The risk of lung cancer is related to cumulative dose, which for cigarettes is quantified in "pack-years." One in seven persons who smoke more than two packs per day will die of lung cancer. The incidence of death from lung cancer begins to be above that of the nonsmoking population at 10 pack-years. It is proved, that the tobacco smoke influences equally on smokers and non-smokers. Smoking cigars or pipes doubles the risk of lung cancer compared to the risk in nonsmokers. Nonsmoking wives of husbands-smokers fall ill with a LC in 2 times more often, than wives of nonsmoking husbands. Therefore the constant presence in a room where someone smokes is dangerous for nonsmokers. Passive smoking probably increases the risk of lung cancer about twofold, but because a proportion of the risk associated with active inhalation is about 20-fold, the actual risk is quite small. Following the cessation of smoking, the risk steadily declines, approaching but not quite reaching that of nonsmokers after 15 years of abstinence for patients who smoked for less than 20 years. The risk is reduced for patients who smoked for more than 20 years but never approaches that of nonsmokers. Fig. 2. Mortality among nonsmokers and smokers (by Hammond & Horn): a – nonsmokers, b – ½ of pack per day, c – ½-1 pack per day, d – 1-2 packs per day, e – more than 2 packs per day. Asbestos is causally linked to malignant mesothelioma. Asbestos exposure also increases the risk of lung cancer, especially in smokers (three times greater risk than smoking alone). Thus the risk of lung cancer in smokers who are exposed to asbestos is increased 90-fold. Radiation exposure may increase the risk of small cell lung cancer in both smokers and nonsmokers. Other substances associated with lung cancer include arsenic, nickel, chromium compounds, chloromethyl ether, and air pollutants. It is necessary to note, that smoking and professional factors simultaneously increase risk of LC. Lung cancer is itself associated with an increased risk of another lung cancer occurring both synchronously and subsequently. Other lung diseases. Lung scars and chronic obstructive pulmonary disease are associated with an increased risk of lung cancer. Scleroderma is associated with alveolar carcinoma. The knowledge of the majority of factors conducting to development of a LC allows to establish groups of the increased risk.
PATHOGENESIS AND PATHOMORPHOLOGY OF THE LUNG CANCER It is possible to divide pulmonary cancerogenesis into three stages: initiation, promotion (activation) and a tumor progression. The first phase initiation is the occurrence of pretumor cells with genetically fixed properties: immortality, blocked terminal differentiation, ability to promotion. The basic condition of initiation is interaction of carcinogen with cellular DNA, promoting mutational and other changes of DNA of cells-targets. Following initiation phase is a promotion. This is a phase of a malignant transformation, in which cells under influence of the certain factors (promotors) are transformed and growing as a tumor. Promotors may be chemical compounds of an exogenous nature and endogenic one. The third phase of a carcinogenesis is the progression. It is purchase by a tumor during its growth of more malignant properties, simplification of structure and function of its cells. The progression of a tumor is due to heterogeneity of a neoplastic population and it's genetic instability. Populations of malignant cells of the same tumor differ on metastatic potential, radioresistance, sensitivity to antitumoral therapy. Malignant lung tumors have great metastatic potential that is caused by their ability to invasive growth. It is shown in fast local diffusion of a tumor with infiltration of adjucent anatomic structures: mediastinum, pericardium, diaphragm, ribs etc. (Fig. 3), and also in a rough lymphogenous and hematogenous innidiation. "Target" organs for distant metastases are liver, brain, bones, kidneys, opposite lung.
Now the most widespread is morphological classification of a LC by N.A. Kraevsky, A.S. Yagubova and I.G. Olhovsky (1982), which is taking into account a morphological type and grade differentiation. 1. Epidermoid carcinoma: а) high differentiated; b) average differentiated; c) low differentiated. 2. Small cell cancer: а) oat cell; b) lymphocyte-similar; c) spindle-cell; d) pleomorph. 3. Adenocarcinoma: а) high differentiated; b) glandular-solid structure; c) low differentiated; d) bronchoalveolar. 4. Large cell carcinoma: а) giant cell; b) clear cell. 5. The mixed cancer. Specified groups make about 90 % of all cases of a LC: epidermoid cancer meets in 40 % of patients, adenocarcinoma is in 15-20 %, small cell lung cancer - in 20-25 %, large cell cancer - in 10-15 %. The other 10% are carcinoid, sarcomas, melanomas, mesothelioma of pleura, etc. Most classifications, including the one by the World Health Organization, divide lung cancer into four major types: squamous or epidermoid, adenocarcinoma, large-cell carcinoma, and small-cell carcinoma (SCLC) (Fig. 4). With the exception of the small-cell type, these classifications are poorly predictive of tumor behavior. As a result, the clinician has been concerned primarily with the division of lung cancer into SCLC and non-SCLC types.
Squamous cell carcinoma arises from altered bronchial epithelium and is preceded by years of progressive mucosal changes that include squamous metaplasia, dysplasia, and carcinoma in situ. In its early stages of growth, the tumor may appear as a small, red, granular plaque or as a focus of whitish leukoplakia. Later, it may appear as a large intrabronchial gray-white or yellow mass. Cavitation may occur in the lung distal to the obstructing mass. Microscopically, there are intercellular bridges connecting the abnormal neoplastic cells and abundant keratin formation. Adenocarcinomas are classically peripheral tumors arising from the peripheral airways and alveoli but may arise proximally from the epithelium or submucosal glands. When bronchial in origin, they are almost impossible to distinguish on a cytologic basis from metastatic pancreatic, renal, breast, and colonic adenocarcinoma. When peripheral, they may be similarly difficult to distinguish from metastatic adenocarcinoma or malignant mesothelioma. Peripheral adenocarcinomas are usually well-circumscribed, gray-white masses that rarely cavitate. Microscopically, there is a spectrum of well-developed to poorly developed cuboidal or columnar cells having microvilli and forming glandlike structures that may or may not produce mucin. In the bronchoalveolar type, 50% of which secrete mucin, the cylindrical tumor cells grow along the wall of the alveoli. Small-cell carcinomas usually develop proximally as large, bulky, soft, gray-white masses. When bronchial narrowing occurs, it commonly results from circumferential narrowing by extraluminal tumor. Microscopically, small-cell carcinomas are composed of fusiform, round, or polygonal cells about twice the size of lymphocytes with inconspicuous nucleoli and modest amounts of cytoplasm. The presence of cytoplasmic dense-core granules has led to the concept that SCLC belongs in a group of tumors derived from neuroendocrine cells, responsible for the production and secretion of specific peptide products. Although SCLC is divided into oat-cell, intermediate cell, and combined cell patterns, it is unclear whether these subtypes differ in their natural history or response to therapy. Large-cell carcinomas, like adenocarcinomas, are usually located peripherally. They may be quite large and not infrequently cavitate. Microscopically, they have large nuclei, prominent nucleoli, abundant cytoplasm, and distinct cytoplasmic membranes. Large-cell carcinomas lack evidence of either squamous or glandular differentiation; many may represent undifferentiated forms of adenocarcinoma or squamous cell carcinoma. Clinical picture, choice of treatment and the survival depends on the form of growth of a bronchogenic cancer. The most complete and convenient for practical using is clinical-anatomic classification of a LC by A.I. Savitsky:
B. Peripherial cancer:
C. Atypical forms:
Fig. 5. Types of central LC growth: 1 – endobronchial, 2 – peribronchial nodal, 3 – tree-like. In case of the central cancer the tumor affects large bronchi (main, lobular, segmental) and localised closely from heart, esophagus, large vessels etc. Infringement of bronchial air passage is prevailing in manifestation of disease. Central cancers meet in 80 % of cases. The peripherial LC develops in bronchi of finer size, that is why tumor is far from the vital organs and a clinical picture of disease is not so expressed. It is necessary to note Pancoast's cancer which signs are caused by a tumor invasion to an adjacent structures. So, in classical variant the tumor invades first rib, causing its destruction, plexus brahialis and a ganglion “stellatum” of truncus sympathicus. It is accompanied by a pain in the top extremity on the side of defeat and development of Horner's syndrome (ptosis, miosis, enophtalmus). Peripherial LC with a cavity in center meets more often. It is caused by fast growth of a malignant tumor and its backlog of vascularisation that conducts to infringement of trophicity and a necrosis especialy in center. It is necessary to pay attention to the group of atypical forms of a LC. As it was already marked, the tumors reaching 1-2 mm in diameter, may give lymphogenous and hematogenous metastases. Getting in favorable conditions, in some cases, the metastatic tumor begins to grow much faster maternal and results in clinical displays of disease as a pathology of organ with metastase. At the same time the primary lung tumor have small sizes and frequently is not diagnosticated clinically and with the help of special examinations. Yüklə 390,43 Kb. Dostları ilə paylaş:
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