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.     

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.     

Prevalence of short segments of specialized columnar epithelium in distal esophagus: association with gastroesophageal reflux.

BACKGROUND AND AIMS: Recent studies have reported high prevalence rates of short segments of specialized columnar epithelium (SCE) in the distal esophagus. The association of SCE with gastroesophageal reflux disease is not well established. We studied the prevalence and associations of short segments of SCE in the distal esophagus amongst Indians. METHODS: 271 patients (mean age 36 [14] y; 160 men) undergoing diagnostic upper gastrointestinal endoscopy were interviewed regarding symptoms of gastroesophageal reflux, and history of medications, smoking or chewing tobacco and alcohol ingestion. At endoscopy, presence and grade of esophagitis and hiatus hernia were recorded. One biopsy each was taken from the squamocolumnar junction and 2 cm proximal to it. Biopsies were stained with hematoxylin/eosin and alcian blue/periodic acid-Schiff. The pathologist was blinded to the clinical and endoscopic data. RESULTS: Short segments of SCE in the distal esophagus were present in 16/271 (6%; CI 5.03-6.97) patients. Increasing age (p<0.01), and endoscopic (p<0.01) and histologic (p<0.001) esophagitis were associated with its presence, whereas symptoms of gastroesophageal reflux, smoking, tobacco chewing, use of alcohol or non-steroidal anti-inflammatory drugs, and hiatus hernia were not. One patient with SCE had dysplasia. CONCLUSION: Prevalence of short segments of SCE in the distal esophagus amongst Indians is low and is usually associated with inflammation in the esophagus.     

Manometric findings in patients with isolated distal gastroesophageal reflux

AIM: To analyze manometric abnormalities in patients with isolated distal reflux and compare these findings in patients with erosive and non-erosive disease.METHODS: Five hundred and fifty patients who presented to the outpatient clinic of Turkiye Yuksek Ihtisas Hospital with gastroesophageal reflux disease-like symptoms were enrolled.Each individual was evaluated with esophageal manometry, 24-h ambulatory pH monitoring, and upper gastrointestinal endoscopy.Manometric findings for the patients with isolated distal reflux were compared to findings in controls who were free of reflux disorders or hypersensitive esophagus.Findings for isolated distal reflux patients with and without erosive reflux disease were also compared.RESULTS: Of the 550 subjects enrolled, 97 (17.6%, mean age 48 years) had isolated distal reflux and 100 had no abnormalities on ambulatory pH monitoring (control group, mean age 45 years).There were no significant differences between the isolated distal re- flux group and control group with respect to age, body mass index, and esophageal body contraction amplitude (EBCA).Mean lower esophageal sphincter pressure was significantly higher in the control group (12.7 ± 10.3 mmHg vs 9.6 ±7.4 mmHg, P = 0.01).Fifty-five (56.7%) of the 97 patients with isolated distal reflux had erosive reflux disease.There were no statistical differences between the erosive reflux disease and non-erosive reflux disease subgroups with respect to mean EBCA, lower esophageal sphincter pressure, or DeMeester score.However, 13% of patients with gastroesophageal re- flux disease had distal wave amplitudes ≤ 30 mmHg, whereas none of the patients with non-erosive reflux disease had distal wave amplitudes in this low category.CONCLUSION: Patients with erosive and non-erosive disease present with similar manometric abnormalities.The only striking difference is the observation of very low EBCA exclusively in patients with erosive disease.     

Barrett＇s esophagus and its correlation with gastroesophageal reflux in Chinese

AIM- To study the prevalence of Barrett‘s esophagus in Chinese and its correlation with gastroesophageal reflux. METHODS: This study was carded out in a large prospective series of 391 patients who had undergone upper endoscopy. The patients were divided into 3 groups according to the position of squamocolumnar junction (SC3). Reflux esophagitis (RE) and its degree were recorded. Intestinal metaplasia (IM) in biopsy specimen was typed according to histochemistry and HE and alcian blue (pH2.5) staining separately. Results correlating with clinical, endoscopic, and pathological data were analysed. RESULTS: The prevalence of IM endoscopically appearing Long-segment Barrett‘s Esophagus (LSBE) was 26.53%, Short-segment Barrett‘s Esophagus (SSBE) was 33.85% and gastroesophageal junction (GEJ) was 34.00%. IM increased with age of above 40 years old and no difference was found between male and female. Twelve were diagnosed as dysplasia (7 low -grade, 5 high-grade), 16 were diagnosed as cardiac adenocarcinoma and 1 as esophageal adenocarcinoma. The more far away the SCJ moved upward above GEJ, the higher the prevalence and the more severe the RE were. CONCLUSION: There was no difference of the prevalence of IM in different places of SCJ, and IM increased with age of above 40 years old. It is important to pay attention to dysplasia in the distal esophagus and gastro-esophageal junction, and adenocarcinoma is more common in cardia than in esophagus. BE is a consequence of gastroesophageal reflux disease.     

Barrett's esophagus, gastroesophageal acid reflux and duodenogastric reflux during the digestive and postprandial period]

Pathologic gastroesophageal acid reflux appears to be involved in the pathogenicity of Barrett's esophagus. The possible pathogenic role of duodenogastric reflux, however, has been suggested by several studies. The aim of this prospective study was to assess the prevalence of acid or duodenogastric reflux in patients with Barrett's esophagus. Nine patients with histologically proven Barrett's esophagus (mean length: 7.7cm; range: 2-13 cm) were studied by esophageal manometry and 24 hour pHmetry. Duodenogastric reflux was measured in the interdigestive period by aspiration and during the postprandial period using an isotopic method. The results of these different investigations were compared with healthy volunteers (n = 20 to 27). Three patients had complicated Barrett's esophagus (Barrett's ulcer: n = 2, high-grade dysplasia: n = 1). The results of the different investigations showed that a) all patients had abnormal acid exposure and an esophageal motor dysfunction (decrease in lower esophageal sphincter pressure, amplitude and duration of contractions and increase in percentage of peristaltic dysfunction); b) none of the patients had any pathologic duodenogastric reflux neither in the interdigestive nor in the postprandial period. These results a) confirm the high prevalence of acid reflux in patients with Barrett's esophagus, b) show that bile or pancreatic secretions are not involved in the pathogenicity of Barrett's esophagus.     

胃食管反流病患者口腔pH值变化的探讨

目的比较健康人与胃食管反流病（GERD）患者不同口腔黏膜的pH值及唾液缓冲能力。 方法采用二点测试法对30例胃食管反流病患者使用精密pH试纸测试不同口腔黏膜的pH值及唾液缓冲能力,并与34名健康人作对照。 结果GERD组平均pH值为6.38±0.33,显著低于对照组7.11±0.17,GERD组唾液缓冲能力3.37±0.29也显著低于对照组5.07±0.23。GERD组不同时间的口腔pH值之间存在差异,上午9: 00~11: 00口底黏膜的pH值最低,下午2: 30~4: 30硬腭黏膜pH值最高。 结论胃食管反流患者口腔呈酸性,应根据患者口腔具体情况合理用药,纠正口腔pH值异常,以预防口腔并发症的发生。     

Acid reflux immediately above the squamocolumnar junction and in the distal esophagus: simultaneous pH monitoring using the wireless capsule pH system

OBJECTIVES: The pattern of reflux in the most distal esophagus of asymptomatic individuals is largely unknown. Using a wireless technique we compared the degree and the pattern of acid reflux just above the squamocolumnar junction (SCJ) with that measured at the conventional level for pH monitoring. METHODS: Fifty-three asymptomatic volunteers underwent endoscopy with transoral placement of two pH recording capsules, one immediately above and one 6 cm above the SCJ. Ambulatory pH monitoring was performed during 48 h. RESULTS: Three subjects were excluded as the distal capsule was inadvertently placed with the pH electrode below the SCJ. The median percent time with pH < 4 and the median number of reflux episodes were significantly higher immediately above the SCJ compared with that found more proximally (1.6%vs 0.9% and 67 vs 26, p < 0.0001). Of all acid reflux events, 69% were isolated episodes immediately above the SCJ. Only 26% of reflux episodes detected at the SCJ extended to the more proximal pH electrode. Reflux events occurring just above the SCJ were more acidic. The number of reflux events with a minimum pH below 2 or 3 was significantly higher at the SCJ compared with that recorded by the upper capsule (16% and 44%vs 6% and 34%, p < 0.0001). CONCLUSIONS: Conventional pH monitoring substantially underestimates the degree of acid exposure in the most distal esophagus. In healthy subjects, acid exposure immediately above the SCJ was considerably higher and was characterized by shorter reflux episodes that had a lower minimum pH compared with that measured at the traditional level for pH monitoring.     

Laparoscopic fundoplication in patients with an aperistaltic esophagus and gastroesophageal reflux

A minority of patients with severe gastroesophageal reflux who present to surgeons for antireflux surgery have absent esophageal peristalsis when investigated before surgery with esophageal manometry. Some of these patients also have systemic sclerodema. While conventional wisdom suggests that these patients are at risk of a poor outcome if they proceed to fundoplication, some will have severe reflux symptoms, which are poorly controlled by medical therapy, and surgery will therefore offer the only chance of 'cure'. We performed this study to determine the outcome of laparoscopic fundoplication in the subset of patients with gastroesophageal reflux and an aperistaltic esophagus. From 1991 to 2003, the operative and follow-up details for all 1443 patients who underwent a laparoscopic fundoplication in our Departments have been prospectively collected on a database. These patients were then followed yearly using a standardized symptom assessment questionnaire. A subset of patients whose preoperative esophageal manometry demonstrated complete absence of esophageal body peristalsis and absent lower esophageal sphincter tone (aperistaltic esophagus) were identified from this database, and their outcome following laparoscopic fundoplication was determined. Twenty-six patients with an aperistaltic esophagus who underwent a laparoscopic fundoplication were identified. Six of these had a systemic connective tissue disease (scleroderma), and 20 had an aperistaltic esophagus without a systemic disorder. A Nissen fundoplication was performed in four patients, and an anterior partial fundoplication in 22. Follow-up extended up to 12 years (median, 6). A good overall symptomatic outcome was achieved in 88% at 1 year, 83% at 2 years and 93% at 5-12 years follow-up. Reflux symptoms were well controlled by surgery alone in 79% at 1 year, and 79% at 5-12 years. At 2 years, 87% were eating a normal diet. Two patients underwent further surgery - one at 1 week postoperatively for a tight esophageal hiatus, and one at 1 year for recurrent reflux. Patients with troublesome reflux and an aperistaltic esophagus can be effectively treated by laparoscopic fundoplication. An acceptable outcome will be achieved in the majority of patients.     

含餐8 h食管pH监测与常规24 h pH监测对胃食管反流病的诊断价值比较

目的探讨含餐8h食管pH监测对胃食管反流病(GERD)的诊断意义,并以常规24hpH监测为标准验证其灵敏度及特异度。方法对2003年3月至2006年9月北京大学人民医院消化科221例患者进行食管测压和pH监测。首先由系统计算24h DeMeester积分,≥14.72分诊断为胃食管反流病。入选患者晚餐开始共计8h的监测数据,同样计算DeMeester积分,相同的标准诊断胃食管反流病。比较两种方法的一致性及积分的相关性。结果221例患者经常规24hpH监测诊断胃食管反流病124例,正常97例,含餐8hpH监测方法诊断胃食管反流病120例,正常101例。含餐8h的灵敏度为93.5%,特异度95.9%,经Kappa及Mc-nemar检验2种方法具有良好的一致性,部分结果的差异不具有显著性。2种检测方式DeMeester积分的相关系数为0.929。结论含餐8小时监测法和24hpH监测法具有良好的一致性,有望用于GERD特别是内镜阴性GERD的诊断。     

Risk factors for Barrett's esophagus in Indian patients with gastroesophageal reflux disease

Background and Aims: Barrett's esophagus (BE) is reported to be infrequent in Asians, with no data from India regarding its prevalence and risk factors. We investigated the frequency and risk factors of columnar mucosa with or without specialized intestinal metaplasia (SIM) in Indian patients with gastroesophageal reflux disease (GERD). Methods: A total of 278 GERD patients over 2 years underwent gastroscopy and completed a questionnaire for possible BE risk factors. Patients with columnar mucosa on endoscopy underwent four‐quadrant biopsy; BE was histologically defined as columnar mucosa with or without SIM. Patients without columnar mucosa at endoscopy were considered as controls and compared to patients with BE and those with SIM. Results: Forty‐six patients with GERD had columnar mucosa on histology (16.54%); 25 (8.99%) of these had SIM. The risk factors for BE were the presence of hiatus hernia (odds ratio [OR]: 3.14; 95% confidence interval [CI]: 1.2–8.17) and a history of eructation (OR: 2.28; CI: 1.11–4.66). The risk factors for SIM were age ≥ 45 years (OR: 2.63; CI: 1.03–6.71), hiatus hernia (OR: 3.95; CI: 1.24–12.56), and a history of eructation (OR: 3.41; CI: 1.19–9.78). Sex, severity of symptoms, dietary factors, tobacco or alcohol use, and body mass index were not associated with BE. The median circumferential segment length was 2 (1–10) cm, and the maximal length was 3 (2–11) cm in both groups. Conclusion: BE is not an uncommon finding among Indian GERD patients. Age ≥ 45 years, history of eructation, and the presence of hiatus hernia are associated with SIM.     

Recent developments in gastroesophageal reflux disease and Barrett's esophagus: ANNO 2012

The incidence of gastroesophageal reflux disease (GERD) and esophageal columnar metaplasia is rising worldwide. Both mechanical and functional factors perturb the double sphincter barrier at the esophagogastric junction (EGJ). Discovery of the acid pocket is fundamental in understanding postprandial acid reflux. Adding impedencemetry to pH measurements allows detection of non-acid or weakly acidic reflux. Histologic and endoscopic injury of the squamous mucosa rises from dilation of the intercellular spaces, papillary extension, accentuated intrapapillary looping, red streaks, erosive tissue loss, etc., graded with the Los Angeles system. Seventy percent of patients have no recognizable abnormalities (non-erosive or neGERD). Treatment of GERD mainly relates to the control of acid secretion but a revival of alginate/antacid obliterating the acid pocket is to be expected. Weaker heartburn control in neGERD is a misnomer because most studies included patients with no evidence of reflux disease. Traditional (delayed-release) proton pump inhibitors (PPIs) are powerful suppressors of acid secretion but do have limitations such as gradual build up of acid control, weak control of nocturnal acid recovery, possibility of rebound, occasional need for dose escalation, etc. Barrett's esophagus (BE) is endoscopically diagnosed also in the absence of intestinal metaplasia. A prerequisite is the precise location of the EGJ (proximal end of gastric folds, esophageal sphincter pinch, distal extent of palisade vessels). BE is graded with the Prague C & M system. Barrett's cancer develops usually via low-grade and high-grade dysplasia. Endoscopic examination may indicate suspicious areas, amenable for targeted biopsy. Otherwise, four quadrant biopsies are obtained when searching for neoplasia. Low-grade dysplasia, especially when it is multifocal and p53 positive, high-grade dysplasia and mucosal cancer should be treated with endoscopic resection of the target area, followed by radiofrequency ablation of the adjacent non-neoplastic columnar mucosa, followed with powerful acid suppressant therapy. The long-term results of the combination of resection and ablation are exiting and at least comparable to surgical resection.     

Comparison of 3 methods of recording esophageal pH in the diagnosis of gastroesophageal acid reflux

The aim of this prospective work was to analyze the results of 3 methods of esophageal pH recording (i. e. short-term pH test, 3-hr postprandial recordings, and 12-hr nocturnal pH recording) in 47 patients with suspected gastroesophageal reflux. Nocturnal pH recording was used as a reference for evaluation of the diagnostic value of the 2 other pH tests. Normal ranges were established from 20 control subjects. Esophageal endoscopy with biopsies were performed systematically in order to evaluate the relationship between pH results and the grades of esophagitis. According to the results of nocturnal pH recordings, 32 patients were considered to suffer from acid gastroesophageal reflux and 15 patients as being free of reflux. The sensitivity and specificity of the pH measurements were 0.94 and 0.13 for the short-term pH test and 0.91 and 0.80 for 3-hr postprandial recordings respectively. The total duration of reflux (expressed as a percentage of total duration of the test) was the most discriminative parameter for the diagnosis of reflux and was simpler to determine than previously described pH scores. Because of the absence of lamina propria in the biopsy specimens obtained at endoscopy, histological diagnosis of esophagitis was possible in only 35 patients (74 p. 100). No relationship was found between the grade of esophagitis and the results of short-term pH tests. On the other hand, the mean duration of reflux episodes, the duration of the longest episode, the total duration of reflux measured by 12-hr nocturnal pH recording, and the number of low pH reflux episodes determined by postprandial tests were significantly higher in patients with macroscopic lesions than in those with normal endoscopic aspect or mild (histological) lesions of esophagitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastroesophageal acid reflux in patients with nutcracker esophagus

BACKGROUND: Hypertensive esophageal contraction, called nutcracker esophagus (NE), is the most common motility abnormality associated with cardiac-like chest pain. However, its significance for the development of symptoms has been a matter of controversy for decades, and recently it has been suggested that NE might represent a primarily acid-related esophageal disorder. The frequency of acid-related esophageal dysfunction is studied in an unselected group of patients with NE. METHODS: During the period March 1993 to June 1998, 572 consecutive patients underwent esophageal manometry and 24-h pH monitoring. RESULTS: A motility pattern consistent with NE was found in 45 subjects referred because of chest pain (n = 35), reflux dyspepsia only (n = 8) or epigastric pain (n = 2). Acid-related esophageal dysfunction was noted in 30 (70%) of the NE patients; abnormal acid exposure time (n = 21), esophagitis (n = 2) or positive symptom index (n = 7). In addition, an increased number of reflux episodes were found in another three subjects. NE was more prevalent in subjects referred for chest pain than in those referred for other symptoms (14.3% versus 4.5%; P < 0.0001) and, conversely, 78% of the patients with NE were referred because of chest pain. CONCLUSIONS: Various aspects of acid-related esophageal dysfunction occur frequently in patients with NE, suggesting that acid may play a role in the development of symptoms in NE. Nonetheless, given its association with chest pain, NE could be a marker of a subgroup of patients with acid reflux, distinct from other reflux patients.     

Effect of severe gastroesophageal reflux on sleep stage in patients with aperistaltic esophagus

Polysomnography and esophageal pH studies were conducted in 13 patients with an aperistaltic esophagus; seven of these had scleroderma and six were patients treated for achalasia. The percentage total time of pH <4.0 when recumbent exceeded 30% for both groups. There was a total of 51 reflux events for both groups. There were 22 reflux events recorded for both groups that were less than 5 min in length and 29 events greater than 5 min. In 26 of 32 (81%) instances, patients either began awake and went to sleep during a reflux event or did not awake during a reflux event. Only six of 32 (19%) reflux events caused sleep disruption. We conclude that even the severe reflux demonstrated in this subset of patients does not always disrupt sleep. Patients may have severe prolonged reflux and not arouse.This paper was presented in part at the AGA meeting, San Diego, California, 1995.