Vertical and horizontal growth features of superficial esophageal squamous cell carcinomas: histopathological evaluation of endoscopically resected specimens

Endoscopic mucosal resection (EMR) has been performed for intramucosal carcinomas with excellent results. To evaluate invasion depth of superficial esophageal squamous cell carcinomas (SESCCs) accurately, it is important to elucidate vertical and horizontal growth features. Using 179 specimens of SESCC taken by EMR, various factors associated with vertical and horizontal growth were examined pathologically to determine which were correlated with invasion depth, classified for this purpose into four levels, m1, m2, m3, and sm. Maximum tumor diameter, including high-grade intraepithelial neoplasia, differed between m1 and m2 cases and for invasive lesions between m2 and m3. Maximum tumor thickness varied between m1 and m2, m2 and m3, and m3 and sm. Multivariate analysis showed tumor thickness and diameter of invasion to be correlated with submucosal invasion. Tumor thickness and depth of the depressed lesions were correlated in depressed/flat type cases. In elevated type cases the thickness of the tumor did not differentiate between m3 and sm. Shape of the elevated lesion also influenced the invasion depth. Frequency of infiltrating type tumors, composed of irregular and small invading nests, was higher with sm than m3. To differentiate m3 and sm tumor the classification of gross type, thickness, depth of depressed lesions, shape of elevated lesions, and invasion patterns should all be evaluated.     

Mutational analyses of the human Rad51-Tyr315 residue, a site for phosphorylation in leukaemia cells

The human Rad51 protein, which plays a central role in homologous recombination, catalyses homologous pairing. The Rad51-Tyr315 residue is known to be constitutively phosphorylated in leukaemia cells and is thought to reside within the subunit-subunit interface of the Rad51 filament. To study the function of the Tyr315 residue, we purified five Rad51 mutants, Y315D, Y315E, Y315R, Y315A and Y315F, in which the Tyr315 residue was replaced by Asp, Glu, Arg, Ala and Phe, respectively. Biochemical studies of these Rad51 mutants revealed that the Y315D and Y315E mutants are defective in homologous pairing due to their impaired ssDNA binding, but their dsDNA binding remained unaffected. The Y315D, Y315E and Y315R mutants are defective in dsDNA unwinding, which depends on Rad51-filament formation, suggesting that these mutants are defective in filament formation on dsDNA. Therefore, the Rad51-Tyr315 residue plays important roles in ssDNA binding and filament formation.     

Predictive Performance of Four Programmed Cell Death Ligand 1 Assay Systems on Nivolumab Response in Previously Treated Patients with Non–Small Cell Lung Cancer

Introduction

Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy.

Efficacy of polyglycolic acid sheets and fibrin glue for prevention of bleeding after gastric endoscopic submucosal dissection in patients under continued antithrombotic agents

Background

A novel method for the prevention of bleeding after gastric endoscopic submucosal dissection (ESD) is necessary, as the numbers of patients taking antithrombotic agents have increased. This study aimed to assess the efficacy and safety of the covering method using polyglycolic acid (PGA) sheets and fibrin glue for ESD-induced ulcer in preventing post-ESD bleeding in patients under continued antithrombotic agents.

Methods

One hundred five consecutive gastric tumors among 84 patients who were treated by ESD under continued antithrombotic agents between April 2014 and September 2015 were enrolled in this study. The patients were classified into two groups, the covering group (52 lesions among 38 patients; those with ESD in whom PGA sheets and fibrin glue were used as the covering method) and the control group (53 lesions among 46 patients; ESD only), and their post-ESD bleeding rates were compared.

Results

No significant differences were seen in the number and type of antithrombotic agents, lesion location, median procedure time, and median resected specimen size between the groups. ESD was completed in all cases, with no cases of uncontrollable bleeding during the procedure. Post-ESD bleeding occurred in 5.8% (3/52) and 20.8% (11/53) in the covering and control groups, respectively. The post-ESD bleeding rate significantly differed between the groups (P = 0.04; odds ratio, 0.23; 95% confidential interval, 0.06–0.89). No adverse events were associated with the use of PGA sheets and fibrin glue.

Conclusions

The covering method using PGA sheets and fibrin glue has the potential to reduce post-ESD bleeding in patients receiving continued antithrombotic agents.

     

Programmed Cell Death Ligand 1 Expression in Non–Small-cell Lung Cancer Patients With Interstitial Lung Disease: A Matched Case-control Study

Background

Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have demonstrated antitumor activity, and immunohistochemical analysis of PD-L1 expression has been used to identify the response in patients with non–small-cell lung cancer (NSCLC). Recently, considerable interest has ensued toward extending the benefit of these inhibitors to high-risk patients, such as those with NSCLC and interstitial lung disease (ILD). However, no studies have compared PD-L1 expression in NSCLC patients with and without ILD. Therefore, we conducted a case-control study to evaluate PD-L1 expression and stromal CD8⁺ lymphocyte density in these patients.

Clinical Characteristics and Prognosis of Patients With Advanced Non–Small-cell Lung Cancer Who Are Ineligible for Clinical Trials

Background

Most patients with non–small-cell lung cancer (NSCLC) are ineligible for clinical trials. However, few studies have reported on the profiles and treatment outcomes for these patients. Therefore, we investigated the characteristics, outcomes, and survival of patients with advanced NSCLC who were ineligible for clinical trials.

Three-phase gadolinium infusion in moving-table three-dimensional MR angiography

Moving-table three-dimensional (3D) MR angiography provides images of long segments of arteries. However, deep veins are sometimes superimposed on the arteries below the knee, and peripheral arteries sometimes fail to be visualized. We have developed an imaging method with three-phase gadolinium infusion according to the mean blood flow velocity of the leg. Nineteen patients with various blood flow velocities were studied. Eighteen of the patients had no venous superimposition. All 19 patients showed good configuration of peripheral arteries with 16-18 ml of gadolinium. This method is useful for better visualization of peripheral arteries without venous superimposition.     

Stimulation of airway ciliary motility by immunologically activated canine pulmonary macrophages: role of leukotrienes

To elucidate a possible interaction between alveolar macrophages and airway epithelial cells in allergic conditions, we studied the effect of immunologically stimulated macrophages on ciliary beat frequency (CBF) of cultured canine tracheal epithelium by a photoelectric method. Administration of supernatants from macrophages incubated with anti-dinitrophenyl (DNP) IgE antibody and anti-dinitrophenyl-human serum albumin dose-dependently increased ciliary beat frequency, the maximal increase from the baseline being 30.4 +/- 5.0% (mean +/- SE, P less than 0.01), an effect that was accompanied by the release of leukotriene (LT) C4 and leukotriene D4. This ciliostimulation was not affected by pretreatment of macrophages with indomethacin but was inhibited by that with nordihydroguaiaretic acid. Addition of FPL 55712 abolished the response of ciliary beat frequency to the stimulated macrophages, and exogenously administered leukotriene C4 and leukotriene D4 dose-dependently increased ciliary beat frequency. These results suggest that macrophages increase respiratory ciliary motility through the IgE-mediated release of leukotrienes and may modulate mucociliary transport function in the airway.