Hybrid Technique of Radial Endobronchial Ultrasound Combined with Lung Cryobiopsy in the Diagnosis of Peripheral Pulmonary Lesions
Corresponding Author: Sameer Arbat, Department of Respiratory Medicine, JNMC Sawangi, Wardha, Mumbai, India; Interventional Pulmonologist One Healthcare, Nagpur Maharashtra, India, e-mail: firstname.lastname@example.org
Received on: 30 June 2022; Accepted on: 12 November 2022; Published on: 14 March 2023
Introduction: The diagnosis of peripheral pulmonary lesions (PPLs) may be challenging as they are bronchoscopically invisible. Radial endobronchial ultrasound (EBUS) is useful for accessing PPL, with the help of transbronchial lung biopsy (TBLB) and cryoprobe. Although PPL can also be accessed with the help of transthoracic ultrasound or computerized tomography (CT)—guided fine-needle aspiration (FNA), there is a significant risk of pneumothorax.
Patients and methods: This was a retrospective observational study. Patients with PPL on CT thorax were subjected to bronchoscopy. Radial EBUS (R-EBUS) via flexible bronchoscope with fluoroscope was used to determine the site and cryobiopsy was taken. Bleeding was controlled by an endobronchial balloon placed through a rigid bronchoscope as a conduit.
Results: A total of 40 patients underwent R-EBUS with fluoroscopy-guided cryobiopsy. Histopathological diagnosis was achieved in 34 (85%) cases. Out of total 40 cases, 10 were diagnosed as adenocarcinoma, 9 as squamous cell carcinoma, and 4 as bronchitis and so on. No complication was seen in 12 cases, and 1 patient required hospitalization for observation.
Conclusions: R-EBUS-guided cryobiopsy in the diagnosis of PPLs is a safe procedure with good diagnostic yield.
How to cite this article: Arbat S, Singh T, Arbat T, et al. Hybrid Technique of Radial Endobronchial Ultrasound Combined with Lung Cryobiopsy in the Diagnosis of Peripheral Pulmonary Lesions. Indian J Respir Care 2023;12(1):42-45.
Source of support: Nil
Conflict of interest: None
Keywords: Bronchoscopy, Endobronchial ultrasound, Pulmonology, Transbronchial lung biopsy, Transbronchial lung cryobiopsy.
Lung cancer holds predominance in cancer-related mortality globally. While performing computed tomography (CT) scans for the screening of lung cancer, peripheral pulmonary lesions (PPLs) are detected. PPLs are described as pulmonary masses having a single, well-restricted boundary surrounded by pulmonary parenchyma.1
Pulmonary lesions are rising and have become an increasingly frequent radiographic finding. In clinical practice, pulmonologists are frequently referred to manage them.2 Some of these lesions are noncarcinogenic, but a significant number are malignant. The malignancy can be predicted using both clinical and radiographic reports. The likelihood of malignancy has to be investigated in accordance with the management of pulmonary nodules.3,4
It is often essential to execute tissue sampling to obtain a precise diagnosis of these lesions. Diagnosis of PPL by CT-guided core biopsy is considered the current gold standard,5 which also carries a high diagnostic yield (90%). Still, it is associated with increased side effects, primarily pneumothorax (up to 34%), pulmonary hemorrhage (27%), and hemoptysis (4%).6 To overcome these limitations and risks, guided bronchoscopy is introduced as it has a lesser risk of pneumothorax compared to CT-guided transthoracic needle aspiration.
Radial endobronchial ultrasound (R-EBUS) with guide sheath is a potential tool with significant diagnostic yield for PPL.7 It is a unique technique that pulmonologists can rely on to obtain target tissue of lung in a minimally invasive way. A few researchers demonstrated the utility of R-EBUS-guided transbronchial cryobiopsy for the analysis of PPL. Furthermore, some studies reported the comparison between yield of cryobiopsy and conventional forceps biopsy and found that bronchoscopic cryobiopsy for PPL sampling is advantageous.8
Cryobiopsy or “cold biopsy” has been in use for bronchoscopic procedures for several years. However, using cryobiopsy to sample PPL is a new application of this old technology.9 The superiority of the cryoprobe lies in its ability to obtain a more extensive tissue, and a 360°/lateral biopsy. For the lesions having an adjacent or eccentric orientation, this ability may be specifically advantageous compared to conventional forceps biopsy.1
Our study aimed to evaluate the performance of hybrid technique of R-EBUS combined with lung cryobiopsy in the diagnosis of PPLs.
PATIENTS AND METHODS
We performed a retrospective observational study on 40 patients at a tertiary care medical center between the years 2019 and 2020. Preevaluation tests such as complete blood count, coagulation profile, serum creatinine, spirometry, pulse oximetry, electrocardiogram, echocardiography, serology against human immunodeficiency virus and hepatitis B and C viruses, and anesthetist evaluation were carried out before performing cryobiopsy. All patients willing to undergo procedure were included in the study. Patients diagnosed with a peripheral pulmonary lesion on high-resolution computed tomography thorax and those who were fit for general anesthesia were included. Patients having high risk for general anesthesia (American Society of Anesthesiologists category 4-6), hemodynamic instability, pulmonary hypertension (PASP >50 mmHg), uncorrected bleeding diathesis (platelet count <50,000 cells/mm3 or INR >1.5), and severe hypoxemia (PaO2 <50 mmHg on room air) were excluded from the study.
All 40 cases underwent R-EBUS-guided transbronchial cryobiopsy. Patients were intubated with artificial airway under GA. Flexible bronchoscopy was performed to rule out endobronchial lesions. A Fogarty balloon of suitable diameter was placed proximal to target bronchial tree and inflated to confirm complete occlusion of bronchial lumen for tamponade. The 20 Hz R-EBUS probe (Olympus Medical) was inserted without a guide sheath into the preplanned target segment via the bronchoscope working channel. Upon identification of the lesion via R-EBUS, the site of R-EBUS was fixed on fluoroscope imaging. The R-EBUS ultrasound image was documented and categorized into concentric, eccentric, and adjacent. The R-EBUS probe was removed. The cryoprobe was advanced via bronchoscope. The site of cryobiopsy was confirmed on fluoroscope imaging. The cryoprobe was activated for 3-4 s and removed en bloc with the bronchoscope. This retrieval process was done rapidly while maintaining cryoprobe activation until the bronchoscope and cryoprobe were completely out from the patient from the artificial airway orifice. The preplaced balloon was inflated immediately upon removal of bronchoscope. Tissue from cryobiopsy was thawed and retrieved in normal saline from the cryoprobe. Bronchoscope was reintroduced via artificial airway. The Fogarty balloon was deflated and amount of bleeding was noted. Repeat biopsy was performed when bleeding was found to be satisfactorily controlled.
Out of total 40 patients, 10 cases underwent both R-EBUS-guided transbronchial forceps biopsy and transbronchial cryobiopsy. At first, patients were intubated with artificial airway under GA. A Fogarty balloon of suitable diameter was placed proximal to target bronchial tree and inflated to confirm complete occlusion of bronchial lumen for tamponade. The 20 Hz R-EBUS probe (Olympus Medical) was inserted within a guide sheath into the preplanned target segment via the bronchoscope working channel. Upon identification of the lesion via R-EBUS, the site of R-EBUS was fixed on fluoroscope imaging. The R-EBUS ultrasound image was documented and categorized into concentric, eccentric, and adjacent. The guide sheath was locked in place and the R-EBUS probe was removed. The standard fenestrated cup flexible forceps were inserted via guide sheath and three samples were obtained. The sample was collected in normal saline. For sampling the same lesions with cryobiopsy, the guide sheath was removed and cryoprobe was introduced. The site of cryobiopsy was confirmed on fluoroscope imaging. The cryoprobe was activated for 3-4 s and removed en bloc with the bronchoscope from the patient. This retrieval process was done rapidly while maintaining cryoprobe activation until the bronchoscope and cryoprobe were completely out from the patient from the artificial airway orifice. The preplaced balloon was inflated immediately upon removal of bronchoscope. Tissue from cryobiopsy was thawed and retrieved in normal saline from the cryoprobe. Further, bronchoscope was reintroduced and amount of bleeding was noted.
Biopsied specimens were fixed in formalin solution and sent to pathology laboratory immediately for processing and analysis. Bronchoscopy was performed again to look for evidence of airway bleeding and other complications after each round of cryobiopsy. Barring any complication, the procedure was repeated again until 3 biopsy tissues were obtained. Before biopsy, 10 cc of normal saline was instilled into the target segment and aspirated for microbiological or cytological examination in cases where infective causes were suspected. Postprocedure, a chest radiograph was performed to look for pneumothorax.
The data were analyzed by using Statistical Package for the Social Science, version 20, I.B.M., and Armonk, New York software. Data were presented as median (interquartile range). Categorical data were expressed as absolute numbers and percentages. Between the two groups (cryobiopsy and forceps biopsy), comparisons of baseline data were performed using the independent sample t-test for variables with assumed normal distribution. All categorical variables were compared between the two groups using Pearson’s Chi-squared test or Fisher’s exact test. A value of P < 0.05 was considered statistically significant.
We screen a total of 40 patients admitted to a tertiary care center between the years 2019 and 2020. In the present study, a number of males were 22 (55%) and a number of females were 18 (45%) with a mean age of 41 years. Among total patients, 20 (50%) were nonsmokers, 6 (15%) were ex-smokers, and 14 (35%) were smokers. Transbronchial lung cryobiopsy (TBLC) was performed on these 40 patients (Table 1).
|TBLC, No. of Cases n (%)|
|Age (Years)||41 (24-60)|
|Non smoker||20 (50)|
TBLC: Transbronchial lung cryobiopsy
Performance of transbronchial lung cryobiopsy
TBLC was performed on these 40 patients.
Orientation of lesions
Overall diagnostic yield for concentric, eccentric, and adjacently oriented lesions was 19 (47.5%), 12 (30%), and 9 (22.5%), respectively (Table 2).
|TBLC, No. of cases n (%)|
|Mild Bleeding||26 (65)|
|Moderate Bleeding||2 (5)|
|No complication||12 (30)|
TBLC: Transbronchial lung cryobiopsy
Bleeding complications were classified as mild, moderate, and no bleeding. Out of total 40 patients, mild bleeding was observed in 26 (65%) patients. Two (5%) patients had moderate bleeding and no bleeding complication was observed in 12 (30%) patients (Table 2).
The histopathology diagnosis of patients showed the presence of bronchitis and neuroendocrine tumor in 4 (10%) patients. Adenocarcinoma was diagnosed in 10 (25%) patients. Six (15%) patients were detected with tuberculosis (TB). Squamous cell carcinoma and hypersensitivity pneumonitis were observed in 9 (23%) and 1 (3%) patient, respectively (Table 3).
|Diagnosis||TBLC, No. of cases n (%)|
|Neuroendocrine Tumor||4 (10)|
|Squamous cell carcinoma||9 (23)|
|Hypersensitivity pneumonitis||1 (3)|
TB: Tuberculosis, TBLC: Transbronchial lung cryobiopsy
Performance of transbronchial forceps biopsy and transbronchial cryobiopsy
Out of total 40 patients, forceps biopsy in addition to cryobiopsy was performed in 10 (25%) patients. Mild bleeding was observed in 6 (60%) patients and 4 (40%) patients in case of forceps biopsy and cryobiopsy, respectively. In case of cryobiopsy, moderate bleeding was observed only in one patient (10%) (Table 4).
|TBLB, No. of cases n (%)||TBLC, No. of cases n (%)||P|
|Mild Bleeding||6 (60%)||4 (40%)||0.37 [NS]|
|Moderate Bleeding||00||1 (10%)||0.30 [NS]|
|Neuroendocrine Tumor||2 (20%)||2 (20%)|
|Adenocarcinoma||1 (10%)||2 (20%)|
|TB||2 (20%)||2 (20%)|
|Squamous cell carcinoma||2 (20%)||3 (30%)|
|Inconclusive||3 (30%)||1 (10%)|
TB: Tuberculosis, TBLC: Transbronchial lung cryobiopsy, TBLB: Transbronchial lung biopsy, NS: Not significance
Neuroendocrine tumor was diagnosed in 2 (20%) patients by both forceps biopsy and cryobiopsy. In case of forceps biopsy, adenocarcinoma was detected in 1 (10%) patient, while in case of cryobiopsy, it was detected in 2 (20%) patients. The presence of TB was observed in 2 (20%) each by forceps biopsy and cryobiopsy. Squamous cell carcinoma was diagnosed in 2 (20%) patients by performing forceps biopsy and in 3 (30%) patients by performing cryobiopsy. The number of patients showing inconclusive diagnosis using forceps biopsy was 3 (30%) and only 1 (10%) patient showed inconclusive diagnosis in case of cryobiopsy. The overall diagnostic yield of TBLB was 70% and of TBLC was 90%.
Diagnosis of peripheral lung lesions (PPLs) is still challenging. Various guided modalities are available to improve bronchoscopic access to PPL, as diagnostic yield would otherwise be <20% in routine unguided bronchoscopies for PPL. One of the concerning challenges is to enhance the biopsy techniques that are currently available.10 R-EBUS is emerging as a safer method when hybridized with cryobiopsy which increases the diagnostic yield up to 90%.5
This retrospective observational study was conducted on 40 patients. In this study, we utilized a hybrid method of R-EBUS in addition to transbronchial cryobiopsy (TBLC) to enhance the diagnostic ability. TBLC was performed on these 40 patients which exhibited 87.5% diagnostic yield. Further, we compared the outcomes of transbronchial biopsy (TBLB) and TBLC via R-EBUS on 10 patients out of total 40 patients. This comparative analysis revealed that R-EBUS TBLC had a better diagnostic yield of 90% (9 out of 10) than TBLB for which the diagnostic yield was 70% (7 out of 10) which was similar to the first multi-center, prospective, randomized, single-blinded, controlled trial conducted by Hetzel et al.11 In case of TBLB, the complication rate in terms of mild bleeding was 60% (6 out of 10) while it was lesser in TBLC, i.e., 40% (4 out of 10). Similar complication rate was observed in the study reported by Ravaglia et al. who showed that TBLC has been well established in terms of safety and lower complication rates when compared to surgical lung biopsy.12 Kho et al. demonstrated contrasting results in case of complication rate in terms of mild bleeding. They observed greater mild bleeding in case of cryobiopsy than in forceps biopsy.7
In conclusion, we demonstrated that R-EBUS-guided cryobiopsy in the diagnosis of PPLs is a safe procedure with a good diagnostic yield. Utilization of cryoprobes for obtaining biopsies from peripheral lung lesions is feasible. Further evidence in the form of prospective studies is needed to prove the technique’s validity.
The authors thank Neuron Institute of Applied Research for editorial support and technical help. The authors thank the study participants and their families, without whom this study would not have been accomplished.
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