Localized malignant mesothelioma in the stomach and mediastinum

Localized malignant mesothelioma is rare. It has a histological pattern identical to diffuse malignant mesothelioma but without diffuse serosal spread. Localized malignant mesothelioma typically originates from the pleura, peritoneum or pericardium, but can occasionally develop from organs. Our cases represent what might be the largest mediastinal localized malignant mesothelioma described and the first presentation of the epithelioid type in the stomach of an adult.     

Clinical evaluation of the TMS-19-Q.GC tablet on superficial suppurative disease. A comparative double blind study with midecamycin

Clinical efficacy and safety of TMS-19-Q.GC tablet (TMS), a new macrolide preparation, were compared with those of midecamycin (MDM) in superficial suppurative skin and soft tissue infections. The study was made by the double-blind controlled trial at the dosage of daily 600 mg in TMS group and 1,200 mg in MDM group. Total 218 cases (106 in TMS, 112 in MDM) were analyzed and the final global improvement rating were 82.1% in TMS and 83.9% in MDM. The clinical effectiveness of TMS was favorable and significantly different from MDM in the aged patients (greater than or equal to 60 years old) and the patients infected with susceptible strains (MIC less than or equal to 3.13) of Staphylococcus aureus. TMS is prepared with a specific formulation to make the absorption easier in the patients with lower acidity of gastric juice, and the favorable effect of TMS is considered to be a contribution of the devise in older patients. Slight adverse reactions were observed at 5.0% (6 cases) in TMS and 2.4% (3 cases) in MDM. In conclusion, TMS at the daily half dose of MDM is as effective as MDM in superficial suppurative skin and soft tissue infections.     

Activated pulmonary intravascular macrophages increase pulmonary microvascular permeability in sheep

Pulmonary intravascular macrophages (PIMs) reside in the alveolar capillaries of sheep lung. However, the role of PIMs activation in the mechanism of increasing pulmonary microvascular permeability is not clear. We determined, using awake sheep with chronic lung lymph fistulas, the effects of intraarterial infusion of latex beads emulsion (1 microns in diameter) on lung lymph-dynamics. Sheep were divided into 3 groups; control, low dose latex and high dose latex groups. In control group, their lymph-dynamics were stable during the experimental period. In low dose latex group (5.46 x 10(9) beads/kg), lung lymph flow increased during the infusion period, but lung lymph protein clearance did not change. In high dose latex group (5.46 x 10(10) beads/kg), lung lymph flow began to increase during the infusion period and remained high, and lung lymph protein clearance increased significantly during and after the infusion of latex beads emulsion. The latex beads mainly distributed to lungs, and 70% of the beads were caught by PIMs in their phagosomes. These findings suggest that the activation of PIMs through their phagocytic uptake of circulating microparticles increases pulmonary microvascular permeability.     

Collapse and reexpansion of lungs increase microvascular permeability in sheep

The pathogenesis of reexpansion pulmonary edema has not been well studied. We tested the hypothesis that both long term collapse and subsequent reexpansion of the lungs cause reexpansion pulmonary edema by increasing pulmonary microvascular permeability. We investigated lymph dynamics in 15 experiments on collapsed lung and 10 experiments after lung reexpansion in 14 unanesthetized sheep with chronic lymph fistulas. We found that 24-hr left lung collapse increased lymph flow through the caudal mediastinal lymph node from the baseline of 1.71 +/- 0.97 (mean +/- S.D.) g/15 min to 2.01 +/- 0.99 g/15 min, although 2-hr collapse did not affect lymph flow. The L/P ratio did not fall below baseline in either experiment. Pulmonary arterial pressure increased by only about 6 cmH2O both in 2-hr and 24-hr collapse. Reexpansion after 24-hr lung collapse also increased lymph flow from the baseline of 1.64 +/- 0.52 g/15 min to 3.20 +/- 0.79 g/15 min during the first 2 hr after reexpansion. The lymph-to-plasma protein concentration ratio did not fall below the baseline. Reexpansion after 2-hr collapse did not affect these variables. We conclude that both long term lung collapse and subsequent reexpansion lead to reexpansion pulmonary edema by increasing pulmonary microvascular permeability.     

Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma,after treatment failure on a ramucirumab-based therapy

Based on results of prior trials (TAGS, REGARD, RAINBOW), the combination of ramucirumab beyond progression with TAS-102 (trifluridine/tipiracil) seems to be promising in advanced esophagogastric adenocarcinoma (EGA). In this multicenter, non-randomized, open-label, investigator-initiated pilot trial, ramucirumab-pretreated patients with metastatic EGA received a maximum of 4 cycles of ramucirumab (8 mg/kg i.v. on day 1 and 15, Q2W) plus TAS-102 (35 mg/m² p.o. bid on day 1-5 and day 8-12; Q2W). Primary endpoint was tolerability and toxicity, defining a positive trial if the SAE rate according to CTCAE 5.0 will increase <30% (up to 55%) compared to historical results from TAGS trial (SAE rate 43%). Secondary endpoints were further evaluation of safety and assessment of efficacy according to tumor response and overall and progression-free survival (OS/PFS). Twenty patients, 20% gastric and 80% GEJ cancers and 55% with ECOG 0 were enrolled. In total, nine SAEs were reported in 25% [95% CI: 8.7-49.1] of the patients, all without relationship to the systemic therapy. The median OS and PFS were 9.1 months [5.4-10.1] and 2.9 months [1.7-4.8], respectively. In addition, a disease control rate of 45% was obtained. The trial showed a favorable safety profile with a numerically lower incidence of SAEs for the combination of ramucirumab with TAS-102 compared to historical TAGS trial. Furthermore, the combination demonstrated efficacy in the beyond progression setting and therefore warrants further evaluation in a randomized trial compared to TAS-102 alone.     

The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells

BackgroundAngiogenesis in the alveolar septa is thought be a critical factor in pulmonary emphysema. Angiomotin-like protein 1 (AmotL1) is involved in angiogenesis via regulating endothelial cell function. However, the role of AmotL1 in the pathogenesis of pulmonary emphysema has not been elucidated. The objective of this study is to evaluate the expression of AmotL1 in lung tissues from a murine model with emphysema, as well as from patients with chronic obstructive pulmonary disease (COPD). Furthermore, we analyzed the regulation of AmotL1 expression by TNF-α and IFN-γ in endothelial cells in vitro.MethodsNrf2 knockout mice were exposed to cigarette smoke (CS) for 4 weeks, and the down-regulated genes affecting vascularity in the whole lung were identified by microarray analysis. This analysis revealed that the mRNA expression of AmotL1 decreased in response to CS when compared with air exposure. To confirm the protein levels that were indicated in the microarray data, we determined the expression of AmotL1 in lung tissues obtained from patients with COPD and also determined the expression of AmotL1, NFκB and IκBα in cultured normal human lung microvascular endothelial cells (HLMVECs) that were stimulated by TNF-α and IFN-γ.ResultsWe found that the number of AmotL1-positive vessels decreased in the emphysema lungs compared with the normal and bronchial asthmatic lungs. IFN-γ pretreatment diminished the TNF-α-induced AmotL1 in the cultured HLMVECs by blocking the degradation of IκBα.ConclusionsThese results suggested that IFN-γ exhibits anti-angiogenesis effects by regulating the expression of TNF-α-induced AmotL1 via NFκB in emphysema lungs.