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An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

ABSTRACT: Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870-80. ©2016 AACR.

SUBMITTER: Jin CS

PROVIDER: S-EPMC5050138 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

Jin Cheng S CS Wada Hironobu H Anayama Takashi T McVeigh Patrick Z PZ Hu Hsin Pei HP Hirohashi Kentaro K Nakajima Takahiro T Kato Tatsuya T Keshavjee Shaf S Hwang David D Wilson Brian C BC Zheng Gang G Yasufuku Kazuhiro K

Cancer research 20160819 19

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes ac ...[more]

PMID: 27543602

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Project description:Background:Metagenomic next-generation sequencing (mNGS) is a new technology that allows for unbiased detection of pathogens. However, there are few reports on mNGS of lung biopsy tissues for pulmonary infection diagnosis. In addition, radial endobronchial ultrasound (R-EBUS) is widely used to detect peripheral pulmonary lesions (PPLs), but it is rarely used in the diagnosis of peripheral lung infection. Objective:The present study aims to evaluate the combined application of R-EBUS-guided transbronchial lung biopsy (TBLB) and mNGS for the diagnosis of peripheral pulmonary infectious lesions. Methods:From July 2018 to April 2019, 121 patients from Tianjin Medical University General Hospital diagnosed with PPLs and lung infection were enrolled in this prospective randomized study . Once the lesion was located, either TBLB or R-EBUS-guided-TBLB was performed in randomly selected patients, and mNGS was applied for pathogen detection in lung biopsy tissues. The results of mNGS were compared between the TBLB group and R-EBUS-guided TBLB group. In addition, the clinical characteristics and EBUS images from 61 patients receiving bronchoscopy for peripheral lung infectious detection were analyzed and compared with the results of mNGS. Results:The positivity rate of mNGS in R-EBUS-guided TBLB was (78.7%, 48/61) that was significantly higher than (60.0%, 36/60) in the TBLB group. Difference in the position of R-EBUS probe and image characteristics of peripheral lung infectious lesions affected the positivity rate of mNGS. Tissue collected by R-EBUS within the lesion produced higher positivity rate than samples collected adjacent to the lesion (P=0.030, odds ratio 17.742; 95% confidence interval, from 1.325 to 237.645). Anechoic areas and luminant areas of ultrasonic image characteristics were correlated with lower positivity rate of mNGS (respectively, P=0.019, odds ratio 17.878; 95% confidence interval, from 1.595 to 200.399; P=0.042, odds ratio 16.745; 95% confidence interval, from 1.106 to 253.479). Conclusions:R-EBUS-guided TBLB is a safe and effective technique in the diagnosis of peripheral lung infectious lesions. R-EBUS significantly facilitates the accurate insertion of bronchoscope into the lesions, which improves positivity rate of mNGS analysis in pathogen detection. The R-EBUS probe position within lesion produced a higher positivity rate of mNGS analysis. Nevertheless, the presence of anechoic and luminant areas on ultrasonic image was correlated with poor mNGS positivity rate.

Project description:Objective. Stereotactic technology enables fine navigation to small structures in the human body. While current stereotactic systems facilitate accurate targeting, they are mechanically cumbersome and limited in scope. Here, we hypothesized that a stereotactic system could be developed with a reduced footprint while maintaining broad targeting capabilities in order to improve versatility in frame placement location and surgical workflow.Approach. We designed a stereotactic system around the center-of-arc principle, with mechanical properties that would enable a compact design and ample targeting and trajectory maneuverability. To examine the opportunity for a low-cost rapidly-deployable system we developed two fabrication variants, one using three dimensional (3D)-printing and the other using conventional machining. Mechanical and image-guided accuracies were tested in phantom studies using magnetic resonance imaging (MRI) and computed tomography. Using human cadaver head specimens, we assessed the system's surgical workflow and its ability to reliably and accurately implant electrodes in deep brain stimulation (DBS) surgery.Main results. We developed a small 7.7 × 5.4 cm2device platform that rigidly mounts to curvilinear bone and supports the attachment of surgical instrumentation. Attachment of two surgical instruments, an imaging localizer and a compact targeting device, demonstrated successful MRI-guided intervention in phantom studies with a vector error of 1.79 ± 0.41 mm. Evaluation of the 3D-printed system for DBS surgery confirmed ease of device platform attachment and instrument functionality, as well as demonstrated a surgical targeting accuracy of 1.83 ± 0.15 mm. In addition, we found the surgical time to be 78.3 ± 5.4 min for bilateral electrode implantation.Significance. We developed a light and compact stereotactic system whose accuracy is on par with those used clinically. This technology is suitable for clinical translation and its flexibility in positioning will seamlessly expand the capabilities for stereotaxy to treat a wide range of conditions, both within neurosurgery and beyond.

Project description:BACKGROUND:Radial endobronchial ultrasound (R-EBUS) transbronchial lung biopsy (TBLB) improves the diagnostic yield from peripheral pulmonary lesions (PPLs). However, the small specimens obtained using small forceps through a guide sheath (GS) may impede diagnosis and molecular analysis. Here, we investigated the diagnostic significance of additional conventional TBLB with standard forceps after R-EBUS-GS-guided TBLB. METHODS:We retrospectively reviewed data from 55 patients who underwent conventional TBLB after R-EBUS-GS-guided TBLB for PPL diagnosis. Procedures were performed on single PPLs with no visible lesions on bronchoscopy. In cases with inconclusive pathologic confirmation, final diagnoses were made based on pathologic specimens or clinical observations. RESULTS:The median size of the target lesions was 28?mm. The appearances on computed tomography images were solid (n = 45, 81.8%), part-solid (n = 7, 12.7%), and cavitary nodules (n = 3, 5.5%). A computed tomography bronchus sign was present in 35 (63.6%) cases, and a radial probe was positioned within target lesion in 32 (58.2%) cases. R-EBUS-GS-guided TBLB was diagnostic in 30 (54.5%) patients, and subsequent conventional TBLB yielded additional diagnostic information in 8 (14.5%) patients. Probe positioning within target lesions and the outer margin of PPLs more than 1 cm from pleura were significantly associated with enhanced diagnostic yield from the combined procedures. In conventional TBLB, probe positioning within target lesions (75.0% vs. 11.8%, P = 0.004) and characteristic of nonsolid nodules (83.3% vs. 15.8%, P = 0.006) were significantly associated with additional diagnostic utility. CONCLUSIONS:Conventional TBLB following R-EBUS-GS-guided TBLB could be a useful procedure for diagnosing PPLs, especially for nonsolid nodules. KEY POINTS:Significant findings of the study: Additional conventional TBLB with standard forceps after R-EBUS-GS-guided TBLB yielded an additional 14.5% diagnostic utility for peripheral pulmonary lesions. For conventional TBLB, probe positioning within target lesions and nonsolid nodules were significantly associated with additional diagnostic utility. WHAT THIS STUDY ADDS:Conventional TBLB with standard forceps after R-EBUS-GS-guided TBLB is an effective and economically accessible diagnostic tool for peripheral pulmonary lesions.

Project description:The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.

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An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

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An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

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