Peripheral pulmonary lesions (PPLs) present a significant diagnostic challenge due to their location beyond the reach of traditional bronchoscopy. With lung cancer being the leading cause of cancer-related mortality worldwide, accurate and early diagnosis of PPLs is crucial. Virtual bronchoscopic navigation (VBN) combined with radial endobronchial ultrasound (R-EBUS) has emerged as a promising technique to enhance the diagnostic yield for these lesions. This retrospective observational study evaluated the diagnostic yield of VBN-guided R-EBUS in patients with PPLs identified on computed tomography. The study included nine patients who underwent VBN-guided R-EBUS biopsy sampling. Patient demographics, lesion characteristics, and procedural outcomes were analyzed using descriptive and inferential statistics. The mean age of the patients was 57.33 years, with a mean lesion size of 3.24 cm. The diagnostic yield of VBN-guided R-EBUS was 77.7% (95% confidence interval: 68.5-85.8%). Non-small cell carcinoma was the most frequent histopathological diagnosis (55.5%). Complications included bleeding in two patients (22.2%) and bronchospasm in one patient (11.1%), all managed conservatively. VBN-guided R-EBUS provides high diagnostic accuracy and a low risk of complications in patients with PPLs.

Diagnosis of peripheral pulmonary lesion (PPL) is the most challenging field in bronchoscopy and interventional pulmonology, which concerns early lung cancer diagnosis. Despite novel techniques and new approaches to the periphery of the lung, almost 25% of PPLs remain undiagnosed. Bronchoscopy with guide systems, virtual and/or electromagnetic navigation, robotic bronchoscopy, and transparenchymal nodule approaches tend to provide a higher percentage of reaching the lesion, but the diagnostic yield rarely exceeds 75%, regardless of the instruments used. Further studies are needed to evaluate what the main constraints of this discrepancy are and if a combined use of these techniques and instruments can provide an increased diagnostic yield.

Lung cancer is a major global health issue, with 2.21 million cases and 1.80 million deaths reported in 2020. It is the leading cause of cancer death worldwide. Most lung cancers have been linked to tobacco use, with changes in cigarette composition over the years contributing to shifts in cancer types and tumor locations within the lungs. Additionally, there is a growing incidence of lung cancer among never-smokers, particularly in East Asia, which is expected to increase the global burden of the disease. The classification of non-small cell lung cancer (NSCLC) into distinct subtypes is crucial for treatment efficacy and patient safety, especially as different subtypes respond differently to chemotherapy. For instance, certain chemotherapeutic agents are more effective for adenocarcinoma than for squamous carcinoma, which has led to the exclusion of squamous carcinoma from treatments like Bevacizumab due to safety concerns. This necessitates accurate histological diagnosis, which requires sufficient tissue samples from biopsies. However, acquiring adequate tissue is challenging due to the complex nature of lung tumors, patient comorbidities, and potential complications from biopsy procedures, such as bleeding, pneumothorax, and the purported risk of local recurrence. The need for improved diagnostic techniques has led to the development of advanced technologies like electromagnetic navigation bronchoscopy (ENB), radial endobronchial ultrasound (rEBUS), and robotic bronchoscopy. ENB and rEBUS have enhanced the accuracy and safety of lung biopsies, particularly for peripheral lesions, but both have limitations, such as the dependency on the presence of a bronchus sign. Robotic bronchoscopy, which builds on ENB, offers greater maneuverability and stability, improving diagnostic yields. Additionally, new imaging adjuncts, such as Cone Beam Computed Tomography (CBCT) and augmented fluoroscopy, further enhance the precision of these procedures by providing real-time, high-resolution imaging. These advancements are crucial as lung cancer is increasingly being detected at earlier stages due to screening programs, which require minimally invasive, accurate diagnostic methods to improve patient outcomes. This review aims to provide a comprehensive overview of the current challenges in lung cancer diagnostics and the innovative technological advancements in this rapidly evolving field, which represents an increasingly exciting career path for aspiring pulmonologists.

Various bronchoscopic guidance techniques have emerged to improve the diagnostic yield of peripheral pulmonary lesions (PPLs), especially when combined with ultra-thin bronchoscopy. However, uncertainties exists in the convenience, accuracy rate, and complications of these techniques. We compared the feasibility, accuracy rate, and complication rates of transbronchial biopsy of PPLs sampled by the standard thin-layer CT navigation combined with ultrathin bronchoscopy (CTNUTB), the Lungpro virtual navigation combined with ultrathin bronchoscopy (VNUTB), and electromagnetic navigation combined with ultrathin bronchoscopy (ENUTB).

Retrospectively identified were 256 patients sampled with transbronchial biopsy of PPLs. Eligible patients referred for CTNUTB, VNUTB, and ENUTB from January 2017 to December 2021 were included. We comprehensively compared the accuracy rate, feasibility, and complication rates for each method.

There was no significant difference in the accuracy rate of CTNUTB, VNUTB, and ENUTB (p = 0.293). The operation time via Lungpro navigation was the shortest (14.4 min, p < 0.001). The planning time via CT planning was the shortest (7.36 min, p < 0.001). There was no difference in the incidence of complications such as hemorrhage, pneumonia, and pneumothorax (p = 0.123). Besides, ENUTB costs more than $2000, while CTNUTB and VNUTB cost only about $130-230.

CTNUTB is still the main bronchoscopy method we recommended, which has low cost, simple operation, and safety no less than the others. In contrast, ENUTB provides a higher accuracy rate for small diameter nodules (less than 2 cm), which has a high use value and is worth promoting in the future.

Peripheral pulmonary lesions (PPLs) with ground-glass opacity (GGO) are generally difficult to diagnose via bronchoscopy. Cryobiopsy, a recently introduced technique, provides quantitatively and qualitatively superior tissues compared with conventional biopsy methods and can improve diagnostic outcomes. However, its diagnostic accuracy has not been specifically investigated. Therefore, this study aimed to determine whether the combined use of cryobiopsy improves the diagnostic yield for PPLs with GGO.

Consecutive patients who underwent bronchoscopy combined with radial endobronchial ultrasound and virtual bronchoscopic navigation for PPLs with GGO were retrospectively reviewed between June 2014 and May 2020. Cryobiopsy was introduced at our institution in June 2017. Patients who underwent only conventional biopsy (forceps and/or needle aspiration) between June 2014 and May 2017 were classified as the conventional group, whereas those who underwent cryobiopsy with or without conventional biopsy between June 2017 and May 2020 were categorized as the "cryo" group. The diagnostic performance of the two groups was compared using propensity score-matched analysis.

Overall, 553 cases were identified, including 250 and 303 in the cryo and conventional groups, respectively. Propensity scoring was implemented to match lesion characteristics and intraprocedural findings, leading to the selection of 232 pairs of cases for each matched (m) group. The diagnostic yield in the m-cryo group was significantly higher than that in the m-conventional group [88.8% vs. 63.8%, odds ratio: 4.50 (95% confidence interval: 2.76-7.33), P<0.001]. Although the incidence of grade 2 and 3 bleeding in the m-cryo group was higher than that in the m-conventional group (40.5% vs. 8.6% and 2.6% vs. 0.4%, respectively; P<0.001), grade 4 bleeding was not reported.

The combined use of cryobiopsy provides improved diagnostic yield for PPLs with GGO compared with conventional biopsy methods.

Previous studies have shown that rapid on-site evaluation (ROSE) improves the diagnostic yield of bronchoscopy using endobronchial ultrasound with a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPL). While ROSE of imprint cytology from forceps biopsy has been widely discussed, there are few reports on ROSE of brush cytology. This study investigated the utility of ROSE of brush cytology during bronchoscopy. We retrospectively analyzed data from 214 patients who underwent bronchoscopy with EBUS-GS for PPL. The patients in the ROSE group had significantly higher diagnostic sensitivity through the entire bronchoscopy process than in the non-ROSE group (96.8% vs. 83.3%, P = 0.002). The use of ROSE significantly increased the sensitivity of brush cytology with Papanicolaou staining (92.9% vs. 75.0%, P < 0.001). When ROSE was sequentially repeated on brushing specimens, initially negative ROSE results converted to positive in 79.5% of cases, and the proportion of specimens with high tumor cell counts increased from 42.1 to 69.0%. This study concludes that ROSE of brush cytology improves the diagnostic accuracy of bronchoscopy and enhances specimen quality through repeated brushing.

The use of sublobar resection has increased with advances in imaging technologies. However, it is difficult for thoracic surgeons to identify small lung tumours intraoperatively. Radiofrequency identification (RFID) lung-marking systems are useful for overcoming this difficulty; however, accurate placement is essential for maximum effectiveness.

We retrospectively reviewed patients who underwent RFID tag placement via fluoroscopic bronchoscopy under virtual bronchoscopic navigation (VBN) guidance before our institution's sublobar resection of lung lesions. Thirty-one patients with 31 lung lesions underwent RFID lung-marking with fluoroscopic bronchoscopy under VBN guidance.

Of the 31 procedures, 26 tags were placed within 10 mm of the target site, 2 were placed more than 10 mm away from the target site, and 3 were placed in a different area from the target bronchus. No clinical complications were associated with RFID tag placement, such as pneumothorax or bleeding. The contribution of the RFID lung-marking system to surgery was high, particularly when the RFID tag was placed at the target site and tumour was located in the intermediate hilar zone.

An RFID tag can be placed near the target site using fluoroscopic bronchoscopy in combination with VBN guidance. RFID tag placement under fluoroscopic bronchoscopy with VBN guidance is useful for certain segmentectomies.

In the past two decades, bronchoscopy of peripheral pulmonary lesions (PPLs) has improved its diagnostic yield due to the combination of various instruments and devices. Meanwhile, the application is complex and intertwined.

This review article outlines strategies in diagnostic bronchoscopy for PPLs. We summarize the utility and evidence of key instruments and devices based on the results of clinical trials. Future perspectives of bronchoscopy for PPLs are also discussed.

The accuracy of reaching PPLs by bronchoscopy has improved significantly with the introduction of combined instruments such as navigation, radial endobronchial ultrasound, digital tomosynthesis, and cone-beam computed tomography. It has been accelerated with the advent of approach tools such as newer ultrathin bronchoscopes and robotic-assisted bronchoscopy. In addition, needle aspiration and cryobiopsy provide further diagnostic opportunities beyond forceps biopsy. Rapid on-site evaluation may also play an important role in decision making during the procedures. As a result, the diagnostic yield of bronchoscopy for PPLs has improved to a level comparable to that of transthoracic needle biopsy. The techniques and technologies developed in the diagnosis will be carried over to the next step in the transbronchial treatment of PPLs in the future.

Diagnosis of peripheral pulmonary lesions (PPL) is one of the most challenging fields in early lung cancer diagnosis. Despite novel techniques and new approaches to the periphery of the lung, almost 25% of PPL remains undiagnosed. Virtual bronchoscopy navigation (VBN) potentially allows to sample PPL previously not reachable with conventional bronchoscopy. In this preliminary report, we described nine cases of PPL (in which conventional bronchoscopy did not reach the lesion) sampled with VBN, from which we obtained a diagnosis in seven out of nine cases (77.8%), consistent with other reported results in literature. More large-scale data are needed to whether VBN can increase diagnostic yield (DY) of PPL.

The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs.

The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1.

An analysis of 46 studies with a total of 7252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4 % (95 % CI: 69.9%-76.7 %), with significant heterogeneity detected among studies (I2 = 90 %, P < 0.001). Further analysis demonstrated PPLs located in the middle or lower lobe, >2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1 % (95 % CI: 2.1%-4.3 %), 0.4 % (95 % CI: 0.1%-0.7 %) and 1.1 % (95 % CI: 0.5%-2.0 %), respectively.

r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

Today, the increasing number of incidentally detected peripheral pulmonary lesions (PPLs) within and outside lung cancer screening trials is a diagnostic challenge. This fact encourages further improvement of diagnostic procedures to increase the diagnostic yield of transbronchial biopsy, which has been shown to have a low complication rate. The purpose of this study was to evaluate the safety and feasibility of a new ultrathin 1.1 cryoprobe that can be placed through an ultrathin bronchoscope (UTB) using fluoroscopy and radial endobronchial ultrasonography (rEBUS) navigation for assessing PPLs.

Thirty-five patients with PPL less than 4 cm in diameter were prospectively enrolled to receive transbronchial cryobiopsies (TBCBs) using the ultrathin 1.1-mm cryoprobe. Navigation to the PPL was accomplished with the UTB. Under rEBUS and fluoroscopy guidance up to 4 cryobiopsies were obtained. The sample sizes of the biopsies were compared to a historic collective derived from a 1.9-mm cryoprobe and standard forceps. The feasibility and safety of the procedure, the cumulative and overall diagnostic yield, and the cryobiopsy sizes were evaluated.

After detection with the rEBUS, TBCB was collected from 35 PPLs, establishing a diagnosis in 25 cases, corresponding to an overall diagnostic yield of 71.4%. There was no difference in diagnostic yield for PPL <20 mm or ≥20 mm. All cryobiopsies were representative with a mean tissue area of 11.9 ± 4.3 mm2, which was significantly larger compared to the historic collective (p = 0.003). Six mild and four moderate bleeding events and 1 case of pneumothorax were observed.

Using the ultrathin 1.1-mm cryoprobe combined with an UTB for rEBUS-guided TBCB of PPL is feasible and safe. This diagnostic approach improves bronchoscopic techniques for diagnosing peripheral lung lesions and may contribute to improve diagnosis of lung cancer even in small PPL.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

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.

Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based fluorescence-lifetime imaging microscopy (FLIM), a technique which measures endogenous fluorophore decay rates, may aid identification of optimal biopsy sites in suspected lung cancer. Our fibre-based fluorescence-lifetime imaging system, utilising 488 nm excitation, which is deliverable via existing diagnostic platforms, enables real-time visualisation and lifetime analysis of distal alveolar lung structure. We evaluated the diagnostic accuracy of the fibre-based fluorescence-lifetime imaging system to detect changes in fluorescence lifetime in freshly resected ex vivo lung cancer and adjacent healthy tissue as a first step towards future translation. The study compares paired non-small cell lung cancer (NSCLC) and non-cancerous tissues with gold standard diagnostic pathology to assess the performance of the technique. Paired NSCLC and non-cancerous lung tissues were obtained from thoracic resection patients (N=21). A clinically compatible 488 nm fluorescence-lifetime endomicroscopy platform was used to acquire simultaneous fluorescence intensity and lifetime images. Fluorescence lifetimes were calculated using a computationally-lightweight, rapid lifetime determination method. Fluorescence lifetime was significantly reduced in ex vivo lung cancer, compared with non-cancerous lung tissue [mean ± standard deviation (SD), 1.79±0.40 vs. 2.15±0.26 ns, P<0.0001], and fluorescence intensity images demonstrated distortion of alveolar elastin autofluorescence structure. Fibre-based fluorescence-lifetime imaging demonstrated good performance characteristics for distinguishing lung cancer, from adjacent non-cancerous tissue, with 81.0% sensitivity and 71.4% specificity. Our novel fibre-based fluorescence-lifetime imaging system, which enables label-free imaging and quantitative lifetime analysis, discriminates ex vivo lung cancer from adjacent healthy tissue. This minimally invasive technique has potential to be translated as a real-time biopsy guidance tool, capable of optimising diagnostic accuracy in lung cancer.

Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs.

Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC.

A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283).

The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Differences between virtual bronchoscopic navigation (VBN) systems and their impacts on the diagnostic yield of transbronchial biopsy (TBB) of peripheral pulmonary nodules (PPNs) remain unclear.

To compare the Synapse 3D system (Version 4.4, Fujifilm, Japan) and DirectPath system (Version 2.0, Olympus, Japan) in the VBN application of PPNs.

Retrospective study with self-paired design and exploratory study with retrospective cohort design.

The study analyzed patients with PPNs using the Synapse 3D system (Group S) and DirectPath system (Group D) and compared differences between the two groups in bronchial tree reconstruction, navigation pathway planning, and VBN-assisted TBB of PPNs.

In all, 289 patients were analyzed ultimately. Bronchial tree reconstruction quality was better in Group S (p < 0.001). Navigation pathway planning duration in Group S was longer than that in Group D (median 1.35 vs 1.04 s, p < 0.001). Automated navigation pathway planning success rate in Group S was higher than that in Group D (36.7% vs 19.7%, p < 0.001), and CT image reconstruction parameter and nodule diameter, bronchus sign, and distance from the hilum had significant effects on it in both groups. Fifty-six patients in Group S and forty-two patients in Group D were analyzed ultimately. The localization success rate and diagnostic yield of PPNs between the two groups were not significantly different (85.3% vs 91.2% and 67.6% vs 61.8%, respectively, p > 0.05).

Synapse 3D system (Version 4.4) and DirectPath system (Version 2.0) had their own merits. Localization success rate and diagnostic yield of VBN-assisted TBB were of no statistical difference for these two VBN systems. Improvements in segmentation algorithms of VBN systems and using the most suitable chest CT scan data for them may be the breakthrough to improve the efficiency of VBN, especially for poor experienced interventional physicians.

Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario.

This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate.

In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred.

This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice.

NCT03716284.

The endoscopic diagnosis of peripheral lung nodules is a challenging aspect of oncological practice. More often than not inaccessible by traditional endoscopy, these nodules necessitate multiple imagery tests, as well as diagnostic surgery for benign lesions. Even though transthoracic ultrasonography has a high diagnostic yield, a sizeable complication rate renders it suboptimal. Over recent years, a number of safe and accurate navigational bronchoscopic procedures have been developed. In this first part, we provide an overview of the bronchoscopic techniques currently applied for the excision and diagnostic analysis of peripheral lung nodules; emphasis is laid on electromagnetic navigation bronchoscopy and the association of virtual bronchoscopy planner with radial endobronchial ultrasound. We conclude by considering recent innovations, notably robotic bronchoscopy.

Bronchoscopes are continuously improving. Increasingly, thinner bronchoscopes with larger working channels and better imaging quality are becoming available for clinical use. Concurrently, useful ancillary devices have been developed, such as radial probe endobronchial ultrasound (rEBUS) and navigation devices. Randomized studies have demonstrated the diagnostic superiority of ultrathin bronchoscopy over thin bronchoscopy under rEBUS and virtual bronchoscopic navigation guidance for small, peripheral pulmonary lesions. Furthermore, biopsy needles and cryoprobes have been miniaturized and adapted to the working channel of the new ultrathin bronchoscopes. Multi-modality and multi-instrumental ultrathin bronchoscopy using such new technologies has facilitated high diagnostic yields.

Transbronchial cryobiopsy (TBCB) is a novel technique for the diagnosis of peripheral lung lesions (PLLs). We aim to evaluate the clinical outcomes of TBCB using a new 1.1-mm diameter cryoprobe for the diagnosis of PLLs.

We performed a prospective observational pilot study on the diagnosis of PLLs (diameter ≤30 mm) by TBCB, using a 1.1-mm diameter cryoprobe with radial endobronchial ultrasound (RP-EBUS), virtual bronchoscopic navigation and fluoroscopy from December 2021 to July 2022. Primary outcome was the pathological diagnostic yield of TBCB, and secondary outcome was adverse event.

A total of 50 patients were enrolled (mean lesion size, 21 mm). TBCB was performed in 49 patients up to three times except for the one with "invisible" finding on RP-EBUS. The overall diagnostic yield of TBCB was 90% (45/50). There was no difference in the diagnostic yield between size (20 mm vs. 20-30 mm; 88% [22/25] vs. 92% [23/25]; P = 1.000), RP-EBUS findings (concentric vs. others; 97% [28/29] vs. 81% [17/21]; P = 0.148), and acute angle location (apical segment of both upper lobes vs. others; 92% [12/13] vs. 89% [33/37]; P = 1.000). The cumulative diagnostic yields of the first, second, and third TBCB were 82% (41/50), 88% (44/50), and 90% (45/50), respectively. Mild bleeding was developed in 56% (28/50), and moderate bleeding was found in 26% (13/50).

TBCB using a 1.1-mm diameter cryoprobe is an effective, reasonable method for the diagnosis of PLLs regardless of its size, RP-EBUS finding, and anatomical location without serious complication.

Clinical Trials.Gov (NCT05046093).

Bronchoscopy with radial-probe endobronchial ultrasound, a guide sheath, and electromagnetic navigation can improve the diagnostic yield of peripheral lung nodules. However, the suitability of specimens for genetic analysis remains unsatisfactory. We hypothesized that a transbronchial biopsy performed after closely approaching the bronchoscope tip to the lesion might provide more suitable specimens for genetic analysis. We enrolled 155 patients with peripheral pulmonary lesions who underwent bronchoscopy with a thin or ultrathin bronchoscope. Bronchoscopy was performed using virtual bronchoscopic navigation and radial-probe endobronchial ultrasound with a guide sheath. The bronchoscope tip was placed closer to the lesion during bronchoscopy to collect larger specimens with higher malignant cell content. The patients who underwent a close-to-lesion biopsy had higher rates of overall diagnostic yield, histopathological diagnostic yield, and specimen quality for genetic testing than those who did not. The significant determinants of the specimen's suitability were the close-to-lesion approach, within-the-lesion image, the use of standard 1.9-mm-forceps, and the number of cancer-cell-positive specimens. The significant predictors of the specimen's suitability for genetic analysis were close-to-lesion biopsy and the number of malignant cell-positive tissue samples. This study demonstrates that the close-to-lesion transbronchial biopsy significantly improves the suitability of bronchoscopic specimens for genetic analysis.

Pulmonary nodules with intermediate to high risk of malignancy should preferably be diagnosed with image guide minimally invasive diagnostics before treatment. Several technological innovations have been developed to endobronchially navigate to these lesions and obtain tissue for diagnosis. This review addresses these technological advancements in navigation bronchoscopy in three basic steps: navigation, position confirmation and acquisition, with a specific focus on cone-beam computed tomography (CBCT). For navigation purposes ultrathin bronchoscopy combined with virtual bronchoscopy navigation, electromagnetic navigation and robotic assisted bronchoscopy all achieve good results as a navigation guidance tool, but cannot confirm location or guide biopsy positioning. Diagnostic yield has seen improvement by combining these techniques with a secondary imaging tool like radial endobronchial ultrasound (rEBUS) and fluoroscopy. For confirmation of lesion access, rEBUS provides local detailed ultrasound-imaging and can be used to confirm lesion access in combination with fluoroscopy, measure nodule-contact area length and determine catheter position for sampling. CBCT is the only technology that can provide precise 3D positioning confirmation. When focusing on tissue acquisition, there is often more than 10% difference between reaching the target and getting a diagnosis. This discrepancy is multifactorial and caused by breathing movements, small samples sizes, instrument tip displacements by tool rigidity and tumour inhomogeneity. Yield can be improved by targeting fluorodeoxyglucose (FDG)-avid regions, immediate feedback of rapid onsite evaluation, choosing sampling tools with different passive stiffnesses, by increasing the number biopsies taken and (future) catheter modifications like (robotic assisted-) active steering. CBCT with augmented fluoroscopy (CBCT-AF) based navigation bronchoscopy combines navigation guidance with 3D-image confirmation of instrument-in-lesion positioning in one device. CBCT-AF allows for overlaying the lesion and navigation pathway and the possibility to outline trans-parenchymal pathways. It can help guide and verify sampling in 3D in near real-time. Disadvantages are the learning curve, the inherent use of radiation and limited availability/access to hybrid theatres. A mobile C-arm can provide 3D imaging, but lower image quality due to lower power and lower contrast-to-noise ratio is a limiting factor. In conclusion, a multi-modality approach in experienced hands seems the best option for achieving a diagnostic accuracy >85%. Either adequate case selection or detailed 3D imaging are essential to obtain high accuracy. For current and future transbronchial treatments, high-resolution (CBCT) 3D-imaging is essential.

Ultrathin bronchoscopy has been reported to have a higher diagnostic yield than thin bronchoscopy for small peripheral lung lesions in transbronchial biopsy under radial endobronchial ultrasonography (EBUS). However, data comparing the number of tumor cells in non-small cell lung cancer (NSCLC) are limited. We retrospectively compared the number of NSCLC tumor cells in peripheral lung lesions obtained using an ultrathin bronchoscope and a thin bronchoscope with radial EBUS between April 2020 and October 2021. In all patients, we used virtual bronchoscopic navigation (VBN) software, and guide sheaths were used in thin bronchoscopy cases. A total of 175 patients were enrolled in this study. Ultrathin bronchoscopy cases (n = 69) had lesions with a smaller diameter that are more peripherally located compared to thin bronchoscopy cases (n = 106) (median, 25.0 vs. 26.5 mm, mean bronchial generations accessed by bronchoscopy; 4.4±1.2 vs. 3.8±1.0, respectively; p<0.010). There were no significant differences in the overall diagnostic yield (ultrathin vs. thin bronchoscopy cases, 68.1% vs. 72.6%, p = 0.610) or diagnostic yield in only lung cancer cases (78.6% vs. 78.5%, p = 1.000). In histologically NSCLC cases (n = 102), the maximum number of tumor cells per slide as the primary endpoint was similar (average, 307.6±246.7 vs. 328.7±314.9, p = 0.710). The success rate of the Oncomine™ analysis did not differ significantly (80.0% vs. 55.6%, p = 0.247). The yield of NSCLC tumor cells was not different between the samples obtained by the ultrathin bronchoscope and those obtained by the thin bronchoscope.

Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes.

A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes.

Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented.

This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

Transbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB.

We performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded.

The total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84).

The probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

Radial probe endobronchial ultrasound (rEBUS) improves the diagnostic yield of peripheral pulmonary lesions (PPLs). A notable methodological limitation of rEBUS is that it does not provide real-time images during transbronchial biopsy (TBB) procedures. To overcome this limitation, a guide sheath (GS) method was developed.

This review covers the procedures and complications of rEBUS-guided TBB with a GS (EGS method). We also present the data from key randomized controlled trials (RCTs) of the EGS method and summarize the usefulness of combining the EGS method with various techniques. Finally, we discuss in which situations EGS should be used.

A large RCT showed that the diagnostic yield of the EGS method for PPLs was significantly higher than that of rEBUS-guided TBB without a GS (non-GS method). However, since the EGS and non-GS methods each have their own advantages and disadvantages, they should be considered complementary and used flexibly in different cases. In some cases, a combination of the two may be an option. The appropriate combination of EGS with various techniques may enhance the diagnostic yield of PPLs and help prevent complications. The choice should be based on the location and texture of the target lesion, as well as operator skill, resource availability, safety, and accuracy.

Guided bronchoscopy is increasingly used to diagnose peripheral pulmonary lesions (PPLs). A meta-analysis published in 2012 demonstrated a pooled diagnostic yield of 70%; however, recent publications have documented yields as low as 40% and as high as 90%.

Has the diagnostic yield of guided bronchoscopy in patients with PPLs improved over the past decade?

A comprehensive search was performed of studies evaluating the diagnostic yield of differing bronchoscopic technologies used to reach PPLs. Study quality was assessed using the Quality assessment of diagnostic accuracy of studies (QUADAS-2) assessment tool. Number of lesions, type of technology used, overall diagnostic yield, and yield by size were extracted. Adverse events were recorded. Meta-analytic techniques were used to summarize findings across all studies.

A total of 16,389 lesions from 126 studies were included. There was no significant difference in diagnostic yield prior to 2012 (39 studies; 3,052 lesions; yield 70.5%) vs after 2012 (87 studies; 13,535 lesions; yield 69.2%) (P > .05). Additionally, there was no significant difference in yield when comparing different technologies. Studies with low risk of overall bias had a lower diagnostic yield than those with high risk of bias (66% vs 71%, respectively; P = .018). Lesion size > 2 cm, presence of bronchus sign, and reports with a high prevalence of malignancy in the study population were associated with significantly higher diagnostic yield. Significant (P < .0001) between-study heterogeneity was also noted.

Despite the reported advances in bronchoscopic technology to diagnose PPLs, the diagnostic yield of guided bronchoscopy has not improved.

Pulmonary nodules are often discovered incidentally during CT scans performed for other reasons. While the vast majority of nodules are benign, a small percentage may represent early-stage lung cancer with the potential for curative treatments. With the growing use of CT for both clinical purposes and lung cancer screening, the number of pulmonary nodules detected is expected to increase substantially. Despite well-established guidelines, many nodules do not receive proper evaluation due to a variety of factors, including inadequate coordination of care and financial and social barriers. To address this quality gap, novel approaches such as multidisciplinary nodule clinics and multidisciplinary boards may be necessary. As pulmonary nodules may indicate early-stage lung cancer, it is crucial to adopt a risk-stratified approach to identify potential lung cancers at an early stage, while minimizing the risk of harm and expense associated with over investigation of low-risk nodules. This article, authored by multiple specialists involved in nodule management, delves into the diagnostic approach to lung nodules. It covers the process of determining whether a patient requires tissue sampling or continued surveillance. Additionally, the article provides an in-depth examination of the various biopsy and therapeutic options available for malignant lung nodules. The article also emphasizes the significance of early detection in reducing lung cancer mortality, especially among high-risk populations. Furthermore, it addresses the creation of a comprehensive lung nodule program, which involves smoking cessation, lung cancer screening, and systematic evaluation and follow-up of both incidental and screen-detected nodules.

Navigation bronchoscopy has seen rapid development in the past decade in terms of new navigation techniques and multi-modality approaches utilizing different techniques and tools. This systematic review analyses the diagnostic yield and safety of navigation bronchoscopy for the diagnosis of peripheral pulmonary nodules suspected of lung cancer.

An extensive search was performed in Embase, Medline and Cochrane CENTRAL in May 2022. Eligible studies used cone-beam CT-guided navigation (CBCT), electromagnetic navigation (EMN), robotic navigation (RB) or virtual bronchoscopy (VB) as the primary navigation technique. Primary outcomes were diagnostic yield and adverse events. Quality of studies was assessed using QUADAS-2. Random effects meta-analysis was performed, with subgroup analyses for different navigation techniques, newer versus older techniques, nodule size, publication year, and strictness of diagnostic yield definition. Explorative analyses of subgroups reported by studies was performed for nodule size and bronchus sign.

A total of 95 studies (n = 10,381 patients; n = 10,682 nodules) were included. The majority (n = 63; 66.3%) had high risk of bias or applicability concerns in at least one QUADAS-2 domain. Summary diagnostic yield was 70.9% (95%-CI 68.4%-73.2%). Overall pneumothorax rate was 2.5%. Newer navigation techniques using advanced imaging and/or robotics(CBCT, RB, tomosynthesis guided EMN; n = 24 studies) had a statistically significant higher diagnostic yield compared to longer established techniques (EMN, VB; n = 82 studies): 77.5% (95%-CI 74.7%-80.1%) vs 68.8% (95%-CI 65.9%-71.6%) (p < 0.001).Explorative subgroup analyses showed that larger nodule size and bronchus sign presence were associated with a statistically significant higher diagnostic yield. Other subgroup analyses showed no significant differences.

Navigation bronchoscopy is a safe procedure, with the potential for high diagnostic yield, in particular using newer techniques such as RB, CBCT and tomosynthesis-guided EMN. Studies showed a large amount of heterogeneity, making comparisons difficult. Standardized definitions for outcomes with relevant clinical context will improve future comparability.

Surgical resection is still the standard treatment for early-stage lung cancer. A multimodal treatment consisting of chemotherapy, radiotherapy and/or immunotherapy is advised for more advanced disease stages (stages IIb, III and IV). The role of surgery in these stages is limited to very specific indications. Regional treatment techniques are being introduced at a high speed because of improved technology and their possible advantages over traditional surgery. This review includes an overview of established and promising innovative invasive loco-regional techniques stratified based on the route of administration, including endobronchial, endovascular and transthoracic routes, a discussion of the results for each method, and an overview of their implementation and effectiveness.

The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs).

From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022.

The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications.

Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Bronchoscopes cannot reach the periphery of the lung because the bronchi are tapered. Therefore, selectively advancing a device-e.g., an endobronchial ultrasonography (EBUS) probe-to the targets can be challenging. Virtual fluoroscopic preprocedural planning (VFPP) is a method in which the route to the target is superimposed on an X-ray fluoroscopy-like image reconstructed from CT images, facilitating the advancement of the EBUS probe to the target. The VFPP method was integrated into the Ziostation2 bronchoscopic navigation system (Ziosoft, Inc., Tokyo, Japan) in 2018. Here, we prospectively examined the feasibility of the VFPP method using Ziostation2 (Zio-VFPP).

Thirty-six patients who had pulmonary lesions with long axes ≤30 mm and who underwent thin-slice CT with ≤0.625-mm thickness were enrolled. We initiated bronchoscopy using EBUS with a guide sheath (EBUS-GS) while referring to Ziostation2 bronchoscopic navigation. When the probe was not "within" a lesion, we attempted to correct its position based on Zio-VFPP. EBUS findings before and after Zio-VFPP were compared.

Zio-VFPP was performed in 24 patients, and EBUS findings improved in nine patients. Before Zio-VFPP, 18 patients were "outside," but after Zio-VFPP, the number decreased to ten. Statistically, this difference was significant (p = 0.0392). There were no cases in which EBUS findings worsened with Zio-VFPP.

Zio-VPFPP improves EBUS findings and significantly reduces "outside" cases. However, further investigation is necessary to verify its effectiveness.

Recently introduced cryobiopsy can provide quantitatively and qualitatively excellent specimens. However, few studies have directly compared the diagnostic yield of cryobiopsy for peripheral pulmonary lesions (PPLs) with that of conventional sampling methods.

We retrospectively reviewed data from consecutive patients who underwent diagnostic bronchoscopy using radial endobronchial ultrasound and virtual bronchoscopic navigation for PPLs (October 2015 to September 2020). Patients who underwent cryobiopsy were assigned to the cryo group, whereas those who did not undergo cryobiopsy were assigned to the conventional group. The diagnostic outcomes of both groups were compared using propensity score analyses.

A total of 2,724 cases were identified, including 492 and 2,232 cases in the cryo and conventional groups, respectively. Propensity scoring was performed to match baseline characteristics, and 481 pairs of cases were selected for each matched group (m-group). The diagnostic yield was significantly higher in the m-cryo group than in the m-conventional group (89.2% vs. 77.6%, odds ratio [OR] = 2.36 [95% confidence interval [CI] = 1.65-3.38], P < 0.001). Propensity score stratification (OR = 2.35 [95% CI = 1.71-3.23]) and regression adjustment (OR = 2.54 [95% CI = 1.83-3.52]) also demonstrated the diagnostic advantages of cryobiopsy. The subgroup analysis revealed that cryobiopsy was notably effective for lesions in the middle lobe/lingula, right/left lower lobe, lesions with ground-glass opacity, and lesions invisible on chest radiography. Although there were more cases of grade 2 and 3 bleeding in the m-cryo group than in the m-conventional group (38.0% vs. 10.2% and 1.5% vs. 0.8%, respectively; P < 0.001), no grade 4 bleeding was observed.

The propensity score analyses revealed that cryobiopsy was associated with a higher diagnostic yield for PPLs than conventional sampling methods. However, increased bleeding risk should be noted as a potential complication.

The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting.

In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy.

Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable.

Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.

The diagnostic yield of thin bronchoscopy with radial probe endobronchial ultrasound (rEBUS) of peripheral pulmonary lesions into which the rEBUS probe cannot be inserted is unsatisfactory. In such cases, adding ultrathin bronchoscopy may be an option. We evaluated the efficacy of sequential ultrathin bronchoscopy for peripheral pulmonary lesions into which the rEBUS probe could not be inserted during thin bronchoscopy.

In this multicentre prospective study, patients with peripheral pulmonary lesions ≤30 mm in diameter underwent rEBUS-guided transbronchial biopsy using a 4.0 mm diameter thin bronchoscope. In patients with lesions into which a rEBUS probe could not be inserted using that bronchoscope, bronchoscopy using a 3.0 mm diameter ultrathin bronchoscope was performed.

A total of 342 patients were enrolled and 340 were analysed. Among them, 87 patients with lesions of a median longest diameter of 17.5 mm underwent thin bronchoscopy followed by ultrathin bronchoscopy. Of the 87 patients, the rEBUS probe was successfully inserted into the lesions via the ultrathin bronchoscope in 50 patients (57.5%). Of the 87 patients, the diagnostic yields of thin bronchoscopy and ultrathin bronchoscopy were 12.6% (11 of 87) and 41.4% (36 of 87), respectively (p < 0.001).

Ultrathin bronchoscopy affords a higher diagnostic yield for lesions into which a rEBUS probe cannot be inserted via a thin bronchoscope.

As the leading cause of cancer-related deaths worldwide, early detection and diagnosis are crucial to reduce the mortality of lung cancer. To date, the diagnosis of the peripheral pulmonary lesions (PPLs) remains a major unmet clinical need. The urgency of diagnosing PPLs has driven a series of development of the advanced bronchoscopy-guided techniques in the past decades, such as radial probe-endobronchial ultrasonography (RP-EBUS), virtual bronchoscopy navigation (VBN), electromagnetic navigation bronchoscopy (ENB), bronchoscopic transparenchymal nodule access (BTPNA), and robotic-assisted bronchoscopy. However, these techniques also have their own limitations. In this review, we would like to introduce the development of diagnostic techniques for PPLs, with a special focus on biopsy approaches and advanced guided bronchoscopy techniques by discussing their advantages, limitations, and future prospects.