Method Article
Transthoracic ultrasound-guided lung biopsy represents a safe, cost-effective, and efficient approach for patients presenting with subpleural lung lesions suspected of malignancy. Employing a systematic, step-by-step process is crucial to achieve optimal patient selection, minimize complication risks, and maximize diagnostic accuracy.
Diagnosing patients with radiological lung lesions, especially those suspected of having primary lung cancer, is a common and critical clinical scenario. When selecting the most suitable invasive procedure to establish a diagnosis in these cases, a delicate balance must be struck between achieving a high diagnostic yield, providing staging information, minimizing potential complications, enhancing the patient experience, and controlling costs. The integration of thoracic ultrasound as a routine clinical tool in respiratory medicine has led to increased awareness and utilization of ultrasound-guided invasive techniques in chest procedures, including transthoracic biopsies. By following a systematic and stepwise approach, transthoracic ultrasound-guided lung biopsy emerges as a safe, cost-effective procedure with a remarkable diagnostic accuracy. These attributes collectively position it as an ideal invasive technique when technically feasible. Consequently, in patients presenting subpleural lung lesions suspected of malignancy, transthoracic ultrasound-guided lung biopsy has become a standard procedure in the realm of modern invasive pulmonology.
Establishing a diagnosis in patients with radiological lung lesions is crucial, particularly when malignancy is suspected. Tissue sampling is essential for confirming malignancy, obtaining additional information like genotyping and staging, and diagnosing non-malignant lung lesions (e.g., infection or vasculitis)1,2.
Several invasive procedures are available for tissue sampling in patients with lung lesions, including conventional bronchoscopy, bronchoscopy supplemented with radial endobronchial ultrasound (REBUS), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound (EBUS), endoscopic ultrasound (EUS), computed tomography guided transthoracic biopsy (CT-TTNB), and surgical biopsy3,4,5,6. The selection of the optimal procedure involves balancing factors like diagnostic yield, complication risks, patient comfort, and resource allocation3.
Most of these techniques have limitations. For instance, conventional bronchoscopy is less effective for peripheral lesions, CT-TTB carries a higher risk of complications (especially pneumothorax), and procedures like ENB and surgical biopsy can be costly4,6,7.
Ultrasound-guided transthoracic needle biopsy (US-TTNB) is an alternative method for obtaining tissue samples from lung lesions. The technique itself is not new, but its use has significantly increased in patients with peripheral lung lesions of unknown origin, particularly among pulmonologists, who now routinely use thoracic ultrasound (TUS) for point-of-care diagnostics and basic procedural guidance in various clinical scenarios8,9. In addition, ultrasound equipment is now more widely available, with TUS training increasingly formalized and made more accessible to clinicians at an earlier stage9,10,11,12,13,14,15,16.
US-TTNB carries several potential advantages. Complication rates and costs related to the procedure are low, while diagnostic yields remain comparable to other approaches, especially CT-TTB17,18,19,18,19,20,21. Its major limitation, however, is its suitability only for a limited proportion of lung lesions that can be appropriately visualized using TUS. Therefore, it cannot be used for lesions that do not contact the parietal pleura at the chest wall, such as any central tumor; lesions behind structures impenetrable to ultrasound waves, such as the scapula; or lesions with a meaningful air content, which also does not transmit ultrasound, such as 'ground glass' opacities seen on CT8,9,17,18,19,20,22,21,22,23,24,25,26. US-TTNB is also unable to definitively assess the N-stage of lung cancer, meaning in some cases, the procedure must be combined with another invasive procedure to provide a full picture1,2.
Nonetheless, US-TTNB remains an important and increasingly used front-line tool in modern invasive pulmonology practice in selected patients with suspected malignant lung lesions9,18.
Indications and contraindications
US-TTNB is indicated when all of the following criteria are met: (1) subpleural lung consolidation that can be visualized using thoracic ultrasound; (2) clinically warranted lung tissue biopsy (e.g., for establishing a diagnosis, obtaining material for supplementary diagnostic analyses). US-TTNB should not be performed when one or more of the following criteria are met: (1) manifest chronic or acute respiratory failure; (2) hemorrhagic diatheses; (3) ongoing treatment with anticoagulants or platelet aggregation inhibitors; (4) another invasive method for tissue sampling can establish a diagnosis and simultaneously provide N- or M-staging (e.g., EBUS/EUS-B in patients with suspected lung cancer and suspected involvement of mediastinal lymph nodes).
It should be noted, however, that the listed contraindications are generally relative. The physician, in agreement with the patient, should consider the clinical consequences of obtaining a biopsy by US-TTNB and balance this against the risk of complications and other potential invasive or diagnostic methods that could be performed instead of US-TTNB.
The described protocol below follows the human care guidelines of Odense University Hospital, Odense, Denmark, and the University of Southern Denmark, Odense, Denmark. The step-wise protocol described below represents a potential, systematic approach for a typical patient with suspected lung cancer for whom US-TTNB was performed in an outpatient or daycase setting. Informed written consent was obtained from the patient. We have taken into account current clinical practices at the authors' institutions, as well as descriptions from previously published papers9,13,17,26, and have sought to achieve a balance between likely diagnostic success, costs, and patient experience, as described in the introduction. However, the approach can and should be modified in line with local differences in available equipment, clinical settings, patient preferences, and specific requirements for the obtained biopsy material, including if a non-malignant lesion is suspected. Any US-TTB should also be performed in accordance with existing local, national, and international guidelines and standards, where applicable. The protocol depends on there being one physician who is trained and competent in performing US-TTNB and one assistant, such as a procedural nurse. Both should have sufficient experience with the procedure and should be confident in the management of possible acute complications.
1. Preprocedural assessment of available clinical information and imaging
2. Preprocedural equipment control
3. Checking and consenting the patient
4. Patient positioning
5. Preprocedural thoracic ultrasound
6. Patient monitoring and safety
7. Biopsy equipment preparation
8. Injection of local anesthetics
9. Biopsy procedure
10. Postprocedural thoracic ultrasound
11. Postprocedural patient observation and information
The overall diagnostic yield of US-TTNB in patients with lung lesions has been reported as 88.7% in a meta-analysis by DiBardiono et al.18. However, it should be noted that other studies have reported lower diagnostic yields of US-TTNB17,23,25. Several patient factors have been shown to affect the diagnostic yield of US-TTNB, including: (1) whether there is a malignant or non-malignant condition; (2) the size of the target lesion; (3) the presence of invasive growth; (4) the length of pleural contact17,25,28,29.
The US-TTNB protocol described above is for obtaining a US-TTNB core needle biopsy (Figure 8) for histological assessment, but it is also possible to use the same principles for obtaining an ultrasound-guided transthoracic needle aspiration (US-TTNA) for cytology assessment. A single study has indicated that the diagnostic yield of US-TTNA and US-TTNB might vary between different types of lung cancer, suggesting that the choice of sampling technique might not always be a matter of obtaining the "largest possible biopsy"30. Some studies have described a combined procedure approach in which US-TTNA is initially performed, followed by US-TTNB in the same procedure, possibly increasing the diagnostic yield24,30.
US-TTNB can also be combined with contrast-enhanced ultrasound (CEUS) as an extension of the preprocedural thoracic ultrasound assessment31. The use of preprocedural CEUS has been shown to increase the diagnostic yield of US-TTNB32. As with other invasive chest procedures, US-TTNB can also be combined with rapid on-site evaluation (ROSE) of the obtained tissue samples to improve diagnostic efficiency33.
Figure 1: Patient positioning. Baseline 2D thoracic ultrasound assessment of the target lesion is performed before the procedure, simultaneously determining the optimal patient positioning for the intervention. Please click here to view a larger version of this figure.
Figure 2: Baseline ultrasound measurements. Baseline 2D thoracic ultrasound assessment and inserted measurements of the target lesion before the procedure. Measurements for the width (1), depth (2), and length of pleural contact (3) are marked in the ultrasound image. The lesion is visualized as a well-defined, rounded, hyperechoic (grey) structure. Please click here to view a larger version of this figure.
Figure 3: Prepared procedure trolley. The equipment required for the US-TTNB (Ultrasound-Guided Transthoracic Needle Biopsy) procedure is organized and ready on a sterile trolley. Please click here to view a larger version of this figure.
Figure 4: Injection of local anesthetic. The syringe containing the local anesthetic is positioned in the biopsy guidance system and injected into the skin and subcutaneous tissue with continuous visualization of the needle tip on the ultrasound screen. Please click here to view a larger version of this figure.
Figure 5: Assessment of local anesthetic needle tip placement. The tip of the local anesthetic needle is visible (A) at the border zone between the pleural line and the underlying lung tumor. Please click here to view a larger version of this figure.
Figure 6: Core biopsy needle placement. The core biopsy needle is gradually introduced while carefully monitoring the advancement of the needle tip on the ultrasound screen. Please click here to view a larger version of this figure.
Figure 7: Core biopsy needle prior to biopsy. The core needle biopsy is visible just before it is "fired." The needle tip (A) is positioned approximately 2 cm within the tumor, allowing for a full 2 cm core biopsy. Please click here to view a larger version of this figure.
Figure 8: Obtained core biopsy specimen. A 2 cm core biopsy specimen from the lung tumor has been placed in the specimen container. Please click here to view a larger version of this figure.
Appropriate patient selection and a careful initial TUS assessment are crucial steps before performing US-TTNB. If the lung lesion cannot be visualized, US-TTNB is not a viable option. Ideally, TUS should be conducted before scheduling the procedure during the clinic visit to prevent last-minute cancellations in the procedural room17. This approach also allows for more comprehensive planning and a potential shift to an alternative invasive procedure if the lesion cannot be visualized17.
Three studies directly comparing US-TTNB with computed tomography transthoracic needle biopsy (CT-TTNB) have found comparable diagnostic yields19,20,34. These findings are consistent with the comparison between US-TTNB and CT-TTNB as part of the previously mentioned meta-analysis by DiBardiono et al.18.
The complication rate for US-TTNB is generally very low17. The pooled proportion of patients experiencing pneumothorax following US-TTNB has been noted to be 4.4%18, significantly lower than when directly compared to CT-TTNB18,19,20,21.
While studies assessing US-TTNB procedure time are limited, when compared with CT-TTNB, US-TTNB has a shorter median procedure time20,21. From cost, radiation, and environmental perspectives, US-TTNB is significantly less burdensome than CT-TTNB, which exposes both patients and staff to radiation and has a greater carbon footprint than ultrasound20,35.
Despite numerous studies on education, training, and competency assessment in the field of thoracic ultrasound, research specifically evaluating these aspects in relation to US-TTNB is rare and is not included in the European Respiratory Society's certified training program in thoracic ultrasound15,16,36,37. A single study has assessed US-TTNB learning curves and found that several operators with proficiency in thoracic ultrasound did not achieve competency in US-TTNB despite performing multiple procedures38. Therefore, further research on education, training, and competency assessment in US-TTNB is still needed.
The described US-TTNB approach can be modified by incorporating contrast-enhanced ultrasound (CEUS) as part of the initial baseline thoracic ultrasound assessment before the biopsy is performed. This approach offers improved visualization of the specific biopsy site within the lesion, more accurate differentiation between benign and malignant lung tissue, and easier identification of necrotic areas31. CEUS-guided US-TTNB can be seamlessly integrated into the protocol described above, and the literature reports a significant increase in diagnostic yield compared to conventional US-TTNB32,39.
While the focus of our protocol has been on its use in patients with lung lesions suspected of malignancy in the lungs, the protocol's principles remain generally applicable when sampling other structures in the chest, such as the parietal pleura or the anterior/superior mediastinum9,14,17,40,41,42,43,44. The clinical utility of US-TTB and its utilization by pulmonologists are expected to expand in the coming years.
In summary, US-TTNB is a safe, cost-effective procedure with a high diagnostic yield in patients with subpleural lung lesions suspected of malignancy. When technically feasible, US-TTNB should be considered the transthoracic biopsy technique of choice.
The authors have nothing to disclose.
None.
Name | Company | Catalog Number | Comments |
Ambu BlueSensor R | Ambu | R-00-S/25 | ECG patches |
BD Nexiva Closed IV Catheter System (20 GA x 1.25 in)(1.1 x 32 mm) | BD | 383667 | Intravenous accesskit |
BD PosiFlush SP Syringe 5 mL | BD | 306574 | Syringe with 5 mL 0.9% NaCl |
Blunt Fill Needle with 5 Micron Filter (18 G x 11/2") | Sol-Millennium Medical Inc. | BN1815F | 18 G needle |
C1-6VN ultrasound transducer | GE Healthcare | 5476279 | Ultrasound transducer |
C2-9D ultrasound transducer | GE Healthcare | 5405253 | Ultrasound transducer |
CARBON STEEL SURGICAL BLADES | Swann-Morton | 203 | Scalpel blade |
Disinfection wipe (82% ehanol + 0.5% chlorhexidine) | Vitrex Medical A/S | 527297 | Disinfection wipe |
Disposable needle single use (0.80 mm x 80 mm) | Misawa Medical Industry Co., Ltd. | K070001 | 80 mm 21 G hypodermic needle |
EKO GEL | Ekkomed A/S | 29060008-29 | Ultrasound gel |
Formalin system, buffered formalin solution 450 mL | Sarstedt | 5,11,703 | Biopsy specimen contained and relevant fixation liquid (e.g. formaldehyde) |
GAMMEX Latex | Ansell | 330048075 | Sterile gloves |
KD-JECT 20 mL | KD Medcial GmbH | 820209 | 20 mL syringe |
Klorhexidin sprit 0.5% 500 mL | Fuckborg Pharma | 212045 | Disinfectant |
Lidokain Mylan 10 mg/mL, 20 mL | Mylan | NO-6042A1 | Local anesthetic (20 mL, 2% lidocaine) |
LOGIQ E10 | GE Healthcare | NA | High-end ultrasound machine |
Mölnlycke BARRIER Adhesive Aperture Drape (50 x 60 cm / 6 x 8 cm) | Mölnlycke Healthcare AB | 906693 | Adhesive surgical drape with a central hole |
Mölnlycke Gauze 10 x 10 cm | Mölnlycke Healthcare AB | 158440 | Swaps for applying disinfectant |
Philips IntelliVue X2 | Philips | NA | Patient monitoring system |
Raucodrape PRO 75 x 90 cm | Lohmann & Rauscher International GmbH & Co | 33 005 | Sterile drape for procedure table |
SEMICUT 18 G x 100 mm | MDL | PD01810 | 18 G x 100 mm core biopsy needle |
SEMICUT 18 G x 160 mm | MDL | PD01816 | 18 G x 160 mm core biopsy needle |
S-Monovette, 25 mL, for Formalin system, (LxØ): 97 x 25 mm, with paper label | Sarstedt | 9,17,05,001 | Biopsy specimen container |
Sterican (0.80 x 120 mm BL/LB) | Braun | 4665643 | 120 mm 21 G hypodermic needle |
Tegaderm I.V. | 3M | 1633 | I.V. Transparent film dressing with border |
Ultra-Pro II Disposable Replacement Kits | CIVCO | 610-608 | For use with GE Healthcare C2-9 transducer |
Ultra-Pro II In-Plane Ultrasound Needle Guides-Multi-Angle | CIVCO | H4913BA | For use with GE Healthcare C2-9 transducer |
Verza Needle Guidance System for VerzaLink™ Transducers | CIVCO | 610-1500-24 | For use with GE Healthcare C1-6 transducer |
Verza Ultrasound Needle Guidance System | CIVCO | H4917VB | For use with GE Healthcare C1-6 transducer |
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