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Barrett's oesophagus (BO) is the primary precursor lesion for oesophageal adenocarcinoma (ADC). The natural history of metaplasia-dysplasia-carcinoma sequence remains largely unknown. HER2/neu oncogene results overexpressed/amplified in preneoplastic lesions and in ADC of the oesophagus and it has been associated with poor prognosis. Our aim was to evaluate the role of HER2 overexpression/amplification in predicting the conversion from precursor lesions to ADC. We retrospectively evaluated by univariate analysis of single variables clinical records and histological specimens of 21 patients with a confirmed diagnosis of BO and/or oesophageal dysplasia. Clinical variables included age, gender, alcohol and smoking intake, presence of symptoms (pyrosis, disphagia) and endoscopic features (length). HER2 status was studied by immunohistochemistry and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue. The end-points were the occurrence of progression and the time-to-progression (TTP) from the initial histologic lesion to the worst pathological pattern. Median age at diagnosis was 63 years (range 37-84). BO median length was 4.5 cm. Progression occurred in 11 of 21 patients and median TTP was 24 months. HER2 was overexpressed/amplified in 8 of 21 (38%) patients. HER2 overexpression/ amplification and the presence of dysplasia were statistically associated with progression (P= 0.038). This study provides evidence for a possible role of HER2 in the transition from dysplasia to ADC of the oesophagus. This fact could help in identifying patients at high risk of malignant transformation.
J Cell Mol Med 2009 Sep
PMID:HER-2 overexpression/amplification in Barrett's oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico-pathologic study. 1929 34

Barrett's esophageal adenocarcinoma (BEAC) arises from Barrett's esophagus (BE), a premalignant lesion caused by acid reflux (heartburn). Although the cancer is uncommon, its incidence is rapidly rising in western countries. Like most other cancers, BEAC cells also have elevated telomerase activity which maintains telomere length and supports continued proliferation of these cells. It is not clear if telomerase is activated early at premalignant (BE) stage, because reports of telomerase activity in Barrett's and normal esophagi have been controversial. We have shown that detection of telomerase and telomeres becomes easier and much more reliable if purified BE cells are used instead of tissue specimens. This chapter, therefore, emphasizes the importance of laser capture microdissection and provides the method to purify Barrett's esophagus related cells, using this technique.
Methods Mol Biol 2011
PMID:Purification of diseased cells from Barrett's esophagus and related lesions by laser capture microdissection. 2176 3

Data are limited regarding the role of proteinase-activated receptor-2 (PAR-2) in the esophageal mucosa in gastroesophageal reflux disease (GERD) patients. Our aim was to study PAR-2 expression and its relationship with different GERD-related clinical and pathologic parameters. Histomorphologic alterations in eosophageal mucosa in nonerosive reflux disease (NERD) and erosive reflux disease (ERD) were also, evaluated. Endoscopic biopsies of the esophageal mucosa were obtained from 94 GERD patients and 20 participants for histopathologic analysis and PAR-2 immunohistochemical staining. The present study demonstrated significantly higher PAR-2 expression in GERD patients compared with control, whereas no significant differences were seen between NERD and ERD groups. PAR-2 expression significantly correlated with histologic score (r=0.572, P<0.001) and severity of heartburn (r=0.541, P<0.001). PAR-2 expression was significantly associated with basal cell hyperplasia, and dilated intercellular spaces and inflammatory cell count (P<0.05). Histologic analysis revealed GERD-related histomorphologic alterations in the esophageal mucosa of GERD patients with significant differences (P<0.05) among groups. Total histologic score was significantly correlated with heartburn (r=0.299, P=0.025) and endoscopic severity (r=0.359, P=0.027) in NERD and ERD patients, respectively. Taken together, this study provides evidence for the major role of PAR-2 in the pathogenesis of GERD and GERD-associated mucosal alterations.
Appl Immunohistochem Mol Morphol 2015 Oct
PMID:Expression of Proteinase-activated Receptor-2 in the Esophageal Mucosa of Gastroesophageal Reflux Disease Patients: A Histomorphologic and Immunohistochemical Study. 2526 27

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls.
Int J Mol Sci 2017 May 19
PMID:Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease. 2853 50

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.
Int J Mol Sci 2017 Aug 01
PMID:Gastro-Esophageal Reflux in Children. 2876 23

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first-line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD-Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d-ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.
J Cell Mol Med 2018 05
PMID:Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision. 2951 23

Bronchogenic cyst is a relatively rare congenital malformation that is often identified in the mediastinum. The occurrence of bronchogenic cysts in the intramural esophagus and gastroesophageal junction is rare. The present report describes three cases of intramural bronchogenic cysts of the esophagus and gastroesophageal junction and reviews the clinicopathological features of these lesions. A 35-year-old Japanese male (Case 1), a 50-year-old Japanese woman (Case 2) and a 34-year-old Japanese man (Case 3) presented with dysphagia, pharyngeal pain and heartburn, respectively. Upper endoscopic examination revealed submucosal tumors in the esophagus (Case 1 and 2) and gastroesophageal junction (Case 3). Subsequent endoscopic examination revealed perforation of the cyst into the surface of the esophageal mucosa (Case 2). Surgical resection was performed in all cases. Histopathological examinations revealed that the submucosal cysts were covered by respiratory-type ciliated epithelium without atypia. Cartilage and bronchial glands were not observed in any of the cases. The present review of the clinicopathological characteristics of bronchogenic cysts of the esophagus and gastroesophageal junction revealed that males and females were equally affected. The median age of the patients was 34.5 years with a wide age distribution. The most common main complaint was dysphagia. A pre-operative diagnosis of bronchogenic cyst is difficult because no specific imaging features are present. As surgical resection is recommended for this lesion, recognition of the clinicopathological features of bronchogenic cysts is important for an accurate pre-operative diagnosis.
Mol Clin Oncol 2020 Aug
PMID:Intramural bronchogenic cysts of the esophagus and gastroesophageal junction: A case report. 3271 40

Gastric cancer has been known as the third leading cause of cancer-related death in the world. It is when cancer cells form on the lining of the stomach. Early symptoms include heartburn, upper abdominal pain, nausea, and loss of appetite. Helicobacter pylori is the most common microscopic creature that has infected humans worldwide. More than half of the world's population is infected with the bacterium. It is the main cause of diseases such as stomach ulcers and stomach and intestinal disorders. H. pylori infection is related to gastric adenocarcinoma and cagA genotype is believed to be related to cancer development. cytotoxin-associated gene A (CagA) is a 120-145kDa protein encoded on the 40kb cag pathogenicity island (PAI). This study investigates the association between cagA H. pylori genotypes and gastric cancer. For this purpose, 65 stomach biopsies of the gastric cancer patients and 100 saliva samples were collected from healthy and H. pylori-infected individuals. Then genomic DNA was purified and Polymerase Chain Reaction (PCR) was performed for the studied gene using specific primers. The presence of H. pylori was investigated by PCR and a pair of specific primers for a protected region in the bacterium glmM gene. Then cagA+ and cagA- genotypes frequencies were determined in H. pylori-infected cases. Statistical analysis showed that there were significant differences between healthy and diseased ones for genotypes cagA+ and cagA-. Then the cagA+ can be a risk factor genotype for gastric cancer.
Cell Mol Biol (Noisy-le-grand) 2020 Oct 31
PMID:The relationship between gastric cancer and Helicobacter pylori cytotoxin-related gene A genotypes. 3328 14