Ayako Shimada

Gastrointestinal (GI) metastases from lung cancer are relatively rare, and their management strategies and outcomes in the era of immune checkpoint inhibitors are unknown. A 59-year-old man with lung cancer was hospitalized. He presented with vomiting due to a small intestinal metastasis. The metastatic lesion reduced in size with pembrolizumab treatment. However, the patient could not feed orally and required continuous central venous nutrition. Following the recurrence of a catheter-related bloodstream infection, the patient underwent small intestinal resection and gastrojejunal bypass surgery. Surgical specimens from the site of intestinal stenosis showed tumor disappearance and inflammatory cell invasion. GI stenosis due to lung cancer metastasis can persist even after effective treatment with immune checkpoint inhibitors. Therefore, surgery for GI metastases should be considered as necessary.

In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast activation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia.

Purpose Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation and breathing difficulty, is usually caused by prolonged inhalation of toxic substances or long-term smoking habits. Some abnormal features of COPD can be observed using medical imaging methods, such as magnetic resonance imaging (MRI) and computed tomography (CT). This study aimed to conduct a multi-modal analysis of COPD, focusing on assessing respiratory diaphragm motion using MRI series in conjunction with low attenuation volume (LAV) data derived from CT images. Materials and method This study utilized MRI series from 10 normal subjects and 24 COPD patients, along with thoracic CT images from the same patients. Diaphragm profiles in the sagittal thoracic MRI series were extracted using field segmentation, and diaphragm motion trajectories were generated from estimated diaphragm displacements via registration. Re-sliced sagittal CT images were used to calculate regional LAVs for four distinct lung regions. The similarities among diaphragm motion trajectories at various positions were assessed, and their correlations with regional LAVs were analyzed. Results Compared with the normal subjects, patients with COPD typically exhibited fewer similarities in diaphragm motion, as indicated by the mean normalized correlation coefficient of the vertical motion component (0.96 for normal subjects vs. 0.76 for severity COPD patients). This reduction was significantly correlated with the LAV% in the two lower lung regions with a regression coefficient of 0.81. Conclusion Our proposed evaluation method may assist in the diagnosis and therapy planning for patients with COPD.

Background: Chronic obstructive pulmonary disease (COPD) typically causes airflow blockage and breathing difficulties, which may result in the abnormal morphology and motion of the lungs or diaphragm. Purpose: This study aims to quantitatively evaluate respiratory diaphragm motion using a thoracic sagittal magnetic resonance imaging (MRI) series, including motion asynchronization and limitations. Method: First, the diaphragm profile is extracted using a deep-learning-based field segmentation approach. Next, by measuring the motion waveforms of each position in the extracted diaphragm profile, obvious differences in the independent respiration cycles, such as the period and peak amplitude, are verified. Finally, focusing on multiple breathing cycles, the similarity and amplitude of the motion waveforms are evaluated using the normalized correlation coefficient (NCC) and absolute amplitude. Results and Contributions: Compared with normal subjects, patients with severe COPD tend to have lower NCC and absolute amplitude values, suggesting motion asynchronization and limitation of their diaphragms. Our proposed diaphragmatic motion evaluation method may assist in the diagnosis and therapeutic planning of COPD.

Remdesivir, dexamethasone, and baricitinib have recently been used to treat patients with coronavirus disease 2019 (COVID-19) and respiratory failure. However, the adverse effects of combination therapy have not been fully explored. A 64-year-old man was diagnosed with COVID-19 and was treated with remdesivir, dexamethasone, and baricitinib. His respiratory condition worsened on day 17, and in the following days, he was diagnosed with pneumomediastinum and COVID-19-associated pulmonary aspergillosis (CAPA). His condition improved with a reduction in the corticosteroid regime and antifungal treatment. This is the first case of pulmonary aspergillosis in a patient with COVID-19 that was treated with remdesivir, dexamethasone, and baricitinib.

Purpose: Quantification of emphysematous and fibrotic lesion using MDCT in patients with combined pulmonary fibrosis and emphysema (CPFE) reflects the severity of pulmonary function and clinical events. However, there is limited data on longitudinal structural lung abnormalities. We aimed to investigate whether the radiological changes are associated with other clinical indicators in the patients with CPFE using multidetector CT. Patients and methods: We enrolled 36 CPFE patients who underwent CT and pulmonary function testing (PFT) at initial diagnosis and two years after. We measured the extent of emphysema as the low attenuation volume (%LAV) and the extent of fibrotic lesions as the high attenuation volume (%HAV). The sum of the %LAV and %HAV was calculated as the abnormal volume (%AV). Results: The median (IQR) CT measured lung volume (LV), %LAV, %HAV and %AV at baseline were 3982cc (3233-4478cc), 2.8% (1.3-5.5%), 10.6% (8.8-12.8%) and 14.9% (11.7-19.6%), respectively. After two years, median rate of changes were -5.2%(-9.3-0.5%) in LV, 41% (4.1-80%) in LAV, 2.3% (-5.7-12%) in HAV and 18% (5.0-33%) in AV. The change in %AV significantly correlated with the change in forced vital capacity (FVC) (ρ=-0.4, p=0.007), forced expiratory volume in one second (FEV₁) (ρ=-0.3, p=0.007) and diffusing capacity for carbon monoxide (DLco) (ρ=-0.50, p=0.02) Conclusion: Quantitative CT measurements on longitudinal structural lung abnormalities reflected a pulmonary function deterioration in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and patients9 clinical course with CPFE.

Purpose: Lung hyperinflation and chest wall geometry change occur in advanced chronic obstructive pulmonary disease (COPD). However, impact of hyperinflation on lung and mediastinum in continuous breathing are unknown. We aimed to investigate the differences in lung/mediastinal area changes in COPD and normal groups using dynamic breathing MRI and analyze the relations between these changes and pulmonary function. Patients and Methods: We enrolled 10 normal subjects and 21 patients with COPD who underwent dynamic breathing MRI and pulmonary function tests (PFTs). We measured lung areas using four coronal images and mediastinal area on one coronal image, each for maximal inspiratory and expiratory phase. We compared the MRI indices between patients with COPD and normal subjects. We also evaluated the relationships between the MRI lung area ratio and mediastinal-thoracic area ratio with the clinical values. Results: The ratio of expiratory lung areas to inspiratory lung area was significantly larger in the COPD group compared to the normal group (0.91±0.04 vs 0.86±0.02, p=0.002). The mediastinal-thoracic area ratio was significantly smaller in the COPD patients than in the normal subjects. Lung area ratio showed a negative correlation with FEV₁/FVC, and positive correlations with FRC%predicted and CT lung volume/ pTLC. Expiratory mediastinal-thoracic area ratio positively correlated with FEV₁%predicted and inversely correlated with RV/TLC. Conclusion: The analysis of lung area ratio and mediastinal-thoracic area ratio using dynamic breathing MRI may be useful in investigating hyperinflation and airflow limitation in patients with COPD.

The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, high mobility group box 1 (HMGB1), S100A12, and N-epsilon-(carboxymethyl) lysine (CML), on human fibronectin-directed human fetal lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited, HFL-1 migration in a concentration-dependent manner. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE, but not Toll-like receptor 4. S100A12 did not exert a chemoattractant effect, but inhibited HFL-1 chemotaxis and/or chemokinesis. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK) but not through nuclear factor-kappa B, protein kinase A, phosphatase and tensin homolog deleted on chromosome 10, or cyclooxygenase. In addition, western blot analysis showed that S100A12 augmented p38 MAPK activity in the presence of human fibronectin. In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.