Introduction: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. Methods: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. Results: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86–3.72; p < 0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). Conclusion: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

1.
Navani
N
,
Nankivell
M
,
Lawrence
DR
,
Lock
S
,
Makker
H
,
Baldwin
DR
, et al
.
Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomized controlled trial
.
Lancet Respir Med
.
2015
;
3
(
4
):
282
92
.
2.
Figueiredo
VR
,
Cardoso
PFG
,
Jacomelli
M
,
Santos
LM
,
Minata
M
,
Terra
RM
.
EBUS-TBNA versus surgical mediastinoscopy for mediastinal lymph node staging in potentially operable non-small cell lung cancer: a systematic review and meta-analysis
.
J Bras Pneumol
.
2020
;
46
(
6
):
e20190221
.
3.
Madan
K
,
Mittal
S
,
Madan
NK
,
Tiwari
P
,
Jain
D
,
Arava
S
, et al
.
EBUS-TBNA versus EUS-B-FNA for the evaluation of undiagnosed mediastinal lymphadenopathy: the TEAM randomized controlled trial
.
Clin Respir J
.
2020
;
14
(
11
):
1076
82
.
4.
Detterbeck
FC
,
Jantz
MA
,
Wallace
M
,
Vansteenkiste
J
,
Silvestri
GA
;
American College of Chest Physicians
.
Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition)
.
Chest
.
2007
;
132
(
3 Suppl l
):
202S
20S
.
5.
Bolliger
CT
,
Mathur
PN
,
Beamis
JF
,
Becker
HD
,
Cavaliere
S
,
Colt
H
, et al
.
ERS/ATS statement on interventional pulmonology. European respiratory society/American thoracic society
.
Eur Respir J
.
2002
;
19
(
2
):
356
73
.
6.
Eapen
GA
,
Shah
AM
,
Lei
X
,
Jimenez
CA
,
Morice
RC
,
Yarmus
L
, et al
.
Complications, consequences, and practice patterns of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE registry
.
Chest
.
2013
;
143
(
4
):
1044
53
.
7.
Franke
KJ
,
Bruckner
C
,
Szyrach
M
,
Ruhle
KH
,
Nilius
G
,
Theegarten
D
.
The contribution of endobronchial ultrasound-guided forceps biopsy in the diagnostic workup of unexplained mediastinal and hilar lymphadenopathy
.
Lung
.
2012
;
190
(
2
):
227
32
.
8.
Gonuguntla
HK
,
Shah
M
,
Gupta
N
,
Agrawal
S
,
Poletti
V
,
Nacheli
GC
.
Endobronchial ultrasound-guided transbronchial cryo-nodal biopsy: a novel approach for mediastinal lymph node sampling
.
Respirol Case Rep
.
2021
;
9
(
8
):
e00808
.
9.
Zhang
J
,
Guo
JR
,
Huang
ZS
,
Fu
WL
,
Wu
XL
,
Wu
N
, et al
.
Transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: a randomised trial
.
Eur Respir J
.
2021
;
58
(
6
):
2100055
.
10.
Ariza-Prota
MA
,
Pérez-Pallarés
J
,
Fernández-Fernández
A
,
López-González
F
,
Cascón
JA
,
García-Alfonso
L
, et al
.
Transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lymph nodes: a case series- How to do it
.
Arch Bronconeumol
.
2022
;
58
(
10
):
718
21
.
11.
Genova
C
,
Tagliabue
E
,
Mora
M
,
Aloè
T
,
Dono
M
,
Salvi
S
, et al
.
Potential application of cryobiopsy for histo-molecular characterization of mediastinal lymph nodes in patients with thoracic malignancies: a case presentation series and implications for future developments
.
BMC Pulm Med
.
2022
;
22
(
1
):
5
.
12.
Gershman
E
,
Amram Ikan
A
,
Pertzov
B
,
Rosengarten
D
,
Kramer
MR
.
Mediastinal “deep freeze”-transcarinal lymph node cryobiopsy
.
Thorac Cancer
.
2022
;
13
(
11
):
1592
6
.
13.
Fan
Y
,
Zhang
AM
,
Wu
XL
,
Huang
ZS
,
Kontogianni
K
,
Sun
K
, et al
.
Transbronchial needle aspiration combined with cryobiopsy in the diagnosis of mediastinal diseases: a multicentre, open-label, randomised trial
.
Lancet Respir Med
.
2023
;
11
(
3
):
256
64
.
14.
Ariza-Prota
M
,
Pérez-Pallarés
J
,
Fernández-Fernández
A
,
García-Alfonso
L
,
Cascón
JA
,
Torres-Rivas
H
, et al
.
Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: safety, feasibility and diagnostic yield-experience in 50 cases
.
ERJ Open Res
.
2023
;
9
(
2
):
00448
2022
.
15.
Salcedo Lobera
E
,
Codeso
FMP
,
Casado Miranda
E
.
Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy: series of 50 cases
.
Rev Clin Esp
.
2023
;
223
(
9
):
578
81
.
16.
Velasco-Albendea
FJ
,
Cruz-Rueda
JJ
,
Gil-Belmonte
MJ
,
Pérez-Rodríguez
Á
,
López-Pardo
A
,
Agredano-Ávila
B
, et al
.
The contribution of mediastinal transbronchial nodal cryobiopsy to morpho-histological and molecular diagnosis
.
Diagnostics
.
2023
;
13
(
22
):
3476
.
17.
Maturu
VN
,
Prasad
VP
,
Vaddepally
CR
,
Dommata
RR
,
Sethi
S
.
Endobronchial ultrasound-guided mediastinal lymph nodal cryobiopsy in patients with nondiagnostic/inadequate rapid on-site evaluation: a new step in the diagnostic algorithm
.
J Bronchology Interv Pulmonol
.
2024
;
31
(
1
):
2
12
.
18.
Annema
JT
,
Rozman
A
.
Endobronchial ultrasound-guided cryobiopsy-when it is indicated
.
Lancet Respir Med
.
2023
;
11
(
3
):
e23
.
19.
Botana-Rial
M
,
Lojo-Rodríguez
I
,
Leiro-Fernández
V
,
Ramos-Hernández
C
,
González-Montaos
A
,
Pazos-Area
L
, et al
.
Is the diagnostic yield of mediastinal lymph node cryobiopsy (cryoEBUS) better for diagnosing mediastinal node involvement compared to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)? A systematic review
.
Respir Med
.
2023
;
218
:
107389
.
20.
McInnes
MDF
,
Moher
D
,
Thombs
BD
,
McGrath
TA
,
Bossuyt
PM
;
The PRISMA-DTA Group
, et al
.
Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement
.
JAMA
.
2018
;
319
(
4
):
388
96
.
21.
Whiting
PF
,
Rutjes
AW
,
Westwood
ME
,
Mallett
S
,
Deeks
JJ
,
Reitsma
JB
, et al
.
QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies
.
Ann Intern Med
.
2011
;
155
(
8
):
529
36
.
22.
Du Rand
IA
,
Blaikley
J
,
Booton
R
,
Chaudhuri
N
,
Gupta
V
,
Khalid
S
, et al
.
British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE
.
Thorax
.
2013
;
68
(
Suppl 1
):
i1
i44
.
23.
Dong
Z
,
Li
H
,
Jiang
H
,
Wu
C
.
Evaluation of cytology in lung cancer diagnosis based on EBUS-TBNA
.
J Cytol
.
2017
;
34
(
2
):
73
7
.
24.
Erer
OF
,
Erol
S
,
Anar
C
,
Aydoğdu
Z
,
Özkan
SA
.
Diagnostic yield of EBUS-TBNA for lymphoma and review of the literature
.
Endosc Ultrasound
.
2017
;
6
(
5
):
317
22
.
25.
Wong
M
,
Yasufuku
K
,
Nakajima
T
,
Herth
FJ
,
Sekine
Y
,
Shibuya
K
, et al
.
Endobronchial ultrasound: new insight for the diagnosis of sarcoidosis
.
Eur Respir J
.
2007
;
29
(
6
):
1182
6
.
26.
Reck
M
,
Rabe
KF
.
Precision diagnosis and treatment for advanced non-small-cell lung cancer
.
N Engl J Med
.
2017
;
377
(
9
):
849
61
.
27.
Ray
AS
,
Li
C
,
Murphy
TE
,
Cai
G
,
Araujo
KLB
,
Bramley
K
, et al
.
Improved diagnostic yield and specimen quality with endobronchial ultrasound-guided forceps biopsies: a retrospective analysis
.
Ann Thorac Surg
.
2020
;
109
(
3
):
894
901
.
28.
Darwiche
K
,
Freitag
L
,
Nair
A
,
Neumann
C
,
Karpf-Wissel
R
,
Welter
S
, et al
.
Evaluation of a novel endobronchial ultrasound-guided lymph node forceps in enlarged mediastinal lymph nodes
.
Respiration
.
2013
;
86
(
3
):
229
36
.
29.
Mehta
RM
,
Aurangabadbadwalla
R
,
Singla
A
,
Loknath
C
,
Munavvar
M
.
Endobronchial ultrasound-guided mediastinal lymph node forceps biopsy in patients with negative rapid-on-site-evaluation: a new step in the diagnostic algorithm
.
Clin Respir J
.
2020
;
14
(
4
):
314
9
.
30.
Bramley
K
,
Pisani
MA
,
Murphy
TE
,
Araujo
KL
,
Homer
RJ
,
Puchalski
JT
.
Endobronchial ultrasound-guided cautery-assisted transbronchial forceps biopsies: safety and sensitivity relative to transbronchial needle aspiration
.
Ann Thorac Surg
.
2016
;
101
(
5
):
1870
6
.
31.
Troy
LK
,
Grainge
C
,
Corte
TJ
,
Williamson
JP
,
Vallely
MP
,
Cooper
WA
, et al
.
Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study
.
Lancet Respir Med
.
2020
;
8
(
2
):
171
81
.
32.
Tomassetti
S
,
Ravaglia
C
,
Wells
AU
,
Cavazza
A
,
Colby
TV
,
Rossi
G
, et al
.
Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study
.
Lancet Respir Med
.
2020
;
8
(
8
):
786
94
.
33.
Griff
S
,
Ammenwerth
W
,
Schönfeld
N
,
Bauer
TT
,
Mairinger
T
,
Blum
TG
, et al
.
Morphometrical analysis of transbronchial cryobiopsies
.
Diagn Pathol
.
2011
;
6
:
53
.
34.
Schuhmann
M
,
Bostanci
K
,
Bugalho
A
,
Warth
A
,
Schnabel
PA
,
Herth
FJ
, et al
.
Endobronchial ultrasound-guided cryobiopsies in peripheral pulmonary lesions: a feasibility study
.
Eur Respir J
.
2014
;
43
(
1
):
233
9
.
35.
Rodrigues
I
,
Estêvão Gomes
R
,
Coutinho
LM
,
Rego
MT
,
Machado
F
,
Morais
A
, et al
.
Diagnostic yield and safety of transbronchial lung cryobiopsy and surgical lung biopsy in interstitial lung diseases: a systematic review and meta-analysis
.
Eur Respir Rev
.
2022
;
31
(
166
):
210280
.
36.
DeMaio
A
,
Thiboutot
J
,
Yarmus
L
.
Applications of cryobiopsy in airway, pleural, and parenchymal disease
.
Expert Rev Respir Med
.
2022
;
16
(
8
):
875
86
.
37.
Ganganah
O
,
Guo
SL
,
Chiniah
M
,
Li
YS
.
Efficacy and safety of cryobiopsy versus forceps biopsy for interstitial lung diseases and lung tumours: a systematic review and meta-analysis
.
Respirology
.
2016
;
21
(
5
):
834
41
.
You do not currently have access to this content.