Is prophylactic treatment after myocardial infarction evidence-based?

In Barrett's esophagus, the squamous lining of the lower esophagus is replaced by columnar epithelium. Barrett's esophagus is associated with gastroesophageal reflux and an increased risk of the development of esophageal cancer. Endoscopy shows red columnar epithelium in the lower esophagus. Biopsy is needed to confirm intestinal metaplasia. Some cases progress from dysplasia to invasive adenocarcinoma. Medical or surgical antireflux treatment controls symptoms and esophagitis, but Barrett's esophagus remains. Patients are usually followed up by endoscopy for detection of dysplasia or early cancer. For patients with low-grade dysplasia, follow-up is adequate; however, for those with high-grade dysplasia, esophagectomy or experimental endoscopic mucosal ablation is advised.     

Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.     

Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.     

Barrett's esophagus

The columnar replacement of squamous epithelium in the lower esophagus is the result of gastroesophageal reflux. Whether the squamous cells are replaced or undergo metaplasia is still conjectural. This neoepithelium is unstable in the presence of continued reflux and prone to complications of stricture, ulceration, and adenocarcinoma. Considerable evidence supports the hypothesis that duodenal contents play a role in the development of Barrett's esophagus and its complications. The increasing incidence of adenocarcinoma in Barrett's esophagus is of concern in the Western World. Surveillance programs in some centers have been successful in early diagnosis, and excellent survival periods have been reported following resection in these cases. Both medical and surgical antireflux treatment is successful in symptom relief, but even in the absence of symptoms, reflux may continue. Surgery offers better overall results than proton pump inhibition of gastric acid and has been more popular since less aggressive (minimally invasive) techniques have been popularized. Mucosal ablation and antireflux measures by medicine or surgery are still in the experimental stages but hold considerable promise for the future.     

Barrett's esophagus. Clinical review of 26 cases

Barrett's esophagus was diagnosed in 26 men in a five-year period by demonstrating esophageal specialized columnar epithelium in target biopsies obtained at endoscopy or in peroral suction biopsies of the esophageal mucosa. The clinical, radiologic and manometric features of these patients were reviewed retrospectively. Esophageal lesions associated with this epithelium included distal and midesophageal strictures and ulcers, alone or in combination, or simply esophagitis. One patient had an associated adenocarcinoma. Twenty of 26 (77%) had heartburn or regurgitation, 16 (62%) had easily elicited reflux of barium while supine and 16 of 17 tested had lower esophageal sphincter pressure in the incompetent range. Ninety-six percent had one or more of these parameters positive. This series demonstrates a wide spectrum of esophageal lesions in Barrett's esophagus, and supports the concept that this lesion occurs as a consequence of gastroesophageal reflux and erosive esophagitis. The case of adenocarcinoma in this series adds to the concern that the columnar lined lower esophagus may be a premalignant lesion.     

Detection of donor-derived Langerhans cells in MHC class II immunodeficient patients after allogeneic bone marrow transplantation

Barrett's esophagus can progress to dysplasia and adenocarcinoma. Although the incidence of adenocarcinoma of the gastroesophageal junction has increased suddenly in the United States and Europe, we do not know how much of this increase is related to Barrett's esophagus. Interest in mucosal cell abnormalities at the gastroesophageal junction has led researchers to re-examine short-segment Barrett's esophagus. In this recently described condition, specialized columnar epithelium is found in the distal 2 to 3 cm of the esophagus, yet it is not clear how it relates to conventional long-segment Barrett's esophagus, in which the metaplastic epithelium extends higher than 2 to 3 cm above the squamocolumnar junction. The reported prevalence of short-segment Barrett's esophagus found on diagnostic endoscopy varies from 8% to 32%. This wide variation would be lessened by standardized location of biopsy specimens and of endoscopic and histologic staining techniques. Based on the information available, it is apparent that the age range and sex ratios are similar. Although reflux symptoms may be more common in short-segment Barrett's esophagus, disturbances in esophageal motility are less severe and there is less reflux as measured by continuous pH monitoring. Furthermore, recognized complications of Barrett's esophagus, such as ulceration, stricture, high-grade dysplasia, and adenocarcinoma, appear to be uncommon in short-segment Barrett's esophagus.     

Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett's esophagus

Barrett's esophagus, morphologically analogous to gastric intestinal metaplasia, often precedes the development of esophageal adenocarcinoma. In the stomach, expression of sulfomucins and aberrant Lewis(a) (Le[a]) antigen is an excellent predictor of premalignant progression, and Helicobacter pylori infection is a crucial determinant for the development of atrophy, metaplasia, and adenocarcinoma. In the esophagus, the significance of sulfomucin expression is controversial, the aberrant expression of Le(a) has not been explored, and the role of H pylori in the evolution of preneoplastic conditions is unknown. We investigated in 155 patients referred for endoscopy the association of Barrett's esophagus with expression of sulfomucins, Lewis, secretor, and ABO phenotypes, and H pylori infection. We report a subtype of intestinal metaplasia, present in all patients with esophageal adenocarcinoma, similar to gastric intestinal metaplasia of colonic type (type III or incomplete), that expresses sulfomucins and aberrant Le(a) in goblet and columnar cells. Lewis(a+b-), nonsecretor and blood group A phenotypes, were all positively associated with esophageal adenocarcinoma, suggesting a genetic susceptibility. H pylori infection was detected in 75% of patients with esophageal adenocarcinoma.     

Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor

Barrett's esophagus is found in about 1% of the older population and in 3% to 5% of persons with gastroesophageal reflux. It is acquired more commonly by men and the prevalence increases with age. Most cases in the population remain undiagnosed. The incidence of adenocarcinoma of the esophagus and esophagogastric junction is increasing, both being related to Barrett's esophagus. Small areas of intestinal metaplasia are common but of uncertain significance.     

Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP)

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett's esophagus, but clinical studies in patients with adenocarcinoma arising in Barrett's esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatic volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett's esophagus, and 14 patients with early adenocarcinoma arising in Barrett's esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopic Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett's esophagus and was highest in patients with early carcinoma in Barrett's esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett's esophagus and 11 (78.6%) of 14 patients with early adenocarcinoma in Barrett's esophagus. Nissen fundoplication but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett's esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone.     

Incidence of Barrett's adenocarcinoma in an Italian population: an endoscopic surveillance programme. Gruppo Operativo per lo Studio delle Precancerosi Esofagee (GOSPE)

BACKGROUND: Barrett's oesophagus is a premalignant condition leading to adenocarcinoma. The incidence of adenocarcinoma of the oesophagus and the gastrooesophageal junction is rapidly increasing in the USA, northern and central Europe. Data from southern Europe are still unavailable. OBJECTIVE: To evaluate the incidence of oesophageal adenocarcinoma in a large cohort of Italian patients with Barrett's oesophagus. METHODS: A total of 344 patients (253 males and 91 females, age range 19-75 years) with histologically proven Barrett's oesophagus (length of metaplasia > or = 3 cm) were enrolled from November 1987 to June 1995. Endoscopic and histological examinations were scheduled at yearly intervals. RESULTS: One hundred and eighty-seven patients complied with the follow-up. The mean duration of the follow-up period was 36 months (total follow-up 562 patient-years; range 12-90 months). Low grade dysplasia was found in five patients at the initial examination. During the surveillance period, dysplasia increased in frequency as well as in severity and was found exclusively in the intestinal type of Barrett's oesophagus. In all, dysplastic changes were found in seven patients (five low grade and two high grade) and adenocarcinoma developed in three patients during the follow-up. In a single case, both adenocarcinoma and specialized columnar epithelium developed without any evidence of dysplasia or intestinal metaplasia at the previous follow-up examination. This prospective study shows an incidence of adenocarcinoma in Barrett's oesophagus of 1/187 patient-years. When only patients with specialized columnar epithelium were considered, the risk of adenocarcinoma was 1/88 patient-years. CONCLUSION: The present report shows that the incidence of adenocarcinoma in Italian Barrett's oesophagus patients is in the range of that reported from other Western countries.     

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 < or = 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.     

Comorbidities and prediction of length of hospital stay

Columnar epithelium-lined esophagus (Barrett's esophagus) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Columnar epithelium resembling intestinal metaplasia (IM) is especially important, since it is considered to be a premalignant condition. The aim of this study was to define the sulfated carbohydrate chain of mucin and its core peptide profile in Barrett's esophagus (BE) and to compare it with the profile in Barrett's adenocarcinoma and lower esophageal adenocarcinoma. The sulfated carbohydrate chain was not expressed in 16 specimens of normal esophageal epithelium, but in BE, it was expressed in 50% (8/16) of the specimens. This chain was detected in 100% (7/7) of esophageal adenocarcinoma specimens, including four cases of Barrett's adenocarcinoma. These data suggest that the sulfated carbohydrate chain may be associated with malignant phenotype of the esophagus. MUC1 core peptide was positive in 87% (13/15) of BE specimens and in 29% (2/7) of the esophageal adenocarcinoma specimens. MUC2 core peptide was present in 57% (8/14) and 43% (3/7) of these specimens, respectively. These data suggest that Barrett's epithelium, which is similar to IM, but not normal esophageal epithelium, expresses the sulfated sugar chain which is known to be present in gastric IM and colonic mucosa. However, there was no significant correlation between the expression of the sulfated sugar chain and the expression of either mucin core peptide MUC1 or MUC2. Thus, this carbohydrate chain may be expressed on as yet unidentified core proteins, other than MUC1 or MUC2 core peptide, in BE and esophageal adenocarcinoma. Identification of these proteins may be very important in helping to detect premalignant status in BE.     

Gastroesophageal reflux disease in patients with columnar-lined esophagus

Columnar-lined esophagus or Barrett's esophagus is closely associated with gastroesophageal reflux disease. Animal and human studies have shown not only acid but duodenogastroesophageal reflux acting in synergy with acid causes the most esophageal injury. Patients with Barrett's esophagus manifest typical and atypical symptoms of reflux. Ten percent to 25%, however, have clinically silent reflux. Early diagnosis is essential for this disease as it is a risk factor for the development of adenocarcinoma of the esophagus.     

National survey of stress ulcer prophylaxis

OBJECTIVE: Adenocarcinoma around the esophagogastric junction (EGJ) is increasing in incidence, and is frequently associated with areas of macroscopic or microscopic intestinal metaplasia (IM). The aim of this study was to define the incidence and type of metaplastic changes in the cardia and at the EGJ in symptomatic patients in whom there was no endoscopic columnar segment. METHODS: Patients attending for open-access gastroscopy had three sets of endoscopic biopsies taken at 3-cm intervals, from cardia, EGJ, and distal esophagus. Hematoxylin and eosin, Alcian blue/PAS (AB/PAS), and high-iron diamine/Alcian blue (AB/HID) were used to define and characterize IM. RESULTS: Of 225 patients, eight (4%) had carcinoma, eight (4%) had conventional long-segment Barrett's esophagus, 15 (7%) showed endoscopic short-segment Barrett's change, with no endoscopic Barrett's in 194 (86.2%). Of the latter, 34 (17.5%) had IM at the EGJ, and nine (4.6%) had IM at the cardia on hematoxylin and eosin. Acid mucin stains were positive at the EGJ in 135 (69.6%) and at the cardia in 75 (38.7%). Metaplasia at the EGJ was associated with sulphomucins (p < 0.0001) and involved the surface glandular epithelium (p < 0.0001) more frequently than the cardia. Metaplasia was not related to reflux symptoms, hiatus hernia, or endoscopic esophageal inflammation. Ninety percent of those with IM detectable by hematoxylin and eosin were taking acid suppression, compared with 72.8% overall. CONCLUSIONS: Intestinal metaplasia is very common at the esophagogastric junction and gastric cardia, with marked differences in incidence and characteristics of mucin staining between the two sites. The relationship of intestinal metaplasia to the development of carcinoma is yet to be determined.     

K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus

OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal carcinomas, K-ras point mutations are thought to be a frequent event. The frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is currently not known. To establish the frequency of K-ras mutations in premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy specimens with Barrett's metaplastic and dysplastic epithelium for point mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from patients with Barrett's oesophagus were histologically classified into biopsies with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by polymerase chain reaction (PCR) with a modified primer for generating a restriction site in the case of wild type in codon 12. Wild-type or point mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12 were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations in K-ras/codon 12 were rarely found in premalignant forms of Barrett's oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites of Barrett's epithelium seems not to be of practical value, the screening for mutations in dysplastic lesions might be helpful to estimate the individual risk for progression of Barrett's epithelium to adenocarcinoma. A further evaluation in larger numbers of patients is needed.     

Recent developments in the molecular characterization of Barrett's esophagus

Barrett's esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett's esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett's esophagus leading to more effective surveillance and treatment.     

Barrett's esophagus: a review

Complications of Barrett's esophagus include ulceration, stricture, hemorrhage, perforation, and the development of malignancy. Barrett's esophagus and adenocarcinoma may be diagnosed simultaneously and that gastroesophageal reflux symptoms may be absent in many cases. Although endoscopic surveillance is justified, no agreement on the frequency can be made. Survival of patients with adenocarcinoma in Barrett's esophagus depends on the stage at diagnosis.     

The surgical management of Barrett's esophagus

Barrett's esophagus is an increasing health concern in most Western countries. The diagnosis is usually made during investigation of patients with symptoms of gastroesophageal reflux disease. The appropriate antireflux procedure, performed in properly selected patients, provides long-term symptomatic relief in 80% to 90% of patients. The effect of reliable and complete control of gastroesophageal reflux on the natural history of Barrett's metaplasia once it has developed and on its prevention in symptomatic patients who have not yet developed Barrett's changes is one of the most important areas of study over the next decade.     

Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization

BACKGROUND: The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barrett's esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barrett's esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barrett's esophagus. METHODS: Eight men and 2 women 43 to 84 years of age with short segments of Barrett's esophagus or traditional Barrett's esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barrett's mucosa. RESULTS: Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS: KTP laser destruction of Barrett's esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barrett's esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barrett's esophagus seems to be feasible and safe in short segments of Barrett's esophagus with dysplasia or early cancer.