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There is a growing demand for lung parenchymal-sparing localized therapies due to the rising incidence of multifocal lung cancers and the growing number of patients who cannot undergo surgery. Lung cancer screening has led to the discovery of more pre-malignant or early-stage lung cancers, and the focus has shifted from treatment to prevention. Transbronchial therapy is an important tool in the local treatment of lung cancers, with microwave ablation showing promise based on early and mid-term results. To improve the precision and efficiency of transbronchial ablation, adjuncts such as mobile C-arm platforms, software to correct for computed tomography (CT)-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy are useful. Other forms of energy such as steam vapor therapy, pulsed electric field, and photodynamic therapy are being intensively investigated. In addition, the future of transbronchial therapies may involve the intratumoral injection of novel agents such as immunomodulating agents, gene therapies, and chimeric antigen receptor T cells. Extensive pre-clinical and some clinical research has shown the synergistic abscopal effect of combination of these agents with ablation. This article aims to provide the latest updates on these technologies and explore their most likely future applications.
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The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.
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Background. Neuroendocrine lesions arising from mediastinal teratomas are rare tumors with only small number of patients reported in literature. The behavior of these lesions appears to be different from traditional neuroendocrine neoplasms. A comprehensive review will be valuable for histologic assessment and treatment planning for similar cases. Case presentation. We present an example of a 57-year-old man who presented with cough. Subsequent work-up revealed an anterior mediastinal mass of 2.1 cm on computed tomography. The patient underwent robot-assisted thoracoscopic thymectomy. Histological examination revealed a mature cystic teratoma with a neuroendocrine component consisting of clusters of tumor cells with round to oval nuclei and a "salt-and-pepper" chromatin pattern. The tumor cells were immunoreactive to cytokeratin, synaptophysin, chromogranin, and INSM1, with a Ki-67 proliferative index of 4%. A histological diagnosis was mature teratoma with well-differentiated low-grade neuroendocrine tumor (carcinoid) was made. The patient was well and without disease after complete surgical excision at 10 months. Literature review. Literature reviewed yielded 13 examples of neuroendocrine lesions arising from mediastinal teratomas. No disease-related mortality was reported, even in lesions with high-grade neuroendocrine, carcinomatous, or immature teratomatous components. Conclusions. Surgical removal is the mainstay of treatment of these lesions, and the presence of a neuroendocrine component does not appear to negatively affect prognosis.
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BACKGROUND: Image-guided thermal ablation is a minimally invasive local therapy for lung malignancies. NAVABLATE characterized the safety and performance of transbronchial microwave ablation (MWA) in the lung. METHODS: The prospective, single-arm, 2-center NAVABLATE study (NCT03569111) evaluated transbronchial MWA in patients with histologically confirmed lung malignancies ≤30 mm in maximum diameter who were not candidates for, or who declined, both surgery and stereotactic body radiation therapy. Ablation of 1 nodule was allowed per subject. The nodule was reached with electromagnetic navigation bronchoscopy. Cone-beam computed tomography was used to verify the ablation catheter position and to evaluate the ablation zone postprocedure. The primary end point was composite adverse events related to the transbronchial MWA device through 1-month follow-up. Secondary end points included technical success (nodule reached and ablated according to the study protocol) and technique efficacy (satisfactory ablation based on 1-month follow-up imaging). RESULTS: Thirty subjects (30 nodules; 66.7% primary lung, 33.3% oligometastatic) were enrolled from February 2019 to September 2020. The pre-procedure median nodule size was 12.5 mm (range 5 to 27 mm). Procedure-day technical success was 100% (30/30), with a mean ablative margin of 9.9±2.7 mm. One-month imaging showed 100% (30/30) technique efficacy. The composite adverse event rate related to the transbronchial MWA device through 1-month follow-up was 3.3% (1 subject, mild hemoptysis). No deaths or pneumothoraces occurred. Four subjects (13.3%) experienced grade 3 complications; none had grade 4 or 5. CONCLUSION: Transbronchial microwave ablation is an alternative treatment modality for malignant lung nodules ≤30 mm. There were no deaths or pneumothorax. In all, 13.3% of patients developed grade 3 or above complications.
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Ablación por Catéter , Neoplasias Pulmonares , Humanos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Microondas/uso terapéutico , Neumotórax/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, the authors aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel 'immunotherapy-driven' LN dissection strategy. MATERIALS AND METHODS: The authors conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification. RESULTS: A total of 144 patients were included, of whom 59 had a DLN count less than or equal to 16 (median, IQR: 11, 7-13); 66 had a DLN count greater than 16 (median, IQR: 23, 19-29). With a median follow-up time of 14.3 months (95% CI: 11.0-17.6), the overall median progression-free survival (PFS) was 7.9 (95% CI: 4.1-11.7) months, 11.7 (95% CI: 7.9-15.6) months in the combination therapy subgroup, and 4.8 (95% CI: 3.1-6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count less than or equal to 16 is associated with an improved PFS in all cohorts [primary cohort: HR=0.26 (95% CI: 0.07-0.89), P =0.03]; [validation cohort: HR=0.46 (95% CI: 0.22-0.96), P =0.04]; [entire cohort: HR=0.53 (95% CI: 0.32-0.89), P =0.02]. The prognostic benefit of DLN count less than or equal to 16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065-0.845, P =0.027). CONCLUSIONS: An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in the immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Femenino , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Escisión del Ganglio Linfático , InmunoterapiaRESUMEN
PURPOSE OF REVIEW: Technological advancement in low-dose computed tomography resulted in an increased incidental discovery of early-stage lung cancer and multifocal ground glass opacity. The demand for parenchyma-preserving treatment strategies is greater now than ever. Pulmonary ablative therapy is a groundbreaking technique to offer local ablative treatment in a lung-sparing manner. It has become a promising technique in lung cancer management with its diverse applicability. In this article, we will review the current development of ablative therapy in lung and look into the future of this innovative technique. RECENT FINDINGS: Current literature suggests that ablative therapy offers comparable local disease control to other local therapies and stereotactic body radiation therapy (SBRT), with a low risk of complications. In particular, bronchoscopic microwave ablation (BMWA) has considerably fewer pleural-based complications due to the avoidance of pleural puncture. BMWA can be considered in the multidisciplinary treatment pathway as it allows re-ablation and allows SBRT after BMWA. SUMMARY: With the benefits which ablative therapy offers and its ability to incorporate into the multidisciplinary management pathway, we foresee ablative therapy, especially BMWA gaining significance in lung cancer treatment. Future directions on developing novel automated navigation platforms and the latest form of ablative energy would further enhance clinical outcomes for our patients.
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Neoplasias Pulmonares , Radiocirugia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Pulmón/patología , Tomografía Computarizada por Rayos XRESUMEN
Objectives: Transbronchial microwave ablation of lung nodules using electromagnetic navigation bronchoscopy is an emerging local therapy for lung oligometastases and multifocal lung cancers as part of a lung-preserving strategy. Concomitant ablation of multiple lung nodules in a single operating session may provide a one-stop solution. Methods: Between April 2019 and April 2023, 25 patients had 2 or more lung nodules ablated concomitantly in our hybrid operating room. Nodules were proven or highly suspicious of malignancies or metastases. Feasibility and safety were retrospectively reviewed. Results: A total of 56 nodules in 25 patients received concomitant multi-nodular ablation. The mean age of patients was 60 years, and the reasons for the lung-preserving strategy were multifocal lung cancers (80%) and lung oligometastases (20%). Among those with multifocal disease, 65% had previous major lung resection for lung cancer. Two to 4 nodules were ablated in each session. The mean nodule size was 9.9 mm (range, 5-20 mm), and the mean minimal margin was 5.9 mm. When comparing concomitant nodule ablation with the 103 single-nodule ablations performed in our institute, a mean of 86 minutes of operative time and 131 minutes of anesthetic time were saved. There were no increased complications despite overlapping ablation zones, and the mean hospital stay was 1.23 days. The rate of pneumothorax was 8%, and that of pleural effusion, pain, and fever was 4% respectively. Conclusions: Concomitant transbronchial microwave ablation of multiple lung nodules is feasible, safe, and associated with reduction in overall anesthetic and operative time. It is an important armamentarium in the contemporary lung-preserving strategy for battling multifocal lung cancers or lung oligometastases.
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Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.
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Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.
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Background: Transbronchial ablation of lung nodules is gaining popularity as part of lung-preserving strategy for patients with multifocal lung cancers or multiple lung oligometastases. Accuracy in placement of ablation catheter is of utmost importance in order to achieve adequate ablation margin. However, older systems are not precise enough for confident placement of ablation catheter and often require multiple cone-beam CT (CBCT) to confirm and readjust its position. The following case is the first microwave lung ablation utilizing the novel IllumisiteTM platform (Medtronic, Minneapolis, MN, USA) in the hybrid operating room (HOR), with enhanced accuracy and workflow. Case Description: A 66-year-old lady had multiple resected adenocarcinomas in bilateral lungs. Upon CT monitoring a right middle lobe (RML) ground glass opacity with solid centre was found to be suspicious due to increasing size and density. Transbronchial electromagnetic navigation bronchoscopy (ENB) microwave ablation of the lesion was performed as part of lung-conserving strategy. After initial navigation, the adjusted nodule position provided by the IllumisiteTM platform after correcting the CT-to-body divergence prompted operators to renavigate and readjust the position of the locatable guide (LG) swiftly to gain accurate access to the nodule, which was confirmed by CBCT. Positional data at the tip of extended working channel (EWC) also allowed precise placement of needle for subsequent ablation. Conclusions: IllumisiteTM is a novel electromagnetic navigational platform that corrects for CT-to-body divergence and ensures continuous locational information by an additional positional coil in the tip of EWC. This precision is especially important for the placement of ablation catheter, as slight deviation would lead to insufficient ablation margin and future recurrence. Workflow is improved by reducing the number of CBCT required for instrument position adjustment.
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The demand for parenchyma-sparing local therapies for lung cancer is rising owing to an increasing incidence of multifocal lung cancers and patients who are unfit for surgery. With the latest evidence of the efficacy of lung cancer screening, more premalignant or early-stage lung cancers are being discovered and the paradigm has shifted from treatment to prevention. Transbronchial therapy is an important armamentarium in the local treatment of lung cancers, with microwave ablation being the most promising based on early to midterm results. Adjuncts to improve transbronchial ablation efficiency and accuracy include mobile C-arm platforms, software to correct for the CT-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy. Other forms of energy including steam vapor therapy and pulse electric field are under intensive investigation.
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OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.
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Although in the last few decades we have witnessed the rapid development of treatments for non-small cell lung cancer (NSCLC), it still remains the leading cause of cancer-related death. Increasing efforts have been devoted to exploring potential biomarkers and molecular targets for NSCLC. Foxp3, a transcription factor that was discovered as a master regulator of regulatory T cells (Tregs), has been found to express abnormally in tumoral cells including lung cancer cells. In recent years, increasing evidence have surfaced, revealing the carcinogenic effect of FOXP3 in lung cancer. In this review, we analyzed and summarized the function of FOXP3, its regulation and therapeutic potentials in NSCLC, with a hope to facilitate the development of novel treatments for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Factores de Transcripción Forkhead , Pulmón/metabolismo , Linfocitos T ReguladoresRESUMEN
Introduction: Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. Methods: To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Results: Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. Discussion: This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.
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In the era of modernized medicine, thoracic surgery has been focusing on achieving minimally invasive surgery and providing a one-stop solution in treating thoracic diseases. Particularly in the Asia population, where patients are keen to have smaller wound and shorter hospital stay, thoracic surgery in Hong Kong has evolved from the traditional open thoracotomy approach to video-assisted thoracoscopic surgery (VATS). In our institution, uniportal VATS for major lung resection was developed in 2012. While uniportal VATS has brought advantages into managing thoracic pathologies, it also brought challenges like instrument fencing during manipulation and suboptimal visualization angle. To improve the procedure and its outcomes, novel techniques and equipment have been developed, for example, double-hinged instruments, robotic assisted technology and magnetic anchored and guided endoscopes (MAGS). With advanced medical imaging nowadays, management of small lung nodules or ground glass opacity (GGO) is in higher demand than ever before. Our hybrid operating room (HOR) can incorporate instant and real-time imaging in lesion localization, and provide treatment via VATS or electromagnetic navigated bronchoscopic (ENB) ablation in a one-stop manner. This paper will review the literature related to the historical development and clinical outcomes of thoracic surgery in Hong Kong and discuss the future perspective of ongoing development.
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Background: Influenza virus (IV) and the rhinovirus (RV) are the two most common circulating respiratory viruses circulating. Natural viral interference has been suggested between them. The effect of such at the population level has been described in temperate region, while its effect at the individual and cellular levels warrants further validation. In this study, we described the respiratory virus epidemiology and the co-infection landscape in the hospitalized population and investigated the distinct molecular pathways involved in the inhibition of virus replication. Methods: Nasopharyngeal aspirates (NPAs) collected from patients during 2015 to 2019 were examined for the presence of respiratory viruses. The correlation of the monthly prevalence between all the tested respiratory viruses, the co-infection rate and the temporal interference of RV and IV were tested. The viral interference was validated in vitro by conducting sequential RV and IV infections in the well-differentiated primary human airway epithelial cells. The contributing molecular pathways were determined by transcriptome analysis. Findings: A total of 112,926 NPAs were evaluated, and the Enterovirus/RV was the most prevalent respiratory virus detected. The negative correlation between EV/RV and IVs prevalence was independent of age and meteorological factors. Compare with other viruses, EV/RV had a significantly lower incidence of co-infection with IVs. Prior exposure to RV inhibited the replication of IV species A, B and oseltamivir-resistance stain in vitro. RV uniquely downregulated genes related to processing of viral mRNA, ribosomal proteins, translation and influenza infection. Interpretation: Epidemiological surveillance and the sequential infection in vitro suggested viral interference between EV/RV and IV operates at the population, individual and cellular levels. Funding: This study was supported by the General Research Fund (Ref: 24107017 and 14103119 to RWYC) and the Chinese University Direct Grant for Research (Ref: 2019·073 to RWYC).
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Electromagnetic navigation bronchoscopy (ENB)-guided indocyanine green (ICG) fluorescence dye marking of subsolid, small and deep lung lesions facilitates subsequent minimally invasive lung resection surgeries. The novel robotic-assisted bronchoscopy (RAB) platform can improve the accuracy and yield of ENB biopsy, and the use of RAB has been extended to ICG dye marking. However, performing this procedure in the hybrid operating room guided by cone-beam CT (CBCT) with immediate proceed to lung surgery has not been well reported. We studied the safety, feasibility and clinical outcomes of 5 consecutive cases performed between December 2021 and March 2022. Navigation success was 100% while localization success using ICG was 80%. The benefits and pitfalls of robotic bronchoscopy procedures, and challenges of combining with hybrid operating room CBCT were discussed in detail. In conclusion, robotic-assisted bronchoscopy is a promising and useful tool for ICG fluorescence dye-marking, providing accurate navigation, superior maneuverability and improved ergonomics compared to conventional bronchoscopy-guided ENB procedures. Learning curve is reasonable, but meticulous system set up to incorporate the robotic system into existing CBCT platform may be required to ensure a smooth procedure.