Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis
AMERICAN JOURNAL OF GASTROENTEROLOGY
Authors: Bolton, Scott M.; Kagalwalla, Amir F.; Arva, Nicoleta C.; Wang, Ming-Yu; Amsden, Katie; Melin-Aldana, Hector; Dellon, Evan S.; Bryce, Paul J.; Wershil, Barry K.; Wechsler, Joshua B.
Abstract
OBJECTIVES: Mast cells (MCs) are increased in eosinophilic esophagitis (EoE). Endoscopic abnormalities, symptoms, and epithelial changes can persist after treatment despite a reduction of esophageal eosinophilia. It is unknown whether this could be due to persistent MC infiltration. We aimed to determine whether patients with histologically inactive (HI) EoE (defined as <15 eosinophils per high-powered field) with persistent symptoms, endoscopic, or epithelial abnormalities after treatment have increased MCs. METHODS: Secondary analysis of prospective data from 93 children with EoE undergoing post-treatment endoscopy between 2011 and 2015. Thirty-five non-EoE controls were included. Immunohistochemistry for tryptase, an MC marker, was performed on mid and distal esophageal biopsies. Total and degranulated intraepithelial MCs per high-powered field (MC/hpf) were quantified. Symptoms and endoscopic findings were recorded at time of endoscopy. MC/hpf were compared between HI-EoE and control, and among HI-EoE based on endoscopic and histologic findings, and symptoms. Nine clinical remission (CR) patients were identified, with absence of endoscopic abnormalities and symptoms. RESULTS: MC/hpf were increased in HI-EoE compared with control (17 +/- 11 vs 8 +/- 6, P < 0.0). Patients with persistent endoscopic abnormalities had increased total (20 +/- 12 vs 13 +/- 10, P = 0.001) and degranulated (8 +/- 6 vs 5 +/- 4, P = 0.002) MC/hpf, with no difference in eosinophils. MC/hpf predicted furrowing (odds ratio = 1.06, P = 0.01) and rings (odds ratio = 1.05, P = 0.03) after controlling for treatment type, proton-pump inhibitor, eosinophils, and duration of therapy. Patients with persistent basal zone hyperplasia and dilated intercellular spaces had increased MC/hpf. Eosinophils were weakly correlated with MC/hpf in the mid (r = 0.30, P < 0.001) and distal (r = 0.29, P < 0.001) esophagus. Clinical remission patients had lower MC/hpf compared with patients with persistent symptoms and/or endoscopic abnormalities. DISCUSSION: MC density is increased in patients with endoscopic and epithelial abnormalities, as well as a few symptoms, despite resolution of esophageal eosinophilia after treatment. This association warrants further study to ascertain whether MCs play an eosinophil independent role in EoE.
Microvascular density, macrophages, and mast cells in human clear cell renal carcinoma with and without bevacizumab treatment
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
Authors: Tamma, Roberto; Rutigliano, Monica; Lucarelli, Giuseppe; Annese, Tiziana; Ruggieri, Simona; Cascardi, Eliano; Napoli, Anna; Battaglia, Michele; Ribatti, Domenico
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) represents a highly vascularized aggressive kidney cancer. Due to ccRCC chemotherapy resistance, antiangiogenesis is one of the most innovative targeted therapies for this tumor. The tumor microenvironment exerts important roles in tumor growth, angiogenesis, and metastatic escape. Materials and methods: In this study, we investigated the composition of tumor cell microenvironment including mast cells, macrophages, and microvascular density in ccRCC tumor tissues collected from patients who underwent nephrectomy treated or not with bevacizumab as neoadjuvant therapy before surgery. Results: The results of this study indicate that bevacizumab-treated ccRCC samples present reduced microvascular density as well as a lower number of CD68-positive macrophages and tryptase-positive mast cells in comparison with the untreated patients. Conclusions: It follows that the antiangiogenic activity of bevacizumab may be due to a direct effect on angiogenic cytokines released by tumor cells and an indirect effect on the release of pro-angiogenic factors by inflammatory stromal cells. (C) 2019 Elsevier Inc. All rights reserved.