Diagnostic Workup of Pleural Effusion and Medical Thoracoscopy –Current Status

Introduction

Normally a small amount of pleural fluid is present in the pleural space. The mean amount of fluid in the pleural space in normal individuals is 8.4 ± 4.3 ml.¹ When more than this fluid accumulates, then it is labelled as pleural effusion. It can be detected clinically when about 300- 500 ml fluid is present. The minimum volume of fluid required for detection on a chest X-ray PA film ranges from 250 to 600 ml.^2,3 Lateral view can detect 75 to 100 ml of fluid. Decubitus view can detect 125 to 150 ml of fluid.^4,5 Less than 50 ml of pleural fluid can only be detected by CT scan or ultrasonography (USG)6 . When a patient is found to have pleural effusion, an effort should be made to determine the cause (Table 1).

Though there are many causes, the common causes for transudative pleural effusion are congestive heart failure, nephrotic syndrome, cirrhosis of liver, peritoneal dialysis, hypoproteinaemia. While the common causes of exudative pleural effusion are tuberculosis, pneumonia,neoplastic diseases, pulmonary embolism and collagen vascular diseases.

Besides clinical and X-ray chest examination, the following investigations can be helpful in the diagnosis of aetiology of pleural effusion:

1. Pleural fluid analysis

2. USG of chest & abdomen

3. CT thorax with pulmonary angiography

4. Bronchoscopy

5. Pleural biopsy

6. Thoracoscopy

Various diagnostic algorithms using above mentioned investigations have been suggested by British Thoracic Society (BTS), American Association of Family Physicians (AAFP), Light, Harrison etc. But I feel the most practicable in our country will be as shown in Figure 1. According to this algorithm, if Congestive Heart Failure (CHF) is associated with pleural effusion, then a trial of diuretics should be given. If pleural effusion improves or disappears, then find and treat the cause of CHF. If it is massive pleural effusion or it does not improve with diuretics, then thoracentesis should be done.

Macroscopic examination of pleural fluid may sometimes help in determining the aetiology of pleural effusion like –

• Straw yellow colour – Possibility of tuberculosis

• Haemorrhagic red or dark brown colour – Possibility of malignancy

• Purulent fluid – Empyema

• Black colour – Aspergillus infection

• Brown anchovy sauce – Amoebic liver abscess draining into pleural space

• Food particles – Esophageal rupture

• Milky white – Chylothorax, Pseudochylothorax

• Urine odour – Urinothorax Besides macroscopic examination of pleural fluid, pleural fluid analysis should also be routinely done for sugar, proteins including albumin, Lactate Dehydrogenase (LDH), Adenosine Deaminase (ADA), cytology and sometimes for triglycerides, cholesterol, amylase etc. When required, microbiological examination, immunohistochemical studies and tumour marker detection as per the clinical requirements may be conducted. Simultaneously serum protein (albumin) & serum LDH examination may also be done.

First aim of pleural fluid analysis is to differentiate between transudate and exudate (Table 2). The pleural fluid analysis is sufficient in most of the cases to differentiate between tubercular and non-tubercular effusions (Table 3).

If pleural fluid analysis is inconclusive, then CT scan thorax with contrast including CT pulmonary angiography, should be done to confirm or exclude pulmonary embolism, to differentiate between benign & malignant nature of disease, mediastinal and underlying lung anomalies.⁷ If large pleural mass or nodule or mass in the lungs is found, then simultaneously CT guided needle biopsy should be attempted.⁸

Now if pulmonary embolism is excluded by CT scan examinations, then the patient should be assessed for bronchoscopy/ thoracoscopy. If there are parenchymal infiltrates, central mass or mediastinal adenopathy, then bronchoscopy with or without Transbronchial Needle Aspiration (TBNA) should be preferred.⁹ Here, I would like to specially mention that bronchoscopy should be performed after thoracentesis, as pleural fluid may compress the airways and limits bronchoscopic views. But if no definite lung parenchymal or mediastinal lesions are visible on CT thorax, then thoracoscopy should be done.^10,11,12,13 In such cases, sensitivity & specificity of thoracoscopy including pleural biopsy is more than 90%. Here again, I would like to suggest that pleural biopsy should also be sent in normal saline for Acid Fast Bacilli (AFB) smear, culture and TB PCR if tuberculosis is suspected, in addition to histopathological examination in formalin.

In our country, if any pleural effusion remains undiagnosed even after thoracoscopy, and Mantoux test / QuantiFERON TB Gold is positive, then a trial of antitubercular therapy should be given because more than 50% of such cases may later on develop parenchymal pulmonary tuberculosis. Lastly, if the pleural effusion is minimal without breathlessness or no parenchymal infiltrates or mediastinal disease on CT examination with stable or improving clinical status, then the patient may be kept under observation.¹⁴

Medical Thoracoscopy– Current status

Pleural conditions comprise approximately 25% of cases presenting to pulmonologists. Hence, there has been an increasing interest in novel investigations by pulmonologists in pleural diseases. Investigative modalities have included radiography, ultrasound and CT (Figure 2-6).

Thoracoscopy was first described by Jacobaeus using rigid instruments in 1910. It is important to understand that there are two different techniques for thoracoscopy – Video- Assisted Thoracoscopic surgery (VATS) and medical thoracoscopy (MT). MT is performed by a pulmonologist (usually) on spontaneously breathing patients commonly via a single port and is often a diagnostic procedure in undiagnosed pleural effusion cases, and occasionally done for pleurodesis with talc. Whereas VATS is performed by several ports by a thoracic surgeon on an intubated patient with a doublelumen tube and is primarily performed with a therapeutic intent.¹⁹

Patient selection

Patients with unexplained pleural effusion, pneumothorax, empyema may potentially be suitable for MT. The only absolute contraindication is lack of a pleural space due to adhesions, as a partially collapsed lung is required to safely introduce the thoracoscope into the pleural cavity. Other contraindications include refractory cough, hypoxemia unrelated to the effusion, pulmonary hypertension, unstable cardiovascular status, bleeding diathesis.

Training requirements for Medical Thoracoscopy

The guidelines from the American College of Chest Physicians (ACCP) recommend that trainees should perform at least 20 procedures in a supervised setting to establish basic competency and then a minimum of 10 per year to maintain competency.²⁰

Clinical Applications

Pleural effusion of unknown aetiology

Pleural malignancy

The main indication of MT is in the evaluation of pleural effusion of unknown aetiology. MT is often needed because of the limitations of less invasive diagnostic techniques. Thoracocentesis is the first investigation in unexplained pleural effusions but pleural cytology is diagnostic only in 62% of cases for malignancy,²¹ with a much lower yield in mesothelioma²² and in early cancers. Even after further sampling with larger volumes, at least 25% of suspected malignant effusions remain undiagnosed. If there is a suspicion of malignancy, then MT should be done, unless there is an ipsilateral shifting or midline mediastinum in the presence of an effusion, which would suggest main bronchus obstruction, which may require bronchoscopy as an initial diagnostic test.

Closed pleural biopsy using an Abram’s needle only increases the yield for malignancy over cytology by 7% to 27%23 and has a lower yield compared with CT guided pleural biopsy or MT.²⁴ CT-guided pleural biopsy can achieve yield of 87% to 88% for malignancy and 86% for mesothelioma.^24-26 The yield of MT is superior with 90% to 95% yield.^27,28 Although CT-guided pleural biopsy gives a better yield than closed pleural biopsy ( 87% vs 44%),²⁴ MT is superior as it allows combined diagnostic and therapeutic options ( drainage, adhesiolysis and pleurodesis) in a single visit, if indicated, with a larger tissue sample for analysis. The main benefits of MT in malignancy are diagnosing pleural metastasis by guided biopsy under direct vision and providing large amounts of tissue to allow histologic confirmation,²⁹ histologic differentiation (especially mesothelioma from adenocarcinoma), hormone receptor analysis, and assessment of lung expandability.

Tuberculous pleural effusion

For TB pleural effusion, closed pleural biopsy has a much higher yield than in pleural malignancy due to the more diffuse nature of the pleuritis with combined yield of histology, tissue culture, pleural fluid smear, and culture varying between 80% and 90%.²³ MT remains superior to closed pleural biopsy ( 98% vs 80% )³⁰ in areas with a high TB prevalence.³¹ MT has the advantage over closed and CT-guided pleural biopsy of obtaining a greater amount of tissue, which may be relevant when the diagnosis is in doubt or when there is a need to obtain anti-TB Drug Susceptibility test (DST) for suspected drug-resistant cases. MT also allows the simultaneous opportunity to break down adhesions and drain the effusion which may be necessary for larger effusions while waiting for response to anti-TB treatment.

Pleural infection and empyema

In pleural infection, loculations may impede drainage via a conventional chest tube and intra-pleural fibrinolysis is not recommended in this context.³² MT can be useful early in the course of empyema when thin fibrinous adhesions can be broken down and the fluid and the infected material can be removed to allow lung expansion, providing an opportunity to take biopsies to exclude occult undiagnosed infection or malignancy.^33,34 I had done MT in a 13-year old patient who presented with empyema. Thoracoscopy was done which showed thick adhesions (Figure 8) and fibrinopurulent material all over the pleurae. I did adhesiolysis, drained the pus and then inserted intercostal tube. The patient was puton long-term antibiotics and there was gradual and complete expansion of the lung without the further need for VATS.

In the later phase of empyema, when there are thick fibrous adhesions (Figure 8),³⁵ trapped lung, early VATS decortications may be required.^36,37 Experts can also perform MT in empyema in the fibrinopurulent stage; however, this may be a preferred option in frail or elderly patients, where conventional chest drainage has not been successful and patients are at a high risk for VATS.^19,38 Existing data on MT in pleural infection is sparse but a 93% primary success rate in avoiding surgical intervention has been achieved in early stage pleural infection.³⁹

Pneumothorax

With MT, blebs and bullae can be visualised in patients with spontaneous pneumothorax. MT with talc poudrage may be particularly helpful in the setting of patients with significant morbidity and advanced lung disease that may not be suitable for VATS 40 and is superior to standard pleurodesis via a chest tube.⁴¹ In suitable patients, VATS or thoracotomy detects blebs or bullae better than MT and VATS bullectomy, pleural abrasion, or pleurectomy is superior to MT for recurrent pneumothoraces.⁴²

Pleurodesis

MT can be used for talc pleurodesis. MT talc poudrage has been shown superior to talc slurry via a normal chest drain in a recent Cochrane systematic review.⁴³

Other Benign Pleural Diseases

If thoracocentesis is unhelpful, MT can also help to diagnose other benign pleural disorders. The parietal pleura can have a gritty appearance in rheumatoid effusion⁴⁴ and asbestos pleural plaques have a characteristic smooth, white, but hard consistency that is difficult to biopsy.

Advanced techniques

Advanced applications of MT include visceral pleural and lung biopsy and sympathectomy. Sympathectomy has been used for the treatment of hyperhidrosis or chronic pancreatic pain in particular. Although generally performed by thoracic surgeons at VATS,⁴⁵ advanced pleuroscopists have described a single port technique via a single lumen endotracheal tube using electrocautery.^46,47

Thoracoscopic appearances of some of the pathologies are shown in Figure 9.

Complications of MT

Thoracoscopy has a relatively low rate of complications. Data collected on 1820 patients from the VATS study group registry48 in 1993 revealed that the overall mortality was 2%. The complications of medical thoracoscopy are fewer than those of VATS.⁴⁹ The mortality rate is less than 0.5% and most deaths are thought to be unrelated to the procedure.⁴⁹ The same type of complications occur with medical thoracoscopy as with VATS and include intrapleural bleeding, prolonged air leak, and empyema etc.⁵⁰

Summary

MT offers pulmonologists an opportunity to take multiple pleural biopsies to diagnose malignant and non-malignant pleural diseases. In addition, operators may drain large pleural effusions, break down adhesions, and perform an effective pleurodesis with talc poudrage under direct vision, using conscious sedation. Advanced operators may treat pneumothorax and take lung parenchymal or visceral pleural biopsies. Close collaboration between the pleuroscopist, thoracic surgeon, and radiologist is the key as MT remains an invasive procedure requiring training and careful patient selection.

Conflict of interest

Nil.