Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal acid reflux in patients with Barrett's esophagus

Objective: Normalization of intraesophageal acid exposure is increasingly recognized as a desired goal in the management of Barrett's esophagus. In this prospective trial, we studied patients with Barrett's esophagus by 24-h intraesophageal pH monitoring after having completely eliminated their reflux symptoms with lansoprazole, to determine whether they had achieved normalization of intraesophageal pH.
Methods: Thirty patients with Barrett's esophagus, all of whom had presented with reflux symptoms, were treated with lansoprazole (15–30 mg/day) until they were asymptomatic. Twenty-four-hour ambulatory pH monitoring was performed while they were receiving lansoprazole and were asymptomatic.
Results: Twelve patients (40%) showed persistent bipositional, pathologic acid reflux while on therapy, with a mean DeMeester score of 52.8 (95% CI: 33.8–71.8); the remaining 18 (60%) exhibited normalization of intraesophageal acid exposure with a score of 4.4 (95% CI: 2.3–6.6,   p < 0.001  ). This inadequate control of intraesophageal pH is most likely due to incomplete gastric acid suppression induced by the drug and is associated with a variable acid (distal > proximal) exposure within the esophagus. The two groups were not different in regard to their symptom frequency and severity before therapy, amount of lansoprazole dosage required to eliminate symptoms, length of Barrett's metaplasia, presence of hiatal hernia, lower esophageal sphincter resting tone and length, or esophageal peristaltic function.
Conclusions: Complete symptom eradication with lansoprazole (15–30 mg daily) in patients with Barrett's esophagus does not guarantee normalization of intraesophageal pH profile. If the goal of therapy in such patients is to achieve complete intraesophageal acid suppression, 24-h ambulatory esophageal pH monitoring should be performed to titrate therapy.     

Laparoscopic myotomy in achalasia: intraoperative evidence for myotomy of the gastric cardia

The myotomy performed for achalasia of the esophagus should divide all of the constricting, diseased muscular elements that obstruct the esophagogastric junction (EGJ). Whether the disease process includes proximal gastric as well as esophageal components is as yet unclear, but anatomic evidence complemented by clinical data suggest that the disease process does not end at the evanescent and poorly defined EGJ. Clinical reports from enthusiastic proponents of a particular operative approach for achalasia have not been illuminating in this regard, because all patients are improved to some degree post-operatively, and there are no objective parametric standards for the evaluation of swallowing function. This study reports a series of patients in whom endoscopic viewing was used to judge the adequacy of myotomy after ‘esophageal’ myotomy. The question posed by this study was, ‘Does esophageal myotomy remove all constricting elements at the gastroesophageal junction?’ Laparoscopic myotomy was performed in 48 patients with a diagnosis of achalasia; these patients are the most recent in a total cohort of 72 patients operated upon for achalasia during the past 20 years. Myotomy was begun on the esophagus, and extended to the esophagogastric junction; anatomic landmarks, including the appearance of submucosal veins, guided the initial dissection. Intraoperative endoscopy was then performed to determine whether there was residual constriction of the channel between the esophagus and stomach; if so, myotomy was extended onto the gastric cardia until visual evidence of obstruction had disappeared. All patients had either Toupet fundoplication or Dor fundoplication after myotomy. There were obvious constricting elements distal to the gastroesophageal junction in 90% of the patients. These patients required extension of the myotomy onto the stomach for an average of 15 mm. All but one patient had improved swallowing post-operatively. Eight patients required ‘stretch’ of the distal esophagus/cardia within the first year post-operatively; one patient was reoperated for fibrous scar obstruction of the distal esophagus. Esophageal myotomy limited to the esophageal muscle does not remove all constricting elements at the gastroesophageal junction; as a result, the extended myotomy must be complemented by an antireflux procedure during operations for achalasia.     

Histological and anatomic changes in Barrett's esophagus after antireflux surgery

Objective: The best treatment approach for patients with documented Barrett's esophagus remains controversial. There is currently no well designed prospective study examining the effect of successful antireflux surgery on Barrett's esophagus. Methods: Fourteen patients with histologically proven Barrett's esophagus underwent standard antireflux surgery followed by careful endoscopic, histological, and symptomatic follow-up beginning at 2–4 wk after surgery. Pre- and postoperative symptoms, patient functional assessment scores, lower esophageal sphincter pressure, and 24-h pH studies were compared, in addition to monitoring patients for evidence of squamous re-epithelialization and dysplasia. Results: Patients demonstrated statistically significant improvement in symptoms, functional assessment scores, lower esophageal sphincter pressure, and 24-h pH assessments after antireflux surgery. Two patients had complete disappearance of short segments (2 and 3 cm) of Barrett's esophagus. Ten additional patients demonstrated evidence of squamous re-epithelialization, although biopsies often showed mixed components of squamous and columnar epithelium. No patients showed progression of dysplastic change, and four patients demonstrated the disappearance of low grade dysplasia throughout the period of the study. Conclusion: Successful antireflux surgery can produce at least partial squamous re-epithelialization in Barrett's metaplasia and stabilization or apparent improvement in dysplasia in some patients without the need for long term medication. Continued long term endoscopic and histologic follow-up is still required in all patients with Barrett's esophagus after antireflux surgery.     

贲门失弛缓症治疗方式的探讨

目的比较胸腔镜辅助Heller手术、开胸Heller手术、消化内镜下球囊扩张及消化内镜下肉毒毒素注射治疗贲门失弛缓症疗效，探讨贲门失弛缓症合理有效的治疗方法。方法81例贲门失弛缓症患者按不同治疗方式分为4组：胸腔镜辅助Heller手术18例；开胸Heller手术21例；消化内镜下球囊扩张22例；肉毒毒素注射治疗20例。比较各组治疗前后症状评分、食管末端直径、食管下段括约肌压力、食管末端pH和各组有效率。结果4组患者治疗前后相比，症状评分、食管末端直径、食管下段括约肌压力、食管末端pH差异均有统计学意义（P〈0．05），治疗有效率胸腔镜组为94．4％、开胸组为95．2％、球囊扩张组为63．6％、肉毒素注射组为55．0％，Heller手术较消化内镜下治疗更为有效（P〈0．05）。结论Heller手术治疗效果较球囊扩张及肉毒素注射为佳，胸腔镜辅助Heller手术较开胸Heller手术具有创伤小、恢复快、住院时间短等优势。     

Relationship between rate of change in acid exposure along the esophagus and length of Barrett's epithelium

OBJECTIVE: Gastroesophageal reflux disease (GERD) plays a major role in the development of Barrett's esophagus. Recently, we demonstrated that duration of esophageal acid exposure in the distal esophagus correlates with the length of Barrett's mucosa. The aim of this study was to determine whether there is a relationship between the rate of the change in acid exposure along the esophagus and the length of Barrett's esophagus. METHODS: A total of 17 patients (16 men and one woman; mean age 66 +/- 15 yr, range 41-83 yr) with varying lengths of biopsy-proven Barrett's esophagus were recruited prospectively into the study. Ambulatory 24-h esophageal pH monitoring was performed using a commercially available pH probe with four sensors located 5 cm apart. For each patient, a least squares regression line of the fraction of the study that the pH was <4 against the height of the sensor above the lower esophageal sphincter was fit. The slope of the regression line was used to represent the rate of change in acid exposure. Linear regression analysis was conducted to analyze the relationship between the rate of change in acid exposure and the length of Barrett's mucosa. RESULTS: The mean Barrett's length was 5 +/- 3 cm (range 1-11 cm). Linear regression demonstrated a statistically significant relationship between the rate of change in acid exposure and the length of Barrett's esophagus for the 24-h duration of the study, as well as for the fraction of the study that patients were in the upright position (p = 0.0096 and 0.0076, respectively). For the supine position, the relationship did not reach statistical significance (p = 0.095). CONCLUSIONS: We demonstrated a significant relationship between the rate of change in acid exposure and the length of Barrett's mucosa. Thus, as the rate at which recorded acid exposure values increases from the proximal to distal esophagus, the length of Barrett's esophagus significantly increases (for percent total time and upright position).     

Intestinal metaplasia in the distal esophagus and correlation with symptoms of gastroesophageal reflux disease

Barrett's esophagus is a metaplastic condition that occurs in patients with gastroesophageal reflux disease (GERD) and its importance lies in its potential to develop adenocarcinoma of the esophagus. The diagnosis of Barrett's esophagus is based on finding of intestinal metaplasia of at least 3 cm of the distal esophagus. The diagnosis of intestinal metaplasia of less than 3 cm of the distal esophagus is controversial, regarding implications with GERD, adenocarcinoma, and Helicobacter pylori. The aims of the study were to determine the prevalence of intestinal metaplasia in the distal esophagus in patients with short segments of esophageal columnar-appearing mucosa (less than 3 cm), diagnosed endoscopically, in two groups of patients, with and without symptoms of GERD. In total, 97 patients were examined, with endoscopic finding of esophageal columnar-appearing mucosa less than 3 cm. From the total, 52 patients had symptoms of GERD and 45 patients were without these symptoms. These patients were subjected to distal esophageal biopsies obtained immediately below the epithelial transition. The biopsies were stained with hematoxylin-eosin and alcian blue at pH 2.5. Urease test for H. pylori detection in two fragments of gastric antrum was carried out. The presence of intestinal metaplasia in the distal esophagus was diagnosed in 16 (30.8%) patients in the GERD group and 12 (26.7%) patients without GERD symptoms. No statistical differences were observed (P = 0.82; 95% CI: 0.61-2.17). The variables sex, mean age and positivity for H. pylori did not show statistical differences. This study diagnosed high prevalence of intestinal metaplasia in the distal esophagus with columnar-appearing mucosa, less than 3 cm, with no statistical differences in the two groups studied with and without GERD symptoms.     

Short segment Barrett's esophagus and distal gastric intestinal metaplasia

BACKGROUND: Short segment Barrett's esophagus is defined by the presence of <3 cm of columnar-appearing mucosa in the distal esophagus with intestinal metaplasia on histophatological examination. Barrett's esophagus is a risk factor to develop adenocarcinoma of the esophagus. While Barrett's esophagus develops as a result of chronic gastroesophageal reflux disease, intestinal metaplasia in the gastric cardia is a consequence of chronic Helicobacter pylori infection and is associated with distal gastric intestinal metaplasia. It can be difficult to determine whether short-segment columnar epithelium with intestinal metaplasia are lining the esophagus (a condition called short segment Barrett's esophagus) or the proximal stomach (a condition called intestinal metaplasia of the gastric cardia). AIMS: To study the association of short segment Barrett's esophagus (length <3 cm) with gastric intestinal metaplasia (antrum or body) and infection by H. pylori. PATIENTS AND METHODS: Eight-nine patients with short segment columnar-appearing mucosa in the esophagus, length <3 cm, were studied. Symptoms of gastroesophageal reflux disease were recorded. Biopsies were obtained immediately below the squamous-columnar lining, from gastric antrum and gastric corpus for investigation of intestinal metaplasia and H. pylori. RESULTS: Forty-two from 89 (47.2%) patients were diagnosed with esophageal intestinal metaplasia by histopathology. The mean-age was significantly higher in the group with esophageal intestinal metaplasia. The two groups were similar in terms of gender (male: female), gastroesophageal reflux disease symptoms and H. pylori infection. Gastric intestinal metaplasia (antrum or body) was diagnosed in 21 from 42 (50.0%) patients in the group with esophageal intestinal metaplasia and 7 from 47 (14.9%) patients in the group with esophageal columnar appearing mucosa but without intestinal metaplasia. CONCLUSION: Intestinal metaplasia is a frequent finding in patients with <3 cm of columnar-appearing mucosa in the distal esophagus. In the present study, short segment intestinal metaplasia in the esophagus is associated with distal gastric intestinal metaplasia. Gastroesophageal reflux disease symptoms and H. pylori infection did not differ among the two groups studied.     

The impact of antireflux surgery on oxidative stress of esophageal mucosa caused by gastroesophageal reflux disease: 4-yr follow-up study

BACKGROUND AND AIM: Oxidative stress to esophageal mucosa plays a key role in the pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus, and adenocarcinoma. We investigated whether successful antireflux surgery eliminates oxidative stress. METHODS: Oxidative stress of esophageal mucosa was measured in 20 GERD patients, before antireflux surgery and 6 and 48 months after it, and compared with normal controls' mucosa (N = 9). Preoperatively, 12 of the 20 had erosive esophagitis or Barrett's metaplasia. Postoperatively, healing of GERD was verified with endoscopy and 24-h pH monitoring. We measured oxidative stress by myeloperoxidase activity (MPA), superoxide dismutase activity, and glutathione content (GSH) in distal esophagus samples from endoscopy. RESULTS: No patient had reflux symptoms after surgery, and pH measurements had normalized. MPA in the distal esophagus decreased (p < 0.05) after successful antireflux surgery, but remained higher than that of controls both 6 months and 4 yr postoperatively (p < 0.05). At all time-points, MPA was higher in patients with preoperatively detected erosive reflux disease (ERD) as compared to non-erosive reflux disease (NERD) (p < 0.01, p < 0.05, and p < 0.05, respectively). GSH values decreased with time only in NERD. At all time-points, GSH levels in distal esophagus were lower than control levels. CONCLUSIONS: Antireflux surgery can heal macroscopic esophagitis but cannot fully reverse the oxidative stress (as reflected by MPA and GSH) upon the distal esophageal mucosa.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.     

Cytokeratin subsets for distinguishing Barrett's esophagus from intestinal metaplasia in the cardia using endoscopic biopsy specimens

OBJECTIVES: It has been suggested that Barrett's epithelium and intestinal metaplasia in the gastric cardia have different cyotokeratin (CK) staining patterns and that Barrett's epithelium can be distinguished by CK staining pattern. The aim of this study was to test the utility of CK staining for distinguishing Barrett's esophagus from gastric intestinal metaplasia. METHODS: Topographically mapped gastric biopsy specimens were obtained from patients without Barrett's esophagus, and esophageal biopsies were obtained from patients with long-segment Barrett's esophagus (>3 cm). Serial sections were stained with Genta or El-Zimaity triple stain, and biopsies with intestinal metaplasia were stained with antibodies against CK 4, 13, 7, and 20. RESULTS: Sections from 33 biopsies with Barrett's esophagus, 23 with intestinal metaplasia of the gastric cardia, 27 with intestinal metaplasia of the gastric body, and 33 with intestinal metaplasia of the antrum were examined. CK 4 and CK 13 stained squamous epithelium only. The proposed "diagnostic" CK Barrett's 7/20 pattern was found in only 39% of long-segment Barrett's compared to 35%, 4%, and 24% in intestinal metaplasia from the gastric cardia, body, and antrum, respectively. The criteria proposed had a sensitivity of 45% and a specificity of 65%. CONCLUSIONS: These results do not support keratin phenotyping as a tool for differentiating intestinal metaplasia originating in the cardia from intestinal metaplasia of Barrett's.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

Objective: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis.
Methods: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy ≤3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects.
Results: Patients with Barrett's esophagus had significantly increased acid reflux time (   p < 0.01  –0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (   p < 0.01  –0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis.
Conclusion: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Shorter myotomy on the gastric site (≤2.5 cm) provides adequate relief of dysphagia in achalasia patients

The right length of the myotomy on the gastric side for esophageal achalasia is still a debated issue. We aimed to investigate the final outcome after classic myotomy (CM) as compared with a longer myotomy on the gastric side (LM) in two cohorts of achalasia patients. Forty‐four achalasia patients who underwent laparoscopic Heller–Dor were considered; patients with a sigmoid‐shaped esophagus were excluded. Symptoms were scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain. Barium swallow, endoscopy, and esophageal manometry were performed before and 6 months after the surgical treatment; 24‐hour pH‐monitoring was also performed 6 months after the procedure. CM was defined as a gastric myotomy length in the range of 1.5–2.0 cm, while LM was 2.5–3 cm in length. The surgical treatment (CM or LM) was adopted in two consecutive cohorts. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. >8). Of the 44 patients representing the study population, 20 had CM and 24 had LM. The patients' demographic and clinical parameters (age, sex, symptom score, duration of symptoms, esophageal diameter, and manometric pattern) were similar in the two groups. The median follow up was 24 months (interquartile range 12–39). One patient in each group was classified as a treatment failure. After the treatment, there was a significant decrease in both groups' symptom score, and resting and residual pressure (P < 0.01), with no statistically significant differences between the two groups in terms of postoperative symptom score, resting and residual pressure, or total and abdominal lower esophageal sphincter length and esophageal diameter. Extending the length of the myotomy on the gastric side does not seem to change the final outcome of the laparoscopic Heller–Dor procedure.     

Spectrum of histopathologic findings in patients with achalasia reflects different etiologies

BACKGROUND: The etiology of achalasia is still unknown. The aim of the present study was to elucidate its underlying pathologies and their chronology by investigation of esophageal specimens in patients undergoing surgery (esophageal resection or myotomy) for achalasia. METHODS: In 17 patients with achalasia, histopathologic examinations of the esophageal wall focussing on the myenteric plexus were performed. Preoperative diagnosis was based on clinical evaluation, esophagogastroscopy, barium esophagogram in all, and esophageal manometry in eight patients. The median age at the time of surgery was 54 years (range: 14-78 years). In eight cases, the complete esophageal, body and in nine cases a smooth muscle biopsy including parts of the myenteric plexus from the distal part of the esophagus (high pressure zone) was available. The tissue specimens were fixed in formalin and embedded in paraffin. The staining procedures were hematoxylin and eosin (HE), Elastica van Gieson (EvG), and periodic acid-Schiff (PAS) reaction. Immunohistochemical examinations were performed with antibodies against B and T lymphocytes, neurofilament, protein gene-related product (PGP 9.5), S-100 protein, myosin, desmin, smooth muscle actin and substance P. RESULTS: In 13 of 17 patients, a significant reduction of the number of intramural ganglion cells was present. Common findings were a severe fibrosis of the smooth muscle layer (10/17) and obvious myopathic changes of the smooth muscle cells (5/17). Staining for B and T lymphocytes found signs of inflammation in mucosal and muscular areas. Three patients exhibited a marked invasion of eosinophilic granulocytes of the muscularis propria (eosinophilia). Esophageal carcinoma had developed in three patients (squamous cell carcinoma in two and carcinoma in situ in another patient with Barrett's esophagus and high-grade dysplasia). Severe inflammatory reactions (neural, eosinophilic and mucosal) dominated in patients with a longstanding history of achalasia (>10 years) as well as a marked endomysial fibrosis. CONCLUSIONS: The histopathological investigations of the esophageal wall in 17 patients undergoing esophageal resection or myotomy for achalasia suggest that the reduction of intramural ganglion cells might be a secondary change, probably due to inflammation triggered by autoimmune mechanisms or a chronic degenerative process of the central and/or peripheral part of the vagal nerve. The primary lesion could also be a severe myopathy of the smooth muscle cells.     

Specialized intestinal metaplasia of the distal esophagus in gastroesophageal reflux disease: prevalence and clinico-demographic features

BACKGROUND: Specialized intestinal metaplasia can be categorized according endoscopic and histological findings in long segment Barrett, short segment Barrett and specialized intestinal metaplasia of cardia. Barrett's esophagus is an acquired disease that is found in about 10%-13% of patients undergoing endoscopy for symptoms of gastroesophageal reflux disease and it is well established as predisposing to esophageal adenocarcinoma. The columnar epithelium with goblet cells replaces the normal squamous epithelium. OBJECTIVE: To determine the prevalence and clinical-demographic characteristics of specialized intestinal metaplasia of distal esophagus in the gastroesophageal reflux disease. METHODS: From April to October 2002, 402 patients referred to upper endoscopy due gastroesophageal reflux disease were evaluated through of a symptom questionnaire about clinical and demographic features and submitted to upper endoscopy with four-quadrant biopsies 1 cm below escamocolumnar junction. RESULTS: Eighteen point four percent of patients had specialized intestinal metaplasia, 0.5% long segment Barrett esophagus, 3.2% short segment Barrett's esophagus and 14.7% specialized intestinal metaplasia of cardia. Patients with Barrett's esophagus showed a tendency to be male and specialized metaplasia of cardia to be female. All patients with Barrett's esophagus were white. There was not association between symptoms of gastroesophageal reflux disease and specialized intestinal metaplasia, but patients with Barrett's esophagus showed a tendency to have symptoms over 5 years and had more hiatal hernia and esophagitis. The use of alcohol and tobacco was not related to the presence of specialized intestinal metaplasia. CONCLUSIONS: Barrett's esophagus was more related to the male gender, gastroesophageal reflux disease symptoms for 5 years or longer, more intense esophagitis and hiatal hernia, but was not related to the use of tobacco and alcohol.     

Gastric metaplasia of the proximal esophagus associated with esophageal adenocarcinoma and Barrett's esophagus: what is the connection? Inlet patch revisited

BACKGROUND/AIM: The inlet patch is an area of heterotopic gastric mucosa found in the proximal esophagus at the level of the upper esophageal sphincter. Limited data are available regarding this form of gastric metaplasia and its incidence, significance, and possible association with other esophageal diseases. We report our observations of such gastric metaplasias in patients with esophageal adenocarcinoma or Barrett's esophagus and high-grade dysplasia. METHODS: All patients having Barrett's esophagus and adenocarcinoma referred for photodynamic therapy were included in this study. The patients were prospectively evaluated endoscopically for the presence of gastric metaplasia of the proximal esophagus (salmon-colored area of a least 5 mm in diameter with cardia-type gastric metaplasia on biopsy). RESULTS: A total of 36 patients were included in this study: 11 patients with dysplastic Barrett's esophagus (8 males, mean age 79 years) and 25 adenocarcinoma patients (18 males, mean age 71 years). At endoscopy prior to photodynamic therapy, 11 patients (31%; 8 adenocarcinoma, 3 dysplastic Barrett's esophagus) were noted to have an area of gastric mucosa in the proximal esophagus. In each patient, there was at least 5 cm of normal squamous mucosa between gastric metaplasia and distal esophageal pathology. CONCLUSIONS: In this selected group of patients with high-grade dysplastic Barrett's esophagus or adenocarcinoma referred for photodynamic therapy, gastric metaplasia of the proximal esophagus was found in nearly one third. Prospective studies are under way to test more widely for this association and to determine whether this is a marker of disease severity and the result of similar pathogenetic mechanisms.     

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.     

Esophageal pH exposure and epithelial cell differentiation

It is proposed that epithelial changes induced by gastroesophageal reflux disease are related to the pH environment of the esophageal lumen. We hypothesized that the various types of esophageal epithelium are associated with specific pH environments that induce their formation. The aim of this study was to compare the luminal pH environment to the histology of the distal esophageal epithelium in patients with gastroesophageal reflux disease. A total of 197 symptomatic patients with increased esophageal acid exposure on 24-hour pH monitoring were grouped according to the histology based on biopsies from the distal esophagus: 17 with squamous epithelium, 126 with cardiac epithelium (CE), and 54 with Barrett's epithelium (BE). All were free of Helicobacter pylori infection and monitored off acid suppression therapy. Acid exposure was expressed as the percent of time the luminal pH was at intervals of 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, and 6–7 over a 24-hour period. Patients with BE spent significantly more time at pH intervals 2–3, 3–4, and 4–5 than those with CE. This pattern switched at pH interval 5–6, where patients with cardiac mucosa spent more time than those with BE. Patients with squamous and CE had similar pH exposure at all intervals. Patients with BE have significantly longer exposure time at the pH interval of 2 to 5 compared to those with cardiac and squamous epithelium. This suggests that the exposure of stem cells to a luminal pH between 2 and 5 may trigger the differentiation of CE into intestinalized CE.     

The Prevalence of Intestinal Metaplasia in Patients With and Without Peptic Strictures

Objective: Several studies suggest that patients with esophageal peptic strictures have a high prevalence of Barrett's esophagus. However, these studies did not include appropriate control groups, were retrospective in nature, or did not strictly define Barrett's esophagus. Our aim was to compare the prevalence of Barrett's esophagus in patients with and without gastroesophageal reflux disease strictures in a prospective study.
Methods: Seventy-nine patients referred for endoscopy for gastroesophageal reflux disease symptoms were evaluated. We collected demographic information and an esophageal symptom assessment. Biopsy specimens were obtained from peptic strictures, Schatzki rings, or from any areas of columnar-lined esophagus or mucosal injury. Barrett's esophagus was strictly defined as the presence of intestinal metaplasia from tubular esophagus.
Results: There were 46 patients without strictures and 28 patients with peptic strictures. Five patients had Schatzki's rings. The prevalence of intestinal metaplasia was 23.9% in patients without strictures, and 25% in patients with peptic strictures ( p = NS ). There was no difference in prevalence of short- or long-segment Barrett's esophagus between the groups. Patients with strictures were older than patients without strictures (mean age 58.9 vs 48.6 yr), and more likely to have mucosal injury (50% vs 26.1%). Otherwise, there were no significant differences with regards to gender, race, heartburn duration or frequency.
Conclusions: Barrett's esophagus, as defined by the presence of intestinal metaplasia in the tubular esophagus, is equally common in patients with and without peptic strictures. There does not appear to be an association between Barrett's esophagus and peptic strictures.     

Barrett's esophagus: a retrospective analysis of 13 years surveillance

Background and Aims:  The incidence of esophageal adenocarcinoma has increased significantly. Barrett's esophagus (BE), a known precursor, has a high prevalence but only few patients with this condition progress to malignancy − surveillance and screening programs are controversial and lack proven efficacy. This retrospective analysis reviews the 13-year outcome for patients entered into a surveillance program.
Methods:  Data from patients with histologically proven Barrett's esophagus (1992–2003) that participated in a surveillance program were identified and analyzed retrospectively until 2005.
Results:  404/536 patients had Barrett's esophagus confirmed histologically of which 212 (53%) were followed in a surveillance program (mean 3.95 years per patient). This resulted in 749 gastroscopies (3.5/patient). Histologically, Barrett's mucosa was seen in 54%, low-grade dysplasia in 18%, ulcerations in 9%, high-grade dysplasia in 2%. No metaplasia was seen in 13%, no biopsy was obtained in 3%. Nine of 212 patients (4.3%) under surveillance developed esophageal cancer; two presented with symptoms, requiring gastroscopy outside the surveillance program (1/2 was operated successfully, one had advanced disease). In seven asymptomatic patients, cancer was detected on routine endoscopy; curative esophagectomy was performed in six. All patients who developed cancer were male and all but one patient had dysplasia or ulcerations on index endoscopy.
Conclusion:  During 13 years of Barrett's surveillance, 88% of all adenocarcinoma occurred in a subset of only 11% patients. To stratify surveillance for Barrett's esophagus, programs could focus on male patients with dysplasia or ulcerations on index endoscopy. However, the cost-effectiveness of this remains unproven.     

Cardia-type metaplasia arising in the remnant esophagus after cardia resection

BACKGROUND: Specialized intestinalized metaplasia in the distal esophagus (Barrett's esophagus) is a recognized precursor of esophageal adenocarcinoma, but its pathogenesis is incompletely understood. The aim of this study was to investigate the mucosal effects of esophagogastrostomy, an artificial interface between esophageal squamous and gastric oxyntic epithelium. METHODS: EGD was performed in 14 consecutive patients (median age 63 years, range 26-71 years) who had undergone esophagogastrostomy from 3 to 88 months earlier. Biopsy specimens were obtained in 13 patients from the anastomosis and, when present, columnar epithelium in the remnant esophagus. RESULTS: In 10 patients, EGD demonstrated tongue-shaped segments of columnar epithelium extending from 0.3 to 7 cm into the remnant esophagus. Biopsy specimens revealed cardia-type mucosa in all patients, whether at the anastomosis or proximally in esophageal segments of columnar epithelium. Magnification endoscopy of cardia-type mucosa visualized a long-oval, tubular, or ridged surface pattern. In 3 cases, complete intestinal metaplasia was observed within the cardia-type mucosa. CONCLUSIONS: The frequent transformation of squamous epithelium into cardia-type mucosa in the distal remnant esophagus after esophagogastrostomy supports the concept that cardia-type mucosa is a reflux-induced metaplasia that may give rise to the subsequent development of specialized intestinalized metaplasia.