A case of epidermal growth factor receptor tyrosine kinase inhibitor effectiveness in epidermal growth factor receptor mutation-positive squamous cell carcinoma.

A 71-year-old non-smoker woman was admitted to our hospital because of left front chest pain. A computed tomography scan showed a large mass of >7.0 cm in the lower left part of the lung and multiple organ metastases in the liver, brain, bone, and left adrenal gland. Pathological analysis of a resected specimen obtained by bronchoscopy revealed keratinization. In addition, p40 was positive and thyroid transcription factor-1, synaptophysin, CD56, and chromogranin A were negative by immunohistochemistry. Programmed cell death ligand 1 expression was 1%-10%, and exon 19 deletion was detected. We diagnosed the patient with stage IVB lung squamous cell carcinoma and administered osimertinib. Osimertinib was later replaced with afatinib because of grade 3 skin rash. Overall, the size of the cancer was decreased. Furthermore, her symptoms, laboratory data, and computer tomographic findings markedly improved. In summary, we experienced a case of epidermal growth factor receptor-positive lung squamous cell carcinoma that was responsive to epidermal growth factor receptor tyrosine kinase inhibitors.

Transcriptome genetic differences between responders and non-responders before bronchial thermoplasty.

BACKGROUND: Bronchial thermoplasty (BT) is an endoscopic therapy used for the treatment of refractory asthma. Some predictive factors, for example the number of activations and severity of disease at baseline, have been used to determine the effectiveness of BT in treating patients with asthma. The aim of the present study was to comprehensively analyze RNA samples from the airway bronchial tissues of patients with severe asthma treated by BT, and to characterize each patient as a BT responder or non-responder. METHODS: Eight patients with severe asthma scheduled to undergo BT and bronchus biopsies were recruited before the procedures were conducted. Extracted RNA samples from bronchial tissues were sequenced and differential gene expression analysis was carried out.Results/discussion: Subjects with Asthma Quality of Life Questionnaire score changes ≥0.5 for a period of 12 months were considered BT responders. Non-responders had score changes <0.5 for 12 months. Histopathology findings were similar to those reported previously, and no significant differences in the expression of α-smooth muscle actin and protein gene product 9.5 were observed between responders and non-responders. Transcriptome analysis at baseline identified 67 genes that were differentially expressed between responders and non-responders, including SLPI, MMP3, and MUC19, which were upregulated in responders. Although the differentially expressed gene products may have conflicting effects, genes in the airway epithelium and extracellular matrix of patients with severe asthma may determine the BT response. Our results identified possible transcriptomic changes that could be used to identify BT responders.

Association between time to treatment failure and peripheral eosinophils in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Introduction: There is an unmet clinical need to identify biomarkers predicting which patients with non­small cell lung cancer (NSCLC) would benefit from treatment with immune checkpoint inhibitors (ICPIs). Objectives: The purpose of this study was to draw a detailed time to treatment failure (TTF) curve with information on the changes in peripheral eosinophil expression during ICPI treatment for NSCLC, and to clarify whether eosinophil expression can predict prolonged TTF. Patients and methods: In 259 patients with NSCLC treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of each ICPI administration were evaluated from the beginning of ICPI treatment up to TTF. Univariable and multivariable analyses were performed to identify clinical factors associated with TTF. Results: Patients receiving ICPI monotherapy (n = 180) were divided into 3 groups (TTF ≤6 weeks, TTF >6 weeks and ≤24 weeks, and TTF >24 weeks) and the number of patients with an eosinophil percentage of 5% or more within 6 weeks of ICPI therapy initiation was significantly different among these groups. In univariable and multivariable analyses, performance status of 0 to 1, immune-related adverse event not requiring ICPI discontinuation as well as an eosinophil percentage of 5% or more and an eosinophil count of 330/µ or more within 6 weeks of ICPI therapy initiation were significant favorable factors for prolonged TTF. In patients treated with combination therapy of ICPI and chemotherapy (n = 79), the number of patients with an eosinophil percentage of 5% or more within 12 weeks of therapy initiation was significantly different between patients with a TTF of up to 12 weeks and those with a more prolonged TTF. However, the only significant favorable factor for TTF was female sex. Conclusions: In NSCLC patients treated with ICPI therapy, particularly ICPI monotherapy, eosinophil measurements during treatment might be useful for predicting prolonged TTF.

Effect of Shakuyakukanzoto on Chemotherapy-Induced Hiccups in Patients with Lung Cancer.

OBJECTIVE: Shakuyakukanzoto, one of the traditional herbal medicines commonly used in North-East Asian countries, is known to be effective for muscle cramps. This retrospective study aimed to evaluate the effect of shakuyakukanzoto on chemotherapy-induced metoclopramide-uncontrolled hiccups. MATERIALS AND METHODS: We retrospectively investigated the medical records of all the consecutive patients with lung cancer who were prescribed with shakuyakukanzoto (Tsumura Co. Tokyo, Japan) for chemotherapy-induced hiccups in our hospital from September 2013 to November 2017. In the medical record from the initiation of shakuyakukanzoto until the start of the next chemotherapy, when there was description of "complete or partial disappearance of hiccups" after the prescription of shakuyakukanzoto, it was judged as a complete or partial response. A statement of "unchanged," no description of improvement, or exacerbation was judged as no change. RESULTS: Of the 49 chemotherapy courses in 15 patients with lung cancer, 93.9% had a "partial or complete" response within a few hours after the administration of shakuyakukanzoto. The effect of shakuyakukanzoto was observed irrespective of the pathological type of lung cancer, platinum-containing or non-platinum chemotherapy, and with or without other anti-hiccup drugs. No adverse event was observed. CONCLUSION: Shakuyakukanzoto may offer an effective pharmacological approach to treat chemotherapy-induced metoclopramide-uncontrolled hiccups. Well-planned prospective studies will confirm our results.

Nrf2 Regulates Granuloma Formation and Macrophage Activation during Mycobacterium avium Infection via Mediating Nramp1 and HO-1 Expressions.

Nrf2 is a redox-sensitive transcription factor that is thought to be important in protection against intracellular pathogens. To determine the protective role of Nrf2 in the host defense against Mycobacterium avium complex (MAC), both wild-type and Nrf2-deficient mice were intranasally infected with MAC bacteria. Nrf2-deficient mice were highly susceptible to MAC bacteria compared with wild-type mice. There were no significant changes in the levels of oxidative stress and Th1 cytokine production between genotypes. Comprehensive transcriptome analysis showed that the expressions of Nramp1 and HO-1 were much lower in the infected lungs, and the expression of Nramp1 was especially lower in alveolar macrophages of Nrf2-deficient mice than of wild-type mice. Electron microscopy showed that many infected alveolar macrophages from Nrf2-deficient mice contained a large number of intracellular MAC bacteria with little formation of phagolysosomes, compared with those from wild-type mice. Treatment with sulforaphane, an activator of Nrf2, increased resistance to MAC with increased lung expression of Nramp1 and HO-1 in wild-type mice. These results indicate that Nramp1 and HO-1, regulated by Nrf2, are essential in defending against MAC infection due to the promotion of phagolysosome fusion and granuloma formation, respectively. Thus, Nrf2 is thought to be a critical determinant of host resistance to MAC infection.IMPORTANCE Nontuberculous mycobacteria (NTM) are an important cause of morbidity and mortality in pulmonary infections. Among them, Mycobacterium avium complex (MAC) is the most common cause of pulmonary NTM disease worldwide. It is thought that both environmental exposure and host susceptibility are required for the establishment of pulmonary MAC disease, because pulmonary MAC diseases are most commonly observed in slender, postmenopausal women without a clearly recognized immunodeficiency. However, host factors that regulate MAC susceptibility have not been elucidated until now. This study shows that Nrf2 is a critical regulator of host susceptibility to pulmonary MAC disease by promoting phagolysosome fusion and granuloma formation via activating Nramp1 and HO-1 genes, respectively. The Nrf2 system is activated in alveolar macrophages, the most important cells during MAC infection, as both the main reservoir of infection and bacillus-killing cells. Thus, augmentation of Nrf2 might be a useful therapeutic approach for protection against pulmonary MAC disease.

Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients.

Background/Aim: To clarify the clinical significance of the absolute increase in the number and proportion of peripheral eosinophils associated with immune checkpoint inhibitor (ICPI) treatment in non-small cell lung cancer (NSCLC) patients. Patients and Methods: We performed a retrospective study, by reviewing the medical charts of 191 patients who were treated with ICPI monotherapy and 80 patients treated with the combination of ICPI and chemotherapy during the period from February 2016 and April 2021. Results: In patients treated with ICPI monotherapy, there was a significant difference in time to treatment failure (TTF) between the two groups divided by eosinophils ≥ or <10%. Similarly, a significant difference was found in TTF between the two groups divided by eosinophils ≥ or <1,500/µl. Factors related to both an increase in the number and percentage of peripheral eosinophils were "immune-related adverse effects (irAE) that did not lead to discontinuation of administration". Conclusion: Some patients with irAE might have a 'favorable' absolute increase in peripheral eosinophils.

Rinsing of oropharynx and storage place of respiratory medicine inhaler: A cross-sectional audit.

BACKGROUND: In patients with bronchial asthma and those with chronic obstructive pulmonary disease (COPD), inhalation therapy and rinsing of the mouth and the oropharynx by gargling ("RMOG") after inhalation are recommended. We performed a cross-sectional audit aimed at investigating (a) the proportion of patients performing "RMOG" after inhalation and (b) storage place of patients' inhaler. METHODS: Patients with bronchial asthma and those with COPD were asked by medical aids at outpatient visits whether they did "RMOG every time," "RMOG sometimes," or "no RMOG" after inhalation, and where they stored their inhaler. RESULTS: During a six month study period up to September 2017, 330 consecutive patients with asthma and those with COPD were included in the study. Two hundred and thirty-two (70.3%) of the 330 patients answered "RMOG every time" and 98 (29.7%) of them did "RMOG sometimes" and did "no RMOG." There was a difference in the proportion of patients performing RMOG after inhalation with patient age. With regard to the storage location of inhaler, we found the proportion of patients performing RMOG was higher in those who stored inhalers in a room with running water than in those who stored inhalers at other places. This difference was found in patients with both bronchial asthma and those with COPD. CONCLUSIONS: Further implementation of "patient education" on performing RMOG after inhalation for patients receiving inhaled medication is still necessary. Our results suggest that it is better to store inhalers in places where there is easy access to tap water used for RMOG.

A Long-Term Control of Intramedullary Thoracic Spinal Cord Metastasis from Small Cell Lung Cancer.

Radiotherapy with systemic corticosteroid therapy has been used to treat intramedullary spinal cord metastasis (ISCM), but recovery of function and long-term survival of these patients has been rarely observed. We report herein a small cell lung cancer (SCLC) patient with recurrent thoracic ISCM, who was successfully treated with radiotherapy and systemic corticosteroid therapy. A 70-year-old man, who was diagnosed as having SCLC seven months previously, developed thoracic ISCM. Soon after the detection of the lesion, the patient received radiotherapy with systemic corticosteroid therapy. Sensory disturbance in both extremities and neurogenic bladder and bowel dysfunction was recovered. The patient could walk after irradiation again. The patient received additional chemotherapy and survived 20 months after the diagnosis of ISCM recurrence. Prompt diagnosis and appropriate treatment for ISCM and effective chemotherapy for recurrent SCLC might be the favorable factors for such patients. Further studies will be required to define a favorable subset of patients most likely to benefit from a conventional approach.

Paradoxical response to osimertinib therapy in a patient with T790M-mutated lung adenocarcinoma.

A 'paradoxical response' to cancer treatment is a term used to describe the emergence of unexpected new lesions and the progression of existing lesions, despite appropriate and effective therapy. 'Pseudo-progression' is a phenomenon in which lymphocytes activated by an immune checkpoint inhibitor accumulate in a tumor and expand its shadow, mimicking enlargement of the primary lesion or development of a new metastatic lesion. Patients receiving cancer chemotherapy may respond differently to treatment, by exhibiting a response, deterioration, or the simultaneous occurrence of both. These variations may be attributed to the heterogeneity of the cancer. However, differences in the temporary response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment are rarely observed. If such a phenomenon is observed, it should not affect the evaluation of the therapeutic effect or be considered as an indication for the discontinuation of treatment. We herein report a rare case of a transient increase in carcinomatous pleural fluid as a paradoxical response to osimertinib treatment in a patient with T790M-mutated lung adenocarcinoma. The primary lesion and pulmonary metastases responded well to therapy. Although this paradoxical response is very rare, of non-malignant nature, and does not usually require treatment modification of, physicians must acknowledge that it is not a clinically discouraging characteristic when using EGFR-TKI to treat T790M-mutated lung adenocarcinoma.

[Three cases of long-term control of non-small-cell lung cancer via S-1 monotherapy in elderly patients].

We report 3 cases of long-term control achieved via S-1 monotherapy in elderly patients with advanced non-small-cell lung cancer. In case 1, a 75-year-old man clinically diagnosed with stage IIIA lung adenocarcinoma received S-1 as fourthline chemotherapy. PR was achieved, and PFS was 8 months. In case 2, a 78-year-old woman clinically diagnosed with stage IV lung squamous cell carcinoma received S-1 as third-line chemotherapy. A PR was achieved, and PFS was 14 months. In case 3, an 83-year-old man clinically diagnosed with stage IV lung squamous cell carcinoma received CBDCA plus PTX, followed by S-1 on alternate days. Although tumor size was not reduced, SD was maintained for 11 months.

Emergency coronary artery bypass grafting for left main shock syndrome.

OBJECTIVE: Acute myocardial infarction (AMI) complicated by cardiogenic shock and left main coronary artery disease (left main shock syndrome) shows high morbidity, and whether early coronary artery bypass grafting (CABG) improves the clinical outcome remains unclear. METHODS: Six consecutive patients (mean age, 61.6 years) with MI complicated by left main shock syndrome underwent emergency CABG. Patients were divided into 2 groups according to the time from MI to reperfusion; within 8 hours in 3 patients and beyond 8 hours in the remaining. Average postoperative peak creatinine kinase (CK) and creatinine kinasemyosin band (CK-MB) levels were recorded, and the ejection fraction (EF) was measured with ultrasound cardiography. RESULTS: Significant differences in postoperative EF and CPK-MB were observed between the 2 groups. The 30-day survival rate was 100%. Five patients left the hospital alive, while 1 died on postoperative day 78. CONCLUSIONS: AMI complicated by cardiogenic shock and left main coronary artery disease can be effectively treated with emergency CABG, with acceptable mortality and morbidity. Emergency CABG for MIs within 8 hours can improve survival in patients with left main shock syndrome.