磯谷 澄都

BACKGROUND: Patients with thoracic malignancy and interstitial pneumonia (IP) are often excluded from clinical trials, consequently lacking quantitative evidence of poorer prognosis and lower programmed death-ligand 1 (PD-L1) testing rates. METHODS: We evaluated the real-world impact of comorbid IP on biomarker adoption and survival in thoracic malignancy patients receiving first-line systemic therapy at a tertiary teaching hospital between 2016 and 2023. RESULTS: Among 1247 patients, 98 (7.5%) had comorbid IP. Multigene testing rates in IP patients were similar to those in non-IP patients. Only three actionable genomic alterations were found in the IP group, highlighting PD-L1 testing as the key element. PD-L1 testing was underutilized in the IP group (63.3%) compared with the non-IP group (75.1%). Immune checkpoint inhibitor (ICI) therapy was utilized in 12.2% of IP versus 29.3% in non-IP, despite comparable clinical situations. Comorbid IP predicted worse survival (hazard ratio: 1.789; 95% confidence interval: 1.373-2.331; p < 0.001). Although survival significantly improved in non-IP after 2020, no benefit was observed in IP. A multivariable model incorporating an IP × Period interaction confirmed comorbid IP remained a negative prognostic factor, highlighting recent advances have not bridged the survival disparity for this high-risk group. CONCLUSIONS: Despite recent progress, patients with comorbid IP experience limited clinical benefit, characterized by lower rates of PD-L1 testing, restricted use of immune checkpoint inhibitors, and absence of post-2020 survival gains. This large-scale and quantitative evidence demonstrates persistent disparities and their prognostic significance, reflecting the limited applicability of current immunotherapy-based strategies in this high-risk population.

There is limited data on BRAF V600E-mutant squamous cell carcinoma (SCC). We report three cases of SCC of the lung with a history of resected papillary thyroid carcinoma (PTC), showing p40 positivity, TTF-1 negativity, and PAX8 expression. While treated as lung SCC, metastatic thyroid carcinoma was unconfirmed due to absence of PTC recurrence, clinicopathologic features consistent with primary lung origin, and unavailable archival PTC pathology. BRAF inhibitors yielded only transient responses, and outcomes were poor. These cases underscore the diagnostic and therapeutic value of multigene testing in SCC, highlighting the need to integrate detailed clinical history into precision oncology strategies.

Bronchoscopic lung volume reduction (BLVR) with endobronchial valves is an established treatment for selected patients with advanced emphysema. A 74-year-old male patient with chronic obstructive pulmonary disease and severe dyspnea was scheduled to undergo BLVR targeting the right middle lobe bronchus based on high-resolution CT findings, which showed severe emphysematous changes with hyperinflation and fissure completeness of 98% in the right middle lobe. The physician conducted preoperative virtual reality (VR)-assisted planning using the patient's imaging data, enabling comprehensive visualisation of the bronchial tree, airway measurements, and procedural simulation. The Chartis system confirmed a 'no flow' pattern, supporting the absence of collateral ventilation. During the procedure, a size 5.5 valve was placed in the right B4/5 bronchus following VR and intraoperative assessments. The patient remained stable postoperatively without complications. VR enhanced procedural planning by improving airway assessment, optimising valve sizing, and reducing cognitive load, leading to increased efficiency and operator confidence. Further research is warranted to validate the utility of VR in bronchoscopic interventions.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

BACKGROUND: Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. OBJECTIVES: To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). DESIGN: This was a single-center, retrospective, observational cohort study. METHODS: We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. RESULTS: Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). CONCLUSION: BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.