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Performance Characteristics of Semirigid Thoracoscopy in Pleural Effusions of Undetermined Etiology

Mohan, Anant MD*; Naik, Samir MRCP; Naseer, Rehan MRCP; Boon, Cheng; Mills, Janet; Pandey, Ravinder M. MD*; Munavvar, Mohammed FRCP

Journal of Bronchology & Interventional Pulmonology: October 2010 - Volume 17 - Issue 4 - p 289-294
doi: 10.1097/LBR.0b013e3181f9ebca
Original Investigations
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Background The utility of the recently introduced semirigid thoracoscopy in undiagnosed pleural effusions is still unclear.

Methods A single-center, 4-year retrospective analysis of all semirigid medical thoracoscopy procedures was done. The diagnostic accuracy of thoracoscopy was calculated as the number of positive diagnoses achieved by thoracoscopy in relation to the end-diagnosis achieved in the patient group by any means.

Results One hundred fifty procedures were analyzed. Ninety-two patients (62.3%) were diagnosed as having a malignant disorder, of which mesothelioma was the most common (26%). Pleural thickening and nodularity were the most common abnormalities noted. The combined presence of nodules and hemorrhagic fluid increased the likelihood of malignancy 9-fold. Thirteen patients with a high clinical suspicion of malignancy but negative by thoracoscopy underwent mediastinoscopy, computed tomography-guided biopsy, or open thoracotomy. A malignant etiology was confirmed in all of them. Overall, thoracoscopy provided a diagnostic accuracy of 91.3%, sensitivity of 87%, and specificity of 100%. The addition of a second procedure in selected patients improved the diagnostic accuracy for malignancy by 8.7%. The procedures were well tolerated and only 6 patients developed minor and transient complications such as pain, hypoxia, and bradycardia.

Conclusion Semirigid thoracoscopy is a safe, well-tolerated, and efficacious procedure for establishing the diagnosis in pleural effusions of undetermined etiology.

*All India Institute of Medical Sciences, New Delhi, India

Royal Preston Hospital, Preston, UK

Source of Funding: None.

The authors had the following role in this manuscript: Anant Mohan—study concept, collection and entry of data, statistical analysis, writing, and submission of the manuscript. Samir Naik—study concept, collection and entry of data. Naseer Rehan—study concept, collection and entry of data. Janet Mills—collection and entry of data. Cheng Boon—collection and assimilation of data and literature review. Mohammed Munavvar—study concept, performance of all procedures on patients, writing of manuscript.

Reprints: Anant Mohan, MD, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India (e-mail: anantmohan@yahoo.com).

Received for publication July 1, 2010; accepted August 28, 2010

Conflict of Interest: None to declare.

Medical thoracoscopy is a safe, effective, and valuable diagnostic and therapeutic tool, especially in patients with suspected malignant pleural effusions. The earliest description of the technique, along with indications and complications of the procedure, was published more than 3 decades ago.1 Until recently, thoracoscopy has been performed using rigid scopes with variable results.2,3 Comparison between rigid and flexible instruments showed slightly superior results in initial studies.3 However, a rigid scope can be perceived as cumbersome and most pulmonary physicians are not trained in its use, even in Western countries. Hence, the semirigid thoracoscope has been recently devised and evaluated in pleural diseases. Preliminary reports have proved encouraging4; however, there is still paucity of data regarding the diagnostic yield and safety profile of this procedure in the evaluation of pleural effusions. We conducted an audit into all semirigid thoracoscopic procedures performed at the Chest Medicine Unit of the Royal Preston Hospital, Lancashire, UK, over a 4-year period.

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PATIENTS AND METHODS

Thoracoscopic procedures performed between 2004 and 2008 were included for analysis. All patients were evaluated for pleural effusion and no conclusive diagnosis was achieved after needle pleural aspiration followed by cytologic and biochemical examination of the fluid. Blind pleural biopsy is not routinely performed at this center. Each patient underwent a computed tomogram of the chest before the procedure to exclude any other pathology which might preclude thoracoscopy, such as mediastinal lymphadenopathy or an eminently accessible lung mass. Patients were assessed for fitness for thoracoscopy by spirometry and routine blood testing, and arterial blood gas analysis wherever indicated. Presence of bleeding disorders, ongoing anticoagulation therapy, lack of pleural space because of marked adhesions/frank empyema, severe persistent cough, and marked hypoxia were considered contraindications. The patients were admitted the evening before the procedure and were kept fasting for 8 hours before thoracoscopy. The procedure was explained in detail and written consent was obtained. Prior approval for the study was obtained from the institution's Internal Review Board.

The instrument used was a prototype semirigid thoracoscope (LTF-160Y1; Olympus, Tokyo, Japan; supplied by Olympus KeyMed UK, Southend-on-Sea, UK). It has controls similar to that of a flexible bronchoscope. The total length of the instrument is 52 cm, with the insertion portion being 27 cm long. Of this, the proximal 22 cm are rigid and the distal 5 cm are flexible. The external diameter of the insertion portion is 7 mm. The tip is bendable in one plane, with an upward angulation of 160 degrees and downward angulation of 130 degrees. The 2.8-mm inner working channel accommodates the biopsy forceps and other instruments. It has a yttrium aluminum-garnet 810-nm diode laser and high-frequency compatibility. It is compatible with the EVIS EXERA 160 and 145 and EVIS 100 and 140 Series video processors and light sources (Olympus). Sterilization is achieved by autoclaving.

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Procedure

All the procedures were performed by a single operator (M.M.) in the endoscopy suite of Royal Preston Hospital, Preston, UK. Ultrasound was performed to confirm the safest point of entry. The patients were positioned in the lateral decubitus position with the diseased side up. Sedation was administered with intravenous midazolam and alfentanil; supplementary oxygen was given through nasal cannulae; oxygen saturations and heart rate were monitored throughout. A lignocaine solution (2%) was used for local anesthesia at the puncture site. The presence of fluid was first confirmed by aspiration; if this failed, the site was changed and aspiration was attempted again. After the fluid was obtained, an incision was made in the midaxillary line and a 10-mm trocar was inserted. A single-puncture technique was used. The full surgical aseptic technique was adhered to. The thoracoscope was then inserted and, after drainage of all the fluid to dryness, the pleural surfaces were inspected. Pleural fluid and parietal pleural biopsy samples were obtained where indicated.

Between 6 and 10 biopsy specimens were taken per patient. An FB-240 K oval fenestrated biopsy forceps (Olympus) was used. Talc poudrage, with a 5-g sterile talc (Novatech, La Ciotat, France), was carried out where appropriate. A 24F chest drain (Portex; Smiths Medical International Ltd, Hythe, UK) was inserted through the trocar. All the patients underwent a chest radiograph after the procedure. The chest tube was removed as soon as full expansion of the lung was confirmed radiologically.

The operator recorded the image quality, the presence of pleural abnormalities on inspection, the duration of chest drainage after the procedure, and the occurrence of complications. A chest radiograph was subsequently taken to monitor the reexpansion of the lung and check the position of the chest tube, which was removed as soon as full lung expansion was achieved. Postprocedural analgesia was achieved by the administration of paracetamol and tramadol.

Patients with a nonmalignant pathologic diagnosis after thoracoscopy were given appropriate treatment and followed for response. The resolution of the pleural effusion with clinical improvement was considered as diagnostic evidence of a benign etiology. The patients who were initially considered highly suspicious for malignancy, but had tested negative after thoracoscopy, were subjected to another procedure such as computed tomography (CT)-guided fine-needle aspiration/biopsy, Video assisted Thoracoscopic Surgery (VATS), mediastinoscopy, or open thoracotomy after discussion in the Lung Cancer Multidisciplinary Conference. The flow algorithm followed for the patients' work-up is shown in the Figure 1.

FIGURE 1.

FIGURE 1.

Statistical analysis was done using STATA, version 10. Data were expressed as mean±standard deviation (SD), or percentage. A P value of less than 0.05 was considered statistically significant. Diagnostic accuracy of thoracoscopy was calculated as the number of positive diagnoses achieved by thoracoscopy in relation to the end-diagnosis achieved in the patient group by any means.

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RESULTS

A total of 171 procedures were performed during this period. Of these, the histologic reports could not be located in 11 procedures, whereas 10 reports were inconclusive because of insufficient tissue provided. Hence, analysis was done for the 150 patients whose final diagnosis was available.

The patients were predominantly male (66.7%), with mean (SD) age of 68.2 (14) years. Of these, 16.7% patients offered a significant history of earlier asbestos exposure. The demographic characteristics of the study population are shown in Table 1.

TABLE 1

TABLE 1

Between 6 and 10 pleural biopsies were taken in 146 patients (97.3%) and pleurodesis was performed by talc poudrage in 52 patients (34.7%). Three patients experienced significant pain during the procedure, 2 developed transient hypoxia, and 1 had bradycardia that improved spontaneously.

The observed thoracoscopic findings are tabulated in Table 1. Pleural thickening and nodules were the most common abnormalities, noted in 56% and 46% of patients, respectively. Hemorrhagic fluid was aspirated in approximately half of the patients.

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Etiology

Of the 150 procedures, a diagnosis was obtained in 137 patients (91.3%). Of these, 50 patients (33%) had a benign disorder, including tuberculosis. Pleural fluid was positive for malignant cells in 12 patients (8% of whole group and 11.4% of the patients with a final diagnosis of malignancy). By thoracoscopy, 92 patients were found to be positive for malignancy, with mesothelioma and bronchogenic carcinoma being the most common, thus providing a diagnostic yield of 61.3% [confidence interval (CI), 53.0-69.1]. Four patients had normal pleura. The 13 patients, who remained undiagnosed after thoracoscopy, underwent other procedures, such as VATS, open thoracotomy, mediastinoscopy, or a CT-guided procedure. A diagnosis of malignancy was obtained in all these patients. These included 3 mesotheliomas, 1 lymphoma, and 9 carcinomas. Forty-four patients had nonspecific inflammation whereas 7 had histologic features consistent with tuberculosis (Table 2). The overall diagnostic accuracy of thoracoscopy with respect to the end diagnosis was 137 of 150 patients, that is, 91.3% (CI, 85.6-95.3).

TABLE 2

TABLE 2

A sensitivity analysis was also done to account for the 21 patients who were initially screened but excluded because of the absence of the end diagnosis. If all these patients were assumed to be suffering from a malignant disease, the diagnostic yield of thoracoscopy was 66.1% (CI, 58.5-73.1), whereas it was 53.8% (CI, 46.0-61.4) if all the 21 patients were assumed to be nonmalignant.

Among our patients, the presence of pleural nodules and infiltration was significantly associated with the likelihood of malignancy (Tables 3 and 4).

TABLE 3

TABLE 3

TABLE 4

TABLE 4

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DISCUSSION

Semirigid thoracoscopy is a useful diagnostic tool and aids in establishing the diagnosis of malignancy in more than 85% of patients with undiagnosed pleural effusion.5,6 This is a significant improvement over the yield obtained by a single pleural aspiration, which is positive in only up to 62% of patients with metastatic pleural involvement.7 Pleural fluid examination is particularly unreliable for mesothelioma, providing a diagnosis in only 20% patients.8 Closed-needle pleural biopsy may be successful in only 50% of metastatic pleural disease9 and the addition of this procedure to pleural fluid cytology merely increases the yield by an additional 10%. Moreover, it has limited accessibility to tumors confined to the diaphragmatic, visceral, or mediastinal pleura. The poor yield of pleural fluid cytology and closed-needle biopsy prompted the use of open thoracotomy and biopsy. However, thoracoscopy provides a similar diagnostic efficacy with fewer complications and morbidity and it is now increasingly favored over the more invasive surgical procedures.10

In this study, overall, thoracoscopy proved to be 91.3% accurate for obtaining a definitive diagnosis in pleural effusion, with a sensitivity of 87% for malignancy and a negative predictive value of 77%. These figures compare well with the yield obtained in earlier studies conducted for the evaluation of pleural effusion. In fact, a diagnostic yield of more than 90% had been reported in most studies using semirigid instruments to investigate undiagnosed pleural effusions,4,11,12 although lower yield has also been reported in a study with a smaller number of patients.13 The yield of the semirigid instrument is comparable with the 80% to 96% average yield achieved with its rigid counterparts.1,5,14–16 One study found a 96% diagnostic accuracy, with a sensitivity of 91% and specificity of 100%.16 The negative predictive value for the diagnosis of pleural malignancy, with a follow-up of 2 years, was 93%. Similarly, a retrospective study of 138 patients reported an overall diagnostic efficacy of 97%, including 93% for carcinoma, 100% for mesothelioma, and 94% for tuberculosis.17 In a series of 1000 consecutive patients with pleural effusions, 215 patients had pleural effusions of unknown etiology despite repeated thoracentesis and percutaneous needle biopsy of the pleura.15 Thoracoscopy resulted in a diagnosis of malignancy in 150 (70%) of the patients, including mesothelioma in 35 patients. Similar levels of diagnostic accuracy have been reported by other investigators.3,18,19 Overall, the diagnostic sensitivity of thoracoscopy for malignancy ranges from 92% to 99% and a likelihood ratio from 3.67 to 7.71 (95% CI, 0.33-103.32).4,11,13,20,21

In this study, of the 105 patients diagnosed with malignancy, thoracoscopy detected 92, whereas 13 patients were diagnosed by other methods. The procedures performed in these 13 patients who tested negative for malignancy by thoracoscopy were VATS, open thoracotomy, mediastinoscopy, and CT-guided transthoracic biopsy. The sensitivity for diagnosing malignant disorders by thoracoscopy was 87.6% with 100% specificity. The addition of another investigation after thoracoscopy improved the yield up to 100%. The reasons for missing the diagnosis of malignancy in 13 patients (false negatives) could be multifactorial and attributed to very early disease with apparently normal-looking pleura or with small focal lesions, extensive adhesions that limit visibility and sampling, and the physician's learning curve.

Mesothelioma was the most common single malignant disorder detected, followed by bronchogenic carcinoma. Overall, thoracoscopy provided a diagnostic accuracy of 61.3% for malignancy in the entire study group, a figure that improved to 70% with the addition of a second procedure. During the last 30 years, the incidence of mesothelioma has been increasing steadily, accounting for 1% of all deaths.22 Mesothelioma often presents a diagnostic difficulty because closed-needle biopsy specimens are rarely of sufficient size to allow a definitive diagnosis. Thoracoscopy establishes a diagnosis in 60% to 75% of patients,2,16,23 compared with 88% with open thoracotomy.24 In addition, if future surgical resection is not a consideration, thoracoscopy permits pleurodesis in the same sitting.

Macroscopic appearances during thoracoscopy help to establish the diagnosis of malignancy in more than 85% of patients (especially if polypoid lesions, localized tumoral masses, thickened pleura, or “candle wax drops” are observed).5,25 Other common findings, which suggest malignancy, include pleural infiltration, nodules, and masses.15

The presence of hemorrhagic pleural effusion was significantly associated with malignant disease. Overall, 60% of our patients had hemorrhagic effusions, of which 25% were present in those with benign disease. In fact, 38.6% of patients with benign disease had bloody pleural effusion. Although malignant effusions are typically described as hemorrhagic, earlier studies have shown that up to 46% of patients with malignancy may have straw-colored fluid, and hence, the color of fluid is not always a reliable indicator of the presence of malignancy, despite the results obtained in our group. Apart from the diagnostic utility, thoracoscopy allowed removal of large amounts of fluid (up to 3 L), thus markedly improving pulmonary reserve.

Almost 30% of the procedures yielded nonspecific inflammation in the pleura. These may be because of persistent pleural inflammation associated with pulmonary infections, or reactive changes because of another disease. Such indeterminate/inconclusive results have been observed earlier as well where it was shown that in nonmalignant conditions, histologic study of the biopsy specimen is useful in confirming a benign cause but was usually not helpful in clarifying the real cause of a pleural effusion, except in patients with pleural tuberculosis.1

The diagnostic accuracy of thoracoscopy, however, depends on the duration of follow-up1,3,6,19,23,26 and false-negative rates increase with time. Although 1 study noted a false-negative rate of 15% after 1-year follow-up,15 another found a diagnostic accuracy of 69% among patients followed for 5 years.27 In the latter study, 25% of patients labeled as having benign pleural disease after thoracoscopy were diagnosed within 6 months as having a malignancy. It must be noted, however, that these results were obtained using the rigid thoracoscope. Long-term follow-up studies after semirigid thoracoscopy are not yet available.

Thoracoscopy is useful in nonmalignant disorders as well. The diagnostic yield of a closed pleural biopsy is 70% to 90% in exudative pleural effusions because of tuberculosis.19 Therefore, thoracoscopy is often considered unnecessary to establish the diagnosis of a tuberculous effusion, except in special circumstances in which lysis of adhesions is necessary, or when larger amounts of tissue are necessary for determination of drug resistance. However, the diagnostic accuracy of thoracoscopy in suspected tuberculosis is 100%.28

Apart from showing a high diagnostic yield for both malignant and benign disorders, the findings during thoracoscopy directly influence patient management in most cases.29 Consequently, the 2000 American Thoracic Society statement on the management of malignant pleural effusions states that “in cases of undiagnosed exudative effusions with a high clinical suspicion for malignancy, some clinicians may proceed directly to thoracoscopy if the facilities are available.” Similar views were expressed a few years later by the British Thoracic Society, virtually establishing the utility of this procedure in the diagnostic work-up of pleural effusions.30

The dose of midazolam and fentanyl used in this study was much higher than that in earlier reports, probably accounting for the high level of comfort and tolerability of the procedure by the patients.11,13 Only a few patients reported minor and transient complications, such as local pain, fever, nausea, and vomiting. These are in accordance with earlier studies wherein thoracoscopy has been found to be a very safe procedure, with extremely good patient tolerability.31 No procedure-related mortality has been reported so far.

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Limitations

This study had certain limitations. First, it was a retrospective analysis of only those patients whose final diagnosis was available either by histology or by clinical recovery. Patients who were referred from out of the catchment area of the hospital and whose follow-up details were unavailable had to be excluded. Information regarding functional class and radiographic amount of fluid was not available for all patients and objective evidence of preprocedure and postprocedure improvement was not assessed. Closed pleural biopsy was not performed in any patient; hence, comparisons among pleural aspiration, pleural biopsy, and thoracoscopy could not be made.

In summary, semirigid thoracoscopy is a simple, safe, and well-tolerated procedure with high diagnostic accuracy in pleural effusions. Although false negatives are a concern, thoracoscopy is worth pursuing actively as the initial technique for patients with definite indications, if the facilities are available.

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Keywords:

thoracoscopy; malignancy; semirigid thoracoscopy; pleural effusion; effusion

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