Medical thoracoscopy.

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Medical Thoracoscopy Joseph H. Skalski, MD1

Philippe J. Astoul, MD, PhD2

1 Division of Pulmonary and Critical Care Medicine, Mayo Clinic,

Rochester, Minnesota 2 Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, Aix-Marseille University, Chemin des Bourrely, France

Fabien Maldonado, MD, FCCP1 Address for correspondence Fabien Maldonado, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (e-mail: [email protected]).

Abstract

Keywords

► ► ► ► ►

pleuroscopy thoracoscopy pleural biopsies pleurodesis malignant pleural effusions ► pneumothorax

The burden of pleural diseases continues to rise and affects an increasingly complex and aging patient population. As such, thoracentesis is one of the most common procedures performed by respiratory physicians, as pleural fluid analysis can establish the diagnosis of pleural effusions in approximately 75% of the cases. When a diagnosis is not reached, options include image-guided biopsies, only possible when focal pleural lesions can be identified by computed tomography or ultrasound; closed pleural biopsies, associated with a relatively low diagnostic yield; and surgical pleural biopsies, which typically require general anesthesia and a hospital stay. Medical thoracoscopy addresses some of the limitations of these techniques, allows a comprehensive pleural examination and targeted pleural biopsies, and offers the possibility of treatment of recurrence in the same setting. As such, medical thoracoscopy is ideally positioned as a valuable tool in the diagnosis of unexplained exudative pleural effusions.

Pleural effusions represent a common problem in pulmonary medicine. Approximately 1.5 million new pleural effusions are diagnosed yearly in the United States, 200,000 of which will ultimately be proven malignant.1,2 As such, thoracentesis is one of the most common procedures performed by respiratory physicians, with an estimated 180,000 thoracenteses performed annually in the United States alone. However, thoracentesis provides a definitive or presumptive diagnosis in only 73% of the cases, and additional diagnostic investigations are often needed.3 Medical thoracoscopy (MT), also referred to as pleuroscopy or local anesthesia thoracoscopy, is a minimally invasive technique that allows detailed examination of the pleural space and parietal pleural biopsies.4 The distinction from surgical thoracoscopy is more than semantic: as a general rule, MT is performed by pulmonologists using moderate sedation in spontaneously breathing patients, and may or may not require a hospital stay. The safety profile of MT compares favorably to other procedures routinely performed by pulmonologists, such as bronchoscopy and thoracentesis, and is notably well tolerated by patients. As such, MT is recommended as the method of choice to

Issue Theme Interventional Pulmonology; Guest Editors: David Feller-Kopman, MD, and Lonny Yarmus, DO, FCCP

investigate unexplained exudative pleural effusions after nondiagnostic pleural fluid analysis, allowing targeted pleural biopsies under direct visualization and associated with a diagnostic yield approaching that of more invasive surgical approaches. In addition, when needed, treatment of recurrent pleural effusions can be performed in the same setting, via pleurodesis or insertion of an indwelling pleural catheter. Advanced indications for MT have been proposed, such as lung biopsies, sympathectomy, and treatment of pleural space infections, but these remain anecdotal at best and are thus beyond the scope of this review. As the burden of pleural diseases continues to grow and affects an aging and more complex patient population, MT appears ideally positioned to become an increasingly attractive option for the diagnosis and treatment of unexplained exudative pleural effusions. Herein, we will review the general equipment and techniques used to perform MT, the indications for the procedure as well as its contraindications and reported complications, and discuss its role in commonly encountered clinical situations. While MT remains arguably underutilized by respiratory physicians, the ongoing development and standardization

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Semin Respir Crit Care Med 2014;35:732–743.

of dedicated interventional pulmonology training programs in the United States could foster a more widespread recognition of the technique as a central component of the necessary multidisciplinary approach to pleural diseases.

History Although the first thoracoscopic examination was likely performed in 1866 by Francis Cruise, an Irish physician, on a young patient with empyema, Dr. Hans Christian Jacobaeus, a Swedish internist, is generally recognized as the father of modern thoracoscopy.5 From 1910 into the 1930s, Jacobaeus provided extensive descriptions of the technique, described its indications and contraindications, and generated considerable interest for the procedure in the medical community.5,6 In the pre-antibiotic era, thoracoscopy became central in the treatment of pulmonary tuberculosis, allowing the use of galvanocautery to break down pleural adhesions interfering with therapeutic lung collapse, a standard treatment of tuberculosis at that time. As such, MT was quickly adopted as a popular procedure and became known as the “Jacobaeus operation.”7 With the discovery of streptomycin by Waksman and Schatz in 1943, the main indication for MT became obsolete and its use rapidly declined. Realizing the diagnostic limitations of pleural fluid analysis and closed pleural biopsies, several visionary physicians, such as Brandt and Loddenkemper in Germany and Boutin in France, resurrected MT in Europe in the 1970s, primarily for the purpose of providing quality specimens for the diagnosis of unexplained exudative pleural effusions. The first commercially available flexiblerigid (or “flex-rigid”) thoracoscope was developed in the late 1990s as an appealing alternative to the traditional rigid instruments. Indeed, it offered controls similar to those of flexible bronchoscopes, familiar to most respiratory physicians.8 Over the past two decades, as the incidence of pleural diseases has continued to rise and affect an increasingly fragile population, the interest in MT, viewed as a less invasive and equally-effective alternative to surgical thoracoscopy, has continued to gain popularity among pulmonologists.9 While MT is not commonly performed in the United States, the number of centers offering MT in the United Kingdom has exponentially risen in the past decade from 11 to 37 centers, and the first consensus guidelines for MT were published by the British Thoracic Society in 2010.4

Technique Description A comprehensive medical history should be obtained and a detailed physical examination carefully performed as part of the preprocedural evaluation. Basic laboratory studies should confirm the absence of coagulopathy, and the patient medication list should be thoroughly reviewed to ensure that anticoagulants or antiplatelet agents have been appropriately held before the procedure.10 All available imaging studies should be reviewed, and, when available, a focused pleural ultrasound examination to assess the volume and characteristics of the pleural effusion is strongly encouraged. Pleural

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ultrasound facilitates the identification of an ideal trocar entry site and allows visualization of pleural loculations not easily predictable with standard imaging techniques, such as computed tomography (CT). Extensive adhesions resulting in complex organization of the pleural space will prevent lung collapse and interfere with the procedure. The indications for the procedure always need to be carefully assessed and understood. Procedures unlikely to affect a change in patient management should be avoided. Ideally, all cases should be reviewed in a multidisciplinary fashion by pulmonologists and thoracic surgeons before the procedure.11 Pulse oximetry, noninvasive blood pressure measurements, and electrocardiogram tracing should be monitored continuously throughout the procedure. We also recommend the use of capnometry, as significant hypoventilation has been described during MT, usually as a consequence of oversedation rather than the procedure itself.12 The procedure is typically performed under moderate sedation, usually with the administration of short-acting intravenous benzodiazepines (e.g., midazolam) and opioid medications (e.g., fentanyl). The use of propofol remains controversial in physiciandirected sedation without endotracheal intubation. In a recent study, 90 consecutive patients were randomized to sedation with propofol or midazolam. There were significantly more episodes of hypoxemia (27 vs. 4) and hypotension (82 vs. 40) in the propofol group compared with the midazolam group. As such, propofol should generally be avoided as firstline sedation agent.13 Intubation is generally not required, as the patient remains awake and spontaneously breathing throughout the procedure, but anesthesia support and a fully equipped resuscitation cart should be readily accessible. Surgical backup is mandatory and should be immediately available, in case complications requiring conversion to thoracotomy were to occur. Supplemental oxygen is administered via nasal cannula or facemask as needed. Generous administration of local anesthesia to all four layers (epidermis, aponeurosis, intercostal muscle, and parietal pleura) is of paramount importance and can substantially reduce the amount of sedation required. If talc poudrage is performed, the patient may require increased pain control and sedation, and some advocate the use of lidocaine spray (1% lidocaine using a spray catheter inserted in the working channel) before talc administration. The patient is positioned in the lateral decubitus position with the pleural space to be investigated facing upward. The procedure is typically performed with the proceduralists facing the patient to allow optimal exposure of the posterior parietal pleura. ►Fig. 1 shows a typical equipment setup for MT. Ultrasound, when available, should be used to identify a point of entry, typically located in the mid- to anterior axillary line, in the fifth to seventh intercostal spaces when malignant pleural effusion (MPE) is suspected and the third to fourth intercostal spaces for pneumothorax (so that apical blebs may be visualized during the procedure). The thoracoscope entry site is then anesthetized as described earlier. If no pleural effusion is visible, which is often the case in the lateral decubitus position, a Boutin needle with real-time ultrasound guidance is used to allow creation of a pneumothorax, Seminars in Respiratory and Critical Care Medicine

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Fig. 1 Typical equipment and setup for medical thoracoscopy including flexible-rigid scope (right image).

allowing safe entry in the pleural space. In this situation, the absence of a sliding sign on ultrasound examination suggests the possibility of a fused pleural space, and an alternative approach, such as video-assisted thoracoscopic surgery (VATS) or image-guided biopsies, should be considered. In some instances, trained pulmonologists may decide to perform real-time ultrasound-guided cutting needle biopsies in the same setting, which were recently shown to provide useful information in the majority of technically difficult MT procedures.14 A small skin incision followed by blunt dissection is performed to introduce the trocar in the pleural space. The thoracoscope can then be safely inserted and the pleural fluid evacuated, allowing inspection and other interventions in the pleural space. Upon completion of the procedure, a chest tube drain is inserted through the tract into the pleural space and connected to a water seal device with suction. Alternatively, a small bore chest tube or a tunneled indwelling pleural catheter (TIPC) may be placed under direct visualization at a different site. The patient is allowed to rest while the lung reexpands and a chest X-ray is performed to confirm reexpansion of the lung. If there is no air leak, the chest tube can be removed unless talc pleurodesis was performed or a TIPC inserted. Patients are generally admitted for observation, although outpatient MT has been shown to be feasible and safe (see later).11 Biopsies of the parietal pleura are generally safe as long as certain rules are followed. Conveniently, most pleural abnormalities are localized in the inferior portion of the posterior parietal pleura, an area devoid of large blood vessels and easily accessible to MT, mitigating the risk of biopsy-induced bleeding.15 To avoid intercostal vessels, the ribs should be palpated first with closed forceps, and then the parietal pleura should be grasped over the rib, or on its superior surface, and peeled to provide large biopsy samples. The same technique is used during rigid and flex-rigid thoracoscopy. The apices of the lungs and the anterior parietal pleural should be avoided due to the presence of major arteries (subclavian and internal mammary arteries, respectively). Likewise, the highly vascularized diaphragmatic pleura should generally be avoided, and if biopsies are necessary, we recommend the use electrocautery forceps. In spite of Seminars in Respiratory and Critical Care Medicine

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these precautions, bleeding complications remain possible, but can generally be managed by external compression of the intercostal space, internal compression with closed forceps holding folded gauze, and electrocauterization of the bleeding site (which may require a second port of entry). Rarely, conversion to thoracotomy with ligation of the bleeding vessels is required, highlighting the need for surgical backup.

Outpatient Medical Thoracoscopy The absence of a minimally invasive alternative to surgery for pleural biopsies in patients without focal lesions amenable to image-guided biopsy led us to initiate an outpatient MT program as part of a collaborative effort between interventional pulmonology and thoracic surgery. In a recently published study,11 outpatient MT was performed in 51 consecutive patients with undiagnosed exudative pleural effusions without major complications, as previously defined by Colt.16 Three patients had to be admitted for pain management (n ¼ 2) and confusion after the procedure (n ¼ 1). Procedural time averaged 40 minutes (range, 19–75) and the procedure-related health care visit time was 294 minutes (range, 174–479). The procedure was generally well tolerated, and this study suggests that outpatient MT may represent a safe alternative to either observation or surgical pleural biopsies in patients with undiagnosed exudative pleural effusion.

Contraindications The safety record of MT compares favorably with other procedures commonly performed by pulmonologists, with a mortality rate estimated at 0.34% (95% confidence interval, 0.19–0.54%),4 but few contraindications should be considered (►Table 1). The only absolute contraindication specific to MT is the absence of a pleural space such as in the setting of dense pleural adhesions or previous pleurodesis. Other absolute contraindications are similar to those of other elective diagnostic procedures and include hemodynamic instability, severe hypoxemia, uncorrectable coagulopathy, lack of informed consent, inexperienced operator, inadequate facility (including absence of surgical or anesthesia backup), or inability to tolerate sedation. Relative contraindications


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Medical Thoracoscopy Table 1 Contraindications to medical thoracoscopy

suggested in elsewhere.10

expert

recommendations

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summarized

Absolute contraindications

Hemodynamic instability Severe untreated hypoxemic or hypercapnic respiratory failure Uncorrectable coagulopathy Lack of informed consent Inexperienced operator or inadequate facility (including absence of surgical or anesthesia backup) Inability to tolerate sedation or allergy to sedation medications Relative contraindications Severe cardiopulmonary disease such that the patient may have difficulty tolerating unilateral lung collapse Very severe obesity Bleeding diathesis Intractable cough

include respiratory insufficiency such that the patient may have difficulty tolerating unilateral lung collapse (unless a large pleural effusion is the main cause for the dyspnea), bleeding diathesis, very severe obesity, which makes access to the pleural space difficult, or intractable cough. A platelet count of >60 103/µL and an international normalized ratio of 60,000/µL

International normalized ratio

3.0 mg/dL

Medications Aspirin

Interval between last dose and MT10 No need to withhold

Unfractionated heparin Intravenous infusion

6h

Subcutaneous (DVT prophylaxis)

12 h

Subcutaneous (therapeutic)

24 h

Low-molecular-weight heparin (subcutaneous)

24 h

Clopidogrel (Plavix)

5d

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Absence of a pleural space such as in the setting of dense pleural adhesions


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Fig. 2 Forceps biopsy of a pleural abnormality. Note that pleura is being peeled laterally to obtain large sample. Picture courtesy of Philippe Astoul.

either rigid or flex-rigid thoracoscopy may be appropriate in specific clinical situations. The primary advantage of the flexrigid scope is its increased maneuverability within the pleural space, particularly when the induced lung collapse is incomplete or when dense adhesions are present. This flexibility may allow a more exhaustive inspection of the pleura and is probably better tolerated than rigid thoracoscopy when moderate sedation is used. Rigid thoracoscopy requires substantial angulation of the trocar against the ribs, which may occasionally result in significant discomfort for patients from the pressure imposed on the periosteum and intercostal nerve.19 The main disadvantage of the flex-rigid scope is that only flexible instruments small enough to fit through the working channel of the scope can be used to obtain samples and perform interventions. These small biopsy samples could theoretically negatively impact the diagnostic yield of the procedure, particularly when malignant pleural mesothelioma (MPM) is suspected. Several techniques have been proposed to increase the size of biopsies obtained via flex-rigid thoracoscopy: the use of an electrocautery knife with insulated tip to carve out full-thickness parietal pleural biopsies was shown to increase the diagnostic yield from 60 to 85% in one study.20 Cryobiopsies using flexible cryoprobes (Erbe, Tubingen, Germany) have been proposed in the case of nodular metastases and the technique is currently under evaluation (http://clinicaltrials.gov/show/NCT01472172). One relatively straightforward method harnesses the advantages of both rigid and flex-rigid techniques by using a second port of entry to introduce rigid forceps in the pleural space, using the flex-rigid thoracoscope for visualization only. Most of the literature published describes rigid rather than flex-rigid thoracoscopy. However, limited data suggest that flex-rigid thoracoscopy may have a safety profile and diagnostic yield similar to rigid thoracoscopy.21 In patients with pleural effusions of unknown cause, case series of flex-rigid thoracoscopy have reported a diagnostic yield ranging from 88 to 98% depending on the population studied.22–25 Talc poudrage with the flex-rigid scope has also been described.23 Seminars in Respiratory and Critical Care Medicine

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Rigid thoracoscopy provides larger biopsy samples and thus might be expected to have a better diagnostic yield, but it is unclear whether this is indeed the case. One prospective study included 66 patients who underwent 39 flex-rigid and 27 rigid thoracoscopies. The diagnostic yield (92.3 vs. 96.3%, respectively) was not significantly different between the two techniques.26 Two randomized controlled trials have also been reported. One study included 90 patients and showed a similar safety profile for both techniques, but the diagnostic yield for pleural biopsies performed with rigid thoracoscopy was significantly better than that of flex-rigid thoracoscopy (97.8 vs. 73.3%, respectively). The size of biopsies obtained during rigid thoracoscopy was also significantly larger than during flex-rigid thoracoscopy (mean standard deviation, 13.9 4.4 mm vs. 4.4 1.4 mm, respectively). However, a substantial number of patients crossed over to the rigid group, and after excluding patients in whom pleuroscopy was not technically feasible due to dense adhesions, the yield was in fact similar for both techniques.19 In another randomized study that included 84 patients, there was no significant difference between rigid and flex-rigid thoracoscopy with high (98–100%) diagnostic yield in both groups, though biopsy samples were twice as large with rigid compared with flex-rigid thoracoscopy (24.7 mm2 12.9 vs. 11.7 mm2 7.6, respectively).25 However, both studies were limited by small sample size and limited power, and it is our opinion that in selected situations, such as in the case of a high pre-test probability of MPM, for example, larger biopsy samples may be preferable.

Comparison to Video-Assisted Thoracoscopic Surgery There are no head-to-head comparisons between MT and VATS for the diagnosis of unexplained exudative pleural effusions. Nonetheless, a recent review of the literature published to date suggests that both techniques may have very similar yields. It is, however, important to understand the fundamental differences between MT and VATS (►Table 3). The terminology is somewhat misleading in that both MT and VATS are video-assisted techniques that allow exploration of the pleural space. However, VATS is generally regarded as a surgical procedure performed under general anesthesia with double-lumen intubation and single lung ventilation requiring at least three entry ports, and allows a broad range of interventions beyond simple biopsies of the parietal pleura and pleurodesis. Conversely, MT is typically performed in an awake, spontaneously breathing patient under moderate sedation through one or two entry ports at most. There is admittedly considerable overlap between the two techniques. For instance, VATS has been described in awake patients with moderate sedation,27 while advanced procedures such as adhesiolysis, lung biopsies, and even sympathectomy for hyperhidrosis, which usually require general anesthesia and endotracheal intubation, have been described with MT.4 For the vast majority of pulmonologists and thoracic surgeons, however, the usual definitions hold and are used in this review. Ideally, VATS and medical pleuroscopy should be considered as complementary procedures with overlapping but


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Table 3 Comparison between VATS and MT VATS

MT

Performed by a surgeon

Performed by an interventional pulmonologist

General anesthesia

Moderate sedation

Operating room

Endoscopy suite or operating room

Double lumen intubation with single-lung ventilation

Spontaneously breathing patient

At least three entry ports

One or two entry ports

Common indications: pleural inspection, pleural biopsy, pleurodesis, lung wedge resection, lobectomy, decortication, esophageal surgeries, and pericardial window

Common indications: pleural inspection, pleural biopsy, pleurodesis

mostly distinct indications. Pleural biopsies and pleurodesis can be performed by either VATS or MT. As discussed, VATS permits a wider range of interventions including lung wedge resection, lobectomy, decortication, esophageal surgeries, and pericardial window.28 A distinct advantage of VATS is the ability to convert to open thoracotomy if needed, in case access to the pleural space is not possible. The primary advantage of MT is that it is a less invasive procedure compared with VATS, which can be performed safely in the outpatient setting. The cost of MT is generally believed to be less than that of VATS, although no formal cost-effectiveness study is available at this time.

Diagnostic Indications Recurrent Exudative Effusions MT is often indicated to investigate undiagnosed recurrent exudative pleural effusions. Pleural effusions have been estimated to arise in nearly 0.5% in the general population,29 and approximately 25% of pleural effusions will remain undiagnosed even after careful history, physical examination, and pleural fluid analysis.30 More than half of exudative pleural effusions will be proven to be malignant in the Western world. Yet, the overall sensitivity of pleural fluid analysis for MPEs is only 60%, and only increases by 15% after a second procedure.31 In Bayesian terms, considering a pre-test prob-

ability of 50% for MPE (and assuming a specificity of 100% for thoracentesis), the post-test probability for malignancy after a negative thoracentesis will still be approximately 25%. Additional investigations are clearly warranted in this situation. Furthermore, while debated, it is our belief that the diagnosis of MPM cannot reliably be established by cytology only. Image-guided pleural biopsies (via CT or ultrasound) may represent suitable alternatives in the case of focal pleural abnormalities, but are of limited value otherwise. And aside from pleural tuberculosis, which is characterized by evenly distributed pleural lesions, closed (blind) pleural biopsies demonstrate low diagnostic yield and have generally fallen out of favor.32 MT allows for visual inspection of the entire pleural space, has a very high diagnostic yield exceeding 90% in most published series, and therefore represent an attractive next step after a negative thoracentesis. As such, the recently published British Thoracic Society guidelines recommended MT as the standard diagnostic test in any patient with exudative pleural effusion when the diagnosis remains uncertain after thoracentesis.4,31

Diagnostic Yield in Malignant Pleural Effusion Most patients presenting with MPE should initially undergo simple thoracentesis, unless it is recurrent and a definitive treatment is desirable in the same setting. The diagnostic sensitivity of thoracentesis in MPE has recently been reviewed

Table 4 Comparison of diagnostic yield in malignant pleural effusion Procedure

Diagnostic yield in malignant pleural effusion

Medical thoracoscopy

92.7%4

VATS under general anesthesia

95%35

CT-guided pleural biopsy

87%37

Thoracentesis

60%31

Second thoracentesis

75% (cumulative yield)4

Third thoracentesis

Does not improve cumulative yield4

Closed (“Blind”) pleural biopsy

57%31,91

Abbreviations: CT, computed tomography; VATS, video-assisted thorascopic surgery. Seminars in Respiratory and Critical Care Medicine

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Abbreviations: MT, medical thoracoscopy; VATS, video-assisted thorascopic surgery.


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and estimated around 60%, with an modest 15% increase after a second procedure.31 Repeating a third thoracentesis does little to improve the yield.33 With over 200,000 new patients presenting with a malignant effusion each year in the United States alone, this is a common diagnostic dilemma.34 Most MPEs are due to lung and breast cancer, followed by lymphoma, gastrointestinal, and genitourinary cancers. MT is a highly effective procedure to diagnose MPE when simple thoracentesis does not establish a diagnosis (►Table 4). A review of 22 studies including a total of 1,369 patients reported a pooled diagnostic sensitivity of 92.6% for MT in MPE.4 This overall sensitivity is similar to that of VATS performed under general anesthesia.4,35,36 A major advantage of MT compared with closed pleural biopsies, or imageguided biopsies when no focal abnormalities are easily identified, is that the physician can visualize the pleura and selectively target areas with abnormal appearance. Malignant involvement of the pleura is often “patchy” with abnormal areas interspersed within normal pleural tissue (►Fig. 3). In addition, the majority of pleural abnormalities are preferentially located on the most inferior portion of the posterior parietal pleura, in close proximity to the diaphragm. This location is unlikely to be chosen for obvious technical reasons

during closed or “blind” pleural biopsy, such as those performed with an Abrams needle.15 Performing a pleural biopsy under CT guidance may improve the diagnostic yield, and sensitivity in malignant pleural disease has been reported to be as high as 87%; however, the sensitivity is decreased unless the patient has an abnormal area of pleura visible on CT that is > 5mm in thickness.37 Even with the use of high-resolution CT imaging, many patients with malignant effusion do not have focal pleural abnormalities that can be easily identified. As such, MT, offering a “window into the pleural space,” allows a comprehensive examination of the parietal pleura and biopsy of subtle abnormalities below the definition of currently available imaging techniques. Advanced endoscopic image processing has also been proposed to enhance the diagnostic yield of MT. Autofluorescence pleuroscopy and narrow-band imaging have been extensively studied as adjunct technology in the bronchoscopic evaluation of premalignant lesions in the tracheobronchial tree, but have so far been found of limited practical utility in the diagnosis of MPE.38,39

Malignant Pleural Mesothelioma MPM can be particularly challenging to diagnose without the use of thoracoscopy. It is often difficult to differentiate malignant cells suspended in the pleural fluid from benign inflammatory mesothelial cells or other types of malignancy.40 The diagnosis of MPM in general requires the acquisition of sizable and deep biopsies with evidence of invasion on histology. This explains the relatively poor yield of simple thoracentesis for the diagnosis of mesothelioma, ranging at best from 26 to 32%.41,42 Thoracentesis followed by closed pleural biopsy only increases the net diagnostic yield to 39%.41 Conversely, MT is highly effective for tissue acquisition in the diagnosis of MPM. In one case series of 188 patients with mesothelioma, the diagnostic sensitivity of MT was 98.4%.41 In addition, MT allows treatment of recurrence in the same setting, either via talc pleurodesis or TIPC insertion. One caveat with TIPC in the setting of MPM is the high reported rate of metastatic seeding of the tract, estimated between 5 and 10%.43 Prophylactic irradiation has been proposed to mitigate this problem and typically consists of 21 Gy in three fractions, although the evidence supporting its routine use is debated.44,45

Nonspecific Pleuritis The problem of false-negative thoracoscopic pleural biopsies should be briefly mentioned. Nonspecific, or so-called idiopathic, pleuritis is identified in approximately 25% of thoracoscopic pleural biopsies, and 5 to 10% of these patients are ultimately found to develop malignancy, specifically MPM. For this reason, the diagnosis of nonspecific pleuritis should be considered provisional and one of exclusion, and appropriate follow-up imaging for at least a year is strongly recommended.46,47 Fig. 3 Malignant disease involving the pleura as viewed during medical thoracoscopy. Panel A shows malignant mesothelioma. Panel B shows metastatic breast cancer with pleural studding. Note patchy nature of involvement with abnormal nodules interspersed between normal appearing pleura. Pictures courtesy of Philippe Astoul. Seminars in Respiratory and Critical Care Medicine

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Tuberculosis MT has been used in patients with tuberculosis since its inception, and remains a very useful tool for the diagnosis of


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Other Diagnostic Indications: Diffuse Parenchymal Lung Diseases Diffuse parenchymal lung diseases (DPLD) encompass a vast and heterogeneous group of diseases with variable etiologies, natural history, clinical and radiologic manifestations, and response to treatment. Idiopathic pulmonary fibrosis is a relentless fibrotic lung disease that accounts for the majority of these diseases, and, until recently, had no proven effective treatment. While high-resolution CT has revolutionized the diagnosis of DPLDs, the diagnosis often relies on adequate lung biopsy specimens when CT findings are atypical. Traditionally, VATS biopsies have been recommended, but are often associated with prohibitive complications such as acute exacerbations, and a mortality rate approaching 15% in some studies.52 As such, alternative approaches have been proposed. Lung biopsies obtained via MT were prospectively evaluated by Vansteenkiste and colleagues in a study that included 118 biopsy samples from 24 consecutive patients.53

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These biopsies were obtained with diathermy coagulation cup forceps during rigid thoracoscopy with an adequate diagnosis established in 22 of 24 patients. No complications were observed. Combining these results with those of two older retrospective studies, the diagnostic yield of MT lung biopsies is approximately 90%.54,55 While encouraging, the absence of comparison with the gold standard of surgical lung biopsy limits the clinical relevance of these findings, and the evidence for lung biopsy obtained during MT remains anecdotal at best. In addition, peripheral cryobiopsy techniques via flexible bronchoscopy have recently been shown to be both safe and effective and could potentially replace thoracoscopic biopsies in the near future.56

Therapeutic Indications Malignant Effusions Dyspnea due to MPE can be a debilitating problem for patients with malignancy. MPEs are common, occurring in up to 15% of all patients who die of malignancy,57 and generally portend a poor prognosis, with a median survival ranging approximately from 4 to 10 months depending on the type of malignancy.58–60 Simple therapeutic thoracentesis often results in symptom relief, but the dyspnea commonly recurs as the malignant effusion reaccumulates. More definitive techniques, such as pleurodesis and placement of a TIPC, have been described to achieve sustained palliation of symptomatic malignant effusions. The relative efficacy of these techniques has been extensively debated, and presently no single technique is felt to be uniformly superior for all patients with symptomatic malignant effusion.61–64 Either pleurodesis or placement of an indwelling pleural can be performed with or without the assistance of MT. Pleurodesis during MT is generally performed using talc poudrage, which is supported by a large body of evidence.4 Although the choice of sclerosing agents remains debated, talc is usually recognized as the superior sclerosing agent for pleurodesis as supported by several meta-analyses.65,66 Talc poudrage refers to thoracoscopic talc insufflation (TTI) under direct visualization. This technique allows for a more uniform distribution of talc particles across the pleural surfaces, which should theoretically result in a more predictable pleurodesis compared with talc slurry (TS) instilled blindly into the pleural space via a chest tube, but this has not been clearly demonstrated in clinical trials. The largest randomized controlled trial of TS versus talc poudrage for pleurodesis in MPE included 482 patients randomized to TTI (n ¼ 242) or TS (n ¼ 240). The study reported similar outcomes in the two groups, defined as successful pleurodesis at 30 days, achieved in 78% of patients in the TTI group compared with 71% in the TS group. The study, however, suffers from significant methodological flaws, and has been extensively discussed. The main issue is the exclusion from analysis after randomization of patients deemed ineligible for the study (due to poor lung reexpansion preventing apposition for pleural surfaces, a sine qua non for successful pleurodesis) and those who died during the 30-day period. In subgroup analyses, patients with breast and lung cancer fared better with talc poudrage, Seminars in Respiratory and Critical Care Medicine

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tuberculosis pleuritis. Pleural effusions are a relatively common manifestation of tuberculosis accounting for approximately 5% of initial presentations. They result from a Th1driven immune reaction to the mycobacteria and should be distinguished from tuberculous empyema, which is comparatively very rare. The diagnosis of tuberculous pleuritis may be challenging with simple thoracentesis, often requiring the performance of additional pleural fluid tests such as adenosine deaminase (ADA), which must be interpreted in the context of the patient’s pre-test probability of disease.31,48,49 Closed or “blind” pleural biopsies, such as those performed with an Abrams needle, have historically been the next step when there is diagnostic uncertainty after thoracentesis.48,50 Unlike in malignant pleural disease, blind pleural biopsies remain a reasonably sensitive test in endemic areas, as tuberculous pleuritis is generally homogeneously distributed on the pleural surface. Nonetheless, the diagnostic yield is widely variable and ranges from 60 to 80% at best, indicating that some patients will remain undiagnosed even after closed pleural biopsy.32,49 Furthermore, following a sharp decline in tuberculosis in the developed world, fewer pulmonary physicians are adequately trained in the performance of closed pleural biopsy.50 MT with pleural biopsies is a highly effective test for the diagnosis of tuberculous pleuritis. The sensitivity is 93.3% when performed in regions with low prevalence of tuberculosis.4 The sensitivity is likely even higher in areas with high prevalence. One prospective study that included 51 patients (tuberculous pleurisy, n ¼ 42; MPE, n ¼ 5; and idiopathic pleurisy, n ¼ 4) performed in an endemic area reported a diagnostic sensitivity of 100% for MT compared with 79% for blind pleural biopsy when both histology and microbiology were combined.51 Interestingly, the addition of a high pleural fluid ADA level to closed pleural biopsies yielded a sensitivity of 93%, and may represent an interesting option in endemic areas with limited access to MT. All three methods had 100% specificity. These results again highlight the fact that MT is a highly useful test in recurrent exudative pleural effusions when simple thoracentesis does not establish a diagnosis.

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but for the same reasons, these results should be considered hypothesis generating at best.67 Another issue raised with this study was the very high rate of complications observed, with a total of 11 respiratory-related deaths noted. Possible explanations include the use of surgical thoracoscopy rather than MT (which implies that additional interventions were performed besides talc pleurodesis) and the use of nongraded talc, which has been associated with rare but potentially catastrophic episodes of acute respiratory distress syndrome.68,69 Two large prospective European studies have since established the safety of graded talc in the treatment of MPE and pneumothorax.70,71 A study reevaluating the respective roles of TTI and TS is currently underway (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID¼12537). Regardless, for eligible patients, talc poudrage performed during MT is an effective option for the treatment of malignant effusion and has generally good results with approximately 77 to 100% of patients achieving pleurodesis.4 Placement of a TIPC, such as Pleurx (CareFusion, San Diego CA), Aspira (Bard, Salt Lake City, UT), or Rocket (Rocket Medical, Tyne and Wear, England), is another option for the treatment of malignant effusion during MT. A TIPC is a silastic fenestrated pleural drain that allows as-needed self-drainage of recurrent pleural effusions. It can remain in place indefinitely and is tunneled to reduce the risk of infection or accidental dislodgement. One advantage of TIPCs is the ability to provide symptom relief in patients with partially or nonexpandable lungs that prevent adequate apposition of the visceral and parietal pleural surfaces, and are by definition unsuitable for talc pleurodesis. Another key advantage of TIPCs compared with pleurodesis is that patients do not need to remain in the hospital overnight following the procedure, and several studies have demonstrated reduced hospital stay even after the initial treatment, a desirable endpoint in patients with limited life expectancy.61,64 Thus, selected patients with recurrent exudative effusion who undergo MT diagnosed with malignant effusion can benefit in the same setting from TIPC placement in a single outpatient procedure. The rate of “spontaneous pleurodesis” after TIPC placement is approximately 50%, though may approach that of talc pleurodesis in good candidates for talc pleurodesis.72,73 While purely hypothetical, it is possible that the inflammation and bleeding resulting for pleural biopsies during MT may improve these numbers further. Preliminary data suggest that combining the benefits of talc pleurodesis and TIPC placement may be possible, limiting both hospitalization time and hastening withdrawal of the TIPC, and could represent an attractive option for these patients in the future.74,75

Pneumothorax With approximately 20,000 new cases diagnosed yearly in the United States, spontaneous pneumothorax is another common clinical problem that, in some cases, can be managed with MT. Spontaneous pneumothorax may be primary, occurring in a patient with no underlying lung disease, or secondary, occurring in the setting of a predisposing lung disease. Generally, first-line treatment consists Seminars in Respiratory and Critical Care Medicine

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of aspiration or chest tube drainage, but when the pneumothorax is recurrent or in the case of persistent air leak, pleurodesis may be indicated.76 A variety of sclerosing agents have been described with talc and tetracycline being the most studied, with perhaps a small advantage for talc. The reported recurrence rate after pleurodesis via TS is approximately 10%, clearly inferior to surgical approaches that reduce the recurrence rate below 5%. The best approach, however, remains a matter of intense debate in the pleural community. A consistent finding during thoracoscopy performed for treatment of pneumothorax is the presence of apical subpleural blebs or bullae, which are thought to contribute to the pathophysiology of the disease. As such, it has been traditionally accepted that resection of these lesions should be performed before pleurodesis. Interestingly, fluorescein-enhanced autofluorescence thoracoscopy (after inhalation of fluorescein) suggests that diffuse visceral pleural lesions may be responsible for the air leak (so-called pleural porosity) rather than the blebs identified during pleural examination. 77 A previous study suggested that simple talc pleurodesis via MT may suffice in the treatment of pneumothorax unless blebs > 2 cm are present, in which case blebectomy should be considered.78 An ongoing European trial comparing simple talc pleurodesis to standard surgical approach has nearly completed enrollment and should provide definitive data in the near future (http:// clinicaltrials.gov/ct2/show/NCT00767962). Multiple studies have evaluated MT with talc poudrage in patients with pneumothorax, generally with good results. One case series reported 95% long-term success rate over 5 years with no significant complications.78 Another study randomized patients with primary spontaneous pneumothorax to early MT with pleurodesis or simple chest tube drainage.79 There were no significant adverse events, and the MT group had a lower rate of recurrence of pneumothorax after 5 years (5 vs. 34%) as well as lower overall cost of medical care.79 Chronic obstructive pulmonary disease and emphysema are the most common cause of secondary pneumothorax.80 Patients with severe emphysema are at higher risk for spontaneous pneumothorax and nonresolving air leak resulting in prolonged hospitalization.81 Because of their severe underlying lung disease, these patients are often suboptimal candidates for VATS or open thoracotomy, which require general anesthesia with single lung ventilation. MT under moderate sedation is therefore a potentially appealing treatment option for these high-risk patients. One case series evaluated MT for the treatment of secondary spontaneous pneumothorax in severe obstructive lung disease.82 Although the authors reported a 95% long-term success rate in achieving pleurodesis, almost 10% of the patients died within 30 days (all with FEV1 < 40% predicted).82 By comparison, studies of VATS with pleurodesis for spontaneous pneumothorax in patients with moderate-to-severe emphysema have reported mortality ranging from 5 to 9%.83,84 Further randomized controlled studies are needed to determine whether MT offers advantages in patients with secondary pneumothorax who are poor surgical candidates due to severe COPD.


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MT has been suggested as a potential treatment for empyema. In general, the initial treatment of empyema consists of antibiotics and chest tube drainage to evacuate the pleural space. When chest tube drainage is unsuccessful due to loculations and organization of the pleural space, surgical approaches are recommended.85 MT is an interesting alternative to surgery and has been the object of several studies with encouraging preliminary results. In 1995, Colt reported success in treatment of empyema in six of seven patients (including four who had failed chest tube drainage) who underwent MT.16 A larger case series of 127 patients with loculated empyema who underwent MT reported a 91% success rate in evacuation of the empyema, with success defined as no further invasive procedure required after the MT.86 Only 6% of patients in this case series ultimately required more invasive surgery. Overall, the role of MT in the treatment of pleural space infections remains unclear and cannot be recommended in the absence of more definitive data, particularly in light of recent data, suggesting an expanded role for medical therapy in pleural space infections using a combination intrapleural therapy.87 Other advanced therapeutic interventions can be performed via MT. Thoracic sympathectomy for conditions such as hyperhidrosis has been performed via MT with good result.88,89 Pericardial window and splanchnicectomy performed by advanced medical thoracoscopists have also been rarely described, but these procedures are performed under general anesthesia in an operating room and thus are beyond the scope of this article.7

diagnostic test for recurrent exudative pleural effusions when simple thoracentesis fails to establish a diagnosis. MT has also been established as a safe and effective method to perform talc poudrage pleurodesis for malignant effusions or pneumothorax. As the burden of pleural diseases continues to grow and affect an increasingly aging and fragile patient population, MT appears uniquely positioned to address some of the diagnostic and therapeutic challenges facing respiratory physicians. MT answers the diagnostic gap between nondiagnostic thoracenteses and surgical pleural biopsies, and can be performed safely in the outpatient setting with a diagnostic yield that compares favorably with that of surgical thoracoscopy. While it remains arguably underutilized, the ongoing development of interventional pulmonology training programs around the United States and the world will likely result in the more widespread dissemination of the technique.

References 1 Light RW. Clinical practice. Pleural effusion. N Engl J Med 2002;

346(25):1971–1977 2 Lee P, Colt HG. Rigid and semirigid pleuroscopy: the future is

bright. Respirology 2005;10(4):418–425 3 Collins TR, Sahn SA. Thoracocentesis. Clinical value, complications,

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MT has a safety profile that compares favorably with that of other procedures commonly performed by pulmonologists. The mortality rate is extremely low. A review of 4,736 thoracoscopies across 47 published studies reported an overall 0.3% periprocedural mortality rate, with all deaths occurring in patients who received talc poudrage, raising the possibility of talc-related respiratory complications.4,16,23 Complications resulting in need for open surgery are also extremely rare.23 Other major complications can include prolonged air leak, hemorrhage, subcutaneous emphysema, empyema, wound infection, and complications related to the moderate sedation such as arrhythmia or hypotension. The incidence of major complication during MT is approximately 1.8%.4 Flex-rigid thoracoscopy is a relatively newer technique that may be even safer than rigid thoracoscopy. A metaanalysis of 17 studies involving 755 patients reported no periprocedure mortality and a 1.5% rate of major complications.90

Conclusion MT is a safe and highly effective procedure for patients with pleural abnormalities or pleural effusion and can be performed by trained pulmonologists on an outpatient basis. There is strong evidence to support the use of MT as a definitive

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Skalski et al.

Sudden death during medical thoracoscopy.

Medical thoracoscopy: rigid thoracoscopy or flexi-rigid pleuroscopy?

Medical thoracoscopy: the green shapes of grey.

pleuroscopy: is it underutilized?

The role for medical thoracoscopy in pneumothorax.

Safety and Complications of Medical Thoracoscopy.

Evolution of medical thoracoscopy in developing countries.

Diagnostic value of medical thoracoscopy in malignant pleural effusion.

Ultrasound-guided medical thoracoscopy in the absence of pleural effusion.

Propofol: is it really worse than midazolam in medical thoracoscopy?

Diagnostic Yield of Medical Thoracoscopy in Undiagnosed Pleural Effusion.

Thoracoscopy: medical versus surgical-in the management of pleural diseases.

Medical thoracoscopy in China-the present status and the future.

Medical thoracoscopy for the treatment of complicated hepatic hydrothorax.

Thoracoscopy.

Thoracoscopy forum: continuing dialogue.

Who should perform thoracoscopy?

Role of medical thoracoscopy in the treatment of tuberculous pleural effusion.

Thoracoscopy in children.

Application of medical thoracoscopy in diagnosis of sarcoidosis-related pleural effusion.

Thoracoscopy forum: continuing dialogue.

Thoracoscopy forum: continuing dialogue.

Medical Thoracoscopy in Pleural Disease: Experience from a One-Center Study.

Anesthetic drugs managed by pulmonologists during medical thoracoscopy: one size does not fit all!