Esophageal Mucosa Of Patients Research Articles

Histological Esophagitis Before and After Surgical Treatment of Morbid Obesity (Capella Technique): A Prospective Study

The effects of vertical banded gastroplasty/Roux-en-Y gastric bypass (Capella) on the esophageal mucosa of patients with histological esophagitis are poorly understood. To evaluate long-term effects, we investigated the persistence, aggravation or disappearance of histological esophagitis in patients with morbid obesity and reflux esophagitis (diagnosed by endoscopic biopsy) after Roux-en-Y gastric bypass. Twenty-one patients with morbid obesity and esophagitis (histological diagnosis) were submitted to gastric bypass (Fobi-Capella technique) and underwent upper endoscopy and esophageal biopsy during the late postoperative period. The mean age of the patients was 42.57 +/- 7.49 years (30 to 56). Nineteen (90.48%) patients were women, and two (9.52%) were men. Before surgery, the patients presented a mean weight of 124.26 +/- 19.09 kg and a mean body mass index (BMI) of 48.46 +/- 6.37 kg/m(2). Thirteen (61.90%) patients had endoscopic esophagitis before surgery. The mean weight and BMI were 81.65 +/- 13.16 kg and 31.91 +/- 4.99 kg/m(2), respectively, during the late postoperative period (29.80 +/- 8.91 months). The mean percentage of excess weight loss was 68.7 +/- 14.6%. Among the 21 patients with a preoperative histological diagnosis of reflux esophagitis, five (23.18%) had the same diagnosis after surgery, and four (19.04%) continued to present findings of endoscopic esophagitis. Vertical banded gastroplasty/Roux-en-Y gastric bypass (Capella technique) is effective in the treatment of reflux esophagitis. No association was observed between the percentage of excess weight loss and improvement of esophagitis.

Expression of inducible nitric oxide synthase and heme oxygenase-1 in the esophageal mucosa of patients with reflux esophagitis

Expression of inducible nitric oxide synthase and heme oxygenase-1 in the esophageal mucosa of patients with reflux esophagitis

P16, MGMT, RARβ2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions

Esophageal squamous cell carcinoma (ESCC) is a common cancer with a very poor prognosis. New methods are needed to screen high-risk populations and identify curable tumors and precursor lesions early. Molecular markers may be useful in such screening efforts. This study was designed to determine the prevalence of p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in patients with ESCC to evaluate the variation of gene methylation across a spectrum of preneoplastic lesions, and assess the feasibility of using gene methylation in a primary screening test utilizing frozen esophageal cells collected by balloon cytology samplers. Samples were obtained from high-risk subjects from north central China. These samples included 11 foci of histologically normal mucosa, 8 foci of low-grade squamous dysplasia, 7 foci of high-grade squamous dysplasia, and 13 foci of ESCC from 6 fully embedded resection specimens; endoscopic biopsies from 6 individuals with no histological evidence of disease; and frozen esophageal balloon samples from 12 asymptomatic subjects. Promoter CpG site-specific hypermethylation status was determined for each gene using real-time methylation-specific PCR (qMS-PCR) based on Taqman chemistry. Of the 6 ESCC patients, 5 showed methylation of at least one gene. For most genes, methylation occurred with increasing frequency during neoplastic progression, with the largest increase found between low- and high-grade dysplasia. There was considerable variation in methylation patterns among different foci of the same histological grade, even within individual patients, but 16/20 (80%) of high-grade dysplastic and cancer foci had >or= 2 methylated genes, while 17/19 (89%) of normal and low-grade dysplastic foci had <2 methylated genes. These genes were rarely methylated in histologically normal mucosa from patients with or without ESCC. Gene methylation was common and easily detectable in the frozen esophageal cells collected by balloon cytology samplers. Our data suggest that methylation of p16, MGMT, RARbeta2, CLDN3, CRBP, and MT1G is common in the esophageal mucosa of patients with ESCC in this high-risk population, and tends to increase in prevalence in foci with increasing histological severity of disease. Methylation data from panels of genes may be able to identify patients with high-grade lesions. Balloon cytology may be able to screen the length of the esophagus effectively for a subset of cells with abnormal methylation, and may be useful in a primary screening test for ESCC and its precursor lesions.

Histopathological study of oesophageal mucosa in patients with varices: A comparison between bleeders and non-bleeders

Thirty-six patients with oesophageal varices underwent a non-shunting operation including oesophageal transection. Of these, 16 had an emergency or elective operation (bleeders) and the remaining 20 had prophylactic surgery (non-bleeders). A comparative study was performed between the bleeders and non-bleeders in terms of preoperative endoscopic findings and histopathology of the oesophagus. The severity of red colour sign showed no significant difference between the two groups. The venous dilatation in each of the three layers of the oesophageal mucosa was demonstrated histologically to be of the same degree in bleeders and non-bleeders. In addition, the hepatic venous pressure gradient in cirrhotic patients did not differ between the two groups; for bleeders this was a mean(s.d.) of 15.2(6.1) mmHg and for non-bleeders 14.4(2.9) mmHg. We were unable to find any factors differentiating bleeders from non-bleeders, although these results do not justify prophylactic surgery for oesophageal varices.

Endoscopic and histologic evaluation of advanced megaesophagus after esophagocardioplasty, vagotomy-antrectomy and roux-en-Y gastrojejunostomy (Serra Dória operation)

To evaluate the endoscopic and histologic aspects of the esophageal mucosa in patients who underwent the Serra Dória operation for advanced megaesophagus. Thirty patients with advanced megaesophagus underwent the Serra Dória operation (operated group) and 15 patients were not submitted to surgery (non-operated group). The esophageal mucosa was evaluated by macroscopy and histologic examinations. In the operated group, 21, five and four patients with mild, moderate and severe esophagitis, respectively, were identified by endoscopy. In the non-operated group, 4 and 11 patients had moderate and severe esophagitis, respectively. The histologic examinations identified 19, six and five specimens with mild, moderate and severe esophagitis, respectively, in the operated group as opposed to one, three and 11 specimens with mild, moderate and severe esophagitis, respectively, in the non-operated group. The prevalence of severe esophagitis was high in the non-operated group while, after the Serra Dória operation, mild esophagitis was prevalent.

Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season

The oesophagus is normally devoid of eosinophils. There are some disorders accompanying with eosinophil infiltration. Food allergy has been reported as a common reason, especially in children but some other studies have also indicated that aeroallergens might have a role in oesophageal eosinophil accumulation. In this study we investigated whether there is any eosinophil recruitment in the oesophagus of pollen-allergic patients who had respiratory symptoms during the season. Thirty-eight symptomatic patients (allergic rhinitis (AR) with or without asthma) who had sensitization to grass pollen were included in the study during the pollen season. Controls were composed of 25 healthy non-atopics and 24 patients diagnosed as having gastro-oesophageal reflux disease. Reflux was excluded in allergic and non-atopic groups, whereas the presence of allergy was eliminated in control groups. Gastrointestinal endoscopy was performed in all participants, and biopsy specimens were taken from both the proximal and the distal oesophagus to evaluate eosinophil accumulation. At the same time, blood eosinophil numbers were counted. Results Oesophageal eosinophil accumulation was found in 10 allergic patients (26%) and in five patients (21%) with gastro-oesophageal reflux disease but none of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were higher in these 10 patients than the rest of the 28 patients without infiltration. In this group, blood eosinophils were also correlated with the number of accumulated eosinophils in the oesophagus (P<0.001). There was more intense eosinophil infiltration at the distal part of the oesophagus in the reflux group when compared with the allergic group (mean 7.6+/-5.6 vs. 3.2+/-3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5+/-7.3) in the proximal oesophagus of allergic patients, although it was 1.7+/-1.5 in reflux patients (P>0.05). Conclusion Our results showed that eosinophil infiltration might be observed in oesophageal tissue of patients with respiratory tract allergy during the symptomatic period. This finding may possibly reflect the systemic and common mucosal aspects of allergic inflammation.

Expression of CXC receptor 1 and 2 in esophageal mucosa of patients with reflux esophagitis

Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about the two distinct receptors, CXC receptor (CXCR)-1 and -2. The purpose of this study was to determine CXCR-1 and -2 messenger RNA expression levels in RE. We studied 26 patients with RE and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of CXCR-1 and -2 mRNA levels by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and another was formalin-fixed for histopathological evaluation. We also examined the association of the expression levels of CXCR-1 and -2 mRNA with histopathological hallmarks of RE. The relative CXCR-1 and -2 mRNA expression levels were rather decreased in esophageal mucosa of patients with RE, compared to those in normal esophagus of controls. There were no significant difference in the relative mRNA expression levels of CXCR-1 and -2 among endoscopic grades of RE based on the Los Angeles classification. Each histopathological hallmark of GERD was not associated with the expression levels of CXCR-1 and -2 mRNA. Apart from overexpression of IL-8, the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with RE.

Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus

BackgroundWorldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARα, β, γ, and RXRα, β, γ) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors (i.e. RARα, β, γ, and RXRβ) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls.MethodsAll study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARα, β, γ, and RXRβ were determined by Western Blot in normal esophageal tissue and tissue obtained from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal tissue of 10 controls.ResultsProtein levels of RARγ were significantly lower by ~68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARα protein levels were significantly lower (~- 45%) in SCC in comparison to normal esophageal mucosa in patients with elevated alcohol intake. When comparing protein levels of retinoic acid receptors between normal tissue of patients with SCC and controls, RARγ protein levels were found to be significantly higher (~2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARα, β, and RXRβ protein levels between normal esophageal tissue of patients and that of controls.ConclusionIn conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus and that in some patients life style (e.g. smoking and alcohol consumption) may be a critical component in the alteration of retinoic acid receptor levels in esophagus.

Expression of Interleukin 8 Messenger Ribonucleic Acid in Esophageal Mucosa of Patients with Gastroesophageal Reflux Disease in Terms of Helicobacter pylori Status: Response

Expression of Interleukin 8 Messenger Ribonucleic Acid in Esophageal Mucosa of Patients with Gastroesophageal Reflux Disease in Terms of Helicobacter pylori Status: Response

P0850 DOES THE LEVEL OF BIOPSY PROVEN ESOPHAGITIS PREDICT OCCURRENCE OF RESPIRATORY SYMPTOMS IN CHILDREN WITH GASTROESOPHAGEAL REFLUX?

Introduction: A group of pediatric patients with gastro-esophageal reflux (GER) may have concomitant airway manifestations. It has been suggested that this association may occur directly through the effect of gastric juice upon upper airway tissue or indirectly through the neural stimulation. It was demonstrated in animal studies that the contents of gastric juice damage the esophageal and laryngeal tissue. There is limited data on the histological changes of the upper esophageal mucosa in patients with GER who have respiratory symptoms. The objective of the study was to assess the mucosal changes in the proximal esophagus in children who have endoscopically diagnosed GER and to analyse laboratory, laryngeal and esophageal findings with respect to the presence of respiratory symptoms. Methods: A total of 27 patients aging 9–198 months who have histological esophagitis were included in the study. The patients were prospectively divided into two groups with respect to the presence of airway symptoms: 9 (33.3%) patients had respiratory symptoms while the remaining 18 (66.7%) patients did not have respiratory complaint. The larynx and vocal cords were evaluated in each patient who underwent endoscopy, and biopsies were obtained from the upper and lower third of esophagus. Two groups were compared on the basis of the presence of atopy, anemia and allergological test results (skin prick test, specific RAST, IgE level, eosinophilia in blood smear). Results: Laryngeal appearance was abnormal in 8 out of 27 (29.6%) children in study group, and 4 of them had respiratory symptoms. Esophageal hyperemia was observed in 15 (55.5%) children, 6 of which had respiratory complaints. There was not statistical difference in endoscopic appearance of the larynx, proximal and distal esophageal mucosa in both groups. Proximal esophageal biopsies revealed esophagitis in 6 of 9 (66.6%) patients having respiratory symptoms, and 15 of 18 (83.3%) patients who do not have any airway complaint. The difference between groups was not statistically significant. The results of all other parameters for anemia, IgE level, peripheral eosinophilia and skin prick test were also comparable in both groups. The only statistically significant difference was the presence of atopy, which was positive in 55.5% (5/9) in children having respiratory symptoms and 11.1% (2/18) in children who do not have respiratory complaint (p<0.05). Conclusion: The results of the study suggest that the laryngeal appearance and proximal esophagitis and the occurrence of respiratory symptoms were not correlated in children with histologically proven GER. Further studies with a large number of patients are needed to assess the mechanism of GER related respiratory symptoms in children.

Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease.

Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

Interleukin‐8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

Background: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)‐8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. Methods: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non‐erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL‐8 mRNA was quantified by real‐time polymerase chain reaction (PCR). Localization of IL‐8 protein in the esophageal mucosa was done by immunostaining. Results: Expression of IL‐8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL‐8 mRNA was also detected in all patients with non‐erosive GERD. The level of IL‐8 expression in non‐erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL‐8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton‐pump inhibitor, decreased both IL‐8 mRNA and protein levels in the esophageal mucosa. Conclusion: These results suggest that IL‐8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non‐erosive GERD.

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis.

Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1 beta by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1 beta levels between the RE and control groups, but IL-1 beta levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis

Objective Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. Methods A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1β by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. Results IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1β levels between the RE and control groups, but IL-1β levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. Conclusion Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

The potential role of the esophageal pre-epithelial barrier components in the maintenance of integrity of the esophageal mucosa in patients with endoscopically negative gastroesophageal reflux disease

OBJECTIVE: Patients with gastroesophageal reflux disease (GERD) accompanied by erosive reflux esophagitis (RE) exhibit an impairment within the esophageal pre-epithelial barrier protective components that may facilitate the development and/or progression of the mucosal injury. Little is known, however, whether such impairment is a general phenomenon affecting all patients with GERD or whether this is a characteristic feature only of patients with erosive RE. We therefore studied the rate of secretion of esophageal inorganic and organic protective factors in patients with endoscopically negative [E (−)] GERD and compared these results with the corresponding values in asymptomatic volunteers (CTRL). METHODS: The study was conducted on 33 white asymptomatic volunteers and 10 white patients with a long history of GERD confirmed by 24-h pH monitoring and a grossly negative upper endoscopy. Esophageal secretion was collected during mucosal exposure to NaCl, HCl, HC/pepsin and NaCl using the esophageal perfusion catheter. In collected samples all investigated parameters were measured. RESULTS: The pH of esophageal secretion and its content of bicarbonate, EGF, and PGE 2 in patients with E (−) GERD and asymptomatic volunteers were similar. Unexpectedly, the rate of esophageal glycoconjugate (predominantly mucin) secretion was significantly higher in patients with E (−) GERD than in controls during perfusion with HCl ( p < 0.05). Furthermore, secretion of protein in patients with E (−) GERD was significantly higher than in the control group during the mucosal exposure to HCl/Pepsin ( p < 0.05). The nonbicarbonate buffer secretion during perfusion with HCl and HCl/Pepsin as well as the rate of esophageal TGFα output during infusion of final saline in patients with E (−) GERD were significantly lower than in CTRL group ( p < 0.05). CONCLUSIONS: Our data indicate that patients with E (−) GERD have an esophageal secretory potential, in terms of glycoconjugate and protein, higher than that in asymptomatic controls. This phenomenon in patients with E (−) GERD may, by enhancing the quantity of the esophageal pre-epithelial barrier, help to prevent the development of erosive esophagitis. A significantly lower esophageal secretory response in patients with E (−) GERD in terms of nonbicarbonate buffers and TGFα may facilitate the development of GERD symptoms and histological changes of GERD, respectively.

The potential role of the esophageal pre-epithelial barrier components in the maintenance of integrity of the esophageal mucosa in patients with endoscopically negative gastroesophageal reflux disease.

Patients with gastroesophageal reflux disease (GERD) accompanied by erosive reflux esophagitis (RE) exhibit an impairment within the esophageal pre-epithelial barrier protective components that may facilitate the development and/or progression of the mucosal injury. Little is known, however, whether such impairment is a general phenomenon affecting all patients with GERD or whether this is a characteristic feature only of patients with erosive RE. We therefore studied the rate of secretion of esophageal inorganic and organic protective factors in patients with endoscopically negative [E (-)] GERD and compared these results with the corresponding values in asymptomatic volunteers (CTRL). The study was conducted on 33 white asymptomatic volunteers and 10 white patients with a long history of GERD confirmed by 24-h pH monitoring and a grossly negative upper endoscopy. Esophageal secretion was collected during mucosal exposure to NaCl, HCl, HC/pepsin and NaCl using the esophageal perfusion catheter. In collected samples all investigated parameters were measured. The pH of esophageal secretion and its content of bicarbonate, EGF, and PGE2 in patients with E (-) GERD and asymptomatic volunteers were similar. Unexpectedly, the rate of esophageal glycoconjugate (predominantly mucin) secretion was significantly higher in patients with E (-) GERD than in controls during perfusion with HCl (p < 0.05). Furthermore, secretion of protein in patients with E (-) GERD was significantly higher than in the control group during the mucosal exposure to HCl/Pepsin (p < 0.05). The nonbicarbonate buffer secretion during perfusion with HCl and HCl/Pepsin as well as the rate of esophageal TGFalpha output during infusion of final saline in patients with E (-) GERD were significantly lower than in CTRL group (p < 0.05). Our data indicate that patients with E (-) GERD have an esophageal secretory potential, in terms of glycoconjugate and protein, higher than that in asymptomatic controls. This phenomenon in patients with E (-) GERD may, by enhancing the quantity of the esophageal pre-epithelial barrier, help to prevent the development of erosive esophagitis. A significantly lower esophageal secretory response in patients with E (-) GERD in terms of nonbicarbonate buffers and TGFalpha may facilitate the development of GERD symptoms and histological changes of GERD, respectively.

Effects of treatment with bisphosphonates on gastrointestinal and esophageal mucosa in patients with osteoporosis: Pamidronate versus alendronate

The gastrointestinal tolerability of 2 aminobisphosphonates was assessed by upper endoscopy in 38 patients with postmenopausal osteoporosis who received pamidronate disodium 200 mg/d or alendronate sodium 10 mg/d for 1 month. After treatment, 89.5% of patients in the pamidronate group and 76.2% of patients in the alendronate group had normal mucosa or superficial ulceration, whereas 10.5% of the pamidronate group and 23.8% of the alendronate group had more severe ulceration. Adverse gastrointestinal effects were seen in 2 patients in the alendronate group. Two alendronate-treated patients with severe ulceration did not develop symptoms despite the severity of their condition.

Double reflux: double trouble

See article on page 598 The noxious agents responsible for injuring the oesophageal mucosa in patients with gastro-oesophageal reflux disease (GORD) may originate from two possible sources, the stomach and...

Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines.

Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to malignant degeneration is clinically important. Glutathione s-transferase (GST)-pi belongs to a class of protective enzymes whose activity has been shown to be much lower in Barrett's metaplasia than in the normal esophagus, where this form of GST is predominant. In the studies described here, using immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia than in normal esophagus or adenocarcinomas from the same patients. Using as model systems three Barrett's adenocarcinoma cell lines and short-term organ culture of freshly resected normal esophagus and Barrett's metaplasia, dose-dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM dexamethasone after 24 h. These studies demonstrate the ability to induce protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future chemoprevention studies in patients with this type of epithelium, which is at high risk for malignant degeneration.

Does duodenal juice reflux into the esophagus of patients with complicated GERD? evaluation of a fiberoptic sensor for bilirubin

It is controversial whether duodenal juice can damage esophageal mucosa in patients with gastroesophageal reflux disease (GERD). The issue remains unresolved partly because of difficulties in detecting the presence of duodenal juice in the lower esophagus. This study utilized an in vitro portable spectrophotometer with a fiberoptic probe capable of detecting bile as a marker of duodenal juice. Absorbance/concentration curves were established with known bilirubin concentrations at pH 1.4 and pH 7.7. Esophageal pH and bilirubin absorbance were monitored in vivo over a 24-hour period in 20 healthy volunteers to determine the absorbance threshold for clinical use. The study population consisted of 21 patients with GERD. Four had no mucosal injury, 5 erosive esophagitis, and 12 Barrett's esophagus. The correlation between absorbance and bilirubin concentration was 0.98 and 0.99 for acid and alkaline environments, but bilirubin absorbance was 35% less in an acid environment. Using an absorbance threshold of 0.14, patients with GERD taken in toto had elevated esophageal exposure to bilirubin. No difference was observed in bilirubin exposure between reflux patients without mucosal injury and controls. Highest exposure occurred in patients with Barrett's esophagus. An important observation was that esophageal bilirubin exposure frequently occurred during periods when the esophageal pH was in the normal range. The fiberoptic probe accurately detects esophageal bilirubin as a marker of duodenal juice. Esophageal exposure to bilirubin is uncommon in normal subjects. Patients with erosive esophagitis and Barrett's metaplasia have increased esophageal exposure to duodenal juice compared to normal subjects. Reflux of duodenal juice into the esophagus can occur when the esophageal pH is within its normal range and is undetectable by pH monitoring alone.