Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and Lung Cancer Maximino G. Bello III,...
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Transcript of Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and Lung Cancer Maximino G. Bello III,...
Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and
Lung Cancer
Maximino G. Bello III, MD, FPCP, FPSMOExecutive Secretary, Cancer Institute
Take note!
• All exams are Harrison based• Rapid advances in oncology, new findings may
supersede Harrison– Take note if I stressed a particular fact or
statement
• Topics not discussed in today's lecture does NOT mean it would not be included in exams
Pleural diseases
• Pleural effusion– Pleural space from the capillaries in the parietal
pleura removed via lymphatics– Interstitial spaces from the lung via visceral pleura– Peritoneal cavity via diaphragm
• Pneumothorax– Air in the pleural space
Diagnostic approach
• Transudate: systemic factors• Exudate: local factors
• Light’s Criteria– Pleural fluid CHON /serum CHON >0.5– Pleural fluid LDH/serum LDH >0.6– Pleural fluid LDH more than 2/3 normal upper
limit for serum
Light’s Criteria misidentifies ≈25% of transudates as exudates
Light’s Criteria
Transudate• CHF• Cirrhosis• PE• Nephrotic syndrome• Peritoneal dialysis• SVC• Myxedema
Exudate• Infectious• Neoplastic • GI disease• Collagen vascular dse• P CABG• etc
Parapneumonic effusions
• Associated with bacterial infection, lung abscess or bronchiectasis
• Empyema: grossly purulent effusion– Condensed milk
• “significant effusion”– Lateral decubitus view shows 10mm layering of
fluid drainage of effusion
Drainage of effusion
• Need for a more invasive procedure (other than thoracentesis)– Loculated pleural effusion– Pleural fluid pH <7.20– Pleural fluid glucose < 3.3mmol/L– + gram stain or culture of the pleural fluid– empyema
Effusion secondary to malignancy
• Lung and breast carcinoma and lymphoma– 75% of malignant effusion
• Dyspnea is NOT proportionate to the amount of effusion– Lung metastasis
• Treatment– Drainage of the fluid sclerosing agent
treatment of the malignancy
Effusion secondary to mesothelioma
• Primary tumor of the mesothelial cells– Line the pleural cavity
• Significant asbestos exposure• Imaging:
– Effusion, thick pleura, collapse hemithorax• Treatment:
– Surgery– pretexemed
Pneumothorax
• Primary spontaneous pneumothorax– Rupture of apical bleb– It typically occurs in tall, thin boys and men
between the ages of 10 and 30 years– rarely occurs in persons over the age of 40.– Appears almost exclusively in smokers– ½ will have recurrences
• Treatment: aspiration
Pneumothorax
• Secondary spontaneous pneumothorax– COPD– More fatal lesser physiologic reserve
• Treatment– Tube thoracostomy
Pneumothorax
• Traumatic pneumothorax– Penetrating– Non penetrating injuries
• Tension pneumothorax– Medical emergency– During resuscitation
• Cyanosis, hypotension
Diaphragmatic Hernia
Most Diaphragmatic Hernia’s are detected in childhood.
Rare in adults!
Most Diaphragmatic Hernia’s are detected in childhood.
Rare in adults!
Diaphragmatic Hernia
Congenital diaphragmatic hernia • Bochdalek:
– More common– postero-lateral diaphragmatic hernia – majority of Bochdalek hernias (80-85%) occur on
the left side • Morgagni
– Less common– Anterior, right
Mediastinum
• Occupies the central portion of the thoracic cavity
• Boundaries:
1. Lateral- pleural cavity
2. Superior- thoracic inlet
3. Inferior- diaphragm
4. Anterior- sternum
5. Posterior- chest wall
De Vita, et al .Principles & Practice of Oncology 8th ed
De Vita, et al .Principles & Practice of Oncology 8th ed
anterioranterior
posteriorposterior
middlemiddle
Mediastinal tumors:
Feature Thymoma Lymphoma Germ cell tumor
Mesenchymal
Incidence - most common anterior Mediastinal neoplasm
- 20-25% of Mediastinal tumors
- equal in male and female
- ages 30 - 50.
-10-20 % of primary Mediastinal masses
- 2nd most common anterior Mediastinalmass
- Most Mediastinal lymphomas areseen in the anterosuperior mediastinum.
-15% of anterior Mediastinal tumors inadults.(24% in children)
- Rarely, they are found in the posteriormediastinum
- 6% of Mediastinal tumors.
- More than 50% are malignant
Mediastinal tumors:
Feature Thymoma Lymphoma Germ cell tumor
Mesenchymal
Radiographic findings:
•X-ray
-smooth mass in the upper half of the chest.
-Overlying the superior portion of the cardiac shadow.
-The mass projects predominantly into one of the hemithoraces.
- Lobulated with enlargement of hilar and media- stinal lymph nodes.
- well defined mass occasionally containing calcifications.
- Mediastinal widening on CXR
Mediastinal tumors:
Feature Thymoma Lymphoma Germ cell tumor
Mesenchymal
Radiographic findings:
•CT scan
- demonstrates uniform enhancement
- conglomerate of lymph nodes
- discrete enlarged LN with cystic degeneration
-lobulated, asymmetrical, homogenous tumors
- with/ without cystic components
-can determine components of tumor (fat, soft tissue)
- defines the relation of tumor to adjacent tissues.
Mediastinal tumors:
Feature Thymoma Lymphoma Germ cell tumor
Mesenchymal
Signs and symptoms
- 50% asymptomatic
- symptoms due to myasthenia in 35% of patients
- others with substernal pains, dyspnea, cough
- Invasive thymoma cause local compression /svc syndrome
-Majority of are symptomatic at diagnosis.
- Common: fever, weight loss, night sweats
- Compression symptoms: pain, dyspnea, stridor, or superior vena cava syndrome
- Associated pleural effusions are common
-malignant tumors are symptomatic in 85% of patients:-chest pain, -hemoptysis, -cough, -fever, -weight loss.
- Superior vena caval syndrome is occasionally seen
- Compressive sign and symptoms based on adjacent tissues involved.
Lung Cancer
Made Ridiculously simple!
MORTALITY: TEN LEADING (10) LEADING CAUSES Number and rate/100,000 Population Philippines
5-Year Average (2000-2004) & 2005
5 Year Average (2000-2004)
2005* Cause
Number Rate No. Rate 1. Diseases of the Heart 66,412 83.3 77,060 90.4 2. Diseases of the Vascular system 50,886 63.9 54,372 63.8 3. Malignant Neoplasm 38,578 48.4 41,697 48.9 4. Pneumonia 32,989 41.4 36,510 42.8 5. Accidents 33,455 42.0 33,327 39.1 6. Tuberculosis, all forms 27,211 34.2 26,588 31.2 7. Chronic lower respiratory diseases 18,015 22.6 20,951 24.6 8.Diabetes Mellitus 13,584 17.0 18,441 21.6 9. Certain conditions originating in the perinatal period
14,477 18.2 12,368 14.5
10. Nephritis, nephrotic syndrome and nephrosis
9.166 11.5 11,056 3.6
Area Nutritional
Deficiencies
Chronic Lower Resp. Dis.
Pneumonia Cerebro Vascular Diseases
Disorder of the Heart
Transport Accidents
Malignant Neoplasm
of Lung
Philippines 2,607 15,904 32,637 21,705 60,417 5,680 6,395 NCR 220 2,056 4,344 2,840 11,799 653 1,194 CAR 19 167 494 319 642 98 103 Region 1 151 1,309 3,056 2,029 4,345 484 530 Region 2 54 850 1,667 658 1,921 326 266 Region 3 251 2,374 2,652 3,405 7,638 528 966 Region 4 397 2,860 4,060 3,669 10,101 816 1,255 Region 5 228 1,079 2,706 1,359 4,107 366 166 Region 6 369 1,584 4,724 2,057 4,660 438 557 Region 7 264 1,061 2,932 1,416 4,643 335 447 Region 8 155 620 1,978 835 2,764 238 134 Region 9 90 415 671 535 1,404 163 112 Region 10 129 3 59 918 503 1,508 269 150 Region 11 153 587 1,356 1,181 2,727 481 307 Region 12 70 288 416 397 823 203 102 ARMM 9 46 54 48 167 108 12 CARAGA 48 246 609 450 1,141 167 90
Foreign Country
0 3 0 4 27 7 4
Change in the US Death Rates* by Cause, 1950 & 2005
* Age-adjusted to 2000 US standard population.Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised.2005 Mortality Data: US Mortality Data 2005, NCHS, Centers for Disease Control and Prevention, 2008.
20.3
180.7
48.1
586.8
193.9
46.6
183.8211.1
0
100
200
300
400
500
600
HeartDiseases
CerebrovascularDiseases
Influenza &Pneumonia
Cancer
1950
2005
Rate Per 100,000
Lung Cancer1975-1977: 13%1984-1986: 13%1996-2003: 16%
World Incidence1 World Mortality1
Lung Cancer
1.5 Mio 90%1. Lung Cancer: Kamangar et al. J Clin Oncol. 2006;24:2137-
2150.
Worldwide Incidence and Mortality for Lung Cancer
• Lung cancer is the most common cancer in the world
• Smoking is the most important risk factor
Host Susecptibility
1. Family Hx
2. Inherited cancer syndrome
3. P53 mutation
4. EGFR mutation
5. Retinoblastoma
6. SNP variation at 15q24–15q25.1
7. susceptibility and risk also increase with reduced DNA repair capacity ERCC1
Host Susecptibility
1. Family Hx
2. Inherited cancer syndrome
3. P53 mutation
4. EGFR mutation
5. Retinoblastoma
6. SNP variation at 15q24–15q25.1
7. susceptibility and risk also increase with reduced DNA repair capacity ERCC1
Clonal Evolution
Changes in certain genes occur in nonmalignant lung tissue of smokers and patients with lung cancer
Early events in the development of NSCLCA include loss of heterozygosity at chromosomal region 3p21.3 , 3p14.2, 9p21 (p16), and 17p13 (p53)
Clonal Evolution
Changes in certain genes occur in nonmalignant lung tissue of smokers and patients with lung cancer
Early events in the development of NSCLCA include loss of heterozygosity at chromosomal region 3p21.3 , 3p14.2, 9p21 (p16), and 17p13 (p53)
Lung Cancer: HistologyThe Clinical Importance
Histological types
NSCLC 80%
Non Small Cell Lung Cancer
SCLC 20 %
Small Cell Lung Cancer
10 %Large Cell Ca.
50 %Adeno-ca.
40 %Squamous-ca.
NSCLC Histological Subtype
non-squamous: 60%
squamous: 40%
Grouping bet. Squamous vs non squamous is an oncologic/clinical classification
Clinical Classification are always clinically useful
Lung Cancer
• NSCLCA• AJCC staging (I to IV)
• Less chemo sensitive• Less radio sensitive• Established role of
surgery
• Small Cell Lung Cancer• Veterans Affairs Staging
(limited vs. extensive)• More chemo sensitive• More radio sensitive• No role for surgery
The difference
• Squamous• Harder to treat• Not susceptible to TKI• Stronger smoking
association
• Males
• TX: gemcitabine
• Non squamous• More “easier to treat”• Sensitive to TKI• Lesser smoking
association: adenocarcinoma
• Females: adenocarcinoma• TX:
– TKI’s bevasizumab & pretexemed
StagingStaging
•
Surgery + chemotherapy
Or chemoRT
Surgery + adjuvant chemo
Surgery Chemoradiotherapy
ChemotherapyChemotherapy
NSCLC treatment
Stage IIIB/IVStage I Stage II Stage IIIA
Platinum = Cisplatin or Carboplatin
1st line
2nd line pemetrexed
platinum + docetaxel
platinum + vinorelbine
docetaxel
3rd line
erlotinib
platinum + paclitaxel
platinum + gemcitabine
gefitinib(Asia)
erlotinib gefitinib(Asia)
The majority
ERBITUX
NSCLC Tumor Stages: IIIB and IV
Stage IIIB Stage IV
Clinical Manifestations
• Tumors in the large airways- cough, wheezing, hemoptysis
• With atelectasis and with pleural space involvement
- pleuritic chest pain• Tumors invading the chest wall
- stabbing or burning radicular pain
Methods to Establish Tissue Diagnosis
• Sputum Cytology-sensitivity is 65% (22%- 98%) -molecular techniques (p53, A2/B1expression,k-ras)
• Percutaneous Fine-Needle Aspiration-fluoroscopic or CT-guided techniques-The positive yield exceeds 95% (even iflesions are less than 1 cm in diameter)
Methods to Establish Tissue Diagnosis
• Bronchoscopy• minimal morbidity,safe• visualization of the tracheobronchial tree to the
2nd or 3rd segmental divisions • cytologic or histologic specimens can be obtained
– -diagnostic yield of FOB with cytologic
– brushings or biopsy of visible lesionsexceeds 90%
Methods to Establish Tissue Diagnosis
• Mediastinoscopy, Mediastinotomy, and Endoscopic Ultrasound-Fine-Needle Aspiration
• most accurate technique to assess paratracheal, proximal peribronchial, and subcarinal lymph nodes in lung cancer patients
• indicated in any patient suspected of having locally advanced disease
• mediastinoscopy before surgical intervention for lung cancer has evolved during recent years
Methods to Establish Tissue Diagnosis
• Thoracentesis• identify inoperable, pleural disease (T4)• unless malignant cells are identified, a bloody pleural effusion
should be considered traumatic• diagnosis of cancer in can be established in 70% of malignant
effusions by thoracentesis
• Thoracoscopy• Video-assisted thoracoscopy is frequently used for the diagnosis,
staging, and resection of lung cancer• valuable for evaluation and palliation of suspected pleural disease,
particularly when thoracentesis has been nondiagnostic
Methods to Establish Tissue Diagnosis
• Thoracotomy• diagnosis often can be obtained via multiple FNAs with
immediate cytologic analysis, or incisional (or preferably excisional) biopsy with frozen section
• intraoperative biopsies of hilar and mediastinal lymph nodes
• resection of the primary lesion and complete mediastinal lymph node dissection
Taxotere 75 mg/m2 over 1 hr day 1Cisplatin 75 mg/m2 day 1q 3 wks
Vinorelbine 25 mg/m2 /wkCisplatin 100 mg/m2 day 1q 4 wks
Paclitaxel 225 mg/m2 over 3 hrs day 1Carboplatin AUC 6 day 1q 3 wks
Gemcitabine 1,000 mg/m2 days 1, 8, 15Cisplatin 100 mg/m2 day 1 q 4 wks
ECOG 1594 (n = 1,207)
SWOG 9509 (n = 408)
Paclitaxel 225 mg/m2 over 3 hrs day 1Carboplatin AUC 6 day 1q 3 wks
Paclitaxel 135 mg/m2 over 24 hrs day 1Cisplatin 75 mg/m2 day 2 q 3 wks
Comparison of First-Line Doublet Trials: Treatments
TAX 326 (n = 1,218)
Taxotere 75 mg/m2 over 1 hr day 1Cisplatin 75 mg/m2 day 1q 3 wks
Vinorelbine 25 mg/m2 days 1, 8, 15, 22Cisplatin 100 mg/m2 day 1q 4 wks
Taxotere 75 mg/m2 over 1 hr day 1Carboplatin AUC 6 day 1q 3 wks
Vinorelbine 25 mg/m2 /wk 12 wks, then every other wkCisplatin 100 mg/m2 day 1q 4 wks
ILCP (n = 612)
Paclitaxel 225 mg/m2 over 3 hrs day 1Carboplatin AUC 6 day 1q 3 wks
Gemcitabine 1,250 mg/m2 days 1, 8Cisplatin 75 mg/m2 day 2q 3 wks
Comparison of First-Line Doublet Trials: Treatments
Comparison of First-Line Doublet Trials:Median Survival Time
0
4
8
12
Tax 326 ILCP ECOG 1594 SWOG 9509
Med
ian
Su
rviv
al
Med
ian
Su
rviv
al
(mo
nth
s)(m
on
ths)
Vin
+ C
is
Pac
+ C
arb
o
Pac
+ C
arb
o
Vin
+ C
is
Pac
+ C
is
Gem
+ C
is
Gem
+ C
is
Tax
+ C
is
Pac
+ C
arb
o
10.1
11.3
9.99.9 9.59.5 10.010.0 9.89.8
7.8 8.18.1 8.18.17.47.4
8.68.18.1
9.49.4
P = 0.044V
in +
Cis
Tax
+ C
is
Tax
+
Car
bo
Vin
+ C
is
1. Pirker et al, JCO 2008; 18S Abstract 3; 2. Scagliotti et al. JTO 2007; 2, 8 (Suppl 4), 308 (Abstr. PRS-03); 3. Fosella et al. JCO 2003; 21: 3016-24; 4. Schiller et al., NEJM 2002; 346: 92–98; 5. Bonomi et al. JCO 2000; 18: 623-31; 6. Kelly et al. JCO 2001; 19:3210–3218; 7. Scagliotti et al. JCO 2002; 21: 4285-4291; 8. Alberola et al. JCO 2003; 9. Wozniak et al. JCO 1998; 16: 2459-65; 10. Cardenal et al. JCO 1999; 17: 12-18; 11. Roszkowiski et al. Lung Cancer 2000; 27: 145-157; 12. Cullen et al. JCO 1999; 17: 3188-94.
Achievements in NSCLCfor patients across all histologies
30 years: step by step increase in median OS ranged from 1-2 months
0 1 2 3 4 5 6 7 8 9 10 11 12
BSC
Cisplatin Monotherapy
Platinum/Etoposide
Platinum/Vinorelbine
Platinum/Gemcitabine
Platinum/Paclitaxel
Platinum/Docetaxel
Cisplatin/Pemetrexed
Chemotherapy + Erbitux
Median OS
Months
1950‘s
1970‘s
1990‘s
1998-
1995
2007
2008
3rd
Ge
ne
rati
on
C
he
mo
the
rap
y
11,12
5, 10
9, 8
9, 3, 6, 7
2, 8, 4, 7
4, 5, 6, 7
3, 4
2
1
BSC2–5 months
Single-agent platinum6–8 months
Platinum-based doublets8–10 months
Median survival (months)
Schiller, et al. NEJM 2002Sandler, et al. NEJM 2006
0 2 4 6 8 10 1214
2000s
1990s
1980s
1970s
Platinum-based doublet + Avastin12.3 months
Longest overall survival achieved in non-squamous metastatic NSCLC patients
with Avastin
BSC = best supportive care
General Conclution about NSCLCA Chemotherapy
• “platinum based doublet”– Platinum: cisplatin or carboplatin
• All are equally effective• None is superior over the other• Toxicity is different• Addition of a biologic agent improves OS
– Cetuximab– bevasizumab
Thank you!
Questions??