Pulmonologi, pleural effusion

1. dr. Yessi Apriance
Pembimbing : Prof. dr. Zulkarnain Arsyad,
SpPD-KP
Journal reading
Sub bagian Pulmonologi
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2. Introduction
 Malignant pleural effusion
(MPE) is a common
complication of advanced
tumor
 The most common type of
lung cancer (about 24%-
42%), followed breast
cancer dan lymphoma
 About 10% of MPE patients
could not find the primary
lesion
 Patient MPE falls receive
timely treatment  average
survival period 4 months, if
poor general conditions < 30
days
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3. Introduction
The Differential diagnosis of benign and
malignant pleural effusion is still a big
challenge for clinical medical workers
Closed pleural biopsy and
thoracocentesis have routine operations
of pleural effusion
Detection of cancerous cells in the pleural effusion
GOLD STANDARD  only pleural invanded or
metastasized or the malignant tumor tissue falls of
directly into the pleural effusion (single test pleural fluid
sensitifity 60%)
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4. Cont’….
Carcinomaembryonic
antigen (CEA) as
broad-spectrum tumor
marker tends to
accumulate in the
pleural cavity when the
pleura is invanded by
malignant tumors
Recent years  Non
invasive DD of benign
and malignant pleural
effusion has made
progress
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5. Method
Search Strategy
 The Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA)
◦ Three English databases, PubMed, Embase, and Web of
Science, and two Chinese databases, CNKI, and China
Wanfang Database, on the value of CEA in the diagnosis
of lung cancer-related malignant pleural effusion in the
Chinese population.
◦ The last search time was up to 5 Nov 2020
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6. Inclusion and exclusion criteria
 Inclusion
◦ Diagnostic experiments on the
diagnostic accuracy of CEA on lung
cancer-related malignant pleural
effusion published
◦ The sensitivity, specificity, AUC and
other data of CEA derived from pleural
effusion could be calculated from
literature
◦ The sample was CEA derived from
pleural effusion
◦ Patients were treated without surgery,
radiotherapy, and chemoteraphy
◦ The number of cases in each group
was greather than 20
◦ Samples from China
 Exclusion
◦ Reviews, case reports,
systematic reviews, confrence
abstracts, letters, animal, or
laboratory studies
◦ Duplicate samples
◦ Diagnostic sensitivity and
specificity data could not be
extracted
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7. Data Extraction
 Include first author,
publication year, case group ,
number of control cases,
detection method, cutt of
value, true positive (TP),
false positive (FP), false
negative (FN), and true
negative (TN)
 The Quality Assessment
of Diagnostic Accuracy
Studies-2 (QUADAS-2)
tool
Literature quality
evaluation
 Stata 15.0 statistical software
 A bivariate mixed – effects
model combine sensitivity,
specificity, positive likehood
ratio (PLR), negative likehood
ration (NLR) and diagnosis
odds ratio (DOR
Statistical Analysis
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8. Statistical analyses
 The AUC values range from 0,5 to 1,0 with a value
closed to 0,5 indicating poor diagnostic performance
and a value close to 1,0 indicating good diagnostic
performance
 If heterogeneity large (I2 ≥ 50%) meta-regression
and subgroup analyis
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9. Results
• 903 related literatur  125
Embase, 310 PubMed, 277
web of science, 114 CNKI, 77
Wanfang Data
• 15 studies included  7 were
in Chinese, 8 in English
• Total of 2380 samples  1340
case MPE group, 1040 cases
benign pleural effusion
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10. The Basic Characteristics of included
studies
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11. The overall quality of the included
studies
 The 15 included studies all reached
mid-to-high level  biases in the
gold standard and case flow and
progress.
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12. Heterogeneity detection and CEA diagnostic
accuracy evaluation
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13. Continue..
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14. AUC
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15. Meta-regression and
Subgroup analysis
 The combined
sensitivity of
◦ Subgroup published ater
2013 > (0,81 vs 0,76)
◦ Subgroup published in
English > Chines group
(0,81 vs 0,78)
◦ Subgroup < 110 had
higher than with
corresponding group (0,82
vs 0,79)
◦ Samples group ECLIA >
(0,81 vs 0,79)
◦ CEA cutoff value < 6ng/mL
higher than (0,81 vs 0,76)
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16. Publication Bias
 No significant
publication bias was
found (P > 0,05)
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17. Discussion
1. Exfoliative cytology : tumor
cells with significant
hetermorphisme found of the
pleural effusion samples 
gold standard
• Advantages : being safe, effective,
simple to operate, less traumatic
• Specificity diagnosis of MPE 90%,
sensitivity low (30%-60%
2. Pleural biopsy : it could be
performed on patients who
cannot be diagnosed by repeated
pleural effusion exfoliation
cytology or have pleural
thickening and pleural nodules.
(Sensitivity improved to 87%)
 Has risks : pleural hemorrhage,
pneumotorax and needle tract
cancer cell implantation
Clinical diagnosis methods for
benign and malignant pleural
efusion :
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18. Cont’..
3. Thoracoscopy or thoracotomy for
lung biopsy
• Thoracoscopy : determine the
cause MPE and multiple biopsies
under direct vision could improve
(sensitivity of diagnosis 91%-
95%), but expensive (not routine
investigation)
• Thoracotomy : similar in
diagnostic efficiency to
thoracoscopy, not clinically
preferred, for it increased
complication rate and prolonged
the hospitalization
4. CEA was first discovered by Gold
which is secreted by a variety of
malignant tumors.
 Due to the differences between
malignant pleural effusion caused
by multiple tumors
 No unified reference range of CEA
for pleural effusion
 CEA is a representative tumor
marker for adenocarcinoma is
elevated in lung adenoca
(sensitivity 0,80 and specificity
0,92)
Clinical diagnosis methods for
benign and malignant pleural
efusion :
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19. Cont’…
Ressult
Clinical
diagnosis
methods
for benign
and MPE
The combined PLR is 10.46, suggesting that the
probability of a clear positive is 10.46 times that of a
false positive
The combined NLR is 0.22, indicating that the
probability of false negative is 0.22 times that of clear
negative, which reflects the high diagnostic value
The DOR value in this study is 47.26, suggesting that
CEA is generally accurate in diagnosing lung
cancerrelated malignant pleural effusion
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20.  The AUC is an indicator evaluating efficacy of
diagnostic
◦ AUC ≥0,97 : excellent accuracy
◦ 0,93 ≤ AUC < 0,96 : very good
◦ 0,75 ≤ AUC ≤ 0,92 : good
◦ AUC< 0,75 : insufficient accuracy
 The AUC in this study is 0.93 (very good)
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21. LIMITATION
 Heterogeneity exists among studies when the combined effect
size is calculated
 The MPE included in this study are all related to lung cancer,
but the sample composition is different (squamous cell
carcinom, adenoca, small cell carcinoma, and non small cell
carcinoma lung cancer (sensitivity of CEA to lung cancer is
67%, adenoca has the highest 86,2%, followed SCC, NSCLC,
small cell ca.
 The studies included in this meta-analysis do not include all
molecular markers  Combination of multiple molecular
markers has a higher diagnostic value
 Foccuses on the Chines population
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22. Conclusion
 CEA has an excellent diagnostic value in the diagnosis
of lung cancer-related malignant pleural effusion in the
Chinese population, but a large sample size and
prospective study are needed to verify the results.
 Every patient with unexplained pleural effusion should
undergo thoracentesis and measure the level of tumor
markers
 Patients with negative cytology and positive tumor
markers, further invasive tests should be performed,
and treat-ment decisions should be made based on the
results of a pleural biopsy.
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23. THANK YOU
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