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Diagnosis and Management of Pleural Effusions: A Practical Approach

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Title: Diagnosis and Management of Pleural Effusions: A Practical Approach


1
(No Transcript)
2
Pleural Diseases
  • Dr. Mohammad Abdel Sabour
  • Prof. Pulmonary Medicine
  • Ein Shams University

3
Symptomatology
  • Chest Pain
  • Dyspnea, Tachypnea
  • Dry cough
  • Systemic manifestations
  • Underlying disease
  • Asymptomatic

4
  • Pleurisy
  • Pleural effusion
  • Pneumothorax
  • Tumors

5
  • Pleurisy should alert you to exclude underlying
    pulmonary disease
  • Most common cause of recurrent pleurisy on the
    same side
  • Pleuritic chest pain, Nerve supply of the pleura
  • Painless pleurisy

6
Pleural effusion is defined as an abnormal amount
of pleural fluid accumulation in the pleural
space and is the result of an imbalance between
excessive pleural fluid formation and pleural
fluid absorption.
7
The first step in the evaluation of a patient
with a pleural effusion is to perform a thorough
history and a full physical exam.
8
Symptoms
  • Symptoms associated with pleural effusions are
    neither sensitive nor specific for its diagnosis

9
  • Variable degrees of shortness of breath.
  • Pleuritic chest pain.
  • Other forms of chest pain
  • Fever and cough.

10
  • Constitutional symptoms such as weight loss,
    night,sweats, anorexia and malaise may occur in
    association with empyema, malignancy or
    tuberculous pleurisy

11
Physical findings
  • Asymmetric chest expansion
  • Tracheal shift
  • Absence of tactile fremitus
  • Dullness to percussion
  • Decreased breath sounds
  • Egophonism
  • Pleural rub

12
Important clues to look for
  • Lower extremity edema and jugular venous
    distension suggestive of congestive heart failure
  • Ascites suggestive of hepatic hydrothorax

13
Important clues to look for
  • Lymphadenopathy and organomegaly suggestive of
    neoplastic disease
  • Clubbing of fingers

14
Important clues to look for
  • Arthropathy and cutaneous findings suggestive of
    rheumatoid arthritis or other autoimmune process

15
Plain Chest X-ray
  • The initial approach must involve the use of
    imaging to confirm and evaluate the size and
    characteristics of the pleural space
  • 75 ml posterior C/P sulcus
  • 175 ml anterior C/P sulcus
  • 1000 ml 4th rib anteriorly

16
Ultrasonography
  • Superior in clarifying the solid or fluid nature
    of a pleural opacity
  • can detect smaller effusions compared to
    conventional radiology and physical exam.
  • 5 ml

17
Ultrasonography
  • Despite all its advantages, not all the patients
    should be evaluated with an ultrasound,
    particularly if this test would delay performance
    of further diagnostic or therapeutic maneuvers
  • ICU

18
Computed Tomography
  • detects very small pleural effusions
  • provides the physician with a thorough evaluation
    of the pleura (thickness, irregularity, masses,
    etc.)
  • detects underlying parenchymal pathology
    frequently missed on the chest radiograph.

19
Thoracocentesis
  • A diagnostic thoracentesis should always be
    performed in patients with pleural effusion of
    unknown origin.

20
Thoracocentesis
  • Unless there is evidence that the effusion is
    caused only by congestive heart failure, the
    procedure is indicated in all patients if the
    thickness of the fluid is more than 10-mm height
    on an standard lateral decubitus chest radiograph

21
Thoracocentesis
  • the clinician must consider limiting the amount
    of pleural fluid removed to less than 1,500 ml
    unless pleural pressure monitoring is performed
    during the procedure.

22
  • Transudate
  • Liver
  • Heart
  • Kidney

23
  • Exudate
  • Malignant
  • Tuberculous
  • Post-pneumonic
  • Pulmonary embolism
  • Collagen vascular disease

24
  • The first step consists in establishing the
    transudative or exudative nature of the fluid

25
  • Lights criteria continue to be the most useful
    to separate exudates and transudates.
  • Perhaps the only limitation of this criteria is
    the need of a concomitant blood draw for
    measurement of serum levels of LDH and protein.

26
  • A specific problem using Lights criteria occurs
    in patients with congestive heart failure that
    are being treated with diuretics, where the LDH
    levels can be significantly elevated and give the
    false impression of an exudative effusion.

27
Protein and LDH
  • Lights criteria
  • Pleural/Serum Protein Ratio
  • Transudate 0.5 Exudate gt0.5
  • Pleural/Serum LDH Ratio
  • Transudate0.6 Exudategt0.6
  • LDH
  • Transudate 200 U/L Exudate gt200 U/L

28
Cholesterol
  • Levels of cholesterol gt45 mg/dl identifies
    exudates with accuracy similar to Lights
    criteria .

29
Glucose
  • When the levels of glucose are lt60 mg/dl, the
    differential diagnosis is narrowed to a few
    conditions parapneumonic, malignancy, rheumatoid
    arthritis, and tuberculosis.
  • Other less frequent causes include hemothorax,
    lupus pleuritis, paragonimiasis, and
    Churg-Strauss syndrome.

30
pH
  • pH Bicarbonate normally accumulates in the
    pleural space giving the pleural fluid a
    relatively high pH7.6.

31
pH
  • common conditions associated with low pH include
    parapneumonic effusions and malignancy
  • An important exception in parapneumonic effusions
    is the infection with Proteus, organism that
    produces ammonia and typically elevates the
    pleural fluid pH.

32
pH
  • Assesment of pH is also helpful to guide
    management of parapneumonic effusions pHlt7.0
    warrants complete removal of the effusion by
    therapeutic thoracentesis or tube thoracostomy

33
pH
  • pH has prognostic implications in patients with
    malignant pleural effusions patients that have a
    low pH do not respond favorably to pleurodesis
    and have shorter life expectancy

34
pH
  • Unfortunately, measurement of pH is infrequently
    done following the right technique
  • the sample must be processed in an arterial
    blood gas machine, and the fluid must be
    collected into an anaerobic heparinized syringe
    with the same care as an arterial blood gas

35
  • Lipid studies

36
  • Cell Count and Differential
  • RBC Count
  • WBC Count
  • Neutrophils
  • Eosinophils
  • Lymphocytes

37
  • Grams stain
  • Culture aerobic and anaerobic
  • ZN stain
  • Culture for Mycobacterium tuberculosis
  • Culture for fungi

38
  • Cytological examination
  • (sensitivity 40-87)
  • Expertise of cytologist
  • Tumor type
  • Extent of disease

39
  • Bronchoscopy
  • Pleural biopsy
  • Thoracoscopy

40
Bronchoscopy.
  • The role for flexible bronchoscopy is very
    limited
  • it should be considered only when an obstructing
    endobronchial lesion is suspected and the
    physician cannot be certain of its presence based
    on a Computed Tomography (CT) scan.

41
Pleural Biopsy
  • Current recommendations for pleural biopsy
    include suspicion of tuberculous pleuritis and
    malignancy.

42
Pleural Biopsy
  • The procedure can be done blindly using local
    anesthesia
  • it is recommended to obtain at least four
    samples with one dedicated for Mycobacterium
    tuberculosis culture.
  • Use of ultrasound or CT guidance increases the
    yield in cases of malignant pleural effusions.

43
Pleural Biopsy
  • This procedure is currently used less often due
    to the development and wide availability of
    medical and surgical thoracoscopy.

44
Thoracoscopy
  • Involves the passage of an endoscope through the
    chest wall for direct visualization and sampling
    of the pleura.
  • There are two types of thoracoscopy procedures
    medical thoracoscopy and video-assisted thoracic
    surgery (VATS).

45
Thoracoscopy
  • Medical thorascopy is performed under conscious
    sedation and local anesthesia in a procedure
    room.
  • VATS requires general anesthesia and is performed
    in an operating room.

46
Thoracoscopy
  • During both procedures, the entire surface of the
    lung can be examined and biopsies from both the
    parietal and the visceral pleura can be obtained
    VATS offers the added advantage of therapeutic
    intervention.

47
Transudate
  • Congestive heart failure
  • Typically a transudative effusion
  • may be meet exudative criteria by an elevated LDH
    in cases of excessive diuretic use.
  • The diagnosis is frequently suspected based on
    clinical grounds cardiomegaly, bilateral pleural
    effusions, elevated jugular venous pressure,
    cardiac gallop, etc.

48
Transudate
  • Liver cirrohsis
  • CLD, ascites
  • Usually right sided pleural effusion
  • Transudative( diuretics)
  • Simultaneous pleural and ascitic sampling

49
PARAPNEUMONIC EFFUSION
  • should be suspected in all cases of pneumonia
    that do not respond to appropriate antibiotic
    therapy.
  • When present, a diagnostic thoracentesis is
    indicated, and rapid analysis of the fluid is
    warranted to identify all patients with empyema.

50
Malignant Pleural Effusion
  • Metastatic cancer of the lung (43),
  • Carcinoma of the breast (25),
  • Lymphoma (8),
  • Ovarian cancer (4)
  • Unknown primary cancer( 5 to 10)
  • Malignant mesothelioma is the most common primary
    tumor of the pleura and is related to prior
    exposure to asbestos

51
Tuberculous Pleural Effusion
  • Usually unilateral
  • Exudate of lymphocytic predominance
  • Positive tuberculin test
  • Difficult to demonstrate acid fast bacilli in
    pleural fluid or a biopsy specimen.
  • Pleural fluid cultures are positive only in 25
    of the cases, while biopsy increases the yield to
    55

52
Tuberculous Pleural Effusion
  • Adenosine deaminase (ADA) isoenzymes
  • Sensitivity and specificity of the test depends
    on the cut off level used (around 92).
  • ADA levels gt70 U/l are almost diagnostic of
    tuberculosis
  • Levels lt40 U/l are helpful to rule out the
    disease

53
Tuberculous Pleural Effusion
  • Interferon-gamma
  • Using cut-off levels of 3.7 IU/ml, the test
    yields a sensitivity and specificity of 98
  • Given higher cost and similar accuracy,
    currently, measurement of IFN-y instead of ADA is
    not recommended.

54
Post-Coronary Artery Bypass Surgery
  • Pleural effusions are frequently seen in the
    immediate postoperative period, and series have
    reported a frequency up to 40 70 1 week after
    the surgery.
  • Although the effusions can be large, most of the
    times these are small, exudative, unilateral, and
    preferentially located in the left side of the
    chest.

55
Post-Coronary Artery Bypass Surgery
  • The characteristics of the fluid may also vary
    depending on the time to presentation, being
    typically bloody exudates when developing less
    than 30 days after surgery, and nonbloody
    lymphocytic exudates when presenting after 30
    days postoperatively.

56
Dresslers Syndrome
  • described 1 to 3 weeks after myocardial
    infarction, cardiac surgery, chest trauma, or any
    other invasive procedure to the heart.
  • It was characterized by presence of fever, chest
    pain, and pleuro-pericarditis. The effusion is
    typically an exudate and may be unilateral or
    bilateral.

57
Chylothorax
  • Chylothorax is defined as the presence of chyle
    in the pleural space, generally associated with
    disruption of the thoracic duct.
  • This type effusion should be suspected in the
    presence of a milky or turbid pleural fluid.

58
Chylothorax
  • Most common causes are direct trauma to the
    thoracic duct (i.e., surgery) or malignancy
    (i.e., Lymphoma).

59
  • chylous effusions are characteristically
    exudative, although nontraumatic causes such as
    cirrhosis, nephrotic syndrome, or congestive
    heart failure can be associated with a
    transudative chylothorax.

60
Pseudochylothorax
  • Pseudochylothorax is also known as Chyliform
    pleural effusions or Cholesterol effusions. These
    effusions are not associated with trauma to the
    thoracic duct, typically result from long
    standing untreated pleural effusions in patients
    with rheumatoid or tuberculosis pleuritis.

61
  • Systemic Acidosis may lower pH in pleural fluid.
    Parapneumonic effusion, Malignancy, Rheumatoid
    Pleuritis, Tuberculosis, Hemothorax, Urinothorax,
    Esophageal Perforation.
  • Must be measured by a blood gas machine.

62
  • LDH Isoenzyme LDH-1 elevated Bloody pleural
    effusion LDHgt1000 U/L Complicated pleural
    effusion, Tuberculosis

63
  • Centrifugation with milky supernatant Lipid
    effusion
  • Triglycerides TGgt110 mg/dl Chylothorax
  • Chylomycrons Chylomycron screenin Lipoprotein
    fluid analysis Chylothorax

64
  • Cholesterol Pleural fluid to serum cholesterol
    ratiogt1 Cholesterol pleural effusion
    (Pseudochylothorax)
  • PF cholesterolgt200 mg/dl,Cholesterol crystals

65
  • Cell count and differential
  • RBCgt100,000 cells/mm3 Hemothorax
  • WBCgt10,000 cells/mm3 Complicated effusion,
    empyema
  • Eosinophilsgt10 Blood or air in pleural space,
    Parasitic, Drug related, Eosinophilic Pneumonia,
    Churg-Strauss

66
  • Amylase Higher than upper limit of normal (serum
    amylase) Pancreatic disease, malignant tumor or
    esophageal rupture

67
  • Adenosine deaminase (ADA) gt60 U/l Tuberculous
    pleuritis
  • Lower levels (lt45 U/l) Empyema, Parapneumonic
    effusions, Rheumatoid pleuritis.
  • IFN-gamma gt200 pg/ml Tuberculous pleuritis

68
Mesothelioma
  • If your patient, diagnosed to have mesothelioma,
    Lives more than one year, please revise your
    diagnosis,
  • said Prof. Sayed Elwaraky in 1982

69
Mesothelioma
  • Using either combination chemotherapy or
    sequential chemo-radiotherapy did not offer any
    statistical significance regarding the outcome
    response whether objective or subjective ( CT
    response). Both modalities led to poor results.

70
Treatment options
  • Surgery
  • Radiation
  • Chemotherapy
  • Combination (s)

71
Treatment options, Surgery
  • Three procedures are used in the surgical
    management of MPM
  • Thoracoscopy with pleurodesis
  • Pleurectomy/decortication (P/D)
  • Extrapleural pneumonectomy (EPP).

72
Surgery, EPP
  • EPP is the most aggressive procedure. It involves
    the en bloc resection of the visceral and
    parietal pleura, lung, pericardium, and
    ipsilateral diaphragm.

73
Surgery, EPP
  • Patient selection for EPP is critical, as is the
    experience of the surgeon and institution at
    which the procedure is performed.

74
Surgery, EPP
  • Early series showed a prohibitively high
    mortality rate. The 30-day postoperative
    mortality and morbidity in a center with
    extensive experience with the procedure are 3.8
    and 50, respectively.

75
Surgery, P/D
  • P/D involves the removal of the visceral,
    parietal, and pericardial pleura from the apex of
    the lung to the diaphragm.
  • Complete resection is usually only possible at a
    very early stage of the disease,
  • Local recurrence occurs in the majority of these
    patients.
  • In comparison to EPP, postoperative radiation
    doses are limited due to the retained lung.

76
Surgery, Thoracoscopy
  • Thoracoscopy is useful not only in obtaining
    tissue for a diagnosis but also for pleurodesis
    to palliatively treat recurrent or symptomatic
    pleural effusions.

77
Surgery
  • Neither EPP nor P/D appears to offer a
    significant improvement in survival.

78
Treatment options, Radiation
  • Radiation To encompass all known disease and
    areas at high risk, radiation therapy usually
    requires a prohibitively large field, as the
    entire pleural surface is at risk.

79
Radiation
  • In addition to the lung parenchyma itself, other
    thoracic structures can be dose limiting, further
    complicating treatment planning.

80
Radiation
  • Retrospective reviews have shown no suggestion of
    a clear survival benefit for extensive radiation
    therapy. Radiation therapy, therefore, seems to
    have a role in disease palliation but has no real
    impact on survival.

81
Treatment options, Chemotherapy
  • Chemotherapy In general, single-agent response
    rates are lt 20, and survival benefit for
    single-agent chemotherapy has not been suggested
    in single cohort studies. rR

82
Treatment options, Chemotherapy
  • Combination chemotherapy regimens have been
    extensively evaluated in MPM. The majority of
    these regimens are anthracycline based, platinum
    based, or both. With few exceptions, however,
    response rates are 20, and median survival
    remains largely unaffected in the range of 6 to
    12 months.

83
Chemotherapy
  • Response rates as high as 48 have been reported
    with the combination of gemcitabine and
    cisplatin( Byrne et al 1999),
  • However, a trial of similar design but slightly
    higher planned dose intensity of gemcitabine
    failed to duplicate this result, demonstrating a
    response rate of only 16(Van Haarst et al 2002)

84
Chemotherapy
  • Oxaliplatin has been studied in several regimens,
    including combination with gemcitabine. Schuette
    et al 2002, reported a response rate of 40 with
    this promising combination. Its toxicity profile
    is reported as favorable, and responses were
    noted in patients previously identified as
    platinum refractory

85
Chemotherapy
  • By contrast, data in 26 patients receiving the
    combination of vinorelbine and oxaliplatin
    yielded a response rate of only 23, a result
    nearly identical to that for single-agent
    vinorelbine, (Steele et al, 2001).

86
Chemotherapy
  • Overall, despite the testing of a variety of
    older and newer agents in combination, treatment
    for MPM remains inadequate. The incorporation of
    new targeted therapies into the most promising
    cytotoxic regimens of presently marketed agents
    needs to be tested extensively within more novel
    strategies of drug delivery (Pistolesi, and
    Rusthoven, 2004).

87
Chemotherapy
  • Pemetrexed as a single agent administered at a
    dose of 500 mg/m2 every 21 days has demonstrated
    promising activity in several malignancies,
    including non-small cell lung cancer, breast
    cancer, previously untreated colorectal cancer,
    bladder cancer, cervical cancer, and cancer of
    the head and neck.

88
Chemotherapy
  • In a phase I trial of pemetrexed combined with
    cisplatin, 5 of 11 evaluable patients (45) with
    MPM achieved a partial response (Thodtmann et al,
    1999)

89
Chemotherapy
  • A second phase I trial of pemetrexed combined
    with carboplatin in patients with MPM showed
    partial response in 8 of 25 assessable patients
    (32) (Hughes et al 2002).

90
Chemotherapy
  • In the initial stages of development, pemetrexed
    therapy was complicated by severe toxicities,
    thought to be due to deficiencies of folate
    and/or vitamin B12 pools. Subsequent
    supplementation of all patients with vitamin B12
    and folate significantly reduced severe
    toxicities associated with the drug (Bunn et al
    2001)

91
Chemotherapy
  • An open-label, multi-institutional phase II trial
    of pemetrexed as a single agent involving 64
    patients with MPM showed an overall response rate
    of 16 and a median survival of 13 months in
    patients supplemented with folic acid and vitamin
    B12. rR

92
Chemotherapy
  • a large randomized trial comparing
    pemetrexed/cisplatin vs cisplatin in treatment of
    MPM (Vogelzang et al 2003).
  • Pemetrexed/cisplatin was more effective than
    cisplatin alone in terms of median survival (12.1
    months vs 9.3 months, p 0.020), median time to
    disease progression (5.7 months vs 3.9 months),
    and response rate (41 vs 17).

93
Chemotherapy
  • As expected, the pemetrexed/cisplatin arm had a
    higher incidence of laboratory toxicities than
    cisplatin alone, including grade 3/4 neutropenia
    (28) and leukopenia (18), and rare
    nonlaboratory toxicities.
  • Supplementation improved the efficacy and
    toxicity profiles.

94
Chemotherapy
  • pemetrexed/cisplatin showed significant
    improvement in both pulmonary function tests and
    major disease-related symptoms such as dyspnea
    and pain.

95
Treatment options, Multimodality therapy
  • Multimodality therapy combined surgery with
    radiation, chemotherapy or all three modalities,
    this is the most promising approach.

96
Multimodality therapy
  • Those patients with negative margins, epithelial
    histology and node-negative disease had
    remarkable 2- and 5-year survival rates of 68 and
    46 respectively.

97
Multimodality therapy
  • Patients with epithelial histology had 52 and 21
    survival at 2 and 5 years respectively, while
    sarcomatous patients had a 2-year survival of 16
    and no survivors at 5 years.

98
Multimodality therapy
  • Overall survival rates of 38 and 15 were
    achieved for all patients at 2 and 5 years
    respectively, and the postoperative mortality was
    only 3.4.

99
Multimodality therapy
  • De Perrot et al, 2007, demonstrated that survival
    was significantly worse in patients with N2
    disease who underwent EPP with postoperative
    radiation survival was 10 months compared with
    29 month for node-negative patients

100
Multimodality therapy
  • Weder et al 2004, showed that neoadjuvant
    chemotherapy with cisplatin and gemcitabine
    followed by EPP and postoperative radiation could
    produce a median survival 23 months. The 1- and
    2-year survival rates were 79 and 23 months
    respectively.

101
Multimodality therapy
  • Flores et al 2006, found that early-stage MPM
    patients successfully completing a course of
    neoadjuvant chemotherapy with cisplatin and
    gemcitabine, followed by EPP and radiation, had a
    median survival of 33.5 months.

102
Multimodality therapy
  • A more recent Swiss, multicenter Phase II trial
    of induction therapy followed by EPP and
    radiation reported 23-month median survival in
    those patients who underwent EPP. These data
    suggest that induction therapy may prolong
    survival compared with upfront surgery (Weder et
    al, 2007)

103
Multimodality therapy
  • On the other hand, a multicenter US study of
    neoadjuvant pemetrexed and cisplatin, followed
    by EPP and hemithoracic radiation for respectable
    MPM that included 77 patients, illustrated that
    although trimodality therapy was feasible,
    preliminary median survival was only 16.6 months
    (Krug et al2007).

104
  • Despite major developments in assessment and
    treatment, the prognosis in mesothelioma remains
    poor (range 286 months). Various series have
    reported survival data which remain generally
    disappointing, but in most series there are a
    small number of unexpected long term survivors.

105
  • Various prognostic factors permit a degree of
    refinement of survival prediction. Advancing age,
    extensive disease, and sarcomatoid or biphasic
    histological subtypes are independent adverse
    risk factors. Long term survivors tend to be
    almost exclusively from the epithelioid group.

106
  • Initial results appeared promising, although the
    patients were highly selected and not
    representative of the overall mesothelioma
    population.

107
  • Only patients with Butchart stage 1 disease, good
    performance status, good cardiovascular status
    (ejection fraction gt45), sufficient respiratory
    reserve, and no significant co-morbidity were
    deemed eligible, and some of these patients were
    re-staged at thoracotomy.

108
  • With increasing surgical experience, 30 day
    mortality from EPP can be reduced to 4, although
    the morbidity remains significant. The results of
    trimodality therapy with less aggressive surgery
    are less promising.

109
  • Only 12 of patients are likely to be eligible
    for consideration of multimodality therapy. At
    presentation less than 20 have stage 1 disease.
    Many have co-morbidity with reduced cardiac or
    respiratory function that precludes aggressive
    surgery.

110
  • Multivariate analyses suggest that patients with
    epithelioid tumours, no extrapleural
    lymphadenopathy, and negative resection margins
    have the best prognosis, hence projections of
    benefit of this treatment are disappointing. It
    is highly unlikely that this form of treatment
    will impact significantly on the current
    management crisis for the majority of patients
    with malignant mesothelioma.

111
  • Although Sugarbaker presents some prospect of
    survival in an otherwise bleak environment, his
    results must be interpreted on a background of a
    selection policy that may exclude 9899 of
    patients, and where 12 of all patients may
    survive more than 5 years without any active
    treatment.

112
  • Br J Cancer. 2008 Jul 899(1)44-50.
  • Cisplatin and vinorelbine first-line chemotherapy
    in non-resectable malignant pleural mesothelioma.
  • Sørensen JB, Frank H, Palshof T.

113
  • CTC grade 3 or 4 toxicity occurred with respect
    to leukocytopenia (48 of patients, grade 4 in
    13), nausea (13), neurotoxicity (11),
    nephrotoxicity (4), and other toxicities (9).
    There were no toxic deaths.

114
  • The fraction of patients alive at 1-, 2-, and
    3-years were 61, 31, and 4, respectively, and
    median survival and median time to progression
    were 16.8 months (0.5 to 46.4 months) and 7.2
    months (1.6 to 40.6 months).

115
  • Survival with supportive care alone varies
    between 2 and 86 months, including occasional
    long term survivors.

116
  • Most patients require symptom palliation from the
    time of initial diagnosis.

117
  • No treatment has so far conclusively improved
    survival significantly beyond supportive care.

118
  • The main emphasis of treatment should be on
    symptom control, organised through a
    multidisciplinary team

119
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120
  • Thank you
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