Endobronchial Ultrasonography With Guide Sheath for the Diagnosis of Peripheral Pulmonary Lesions in Japan: A Literature Review

We evaluated the usefulness of endobronchial ultrasonography with guide sheath (EBUS-GS) for the diagnosis of peripheral pulmonary lesions (PPLs) in Japan. We searched the PubMed/Medline database using the keywords “EBUS guide sheath” for Japanese studies on EBUS-GS published between January 2004 and August 2023. We included 32 original articles that evaluated the diagnostic yield of EBUS-GS for PPLs. Case reports and conference abstracts were excluded due to limited information available for quality assessment. The diagnostic yield of EBUS-GS was 73.6% for 2996 malignant lesions, 65.4% for 752 ground-glass nodules, 59.4% for 414 benign lesions, 61.3% for 1114 lesions of size ≤2 cm, and 75.6% for 1246 lesions of size >2 cm; it was 69.4% for lesions located in the upper lobe (n=793), 71.9% for the middle lobe/lingula (n=121), and 62.5% for the lower lobe (n=334). None of the patients experienced severe complications. In this review, EBUS-GS is effective for the diagnosis of malignant and benign PPLs. A multimodality approach is needed to further enhance its diagnostic performance.


Introduction And Background
Recently, the increased use of imaging has led to a higher frequency of incidentally identified peripheral pulmonary lesions (PPLs).Bronchoscopy is commonly performed in Japan for the diagnosis of PPLs.In 2004, Kurimoto et al. first reported the usefulness of endobronchial ultrasonography with guide-sheath (EBUS-GS) [1].Since then, EBUS-GS has been recognized as one of the most effective bronchoscopic methods for collecting samples from PPLs [2].However, its diagnostic yield has varied widely among previous studies.Moreover, EBUS is increasingly used to guide sampling tools, often in combination with a guide sheath, in multiple countries outside Japan.Roth et al. reported that EBUS did not increase the detection rate of cancer in PPLs [3].In Japan, the procedure is typically performed with a guide sheath to detect PPLs.Here, we reviewed previous studies on the usefulness of EBUS-GS for detecting PPLs conducted in Japan.

Review
We systematically searched the Medline database via PubMed for studies on EBUS-GS during bronchoscopy published between January 2004 and August 2023.The search was performed using the keywords "EBUS guide sheath" and it retrieved 187 studies.After screening, we selected 77 original articles from Japan that reported the diagnostic yield of EBUS-GS for diagnosing PPLs.Case reports and conference abstracts were excluded due to limited information available for quality assessment.Ultimately, 32 studies were selected for inclusion (Figure 1) [1,.We calculated the diagnostic yield as the ratio of the number of successful diagnoses to the total number of malignant lesions.In addition, we recorded the number of ground-glass nodules, lesion size (≤2 or >2 cm), malignancy potential (benign or malignant), and lobar location.Given that we only reviewed previously published data, ethical approval was not required.Tables 1-5 present the diagnostic yields of EBUS-GS for malignant lesions, ground-glass nodules, benign lesions, malignant potential, and size.The overall yields were 73.6%, 65.4%, 59.4%, 73.2%, 61.3%, and 75.6% (for lesions of size ≤2 cm and those >2 cm), respectively.The analysis is performed using the 10 studies [1,5,8,[10][11][14][15]18,24,33] for lobar location.The values were 69.4%, 71.9%, and 62.5% for those in the upper lobe, middle lobe/lingula, and lower lobe, respectively.No patients reported any severe complications.

Discussion
A recent meta-analysis demonstrated that the use of novel techniques such as EBUS-GS is associated with improved diagnostic yield of bronchoscopy (up to 70%) [35].Conversely, a study from Norway demonstrated a low detection rate for cancer in PPLs, although bronchoscopy was performed by bronchoscopists with varying levels of expertise [3].Although EBUS is increasingly being used to guide sample collection in several countries, guide sheaths are not usually used in countries other than Japan.In Japan, guide sheaths are widely used during radial probe EBUS-guided transbronchial biopsy of PPLs [36].Oki et al. demonstrated that the use of a guide sheath enhanced the diagnostic yield for small PPLs [34].Himeji et al. observed that EBUS-GS was useful for detecting pulmonary Actinomyces graevenitzii infection and invasive mucinous adenocarcinoma [37,38].To the best of our knowledge, this review is the first to evaluate the usefulness of EBUS-GS when bronchoscopy is performed by bronchoscopists in Japan with varying levels of expertise.The limitation of this research is that it included the analytical methods and heterogeneity among individual studies.
Recent studies of the use of EBUS-GS for PPLs have reported diagnostic yields ranging from as low as 40% to as high as 90%.Surprisingly, the diagnostic yield was not significantly different for guided bronchoscopy procedures performed before and after 2012 [39].Robotic bronchoscopy was approved by the FDA in 2018 and has received significant attention [40].The combined use of robotic bronchoscopy and other technologies, such as cone-beam computed tomography (CT), prevents CT-to-body divergence to optimize biopsy tool-in-lesion [41].In the present review, the diagnostic yield for 2996 malignant lesions, including lung cancer, was 73.6% (range: 61.9%-88.2%)when bronchoscopy was performed by Japanese operators.In Japan, bronchoscopy is typically performed under moderate sedation with opioids and/or benzodiazepines [42].However, in several other countries, it is performed under general anesthesia [43].In addition, Japanese bronchoscopists are experienced in performing procedures for more peripheral and smaller nodules compared to bronchoscopists from other countries.The Japanese technique of bronchoscopy is high quality, because of the corresponding medical education strategies.The society operates independently from other respiratory societies, establishes an accredited specialist training system, and provides an annual program for continuous education to specialists.This unique approach is notably distinct from other countries.Moreover, a multimodal approach combining EBUS-GS, ultrathin bronchoscopy, and virtual bronchoscopic navigation can improve the diagnosis of PPLs.A 3.0 mm ultrathin bronchoscope has recently been used in clinical practice in Japan [10].Moreover, in clinical trials, virtual bronchoscopic navigation is associated with a higher diagnostic yield than nonvirtual bronchoscopic navigation [28,35].In the present review, the diagnostic yield of EBUS-GS was 65.4% (range: 56.7-77.1%)for 752 ground-glass nodules.Such nodules are typically evaluated using EBUS-GS (GuideSheath Kit 2, K403; Olympus) and large transbronchial biopsy forceps (Radial Jaw™4P; Boston Scientific) [44].For targeted therapies of lung cancer patients based on next-generation sequencing (NGS), sufficiently large tissue specimens are required during bronchoscopy.In Japan, NGS is typically performed using the Oncomine Dx Target Test and AmoyDx® Pan Lung Cancer PCR Panel.The use of the lung cancer compact panel, approved by the Japanese Pharmaceutical Affairs in November 2022 as the third multi-gene panel test, is associated with a high success rate for genetic analysis [45].During EBUS-GS, small forceps are typically used, leading to insufficient sample collection for NGS.The combination of EBUS-GS and the lung cancer compact panel is a promising diagnostic strategy for lung cancer [46].

Conclusions
In Japan, EBUS-GS is effective for the diagnosis of malignant and benign PPLs.The Japanese technique of bronchoscopy is of high quality because of the corresponding medical education strategies.A multimodality approach (such as ultrathin bronchoscopy, virtual bronchoscopic navigation, cryobiopsy, and robotic bronchoscopy) is needed to improve its performance.

Flow diagram showing a summary of the literature search. No. Study Year design Additional guidance Number of lesions Number of diagnosis Yield (%) Complications Sampling method
2024 Minami et al.Cureus 16(3): e55595.DOI 10.7759/cureus.55595 2 of 9