Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach

The histological distinction between intestinal metaplasia involving the distal esophagus (Barrett's esophagus [BE]) and intestinal metaplasia of the stomach has important clinical implications and can be difficult even with the use of histochemical mucin stains. Cytokeratin (CK) 7 and 20 are cytoplasmic structural proteins that show restricted expression in normal and malignant epithelia of the gastrointestinal tract. The aim of this study was to determine the use of CK7 and 20 expression in the histological distinction of BE from gastric intestinal metaplasia. CK7 and 20 immunostaining was performed on randomly selected surgical resection (n = 31) and biopsy specimens (n = 34) from patients with long-segment BE and gastric resection specimens (n = 11) and gastric cardia biopsy specimens (n = 13) in patients with histological evidence of intestinal metaplasia. A unique pattern of immunoreactivity designated the Barrett's CK7/20 pattern showed superficial CK20 staining and strong CK7 staining of both superficial and deep glands in 29 of 31 (94%) esophageal resection specimens and 34 of 34 (100%) esophageal biopsy specimens form patients with long-segment BE. A Barrett's CK7/20 pattern was not observed in gastric cardia biopsy specimens (n = 13) or gastric resection specimens (n = 11) in patients with histological evidence of intestinal metaplasia. The sensitivity, specificity, and positive predictive value of a Barrett's CK7/20 pattern for a diagnosis of long-segment BE was 97%, 100%, and 100%, respectively. CK7 and 20 reactivity patterns can reliably identify the location of intestinal metaplasia in the esophagus and stomach using histological material from both routine endoscopic biopsy and surgical resection specimens.     

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa

OBJECTIVE: The etiology of inflammation below the normal Z-line is an area of intense debate. Some suggest this is the earliest change of chronic gastroesophageal reflux disease (GERD), whereas others indict Helicobacter pylori (H. pylori) as the main cause. The aim of this study was to evaluate the relationship among inflammation of gastric cardiac mucosa (carditis), H. pylori infection, and intestinal metaplasia in patients with GERD and Barrett's esophagus compared with age-matched controls. METHODS: Patients with GERD and Barrett's esophagus were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the gastric cardia (obtained on retroflexed view), fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: The prevalence of H. pylori infection did not significantly differ among the study populations: controls (42%), GERD (33%), and Barrett's esophagus (27%) (p = 0.20). However, the prevalence of carditis significantly decreased from the control group (30%) to those with GERD (23%) and Barrett's esophagus (11%) (p = 0.03). Overall, 42 of 51 (82%) patients with carditis had H. pylori; all had pangastritis. The prevalence of cardia intestinal metaplasia also significantly decreased from the control group (15%) to those with GERD (4%) and Barrett's esophagus (0%) (p = 0.003). Of 13 patients with cardia intestinal metaplasia, 12 had carditis, 10 had H. pylori infection, and seven had intestinal metaplasia elsewhere in the stomach. CONCLUSIONS: Inflammation of gastric cardiac mucosa decreases in prevalence from controls to patients with GERD and Barrett's esophagus and correlates strongly with H. pylori infection. Cardia intestinal metaplasia is associated with H. pylori-related cardiac inflammation and intestinal metaplasia elsewhere in the stomach.     

Mucosal Integrity Testing Can Detect Differences in the Rectums of Patients with Inflammatory Bowel Disease Compared to Controls: A Pilot Study

Digestive Diseases and Sciences - While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in...     

Importance of duodeno-gastro-esophageal reflux in the medical outpatient practice

BACKGROUND/AIMS: The role of acid and duodeno-gastro-esophageal reflux (DGER), also termed bile reflux, in esophageal mucosal injury is controversial. Several recent developments, especially availability of the recent bilirubin monitoring device (Bilitec), have resulted in clarifications in this area. In order to better understand the role of acid and DGER in esophageal mucosal injury, we summarized the recent publications in this area. METHODOLOGY: Review of published medical literature (MEDLINE) on the clinical consequence of esophageal exposure to gastric acid or DGER. RESULTS: Recent data suggest that esophageal pH monitoring and pH > 7 is a poor marker for reflux of duodenal contents into the esophagus. DGER in non-acidic environments (i.e., partial gastrectomy patients) may cause symptoms but does not cause esophageal mucosal injury. Acid and duodenal contents usually reflux into the esophagus simultaneously, and may be contributing to the development of Barrett's metaplasia and possibly adenocarcinoma. Proton pump inhibitors decrease acid and DGER by reducing intragastric volume available for reflux and raising intragastric pH. The promotility agent cisapride decreases DGER by increasing LES pressure and improving gastric emptying. CONCLUSIONS: 1) The term "alkaline reflux" is a misnormer and should no longer be used in referring to reflux of duodenal contents. 2) Bilitec is the method of choice in detecting DGER and should always be used simultaneously with esophageal pH-monitoring for acid reflux. 3) DGER alone is not injurious to esophageal mucosa, but can result in significant esophageal mucosal injury when combined with acid reflux. 4) Therefore, controlling esophageal exposure to acid reflux by using proton pump inhibitors also eliminates the potentially damaging effect of DGER.     

Cytokeratin immunoreactivity patterns in the diagnosis of short-segment Barrett's esophagus

BACKGROUND & AIMS: The origin of intestinal metaplasia in short segments of columnar mucosa at the esophagogastric junction has clinical importance but can be difficult to determine at endoscopy. Cytokeratin (CK) 7 and 20 patterns are specific for long-segment Barrett's esophagus; however, their utility in short-segment Barrett's esophagus has not been assessed. METHODS: Endoscopic biopsy specimens from patients with long-segment Barrett's esophagus (n = 49), suspected short-segment Barrett's esophagus (n = 43), and gastric intestinal metaplasia (n = 26) were immunostained for CK7 and CK20. Comprehensive clinical data were obtained, including age, gender, and hiatal hernia and Helicobacter pylori status. RESULTS: A Barrett's CK7/20 pattern was present in 48 (98%) of 49 patients with long-segment Barrett's esophagus, 35 (82%) of 43 with suspected short-segment Barrett's esophagus, and 0 (0%) of 26 patients with gastric intestinal metaplasia. Patients with suspected short-segment Barrett's esophagus with a Barrett's CK7/20 pattern were clinically similar to those with long-segment Barrett's esophagus. In contrast, patients with suspected short-segment Barrett's esophagus with no Barrett's CK7/20 pattern were clinically similar to those with gastric intestinal metaplasia. CONCLUSIONS: A Barrett's CK7/20 pattern identifies a subset of patients with suspected short-segment Barrett's esophagus who have a patient profile similar to that seen in long-segment Barrett's esophagus. A Barrett's CK7/20 pattern is an objective marker of Barrett's mucosa that in conjunction with appropriate clinical and endoscopic data can be used by clinicians to better define patients with short-segment Barrett's esophagus.     

Does Acid Suppressive Therapy Reduce the Risk of Laryngeal Cancer Recurrence?

OBJECTIVE/HYPOTHESIS: Gastroesophageal reflux disease (GERD) is implicated in laryngeal cancer pathogenesis and recurrence posttherapy. There are currently limited data on the effect of acid suppressive therapy in decreasing the recurrence of laryngeal cancer. Therefore, we conducted this study to identify potential effect of GERD and acid suppressive therapy on recurrences after larynx-preserving therapies. STUDY DESIGN: Case control study. METHODS: Cases and controls, derived from a single tertiary care center, were patients who had newly diagnosed localized laryngeal cancer (T3 or less and absence of nodes) and having undergone larynx-preserving surgery or radiotherapy/chemotherapy were followed between January 1, 2000 and December 31, 2003. Univariable associations were performed for demographics, smoking and alcohol patterns, stage of tumor, initial treatment, surgeon of record, presence of GERD, and the use of acid suppressive medications. Multivariable associations were performed for clinically significant variables. RESULTS: Of 258 patients with laryngeal cancer, 61 satisfied the selection criteria. Twenty-two of 61 (36%) developed recurrence and constituted cases, whereas 39/61 (64%) did not have recurrence and constituted controls. On univariable analysis, significant factors for decreased recurrences were GERD, hazard ratio 0.24 (95% confidence interval [CI] 0.08-0.71), and acid suppressive therapy, hazards 0.22 (95% CI 0.07-0.66). On multivariable analysis, laryngeal cancer recurrence was significantly less in those on acid suppressive therapy, hazard 0.31 (95% CI 0.13-0.75). CONCLUSIONS: Acid suppression postlaryngeal cancer therapies may have protective effect on laryngeal cancer recurrences. A prospective study is needed to better define this perceived beneficial effect.     

Friedreich's ataxia impact scale: A new measure striving to provide the flexibility required by today's studies

To develop, using modern techniques of rating scale construction, a new patient reported rating scale for clinical studies of Friedreich's ataxia (FA) that strives to meet the measurement needs of different types of study. Qualitative research methods were used to generate a conceptual framework of the impact of FA, and a pool of items necessary to construct a subscale for each area identified. This item pool was then administered to 492 people with FA. Rasch measurement methods guided scale construction. Eight areas for measurement were identified (speech, upper limb functioning, lower limb functioning, body movement, complex tasks, isolation, mood, self perceptions), and a 126‐item scale constructed (FA Impact Scale; FAIS). In addition, three shorter versions were developed to illustrate how the FAIS can be adapted for observational studies, more disabled, and less disabled samples of people with FA. The FAIS is a psychometrically sound 126‐item measure from which subsets of items can be selected to meet the needs of different studies. Importantly, all versions can be referred back to the original scale. This study shows one of the many clinical advantages of using Rasch measurement methods to construct rating scales. © 2009 Movement Disorder Society