George K. Anagnostopoulos

Narrow-band imaging with magnification in Barrett's esophagus: validation of a simplified grading system of mucosal morphology patterns against histology.

BACKGROUND AND STUDY AIMS Validation of a simplified classification of mucosal morphology in prediction of histology in Barretts esophagus using narrow-band imaging with magnification (NBI-Z) and assessing its reproducibility by endoscopists experienced in the use of NBI (NBI-experts) and by endoscopists who were new to NBI (non-NBI-experts). PATIENTS AND METHODS In a prospective cohort study of 109 patients with Barretts esophagus at a single tertiary referral center, mucosal patterns visualized in Barretts esophagus on NBI-Z were classified into four easily distinguishable types: A, round pits with regular microvasculature; B, villous/ridge pits with regular microvasculature; C, absent pits with regular microvasculature; D, distorted pits with irregular microvasculature. The NBI-Z grading was compared with the final histopathological diagnosis, and positive (PPV) and negative predictive values (NPV) were calculated. The reproducibility of the grading was then assessed by NBI-expert and non-NBI-expert endoscopists, and interobserver and intraobserver agreement were calculated using kappa statistics. RESULTS Per-biopsy analysis: In 903 out of 1021 distinct areas (87.9%) the NBI-Z grading corresponded to the histological diagnosis. Per-patient analysis: The PPV and NPV for type A pattern (columnar mucosa without intestinal metaplasia) were 100% and 97% respectively; for types B and C (intestinal metaplasia) they were 88% and 91% respectively, and for type D (high-grade dysplasia) 81% and 99% respectively. Inter- and intraobserver agreement: The mean kappa values in assessing the various patterns were 0.71 and 0.87 in the non-expert group; 0.78 and 0.91 in the expert group. CONCLUSIONS This study has validated a simplified classification of the various morphologic patterns visualized in Barretts esophagus and confirmed its reproducibility when used by NBI-expert and non-NBI-expert endoscopists.

Novel endoscopic observation in Barrett’s oesophagus using high resolution magnification endoscopy and narrow band imaging

Background High resolution magnification endoscopy with narrow band imaging (NBI) may improve the detection of specialised intestinal metaplasia (SIM) and dysplasia in Barrett’s oesophagus.

Can somatostatin prevent post‐ERCP pancreatitis? Results of a randomized controlled trial

Background:  Acute pancreatitis is the most common complication of endoscopic retrogade cholangiopancreatography (ERCP), occurring in 1–10% of patients. Several substances have been used, with negative results, in an attempt to prevent this complication.

Clinical Application of Magnification Endoscopy and Narrow-Band Imaging in the Upper Gastrointestinal Tract: New Imaging Techniques for Detecting and Characterizing Gastrointestinal Neoplasia

This article introduces one of the most advanced endoscopy imaging techniques, magnification endoscopy with narrow-band imaging. This technique can clearly visualize the microvascular (MV) architecture and microsurface (MS) structure. The application of this technique is quite useful for characterizing the mucosal neoplasia in the hypopharynx, oropharynx, esophagus, and stomach. The key characteristic findings for early carcinomatous lesions are an irregular MV pattern or irregular MS pattern as visualized by this technique. Such a diagnostic system could be applied to the early detection of mucosal neoplasia throughout the upper gastrointestinal tract.

Esomeprazole versus omeprazole for the eradication of Helicobacter pylori infection: Results of a randomized controlled study

Background: Esomeprazole has higher oral bioavailability and increased antimicrobial activity against Helicobacter pylori than omeprazole. Goals: To compare 7 days esomeprazole with 7 days of omeprazole based triple therapies for the eradication of H. pylori, and to assess whether the administration of higher dose of esomeprazole leads to improved eradication rates. Study: One hundred and fifty-six dyspeptic patients with H. pylori received either: (1) 1-week treatment including esomeprazole 40 mg once daily, amoxicillin 1 g, and clarithromycin 500 mg, both twice daily (EAC1 group, n = 52); (2) 1-week treatment of omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, all administered twice daily (OAC group, n = 52); or (3) 1-week treatment with esomeprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily (EAC2 group, n = 52). Results: H. pylori was eradicated in 37 of 52 patients in the OAC group (Intension to treat [ITT] 71%), and in 42 patients in the EAC1 group (ITT 81%). High eradication rate was achieved by the EAC2 regimen (ITT; 96%), but more patients reported unwanted effects. Conclusion: Seven days of esomeprazole based triple therapy is a satisfactory eradication regimen for H. pylori infection. Higher doses of esomeprazole have excellent eradication rates, but they may lead to increased side effects.

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions

Background:  The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions.

Omeprazole plus azithromycin and either amoxicillin or tinidazole for eradication of Helicobacter pylori infection

Goals To establish whether omeprazole plus azithromycin in association with either amoxicillin or tinidazole is effective in curing Helicobacter pylori infection in dyspeptic patients. Background Many antibiotics in combination with antisecretory drugs have been used in an attempt to find the optimal regimen for eradication of H. pylori. Azithromycin is a macrolide that achieves high concentrations in gastric tissue after a single 500-mg oral dose. Study A total of 160 consecutive symptomatic patients with H. pylori received omeprazole 20 mg twice daily for 1 week, azithromycin 500 mg/d for 3 days, and were randomly assigned to either amoxicillin 1 g twice daily (OAzAm group, n = 80) for 1 week or tinidazole 500 mg twice daily for 3 days (OAzT group, n = 80). H. pylori status was assessed by rapid urease test and histology at entry and by histology and 13C-urea breath test after the end of the therapy. Results H. pylori was eradicated in 62.5% of patients in the OAzAm group (intention to treat [ITT] 62.5%) and in 71.2% of patients in the OAzT group (ITT 71.2%). Conclusions Although the compliance was excellent and the side effects negligible, the regimens used were partially effective for the eradication of H. pylori.

Fulminant pancreatitis associated with ramipril therapy.

To the Editor: The use of ACE-inhibitors for the treatment of heart failure and arterial hypertension is increasing. ACE-inhibitors are rare causes of acute pancreatitis. The offending agents have, so far, included captopril, enalapril, lisinopril, quinapril, and benzanepril. We report a case of a patient who developed acute pancreatitis with a fatal outcome, while receiving ramipril. A 75-year-old man presented at the emergency room with complaints of epigastric pain radiating to the back for 2 days. The pain was accompanied with nausea and vomiting. There was no history of alcohol ingestion or previous abdominal surgery. Medication used regularly prior to admission was only ramipril 2.5 mg bid for arterial hypertension. The patient admitted that he had been using ramipril since 1 month, and that from the 1st days of the therapy, he noticed a mild abdominal pain radiating to the back for a few hours after receiving the drug. The last 7 days the pain was getting worse and he consulted his physician who prescribed an oral proton pump inhibitor and did not correlate the symptoms with the drug used. Vital signs on admission were temperature 37.3°C orally, pulse 102 beats/min, respirations 22/min and blood pressure 180/105 mm Hg. The abdomen was mildly distended with hypoactive bowel sounds and diffuse tenderness which was maximal in the epigastrium. Laboratory data on admission included: hematocrit 60.7%; WBC 21,700/mm; platelets 233,000/mm; amylase 1615 U/L; creatinine 2.1 mg/dL; blood sugar 478 mg/dL; calcium 8.3 mg/dL; LDH 605 IU/L; albumin 3.4 g/dL; ALT 30 U/L; AST 33 U/L, bilirubin 0.8 mg/dL, and triglycerides 151 mg/dL. Arterial blood gases on room air revealed a pH 7.46, pCO2 38.9 mm Hg, pO2 63.7 mm Hg and bicarbonate 28.2 mmol/lt. The patient was admitted to the intensive care unit of our hospital where restoration of intravascular volume, nasogastric decompression, and intravenous antibiotic treatment was instituted. Laboratory data 48 hours after admission included: Ht 33.4%, WBC 34,000/mm, platelets 155,000/mm, amylase 1282 U/L, blood glucose 198 mg./dl, creatinine 2.6 mg/dL, and LDH 1768 U/L. During this period, abdominal ultrasound examination showed a diffusely edematous pancreas while the biliary tree was not dilated and no gallstones were seen. Computerized tomography of the abdomen demonstrated changes consistent with acute necrotizing pancreatitis. One day after his admission the patient underwent endotracheal intubation due to progressive hypoxemia and ventilatory support was instituted. Additionally, continuous intravenous infusion of vasoconstrictors was required to maintain adequate blood pressure and a marginal urine output. Despite our support adult respiratory distress syndrome and renal failure developed. The patient became hemodynamically unstable and died 6 days after admission to the hospital. No autopsy was performed. Time intervals between the start of ACE-inhibitor treatment and the onset of acute pancreatitis varies and ranges between 1 day and 2 years, but generally it occurs early in the course of therapy. The severity of acute pancreatitis is usually mild, but fulminant pancreatitis due to lisinopril has been described. There is little information about the mechanism by which ACE-inhibitors cause acute pancreatitis. Some investigators suggest that ACE-inhibitors lead to elevated bradykinin levels in the pancreatic tissue. Bradykinin has been demonstrated to be involved in the increase of vascular permeability and local vasodilatation in the early stage of pancreatitis induced by the cholecystokinin agonist cerulein. Experimental studies in mammals have confirmed the role of bradykinin in the aggravation of pancreatitis and the protective role of bradykinin antagonists. Therefore, increased vascular permeability leading to localized angioedema and induction of pancreatic duct obstruction is a possible explanation for ACE-inhibitors induced pancreatitis. Additionally, because ACEinhibitors can cause hypoglycemia, these drugs may have a toxic effect on pancreatic cells. Our patient started experiencing epigastric pain after taking the drug, from the first days of his therapy. His physician did not correlate his symptoms with the medication used. Ramipril had not, so far, been associated with acute pancreatitis. Since all other possible causes of acute pancreatitis were excluded, our case report strengthens the association between ACE-inhibitors and pancreatitis. Despite the low incidence of druginduced pancreatitis, all patients with acute pancreatitis of unknown etiology should be carefully questioned on drugs possibly responsible for the induction of the disease. As the use of ACEinhibitors is increasing, physicians should consider the diagnosis of acute pancreatitis in patients who develop abdominal pain that is not explained by another process, while taking these medications. If pancreatitis is suspected, the drug should be stopped and replaced to reduce the possibility of further episodes of pancreatitis.

Development of an E-learning System for the Endoscopic Diagnosis of Early Gastric Cancer: An International Multicenter Randomized Controlled Trial

Background In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. Methods The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. Findings 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P < 0·001). Interpretation This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

Optical Microangiography: High-Definition Magnification Colonoscopy with Narrow Band Imaging (NBI) for Visualizing Mucosal Capillaries and Red Blood Cells in the Large Intestine.

BACKGROUND/AIMS Recent advances in zoom endoscopy have enabled the subepithelial capillary network (SECN) in different organs of the gastrointestinal tract to be visualized. Ex vivo studies have suggested that the SECN demonstrates a honeycomb-like structure in the large intestine, but this has not yet been visualized in vivo. The high clarity and resolution of narrow-band imaging (NBI) may allow visualization at the single red-blood-cell (RBC) level and more accurate visualization of the SECN. We investigated whether high-definition magnification colonoscopy with NBI is useful for visualizing capillaries and RBCs in the large intestine. METHODS Sixteen patients with bowel symptoms undergoing routine colonoscopy with normal findings in a tertiary referral academic gastroenterology and endoscopy unit were included in the study. Total colonoscopies were performed using a high-definition magnification colonoscope (CF-H260AZI, Olympus, Tokyo) and a prototype high-definition electronic endoscopy system capable of NBI. Each part of the large intestine (cecum, ascending, transverse, descending, and sigmoid colon, and rectum) was observed at the maximum magnification with white-light imaging (WLI) and NBI. The normal honeycomb-like SECN and RBC movement by high-definition magnification colonoscopy with either WLI or NBI was prospectively successfully visualized for each part of the large intestine. RESULTS In all subjects, high-definition magnification colonoscopy with NBI allowed the visualization of a honeycomb-like SECN together with RBC movement in each segment of the large intestine except for the rectum. In contrast, with WLI alone, neither this SECN structure nor RBC movement could be detected. CONCLUSIONS High-definition magnification colonoscopy with NBI could be a new optical method for facilitating noninvasive investigations of both the microvascular architecture and microcirculation without the need for contrast materials.