Download - 6 lungcancer
Bronchogenic Carcinoma ( Lung Cancer )
Guo Yubiao, M.D & Ph.D
Pulmonary & Critical Care Medicine The first Affiliated Hospital of Sun-Yat Set University
Outline Epidemiology/Classification
Clinical manifestations
Symptoms
Signs
Diagnostic workup & Differential Diagnosis
Diagnosis
Differential Diagnosis
Treatment & Prevention
Summary
Bronchogenic
Carcinoma
( Lung Cancer )— tumor cell o
riginates from the mucosa or gland
of bronchus.
Definition
Epidemiology
Global Incidence of Lung Cancer(2001)
Global Mortality OF Lung Cancer(2001)
Females Males80
60
40
20
01930 1940 1950 1960 1970 1980 1990 1997
80
60
40
20
01930 1940 1950 1960 1970 1980 1990 1997
UterusBreastPancreasOvaryStomachLung and bronchusColon and rectum
PancreasLiverProstateStomachLung and bronchus Colon and rectumLeukemia
Rat
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Year Year
美国癌症死亡率 :无论男性还是女性,肺癌均为头号致死肿瘤
Lung cancer - US incidence and mortality rates (1973-1996)
10
50
100
Incidence - malesMortality - malesIncidence - femalesMortality - females
Rate per 100,000 people(log scale)
1974 76 78 80 82 84 86 88 90 92 94 96
Year of diagnosis/death
Ries et al 1999
Epidemiological Characteristic of Lung Cancer
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5
10
15
20
25
30
35
40
45
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72--7490--92
Anatomy and Pathology
Thyroid cartilage
Cricothyroid ligament
Cricoid cartilage
Connective tissuesheath (cut away)
Intercartilaginousligaments
Mucosa showinglongitudual folds formedby dense collectionsof elastic fibres
Tracheal cartilages
Toupperlobe
Eparterialbronchus
Tomiddlelobe
Tolowerlobe
R. mainbronchus
L. mainbronchus
Intrapulmonary Extrapulmonary Intrapulmonary
Tolowerlobe
Tolingula
Toupperlobe
Trachealis muscle
Oesophageal muscle
Epithelium
Lymph vesselsElastic fibres
Gland
Small arteries
Nerve
Posterior wall
Cross sectionthrough trachea
Anterior wall
Epithelium
Nerve
Lymph vessels
Small artery
Gland
Elastic fibres
Cartilage
Connective tissue sheath
Structure of trachea and major bronchi
© Novartis
Classifications of Lung Cancer
Classification by Anatomic Site
– Central Lung Cancer
– Peripheral Lung Cancer
Classification by Histopathology
– Small Cell Lung Cancer (SCLC ,15-20%)
– Non-Small Cell Lung Cancer (NSCLC ,80-85%)
Squamous epithelial cell cancer , Adenocarcinoma , Large Cell Cancer
adrnosquamous lung cancer etc.
Histological Types of Lung CancerRelative Incidence
Symptoms and Signs
Clinical Manifestations Development of Lung Cancer Symptoms
– Formation of Lung Cancer Asymptomatic
– Bronchia involved Cough
– Mucosa capillary involved Hemoptysis
– Pleura and chest wall involved Dyspnea, chest pain
– Obstruction of bronchus Short breath, fever
– Pleura spreading Pleural effusions
Non-special symptoms: Anorexia, weight loss
Clinical Manifestations
Symptoms Caused by Tumor Spreading and Metastasis
– Superior Vena Cava Obstruction Syndrome
– Horner’s Syndrome
– Pancoast’s Syndrome
Extra-pulmonary Manifestations
– Hypertrophic Pulmonary Osteoarthropathy
– Carcinoid Syndrome
– Gynaecomastia
Major signs and symptoms of lung cancer
Baseline major presenting symptoms
0
20
40
60
80
100
HemoptysisLoss of appetite
PainCoughDyspnea
Patients(%)
Hollen et al 1999
Para-neoplastic syndromes Not fully understood patterns of organ dysfunction
related to immune-mediated or secretary effects of neoplasm.
Occur in 10%-20% of lung cancer patients. 15% of patients with small cell carcinoma will dev
elop SIADH; 10% of patients with squamous cell carcinoma will
develop hypercalcemia. Digital clubbing is seen in up to 20% of patients at
diagnosis. Other common para-neoplastic syndromes include:
increased ACTH production, anemia, hypercoagulability, peripheral neuropathy
Achropachy (clubbed finger )
Laboratory Findings
Cytology (tissue samples, Sputum, pleural effusions)
Thoracoscopy
Fine needle aspiration of palpable lymph nodes
Fibrotic bronchoscopy - fluorescence bronchoscopy - endoscopic ultrasound - eBUS-TBNA
Mediastinoscopy, video-assisled thoracoscopic surgery (VATS), and thoracotomy
Serum tumor markers are neither sensitive nor specific enough to aid in diagnosis
IMAGING X-ray
NSCLC CT scans
Transthoracic needle aspiration (TTNA) of a non-small cell Pancoast tumor
荧光支气管镜(Auto fluorescence bronchoscope, AFB)
隆突前可见一淋巴结Enlarged Lymph node of Inferior Tracheal Protuberance (Spiral CT Scan )
支气管镜下粘膜表面光滑Smooth mucosa appearanceunder bronchoscope
(BF-UC160F-OL8; Olympus Medical Systems, Tokyo,
Japan)
(BF-UC160F-OL8; Olympus Medical Systems, Tokyo,
Japan)
Linear Real-time Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Scope
支气管内超声可见一异常回声区
超声引导下穿刺针刺入粘膜
超声实时引导下穿刺针刺入病灶
Bronchoscopic View of a Transbronchial Needle Aspiration of a Subcarinal Node
Herth FJ. Eur Respir J 2006
涂片可见癌细胞cancer cells found in the TBNA tissue samples
Mediastinoscopy
Positive Electron Tomography (P
ET) -CT———— 或许是肺癌,甚至是全身实体肿瘤最好的早期诊断方或许是肺癌,甚至是全身实体肿瘤最好的早期诊断方
法,但要用于筛查,还有待经济的发展。法,但要用于筛查,还有待经济的发展。
Diagnosis of Lung Cancer
Principles– Pay attention to the respiratory symptoms ineffectiv
e to treatment
– Pay attention to the extrapulmonary manifestations
– From routine to complicated
From non-invasive to invasive
– Highlight the pathological diagnosis
Cytology , histology
NSCLC diagnosis
Physical examination Detect signs
Visualize and sample mediasturial lymph nodes
Detect position, size, number of tumors
Detect chest wall invasion mediastinal lymphodenopathy distant metastases
Lymph node staging
Detect changes in hormone production, and hematological manifestations of lung cancer
Precise location of tumor obtain biopsy
Chest X-ray
CT scan
PET scan
Laboratory analysis
Bronchoscopy
Mediastinoscopy
FNA Cytology
NCCN Guidelines 2000
Staging and Prognostication
Mountain 1997
NSCLC stages - an overview
Disease
Early
Localized
Advanced
Stage
0IAIB
IIAIIB
IIIA
IIIB
IV
TNM
TIS N0 M0 (carcinoma in situ)T1 N0 M0T2 N0 M0
T1 N1 M0T2 N1 M0T3 N0 M0T3 N1 M0
T1-3 N2 M0
T4, Any N, M0Any T, N3, M0
Any T, Any N, M1
NSCLC stages
Stage 0
Stage IA
Stage IIB
Stage IIIB
Stage IV
Lymph nodes
Main bronchus
Contralateral lymph node
Metastasis to distant
organs
Invasion of chest wall
NSCLC: clinical stage as a prognostic factor
1 year
3 years
5 years
0
10
20
30
40
50
60
70
80
90
100
IA IB IIA
T2N1M0
IVIIB IIIA IIIBClinical stage at presentation
Survival (%)
Mountain 1997
T3N0M0T3N1M0
T1-3N2M0T4
N3
Probability of survival according to clinical stage
Treatment
Strategy of Lung Cancer Treatment
According to the pathological type
– Small Cell Lung Cancer (SCLC)
– Non-Small Cell Lung Cancer (NSCLC)
According to the TNM Clinical Stage
Choose the optimal therapeutic protocols
Follow-up regularly
NSCLC: an overview of treatment options
Localized tumor
surgery
Regional tumor
chemotherapy, radiotherapy (surgery)
Advanced tumor
chemotherapy
PDQ Guidelines
Treatment of NSCLC stage 0
Lobectomy, segmentectomy, or wedge resection
Curative radiotherapy if surgery is contra-indicated
Endoscopic photodynamic therapy (under evaluation in selected patients)
PDQ Guidelines
Treatment of NSCLC stage I and stage II
Lobectomy or pneumonectomy
Curative radiotherapy if surgery is contra-indicated
Adjuvant chemotherapy
Adjuvant radiotherapy
Neoadjuvant chemotherapy
PDQ Guidelines
NSCLC stage I: surgeryLocoregionalrecurrencerate(per person-year)
Locoregionalrecurrencerate(% of patients)
0
10
20
30
40
50
Segmen-tectomy(n=68)
Lobectomy(n=105)
00.0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
Limitedresection
(n=122)
Lobectomy(n=125)
p=0.008
Warren and Faber 1994Ginsberg and Rubinstein1995
p<0.05
Treatment of NSCLC stage III
Surgery alone (selected patients in stage IIIA only)
Postoperative radiotherapy
Chemotherapy + radiotherapy
Radiotherapy alone
Chemotherapy alone (stage IIIB with malignant pleural effusions)
PDQ Guidelines
NSCLC stage III: surgery combination regimens
Study
Pass et al 1992
Roth et al 1994
Rosell et al 1994
Regimens
Surgery plus chemotherapy (n=13)
Surgery plus radiotherapy (n=14)
Surgery plus chemotherapy (n=28)
Surgery alone (n=32)
Surgery plus radiotherapy plus chemotherapy (n=30)
Surgery plus radiotherapy (n=30)
Median survival (months)
28.7
15.6
64
11
26
8
p value
0.095
<0.008
<0.001
NSCLC stage III: combination radiotherapy and chemotherapy
NSCLC Collaborative Group 1995
0.0 0.5 1.0 1.5 2.0Radiotherapy plus
chemotherapy betterRadiotherapy (control)
better
Buenos AiresBrusselsFLCSG 2EssenSLCSGCEBI 138WSLCRG/FIPerugiaCALGB 8433EORTC 08842SWOG 8300aSWOG 8300b
Subtotal
p=0.005
Treatment of NSCLC stage IV
Chemotherapy (platinum-based), modest survival benefits
New chemotherapy agents
External beam radiotherapy (palliative relief)
Endobronchial laser or endobrochial therapy for obstruction
PDQ Guidelines
NSCLC recurrence after chemotherapy
Surgery (selected patients with isolated brain metastases)
Palliative radiotherapy
Palliative chemotherapy
Endobronchial laser therapy or interstitial radiotherapy
PDQ Guidelines
Future Developments
NSCLC: future developments
Current treatment remains unsatisfactory
Prevention
Earlier diagnosis
Improved treatment
PDQ Guidelines
Prevention
Education
– avoidance of environmental carcinogens such as tobacco smoke
Chemoprevention?
– vitamin A
– isotretinoin
Earlier diagnosis
Obstructive lung disease
Genetic risk factors
Sputum cytology
Molecular tumor markers
Computed tomography
Positron emission tomography (PET)
Edell 1997
Treatment
NSCLC
Novel biological
targets
Immunology:- interleukins- interferons- vaccines
Newchemotherapy
drugs
Gene therapy:- interleukins- K-ras
Novel biological approaches- molecular target therapy
Epidermal growth factor (EGF) tyrosine kinase inhibitors (TKI)
Anti-vascular therapy
Metalloproteinase inhibitors
Immunotherapy and gene therapy
Immunomodulators
– interferons, interleukins
Vaccination
– passive immunisation
– active immunisation
Gene therapy?
– oncogenes eg K-ras
– immunomodulators eg interleukins
Thank You!