Malignant pleural effusion

Scope
Definition Causes Pathophysiology Clinical presentation Investigation Diagnosis Management Treatment

Definition
Malignant Pleural Effusion Paramaliganant Pleural Effusion

Malignant Pleural Effusion

Condition that found malignant cell or pleural tissue in pleural fluid by fine needle aspiration, needle biopsy or Surgery

Malignant Pleural Effusion

Condition that found malignant cell or pleural tissue in pleural fluid by fine needle aspiration, needle biopsy or Surgery Most common of MPE is metastasis of cancer

Paramaliganant pleural effusion

Condition that cancer pts have pleural effusion but fluid do not found malignant cell Causing by cancar metastasis, systemic response or compilcations of Chemotherapy or Radiation or Surgery

Causes of MPE

Pathophysiology of MPE
Direct result Indirect result

Direct result
pleural metastasis with increasing permeability pleural metastasis with obstruction of pleural lymphatic vessels mediastinal lymph node involvement with decreased pleural lymphatic drainage bronchial obstruction (decrease pleural pressure) Pericardial involvement

Direct result
pleural metastasis with increasing permeability pleural metastasis with obstruction of pleural lymphatic vessels mediastinal lymph node involvement with decreased pleural lymphatic drainage bronchial obstruction (decrease pleural pressure) Pericardial involvement

Lymphatic obstruction
Postmortem studies, the presene of pleural effusion is correlated with metastases to lymph node complete blockage of lymphatics, the rate of pleural fluid accumulation should only be 15 ml/day Lymphatic obstruction would be transudate , it is always an exudate

Direct result
pleural metastasis with increasing permeability pleural metastasis with obstruction of pleural lymphatic vessels mediastinal lymph node involvement with decreased pleural lymphatic drainage brochial obstruction (decrease pleural pressure) Pericardial involvement

Increasing permeability
In series of Leckie and Tothrill,explain that the pts w bronchogenic carcinoma w metastasis disease to the pleural increased permeability of the pleura pts w bronchogenic had a secondary highest amount of protein entering of plural space Due to the production of vascular endothelial growth factor (VEGF) The madian level of VEGF in pleural effusions secondary to malignancy is higher than that in pts w effusion secondary to inflammatory disease The pleural fluid VEGF levels are also higher in haemorrhagic MPE than in non-haemorrhagic MPE

Direct result
pleural metastasis with increasing permeability pleural metastasis with obstruction of pleural lymphatic vessels mediastinal lymph node involvement with decreased pleural lymphatic drainage bronchial obstruction (decrease pleural pressure) Pericardial involvement

Bronchial obstruction
When neoplasms obs the mainstem bronchus or a lobar bronchus, lung distal to the obs becomes ateletatic Remaining lung must overexpand or the ipsilateral hemithrox must contract to compensate for the loss volume of the atelectatic lung More negative pleural pressure to be causes of pleural fluid to accumulate

Direct result
pleural metastasis with increasing permeability pleural metastasis with obstruction of pleural lymphatic vessels mediastinal lymph node involvement with decreased pleural lymphatic drainage bronchial obstruction (decrease pleural pressure) Pericardial involvement

Pericardial involvement
When Pericardial effusion is caused by such involvement and hydrostatic pressure become elevated in the systemic and pulmonary circulation Transudataive pleural effusion may result

Indirect result
Hypoprotenimia Postobstructive pneumonitis Pulmonary embolism Postradiation therapy Postchemotherapy -Methotrexate -Procabazine -Cyclophosphamide -Mitomycin -Bleomycin

Clinical presentation
Dysnea (MC) 50% Weight loss 32% Malaise 21 % Anorexia 14% Symptomatic Comparision MPE and benign PE Dull chest pain (34% vs 11%) Pleuratic chest pain( 24% vs 51%) Temperature elevation ( 37% vs 73%)

Investigation
Chest radiograph CT scan Pleural fluid examination

Chest radiographs
Pleural effusion varies from a few milliliters to several liters,with the fluid occupying the entre hemithorax and shifting the mediastinum to the contralateral side

Most common cause of massive pleural effusion Series:

(entire hemithorax) 67%
(>2/3 hemithorax)

55%

Chest radiographs
Almost All pts w plural effusion secondary to bronchogenic carcinoma have pulmonary abnormality beside the effusion Almost all pts w plural effusion secondary to lymphoma have mediastinal lymph node involvement , but not always evident in CXR The chest radiographs of patient with pleural effusions due to malignant tumors other than lung carcinoma or lymphoma often reveal only a pleural effusion Underdiagnosis for CXR

CT scan
Useful in indicating whether the effusion has a benign or malignancy etiology Yilmaz et al reported the following suggestive of malignancy
 Pleural nodularity  Pleural rind  Mediastinal pleural invovlement  Pleural thickening > 1 cm But this series are more large % mesothelioma,which are more likely to have abnormality of the pleural surfaces

CT scan
Concurrent abnormalities are frequently present in the pts with documented MPE
The incidence of concurrent abnormailty
      Percardial effusion 3% Pericardial thickinening 14% Mediastinal adenopathy 43 % Chest wall involvement 12 % Lymphangitic carcinoma 7 % Suspeciuos lung masses, nodules or infiltrate 53 %

Pleural fluid
Can be found in serous,serosanguinous and bloody fluids but most common is serosanguinous or bloody fluid (RBCs>100,000 /mm3) Most common is the exudate with protein and lactate dehydrogenase-rich If be transudate, be considered to lymphatic obstruction or bronchial obstruction or with condition of heart failure Most pleural effusions thet meet exudate criteria by the LDH but not by the protien level are malignant pleural effusion

Pleural fluid
WBC count is varible between 1,00010,000 cell/mm3 Predominant cell in the pleural fluid differential white cell count
 Lymphocyte ~45 %  Monocyte ~40 %  Polymorphonuclear leukocyte ~15%  Pleural fluid Eosinophilia ~>10%(old)  Pleural fluid Eosinophilia not associated with pleural air,blood or malignancy

Pleural fluid
Pleural fluid glucose level <60 mg/dl in appoximately 15-20% of MPE Low pleural fluid glucose level in association with MPE with indicates that the pts high tumor burden in pleural space Cytology and pleural biospy are more likely positve in pts with low-glucose pleural effusion Pts w low-glucose pleural effusion have indicated worsen prognosis Caused by impaired glucose transfer from blood to pleural space or Increased glucose

Pleural fluid
1/3 of pts with malignant pleural effusion have a pleural fluid pH below 7.3 Short survival than individuals with mPE and a pH level above than 7.3 Caused by acid production by the pleural fluid or pleura and a block the movement of the carbon dioxide out of the pleural space Appoximately 10% of MPE have an elevated pleural fluid amylase level. Usually primary tumor is not in the pancreas when analysis isoenzymes has demonstrated that amylase is the salivary isoenzyme rather than pancreatic isoenzyme.

Diagnosis
Cytologic Examination Immunohistrochemical test Tumor markers Pleural biopsy Observation,Thoracoscopy or an Open Thoracotomy

Cytologic Examination
The Easiest way to estabish the diagnosis Percentage of cases in which cytologic study establishes the diagnosis of MPE range from 40-87% Three separate pleural fluid specimen from MPE should expect a positve diagnosis is approximately 80% Incidence of positve result depends on the primary tumor , Most case metastatic adenocarcinoma diagnosed by fluid cytology. Positive results are uncommon with squamous cell carcinoma because the pleural effusion are usually due to bronchial obstruction or lymphatic blokade With lymphoma,the cytologic test positve ~25% in HKL and NHKL~50-60% Can identified the histological type, but not identified the primary site of tumor

Immunohistochemical tests
Using a monoclonal antibodies to distinguish malignant or benign antigen Metastic adenocarcinoma tend to positive Carcinoembyonic antigen (CEA), MOC-3,1 , B72.3 , Ber-ER4,BG-8 Malignant mesothelial cell and benign mesothelial cell stain positive with calrinin and cytokeratin Use in unkonwn primary

Tumor marker
Tumor marker evaluated have included CEA,CA15-3,19-9 etc. Some the benign and malignant is overlap

Pleural biopsy
The percentge of positive plural biopsy in pts MPE range from 39% to 75% Plueral biospy is lower diadnosis yield than of pleural fluid cytologic examination Because ~ 50% of MPE is not involved costal parietal pleura If the cytology is negative and thorocoscopy in unavailble or an outpatient procedure is desired, consideration can be give to perfrom needle biopsy of the pleura Alternative to use CT-quided cutiing-needle biopsy

Thoracoscopy and Open Thracotomy

Establish the diagnosis of malignancy in ~90% If Thoracoscopy is not available, an alternative appoach is to perfrom a thoracotomy with open biopsy of the pleura or to perfrom needle biopsy

mangement

mangement

teatment
Systemic chemotherapy Intrapleural chemotherapy Mediastinal Radiation Symtomatic treatment Repeated thoracenteses Indewelling pleural Catheter Pleurodosis Pleuroperitoneal shunt Pleurectomy

Systmic chemotherapy
Cisplatin,ifosfamide,irinotecan for NSCLC and pleural effusion -Complete disappearance of effusion 30% -Partial resolution 21% -mean survival of 362 days 1st Chemotherapy+ bevacizumab(anti-VEGF antibody) -because angiogensis is necessary for pleurodosis -statistically and clinically significant surrival adventage in pts w NSCLC Metastasic breast CA,lymphoma

Intrapleural chemotherpy
Intrapleural chemotherapy decreased the number of tumor cells in the pleural space, the rate of plural fluid fromation should be decrease. One study use cisplatin and gemcitabine by intrapleural chemotheray in NSCLC found that overall respone rate was 55%(complete 7%&partial 48%) Staphylococcus aureus superantigen(SSAg)(T-cell stimulant) - the effusion is complete controlled in some pts and meadian surrival was 7 month Rituximab ,monoclonal antibody directed agianst the CD 20 antigen of B-cell is effective in controlling NonHodgkins lymphoma Intreferon-gramma,tumor necrosis factor,interleukin-2

Mediastinal Radiation
Chylothrox, the throracic duct involved Tumor type that resistant the chemotherapy Lymphoma,metastasic Carcinoma

Symtomatic treatment
Symtomatic MPE with chest pain and shortness of breath -Suffiient analgestics should be control the pain (not worry about narcotic addiction) Symtomatic MPE with dyspnea - Should be given opiates or oxygen,or both

Repeated thoracenteses
Temporary Supportive treatment for dyspnea Recurrent for 1-3 day, After tapping Compilcation
 Pneumothorax tumor implantation  Tapping lung syndrome

Indwelling pleural Catheter(Pleurx)

Pts with recurrent pleural effusion to fluid drained without having to return to the hosipital Applied with local anesthasia by pulmonologists,radiologists and Surgeons Place in chest wall tunnel 5 to 8 cm in length Has a spacial valve on distal end to prevent gas or fluid passing in ether direction Draining the fluid though an external tube into vaccum bottles Tremblay and Michaud reported that tunneled cathete insertion resulted in complete symptom control in 38.8%,patrial control 3.6%,no control inb 3.6% Spontaneous pleurodesis ocurred after 43% of the procedures Be considered as the first-line treatment option in mangement of pts w MPE Pleural fluid production of > 1,000 ml fluid/week after place it for 7-14 days have attempt at chemical pleurodosis through the pleual catheter.

Morbidty of Pleur X
Fever Pneumothorax Misplacement of the catheter Reexpansion pulmonary edema Compilcation (prolonged use) Empyema Tumor seeding of catheter tract Loculation of the plural effusion

Pleurodesis
Pts w MPE are not candidates for tunneled catheter or systemic chemotherapy and do not have a chylothrox Procedure consider for pts whom systemic chemotherapy or mediastinal radiation failed Use in symtomatic MPE: only dyspnea is likely to be relived with pleurodesis Not to improve duration of pts life, but also improve the quality of life

Pleurodesis
Before Pleurodesis should mediastinal CXR, if the mediastinum shifted toward the side of the pleural effusion, the plural pressure is more negative on side of effusion Should bronchoscopy to r/o neoplastic bronchial obstruction. If found,should be considered to relief by radiotherapy,laser therapy or an endotrachial stent Symtomatic pts with relieved by thoracentesis should be considered to use PleurX,Pleuroperitoneal shunt

Technique of Pleurodesis
Tube thoracostomy w sclerotherapy Surgery
 Thoracoscopy w Pleurodesis  Open thoracoscopy w Pleurodesis

Pleuroperitoneal shunt
Use in condition of tapping lung syndrome -Trappinng lung syndromeThe prolonged accumulation of pleural secretion to from fibrin debris or adhesion make lung no full expansion Is a device consist of two catheter connected with pump chamber(1.5ml) Two-one way valves in pump chamber control only flow from the pleural space to peritoneal cavity On evidence of peritoneal tumor seeding but can be found the tumor seeding on surgical site

Pleurectomy
Major- risk operation(10-20)% Use in pts that expected life longer than 6 months No response for pleurosis Breast CA