HER-2 overexpression/amplification in Barrett's oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico-pathologic study.

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.

Improvement of metabolic syndrome following intragastric balloon: 1 year follow-up analysis.

OBJECTIVE: This study aimed to assess the impact of intragastric balloon (IGB)-induced body weight loss on metabolic syndrome in obese patients and evaluate what happens during 1-year follow-up. METHODS: To this end, data were collected on 143 obese patients (body mass index (BMI) 36.2+/-5.7 kg/m2) who underwent IGB insertion between January 2000 and December 2005. Outcomes were recorded at BioEnterics Intragastric Balloon removal time (t0) and at 6-month (t6) and 12-month (t12) follow-up. RESULTS: Significant BMI, excess body weight loss percentage, and body weight loss percentage (BWL%) were observed at t0 (29.6+/-4.6 kg/m2; 29.3+/-4.8%; 14.1+/-5.7%), followed by partial weight regain at t12 (32.4+/-4.3 kg/m2; 26.1+/-4.9%; 11.2+/-4.6%). Incidence of metabolic syndrome dropped from 34.8% (pre-IGB value) to 14.5% (t0) and 11.6% (t12). Likewise, type 2 diabetes mellitus (DM), hypertriglyceridemia, hypercholesterolemia, and blood hypertension (BH) incidence decreased from 32.6%, 37.7%, 33.4%, and 44.9% (pre-IGB values) to 20.9%, 14.5%, 16.7%, and 30.4% at t0 and 21.3%, 17.4%, 18.9%, and 34.8% at t12. HbA1c blood concentration shifted from an initial value of 7.5+/-2.1% to 5.7+/-1.9% (t0), 5.6+/-0.7% (t6), and 5.5+/-0.9% (t12). Patients suffering from DM or BH stopped or diminished relative drug consumption at t12. Negligible modifications were reported as regards HDL cholesterol and hyperuricemia. CONCLUSION: Weight regain is commonly observed during long-term follow-up after IGB removal. Nevertheless, the maintenance of at least 10% of the BWL%, as reported at 1-year follow-up, is associated with an improvement in metabolic syndrome.

The pathology of gastric cardia: a prospective, endoscopic, and morphologic study.

"Carditis" (inflammation of the gastric cardiac mucosa) may be associated with gastroesophageal reflux disease (GERD), whereas other studies argue that Helicobacter pylori could play a significant role in the chronic cardiac damage. We examined prospectively histologic features of gastric cardia, esophagitis, and H. pylori status in 204 consecutive subjects with GERD symptoms (57.3% male, 42.7% female mean age 49.2 y) undergoing upper gastrointestinal endoscopy with multiple biopsies in the distal esophagus, cardiac region, and stomach. These were assessed for esophagitis landmarks [Ismail Beigi grading (g0-3)], gastritis, and H. pylori infection (Sydney classification). The average symptom duration was 10.8 months. Endoscopy showed no erosive disease in 54.5% patients, grade "A" esophagitis in 37.6%, "B" in 8%, and "C" in 1 case. Histologic examination disclosed g0 in 8.3% patients, g1 in 78.4%, g2 in 12.8%, and g3 in 1; analysis of the cardia showed oxyntic mucosa in 27.9% patients and chronic cardiac mucosa inflammation in 72.1%. Carditis was significantly related to macroscopic esophagitis (P=0.044) and heartburn score (P=0.001). H. pylori cardiac infection was present in 27.4% cases (73.2% associated with cardiac mucosa). Gastric H. pylori infection was demonstrated in 35% patients. H. pylori in the cardiac region was associated with gastric H. pylori infection (P=0.001) and with paucity of GERD symptoms (P=0.05). A good correlation between carditis and GERD, concerning symptoms and macroscopic esophagitis was found in this study. H. pylori-related carditis is likely to be differently compared with the GERD-related type.

Her-2/neu in barrett esophagus: a comparative study between histology, immunohistochemistry, and fluorescence in situ hybridization.

Her-2/neu is a protooncogene frequently overexpressed in breast cancer, recently found to be also overexpressed in carcinoma arising on Barrett esophagus (BE). Immunohistochemistry and fluorescence in situ hybridization (FISH) are conventionally used for Her-2 testing in carcinomas, but a single assay is not yet accepted as a "gold standard" in BE. To evaluate the correlation between histopathology variables and gene expression/amplification in the sequence BE-low grade dysplasia-high grade dysplasia-adenocarcinoma, fifty esophageal specimens from patients with a diagnosis of BE (21 BE, 4 low-grade dysplasia, 12 high-grade dysplasia, and 13 adenocarcinomas) were evaluated. Histopathologic evaluation was carried out using hematoxylin and eosin staining. Paraffin-embedded tissues were investigated for Her-2 by immunohistochemistry (HercepTest) and FISH. HercepTest was scored 0, 1+, 2+, and 3+ depending on the percentage (cut off 10%) of membrane staining, whereas gene assessment evaluated by FISH was based on the ratio between Her-2/neu and the 17 chromosome copy number. There was a positive correlation between gene amplification and protein overexpression. No case with HercepTest scoring 0 or 1+ displayed gene amplification, but this was present in 20% of cases scoring 2+ and in all cases scoring 3+. Her-2/neu amplification or overexpression was never observed in BE. Gene amplification and overexpression was observed in more than 50% of dysplasias and adenocarcinomas. Her-2/neu amplification/overexpression might be considered as a marker of progression from BE to dysplasia. FISH may represent a useful diagnostic tool to integrate the result of HercepTest for selecting patients for more targeted therapeutic approaches.

Lack of interference between small bowel capsule endoscopy and implantable cardiac defibrillators: an 'in vivo' electrophysiological study.

BACKGROUND: Capsule endoscopy is a widely performed procedure for small bowel investigation. Once swallowed by the patient, the capsule transmits images to an external recorder over a digital radiofrequency communication channel. Potential electromagnetic interferences with implantable cardiac devices have been postulated. Clinical studies on the safety of capsule endoscopy in patients with cardiac defibrillators are lacking. OBJECTIVE: The aim of this study was to assess potential mutual electromagnetic interferences between capsule and defibrillators. METHODS: This study used the Given M2A video capsule system. Ten different types of defibrillators were tested in a clinical setting. Before capsule ingestion, defibrillator electrical therapies were switched off. During capsule endoscopy patients were monitored with cardiac telemetry. At the end of capsule endoscopy the following defibrillator's parameters were analysed: change in device settings; inappropriate shocks; inappropriate anti-tachycardia therapy; inappropriate sensing or pacing; noise detection; device reset; programming changes; permanent electrical damages. Any technical problem related to capsule image transmission was recorded. RESULTS: Neither defibrillator malfunction nor interference in sensing or pacing was recorded; conversely, no capsule malfunction potentially caused by defibrillators was registered. CONCLUSION: Our results suggest that capsule endoscopy can be safely performed in patients with cardiac defibrillators.