Transbronchial Microwave Ablation of Peripheral Lung Tumors: The NAVABLATE Study.

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.

Concomitant electromagnetic navigation transbronchial microwave ablation of multiple lung nodules is safe, time-saving, and cost-effective.

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.

Electromagnetic navigation bronchoscopy transbronchial lung nodule ablation with IllumisiteTM platform corrects CT-to-body divergence with tomosynthesis and improves ablation workflow: a case report.

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.

Transbronchial Techniques for Lung Cancer Treatment: Where Are We Now?

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.

Thoracic surgery in Hong Kong.

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.

Robotic Assisted-Bronchoscopy With Cone-Beam CT ICG Dye Marking for Lung Nodule Localization: Experience Beyond USA.

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.

Ten-Year Experience of Chest Wall Reconstruction: Retrospective Review of a Titanium Plate MatrixRIB™ System.

Chest wall tumor resection can result in a large defect that can pose a challenge in reconstruction in restoring chest wall contour, maintaining respiratory mechanics, and improving cosmesis. Titanium plates were first introduced for treating a traumatic flail chest, which yielded promising results in restoring chest wall stability. Subsequently, the applications of titanium plates in chest wall reconstruction surgery were demonstrated in case reports and series. Our center has adopted this technique for a decade, and patients are actively followed up after operation. Here, we retrospectively analyze our 10-year experience of using titanium plates and other reconstruction approaches for chest wall reconstruction, in terms of clinical outcomes, complications, and reasons for reoperation to determine long-term safety and efficacy. Thirty-eight patients who underwent chest wall resection and reconstruction surgery were identified. Of these, 11 had titanium plate insertion, 11 had patch repair or flap reconstruction, and the remaining 16 had primary closure of defects. Chest wall reconstruction using titanium plate(s) and patch repair (with or without flap reconstruction) was associated with larger chest wall defects and more sternal resections than primary closure. Subgroup analysis also showed that reconstruction by the titanium plate technique was associated with larger chest wall defects than patch repair or flap reconstruction [286.80 cm2 vs. 140.91 cm2 (p = 0.083)]. There was no 30-day hospital mortality. Post-operative arrhythmia was more commonly seen following chest wall reconstruction compared with primary closure (p = 0.041). Furthermore, more wound infections were detected following the use of titanium plate reconstruction compared with the patch repair (with or without flap reconstruction) approach (p = 0.027). In conclusion, the titanium plate system is a safe, effective, and robust approach for chest wall reconstruction surgery, especially in tackling larger defect sizes.

A human pluripotent stem cell-based model of SARS-CoV-2 infection reveals an ACE2-independent inflammatory activation of vascular endothelial cells through TLR4.

To date, the direct causative mechanism of SARS-CoV-2-induced endotheliitis remains unclear. Here, we report that human ECs barely express surface ACE2, and ECs express less intracellular ACE2 than non-ECs of the lungs. We ectopically expressed ACE2 in hESC-ECs to model SARS-CoV-2 infection. ACE2-deficient ECs are resistant to the infection but are more activated than ACE2-expressing ones. The virus directly induces endothelial activation by increasing monocyte adhesion, NO production, and enhanced phosphorylation of p38 mitogen-associated protein kinase (MAPK), NF-κB, and eNOS in ACE2-expressing and -deficient ECs. ACE2-deficient ECs respond to SARS-CoV-2 through TLR4 as treatment with its antagonist inhibits p38 MAPK/NF-κB/ interleukin-1ß (IL-1ß) activation after viral exposure. Genome-wide, single-cell RNA-seq analyses further confirm activation of the TLR4/MAPK14/RELA/IL-1ß axis in circulating ECs of mild and severe COVID-19 patients. Circulating ECs could serve as biomarkers for indicating patients with endotheliitis. Together, our findings support a direct role for SARS-CoV-2 in mediating endothelial inflammation in an ACE2-dependent or -independent manner.

Organoids in Lung Cancer Management.

Lung cancer is a complex milieu of genomically altered cancer cells, a diverse collection of differentiated cells and nonneoplastic stroma. Lung cancer organoids is a three-dimensional structure grown from patient cancer tissue that could mimic in vivo complex behavior and cellular architecture of the cancer. Furthermore, the genomic alterations of the primary lung tumor is captured ex vivo. Lung cancer organoids have become an important preclinical model for oncology studies in recent years. It could be used to model the development of lung cancer, investigate the process of tumorigenesis, and also study the signaling pathways. The organoids could also be a platform to perform drug screening and biomarker validation of lung cancer, providing a promising prediction of patient-specific drug response. In this review, we described how lung cancer organoids have opened new avenues for translating basic cancer research into clinical therapy and discussed the latest and future developments in organoid technology, which could be further applied in lung cancer organoids research.

Management of bronchopleural fistula with endobronchial valve in hybrid operating room following transbronchial microwave ablation.

Transbronchial microwave ablation for the treatment of lung nodules is gaining popularity. In the present case, transbronchial microwave ablation to a right middle lobe lesion was performed under electromagnetic navigation bronchoscopy guidance. It was complicated with pneumothorax and persistent air leak despite chest drainage and chemical pleurodesis. A diagnosis of bronchopleural fistula was reached and an endobronchial valve was implanted to the middle lobe segmental bronchus with almost immediate cessation of air leak. Our case demonstrated that endobronchial valve is safe and effective in managing bronchopleural fistula after transbronchial microwave ablation.

Transbronchial microwave ablation of lung nodules with electromagnetic navigation bronchoscopy guidance-a novel technique and initial experience with 30 cases.

BACKGROUND: Microwave ablation of lung nodules may provide a faster, larger and more predictable ablation zone than other energy sources, while bronchoscopic transbronchial ablation has theoretical advantage of fewer pleural-based complications than percutaneous approach. Our study aims to determine whether the novel combination of bronchoscopic approach and microwave ablation in management of lung nodules is technically feasible, safe and effective. METHODS: This is a retrospective analysis of a single center experience in electromagnetic navigation bronchoscopy microwave ablation in hybrid operating room. Patients had high surgical risks while lung nodules were either proven malignant or radiologically suspicious. Primary endpoints include technical feasibility and safety. RESULTS: Total of 30 lung nodules from 25 patients were treated. Mean nodule size was 15.1 mm, and bronchus directly leads to the nodules (bronchus sign positive) in only half of them. Technical success rate was 100%, although some nodules required double ablation for adequate coverage. Mean minimal ablation margin was 5.51 mm. The mean actual ablation zone volume was -21.4% compared to predicted, likely due to significant tissue contraction ranging from 0-43%. There was no significant heat sink effect. Mean hospital stay was 1.73 days, and only 1 patient stayed for more than 3 days. Complications included pain (13.3%), pneumothorax requiring drainage (6.67%), post-ablation reaction (6.67%), pleural effusion (3.33%) and hemoptysis (3.33%). After median follow up of 12 months, none of the nodules had evidence of progression. CONCLUSIONS: Bronchoscopic transbronchial microwave ablation is safe and feasible for treatment of malignant lung nodules. Prospective study on clinical application of this novel technique is warranted.

Uniportal video-assisted thoracic surgery for major lung resection is associated with less immunochemokine disturbances than multiportal approach.

Multiportal video-assisted thoracic surgery (VATS) for major lung resection causes less immunochemokine production compared to thoracotomy. Whether uniportal VATS is similarly associated with lower early postoperative circulating levels of immunochemokines compared to multiportal VATS have not been studied. Selected patients who received uniportal or multiportal VATS major lung resection were recruited. Blood samples were collected preoperatively and on postoperative days 1 and 3 for enzyme linked immunosorbent assay of serum levels of Tissue Inhibitor of Metalloproteinase (TIMP)-1, Insulin Growth Factor Binding Protein (IGFBP)-3, and Matrix Metalloproteinase (MMP)-9. A linear mixed-effects models were used to analyze the effects of uniportal VATS on the postoperative circulating chemokine levels. From March 2014 to April 2017, 68 consecutive patients consented for the prospective study and received major lung resection by either uniportal VATS (N = 29) or multiportal VATS (N = 39) were identified. Uniportal VATS major lung resection was associated with lower post-operative levels of TIMP-1 and MMP-9 compared to multiportal VATS after controlling for the effects of the corresponding baseline level and the time of follow-up measurement. No difference was observed for the level of IGFBP-3. Less immunochemokine disturbances was observed after uniportal VATS major lung resection compared to multiportal VATS.

Hybrid Theater Facilitates Lung-Preserving Multimodal Treatment for Multiple Pulmonary Metastases.

A patient with a history of hepatocellular carcinoma was found to have multiple pulmonary metastases. Staged treatments were combined into a single operation session in the hybrid theater, encompassing bronchoscopic microwave ablation of central right upper lobe lesions and uniportal surgical wedge resections of peripheral right middle lobe lesions. All lung metastases were successfully treated with adequate margin clearance. Microwave ablation under the guidance of electromagnetic navigation bronchoscopy in the hybrid theater is a novel contribution to the multimodal operative management of multiple pulmonary neoplasms. It is a unique choice for patients with multilobar, subcentimeter metastases, and with concerns about lung function preservation.

Use of custom made 3-dimensional printed surgical guide for manubrio-sternal resection of solitary breast cancer metastasis: case report.

A 44-year-old lady with solitary 4.4-cm metastasis to the manubrium from a previously resected invasive ductal carcinoma of the left breast underwent manubrio-sternal resection. We describe our unique approach of using 3-dimensional (3D)-computed tomography (CT) image segmentation planning for reconstructing desirable resection boundaries, design of ideal superficial and deep surgical resection guides, and followed by 3D printing of guides using autoclavable thermoplastic for use during surgery. The surgical guides over the ribs and sternum rapidly and accurately define resection lines intraoperatively, achieve good surgical margins, and could reduce resection and reconstruction related morbidity for performing complex surgical resection of the chest wall. The patient was discharged 2 weeks postoperatively and remained free from local recurrence on CT scan 1-year after resection.