0
Original Research: Disorders of the Pleura |

Physician-Based Ultrasound-Guided Biopsy for Diagnosing Pleural DiseaseSuccessful Ultrasound-Guided Biopsy by Physicians FREE TO VIEW

Robert J. Hallifax, BMBCh; John P. Corcoran, BMBCh; Asia Ahmed, BMBCh; Myura Nagendran, BMBCh; Hussam Rostom, BMBCh; Neelam Hassan, BMBCh; Mahiben Maruthappu, BMBCh; Ioannis Psallidas, PhD; Ari Manuel, BMBCh; Fergus V. Gleeson, PhD, FCCP; Najib M. Rahman, PhD
Author and Funding Information

From the Oxford Centre for Respiratory Medicine (Drs Hallifax, Corcoran, Psallidas, Manuel, and Rahman), Oxford Respiratory Trials Unit (Drs Hallifax, Corcoran, Psallidas, Manuel, and Rahman), and Department of Radiology (Drs Ahmed and Gleeson), Churchill Hospital, Oxford; and the University of Oxford Clinical Medical School (Drs Nagendran, Rostom, Hassan, and Maruthappu), Oxford, England.

CORRESPONDENCE: Robert J. Hallifax, BMBCh, Oxford Respiratory Trials Unit, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, England; e-mail: robhallifax@yahoo.com


FUNDING/SUPPORT: This research was supported by the National Institute for Health Research Oxford Biomedical Research Centre, The Oxford University Hospitals Trust, University of Oxford.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1001-1006. doi:10.1378/chest.14-0299
Text Size: A A A
Published online

BACKGROUND:  Definitive diagnosis of pleural disease (particularly malignancy) depends upon histologic proof obtained via pleural biopsy or positive pleural fluid cytology. Image-guided sampling is now standard practice. Local anesthetic thoracoscopy has a high diagnostic yield for malignant and nonmalignant disease, but is not always possible in frail patients, if pleural fluid is heavily loculated, or where the lung is adherent to the chest wall. Such cases can be converted during the same procedure as attempted thoracoscopy to cutting-needle biopsy. This study aimed to determine the diagnostic yield of a physician-led service in both planned biopsies and cases of failed thoracoscopy.

METHODS:  This study was a retrospective review of all ultrasound-guided, cutting-needle biopsies performed at the Oxford Centre for Respiratory Medicine between January 2010 and July 2013. Histologic results were assessed for the yield of pleural tissue, final diagnosis, and clinical follow-up in nonmalignant cases.

RESULTS:  Fifty ultrasound-guided biopsies were undertaken. Overall, 47 (94.0%) successfully obtained sufficient tissue for histologic diagnosis. Of the 50 biopsy procedures, 13 were conducted after failed thoracoscopy (5.2% of 252 attempted thoracoscopies over the same time period); of these 13, 11 (84.6%) obtained sufficient tissue. Thirteen of 50 biopsy specimens (26.0%) demonstrated pleural malignancy on histology (despite previous negative pleural fluid cytology), while 34 specimens (68.0%) were diagnosed as benign. Of the benign cases, 10 were pleural TB, two were sarcoidosis, and 22 were benign pleural thickening. There was one “false negative” of mesothelioma (median follow-up, 16 months).

CONCLUSIONS:  Within this population, physician-based, ultrasound-guided, cutting-needle pleural biopsy obtained pleural tissue successfully in a high proportion of cases, including those of failed thoracoscopy.

Figures in this Article

Pleural disease is common, affecting > 300 people per 100,000 of the population each year.1 The definitive diagnosis of pleural malignancy depends upon histologic proof obtained via pleural biopsy. A number of techniques are available to acquire tissue, from closed-needle biopsy (either Abram’s needle or cutting-needle biopsy), with or without image guidance, to local anesthetic thoracoscopy (LAT) (also known as “medical thoracoscopy”). LAT has a high diagnostic yield for malignancy: 91% to 97%.24 Image-guided sampling is now standard practice,1 as unaided (blind) pleural biopsies have a diagnostic yield of < 60% for pleural malignancy.5 LAT is not always possible; the patient may be too frail to attempt the procedure, pleural fluid may be heavily loculated, or the lung may be adherent to the chest wall (Fig 1). In these cases, achieving an adequate working space in which to safely perform LAT may be suitable only for advanced practitioners or thoracic surgeons.

Figure Jump LinkFigure 1 –  Thoracic ultrasound showing PT and LT. Dynamic ultrasound imaging would show a lack of normal lung sliding. PT = pleural thickening; LT = lung tethering.Grahic Jump Location

All patients being considered for LAT undergo clinical and ultrasonographic evaluation by one of the pleural team in a preassessment clinic to identify individuals who may be too frail due to comorbidities or have challenging anatomy (eg, septated effusion, nonsliding lung) and triage toward the most appropriate diagnostic intervention. However, in a small number of cases, these factors change on the day of the procedure and, therefore, some failures cannot be predicted. Converting “on the table” to real-time, image-guided, transthoracic, cutting-needle biopsy provides a potential alternative route to obtain tissue for histologic analysis, preventing the need for a further pleural procedure and additional inconvenience for the patient. Ultrasound “assisted” techniques, using ultrasound to mark the site and estimate angle and depth prior to biopsy, provide a diagnostic yield of 76% to 85%.6,7 A study from 1991 estimated that using direct, real-time ultrasound guidance provides a diagnostic yield for routine (ie, planned) biopsies of 70% to 86%.8 Subsequent studies conducted by radiologists for ultrasound-guided biopsy of lung parenchymal, pleural, and chest wall masses demonstrated yields of 91% to 98%.9,10 Retrospective case series comparing ultrasound-guided with CT image-guided biopsy for pleural and peripheral lung lesions found comparable high diagnostic yields (97.1% and 96.5%, respectively). The ultrasound-guided procedure was significantly quicker and had a lower rate of complications.11 However, no current evidence exists on the yield in cases of “failed” thoracoscopy, nor on its use by respiratory physicians trained in ultrasound using a direct, guided technique. The aim of this study was to determine the diagnostic yield of a physician-led service in both planned biopsies and cases of on-table conversion to ultrasound-guided biopsy.

A retrospective review was undertaken of all thoracoscopies and pleural biopsies performed at the Oxford Centre for Respiratory Medicine between January 2010 and July 2013. All the patients with planned pleural biopsies and those patients in whom thoracoscopy could not be performed (“failed” thoracoscopy), and so converted to ultrasound-guided biopsy, were further assessed. The histologic results were analyzed to determine the yield of pleural tissue. The patients were followed up in a specialist pleural clinic for assessment of the diagnosis. Patients with benign histology (ie, negative for pleural malignancy) remain under surveillance for 2 years to minimize the risk of potential false-negative results.

Biopsy Procedure

The pleural service in Oxford conducts > 500 pleural procedures (ultrasound-guided aspirations, chest drains, biopsies, and thoracoscopies) per year. All operators were trained to Royal College of Radiology level 2 in thoracic ultrasound and have each performed > 150 pleural procedures. The ultrasonography and biopsy were performed in a bronchoscopy suite without specialist radiology support. The site for the planned biopsies was determined by identification on CT scan (if available) and reconfirmed by ultrasound. The patient’s position for biopsy and for attempted thoracoscopies was the lateral decubitus position. The operator determined the biopsy site using a 4 to 8 MHz curvilinear probe. The dose of sedation used for thoracoscopy was midazolam, 1 to 2 mg, and fentanyl, 50 to 100 μg. Failed thoracoscopies were converted to biopsy on the table. If a Boutin needle had been used to attempt pneumothorax induction, the same anesthetized tract was used for subsequent pleural biopsy if there was sufficient evidence of pleural thickening on ultrasound.

A sterile probe cover allowed real-time ultrasound guidance for the administration of local anesthetic (1% lidocaine, 10-20 mL) and biopsy using a manually operated 18-gauge Temno biopsy needle (CareFusion Corp) (Fig 2). Use of direct-vision, ultrasound-guided biopsy (rather than blind biopsy) enabled the operator to ensure that the samples were being taken from the area of pleural thickening and ensure safety with no penetration of the visceral pleura. Between five and eight passes were performed until macroscopically satisfactory material was collected. Biopsy specimens were sent in formalin. Pleural fluid (if present) was also sent for cytologic examination. An example of the real-time ultrasound image obtained during cutting-needle biopsy is presented (Video 1). During and after the procedure, the site was reexamined with ultrasound to check for intrathoracic bleeding (using color Doppler) or evidence of pneumothorax in the area of the biopsy. All patients were observed for at least 1 h before discharge after plain chest radiograph confirmed no pneumothorax, as is routine practice.

Figure Jump LinkFigure 2 –  Thoracic ultrasound image showing cutting-needle (*) crossing the PT above an SE during biopsy. SE = septated effusion. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Pleural biopsy clip-shortened

Running Time: 0:13

Patients

Over the 3-year period, a total of 252 thoracoscopies were attempted. Of these, 13 (5.2%) were not successful and, hence, were converted on table to image-guided, cutting-needle biopsy. An additional 37 preplanned, ultrasound-guided biopsies were also conducted. These planned biopsies were undertaken in cases in which either there was a small or heavily septated effusion, adhered lung (visualized as a lack of pleural sliding on thoracic ultrasound), or patient frailty. Therefore, a total of 50 biopsies were included in this analysis (Table 1). The mean age of the patients was 65.0 years (SD, 18.4 years). The majority were men (39 of 50 patients [78.0%]). Fourteen of 50 patients (28.0%) had a pleural effusion and thickening alongside a clinical history compatible with pleural TB or empyema. Of 50 patients, 36 (72.0%) were under investigation for potential pleural malignancy (mesothelioma or metastatic disease), 26 (52.0%) had pleural thickening or nodularity on thoracic CT scanning, nine (18.0%) had exudative pleural effusions that were negative on cytology for malignancy requiring further investigation, and one (2.0%) had atypical cells suspicious of malignancy on pleural fluid cytology. Of the nine patients who had exudative pleural effusions that were negative on cytology, CT scanning showed one “likely” malignancy and two “possible” malignancies, and the other five had benign features only. Following the biopsy, there were no immediate or delayed complications (eg, pneumothorax, pleural infection, intrapleural bleed) in any patients.

Table Graphic Jump Location
TABLE 1 ]  Demographics and Indications for Attempted Thoracoscopies and Planned Biopsies
Pleural Thickening

Three patients had clear bulky tumor mass (between 39 and 61 mm thick on CT scan), and six patients did not have a CT scan, as they were being investigated for potential pleural infection (including pleural TB). For the remaining 41 patients, the mean maximal pleural thickness on CT scan was 4.9 mm (SD, 5.6 mm), and the mean pleural thickness in the midaxillary line (the area from which most biopsy specimens are routinely taken) was 1.8 mm (SD, 1.9 mm). Twelve of the 41 patients (29.3%) had no significant pleural thickening on CT scan in the midaxillary line. Five of 12 (41.7%) had malignant disease, as determined from the biopsy specimen from in this area.

Diagnostic Yield

Sufficient tissue for histologic diagnosis was obtained in 47 of 50 cases (94.0%). Of the 13 biopsies conducted after failed thoracoscopy, 11 (84.6%) obtained sufficient tissue. Of the planned biopsies, 97.3% (36 of 37) yielded sufficient tissue (χ2 with Yate’s correction, 0.96; P = .33). Three of 50 biopsies had insufficient or nondiagnostic samples; of these, two patients had benign features on interval imaging with follow-up of 18 and 24 months, respectively; while the other patient had widespread metastatic adenocarcinoma of likely intestinal origin on cross-sectional imaging, and so was treated palliatively for presumed malignant effusion rather than undergoing further investigation. Table 2 presents the final diagnoses for attempted thoracoscopies and planned biopsies.

Table Graphic Jump Location
TABLE 2 ]  Final Diagnoses for Attempted Thoracoscopies and Planned Biopsies

Data given as No. (%) unless otherwise indicated.

a 

Includes one patient subsequently diagnosed with mesothelioma at follow-up.

Histology Results
Malignancy:

Specimens from 13 of the 36 patients (36.1%) demonstrated pleural malignancy on histology (despite previous negative cytology), while 20 of 36 specimens (55.6%) were benign (Fig 3). Of the other benign cases, two (4%) were pleural sarcoidosis, one was pleural TB, and the remaining 16 (44.4%) were labeled as benign pleural thickening or fibrosis. All of the patients with benign thickening are routinely followed up in clinic for any evidence of malignant pleural or other disease. The median follow-up period for these patients was 15.5 months (mean, 17.3 months; SD, 9.6 months), in which time one patient (6.3%) had progressive disease clinically suggestive of mesothelioma (ie, one false-negative diagnosis).

Figure Jump LinkFigure 3 –  Flow diagram of patients undergoing ultrasound-guided biopsy.Grahic Jump Location
Infection:

Of the 10 patients with a history suggestive of pleural TB, nine (90.0%) had TB confirmed by the pleural biopsy sample; the other had benign pleural thickening. One further case of TB was diagnosed in the patient being investigated for potential malignancy. Four patients investigated for suspected empyema were treated for infection with no evidence of malignancy on biopsy specimen.

We have demonstrated that real-time, ultrasound-guided pleural biopsies conducted by respiratory physicians have a high diagnostic yield for both planned biopsies and on-table conversion to biopsy after attempted thoracoscopy. The 94.0% yield for planned biopsy is comparable to the high yield described by radiologists for ultrasound- and CT image-guided biopsies.11

The yield for the 13 patients who were converted to ultrasound-guided biopsy after failed thoracoscopy was 84.6%. This is a population that has not previously been described but achieves results comparable to the yield from combined fine-needle aspiration and ultrasound-assisted, cutting-needle biopsy.7 Therefore, ultrasound-guided, cutting-needle pleural biopsy in the hands of trained respiratory physicians safely and successfully obtains pleural tissue in a high proportion of cases. Even biopsies performed in the absence of CT scanned evidence of thickening in midaxillary line can be sufficient for diagnosis, and the population addressed in this study (failed thoracoscopy, absence of large effusion, and/or adhered lung) is likely to have diagnoses that are challenging to achieve. Therefore, a clinician can be confident of the validity of the result if obtaining sufficient tissue from ultrasound-guided biopsy.

The study was a retrospective audit of clinical practice and, therefore, has the potential for selection bias influencing the high success rate. However, these particular patients were not selected for ultrasound-guided biopsy (over thoracoscopy or CT image-guided biopsy) for simplicity or ease of procedure. Indeed, one could argue that the patients were more complex, as they were either unsuitable for thoracoscopy or the thoracoscopy was not able to be performed. The average follow-up for the benign cases was 16 months. This is a limitation of the study, as not all patients had (at the time of manuscript writing) achieved 2 years follow-up to establish true-negative biopsy results. In addition, the fact that the biopsies were performed at a specialist pleural center, with physicians experienced in performing thoracoscopies and ultrasound-guided biopsies, may limit the applicability of the findings to other nonspecialist respiratory centers, and this study now requires replication in a different context.

Rapid on-site cytologic evaluation, assessment of samples by a pathologist present in the procedural room, has the potential to determine if the operator has achieved a representative sample. This technique is successfully used in endobronchial ultrasound sampling on thoracic lymph nodes, during which the sample is assessed for presence of lymphocytes. In the case of histologic samples of the pleura, however, when the key differential is mesothelioma, assessing whether an “adequate sample” has been achieved may be more difficult. The other limitation for rapid on-site cytologic evaluation in many centers, including the Churchill Hospital in Oxford, is the lack of sufficient resources to provide this service.

A small minority (5.2%) of attempted thoracoscopies were unsuccessful in our series. Common practice in this situation would be to consider referral for either CT image-guided biopsy or surgical biopsy. There is a clear advantage in obtaining pleural tissue in a single procedure using ultrasound-guided, closed pleural biopsy where thoracoscopy has failed: The patient is already prepared and has given consent, it allows the diagnostic procedure to be carried out immediately, and obviates the need for cancelling the procedure and rebooking further investigations. Our series demonstrates that in appropriately trained hands, this is a valid diagnostic algorithm to follow, it obtains comparable results to those reported by radiologists and could be incorporated into clinical practice in respiratory centers regularly performing thoracoscopies. Thoracoscopy centers might develop physician-based, ultrasound-guided biopsies as an interest or consider it as a second-line procedure in patients either unfit for thoracoscopy or those in which thoracoscopy is not possible on that day.

Author contributions: R. J. H. and N. M. R. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. R. J. H., J. P. C., A. M., and N. M. R. contributed to the study concept; R. J. H., J. P. C., M. N., M. M., I. P., A. M., and N. M. R. contributed to data analysis; M. N., H. R., N. H., and I. P. contributed to data collection; A. A. and F. V. G. contributed to analysis of CT images; and R. J. H., J. P. C., A. A., M. N., H. R., N. H., M. M., I. P., A. M., F. V. G., and N. M. R. contributed to drafting and final approval of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Additional information: The Video can be found in the Supplemental Materials section of the online article.

Du Rand I, Maskell N. Introduction and methods: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(suppl 2):ii1-ii3. [CrossRef] [PubMed]
 
Hansen M, Faurschou P, Clementsen P. Medical thoracoscopy, results and complications in 146 patients: a retrospective study. Respir Med. 1998;92(2):228-232. [CrossRef] [PubMed]
 
Lee P, Hsu A, Lo C, Colt HG. Prospective evaluation of flex-rigid pleuroscopy for indeterminate pleural effusion: accuracy, safety and outcome. Respirology. 2007;12(6):881-886. [CrossRef] [PubMed]
 
Froudarakis ME. New challenges in medical thoracoscopy. Respiration. 2011;82(2):197-200. [CrossRef] [PubMed]
 
Tomlinson JR, Sahn SA. Invasive procedures in the diagnosis of pleural disease. Seminars in Respiratory Medicine. 1987;9(1):30-36. [CrossRef]
 
Diacon AH, Schuurmans MM, Theron J, Schubert PT, Wright CA, Bolliger CT. Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists. Respiration. 2004;71(5):519-522. [CrossRef] [PubMed]
 
Diacon AH, Theron J, Schubert P, et al. Ultrasound-assisted transthoracic biopsy: fine-needle aspiration or cutting-needle biopsy? Eur Respir J. 2007;29(2):357-362. [CrossRef] [PubMed]
 
Chang DB, Yang PC, Luh KT, Kuo SH, Yu CJ. Ultrasound-guided pleural biopsy with Tru-Cut needle. Chest. 1991;100(5):1328-1333. [CrossRef] [PubMed]
 
Sheth S, Hamper UM, Stanley DB, Wheeler JH, Smith PA. US guidance for thoracic biopsy: a valuable alternative to CT. Radiology. 1999;210(3):721-726. [CrossRef] [PubMed]
 
Liao WY, Chen MZ, Chang YL, et al. US-guided transthoracic cutting biopsy for peripheral thoracic lesions less than 3 cm in diameter. Radiology. 2000;217(3):685-691. [CrossRef] [PubMed]
 
Sconfienza LM, Mauri G, Grossi F, et al. Pleural and peripheral lung lesions: comparison of US- and CT-guided biopsy. Radiology. 2013;266(3):930-935. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Thoracic ultrasound showing PT and LT. Dynamic ultrasound imaging would show a lack of normal lung sliding. PT = pleural thickening; LT = lung tethering.Grahic Jump Location
Figure Jump LinkFigure 2 –  Thoracic ultrasound image showing cutting-needle (*) crossing the PT above an SE during biopsy. SE = septated effusion. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3 –  Flow diagram of patients undergoing ultrasound-guided biopsy.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Demographics and Indications for Attempted Thoracoscopies and Planned Biopsies
Table Graphic Jump Location
TABLE 2 ]  Final Diagnoses for Attempted Thoracoscopies and Planned Biopsies

Data given as No. (%) unless otherwise indicated.

a 

Includes one patient subsequently diagnosed with mesothelioma at follow-up.

Pleural biopsy clip-shortened

Running Time: 0:13

References

Du Rand I, Maskell N. Introduction and methods: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(suppl 2):ii1-ii3. [CrossRef] [PubMed]
 
Hansen M, Faurschou P, Clementsen P. Medical thoracoscopy, results and complications in 146 patients: a retrospective study. Respir Med. 1998;92(2):228-232. [CrossRef] [PubMed]
 
Lee P, Hsu A, Lo C, Colt HG. Prospective evaluation of flex-rigid pleuroscopy for indeterminate pleural effusion: accuracy, safety and outcome. Respirology. 2007;12(6):881-886. [CrossRef] [PubMed]
 
Froudarakis ME. New challenges in medical thoracoscopy. Respiration. 2011;82(2):197-200. [CrossRef] [PubMed]
 
Tomlinson JR, Sahn SA. Invasive procedures in the diagnosis of pleural disease. Seminars in Respiratory Medicine. 1987;9(1):30-36. [CrossRef]
 
Diacon AH, Schuurmans MM, Theron J, Schubert PT, Wright CA, Bolliger CT. Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists. Respiration. 2004;71(5):519-522. [CrossRef] [PubMed]
 
Diacon AH, Theron J, Schubert P, et al. Ultrasound-assisted transthoracic biopsy: fine-needle aspiration or cutting-needle biopsy? Eur Respir J. 2007;29(2):357-362. [CrossRef] [PubMed]
 
Chang DB, Yang PC, Luh KT, Kuo SH, Yu CJ. Ultrasound-guided pleural biopsy with Tru-Cut needle. Chest. 1991;100(5):1328-1333. [CrossRef] [PubMed]
 
Sheth S, Hamper UM, Stanley DB, Wheeler JH, Smith PA. US guidance for thoracic biopsy: a valuable alternative to CT. Radiology. 1999;210(3):721-726. [CrossRef] [PubMed]
 
Liao WY, Chen MZ, Chang YL, et al. US-guided transthoracic cutting biopsy for peripheral thoracic lesions less than 3 cm in diameter. Radiology. 2000;217(3):685-691. [CrossRef] [PubMed]
 
Sconfienza LM, Mauri G, Grossi F, et al. Pleural and peripheral lung lesions: comparison of US- and CT-guided biopsy. Radiology. 2013;266(3):930-935. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543