Time-Sequential Monitoring of the Early Mesothelial Reaction in the Pleura after Cryoinjury.

(1) Background: An early mesothelial reaction of the pleura, leading to fibrosis, has been reported in animals after chemical or heavy metal exposure. However, the visual monitoring of early time-sequential mesothelial reaction-associated cryoinjury has not been fully investigated. Therefore, this study aimed to evaluate and visualize the early mesothelial reactions seen following cryoinjury using rabbit pleura. (2) Methods: We monitored the early mesothelial reaction in rabbit pleurae after cryoinjury using optical coherence tomography (OCT), in real-time, which was then compared with pathological images. Due to the penetration limit of OCT, we made a thoracic window to image the parietal and visceral pleurae in vivo. We also used an innovative technique for capturing the microstructure in vivo, employing a computer-controlled intermittent iso-pressure breath hold to reduce respiratory motion, increasing the resolution of OCT. We organized three sample groups: the normal group, the sham group with just a thoracic window, and the experimental group with a thoracic window and cryotherapy. In the experimental group, localized cryoinjury was performed. The mesothelial cells at the level of pleura of the cryotherapy-injured site were visualized by OCT within the first 30 min and then again after 2 days at the same site. (3) Results: In the experimental group, focal thickening of the parietal pleura was observed at the site of cryoinjury using OCT after the first injury, and it was then confirmed pathologically as focal mesothelial cell proliferation. Two days after cryoinjury, diffuse mesothelial cell proliferation in the parietal pleura was noted on the reverse side around the cryoinjured site in the same rabbit. In the sham group, no pleural reaction was found. The OCT and pathological examinations revealed different patterns of mesothelial cell reactions between the parietal and visceral pleurae: the focal proliferation of mesothelial cells was found in the parietal pleura, while only a morphological change from flat cells to cuboidal cells and a thickened monolayer without proliferation of mesothelial cells were found in the visceral pleural. (4) Conclusions: An early mesothelial reaction occurs following cryoinjury to the parietal and visceral pleurae.

Transrenal DNA detection of Mycobacterium tuberculosis in patients with pulmonary tuberculosis.

Background: Multiple attempts have been made to use biological samples other than sputum to diagnose tuberculosis (TB). Sputum acid-fast bacillus (AFB) microscopy is the fastest, most straightforward, and most inexpensive method for diagnosing pulmonary TB. However, urine can be used in place of sputum owing to its various advantages, such as a noninvasive method of collection, convenient handling and storage, and minimal risk of infection in health-care workers involved in sample collection. In this study, we aimed to assess the suitability of urine as a sample to obtain transrenal DNA (trDNA) to diagnose TB. This study involved several patients with TB undergoing inpatient treatment, whose AFB microscopy showed negative inversion. Methods: Here, 51 urine samples were collected from 40 patients with TB and examined to confirm the presence of trDNA. First, we compared the efficiency of two trDNA extraction methods.An automated magnetic bead-based method and a more efficient anchoring extraction method. Statistical analyses were performed using Excel software (Microsoft Office Professional Plus 2019). Results: Although molecular diagnosis using GeneXpert yielded negative results, a peculiarity was observed. There was no significant difference between GeneXpert findings and our results nor was there any difference in the sequential trDNA samples obtained. However, even when GeneXpert results were negative, trDNA was detected in seven out of ten samples using the anchor extraction method. Conclusions: Further studies are needed to establish biomarkers for the progression of TB treatment.

Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors.

BACKGROUND: We aimed to validate a pilot study of photodiagnosis using near infrared (NIR) transillumination and assess the clinical efficacy of hypericin-mediated photodynamic therapy (HYP-PDT) in a rabbit laryngeal cancer model in order to develop a novel therapeutic modality with complete remission and preservation of the functional organ. METHODS: (1) In vitro study: VX tumor cells were subcultured and subjected to HYP-PDT. (2) In vivo study: A laryngeal cancer model was developed in which 12 rabbits were inoculated with a VX tumor suspension in the submucosal area of the left vocal fold using a transoral approach. All rabbits underwent NIR transillumination using light with a wavelength of 780 nm. The survival periods of the three treatment groups (6 rabbits in Group A: HYP-PDT, 3 each in Groups B and C: laser irradiation or HYP administration only) were analyzed. RESULTS: The higher the HYP concentration, the lower the VX cell viability in response to HYP-PDT using 590 nm LED. Following HYP-PDT, small tumors in Group A-1 rabbits healed completely and the animals demonstrated a long survival period, and larger tumors in Group A-2 healed partially with a survival period that extended over 3 weeks after inoculation. The survival of Groups B and C were not different over the first 3 weeks of the study, and were shorter than in Group A. CONCLUSION: We found HYP-PDT could be a curative therapy for early-stage cancers that may also preserve organ function, and may inhibit tumor progression and metastasis during advanced stages of laryngeal cancer.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits.

BACKGROUND: Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access. METHOD: In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2-3.4 kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. RESULTS: In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. CONCLUSION: We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model.

BACKGROUND: The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarization-sensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue. METHOD: A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PS-OCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. RESULTS: The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue. The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. CONCLUSION: Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

A randomized, multi-center, open-label study to compare the safety and efficacy between afatinib monotherapy and combination therapy of afatinib and HAD-B1 for the locally advanced or metastatic NSCLC patients with EGFR mutations.

BACKGROUND: Afatinib is an epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy for treating patients with advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, responses are limited by acquired resistance. Because traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy, the aim of our study is to elucidate the efficacy and safety of afatinib plus HangAmDan-B1 (HAD-B1) combination therapy in the treatment of patients with NSCLC, as well as EGFR mutations, who need afatinib therapy. METHODS/DESIGN: This study is a randomized, multi-center, open clinical trial. A total of 178 eligible subjects, recruited at 8 centers, are randomly assigned to take Afatinib (20-40 mg) ±â€ŠHAD-B1 (0.972 g/day) for 48 weeks. In the test group, HAD-B1 and afatinib will be used in combination. The primary outcome is a comparison of progression-free survival (PFS) between afatinib monotherapy and afatinib plus HAD-B1 combination therapy in patients with local advanced or metastatic (Stage IIIA, B, C/IV) NSCLC. Secondary outcomes are the overall survival rates, clinical responses, tumor size reductions, health-related qualities of life, and safety. DISCUSSION: The result of this clinical trial will provide evidence for the efficacy and safety of using HAD-B1 in the treatment of EGFR-positive patients with locally advanced or metastatic NSCLC who require afatinib therapy. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea (ID: KCT0005414), on September 23, 2020.

Characteristics of asbestos fibers in lung tissue from occupational and environmental asbestos exposure of lung cancer patients in Busan, Korea.

The Asbestos Injury Relief Act in Korea requires that asbestos exposure be assessed through clinical examination and chest computed tomography (CT). However, a more specific measurement of asbestos characteristics in the lung tissue may be appropriate. We aimed to investigate the asbestos burden and characterize asbestos fibers in patients with lung cancer and ultimately assess the relationship between occupational and environmental asbestos exposure and lung cancer in Korea. We evaluated 37 lung cancer patients (LCPs) from Busan. The factors affecting asbestos burden in LCPs were analyzed using a multiple regression analysis. History of asbestos exposure (environmental/occupational), male sex, and old age were the main factors affecting asbestos burden in lung tissues of LCPs. These factors had an approximate 37% adjusted coefficient of determination. There was a significant difference in the length of asbestos fibers (4.06-37.6 µm vs. 4.26-91.7 µm) and aspect ratio (4.5-151.9 vs. 5.6-735.6) between those who were occupationally exposed to asbestos and those who were environmentally exposed (P < 0.01). Therefore, both environmental/occupational exposure to asbestos should be strongly managed to reduce the risk of lung cancer, and exposure should be assessed according to the characteristics of asbestos fibers in the lung tissue.

High Serum Folate Concentration Is Associated with Better Lung Function in Male Chronic Obstructive Pulmonary Disease Patients Who Are Current Smokers: Analysis of Nationwide Population-Based Survey.

Folate, folic acid, has a role in mitigating inflammatory reactions in the human body. This study aimed to evaluate the association of serum folate levels with lung function in chronic obstructive pulmonary disease (COPD) patients. Of the 8149 participants of the 2016 Korean National Health and Nutrition Examination Survey (KNHANES), 311 subjects (192 males and 119 females) having COPD defined by the lower fifth percentile of the reference population were selected. Pearson's correlation coefficient was used to investigate the relationship between serum folate level and lung function measurements. The association between the serum folate level and lung function in patients with COPD was evaluated using multivariable linear regression analysis after adjustment for age, sex, height, high sensitivity C-reactive protein, total calorie intake, residence, smoking status and smoking pack-years, education, and household income. The serum folate level showed a positive correlation with the predicted percentage of forced expiratory volume in one second (FEV1%). In males, a trend for a positive correlation with serum folate level was observed in predicted FEV1%, FEV1 value, predicted percentage of forced vital capacity (FVC%), FVC value, and peak expiratory flow (PEF). No significant correlation between the serum folate level and lung function in females was observed. In the multivariable linear regression model, the serum folate level was associated with an increase in predicted FEV1%, FEV1 value, predicted FVC%, FVC value, and PEF; however, the significance was only observed in males, especially among current smokers. High serum folate level was positively associated with lung function measurements in male COPD patients who were current smokers. Further longitudinal studies are needed to elucidate the underlying mechanisms.

Fabrication and biological activity of polycaprolactone/phlorotannin endotracheal tube to prevent tracheal stenosis: An in vitro and in vivo study.

Prolonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti-inflammatory or anti-fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor ß1. Phlorotannin-coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin-coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α-smooth muscle actin. The ability of phlorotannin-coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis.

Tracheal pleomorphic adenoma with coexisting pulmonary tuberculoma.

Tracheal tumors are rare and difficult to diagnose. Moreover, delays in diagnosis are very common because the symptoms are nonspecific. As a result, tracheal tumors are commonly mistreated as chronic obstructive pulmonary disease or bronchial asthma. We report a case of a 49-year-old male who presented with a 3-month history of dyspnea and cough. Chest computed tomography scan showed a 1.5×1.3 cm homogenous tumor originating from the right lateral wall of the tracheobronchial angle into the tracheal lumen as well as a 0.5×0.4 cm round nodular lesion at the right upper lobe with multiple mediastinal lymph nodes enlargement. Bronchoscopic findings revealed a broad-based, polypoid lesion nearly obstructing the airway of the right main bronchus. The patient was diagnosed with pleomorphic adenoma which is the most common benign tumor of the salivary glands, but rarely appears in the trachea. Upon surgery, tracheal pleomorphic adenoma and co-existing active pulmonary tuberculoma that had been mistreated as bronchial asthma over 3 months was revealed. Following surgery, the patient underwent anti-tuberculosis treatment. No recurrence has been detected in the 3 years since treatment and the patient is now asymptomatic.

Near-Infrared Autofluorescence Image-Guided Parathyroid Gland Mapping in Thyroidectomy.

BACKGROUND: Studies to date have shown that near-infrared autofluorescence imaging (NIR) can detect the parathyroid gland during thyroidectomy. However, there are no reports that NIR imaging can identify the parathyroid gland when it's covered with fibrofatty tissue before identification by a surgeon's naked eye. In this study, we investigated the feasibility of parathyroid gland mapping to facilitate early identification of the parathyroid gland during thyroidectomy. STUDY DESIGN: Seventy parathyroid glands from 38 patients who underwent thyroidectomy for papillary thyroid cancer were included in this prospective study. Near-infrared with infrared illumination (NIR-IR) imaging using a 780-nm light-emitting diode was conducted at the predicted locations of the superior or inferior parathyroid glands. Parathyroid mapping was conducted in 3 stages. Stages P1, P2, and P3 were defined as imaging before identification of the gland by direct visualization, imaging after identification, and imaging in the removed specimen, respectively. RESULTS: Sixty-four parathyroid glands (92.8%) could be localized in stage P1 before surgical dissection and exposure of the gland. Five parathyroid glands that were not detected at stage P1 were identified in stages P2 (4 cases, 5.8%) and P3 (1 case, 1.4%). One parathyroid gland was not identified in either the NIR imaging or the pathologic examination. The sensitivity, specificity, and accuracy of parathyroid gland mapping in stages P1, P2, and P3 were all 100%. CONCLUSIONS: Parathyroid gland mapping using our NIR-IR imaging technique was feasible, with an excellent accuracy rate. This technique may be helpful for early identification of parathyroid glands during thyroidectomy.

Rabbit model of tracheal stenosis using cylindrical diffuser.

BACKGROUND AND OBJECTIVE: Variable methods of animal model have been introduced to develop tracheal stenosis. However, none of the prior models allow for predictable determination of the grade of stenosis. This study sought to establish an animal model of tracheal stenosis by using a cylindrical diffuser and to evaluate the feasibility of a reproducible model. STUDY DESIGN/MATERIALS AND METHODS: A cylindrical diffuser was developed to have a 5 mm active segment to emit laser light circumferentially. Twenty one New Zealand white rabbits were enrolled in this study. The cylindrical diffuser was inserted transorally under bronchoscopic view and the diffused light was delivered to tracheal mucosa 2 cm below the level of vocal cord. Input power of irradiation was 10 W, 5 seconds in group A (n = 7), 10 W, 7 seconds in group B (n = 7), and 8 W, 5 seconds in group C (n = 7). The degree of tracheal stenosis was observed weekly and the rabbits were euthanized 4 weeks after the laser irradiation. RESULTS: The degree of stenosis in group B (90-98%) was significantly larger than that of group A (75-92%) (P = 0.004), while degree in group C (24-35%) was significantly smaller than that of group A (P < 0.001). Two rabbits of group A were euthanized at 3 weeks due to costal retraction. In group B, six rabbits died within 3 weeks after laser irradiation due to severe tracheal stenosis and tracheal malacia, while one rabbit was euthanized 16 days after the irradiation. All rabbits in group C survived up to 4 weeks. Survival between three groups showed significant difference (P = 0.001). CONCLUSION: The degree of stenosis was significantly different according to the delivered optical energy to tracheal mucosa. Therefore, the proposed model may be used in animal studies to emulate variable grades of tracheal stenosis. Lasers Surg. Med. 49:372-379, 2017. © 2016 Wiley Periodicals, Inc.

Intraoperative Real-Time Localization of Normal Parathyroid Glands With Autofluorescence Imaging.

CONTEXT: This biomedical investigation is valuable for identification and localization of parathyroid glands during thyroidectomy, which can provide an intraoperative real-time visual guidance. OBJECTIVE: The objective of the study was to investigate the feasibility of real-time autofluorescence imaging of the parathyroid glands without exogenous contrast dye for their localization and demonstration of relation to the background tissues. SETTING: This research was undertaken at Kosin University Gospel Hospital. METHODS: Sixteen normal parathyroid glands from eight patients with papillary thyroid carcinoma were enrolled. Photo images of the surgical field including the parathyroid and background tissues were taken with a digital camera, 780 nm light-emitting diode to excite the parathyroid, and infrared illuminator to visualize the entire neck. The area-averaged autofluorescence intensity of parathyroid over the area-averaged fluorescence intensity of background tissues was measured. MAIN OUTCOME MEASURE: The location of the parathyroid gland was verified with a single image. RESULTS: The area-averaged autofluorescence intensity of parathyroid over the area-averaged fluorescence intensity of background tissues for all parathyroid glands was higher than 1, with a minimum of 1.95 and a maximum of 5.20 (average 2.76, SD 0.79). By our technique, all 16 parathyroid glands were detected (positive predictive value of 100%), and the entire surgical field including the parathyroid and background tissues was visualized as well. The parathyroid glands that were exposed or even covered by connective tissues or blood vessels could be detected with strong emission. CONCLUSIONS: This method showed the precise localization of the parathyroid glands and demonstrated their relation to background tissue. We believe that this simple, nonexogenous dye technique of anatomical guidance can aid surgeons to preserve parathyroid glands during thyroidectomy.

Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response.

BACKGROUND/AIMS: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. METHODS: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. RESULTS: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. CONCLUSIONS: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.

Preliminary study of optical coherence tomography imaging to identify microscopic extrathyroidal extension in patients with papillary thyroid carcinoma.

BACKGROUND AND OBJECTIVES: We evaluated the feasibility of using optical coherence tomography (OCT), to identify microscopic extrathyroidal extension (mETE) in ex vivo thyroidectomy specimens of patients who underwent thyroidectomy for the treatment of papillary thyroid carcinoma (PTC). METHODS: A total of 170 ex vivo OCT images of the tumor, were acquired just after completion of thyroidectomy in 17 patients. The OCT images of each patient were separately evaluated by two blinded investigators, and the outcomes were compared with the histopathology reports. RESULTS: The sensitivity and specificity of mETE identification from the OCT images were 81.4% and 86.0%, respectively, for the first investigator, and 82.9% and 87.0%, respectively, for the second investigator. Substantial agreement between the investigators was verified by Cohen's κ (Cohen's κ = 0.772). CONCLUSION: In this preliminary study of a limited series of ex vivo thyroidectomy specimens, we verified the feasibility of OCT as a method of identifying mETE in patients with PTC.

Rabbit model of tracheal stenosis induced by prolonged endotracheal intubation using a segmented tube.

OBJECTIVE: Animal model of tracheal stenosis based on pathophysiology of prolonged endotracheal intubation has been rarely reported. We sought to verify the feasibility of inducing an animal model of tracheal stenosis by segmented endotracheal tube insertion in the New Zealand white rabbit model. METHODS: Tracheal stenosis was induced by inserting a segmented endotracheal tube of 1.5cm length which was wrapped with a commercialized absorbable hemostat in 15 New Zealand white rabbits, while sham surgery controls (n=3) underwent tracheotomy and direct closure of tracheal exposure. The tube was removed transorally, 1 week after tube insertion. All rabbits were evaluated endoscopically at 1 week, 2 weeks and 3 weeks after the tube insertion. The rabbits were sacrificed 3 weeks after the surgery, and the excised tissue of trachea was processed along with the procedure of standard hematoxylin eosin staining and observed under a microscope. RESULTS: Tracheal stenosis was induced in all rabbits (range 32-84% stenosis) with no death of rabbits during the study. The histological features of tracheal stenosis demonstrated thickening and fibrosis of lamina propria and submucosa with relatively intact cartilage framework. CONCLUSIONS: We developed a rabbit model of tracheal stenosis induced by endotracheal intubation using a segmented tracheal tube. Since the model is based on the physiologic condition of prolonged endotracheal intubation, it may be used in variable studies related to tracheal stenosis.

Multimodal imaging using optical coherence tomography and endolaryngeal ultrasonography in a new rabbit VX2 laryngeal cancer model.

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) provides ultrahigh-resolution imaging of tissues within a depth of a few millimeters, whereas ultrasonography provides good imaging further below the surface. We aimed to develop a minimally invasive rabbit model of VX2 laryngeal cancer, suitable for these two imaging modalities through a transoral approach. We also sought to study the utility of combined OCT and endolaryngeal ultrasonography (EUS) for evaluation of early and advanced laryngeal cancer, using this model. MATERIALS AND METHODS: VX2 tumor suspension was inoculated into the vocal folds of ten rabbits by injection through the trans-thyrohyoid membrane. The tumor model was characterized by rigid laryngoscopy and the tumor generation rate was 80% (8/10). Correlation between frequency-domain OCT and high-frequency EUS were used to visualize laryngeal tumors in the area of protruding mass formation in four rabbits, one week after injection (group A) and the remaining four rabbits two weeks after injection (group B). RESULTS: A small submucosal tumor was observed with rigid laryngoscopy in group A, and pathologic evaluation showed that the tumor was close to the basement membrane of the vocal fold mucosa, but had not invaded. OCT confirmed that the lining of the mucosa and basement membrane of the vocal fold was not broken, but the mucosa had thinned at the most elevated ridge. However, these lesions were not detected by EUS, and the overall shape of the tumor could not be clearly identified by EUS. A large tumor filling the laryngeal lumen was observed with rigid laryngoscopy in group B, and nearly the entire vocal fold, including the paraglottic space, was found to be involved on pathologic analysis. Distinguishing between normal structures and tumor was difficult using OCT; however, EUS confirmed the overall shape, size, and extent of the tumor, and the paraglottic space and thyroid cartilage were shown to be intact. CONCLUSIONS: This study is the first experimental trial, assessing the value of multimodal imaging using OCT and EUS in a rabbit VX2 laryngeal tumor model. Combining OCT and EUS helped to identify changes in laryngeal mucous membranes, and could potentially be used to identify laryngeal tumors and predict how tumors progress. This combined modality could help in determining tumor extent, assisting in diagnosis, and establishing a treatment plan for laryngeal cancer.

The potential application of photodynamic therapy in drug-resistant tuberculosis.

Tuberculosis (TB) is an infectious bacterial disease that has historically created a high global health burden. Unfortunately, the emergence of drug-resistant TB (DR-TB), which includes multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), has greatly affected the treatment of TB. Anti-TB chemotherapy drugs are classified into five groups to facilitate application of effective guidelines for the treatment regimen. However, chemotherapy has a limited ability to treat DR-TB, and therefore a novel alternative treatment for DR-TB is required. In this review, we focused on photodynamic therapy (PDT) as potential treatment for DR-TB. PDT is a widely used cancer treatment that combines photosensitizers and harmless laser light to produce reactive oxygen species that selectively damage the target cells. Initially, PDT was originally developed to target pathogenic microorganisms but fell into disuse because of adverse reactions. Recently, photodynamic antimicrobial chemotherapy is attracting attention again as an alternative treatment for bacterial infections. In our previous study, we suggested that PDT could be a novel option to treat MDR- and XDR-TB in vitro. Despite the limited previous studies regarding PDT in TB models, fast-developing bronchoscopic technologies and clinician experience will soon facilitate the clinical application of safe and minimally invasive PDT for TB.

In vivo real-time imaging of airway dynamics during bronchial challenge test.

BACKGROUND AND OBJECTIVE: Asthmatic patients exhibit airway hyper-responsiveness, which induces bronchoconstriction and results in a ventilation defect. The bronchial challenge test using methacholine is a useful way to measure airway hyper-responsiveness with airway constriction. Anatomical optical coherence tomography has been used to image airway hyper-responsiveness of medium sized bronchus with the aid of an endoscopic probe. Recently, a thoracic window was reported that allows direct visualization of terminal airway such as alveolus. A multi-scale integrated airway dynamics was assessed in this study. We imaged in vivo changes in the right intermedius bronchus and alveolar structure during the bronchial challenge test using two optical coherence tomography systems and correlated the changes with airway resistance. MATERIALS AND METHODS: Rabbits intubated with a non-cuffed endotracheal tube on a ventilator sequentially inhaled normal saline and methacholine (2 or 5 µg/ml). The airway resistance was measured by mechanical ventilation and airway structures were monitored by a commercial endoscopic optical coherence tomography system (1,310 nm) and a house-made table-top spectral-domain optical coherence tomography system (850 nm). RESULTS: We demonstrated an early decrease in the size of the right intermedius bronchus and alveoli in accordance with increased airway resistance after methacholine inhalation. OCT image after inhalation of 2 µg/ml methacholine showed some segmental narrowing of the right intermedius bronchus and the image after inhalation of 5 µg/ml methacholine showed even greater segmental narrowing. The cross-sectional areas were 7.2 ± 3.3 mm2 (normal saline), 3.7 ± 2.1 mm2 (2 µg/ml methacholine), and 2.4 ± 1.1 mm2 (5 µg/ml methacholine), respectively (P = 0.04). Most of the alveolar space was collapsed under elevated airway resistance with methacholine inhalation. The averaged areas per alveolus at the end of inspiration were 0.0244 ±0.0142 mm2 (normal saline), 0.0046 ±0.0026 mm2 (2 µg/ml methacholine), and 0.0048 ±0.0028 mm2 (5 µg/ml methacholine), respectively (P = 0.03). Methacholine induced a dose-dependent increase in airway resistance (1.1 ± 0.3 cm H2O sec/ml for 2 µg/ml methacholine, 1.5 ± 0.5 cm H2O sec/ml for 5 µg/ml methacholine) (P = 0.03). These results were obtained from normal rabbits during the bronchial challenge test with a non-cuffed endotracheal tube on a ventilator. With this setup increased airway resistance possibly resulted in larger leakage around the endotracheal tube, decreased inhaled volumes, and, in turn, alveolar collapse. CONCLUSION: We performed a feasibility study of in vivo visualization of real-time airway dynamics. To our best knowledge, this is the first report of real-time integrated airway dynamics including the right intermedius bronchus and alveoli during a bronchial challenge test. OCT showed bronchial constriction and alveolar collapse with a higher methacholine dose. OCT images correlated with the measured airway resistance. Therefore, OCT could be a potential diagnostic device for airway hyper-responsiveness and airway remodeling.