Download Disorders of the pleura, mediastinum, diaphragm, chest wall and

Disorders of the Pleura, Mediastinum,
Diaphragm, Chest Wall and
Lung Cancer
Maximino G. Bello III, MD, FPCP, FPSMO
Executive 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!
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:
anterior
1. Lateral- pleural cavity
posterior
2. Superior- thoracic inlet
middle
3. Inferior- diaphragm
4. Anterior- sternum
5. Posterior- chest wall
De Vita, et al .Principles & Practice of Oncology 8th ed
Mediastinal tumors:
Feature
Incidence
Thymoma
- most common
anterior Mediastinal
neoplasm
- 20-25% of
Mediastinal tumors
- equal in male and
female
- ages 30 - 50.
Lymphoma
-10-20 % of
primary Mediastinal
masses
- 2nd most common
anterior Mediastinal
mass
- Most Mediastinal
lymphomas are
seen in the
anterosuperior
mediastinum.
Germ cell
tumor
-15% of anterior
Mediastinal tumors in
adults.
(24% in children)
- Rarely, they are
found in the posterior
mediastinum
Mesenchymal
- 6% of Mediastinal
tumors.
- More than 50%
are malignant
Mediastinal tumors:
Feature
Thymoma
Lymphoma
Germ cell
tumor
Radiographic
findings:
-smooth mass in the
upper half of the chest.
•X-ray
-Overlying the superior
portion of the cardiac
shadow.
- Lobulated with
enlargement of
hilar and mediastinal lymph nodes.
- well defined mass
occasionally
containing
calcifications.
-The mass projects
predominantly into one
of the hemithoraces.
Mesenchymal
- Mediastinal
widening on CXR
Mediastinal tumors:
Feature
Radiographic
findings:
•CT scan
Thymoma
- demonstrates
uniform
enhancement
Lymphoma
- conglomerate of
lymph nodes
- discrete enlarged
LN with cystic
degeneration
Germ cell
tumor
Mesenchymal
-lobulated,
asymmetrical,
homogenous
tumors
-can determine
components of
tumor (fat, soft
tissue)
- with/ without cystic
components
- defines the
relation of tumor to
adjacent tissues.
Mediastinal tumors:
Feature
Thymoma
Signs and - 50% asymptomatic
symptoms
- symptoms due to
myasthenia in 35% of
patients
- others with substernal
pains, dyspnea, cough
- Invasive thymoma
cause local
compression /svc
syndrome
Lymphoma
-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
Germ cell
tumor
-malignant tumors
are symptomatic in
85% of patients:
-chest pain,
-hemoptysis,
-cough,
-fever,
-weight loss.
- Superior vena
caval syndrome is
occasionally seen
Mesenchymal
- 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
Cause
(2000-2004)
Number Rate
1. Diseases of the Heart
66,412
83.3
2. Diseases of the Vascular system
50,886
63.9
3. Malignant Neoplasm
38,578
48.4
4. Pneumonia
32,989
41.4
5. Accidents
33,455
42.0
6. Tuberculosis, all forms
27,211
34.2
7. Chronic lower respiratory diseases
18,015
22.6
8.Diabetes Mellitus
13,584
17.0
9. Certain conditions originating in the
14,477
18.2
perinatal period
10. Nephritis, nephrotic syndrome and
9.166
11.5
nephrosis
2005*
No.
Rate
77,060
90.4
54,372
63.8
41,697
48.9
36,510
42.8
33,327
39.1
26,588
31.2
20,951
24.6
18,441
21.6
12,368
14.5
11,056
3.6
Area
Philippines
NCR
CAR
Region 1
Region 2
Region 3
Region 4
Region 5
Region 6
Region 7
Region 8
Region 9
Region 10
Region 11
Region 12
ARMM
CARAGA
Foreign
Country
Chronic
Cerebro Disorder
Malignant
Nutritional Lower
Transport
Pneumonia Vascular of the
Neoplasm
Deficiencies Resp.
Accidents
Diseases Heart
of Lung
Dis.
2,607
220
19
151
54
251
397
228
369
264
155
90
129
153
70
9
48
15,904
2,056
167
1,309
850
2,374
2,860
1,079
1,584
1,061
620
415
3 59
587
288
46
246
32,637
4,344
494
3,056
1,667
2,652
4,060
2,706
4,724
2,932
1,978
671
918
1,356
416
54
609
21,705
2,840
319
2,029
658
3,405
3,669
1,359
2,057
1,416
835
535
503
1,181
397
48
450
60,417
11,799
642
4,345
1,921
7,638
10,101
4,107
4,660
4,643
2,764
1,404
1,508
2,727
823
167
1,141
5,680
653
98
484
326
528
816
366
438
335
238
163
269
481
203
108
167
6,395
1,194
103
530
266
966
1,255
166
557
447
134
112
150
307
102
12
90
0
3
0
4
27
7
4
Change in the US Death Rates* by Cause,
1950 & 2005
Rate Per 100,000
600
586.8
1950
500
2005
400
300
211.1
193.9
180.7
200
183.8
100
46.6
48.1
20.3
0
Heart
Diseases
Cerebrovascular
Diseases
Influenza &
Pneumonia
Cancer
* 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.
Lung Cancer
1975-1977: 13%
1984-1986: 13%
1996-2003: 16%
Worldwide Incidence and Mortality
for Lung Cancer
• Lung cancer is the most common cancer in the world
• Smoking is the most important risk factor
World Incidence1
Lung
Cancer
1.5 Mio
World
Mortality1
90%
1. Lung Cancer: Kamangar et al. J Clin Oncol. 2006;24:2137-2150.
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)
Lung Cancer: Histology
The Clinical Importance
Histological types
NSCLC
NSCLC Histological Subtype
80%
Non Small Cell Lung Cancer
SCLC
Squamous-ca.
40 %
Adeno-ca.
50 %
Large Cell Ca.
10 %
squamous: 40%
non-squamous: 60%
20 %
Small Cell Lung Cancer
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
Staging
•
NSCLC treatment
Stage I
Surgery
Stage II
Surgery +
adjuvant
chemo
Stage IIIA
Surgery +
chemotherapy
Or chemoRT
platinum +
gemcitabine
1st line
platinum +
vinorelbine
2nd line
docetaxel
pemetrexed
3rd line
erlotinib
gefitinib
(Asia)
Stage IIIB/IV
The majority
Chemoradio
Chemotherapy
Chemotherapy
therapy
platinum +
paclitaxel
erlotinib
platinum +
docetaxel
gefitinib
(Asia)
Platinum = Cisplatin or Carboplatin
NSCLC Tumor Stages: IIIB and IV
Stage IIIB
Stage IV
ERBITUX
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/B1
expression,k-ras)
• Percutaneous Fine-Needle Aspiration
-fluoroscopic or CT-guided techniques
-The positive yield exceeds 95% (even if
lesions 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 lesions
exceeds 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
Comparison of First-Line Doublet Trials:
Treatments
ECOG 1594 (n = 1,207)
Paclitaxel
Cisplatin
135 mg/m2 over 24 hrs day 1
75 mg/m2 day 2 q 3 wks
Paclitaxel
Carboplatin
225 mg/m2 over 3 hrs day 1
AUC 6 day 1q 3 wks
Gemcitabine
Cisplatin
1,000 mg/m2 days 1, 8, 15
100 mg/m2 day 1 q 4 wks
Taxotere
Cisplatin
75 mg/m2 over 1 hr day 1
75 mg/m2 day 1q 3 wks
SWOG 9509 (n = 408)
Vinorelbine
Cisplatin
25 mg/m2 /wk
100 mg/m2 day 1q 4 wks
Paclitaxel
Carboplatin
225 mg/m2 over 3 hrs day 1
AUC 6 day 1q 3 wks
Comparison of First-Line Doublet Trials:
Treatments
TAX 326 (n = 1,218)
Vinorelbine
Cisplatin
25 mg/m2 days 1, 8, 15, 22
100 mg/m2 day 1q 4 wks
Taxotere
Cisplatin
75 mg/m2 over 1 hr day 1
75 mg/m2 day 1q 3 wks
Taxotere
Carboplatin
75 mg/m2 over 1 hr day 1
AUC 6 day 1q 3 wks
ILCP (n = 612)
Vinorelbine
Cisplatin
25 mg/m2 /wk 12 wks, then every other wk
100 mg/m2 day 1q 4 wks
Paclitaxel
Carboplatin
225 mg/m2 over 3 hrs day 1
AUC 6 day 1q 3 wks
Gemcitabine
Cisplatin
1,250 mg/m2 days 1, 8
75 mg/m2 day 2q 3 wks
Comparison of First-Line Doublet Trials:
Median Survival Time
P = 0.044
11.3
9.5
10.0 9.8
Tax 326
ILCP
Gem + Cis
Pac + Carbo
Pac + Cis
Gem + Cis
Pac + Carbo
Vin + Cis
Tax +
Carbo
0
Vin + Cis
4
Tax + Cis
8
8.6
8.1
7.4
ECOG 1594
Vin + Cis
9.4
Pac + Carbo
9.9
7.8 8.1 8.1
Vin + Cis
Median Survival
(months)
10.1
Tax + Cis
12
SWOG 9509
Achievements in NSCLC
for patients across all histologies
Median OS
1
2
3rd Generation
Chemotherapy
2008
Chemotherapy + Erbitux
2007
Cisplatin/Pemetrexed
3, 4
Platinum/Docetaxel
4, 5, 6, 7
1998
1995
Platinum/Paclitaxel
2, 8, 4, 7
Platinum/Gemcitabine
9, 3, 6, 7
Platinum/Vinorelbine
5, 10
Platinum/Etoposide
1990‘s
Cisplatin Monotherapy
1970‘s
9, 8
11,12
1950‘s
BSC
0
1
2
3
4
5
6
7
8
9
10
11
12
Months
30 years: step by step increase in median OS ranged from 1-2 months
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: 245965; 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.
Longest overall survival achieved in nonsquamous metastatic NSCLC patients
with Avastin
Platinum-based doublet + Avastin
12.3 months
2000s
Platinum-based doublets
8–10 months
1990s
Single-agent platinum
6–8 months
1980s
BSC
2–5 months
1970s
0
2
BSC = best supportive care
4
6
8
Median survival (months)
10
12
14
Schiller, et al. NEJM 2002
Sandler, et al. NEJM 2006
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??