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Background This study aimed to determine the radiologic predictors and clarify the clinical features related to survival in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer. Methods We retrospectively reviewed the medical chart data and high-resolution computed tomography (HRCT) findings for 81 consecutive patients with CPFE and 92 primary lung cancers (70 men, 11 women; mean age, 70.9 years). We selected 8 axial HRCT images per patient, and visually determined the normal lung, modified Goddard, and fibrosis scores. Multivariate analysis was performed using the Cox proportional hazards regression model. Results The major clinical features were a high smoking index of 54.8 pack-years and idiopathic pulmonary fibrosis (n = 44). The major lung cancer profile was a peripherally located squamous cell carcinoma (n = 40) or adenocarcinoma (n = 31) adjacent to emphysema in the upper/middle lobe (n = 27) or fibrosis in the lower lobe (n = 26). The median total normal lung, modified Goddard, and fibrosis scores were 10, 8, and 8, respectively. TNM Classification of malignant tumors (TNM) stage I, II, III, and IV was noted in 37, 7, 26, and 22 patients, respectively. Acute exacerbation occurred in 20 patients. Multivariate analysis showed that a higher normal lung score and TNM stage were independent radiologic and clinical predictors of poor survival at the time of diagnosis of lung cancer. Conclusions A markedly reduced area of normal lung on HRCT was a relevant radiologic predictor of survival.

Background Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. Methods Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. Results The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09–0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18–25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14–0.73, p = 0.01). Conclusions Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient’s procedural tolerance and lower complications.

Background: To evaluate the safety of bronchoscopy and describe factors affecting its complication rate in patients with hematologic disorders. Methods: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with hematologic disorders and pulmonary lesions were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. Results: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Two patients (0.6%) were intubated within 48 hour of the procedure and prolonged oxygen desaturation (>48 hour) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation ( p = 0.01, hazard ratio 0.23, 95% confidence interval 0.07–0.75). Conclusions: Bronchoscopy is relatively safe in patients with hematologic disorders. Sedation with midazolam may reduce the risk of prolonged oxygen desaturation.

Pathological transformation to squamous cell carcinoma after epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor treatment has been reported, but details of the transformation remain unclear. We report two cases with transformation to squamous cell carcinoma. The first case was a 61‐year‐old man who was an ex‐smoker with stage IV lung adenocarcinoma harbouring EGFR exon 19 insertion. He experienced squamous cell transformation after 28 months of erlotinib therapy. Next‐generation sequencing (NGS) analysis showed EGFR T790M and genomic alterations in PTEN, PDGFR, and HRAS. The second case was a 72‐year‐old man who was an ex‐smoker with stage IV lung adenocarcinoma harbouring EGFR exon 21 L858R. He experienced squamous cell transformation after nine months of erlotinib therapy. NGS analysis showed EGFR T790M and genomic alterations in PTEN, SMARCB1, TP53, and KIT. Both patients had PTEN genomic alterations and the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway might play an important role in squamous cell transformation., Pathological transformation to squamous cell carcinoma after epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) treatment has been reported, but details of the transformation remain unclear. Here, we report two cases with transformation to squamous cell carcinoma after treatment with EGFR‐TKIs. Both patients had PTEN genomic alterations and the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway might play an important role in squamous cell transformation.

Background Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. Case presentation A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. Conclusion PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

A 60-year-old man developed pneumonia after undergoing autologous peripheral blood stem cell transplantation for diffuse large-B cell lymphoma. A urinary antigen test and sputum culture were both negative for Legionella pneumophila; however, a sputum sample that was examined by loop-mediated isothermal amplification (LAMP) was positive for Legionella spp. On admission, the results of blood culturing using a BACTEC system were negative for 7 days. However, L. pneumophila serogroup 5 was detected in a blood subculture using WYOα medium. The patient was successfully treated with a fluoroquinolone-based regimen. LAMP is useful for the diagnosis of Legionella spp.

Background Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. Case presentation A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. Conclusions Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

A 59-year-old man with relapsed epidermal growth factor receptor (EGFR) exon 19 deletion-positive stage IA adenosquamous carcinoma after lobectomy was treated with erlotinib and bevacizumab for 1 year followed by erlotinib alone for 1 year. Because of mediastinal and supraclavicular lymphadenopathy and a nodule on the left anterior chest wall, the patient underwent repeat biopsy from the supraclavicular lymph node. Pathological analysis demonstrated adenosquamous carcinoma harbouring EGFR exon 19 deletion and T790M mutation. Osimertinib treatment was therefore started. Six months later, the patient underwent a second-repeat biopsy from the mediastinal lymph nodes and liver metastases. Both specimens showed small cell lung carcinoma (SCLC). After chemotherapies for SCLC, he died from lung cancer. An autopsy demonstrated tumour heterogeneity, including histological types of adenosquamous, SCLC, and large-cell neuroendocrine carcinoma. Repeat biopsies at the time of disease progression are useful to choose subsequent treatment for patients with EGFR mutation-positive lung cancer.

[Methods] We retrospectively studied 115 con- secutive pulmonary tuberculosis patients whose sputum smear was .negative, diagnosed by positive culture and/or PCR of various samples, or positive QFT. [Results] The culture positive rate of tuberculosis by spu- tum, gastric aspirate, bronchoscopy, and computed tomogra- phy (CT)-guided needle biopsy samples was 55.7%, 45.6%, 73.2%, and 71.4%, respectively. In multivariate analysis, negative or unknown sputum PCR, negative or unknown gastric aspirate, and minimal spread of tuberculosis were risk factors for negative culture from both sputum and gas- tric aspirate. Sputum culture was positive in only one of the four patients with multi-drug resistant Mycobacterium tuberculosis. [Conclusion] Invasive diagnostic procedures such as fiber- optic bronchoscopy should be considered in patients with negative sputum PCR and minimal spread of tuberculosis.

We present the case of an 80-year-old woman with Mendelson's syndrome complicated by bacterial aspiration pneumonia caused by consciousness loss followed by vomiting resulting from putamen bleeding. Her condition worsened rapidly to develop respiratory failure, within a few hours; thereafter, she was intubated. Streptococcus agalactiae and Klebsiella oxytoca were detected from the aspirated sputum sample culture. She was diagnosed with acute respiratory distress syndrome with Mendelson's syndrome complicated by bacterial aspiration pneumonia. Corticosteroid and antibiotic administration improved her condition and led to successful extubation; therefore, these treatment modalities were invaluable. We suggest the clinical considerations for the corticosteroid and antibiotic use in such cases., Highlights • We report a case of Mendelson's syndrome complicated by bacterial aspiration pneumonia. • Use of steroids and antibiotics in such cases is controversial, however, they were reasonable choice in this case. • We discussed this debatable issue in this case report.

e14110 Background: ICIs such as anti-PD-1/-L1 Inhibitor and anti-CTLA-4 Inhibitor have been used in many types of cancer, and irAEs occur in a considerable proportion of patients. Predictive biomarkers could help us to manage irAEs promptly. Methods: We retrospectively analyzed the consecutive patients treated with nivolumab, pembrolizumab, atezolizumab or ipilimumab, not used as investigational drugs, between March 2015 and December 2018 based on the electric medical records in our institution. We evaluated the relationship between clinical and laboratory factors (gender, age, body mass index, lymphocyte-to-monocyte ratio and eosinophilia) and the occurrence of irAEs using univariate and multivariate analyses. Eosinophilia was defined as absolute eosinophil count over 500/mm3 at least once between initiation of treatment and the occurrence of irAEs. We graded irAEs according to CTCAE v. 5.0. Results: Among 139 patients analyzed in this study, 136, 13 and 6 patients were treated with PD-1, PD-L1 and CTLA-4 inhibitors, respectively (cumulative total of 155 patients). This study included non-small cell lung cancer (n = 78; 56.1%), renal cell carcinoma (n = 17; 12.2%), melanoma (n = 16; 11.5%), gastric cancer (n = 15; 10.8%), Hodgkin lymphoma (n = 7; 5.0%), urothelial carcinoma (n = 3; 2.2%), head and neck carcinoma (n = 3; 2.2%) and mesothelioma (n = 1; 0.7%). Any grade and grade 3-5 irAEs occurred in 60 (38.7%) and 23 (14.8%) cumulative patients, respectively. The most common irAEs in any grade were endocrine disorders including thyroid dysfunction and adrenal insufficiency (n = 21) and skin disorders (n = 20). Eosinophilia occurred in 43 cumulative patients (27.7%). Eighteen patients out of them had eosinophilia from baseline. Among the clinical and laboratory factors, only eosinophilia was significantly associated with the occurrence of any grade of irAEs in both univariate (p = 0.0193) and multivariate (p = 0.0464) analysis. Notably, endocrine irAEs were significantly related to eosinophilia (p = 0.0287). Conclusions: Eosinophilia after the initiation of treatment with ICIs predicts succeeding onset of irAEs.

The organ selectivity and the effect on myocardial ischemia-reperfusion injury of (R)-acetoxyhexamide ((R)-ACX), a novel sulfonylurea, were examined. (R)-ACX, as well as glibenclamide, concentration-dependently stimulated insulin release from INS-1 cell, a cell line derived from pancreatic beta-cells. The potency of (R)-ACX was about 1/10 of that of glibenclamide. In isolated guinea pig ventricular myocardial tissue, glibenclamide concentration-dependently inhibited the action potential shortening by NIP-121, an ATP-sensitive potassium channel opener, but (R)-ACX showed only slight inhibition. In isolated rat aortic rings contracted with norepinephrine, glibenclamide concentration-dependently inhibited the relaxation by NIP-121, while (R)-ACX showed only slight inhibition. In coronary-perfused guinea pig ventricular preparations, glibenclamide reduced the recovery of contractile force after ischemia-reperfusion, while (R)-ACX did not. In conclusion, (R)-ACX is a beta-cell selective sulfonylurea which, unlike glibenclamide, does not aggravate cardiac ischemia-reperfusion damage.