Inage Terunaga

BACKGROUND: Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires in vivo study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs. METHODS: An ultra-small parallel-type composite optical fiberscope (COF) with a 0.97 mm outer diameter tip. The integration of illumination and laser irradiation fibers inside the COF allows simultaneous white-light and fluorescence imaging, as well as real-time monitoring of tip position during laser phototherapy. An orthotopic lung cancer mouse model was created with three human lung cancer cell lines transbronchially inoculated into athymic nude mice. The COF was inserted transbronchially into a total of 15 mice for tumor observation. For in vivo fluorescence imaging, an organic nanoparticle, porphysome, was used as a PS. Laser excitation through the COF was performed at 50 mW using a 671 nm source. RESULTS: The overall success rate for creating orthotopic lung tumors was 71%. Transbronchial white light images were successfully captured by COF. Access to the left main bronchus was successful in 87% of mice (13/15), the right main bronchus to the cranial lobe bronchus level in 100% (15/15), and to the right basal trifurcation of the middle lobe, caudal lobe and accessory lobe in 93% (14/15). For transbronchial tumor localization of orthotopic lung cancer tumors, PS-laden tumor with the strong signal was clearly contrasted from the normal bronchial wall. CONCLUSIONS: The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts in vivo. This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in in vivo survival models inoculated with human lung cancer cells.

BACKGROUND: Spontaneous pneumothorax is common in relatively young, healthy patients. The risk factors for postoperative recurrence after correction are not fully understood. METHODS: We retrospectively reviewed the records of patients who underwent surgery for spontaneous pneumothorax between January 2006 and October 2017. We assessed the possible factors causing postoperative recurrence using univariate and multivariate analyses. We then used the inverse probability of treatment-weighted method to correct for confounding factors. RESULTS: Postoperative recurrence was observed in 41 of 233 patients (17.6%). A significant association with recurrence was noted for primary spontaneous pneumothorax (PSP), never smokers, thoracoscopic surgery, patients younger than 30 years, operative time less than 100 minutes, and surgery by a resident surgeon. Patients younger than 30 years of age had a 5-year recurrence-free probability of 46.3%. On multivariate analysis, patients younger than 30 years was an independent risk factor for recurrence. The confounding factors for recurrence of PSP included patients younger than 30 years, surgery by a resident surgeon, and thoracoscopic surgery. After adjusting for confounders, patients younger than 30 years was the only factor associated with recurrence (P=0.015). Patients who underwent bulla ligation with pleural reinforcement using an absorbable polyglycolic acid (PGA) sheet had a 4% recurrence rate and a 5-year recurrence-free probability of 90.0%. CONCLUSIONS: Patients younger than 30 years of age is a significant factor for postoperative recurrence in patients with PSP. Surgeons may attempt to prevent postoperative recurrence by devising the operative method and pleural reinforcement methods.

© 2020 Elsevier Inc. Radiofrequency ablation (RFA) can be a therapeutic option in medically inoperable lung cancer patients. In this study, we evaluated a prototype bipolar RFA device applicator that can be deployed from a standard endobronchial ultrasound (EBUS) bronchoscope to determine feasibility and histopathological analysis in animal models. Rabbit lung cancers were created by transbronchial injection of VX2 rabbit cancer cells. Once the tumors were developed, they were ablated transpleurally, under EBUS guidance using the prototype RFA device. The animals were then sacrificed for specimen resection. Pig inflammatory lung pseudo-tumors and lymphadenopathy were created by transbronchial injection of a talc paste and ablated transbronchially under EBUS guidance. Pigs were evaluated at 5 days, 2 weeks, and 4 weeks following ablation by bronchoscopy and cone beam computed tomography before necropsy. Nicotinamide adenine dinucleotide hydrogen diaphorase staining was employed to measure the ablation area. Twenty-four VX2 rabbit tumors were ablated. The total ablated area ranged from 0.6 to 3.0 cm2 (mean: 1.8 cm2), corresponding to a total energy range of 1 to 6 kJ. Six pig lung pseudo-tumors and 5 mediastinal lymph nodes were ablated. Adjacent airway ulceration was observed in 3 ablations of lymph nodes. These airway complications resolved within 4 weeks of RFA without any treatment. There was no hemoptysis, air embolism, respiratory distress, or other serious complication noted. In these 2 animal models, we provide evidence that EBUS-guided bipolar RFA is feasible and histopathology shows that can ablate lung tumors and mediastinal lymph nodes under real-time ultrasound guidance.

Implementation of lung cancer screening and improvements in imaging are expected to increase the proportion of lung cancer diagnosed at an early stage. The standard of care has historically been anatomic lobectomy; however, there is now an array of surgical and non-surgical approaches for management of local disease either in active use or under investigation. By their nature, these new modalities offer a theoretical trade-off of reduced morbidity in exchange for reduced efficacy in the setting of advanced disease. It is therefore critical that patients being considered for these approaches (e.g. surgical segmentectomy and SABR) be accurately staged to maximize the potential for definitive treatment. In this article, we will review current approaches to the staging of patients being considered for segmentectomy or ablation. This will serve as a foundation to highlight important questions deserving further investigation.

Diagnosis of early-stage lung cancer has become increasingly important as the detection of peripheral pulmonary lesions (PPLs) grows with widespread adoption of CT-based lung cancer screening. Although CT-guided transthoracic needle aspiration has been the standard diagnostic approach for PPLs, transbronchial sampling by bronchoscopy is often performed due to its reduced rate of adverse events. However, the diagnostic yield of conventional bronchoscopy is often poor. Various bronchoscopic technologies have emerged over recent years to address this limitation, including thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (RP-EBUS), virtual navigation bronchoscopy (VBN), electromagnetic navigation bronchoscopy (ENB), and robotic bronchoscopy. Bronchoscopic transparenchymal nodule access (BTPNA) and transbronchial access tool (TBAT) are novel techniques that leverage navigational bronchoscopic technologies to further improve access to lesions throughout the lung. The devices used for sampling tissue have similarly evolved, such as the introduction of cryobiopsy. These innovative bronchoscopic techniques allows higher diagnostic yield even in small PPLs. Given the complexity of these new techniques and technologies, it is important for physicians to understand their strengths and limitations.

BACKGROUND: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed. Gene expression changes in the lung grafts were determined by microarray and immunohistochemical staining, and genes were verified by quantitative PCR in the lungs and mediastinal lymph nodes (LNs). RESULTS: A total of 1343 genes were upregulated in the OB lungs compared to the sham group. Significant upregulation was observed for genes related to innate, e.g. Tlr2 and CCL3 and adaptive immunity, e.g. H2-ab1 and Il-21. Positive labeling for MHC class II antigen was observed in the bronchial epithelium of OB accompanied with B cells. We found increased Tlr2, Ccl3, H2-ab1, Il-21, Ighg3, Ifng, and Pdcd1 mRNA expression in the OB lung, and increased Il-21, Ighg3, and Pdcd1 expression in the OB LNs. CONCLUSIONS: Adaptive and innate immune reactions were involved in OB after lung transplantation, and genetic examination of related genes could be used for detection of OB.

BACKGROUND: The rabbit squamous cell cancer line, VX2, has been used to generate various tumor models in rabbits. It is notable for its ability to generate nodal metastases. However, the timing and extent of nodal metastases vary by primary inoculation site and methodology. The development of metastases specifically in lung cancer models has not been well-described. We sought to characterize the generation of nodal metastases in rabbit transbronchial VX2 lung tumor models. METHODS: Rabbit VX2 lung tumor models were created in the right lung via transbronchial injection and serially imaged by computed tomography. Rabbits (n = 15) were sacrificed from between 5 and 24 days post-inoculation for collection of the ipsilateral and contralateral paratracheal lymph nodes. These underwent histopathological evaluation for metastases using hematoxylin and eosin as well as cytokeratin AE1/AE3 immunohistochemical staining. RESULTS: Nodal metastases were detectable as early as 1 week after inoculation but were more prevalent with longer inoculation; all rabbits at > 2 weeks post-inoculation had nodal metastases. Contralateral metastases were in general seen later than ipsilateral metastases. Lymph node volume did not predict the likelihood of nodal metastases (p = 0.4 and p = 0.07 for ipsilateral and contralateral nodal metastases, respectively), but primary tumor volume was significantly associated with the likelihood of nodal metastases (p = 0.001 and p = 0.005 for ipsilateral and contralateral nodal metastases, respectively). Ipsilateral metastases were detectable at a tumor diameter of 1 cm; contralateral metastases were more variable but in general required a tumor diameter of 2 cm. CONCLUSIONS: Rabbit transbronchial VX2 lung tumor models generate nodal metastases relatively early after inoculation. These results suggest such models may be valuable tools in the investigation of novel therapeutic modalities relevant for the treatment of both early-stage and locally advanced lung cancer.

BACKGROUND: During endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the sonographic findings of B-mode imaging, as well as endobronchial elastography, can be obtained noninvasively and used for the prediction of nodal metastasis. METHODS: Patients with lung cancer or suspected lung cancer who underwent EBUS-TBNA were recorded prospectively and reviewed retrospectively. Both the B-mode sonographic and elastographic findings were independently evaluated for each lymph node. The sonographic features were classified according to previously published criteria. If oval shape, indistinct margins, homogenous echogenicity, and the absence of coagulation necrosis sign were all observed by B-mode imaging, then the lymph node was judged to be benign by sonographic imaging. In addition, if the stiffer area comprised more than 31% of the entire lymph node area, then the lymph node was judged to be malignant by elastography. We compared the results of these imaging-based predictions with the pathological diagnoses. RESULTS: The prevalence of nodal metastasis was 78/228 (34.2%). B-mode sonography predicted 95.8% of benign lymph nodes, and elastography predicted 72.1% of malignant lymph nodes. By combining the two modalities, 59 of 71 (83.1%) lymph nodes judged as malignant by both analyses were pathologically proven to be malignant, and 101 of 105 (96.2%) lymph nodes judged as benign by both analyses were pathologically proven to be benign. CONCLUSION: The combination of elastography and sonographic findings showed good sensitivity and a high negative predictive value, which may facilitate selecting the most suspicious lymph nodes for biopsy. KEY POINTS: Significant findings of the study. The combination of endobronchial elastography and sonography resulted in a higher diagnostic yield than either modality alone for predicting benign and malignant lymph nodes in patients with lung cancer. WHAT THIS STUDY ADDS: The combination of endobronchial elastography and sonography will help clinicians identify the most suspicious lymph nodes for puncturing during EBUS-TBNA, which may improve the efficiency of EBUS-TBNA.

BACKGROUND: Phototherapy is an alternative treatment for patients with localized non-small cell lung cancer who are unable to undergo surgical resection. However, phototherapy is currently limited to treatment of centrally located lung cancer, with the much larger proportion of peripheral lesions remaining inaccessible. There are also concerns over the accuracy of targeted laser treatment because of the need to exchange visualization and irradiation fibers during therapy, preventing the operator from confirming the final location of the irradiation fiber. METHODS: A newly developed parallel-type ultrasmall composite optical fiberscope (Laser-eYe Ultrathin fiberscope [LYU]), which enables simultaneous white-light imaging and phototherapy, was evaluated in preclinical lung cancer models. Three models were used: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lungs into which A549 tumor tissue was transplanted. A multifunctional porphyrin-phospholipid nanoparticle (porphysome) was used as a photosensitizer to evaluate fluorescence-guided photothermal therapy. RESULTS: The LYU's 0.97 mm diameter and hydrophilic coating allowed easy passage through the working channel of all types of bronchoscopes and controlled guidance of the LYU tip in any desired direction. The LYU could visualize the peripheral bronchus and porphysome-laden peripheral tumors. The LYU could also perform photothermal therapy with simultaneous imaging. CONCLUSIONS: The LYU enables simultaneous imaging and phototherapy that allows accurate irradiation of peripheral lung cancers. This new laser device may enable ultraminimally invasive transbronchial treatment of peripheral lung cancer.

Introduction: The incidence of peripheral pulmonary lesions (PPLs) is growing following the adoption of lung cancer screening by low-dose chest CT. Although CT-guided transthoracic needle aspiration has been the standard method to diagnose PPLs, the field of interventional bronchoscopy is rapidly advancing to overcome complications of the transthoracic approach yet maintain the yield. Areas covered: This article reviews the clinical evidence of recent emerging interventional bronchoscopic techniques for diagnosis of PPLs. Expert opinion: Recent advances in interventional bronchoscopy contribute to not only the safety of transbronchial approaches to PPLs but also the higher diagnostic yield. To perform accurate sampling of PPLs, bronchoscopists must select the correct airway, approach the target as close as possible, and confirm the location of the target before sampling. These key steps can be assisted by recently developed technologies. However, it is important for bronchoscopists to understand the strengths and limitations of these emerging technologies.

BACKGROUND: Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope. METHODS: To prepare this technology for clinical translation, we developed a porphysome-specific fiberscope (scanning fiber endoscope and porphysome-specific thoracoscope), both capable of detecting porphysome fluorescence, for image-guided transbronchial and transpleural photothermal therapy to treat endobronchial/peribronchial and subpleural tumors, respectively. These were tested in three animal models: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lung into which A549 tumor tissue was transplanted. RESULTS: The scanning fiber endoscope, with a 1.2-mm diameter, is small enough to pass through the working channel of a conventional bronchoscope and could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The porphysome-specific thoracoscope system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulating tumors close to the pleura. Porphysomes also enhanced the efficacy of scanning fiber endoscope-guided transbronchial photothermal therapy and porphysome-specific thoracoscope-guided transpleural photothermal therapy, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models. CONCLUSIONS: These results support the potential for clinical translation of this novel platform to affect nonsurgical and minimally invasive treatment options for early-stage peripheral lung cancer.

BACKGROUND: The next-generation convex probe endobronchial ultrasound (CP-EBUS) was developed to improve the ease of operation and the acquisition of EBUS skills for new trainees. The aim of this study was to evaluate the changes in the prototype next-generation CP-EBUS compared with the current CP-EBUS. METHODS: The prototype next-generation CP-EBUS, with a decreased forward oblique view, more flexible angulation range, smaller ultrasound probe, and sharper needle angle, was compared with the current CP-EBUS. The operability, which was evaluated by using a 5-level Likert-type scale, and safety were evaluated in 2 live pigs, a cadaveric lung, and 10 ex vivo human lungs by 9 bronchoscopists. The time required to access the upper lobe bronchus and the time required to detect prespecified lymph node stations by 7 novice bronchoscopists with both CP-EBUS were compared with assess the operability difference for new trainees. RESULTS: In all evaluated models, operability (eg, maneuverability, endoscopic visibility, bronchial trees selectivity, insertability to the upper airway) was scored 5 (significantly improved). All trainee bronchoscopists were able to access the upper lobe bronchi and detect each lymph node except 4R significantly faster than with the current CP-EBUS without any airway damage. CONCLUSIONS: The next-generation CP-EBUS has improved operability, which resulted in better access to each lobar bronchus and more prompt detection of mediastinal or hilar lymph nodes. These improvements may allow more precise lymph node staging and diagnosis, as well as improve EBUS procedural skill acquisition, once introduced to clinical practice.

Obtaining biopsy specimens for pathologic diagnosis of primary cardiac tumors is challenging because of their anatomic location and the risk of tumor embolization. Due to the difficulty of histologic diagnosis and limited treatment strategies, it is not uncommon for patients to be treated based on radiologic findings alone. However, a firm pathologic diagnosis may permit more appropriate treatment selection, especially for those with primary cardiac lymphoma. Endoscopic ultrasound with bronchoscope-guided fine-needle aspiration is a minimally invasive modality for sampling mediastinal lymph nodes and mediastinal lesions adjacent to the esophagus. In this case report we present 2 patients with cardiac tumors that were successfully and safely diagnosed by endoscopic ultrasound with bronchoscope-guided fine-needle aspiration.

Lung cancer is the most common cause of cancer deaths worldwide. A major reason for poor prognosis is that patients are usually diagnosed at an advanced stage and thus there are limited options for curative treatment at the time of diagnosis. Early detection may improve lung cancer survival, as demonstrated in computed tomography screening studies. New and innovative bronchoscopic methods have been developed for the early diagnosis of lung cancer. High-precision bronchoscopic imaging technology, such as optical biopsy, may potentially replace traditional biopsy techniques. This article reviews the advanced technologies for detection of early lung cancer.

PURPOSES: To evaluate vertebral artery (VA) dominancy and the risk of brain infarction in T4 lung cancer patients with tumor invasion into the subclavian artery. METHODS: We reconstructed the subclavian artery in 10 patients with T4 non-small cell lung cancer. The histological stages were IIIA in eight patients and IIIB in two patients. We evaluated the VA dominancy by performing a four-vessel study preoperatively and investigated the relationship between the methods of VA treatment and postoperative brain complications, retrospectively. RESULTS: Seven patients had a superior sulcus tumor (SST) and three had direct invasion into the mediastinum. Based on the tumor location, a transmanublial approach was used in five patients and a posterolateral hook incision was used in the other five. All subclavian artery (SA) reconstructions were done using an artificial woven graft. Preoperative angiography of the VA revealed poor development of the contralateral side in two patients. One of these patients suffered a severe brain infarction on postoperative day 2, which proved fatal. In the other patient, the VA was connected to the left SA graft by a side-to-end anastomosis and there was no postoperative brain complication. CONCLUSIONS: Preoperative SA and VA angiography is mandatory for identifying the need for VA reconstruction in lung cancer patients with major arterial invasion.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria. METHODS: Clinical tissue samples that had been obtained by EBUS-TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria. RESULTS: The records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS-TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non-small cell carcinoma with neuroendocrine morphology. CONCLUSION: LCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS-TBNA samples.

BACKGROUND: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. OBJECTIVE: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. METHODS: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis. After having established a cutoff level of expression for each marker to differentiate malignant from benign lymph nodes among surgically dissected lymph nodes, the cutoff level was applied to snap-frozen EBUS-TBNA samples. Archived formalin-fixed paraffin- embedded (FFPE) samples rebiopsied by EBUS-TBNA after induction chemoradiotherapy were also analyzed. RESULTS: The expression of all candidate miRNAs was significantly higher in metastatic lymph nodes than in benign ones (p < 0.05) among the surgical samples. miR-200c showed the highest diagnostic yield, with a sensitivity of 95.4% and a specificity of 100%. When the cutoff value for miR-200c was applied to the snap-frozen EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.4, 81.8, 95.0, 90.0, and 94.0%, respectively. For restaging FFPE EBUS- TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 60.0, 80.0, 100, and 84.6%, respectively. Among the restaged samples, 4 malignant lymph nodes were false negative by EBUS-TBNA, but they were accurately identified by miR-200c. CONCLUSIONS: miR-200c can be used as a highly sensitive molecular staging biomarker that will enhance nodal staging of lung cancer.

BACKGROUND: Appropriate device selection is crucial for endobronchial foreign body removal using a bronchoscope. In pediatric patients, bronchoscopy requires the use of a thin device due to the narrow access to the airway, limiting the range of useful endobronchial devices. We herein review our experience in endobronchial foreign body removal with a focus on the type of bronchoscope and the instruments used in comparison with the literature, and investigate the utility of mini grasping basket forceps (FG-55D, Olympus® ; and Zero Tip™ , Airway Retrieval Basket, Boston Scientific). METHODS: Between April 2008 and April 2016, foreign bodies were removed from the airway of 12 pediatric patients by bronchoscopy. These cases are reviewed in this study. The clinical presentation, location and characteristics of the foreign bodies, and the type of bronchoscope and instruments used were analyzed. RESULTS: A consecutive series of 12 pediatric patients was retrospectively reviewed, and the therapeutic characteristics investigated. Nuts were the most frequently observed foreign body. Seven of the 12 pediatric patients required an ultrathin bronchoscope (diameter, 2.8 mm) for foreign body removal. Only one patient required a rigid scope in addition to flexible bronchoscopy. The most frequently used instrument was a mini grasping basket forceps (n = 7; 58%), which was used with a 1.2 mm instrument channel (n = 4; 33%). CONCLUSIONS: The use of a mini grasping basket forceps in combination with an ultrathin flexible bronchoscope was useful for removing smooth, soft materials such as a nuts or beans in pediatric cases.

Training for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has focused on the procedure itself; however, the techniques for obtaining adequate sample are also important for achieving a pathological diagnosis as well as for molecular testing. The aim of this study was to evaluate the feasibility and efficacy of a biosimulator for training subjects in adequate sample acquisition during EBUS-TBNA.A total of 19 bronchoscopists voluntarily participated in this study. A biosimulator (ArtiCHEST, HARADA Corporation, Tokyo, Japan) was used for the training. After a 10-minute briefing, the first pass was performed by pairs of trainees. The trainees then received a 30-minute lecture that focused on the acquisition of samples using EBUS-TBNA. The trainees next performed their second pass under the supervision of the trainers. Each participant obtained a cytological smear that was coded and evaluated for quantity as well as quality by an independent cytotechnologist.The trainees had an average of 5.9 years of bronchoscopy experience. With regard to the quantity evaluation, 9 (47.4%) subjects sampled a greater number of lymphocytes on the second pass than on the first, whereas 2 were better on the first pass, and the others sampled roughly the same amount both times. With regard to the quality assessment, 9 (47.4%) subjects obtained better quality samples on the second pass, whereas the quality of the first and second pass was deemed to be roughly the same for the remaining subjects.A biosimulator can be used to train doctors in specimen acquisition and evaluate their skills with sampling using EBUS-TBNA.

Anastomotic failure of a gastric tube inserted for reconstruction following esophagectomy, which is relatively rare, causes pleural infection and persistent pleural irritation, leading to communication with the pulmonary parenchyma. Although several interventions have been reported to treat such broncho-gastric tube fistulas, refractory cases remain. We herein report the successful treatment by endoscopic bronchial occlusion with an endobronchial Watanabe spigot in 2 patients who suffered from the above complication.

BACKGROUND: Elastography is a relatively new technology that can generate images reflective of tissue stiffness (elasticity). Neoplastic tissue is usually stiffer than normal structures. OBJECTIVES: The aim of this study was to evaluate the feasibility and utility of elastography when combined with convex-probe endobronchial ultrasound (CP-EBUS) for predicting and localizing metastatic lymph nodes during endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA). METHODS: Consecutive results of endobronchial elastography of lymph nodes performed using EBUS- TBNA were prospectively collected and retrospectively analyzed. Elastography images were acquired as JPEG images and also recorded as video clips. Stiff area ratios [(stiff areas as blue pixels) / (lymph node areas as region of interest pixels)] for each lymph node determined by elastography were collated with the results of pathological diagnosis. We also performed elastography of surgically resected lymph nodes and compared image findings with pathological sections. RESULTS: We evaluated 49 lymph nodes in 21 patients by CP-EBUS. There were 16 metastatic nodes (10 lung cancer metastases and 6 metastases from extrathoracic malignancies). Mean stiff area ratios were significantly greater for metastatic lymph nodes (0.478) than for benign nodes (0.216; p = 0.0002). Using a cutoff value of 0.311 for stiff area ratios, the sensitivity and specificity for predicting metastatic disease were 0.81 and 0.85, respectively. The stiff area was histologically compatible with metastatic distribution in surgically resected lymph nodes. CONCLUSIONS: Endobronchial elastography is feasible for lymph nodes when combined with CP-EBUS. Stiff area ratios are useful for predicting metastatic lymph nodes, which may be an efficient guide for TBNA.

Accurate staging is the first step in the management of lung cancer. Nodal staging is quite important for physicians to be able to judge the primary operability of patients harboring no distant metastasis. For many years, mediastinoscopy has been considered a "gold standard" modality for nodal staging. Mediastinoscopy is known to be a highly sensitive procedure for mediastinal staging and has been performed worldwide, but is invasive. Because of this, clinicians have sought a less invasive modality for nodal staging. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality for diagnosis and staging of lung cancer. EBUS-TBNA is a needle biopsy procedure that has accessibility compatible with the reach of the convex-probe EBUS scope, so N1 nodes are also assessable. The diagnostic yield is similar to that of mediastinoscopy, and the core obtained by the dedicated needle biopsy can be used for histological assessment to determine the subtypes of lung cancer. The samples can also be used to test for various biomarkers using immunohistochemistry, polymerase chain reaction for DNA/complementary DNA, and in situ hybridization, and the technique is useful for selecting candidates for specific molecular-targeted therapeutic agents. According to the newly published American College of Chest Physicians guideline, EBUS-TBNA is now considered "the best first test" for nodal staging in patients with radiologically suspicious nodes. Appropriate training and thorough clinical experience is required to be able to perform correct nodal staging using this procedure.