Bronchogenic Carcinoma

1. Bronchogenic Carcinoma

2. Abstract • Brochogenic carcinoma is also called Lung cancer. • It is a frequent and important neoplasm in both developed country and developing country. • In recent years, It is reported that lung cancer is the leading fatal neoplasm of men and women. • It is strongly associated with the use of tobacco products, particularly with cigarettes.

3. Incidence and prevalence • Lung cancer is the leading cause of cancer-related death of men in 28developed countries of the world • Squamous cell carcinoma is thought to be the most frequent form of the tumor(30-50 percent of all cases),followed by adenocarcinoma, large cell carcinoma, and small cell carcinoma. • Nowadays an increase has occurred in the incidence of adenocarcinoma, which is the most common histologic subtype.

4. Etiology and pathogenesis • Cigarette smoking • Occupational associations: asbestos, uranium( in miners), arsenical fumes, nickel,radon gas ects. • Other factors include air pollutions , ionizing radiation . • Nowadays It is reported that tuberculosis is associated with the incidence of lung cancer.

5. Pathogenesis • Many factors influence the formation of lung cancer. The development of lung cancer is multistep process. The transf- ormation of normal bronchial epithelial cells to malignant cells is unknown. • Perhaps It is related to: damage to cellular DNA; alteration in cellular oncogene expression; tumor-derived factors that stimulate cellular division.

6. Etiology and pathogenesis • Chronic inflammation of the lung, such as from interstitial fibrosis and areas of scarring is associated with the occurrence of adenocarcinoma. • Genetic factors also involve the formation of lung cancer.

7. Major categories of genes that potentially determine susceptibility to lung cancer, include proto-oncogenes, tumor suppressor genes, ects.

8. Oncogene abnormalities Oncogene SCLC NSCLC Ki-ras 0 30-50% of adenocarcinomas H-ras 0 Rare mutation, over expression N-ras 0 Rare mutation, over expression Myc Majority Gene amplification and overexpression

9. Classifications • According to anatomy: (1)Central lung cancer,mostly is squamous cell carcinoma and small cell carcinoma. (2) peripheral lung cancer, mostly is adenocarcinoma. • According to histologic classification: Small cell lung cancer(SCLC) and Non-small cell lung cancer(NSCLC). NSCLC includes Squamous cell carcinoma, large cell carcinoma, adenocarcinoma, adenosquamous carcinoma.

10. Classifications • Squamous cell carcinoma:It is the most common subtype.It arises from altered bronchial epithelium and growth in situ.It is related to cigarette smoking.Cavitation can occure in the distal to the obstructing mass. • Adenocarcinoma: It arises from the submucosal glands,located in peripheral airways and alveoli.Peripheral adenocarcinomas are usually well-circumscribed, grey-white masses that rarely cavitate.

11. Classification • Large-cell carcinoma, are usually located peripherally.They can be quite large and not infrequently cavitate. They have large nuclei,prominent nucleoli,abundant cytoplsma.There are two types , Giant-cell carcinoma and clear-cell carcinoma. • Adenosquamous : There are definite features of adenocarcinoma and squamous ce carcinoma.

12. Classification • Small cell carcinoma has three subtypes , oat-cell carcinoma, intermediate cell type and combined oat- cell carcinoma.SCLC belongs in a group of tumors derived from neuroendocrine cells that are responsible for the production and secretion of specific peptide product.they may related to paraneoplastic syndrome.

13. Clinical Manifestations • Due to primary lesions: cough, dyspnea, hemoptysis, sputum, wheezing, weight loss, fever, pneumonia • Due to local extension: chest pain,hoarseness,superior vena cava syndrome, horner’s syndrome, dysphagia, pericardial effusion,pleural effusion, diaphragm paralysis • Only 5-15 percent of patients are asymptomatic when discovered to have bronchogenic carcinoma.

14. Clinical manifestations Regionnal spread to hilar and mediastinal nodes may cause dysphagia due to esophageal compression, horseness due to recurrent laryngeal nerve compression, horner’s syndrome due to sympathetic nerve involvement, and elevation of the hemidiaphragm from phrenic nerve compression.

15. Clinical manifestations • Superior sulcus, or pancoast’s tumor may involve the brachial plexus, resulting in a c7-t2 neuropathy with pain, numbness, and weakness of the arm. • Cardiac involvement is seen in About 20-25 percent of patients

16. Clinical manifestations • Extrapulmonary manifestations. Including metastasis to other organs, such as brain, central nervous system, skeleton system, liver,adrenal glands and lymph nodes ects. • Paraneoplastic syndromes are remote effects of tumor. They lead to metabolic and neuromuscular disturbances unrelated to the primary tumor, metastases, or treatment. They may be the first sign of the tumor.They do not indicate that a tumor has spread.

17. Clinical manifestations Paraneoplastic syndromes include: hypertrophic pulmonary osteoarthropathy, hypercalcemia,inappropriate antidiuretic hormone secretion syndrome,polymyositis, subacute cerebellar degeneration,peripheral neuropathies and cushing’s syndrome ects.

18. Physical examinations • Usually in early stage, most of the patients with lung cancer have no positive physical findings. • General findings include abnormal percussion, breath sounds changes, moist rales (when pneumonia happens) • Digital clubbing, superior vena cava syndrome, horner’s syndrome(unilaterally constricted pupil, enophthalmos,narrowed palpebral fissure and loss of sweating on the same side of the face.

19. Physical examinations • Endobronchial obstruction may result in a localized wheeze • Lobar collapse may result in an area of decreased breath sounds and dullness to percussion.

20. Chest X-ray • The examination is the most important method. It can detect the presence of lung cancer. The most frequent finding is a mass in the lung field. Secondary manifestations seen on the chest radiograph include lober collapse,pneumonitis because of endobronchial obstruction,elevation of the hemidiaphragm, pleural effusion, hilar and mediastinal adenopathy and erosion of ribs or vertebrae due to metastases. • Alveolar cell cancer can manifest as a localized infiltrate mimicking pneumonia.

21. 阻塞性肺不张 Obstructive atelectasis) 支气管腔内阻塞或腔外压迫 • 一侧性肺不张 患侧均匀致密影 纵隔向患侧移位 肋间隙变窄 健侧代偿性肺气肿

22. 中央型肺癌 （Central bronchogenic carcinoma) • 直接征象 肺门肿块 • 间接征象 阻塞性肺炎 阻塞性肺气肿 阻塞性肺不张

24. Diagnosis of Bronchogenic carcinoma

25. Abstract Diagnosis of lung cancer requires: A: detecting the tumor B: establish the cell type C: define the stage of the tumor among these, Determing cell type is the most important because it influences the treatment.

26. Many methods we used to detect the tumor, including chest X-ray, computer Tomo graphy(CT),Magnetic resounce imaging (MRI), PET, histologic examination (mainly sputum examination, bronchoscopy biopsy,bronchial brushing , bronchial washings, transbronchial needle aspiration and transthoracic needle).

27. If a diagnosis is not established by these imaging examination and cytologic study , we can use thoracotomy. Before we make the decision , we must weigh some foctors,for example , the importance, age of the patientand other complicating illness.

28. Chest X-ray It is the most important method to find lung cancer. If a patient with chronic cough, sputum with few blood, and dyspnea, lower fever he should adopt a chest X-ray. The most frequent finding is a mass in the lung field.

29. On chest X-ray, secondary manifestations include lobar collapse, pleural effusion, pneumonitis, elevation of the hemidiaphragm, hilar and mediastinal adenopathy, and erosion of ribs or vertebrae due to metastases.

30. Central lung cancer manifestations on chest radiography Secondary manifestations we mentioned above may be exist if metastases happen,including lobar collaps, obstuctive pneumonitis, pleural effusion. Mainly shows a mass locate in the one side of hilar,some times it makes the mediastinum widen.

31. Peripheral lung cancer on chest radiography The most frequent finding is a mass in the lung field. Sometimes the mass is not smooth, and with a cavity. Secondary manifestations can be also seen on the chest X-ray, such as pleural effusion.

32. Alveolar cancer on chest radiography The chest X-ray usually shows dissiminated small nodules in the lung field.

33. 细支气管肺泡癌（Bronchiolalveolar carcinoma) • 早期：孤立结节状或肺炎样浸润 • 晚期：弥漫性结节状、斑片影，腺泡结节状占位病变

34. Lung cancer on CT CT is the most useful in evaluating patients with pulmonary and mediastinal masses. It is also useful for detecting multiple metastases. CT can show a mass to be located in which lobe of lung field and the size of the mass. It also shows the nodule in the mediastinum. Sometimes,when a mass locate behind the heart, chest X-ray can`t detect it .CT can detect some secret sites of lung cancer.

35. 周围性肺癌（Peripheral carcinoma)

36. Bronchoscopy It is important both for determining if a tumor is present and for obtaining tissue for histologic diagnosis. Usually, the combination of bronchial brushing and forceps biopsy is positive 90 to 93 percent of the tumors located in proximal airway.

37. Transbronchial lung biopsy • It may be utilized when tumor located • in peripheral airway. • Transthoracic needle with guidance • by CT can be used to detect lesions • located near the chest wall

38. Thoracotomy If the methods mentioned above are not useful for detecting the cell type of lung cancer,thoracotomy may be used. But we should analyse some other factors before we adopt the method, for example the age of the patient,the pulmonary function, and complicating illness.

39. In some circumstances,a histologic diagnosis can be made by biopsy of metastatic sites,such as lymphy nodes, liver, bone or bone marrow.

40. Other laboratory examinations some tumor markers (CEA .CA199. CA211. NSE) Some gene examination, p53gene, ras gene.

41. According to the history, clinical manifestations, physical examination, laboratory examination espically chest X-ray, CT scanning histologic examination of sputum,biopsy tissue,obtained by bronchoscopy, bronchial brushing , transbronchial and transthoracic, we can make a diagnosis.

42. Staging of lung cancer Non-small cell lung cancer. TNM classification of Non-small cell lung cancer. Small cell lung cancer has often metastasized at the time of diagnosis. TNM staging is not suited to small cell lung cancer.Small cell lung cancer is divided into limited and extensive stage disease.

43. TNM classification of lung cancer • Primary Tumor(T) • TX:primary tumor can not be assessed. tumor present as determined by presence of malignant cells in bronchopulmonary secretions, but not radiographically visible; no evidence of primary tumor • T0:No evidence of primary tumor • Tis:carcinoma in situ • T1:Tumor 3 cm or less surrounded by lung or visceral pleura, but without evidence of invasion proximal to lobar bronchus at bronchoscopy • T2:Tumor more than 3 cm or tumor invading visceral pleura or associated with obstructive pneumonitis or atelectasis; involving less than entire lung; at bronchoscopy, proximal extent of visible tumor must be within a lobar bronchus or at least 2 cm distal to carina

44. T3:Tumor of any size with direct extension into chest wall, diaphragm, or mediastinal pleuraor pericardium without involving heart, great vessels, trachea, esophagus, or vertebral body; also includes superior sulcus tumors and • T4:Tumor of any size invading mediastinum or involving heart ,great vessels, trachea,esophagus, vertebral body,or carina or presence of malignant pleural effusion

45. Nodal Involvement(N) Nx: can not assess regional lymph node • N0:No demonstrable metastasis to regional lymph nodes • N1:metastasis to peribronchial or the ipsilateral, or both,hilar lymph nodes,including direct extension • N2:metastasis to ipsilateral mediastinal lymph nodes and subcarinal lymph nodes • N3:metastasis to contralteral mediastinal lymph nodes,contralateral hilar lymph nodes,ipsilateral or contralateral scalene or supraclavicular lymph nodes

46. Distant metastasis(M) • Mx: distant metastasis can not be assessed • M0:No distant metastasis • M1:Distant metastasis present

47. Stage grouping 0 stage TisNoMo Ⅰ stage ⅠA T1N0M0 ⅠB T2N0M0 Ⅱ stage ⅡA T1N1M0 ⅡB T2N1M0, T2N0M0, T3N0M0 Ⅲ stage ⅢA T3N1M0, T1N2M0, T2N2M0, T3N2M0 ⅢB T4N0M0, T4N1M0, T4N2M0, T1N3M0, T2N3M0 , T3N3M0, T4N3M0 Ⅳstage any T and any N, M1

48. Small cell lung cancer has often metastasized at the time of diagnosis. TNM staging is not suited to small cell lung cancer.

49. Treatment Including: A:Surgery B:Chemotherapy C:Radiation therapy D:Some other therapy immunologic therapy, Chinese traditional therapy

50. Surgery Non-small cell lung cancer: patients with stage I and II are considered candidates for surgical resection, with stage III cancer may be candidates for surgery with postoperative radiation of the mediastinum.