Masahiro Katsurada

Endobronchial ultrasound with a guide sheath for small malignant pulmonary nodules: a retrospective comparison between central and peripheral locations

OBJECTIVE Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic accuracy of transbronchial biopsy (TBB) for malignant peripheral pulmonary nodules (PPNs). Many underscore the importance of tumor localization but reproducible results on other aspects that affect yield are few. We aimed to analyze the diagnostic performance of TBB with EBUS-GS and to know what group of patients can benefit most. METHODS The database of patients with malignant PPNs (≤30 mm) who underwent EBUS-GS TBB at the National Cancer Center Hospital, Tokyo, Japan from April 2012 to March 2013 was retrospectively reviewed and analysed based on lesion and procedural characteristics. RESULTS Most PPNs (N=212) were adenocarcinoma, measuring 20 mm [mean, standard deviation (SD) 5.45]. Overall diagnostic accuracy was 67.5% (143 of 212 cases). Factors that significantly affected and predicted diagnostic success were EBUS probe within (P=0.001) and parenchymal location that was not adjacent to the costal visceral pleura (P=0.001). When combined, these variables achieved an 87% (59 of 68 lesions) diagnostic yield. CT scan characteristic, lesion size, lobe location, and GS size were non-contributory. CONCLUSIONS EBUS-GS TBB is an acceptable diagnostic method for small peripheral lung cancer. It can be maximized for PPNs that are away from the pleura and when the EBUS probe can be placed within the lesion.

The time-series behavior of neutrophil-to-lymphocyte ratio is useful as a predictive marker in non-small cell lung cancer

Background Nivolumab improves the survival of advanced non-small cell lung cancer (NSCLC), but a significant number of patients still fail to benefit from this treatment. In this study, we evaluated the efficacy of the time-series behavior of neutrophil-to-lymphocyte ratio (NLR) in a complete blood count from advanced NSCLC patients as a predictive marker of the anticancer effect of nivolumab. Methods We performed a retrospective review of medical records and collected data on patients with advanced NSCLC treated with nivolumab as second- and further-line treatments from December 2015 to March 2017. The NLRs were calculated before each treatment cycle for four cycles. These parameters were tested for its association with the overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF). Results Nineteen patients were treated with nivolumab. Stratified by the response to nivolumab, the median OS was 2.8 months in progressive disease (PD) and 14.0 months in non-PD (p = 0.002). Before discontinuation of PD or toxicity, an NLR is rising from baseline in 5 out of 7 patients with PD and all of 4 patients with discontinuation due to toxicity. Patients with an >30% increase in NLR were associated with a significantly shorter TTF compared with those with stable or decrease in NLR both after first cycle (p = 0.014) and second cycle (p < 0.001). Conclusions The NLR is suggested to be useful not only as a prognostic marker but also as a predictive marker for treatment with nivolumab. Further prospective study is warranted to develop a predictive algorithm to detect PD cases as early as possible by focusing the time-series behavior of NLR.

Successful Erlotinib Treatment for a Patient with Gefitinib-Related Hepatotoxicity and Lung Adenocarcinoma Refractory to Intermittently Administered Gefitinib

A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patients enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity.

Successful Osimertinib Rechallenge with Steroid Therapy after Osimertinib-induced Interstitial Lung Disease: A Case Report

A 62-year-old male with lung adenocarcinoma harboring an exon 19 deletion in the Epidermal growth factor receptor (EGFR) was treated with EGFR-tyrosine kinase inhibitors (TKIs) and several cytotoxic agents. After administering a fifth-line chemotherapy regimen, a liver biopsy revealed a diagnosis of recurrence with a T790M mutation. After an 82-day course of osimertinib therapy, the patient developed osimertinib-induced interstitial lung disease (ILD). Osimertinib was discontinued, and oral prednisolone was started. The ILD quickly improved, but liver metastases progressed and osimertinib was restarted concurrently with prednisolone. The patient showed neither disease progression nor a recurrence of ILD at 5 months. In situations in which no alternative treatment is available, osimertinib rechallenge should thus be considered as an alternative treatment.

Role of S1P/S1PR3 axis in release of CCL20 from human bronchial epithelial cells

Background Sphingosine kinase phosphorylates sphingosine to generate sphingosine 1 phosphate (S1P) following stimulation of the five plasma membrane G-protein-coupled receptors. The objective of this study is to clarify the role of S1P and its receptors (S1PRs), especially S1PR3 in airway epithelial cells. Methods The effects of S1P on asthma-related genes expression were examined with the human bronchial epithelial cells BEAS-2B and Calu-3 using a transcriptome analysis and siRNA of S1PRs. To clarify the role of CCL20 in the airway inflammation, BALB/c mice were immunized with ovalbumin (OVA) and subsequently challenged with an OVA-containing aerosol to induce asthma with or without intraperitoneal administration of anti-CCL20. Finally, the anti-inflammatory effect of VPC 23019, S1PR1/3 antagonist, in the OVA-induced asthma was examined. Results S1P induced the expression of some asthma-related genes, such as ADRB2, PTGER4, and CCL20, in the bronchial epithelial cells. The knock-down of SIPR3 suppressed the expression of S1P-inducing CCL20. Anti-CCL20 antibody significantly attenuated the eosinophil numbers in the bronchoalveolar lavage fluid (P<0.01). Upon OVA challenge, VPC23019 exhibited substantially attenuated eosinophilic inflammation. Conclusions S1P/S1PR3 pathways have a role in release of proinflammatory cytokines from bronchial epithelial cells. Our results suggest that S1P/S1PR3 may be a possible candidate for the treatment of bronchial asthma.

The Dose and Risk Factors for Radiation Exposure from X-Ray Fluoroscopy During EBUS-GS for Peripheral Pulmonary Lesions

The dose of radiation exposure from X-ray fluoroscopy during EBUS-GS is much less than we expect; in fact, it was found to be negligibly low, especially for nurses and radiology technicians who usually stand away from the operating table. Wearing a protector can further reduce the dose of radiation exposure to the trunk of the body. However, great care should be taken because the relationship between radiation exposure dose and health hazards is not well clarified yet.

Anesthesia for Bronchoscopy

Adequate pre-procedural laryngopharyngeal anesthesia is important for smooth insertion of the bronchoscope through the pharynx and vocal cords. Moderate to deep intravenous sedation during bronchoscopy is almost always recommended for patient comfort and for the beneficial effects of retrograde amnesia.

Rice-field drowning-associated pneumonia in which pseudomonas spp., aspergillus fumigatus, and cunninghamella sp. Are isolated

We herein report the case of an 84-year-old who developed pneumonia after drowning in a rice field. Besides Aspergillus fumigatus, many pathogens previously not reported in drowning-associated pneumonia (such as Pseudomonas fluorescens, Pseudomonas putida, Nocardia niigatensis, and Cunninghamella sp.) were isolated from his sputum. He received sulbactam/ampicillin, trimethoprim/sulfamethoxazole, voriconazole, levofloxacin and liposomal amphotericin B, but died due to respiratory failure. Because the patient had drowned in a contaminated stagnant rice field and had multiple lung cavities, zygomycosis was suspected. This report provides invaluable information for the consideration of zygomycosis after an individual drowning in a rice field, even in an immunocompetent patient.