Efficacy and Safety of Docetaxel plus Ramucirumab for Patients with Pretreated Advanced or Recurrent Non-small Cell Lung Cancer: Focus on Older Patients.

Background: Combination therapy with docetaxel (DTX) and ramucirumab (RAM) has been used as a second-line treatment for advanced or recurrent lung cancer. However, there is insufficient evidence regarding the safety of angiogenesis inhibitors in older patients.

Objective: This multicenter retrospective study aimed to investigate the efficacy and safety of second-line treatment regimens in older patients with advanced or recurrent non-small cell lung cancer (NSCLC).

Prospective Observational Study Evaluating the Prognostic Value of the G8 Screening Tool for Extensive-Stage Small Cell Lung Cancer Patients Who Received Programmed Death-Ligand 1 Inhibitor plus Platinum-Etoposide Chemotherapy.

Background: Programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy is used as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), regardless of age.

Objective: We examined the role of the Geriatric 8 (G8) screening tool for evaluating treatment outcomes in patients with ES-SCLC treated with PD-L1 inhibitor plus platinum-etoposide chemotherapy as first-line therapy.

Patients And Methods: Between September 2019 and October 2021, we prospectively evaluated patients with ES-SCLC treated with immunochemotherapy at ten institutions in Japan.

Comparison of the prognosis of symptomatic cerebral infarction and pulmonary embolism in patients with advanced non-small cell lung cancer.

Background: Lung cancer patients face a high risk of thromboembolism (TE), which is considered to be a poor prognostic factor. However, the impact of symptomatic cerebral infarction (CI) and pulmonary embolism (PE) on the prognosis of advanced non-small cell lung cancer (NSCLC) patients is not fully understood.

Methods: We retrospectively identified 46 patients with advanced NSCLC who developed symptomatic CI or PE at five hospitals in Japan between January 2010 and December 2019.

Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial.

Introduction: First-line treatment of -mutated NSCLC with erlotinib plus antiangiogenic inhibitor exhibits promising results. However, the efficacy of this combination has not been fully investigated. Therefore, we evaluated the efficacy and safety of osimertinib plus bevacizumab in patients with -mutated NSCLC complicated with malignant pleural or pericardial effusion (MPE) for whom combination therapy may be particularly effective.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

Background: Topoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear.

Diagnosis of unexposed tumours using endobronchial ultrasonography with a guide sheath and a thin transbronchial needle.

Transbronchial diagnosis of unexposed lung tumours is challenging in clinical practice. Although modified transbronchial needle aspiration (TBNA) is used for this purpose, the diagnostic yield is unsatisfactory. In such cases, conventional endobronchial ultrasonography with a guide sheath and transbronchial biopsy (TBB) is also ineffective.

TTF-1 and c-MYC-defined Phenotypes of Large Cell Neuroendocrine Carcinoma and Delta-like Protein 3 Expression for Treatment Selection.

The standard treatment regimen has not yet been established for advanced pulmonary large cell neuroendocrine carcinoma (LCNEC) because of its rarity. LCNEC can be subdivided into 2 mutually exclusive molecular subgroups: STK11/KEAP1 and TP53 mutated with high neuroendocrine expression and transcriptional profile of ASCL1high/DLL3high/NOTCHlow (non-small cell lung carcinoma, NSCLC-like) or RB1 and TP53 mutated with reduced neuroendocrine markers and transcriptional pattern of ASCL1low/DLL3low/NOTCHhigh (small cell lung cancer, SCLC-like). Model-based clustering shows that SCLC has subdivided into 2 major proteomic subsets defined by either TTF-1high/c-MYClow or TTF-1low/c-MYChigh, which may correspond to 2 mutually exclusive molecular subgroups: NSCLC-like or SCLC-like, respectively.

Multiple primary lung adenocarcinomas pre-operatively diagnosed by discordant epidermal growth factor receptor mutations.

A 49-year-old woman with an abnormal shadow on her chest X-ray visited our hospital. Chest computed tomography revealed a 13-mm diameter nodule in S9 on the right and a 47-mm diameter mass in segment (S) 1 + 2 on the left. She underwent transbronchial biopsy, which revealed that both tumours had the same histology of papillary adenocarcinoma.

Phase II Study of S-1 and Paclitaxel Combination Therapy in Patients with Previously Treated Non-Small Cell Lung Cancer.

Lessons Learned: In terms of efficacy and safety, good results were obtained with S-1 and paclitaxel (PTX) combination therapy.The findings suggest that S-1 and PTX combination therapy is a feasible treatment option in patients with previously treated non-small cell lung cancer.

Background: Although monotherapy with cytotoxic agents, including docetaxel and pemetrexed, is recommended for patients with previously treated advanced non-small cell lung cancer (NSCLC), its outcomes are unsatisfactory.

A Phase II Study of S-1 and Paclitaxel Combination Therapy as a First-Line Treatment in Elderly Patients with Advanced Non-Small Cell Lung Cancer.

Lessons Learned: Coadministration of S-1 and paclitaxel in elderly patients with advanced non-small cell lung cancer showed favorable efficacy.Coadministration of S-1 and paclitaxel in elderly patients with advanced non-small lung cancer showed tolerable toxicity.

Background: Although monotherapy with cytotoxic agents including docetaxel or vinorelbine are recommended for elderly patients with advanced non-small cell lung cancer (NSCLC), the outcome is not satisfactory.

Phase I study of S-1 plus paclitaxel combination therapy as a first-line treatment in elderly patients with advanced non-small cell lung cancer.

This phase I study was aimed at determining the maximum tolerated dose (MTD) and recommended dose (RD) for oral S-1 plus paclitaxel combination therapy in elderly patients with non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients (age, >70 years) with stage III/IV NSCLC were treated with paclitaxel intravenously at four dose levels (DLs), 60, 70, 80, and 90 mg/m, on day 1 and 8, and with S-1 (80 mg/m) orally on days 1-14 every 3 weeks. MTD was defined as the dose at which two of the initial three patients experienced dose-limiting toxicities (DLTs).

[Possible contribution of disseminated Mycobacterium shigaense infection to development of splenic marginal zone lymphoma].

A 73-year-old male who underwent splenectomy was diagnosed with splenic non-caseating granuloma in May 201X, and sarcoidosis was disregarded from the differential diagnosis. Owing to the persisting inflammation, the patient was carefully followed up with no treatment. Four months post splenectomy, the patient was hospitalized due to progressive dyspnea.

Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

Background/aim: The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC).

Patients And Methods: Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs.

Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells.

We and others have shown that epithelial Na(+) channels (ENaC) in alveolar type 2 (AT2) cells are activated by β2 agonists, steroid hormones, elevated oxygen tension, and by dopamine. Although acetylcholine receptors (AChRs) have been previously described in the lung, there are few reports of whether cholinergic agonists alter sodium transport in the alveolar epithelium. Therefore, we investigated how cholinergic receptors regulate ENaC activity in primary cultures of rat AT2 cells using cell-attached patch-clamp recordings to assess ENaC activity.

Procaterol-stimulated increases in ciliary bend amplitude and ciliary beat frequency in mouse bronchioles.

The beating cilia play a key role in lung mucociliary transport. The ciliary beating frequency (CBF) and ciliary bend amplitude (CBA) of isolated mouse bronchiolar ciliary cells were measured using a light microscope equipped with a high-speed camera (500 Hz). Procaterol (aβ(2)-agonist) increased CBA and CBF in a dose dependent manner via cAMP.

Rac1-mediated NADPH oxidase release of O2- regulates epithelial sodium channel activity in the alveolar epithelium.

We examine whether alveolar cells can control release of O(2)(-) through regulated NADPH oxidase (NOX) 2 (NOX2) activity to maintain lung fluid homeostasis. Using FACS to purify alveolar epithelial cells, we show that type 1 cells robustly express each of the critical NOX components that catalyze the production of O(2)(-) (NOX2 or gp91(phox), p22(phox), p67(phox), p47(phox), and p40(phox) subunits) as well as Rac1 at substantially higher levels than type 2 cells. Immunohistochemical labeling of lung tissue shows that Rac1 expression is cytoplasmic and resides near the apical surface of type 1 cells, whereas NOX2 coimmunoprecipitates with epithelial sodium channel (ENaC).

Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia.

We report the effects of new N-acylated ambroxol derivatives (TEI-588a, TEI-588b, TEI-589a, TEI-589b, TEI-602a and TEI-602b: a, aromatic amine-acylated derivative; b, aliphatic amine-acylated derivative) induced from ambroxol (a mucolytic agent to treat human lung diseases) on Cl(-) secretion in human submucosal serous Calu-3 cells under a Na(+)/K(+)/2Cl(-) cotransporter-1 (NKCC1)-mediated hyper-secreting condition. TEI-589a, TEI-589b and TEI-602a diminished hyper-secretion of Cl(-) by diminishing the activity of NKCC1 without blockade of apical Cl(-) channel (TEI-589a>TEI-602a>TEI-589b), while any other tested compounds including ambroxol had no effects on Cl(-) secretion. These indicate that the inhibitory action of an aromatic amine-acylated derivative on Cl(-) secretion is stronger that that of an aliphatic amine-acylated derivative, and that 3-(2,5-dimethyl)furoyl group has a strong action in inhibition of Cl(-) secretion than cyclopropanoyl group.

An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury.

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of N(G)-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI.

[A case of sarcoidosis with diffuse pulmonary arteriovenous malformations].

A 27-year-old woman was admitted because of right dry eye and blurred vision. She was given a diagnosis of uveitis due to sarcoidosis. Chest X-ray film showed bilateral hilar lymphadenopathy and multiple nodules in both lungs.

Influence of depletion of alveolar macrophages on apoptosis in Candida-induced acute lung injury.

Apoptosis plays an important role in acute lung injury (ALI), and alveolar macrophages (AMs) are known to secrete proinflammatory cytokines and promote alveolar inflammation. The authors have previously reported that AMs can be depleted by inhalation of 1 mM 2-chloroadenosine (2-CA). In this study, the authors evaluated the effect of AM depletion by 2-CA inhalation on apoptosis in Candida-induced ALI.

Fluoroscopy-guided barium marking for localizing small pulmonary lesions before video-assisted thoracic surgery.

Purpose: To evaluate the effectiveness of fluoroscopy-guided barium marking for localization of small peripheral pulmonary lesions before video-assisted thoracic surgery (VATS) resection.

Material & Methods: Twenty-one patients with peripheral pulmonary lesions 15 mm or less in diameter who were scheduled to undergo VATS resection were studied. A catheter was inserted bronchoscopically into the target segment and guided to a presumed lesion.

[Six cases of thymic carcinoma: a clinical review].

Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated.

Effect of inhaled NG-nitro-L-arginine methyl ester on Candida-induced acute lung injury.

Study Objectives: Nitric oxide (NO) and peroxynitrite play a crucial role in acute lung injury (ALI). Whether NO synthase (NOS) inhibition is beneficial in the treatment of lung injury remains controversial. The objective of this study was to test the hypothesis that local inhibition of NOS in the lung reduces lung injury.