Associations of immune checkpoint inhibitor therapy efficacy with clinical parameters and tumor­infiltrating CD68­positive cell counts in patients with EGFR­mutant non­small cell lung cancer.

Immune checkpoint inhibitor (ICI) therapy has been less effective in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations than in patients with EGFR wild-type NSCLC. This retrospective study was conducted to investigate the associations of clinical parameters with the efficacy of ICI therapy in patients with EGFR-mutant NSCLC. Clinical information was retrieved from the medical charts, and immunohistochemical analysis was performed in some cases to determine the tumor-infiltrating CD68-positive cell count. Data from 46 patients were included in the analysis. The median (95% confidence interval) progression-free survival and overall survival from the initiation of ICI therapy was 1.4 months (1.0-1.7 months) and 6.4 months (3.9-19.0 months), respectively. Analysis using a Cox proportional hazards model revealed that tumor programmed death-ligand 1 expression was associated with the overall survival of patients with EGFR-mutant NSCLC after ICI treatment. The tumor-infiltrating CD68-positive cell count was evaluated in 11 patients. Comparison using the log-rank test revealed that the progression-free survival time after ICI treatment was longer in the patients with lower tumor-infiltrating CD68-positive cell counts than those with higher tumor-infiltrating CD68-positive cell counts. The present analysis demonstrated that PD-L1 expression and the tumor-infiltrating CD68-positive cell count may be associated with the efficacy of ICI therapy in patients with NSCLC harboring EGFR mutations.

Efficacy of immune checkpoint inhibitor therapy in patients with pulmonary sarcomatoid carcinoma in clinical practice.

OBJECTIVE: Studies have suggested the potential efficacy of immune checkpoint inhibitors (ICIs) for pulmonary sarcomatoid carcinoma. This multicenter observational study was conducted to evaluate the efficacy of systemic ICI therapy and chemoradiation followed by durvalumab therapy for pulmonary sarcomatoid carcinoma. METHODS: We analyzed the data of patients with pulmonary sarcomatoid carcinoma who received systemic ICI therapy or chemoradiation followed by durvalumab therapy between 2016 and 2022. RESULTS: In this study, data of a total of 22 patients who received systemic ICI therapy and four patients who received chemoradiation followed by durvalumab therapy were analyzed. In the patients who received systemic ICI therapy, the median progression-free survival after initiation of therapy was 9.6 months, and the overall survival did not reach the median. The 1-year progression-free survival rate and overall survival rate were estimated to be 45.5% and 50.1%, respectively. Although the log-rank test revealed no significant association between the tumor expression level of programmed death ligand-1 (tumor proportion score evaluated using 22C3 antibody: ≥50% vs. <50%) and the survival duration, the majority of patients showing long-term survival showed a tumor proportion score of ≥50%. Of four patients treated with chemoradiation followed by durvalumab therapy, two patients showed an overall survival of ≥30 months, whereas the remaining two patients died within 12 months. CONCLUSION: The progression-free survival of patients who received systemic ICI therapy was 9.6 months, suggesting that ICI therapy might be effective in patients with pulmonary sarcomatoid carcinoma.

Tracheobronchitis in patients with diffuse wall thickening: Three case reports.

We herein report the cases of three patients with chest symptoms or fever and diffuse wall thickening of the trachea and main bronchi on chest CT. They were diagnosed with various causes of inflammations of the trachea and main bronchi using bronchial or tracheal biopsy specimens and flexible bronchoscopy.

Rare MYH9-ROS1 Fusion Gene-Positive Lung Adenocarcinoma Showing Response to Entrectinib Treatment: A Case Study.

The c-ros oncogene 1 (ROS1) fusion gene is a rare genomic alteration detected in nearly 1-2% of lung adenocarcinomas. The major partner genes of ROS1 include CD74, SDC4, and EZR. Here, we report a case of MYH9-ROS1 fusion gene-positive lung adenocarcinoma, a rare ROS1 fusion gene. The patient was a woman in her 40s who was diagnosed with advanced primary lung adenocarcinoma after a thorough examination. Initial genetic testing conducted using mediastinal lymph node biopsy specimens collected by endobronchial ultrasound-guided transbronchial needle aspiration revealed no driver gene mutations, including the ROS1 fusion gene. The patient was treated with four courses of immunochemotherapy. As the disease worsened, another genetic test was conducted using FoundationOne® CDx, and the MYH9-ROS1 fusion gene was detected. Multiple lung metastases disappeared after the administration of entrectinib; the response persisted up to a year. Adverse events of rash, dysgeusia, and peripheral edema were observed, and the patient required temporary drug interruption; however, we were able to continue entrectinib following a short-term drug interruption. This is the first report on the effectiveness of entrectinib against lung adenocarcinoma with the rare MYH9-ROS1 fusion gene.

Bochdalek hernia with liver herniation.

Bochdalek hernia with liver herniation is rare and mimics a pulmonary mass. This case was hospitalized for masses found in the lower field of the right lung on a chest radiograph. The patient was diagnosed with Bochdalek hernia with liver herniation with three-dimensional images created from thoracoabdominal-enhanced computed tomography.

Chest tightness is relieved with the use of asthma drugs except bronchodilators.

Objective: Many patients with a chief complaint of chest tightness are examined in medical facilities, and a lack of diagnosis is not uncommon. We have reported that these patients often include those with chest tightness relieved with bronchodilator use (CTRB) and those with chest tightness relieved with the use of asthma drugs except bronchodilators (CTRAEB). The purpose of this study was to demonstrate the clinical characteristics of the patients with CTRAEB and compare them with data from patients with CTRB. Methods: Patients with CTRB (n = 13) and CTRAEB (n = 7) underwent a bronchodilator test, assessments of airway responsiveness to methacholine, bronchial biopsy, and bronchial lavage under fiberoptic bronchoscopy before receiving treatment. In all, 10 healthy subjects, 11 bronchial biopsy control patients, and 10 asthmatic patients were recruited for comparison. Results: Inhalation of a short-acting ß2-agonist (SABA) increased the forced expiratory volume in one second (FEV1) by 5.1% ± 4.0% in patients with CTRB and by 1.3% ± 3.5% in patients with CTRAEB, and the difference was statistically significant (p = 0.0449). The bronchial biopsy specimens from the patients with CTRB and CTRAEB exhibited significant increases in T cells (p < .05) compared with those of the control subjects. The bronchial responsiveness to methacholine was increased in only a minor portion of patients with CTRB and CTRAEB. Conclusions: We hypothesized that the clinical condition of patients with CTRAEB involves chest tightness arising from inflammation alone, and this chest tightness is mostly associated with airway T cells, without constriction of the airways. There is little to distinguish CTRAEB from CTRB aside from the response to bronchodilator treatment. This clinical trial is registered at www.umin.ac.jp (UMIN13994, 13998, and 16741).

Multimodal imaging findings in an adult case of Swyer-James-MacLeod syndrome.

Swyer-James-MacLeod syndrome (SJMS) is an uncommon obliterative lung disease that is radiologically characterized by hyperlucency of a part of or the entire lung. A 33-year-old man presented to our hospital for chest tightness. A chest X-ray revealed unilateral hyperlucency of left lower lung, and contrast-enhanced computed tomography (CT) of the chest disclosed a hyperlucent left lung without vascularity. Three-dimensional CT reconstruction and ventilation-perfusion scan findings were concordant with SJMS. We herein report a case of SJMS in a patient who showed the characteristic multimodal imaging findings.

Multiple Metastasizing Pleomorphic Adenomas of the Lung.

A 40-year-old woman was referred to our hospital with abnormal findings on chest X-ray. Her medical history was remarkable in that she had presented with a pleomorphic adenoma in the right parotid gland treated by surgical removal approximately 12 years previously. Chest computed tomography showed well-defined non-calcified nodules of the bilateral lobes, so she underwent segmentectomy of the right upper lobe and middle lobe. The histopathological diagnosis was metastasizing pleomorphic adenoma of the lung, a rare entity.

Bronchial biopsy and reactivity in patients with chest tightness relieved with bronchodilator.

OBJECTIVE: It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks. METHODS: Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß2-agonist. These patients underwent assessments of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage under fiber-optic bronchoscopy before receiving treatment. RESULTS: For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients. CONCLUSIONS: We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).

Utility of creatinine/cystatin C ratio as a predictive marker for adverse effects of chemotherapy in lung cancer: A retrospective study.

OBJECTIVE: To determine whether the creatinine/cystatin C (Cr/CysC) ratio, which is influenced by muscle mass, can be used as a predictive marker of the adverse effects of chemotherapy. METHODS: This single-centre, retrospective, observational study assessed patients with lung cancer. Serum Cr and CysC levels were measured once within 1 month prior the commencement of chemotherapy. RESULTS: A total of 25 patients with lung cancer were enrolled in the study: 22 received first-line therapy; three received second-line therapy. A significant difference was noted regarding the Cr/CysC ratios between patients with nonsmall-cell lung cancer (NSCLC) and those with small-cell lung cancer (0.78 versus 0.92, respectively). A significant difference was also noted in the Cr/CysC ratios of patients with NSCLC with toxicity grades <3 and ≥3 (0.84 versus 0.70, respectively). Similar findings were observed in patients with NSCLC who received platinum-based combination therapy (toxicity grade < 3, 0.85; toxicity grade ≥3, 0.69). CONCLUSION: The Cr/CysC ratio could serve as a useful predictive marker for chemotherapy-related adverse effects in patients with NSCLC.

Diagnostic challenges of tuberculous lymphadenitis using polymerase chain reaction analysis: a case study.

This report presents a case of tuberculous lymphadenitis that was difficult to diagnose using polymerase chain reaction analysis. An 80-year-old Japanese female was hospitalized due to swollen cervical lymph nodes. Her lymph node tests revealed paradoxical polymerase chain reaction results. Polymerase chain reaction analysis of two biopsy tissues using the Cobas TaqMan revealed a positive result for Mycobacterium avium and a negative result for Mycobacterium tuberculosis. However, polymerase chain reaction analysis of a cultured colony of acid-fast bacteria from biopsy tissue using the Cobas TaqMan and an alternative polymerase chain reaction analysis of biopsy tissue yielded discordant results. The patient was diagnosed as having tuberculous lymphadenitis. She was treated with antitubercular drugs and subsequently had a reduction in cervical lymph node swelling. Polymerase chain reaction analysis is not 100% accurate; hence, its use as a diagnostic tool for mycobacterial infection requires increased attention.

Relationship of the urine cortisol level with the performance status of patients with lung cancer: a retrospective study.

PURPOSE: Cortisol plays an important role in the physical status of patients with end-stage lung cancer, but the association of urine cortisol levels with TNM stage/performance status (PS) is unclear in patients with advanced lung cancer receiving chemotherapy. The objective of this study was to examine this association. METHODS: In this single-center, retrospective, observational study, cortisol concentrations in 24-h pooled urine from 22 patients with advanced lung cancer were measured over 2 days. The mean concentration in each patient was compared with PS, TNM stage, and serum sodium and potassium ion levels. RESULTS: The 24-h urine cortisol levels were higher in PS2 or PS3 cases compared to PS1 (p < 0.05) and increased proportionally with PS. Urine cortisol also increased in N2 or N3 cases compared to N1 (p < 0.01) and also increased in M1 cases (p < 0.05). Urine cortisol levels were negatively correlated with serum sodium (R = -0.49, p < 0.05) and had a tendency for a positive correlation with serum potassium (R = 0.40, p = 0.06). CONCLUSION: The 24-h urine cortisol level increased in patients with advanced lung cancer undergoing chemotherapy. Low serum levels of potassium and high levels of sodium may indicate relative adrenal insufficiency.

A history of ischemic heart disease is a common cause of wheezing in the elderly of a Japanese local community.

OBJECTIVE: We conducted a cross-sectional study to investigate which factors have a significant impact on wheezing and QOL in the elderly of a Japanese local community. METHODS: In 2008, 527 participants (250 participants aged 45 to 64 years and 277 participants aged 65 to 88 years) responded to the questionnaire regarding wheezing and disease history. QOL was evaluated by the Short Form-8. The participants underwent airway reversibility testing. The plasma levels of IgE were measured. The plasma levels of N-terminal-pro-B-type natriuretic peptide were measured in twenty-one participants with a history of ischemic heart disease and in thirty-five age-matched participants without that history. RESULTS: Wheezing was reported by 50 (9.5%) participants and was associated with a lower score of QOL. In multivariate analysis, wheezing was associated with sex (OR 3.12, CI 1.10-9.67) and a history of bronchial asthma (OR 22.3, CI 6.50-84.0) among participants aged 45 to 64 years. Among participants aged 65 and over, wheezing was associated with a history of bronchial asthma (OR 4.86, CI 1.39-15.1) and ischemic heart disease (OR 5.12, CI 1.61-15.0). Participants with both a history of ischemic heart disease and wheezing showed higher levels of N-terminal-pro-B-type natriuretic peptide. Airway reversibility was only associated with a history of ischemic heart disease (OR 4.65, CI 1.26-17.6). CONCLUSION: It is suggested that bronchial asthma and heart disease are both significant causes of wheezing and affect the QOL in the elderly of a Japanese local community.