Bronchogenic Carcinoma

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.

Incidence and prevalence

Lung cancer is the leading cause of cancerrelated 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.

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.

Pathogenesis
Many factors influence the formation of lung cancer. The development of lung cancer is multistep process. The transformation 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.

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.

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

Oncogene abnormalities Oncogene SCLC NSCLC

Ki-ras
H-ras N-ras Myc 0 0 0 Majority 30-50% of adenocarcinomas Rare mutation, over expression Rare mutation, over expression Gene amplification and overexpression

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 Nonsmall cell lung cancer(NSCLC). NSCLC includes Squamous cell carcinoma, large cell carcinoma, adenocarcinoma, adenosquamous carcinoma.

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 wellcircumscribed, grey-white masses that rarely cavitate.

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.

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.

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, horners syndrome, dysphagia, pericardial effusion,pleural effusion, diaphragm paralysis Only 5-15 percent of patients are asymptomatic when discovered to have bronchogenic carcinoma.

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

Clinical manifestations
Superior sulcus, or pancoasts 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 2025 percent of patients

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.

Clinical manifestations
Paraneoplastic syndromes include: hypertrophic pulmonary osteoarthropathy,

hypercalcemia,inappropriate antidiuretic
hormone secretion syndrome,polymyositis,

subacute cerebellar degeneration,peripheral

neuropathies and cushings syndrome ects.

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, horners syndrome(unilaterally constricted pupil, enophthalmos,narrowed palpebral fissure and loss of sweating on the same side of the face.

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.

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.

 Obstructive atelectasis)


Central bronchogenic carcinoma)

Diagnosis of Bronchogenic carcinoma

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.

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).

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 patient and other
complicating illness.

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.

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.

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.

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.

Alveolar cancer on chest radiography

The chest X-ray usually shows dissiminated small nodules in the lung field.


Bronchiolalveolar carcinoma)

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.

Peripheral carcinoma)

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.

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

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.

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

Other laboratory examinations some tumor markers

(CEA .CA199. CA211. NSE) Some gene examination, p53gene, ras gene.

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

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.

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

 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

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

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

Stage grouping
0 stage TisNoMo stage A T1N0M0
B stage A B stage A B T2N0M0 T1N1M0 T2N1M0, T2N0M0, T3N0M0 T3N1M0, T1N2M0, T2N2M0, T3N2M0 T4N0M0, T4N1M0, T4N2M0, T1N3M0, T2N3M0 , T3N3M0, T4N3M0

stage any T and any N, M1

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

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

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.

Surgery
More than 90 percent of small cell lung cancer has often metastasized at the time of diagnosis. So these patients usually adopt radiation therapy or chemotherapy before surgery.

Surgery
We must measure pulmonary function before surgical therapy. Forced vital capacity greater than 2 liters and a forced expiratory volume in the first second (FEV1)of greater than 50 percent of the forced vital capacity predict that a patient can tolerate the consequences of pneumonectomy.

Chemotherapy
Non-small cell lung cancer MVP:MMC 6-8mg/m2 (1), VDS 3mg/m2 NP:VP-16 (d1,d8). DDP 100mg/m2 (d1) GP Small-cell lung cancer it is highly responsive to chemotherapy. EP regimen VP-16 100mg/m2 d1~d3. DDP 100mg/m2 d1. GP

Chemotherapy
Aggressive chemotherapy produces complications and symptoms in all patients. All experience anemia,leukepenia and opportunistic infection other complications include nausea,vomiting possible cadiotoxicity, hemorrhagic cystitis and peripheral neuropathy.

Radiation therapy
It is of proven benefit in controlling bone pain,spinal cord compression, superior vena cava syndrome and bronchial obstruction.