Intestinal metaplasia at the gastroesophageal junction is associated with gastroesophageal reflux but not with Helicobacter pylori infection.

OBJECTIVE: Studies of the etiology of intestinal metaplasia (IM) at a normal appearing gastroesophageal junction (GEJ) are conflicting as associations with both H. Pylori (HP) infection and gastroesophageal reflux has been reported. The aim of this study was to investigate whether IM at the GEJ is associated with gastroesophageal reflux or HP infection. MATERIAL AND METHODS: Fifty asymptomatic volunteers and 149 patients with reflux symptoms underwent endoscopy with biopsies obtained from the gastric antrum and the squamocolumnar junction (SCJ). All subjects underwent wireless 48 h pH monitoring with the electrode placed immediately above the SCJ and a fecal antigen test for HP infection. Clinical characteristics and the pattern of reflux were compared in subjects with and without IM. RESULTS: Three asymptomatic volunteers and 35 patients who had clearly irregular SCJs with short extensions of columnar mucosa were excluded from the study. In the remaining 47 asymptomatic volunteers and 114 patients, variables that reached a significance level of 0.1 or less on univariate analyses were used in a binomial regression analysis to assess their relative importance for the finding of IM. IM at the GEJ was significantly associated with abnormal distal esophageal acid exposure (5.5 (1.2-24.6), p = .026), the frequency of reflux episodes/hour (1.5 (1.1-2.2), p = .031), and an endoscopic appearance of the SCJ corresponding to ZAP grade I (4.6 (1.4-15.6), p = .013). There was no association with HP infection. CONCLUSION: The finding of IM at an endoscopically normal-appearing GEJ is associated with gastroesophageal reflux but not with HP infection.

The normal squamocolumnar junction is circumferentially even and minimal irregularities are manifestations of gastroesophageal acid reflux.

BACKGROUND: The macroscopic appearance of the normal squamocolumnar junction (SCJ) is often described as serrated with short projections of columnar mucosa that extend into the esophagus. As studies of the normal SCJ are sparse, the aim of this study was to test the hypothesis that the normal SCJ is even and that irregularities are manifestations of acid reflux. METHOD: Fifty asymptomatic subjects and 149 patients with symptoms suggestive of gastroesophageal reflux disease underwent endoscopy and 48-h pH monitoring with a pH electrode positioned immediately above the SCJ. The shape of the SCJ was assessed according to the Z-line appearance classification and correlated with clinical characteristics and the degree of esophageal acid exposure in the most distal esophagus. RESULTS: Even SCJs without irregularities were significantly more common in asymptomatic subjects compared with patients (50% versus 10%, p < .001) and were never found in patients with erosive esophagitis. The median degree of distal esophageal acid exposure in individuals with an even SCJ was within normal limits. With increasing degree of irregularity of the SCJ, the frequency and duration of reflux episodes, the degree of distal esophageal acid exposure, and the prevalence of abnormal acid exposure increased progressively and significantly. CONCLUSION: The shape of the normal SCJ is even and also minimal irregularities are a consequence of acid reflux, likely due to the formation of small areas of metaplastic columnar mucosa.

The combination of pH monitoring in the most distal esophagus and symptom association analysis markedly improves the clinical value of esophageal pH tests.

OBJECTIVE: The poor sensitivity of esophageal pH monitoring substantially limits the clinical value of the test. The aim of this study was to compare the diagnostic accuracy of esophageal pH monitoring and symptom association analysis performed at the conventional level with that obtained in the most distal esophagus. MATERIAL AND METHODS: Eighty-two patients with typical reflux symptoms and 49 asymptomatic subjects underwent dual 48-h pH monitoring with the electrodes positioned immediately above, and 6 cm above the squamo-columnar junction (SCJ). The degree of esophageal acid exposure and the temporal relationship between reflux events and symptoms were evaluated. RESULTS: The sensitivity of pH recording and the diagnostic yield of Symptom Association Probability (SAP) were significantly higher for pH monitoring performed at the distal compared with the conventional level (82% versus 65%, p<0.001 and 74% versus 62%, p<0.001, respectively). The greatest improvement was observed in patients with non-erosive disease. In this group, the sensitivity increased from 46% at the standard level to 66% immediately above the SCJ, and with the combination of a positive SAP as a marker for a positive pH test, the diagnostic yield further increased to 94%. CONCLUSION: The diagnostic accuracy of esophageal pH monitoring in the most distal esophagus is superior to that performed at the conventional level and it is further improved with the combination of symptom association analysis. PH monitoring with the pH electrode positioned immediately above the SCJ should be introduced in clinical practice and always combined with symptom association analysis.

Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography.

BACKGROUND: Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases. METHODS: Bile samples were obtained at endoscopic retrograde cholangiopancreatography (ERCP) in 59 patients with gallstone, other benign disease, tumour, and primary sclerosing cholangitis (PSC). The NPP7 activity was determined. The appearance of the 1.4 and 1.2 kb products in the bile was examined by Western blot. The results were correlated to the diseases and also plasma bilirubin and alkaline phosphatase. RESULTS: NPP7 activity in the tumour group was significantly lower than in the gallstone group (p < 0.05). The activity in the tumour plus PSC group was also lower than in gallstone plus other benign disease group (p < 0.05). Within the tumour group NPP7 activity was lowest in cholangiocarcinoma patients, being only 19% of that in gallstone patients. Bilirubin correlated inversely to NPP7 and was higher in the tumour than in the gallstone group. Western blot identified both the 1.4 kb and the 1.2 kb products in most bile samples. The density ratio for the 1.4/1.2 kb products correlated to NPP7 activity significantly. Two patients (one PSC and one cholangiocarcinoma) lacking NPP7 activity had only the 1.2 kb form in bile. CONCLUSION: NPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. The implications of the finding in diagnosis of cholangiocarcinoma and 1.2 kb product in hepatobiliary diseases require further investigation.

The postprandial acid pocket does not extend into most distal esophagus: evidence from pH studies performed immediately above the squamocolumnar junction.

OBJECTIVE: The postprandial acid pocket is suggested to be an important factor in the pathogenesis of gastroesophageal reflux disease (GERD) as it according to the theory extends into the distal esophagus. The aim of this study was to test the hypothesis that the acid pocket transverses the squamocolumnar junction (SCJ) and exposes the most distal esophagus to gastric acid for extended periods following a meal. MATERIAL AND METHODS: Fifty asymptomatic volunteers and 75 patients with GERD underwent 48-h pH monitoring with the electrode of a pH capsule placed immediately above the SCJ. The characteristics of esophageal acid exposure from the 90-min postprandial periods were compared with those observed during the upright, preprandial periods. RESULTS: In asymptomatic controls, the degree of postprandial esophageal acid exposure was similar to that observed in the preprandial periods (median % time with pH <4, 2.2 vs. 2.6, p = 0.165). In contrast, symptomatic patients had significantly greater acid exposure in the postprandial compared with the preprandial periods (median % time with pH <4, 15.5 vs. 8.5, p < 0.001). The higher degree of acid exposure during the postprandial periods was due to a significantly higher number of short reflux episodes and reflux events with long durations were infrequent. CONCLUSION: Postprandial acid exposure in the most distal esophagus was characterized by numerous short reflux events, and reflux events of long durations were rare. Our observations suggest that the acid pocket is confined to the stomach, questioning the importance of the acid pocket in GERD.

Wireless pH recording immediately above the squamocolumnar junction improves the diagnostic performance of esophageal pH studies.

BACKGROUND AND AIMS: The optimal position for pH electrode placement in the diagnosis of gastroesophageal reflux disease (GERD) is unknown. The aim of this study was to evaluate the discriminatory power of targeted pH recording immediately above the squamocolumnar junction (SCJ) and to compare the results with those obtained by simultaneous recording at the conventional level for pH monitoring. SUBJECTS AND METHODS: Sixty-two patients with typical reflux symptoms and 49 asymptomatic volunteers underwent 48-h simultaneous wireless pH monitoring with two endoscopically placed pH recording capsules, one immediately above the SCJ and one at the traditional position, 6 cm above the SCJ. The diagnostic accuracy, sensitivity, and specificity of pH monitoring at the two levels were analyzed using receiver operating characteristics (ROC) curves. RESULTS: Of the 62 patients (39 men and 23 women, median age 48 yrs), 32 patients had erosive esophagitis and 30 had no endoscopic evidence of mucosal injury. Analysis of the area under the ROC curve (AUC) indicated that the total percent time with pH<4 for the entire 48-h period was the parameter that best distinguished GERD patients from controls. pH monitoring performed directly above the SCJ significantly increased the number of patients correctly classified with GERD compared to standard electrode placement. With a predefined test specificity of 90%, pH monitoring immediately above the SCJ increased the sensitivity of the test from 63% to 86% in all patients, from 78% to 97% in patients with esophagitis and from 47% to 73% in patients with no esophagitis. CONCLUSIONS: Compared to standard electrode placement, wireless pH recording immediately above the SCJ improved the diagnostic performance of esophageal pH monitoring in patients with GERD.