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Editorial |

Could Cryo-Biopsies Lead Bronchoscopy Into the Ice Age? FREE TO VIEW

Nicholas J. Pastis, MD, FCCP; Gerard A. Silvestri, MD, FCCP
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following: N. J. P. has received honoraria from Olympus for teaching linear and radial endobronchial ultrasound-guided bronchoscopy courses; he also served as a consultant to Cook medical for developing teaching tools for bronchoscopy. None declared (G. A. S.).

Thoracic Oncology Research Group, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC

CORRESPONDENCE TO: Nicholas J. Pastis, MD, FCCP, Thoracic Oncology Research Group, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, 17 Ashley Ave, Room 812-CSB, Charleston, SC 29425-2220


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(2):270-272. doi:10.1016/j.chest.2016.04.008
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Published online

For nearly 40 years following the release of the flexible bronchoscope, only a few procedures (BAL, transbronchial lung biopsies, and transbronchial needle aspiration) were available to diagnose pulmonary diseases. Since then, the most impactful advance in bronchoscopy has been the introduction of endobronchial ultrasound, which revolutionized the bronchoscopic approach to assessing mediastinal adenopathy. In patients with known or suspected lung cancer, the diagnostic yield approaches 90%, and the procedure is useful in diagnosing sarcoidosis and lymphoma., Could cryobiopsies be the next game changer by expanding the capability of transbronchial lung biopsies by providing tissue samples that rival surgical lung biopsies?

FOR RELATED ARTICLE SEE PAGE 329

The diagnostic yield of traditional transbronchial lung biopsy (TBLB) for most interstitial lung diseases is poor because of the small size of lung tissue obtained and lack of enough architecture to make a unifying diagnosis. Even when pathologic findings are present on TBLB (ie, granulomas or organizing pneumonia), there is a conundrum of whether it is a bystander or the primary pathology. In the workup of pulmonary fibrosis, guidelines mandate the use of open lung biopsy (OLB) to establish a histological diagnosis in cases in which there is not a compatible clinical history and typical radiologic pattern for usual interstitial pneumonia on high-resolution chest CT scan.,, In recent large clinical trials on idiopathic pulmonary fibrosis treatment, 22% to 54% of patients underwent surgical lung biopsy to establish the diagnosis.,

Unfortunately, surgical lung biopsies in idiopathic pulmonary fibrosis are risky because most studies report a 3% to 4% mortality within 30 days, with one study suggesting a 16% overall mortality rate. Because of the risks of OLB, cryo-transbronchial biopsy (cryo-TBB) has emerged as a potential alternative. In relatively small case series at single centers, cryo-TBB was noted to be a safe, effective, and minimally invasive alternative for the diagnosis of interstitial lung disease. The samples obtained for histologic examination allowed clinicians to avoid OLB in the majority of patients.,

One can only imagine the litany of other uses for a bronchoscopic technique that could obtain tissue rivaling the amount garnered in surgical biopsies. Two recent studies highlight the need for better approaches to diagnosing nodules and masses in the lung because it appears that bronchoscopy is doing a shockingly poor job of diagnosing lung cancer when it is present. In a multicenter trial evaluating a genomic classifier to aid in the diagnosis of lung cancer, nondiagnostic results occurred in 43% of 639 patients who underwent bronchoscopy. In addition, the American College of Chest Physicians (CHEST) Quality Improvement Registry, Evaluation, and Education (AQuIRE) registry data found an unexpectedly low diagnostic yield for guided bronchoscopy in the diagnosis of pulmonary nodules (47% when radial probe-endobronchial ultrasound is combined with electromagnetic navigation). Could cryo-TBB help in the yield for guided bronchoscopy where a lesion can be reached but sampling is inadequate? Similarly, can the additional tissue obtained by cryo-TBB improve the ability of pathologists to perform mutation analysis that has become increasingly important in managing patients with advanced lung cancer?

In this issue of Chest, Yarmus et al take cryo-TBB to the next level. As with other modern technologies (laptops, smartphones, etc), they fit big things in smaller packages. In a prospective randomized controlled porcine study evaluating a novel sheath cryobiopsy, the authors address a limitation of standard cryo-TBB: that the cryoprobe, the specimen, and the bronchoscope have to be removed from the airway immediately after each freeze biopsy because the specimen obtained is too big to fit through the working channel. When the scope is removed, airway visualization is temporarily lost and major bleeding can occur unchecked, so a secured airway (ie, endotracheal tube) is frequently used to allow rapid reinsertion of the bronchoscope to visualize and attempt to control any bleeding. The sheath cryobiopsy (S-CBx) in this study overcomes this limitation by using a smaller diameter cryoprobe that fits inside a sheath that can be completely retracted through a working channel while the bronchoscope is left in position within the airway.

This study was single blinded because the pathologists were unaware of the method used to obtain each specimen (ie, the 1.1 mm SCBx probe, 1.9 mm cryobiopsy probe, or the 2.0 mm forceps biopsy). Adequate specimens for standard pathologic processing were retrieved with 82.1% of the SCBx specimens, 82.9% of the CBx, but only 30% of the forceps biopsy. Of the biopsies obtained, there was also no difference noted between traditional cryo-TBB and the S-CBx in sample quality, whereas both remained superior to standard TBLB. There were no significant bleeding events in any of the techniques.

As acknowledged by the authors, possible unconscious bias was present in the study. Although the pathologist was blinded to the technique used to acquire each biopsy specimen, the bronchoscopist was not, so could greater effort and care have been taken to acquire the cryobiopies than the traditional TBLBs? That seems unlikely to these authors. In addition, the clinical relevance of representative lung samples of a porcine lung is unknown. Prior studies of cryo-TBB have looked at the ability to diagnose interstitial lung disease, so it may be difficult to correlate the net amount of normal porcine lung tissue with the diagnostic yield or safety in humans with lung pathology.

In comparing publications on cryo-TBB, the lack of an evidence-based approach to the procedure’s technique and training is noteworthy. Should a rigid bronchoscope, endotracheal tube, laryngeal mask airway, or none of these be used for the procedure? Are the authors advocating that the S-CBx will allow the procedure to be done without an advanced airway? Otherwise, for those doing the procedure with a bronchial blocker in position, it may not make a difference to briefly leave the airway if potential bleeding can be contained.

In the future, multicenter trials should be welcomed for this promising technique with the potential to increase the diagnostic yield of flexible bronchoscopy for multiple diseases (ie, interstitial lung disease), certain pulmonary infections such as mycobacterial or fungal, and lung cancer including mutational analysis. Future directions may also evaluate therapeutic capabilities outside the current indications in malignant airway obstruction and foreign body removal. The best safety practices and training requirements for this potentially risky procedure are necessary and evidence-based guidelines could be produced. In the meantime, Yarmus et al propose an interesting and novel modification on cryo-TBB that could make it easier and potentially safer to perform. If further research confirms these findings, the addition of this tool could significantly add to the armamentarium of tools we currently use in the bronchoscopy laboratory to help diagnose diseases of the chest. We are shivering at the possibilities.

References

Silvestri G. .Gonzalez A. .Jantz M. .et al Methods for Staging Non-Small Cell Lung Cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S-e250S [PubMed]journal. [CrossRef] [PubMed]
 
von Bartheld M. .Dekkers O. .Szlubowski A. .et al Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis. JAMA. 2013;309:2457-2464 [PubMed]journal. [CrossRef] [PubMed]
 
Moonim M. .Breen R. .Fields P. .et al Diagnosis and subtyping of de novo and relapsed mediastinal lymphomas by endobronchial ultrasound needle aspiration. Am J Respir Crit Care Med. 2013;188:1216-1223 [PubMed]journal. [CrossRef] [PubMed]
 
Blackhall V.A. .Renieri A. .Civitelli S. .et al The role of surgical lung biopsy in the management of interstitial lung disease: experience from a single institution in the UK. Interact Cardiovasc Thorac Surg. 2013;17:253-257 [PubMed]journal. [CrossRef] [PubMed]
 
Sigurdsson M. .Isaksson H. .Gudmundsson G. .et al Diagnostic surgical lung biopsies for suspected interstitial lung diseases: a retrospective study. Ann Thorac Surg. 2009;88:227-232 [PubMed]journal. [CrossRef] [PubMed]
 
Nguyen W. .Meyer K. . Surgical lung biopsy for the diagnosis of interstitial lung disease: a review of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30:3-16 [PubMed]journal. [PubMed]
 
Noble P. .Albera C. .Bradford W. .et al Perfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomized trials. Lancet. 2011;377:1760-1769 [PubMed]journal. [CrossRef] [PubMed]
 
Richeldi L. .Costabel U. .Selman M. .et al Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079-1087 [PubMed]journal. [CrossRef] [PubMed]
 
Utz J. .Ryu J. .Douglas W. . High short-term mortality following lung biopsy for usual interstitial pneumonia. Eur Respir J. 2001;17:175-179 [PubMed]journal. [CrossRef] [PubMed]
 
Fruchter O. .Fridel L. .El Raouf B. .et al Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Respirology. 2014;19:683-688 [PubMed]journal. [CrossRef] [PubMed]
 
Casoni G. .Tomassetti S. .Cavazza A. .et al Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One. 2014;9:e86716- [PubMed]journal. [CrossRef] [PubMed]
 
Silvestri G. .Vachani A. .Whitney D. .et al A bronchial genomic classifier for the diagnostic evaluation of lung cancer. N Engl J Med. 2015;373:243-251 [PubMed]journal. [CrossRef] [PubMed]
 
Ost D. .Ernst A. .Lei X. .et al Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE registry. Am J Respir Crit Care Med. 2016;193:68-77 [PubMed]journal. [CrossRef] [PubMed]
 
Yarmus L.B. .Semaan R.W. .Arias S.A. .et al A randomized controlled trial of a novel sheath cryoprobe for bronchoscopic lung biopsy in a porcine model. Chest. 2016;150:329-336 [PubMed]journal
 

Figures

Tables

References

Silvestri G. .Gonzalez A. .Jantz M. .et al Methods for Staging Non-Small Cell Lung Cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S-e250S [PubMed]journal. [CrossRef] [PubMed]
 
von Bartheld M. .Dekkers O. .Szlubowski A. .et al Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis. JAMA. 2013;309:2457-2464 [PubMed]journal. [CrossRef] [PubMed]
 
Moonim M. .Breen R. .Fields P. .et al Diagnosis and subtyping of de novo and relapsed mediastinal lymphomas by endobronchial ultrasound needle aspiration. Am J Respir Crit Care Med. 2013;188:1216-1223 [PubMed]journal. [CrossRef] [PubMed]
 
Blackhall V.A. .Renieri A. .Civitelli S. .et al The role of surgical lung biopsy in the management of interstitial lung disease: experience from a single institution in the UK. Interact Cardiovasc Thorac Surg. 2013;17:253-257 [PubMed]journal. [CrossRef] [PubMed]
 
Sigurdsson M. .Isaksson H. .Gudmundsson G. .et al Diagnostic surgical lung biopsies for suspected interstitial lung diseases: a retrospective study. Ann Thorac Surg. 2009;88:227-232 [PubMed]journal. [CrossRef] [PubMed]
 
Nguyen W. .Meyer K. . Surgical lung biopsy for the diagnosis of interstitial lung disease: a review of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30:3-16 [PubMed]journal. [PubMed]
 
Noble P. .Albera C. .Bradford W. .et al Perfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomized trials. Lancet. 2011;377:1760-1769 [PubMed]journal. [CrossRef] [PubMed]
 
Richeldi L. .Costabel U. .Selman M. .et al Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079-1087 [PubMed]journal. [CrossRef] [PubMed]
 
Utz J. .Ryu J. .Douglas W. . High short-term mortality following lung biopsy for usual interstitial pneumonia. Eur Respir J. 2001;17:175-179 [PubMed]journal. [CrossRef] [PubMed]
 
Fruchter O. .Fridel L. .El Raouf B. .et al Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Respirology. 2014;19:683-688 [PubMed]journal. [CrossRef] [PubMed]
 
Casoni G. .Tomassetti S. .Cavazza A. .et al Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One. 2014;9:e86716- [PubMed]journal. [CrossRef] [PubMed]
 
Silvestri G. .Vachani A. .Whitney D. .et al A bronchial genomic classifier for the diagnostic evaluation of lung cancer. N Engl J Med. 2015;373:243-251 [PubMed]journal. [CrossRef] [PubMed]
 
Ost D. .Ernst A. .Lei X. .et al Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. Results of the AQuIRE registry. Am J Respir Crit Care Med. 2016;193:68-77 [PubMed]journal. [CrossRef] [PubMed]
 
Yarmus L.B. .Semaan R.W. .Arias S.A. .et al A randomized controlled trial of a novel sheath cryoprobe for bronchoscopic lung biopsy in a porcine model. Chest. 2016;150:329-336 [PubMed]journal
 
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