Barrett's esophagus and achalasia

Two unusual cases of achalasia with endoscopic and histologic documentation of Barrett's esophagus are presented. One patient had Barrett's esophagus at the time of initial endoscopy for achalasia, before any treatment. The other patient developed specialized columnar epithelia in the esophagus after treatment with pneumatic dilation. Each patient had evidence of low-grade dysplasia. Including these two patients, 30 cases of Barrett's esophagus in patients with achalasia have been reported in the literature. In 73% (22 of 30) of the cases, Barrett's esophagus was detected after esophagomyotomy. In 20% (6 of 30) of the cases of achalasia and Barrett's esophagus, adenocarcinoma developed. The current two cases are unusual because Barrett's esophagus in achalasia generally develops from gastroesophageal reflux after esophagomyotomy. No other patients have been reported to develop Barrett's esophagus after pneumatic dilation alone. Patients with achalasia and Barrett's esophagus may be at a particularly high risk for developing dysplasia and adenocarcinoma.     

Barrett's esophagus complicating achalasia after esophagomyotomy. A clinical, radiologic, and pathologic study of 70 patients with achalasia and related motor disorders

Of 70 patients with achalasia and related motor disorders, 3 developed Barrett's esophagus 5, 8, and 15 years after esophagomyotomy. One of the three had dysplastic changes in the Barrett's mucosa. Although an increased incidence of gastroesophageal reflux, esophagitis, and stricture are well-known complications after esophagomyotomy, the development of Barrett's mucosa has been only recently recognized. Diagnosis of Barrett's esophagus in such patients is difficult and requires a high index of awareness by the radiologist and an endoscopic biopsy for definitive diagnosis. The cumulative effects of achalasia and Barrett's esophagus predispose these patients to higher risks of developing esophageal carcinoma.     

Barrett's esophagus and achalasia. A case report.

A 70-year-old woman with no previous gastroesophageal surgery gave a 6-month history of dysphagia. Barium studies suggested a diagnosis of achalasia. Esophageal manometry showed absence of peristalsis and a high lower esophageal sphincter pressure. Endoscopy showed a dilated esophagus with food residue, and Barrett's esophagus was present. The association of Barrett's esophagus and achalasia must be rare.     

Esophageal adenocarcinoma in a patient with surgically treated achalasia

Summary Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastroesophageal reflux disease.     

Life expectancy and cancer risk in patients with Barrett's esophagus: a prospective controlled investigation.

BACKGROUND: It has been suggested that patients with Barrett's esophagus have a substantially increased risk of esophageal and possibly extra-esophageal cancers. We compared the incidence of cancer and the survival rates of patients with Barrett's esophagus with those observed in patients with achalasia, with Schatzki's ring, and in the general population. PATIENTS AND METHODS: From 1980 through 1994, 60 consecutive patients with newly diagnosed long-segment Barrett's esophagus without dysplasia were seen in a single gastroenterology consultation office and followed until the Fall of 1999. Cancer incidence and survival rates were compared with age- and sex-matched patients with symptomatic Schatzki's ring (n = 60) and achalasia (n = 60). Survival data were also compared with those of the German population. RESULTS: During a mean (+/-SD) observation period of 10 +/- 5 years, 2 patients with Barrett's esophagus (3%; 95% confidence interval [CI]: 0% to 11%) developed esophageal cancer, and 9 (15%; 95% CI: 7% to 27%) developed extra-esophageal cancers. These data differed only slightly from those of patients with Schatzki's ring (esophageal cancer: n = 1, 2%; 95% CI: 0% to 9%; extra-esophageal cancers: n = 9, 15%; 95% CI: 7%-27%) and achalasia (no esophageal cancers, extra-esophageal cancers: n = 3, 5%; 95% CI: 1% to 4%). Estimated 10-year survival was similar in patients with Barrett's esophagus (83%), patients with symptomatic Schatzki's ring (80%), patients with achalasia (87%), and in the general population (82%). CONCLUSIONS: The cancer risk in patients with Barrett's esophagus has been overestimated. If patients with nondysplastic epithelium are followed, the risk of esophageal cancer is about 1 per 300 patient-years.     

Barrett's Metaplasia and Dysplasia in Postmyotomy Achalasia Patients

Three patients who were 8 to 30 years status postmyotomy for achalasia were shown to develop Barrett's columnar metaplasia of the esophagus. In one instance, the patient had multiple areas of severe dysplasia to carcinoma in situ. There have been only a few reports in the world literature of Barrett's metaplasia occurring in postmyotomy achalasia patients. Our experience would indicate it may be a more common complication than previously appreciated. Also, a possible causal relationship between surgical intervention, Barrett's epithelium, and adenocarcinoma in achalasia is suggested.     

Barrett's Esophagus after Cardiomyotomy for Esophageal Achalasia

Heller's myotomy for esophageal achalasia was performed on 64 patients in the 24 yr up to 1988. After follow-up averaging 13 yr, 46 patients were reexamined with endoscopy, biopsy, and manometry. Barrett's metaplasia of the distal esophagus was found in four patients 6, 13, 20, and 23 yr after the myotomy. These four also underwent ambulatory 24-h pH monitoring. They had the lowest distal esophageal sphincter pressures (1–5 mm Hg), and all four had symptoms of gastroesophageal reflux and pathologic pH values (<4 in the distal esophagus for 32–62% of the total recording time). Because of heightened risk for the development of Barrett's metaplasia following cardiomotomy for esophageal achalasia, with increased liability to carcinoma of the esophagus, regular endoscopic surveillance of these patients is advisable.     

Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett''s esophagus

Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.     

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

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

Barrett's esophagus: prevalence in symptomatic relatives

OBJECTIVES: Relatives of patients with Barrett's esophagus have an increased prevalence of reflux symptoms. Our aim was to find if these relatives were at increased risk of having Barrett's esophagus. METHODS: First degree relatives of patients with Barrett's esophagus completed the Reflux Symptom Questionnaire. Relatives with reflux symptoms, never previously investigated. were invited for endoscopy. Controls were patients with similar reflux symptoms and no family histories of Barrett's esophagus. RESULTS: We found previously undiagnosed Barrett's esophagus (>3 cm) in eight of 100 relatives (8%) from 53 families and in five of 100 controls (5%) (adjusted OR = 1.58, 95% CI = 0.46-5.45). Including another 27 previously investigated cases, 10 of the 53 families had two or more cases of Barrett's esophagus. Barrett's esophagus prevalence increased with age (p = 0.014) and was associated with reflux symptoms of >10 yr (p = 0.020), and Barrett's esophagus was twice as common in males (p = 0.28). Reflux esophagitis was found in 74% of relatives and 57% of controls without Barrett's (p = 0.04). CONCLUSIONS: The risk of Barrett's esophagus in any one symptomatic relative of a patient with Barrett's esophagus was not statistically higher than in other persons with reflux symptoms. However, more relatives of Barrett's esophagus patients have reflux symptoms, so the overall prevalence of Barrett's esophagus and reflux esophagitis in relatives may also be greater than in the general population. In considering whether to screen patients with reflux symptoms for Barrett's esophagus, age and duration of symptoms are stronger predictors than having a relative with Barrett's esophagus.     

Controversies in the treatment of gastroesophageal reflux and achalasia

The immense success of laparoscopic surgery as an effective treatment of gastroesophageal reflux disease (GERD) and achalasia has established minimal invasive surgery as the gold standard for these two conditions with lower morbidity and mortality, shorter hospital stay, faster convalescence, and less postoperative pain. One controversy in the treatment of GERD evolves around laparoscopic antireflux surgery (LARS) as the preferred treatment for Barrett's esophagus and the procedure's potential to reduce the risk of adenocarcinoma of the esophagus. GERD has also been associated with respiratory symptoms, asthma and laryngeal injury, and a second controversy prompts discussions about whether total or partial fundoplication is the more appropriate treatment for GERD. A new and promising alternative in the treatment of GERD is endoluminal therapy. Three types of this new treatment option will be discussed: radiofrequency energy delivered to the lower esophageal sphincter, the creation of a mechanical barrier at the gastroesophageal junction, and the direct endoscopic tightening of the lower esophageal sphincter. Laparoscopic surgery is discussed not only as a very effective treatment for GERD but also as permanent cure for achalasia. This review analyzes the three most important treatment options for achalasia: medications, pneumatic dilatation, and surgical therapy. Medications as the only true non-invasive option in the treatment of achalasia are not as effective as LARS because of their short half-life and variable absorption due to the poor esophageal emptying. The second treatment option, pneumatic dilatation, involves the stretching of the lower esophagus and is still considered the most effective non-surgical treatment for achalasia. Finally, surgical therapy for achalasia and the two major controversies concerning this laparoscopic treatment are discussed. The first involves the extent to which the myotomy is extended onto the stomach, and the second concerns the necessity and type of antireflux procedure to prevent GERD after myotomy. LARS and laparoscopic Heller myotomy are the agreed upon as the gold standards for surgical treatment of GERD and achalasia, respectively. In the hands of an experienced laparoscopic surgeon both are safe and effective treatments for patients with excellent subjective and objective long-term results with at least 90% patient satisfaction.     

Cytokeratin immunoreactivity patterns in short-segment Barrett's esophagus in Japanese patients

BACKGROUND: The origin of intestinal metaplasia at the esophagogastric junction has clinical importance. However, it can be difficult to differentiate between intestinal metaplasia of short-segment Barrett's esophagus and cardiac intestinal metaplasia due to Helicobacter pylori infection. Specific patterns of cytokeratin (CK)7 and CK20 have been detected in long-segment Barrett's esophagus. The aim of the present study was to assess the immunostaining patterns associated with short-segment Barrett's esophagus. AIMS: Paraffin-embedded biopsy specimens were prepared from 128 patients with intestinal metaplasia of long-segment Barrett's esophagus (n = 3), short-segment Barrett's esophagus without H. pylori infection (n = 22), short-segment Barrett's esophagus with H. pylori infection (n = 22), and cardiac mucosa (n = 49) and gastric mucosa from antrum and fundus (n = 44) with H. pylori infection. Sections were prepared and immunostained for CK7 and CK20. RESULT: A Barrett's CK7/20 pattern was present in all three patients (100%) with long-segment Barrett's esophagus, 21 of 22 patients (95%) with short-segment Barrett's esophagus without H. pylori infection, and six of 22 patients (27%) with short-segment Barrett's esophagus with H. pylori infection (P < 0.05). CONCLUSION: Intestinal metaplasia of short-segment Barrett's esophagus in patients without H. pylori infection is thought to be similar to that seen in long-segment Barrett's esophagus.     

The prevalence of Barrett's esophagus in patients with chronic peptic esophageal strictures

Both Barrett's esophagus and peptic stricture of the esophagus are consequences of chronic reflux esophagitis. Barrett's esophagus appears to be a premalignant condition, and continued histologic surveillance for dysplasia and carcinoma has been recommended for affected patients. While patients with peptic esophageal strictures and persistent reflux are at risk for the development of Barrett's epithelium, such patients often do not receive continued histologic surveillance if Barrett's epithelium is not identified on the initial endoscopic evaluation. Using endoscopic and peroral aspiration biopsy techniques, we studied the prevalence of Barrett's esophagus in 25 patients with chronic peptic esophageal strictures in whom Barrett's epithelium had not been identified previously. We found Barrett's esophagus in 11 (44%) of our 25 patients. One patient who did not have Barrett's esophagus was found to have an undifferentiated esophageal carcinoma. We conclude that patients with chronic peptic esophageal strictures frequently have Barrett's esophagus. A program of continued histologic surveillance seems advisable for such patients.     

Hiatal Hernia and Acid Reflux Frequency Predict Presence and Length of Barrett's Esophagus

One third of the general population may experience reflux symptoms, yet only a small fraction of patients with gastroesophageal reflux disease (GERD) have Barrett's esophagus. The aim of the present study was to compare the characteristics of GERD patients with and without Barrett's esophagus and identify potential risk factors for the appearance of Barrett's esophagus in reflux disease. Outpatients from a gastroenterology clinic who underwent upper gastrointestinal endoscopy, esophageal manometry, and 24-hr pH monitoring were recruited into a case-control study. A total of 256 case subjects with endoscopically and histologically proven Barrett's esophagus were compared to a control group of 229 subjects with nonerosive reflux disease. As compared to nonerosive reflux disease, Barrett's esophagus was strongly associated with more reflux episodes. Barrett's esophagus occurred more frequently among subjects with hiatus hernia and among subjects who consumed large amounts of alcohol or cigarettes. Frequent reflux episodes, hiatus hernia, smoking, and alcohol consumption were also risk factors for an increased length of Barrett's mucosa. Total esophageal mucosal acid contact time at pH < 4 was a significant risk factor for the length but not the presence of Barrett's esophagus. Intake of aspirin or NSAIDs was similar in patients with and without Barrett's esophagus. In conclusion, in comparison with nonerosive reflux disease, Barrett's esophagus is characterized by risk factors usually indicative of severe types of GERD. Mechanisms in addition to acid reflux must contribute to the development of Barrett's esophagus.     

Schatzki Ring and Barrett's Esophagus: Do They Occur Together?

Our purpose was to determine the prevalence of Barrett's esophagus in the presence of Schatzki ring. We performed a retrospective case-control study with an endoscopic database. Barrett's esophagus was present in 3 of 409 (0.73%) patients with Schatzki ring and in 16 of 888 (1.80%) patients without Schatzki ring. Short segment Barrett's esophagus was present in 3 cases and 10 controls. Long segment Barrett's esophagus was present in no cases and six controls. Logistic regression models adjusting for the presence of a hiatal hernia revealed a significant decrease in the odds of Barrett's esophagus in cases compared to controls (OR, 0.24; 95% CI, 0.07-0.87; P = 0.029). Barrett's esophagus is less prevalent in patients with Schatzki ring compared to patients without Schatzki ring. Long segment Barrett's esophagus was not observed in patients with Schatzki ring. A responsible protective effect or mutually exclusive pathophysiology should be considered.     

Transition from nutcracker esophagus to achalasia. A case report.

We report a middle-aged woman with nutcracker esophagus who progressed to classic achalasia in two years. Several previous reports have documented progression of nutcracker esophagus to diffuse esophageal spasm and diffuse esophageal spasm to achalasia, but the only previous report of nutcracker esophagus progressing to achalasia was in a child. Our case suggests that, in some instances, nutcracker esophagus and achalasia may share the same pathogenesis.     

Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma

BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.     

Barrett's esophagus: prevalence and size of hiatal hernia

OBJECTIVE: Barrett's esophagus is caused by gastroesophageal reflux and predisposes to adenocarcinoma. Hiatal hernia may cause reflux. The prevalence and size of hernias in patients with Barrett's esophagus was investigated. METHODS: Axial hernia length and the width of the diaphragmatic hiatus were measured prospectively at endoscopy. RESULTS: A 2-cm or longer hernia was found in 96% of 46 patients with Barrett's esophagus, in 42% of 103 controls (p < 0.001), and in 72% of 18 patients with short segment Barrett's esophagus (p < 0.05 vs controls). A hernia was found in 71% of 31 controls with esophagitis and in 29% of 72 controls without esophagitis (p < 0.001). Of 54 controls with neither esophagitis or reflux symptoms, 20% had a hernia. Mean hernia length was 3.95 cm in Barrett's esophagus, and 2.81 cm in controls (p < 0.005). Mean hiatus width was 3.52 cm in patients with Barrett's esophagus and hernia, and 2.24 cm in controls with hernia. Hernia length was similar in patients with and without esophagitis, and in short segment Barrett's esophagus. CONCLUSIONS: Most patients with Barrett's esophagus have hiatal hernia; their hernias are longer and the hiatal openings wider than in controls with or without esophagitis. Hiatal hernia likely contributes to the development of Barrett's esophagus.     

Barrett's esophagus and risk of esophageal adenocarcinoma

Barrett's esophagus is most often seen in white men with chronic heartburn who are generally older than 50 years of age. The prevalence of Barrett's esophagus is 10% to 15% in patients who are undergoing endosocopy for gastroesophageal reflux disease and 1% to 2% in asymptomatic American adults. Barrett's esophagus represents metaplastic columnar tissue with specialized intestinal metaplasia, and this condition carries an increased risk of esophageal adenocarcinoma. Patients with Barrett's esophagus have a risk of esophageal adenocarcinoma 30 to 60 times that of the general population with an incidence rate of over 100 times that of the general population. Esophageal adenocarcinoma has increased dramatically over the past few decades with specialized intestinal metaplasia being the most important risk factor for the development of dysplasia and cancer. Barrett's esophagus develops in the presence of persistent gastroesophageal reflux, which is an independent risk factor for adenocarcinoma. Other risk factors for adenocarcinoma in patients with Barrett's esophagus include length of Barrett's epithelium, low-grade dysplasia, and high-grade dysplasia. New data concerning the pathophysiology and biology of Barrett's epithelium may provide answers to prevent or treat esophageal cancer. This article briefly reviews Barrett's esophagus and focuses on the risk factors associated with its progression to adenocarcinoma.