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Familiality in Barrett's esophagus, adenocarcinoma of the esophagus, and adenocarcinoma of the gastroesophageal junction.

BACKGROUND AND AIM: The familial aggregation of Barrett's esophagus, adenocarcinoma of the esophagus, and adenocarcinoma of the gastroesophageal junction, jointly termed familial Barrett's esophagus, may represent a complex genetic trait. The aim of this study was to determine the proportion of patients with these diseases who have familial Barrett's esophagus. METHODS: Information on gastroesophageal reflux symptoms, known risk factors for Barrett's esophagus, and family history of Barrett's esophagus and cancers, was collected at six hospitals using a structured questionnaire from probands with either long-segment Barrett's esophagus, adenocarcinoma of the esophagus, or adenocarcinoma of the gastroesophageal junction. Family history of Barrett's esophagus or esophageal cancer in a first- or second-degree relative was determined by reviewing medical records of all relatives reported to be affected. RESULTS: Seventy one of 411 (17.3%) probands reported an affected first- and/or second-degree relative. Upon review of medical records of the reportedly affected relatives, familial Barrett's esophagus was definitively determined in the case of 30 (7.3%) probands comprising 17 of 276 (6.2%) with Barrett's esophagus, 11 of 116 (9.5%) with adenocarcinoma of the esophagus, and 2 of 21 (9.5%) with adenocarcinoma of the gastroesophageal junction. The diagnosis in the relative reported by the proband to be affected was found not to be Barrett's esophagus or adenocarcinoma in 15 (3.6%) cases. The diagnosis could not be determined in 26 (6.3%) cases in which the proband reported an affected relative. There were no significant differences in age of disease onset, gender, race, or gastroesophageal reflux symptoms between definitive familial Barrett's esophagus probands and nonfamilial probands. CONCLUSION: Familial Barrett's esophagus can be confirmed in 7.3% of persons presenting with Barrett's esophagus, adenocarcinoma of the esophagus, or adenocarcinoma of the gastroesophageal junction.

Adenocarcinoma↗

Comparison of kinome profiles of Barrett's esophagus with normal squamous esophagus and normal gastric cardia.

The precursor metaplastic mucosal lesion that predisposes for esophageal adenocarcinoma is Barrett's esophagus. Because the signal transduction events that occur in Barrett's esophagus are poorly understood, this study aimed at generating a comprehensive description of cellular kinase activity in Barrett's esophagus, normal squamous esophagus, and gastric cardia to gain more insight into the pathogenesis of Barrett's esophagus. Peptide arrays, exhibiting 1,176 specific consensus sequences for protein kinases, were used to produce a global analysis of cellular kinase activity in biopsies of Barrett's esophagus, and results were compared with the neighboring cardia and squamous epithelia. Several differences in kinase activity using immunoblot analysis and enzyme activity assays were validated in biopsies of 27 Barrett's esophagus patients. Three unique kinome profiles are described and compared. We identified cascades of activated kinases showing that mitogen-activated protein kinase and epidermal growth factor receptor activity are both significantly altered in Barrett's esophagus compared with squamous and gastric cardia epithelia. Another novel finding is that the glycolysis pathway is significantly up-regulated in Barrett's esophagus, which is illustrated by an up-regulated pyruvate kinase activity. Here, the unique kinome profile of Barrett's esophagus is made available as a comprehensive database. Several signaling pathways are revealed as specifically expressed in Barrett's esophagus when compared with the adjacent normal epithelia. These unique findings provide novel insight in the pathogenesis of Barrett's esophagus that will ultimately help to resolve the increasing problem of Barrett's esophagus and prevention of esophageal adenocarcinoma.

Adult↗

Prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction.

The prevalence and characteristics of Barrett esophagus in patients with adenocarcinoma of the esophagus or esophagogastric junction are uncertain. We studied 61 consecutive esophagogastrectomy specimens with adenocarcinoma, which were subjected to extensive histopathologic examination. Barrett esophagus was found in 64% of the cases (39 of 61), but had been recognized in only 38% of the patients with Barrett-associated carcinoma who had undergone preoperative endoscopy with biopsy (13 of 34). The median extent of Barrett esophagus with adenocarcinoma was 5 cm (range, 1 cm to 12 cm), and distinctive-type ("specialized") Barrett mucosa predominated (35 of 39; 90%). The Barrett adenocarcinomas were centered in the distal esophagus 2 cm +/- 0.3 cm above the esophagogastric junction. The patients with Barrett adenocarcinoma showed a striking predominance of white men (34 of 39; 87%) in contrast to gastric adenocarcinoma cases (21 of 69; 30%) and to Barrett patients without carcinoma or dysplasia (75 of 149; 50%), but similar to patients having adenocarcinoma of the esophagus or esophagogastric junction without demonstrable Barrett esophagus (16 of 22; 73%). Our findings suggest that most adenocarcinomas of the esophagus or esophagogastric junction are Barrett carcinomas, rather than gastric cardiac cancers or other types of esophageal adenocarcinoma; most Barrett adenocarcinomas occur in short segments of Barrett esophagus, which may be difficult to detect at endoscopy; and white men with Barrett esophagus may constitute a clinically identifiable at-risk group suitable for surveillance.

Adenocarcinoma↗

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.

Adenocarcinoma↗

Squamous carcinoma of the esophagus in patients with Barrett esophagus.

Adenocarcinoma of the esophagus is a well-known complication of Barrett esophagus, especially in white men. We present three cases of squamous carcinoma of the esophagus in Barrett patients. All three patients were white men. None had a history of symptomatic gastroesophageal reflux or of Barrett esophagus, but all had substantial usage of alcoholic beverages and tobacco. All three tumors were located in squamous-lined mucosa above the Barrett mucosa. Columnar epithelial dysplasia was present in the Barrett mucosa of two of our patients, and the third patient had a squamous carcinoma of the pharynx. Squamous carcinoma represented 2% of Barrett-associated esophageal carcinomas at our institution in 1980 through 1986. Five additional cases were found in the literature, and all were also in white men. This demographic predominance stood in striking contrast to the 26% prevalence of white patients among those with squamous carcinoma of the esophagus at our institution (P less than 0.0002) and to the 50% prevalence of white men among our patients with Barrett esophagus (P less than 0.02). Two of the literature cases also had substantial alcohol and tobacco usage and had synchronous adenocarcinoma arising in Barrett mucosa. Our findings of a strikingly high prevalence of white men and of multifocal neoplastic changes in the upper aerodigestive tract suggest a pathogenetic relationship between squamous carcinoma of the esophagus and Barrett esophagus, possibly due to alcoholic beverage and tobacco usage. Endoscopic surveillance of Barrett patients for early detection of adenocarcinoma has been recommended; contemporaneous evaluation of the squamous-lined esophagus by biopsy and cytopathology may be advisable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus.

OBJECTIVES: Barrett's esophagus is associated with adenocarcinoma of the cardia and esophagus, regardless of its extent. The aim of this study was to compare the prevalence and incidence of dysplasia and adenocarcinoma in short segment and traditional long segment Barrett's esophagus. METHODS: Seventy-four patients with short segment Barrett's and 78 with traditional Barrett's entered the study. RESULTS: There were no significant differences in age or gender between the two groups of patients with Barrett's esophagus. A greater percentage of patients with short segment barrett's were black (p = 0.04). The prevalence of dysplasia at diagnosis in patients with short segment Barrett's was 8.1% versus 24.4% in patients with traditional Barrett's (p < 0.007). Adenocarcinoma was noted at diagnosis only in patients with traditional Barrett's (p < 0.0005). Twenty-six patients with short segment Barrett's and 29 with traditional Barrett's were followed prospectively for 12-40 months. Dysplasia developed during follow-up in two patients with short segment Barrett's and in six patients with traditional Barrett's (p < 0.05). Neither high grade dysplasia nor cancer developed in any patients with short segment Barrett's. High grade dysplasia did develop in two patients with traditional Barrett's esophagus, and mucosal adenocarcinoma developed in one. The frequency of dysplasia on the latest surveillance examination continued to be significantly higher for patients with traditional Barrett's (p = 0.03). Follow-up surveillance biopsy specimens of Barrett's mucosa frequently demonstrated an absence of goblet cells in patients with short segment Barrett's compared with patients with traditional Barrett's (p < 0.0001). CONCLUSIONS: The prevalence of dysplasia or adenocarcinoma and the incidence of dysplasia in patients with traditional Barrett's esophagus are significantly higher than in patients with short segment Barrett's esophagus. Further prospective surveillance is required to determine whether the incidence of adenocarcinoma in patients with short segment Barrett's esophagus is significantly lower.

Adenocarcinoma↗

Is Barrett's esophagus the precursor of most adenocarcinomas of the esophagus and cardia? A biochemical study.

OBJECTIVE: To obtain biochemical evidence that Barrett's esophagus (BE) is the precursor of most adenocarcinomas (Adc) of the esophagus and cardia. SUMMARY BACKGROUND DATA: Based on morphologic data, BE was previously proposed as the precursor of most Adc of the esophagus. This hypothesis would receive strong support if biochemical evidence were found to demonstrate a pattern common to BE and Adc of the esophagus and cardia. METHODS: We studied the presence of intestinal-type proteins sucrase-isomaltase (SI) and crypt Cell Antigen (CCAg) in BE, Barrett's Adc, and esophageal-cardial Adc without BE. In each case specimens were collected from normal esophagus, stomach, tumor, and BE mucosa when present. To study related conditions, five specimens of peptic esophagitis and of squamous cell carcinoma were also analyzed. An indirect immunofluorescence technique was employed and sections were analyzed with laser confocal microscopy imaging. RESULTS: Most Barrett's mucosa specimens stained positively for SI (93%) and CCAg (89%). These proteins were detected in BE independently of the type of metaplasia, the coexistence of dysplasia, or the presence of associated Adc. SI and CCAg were present in 25 (96%) and 24 (92%) of the cases of Adc respectively. No statistical difference was detected in SI and CCAg expression between Adc samples with and without BE, between BE and Adc samples with or without BE, and between tumors located in the esophagus versus the cardia. No staining for these proteins was detected in stomach or esophageal mucosa, in submucosal glands of the esophagus, in peptic esophagitis or squamous cell carcinoma. CONCLUSION: These data show that BE and Adc of the esophagus and cardia have a similar phenotype and support the hypothesis that most of these tumors probably originate from preexisting BE.

Adenocarcinoma↗

The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry.

OBJECTIVE: The reported incidence of adenocarcinoma in Barrett's esophagus is variable. The aim of this study was to determine the incidence of dysplasia and adenocarcinoma in a population of patients with Barrett's esophagus followed prospectively and to compare these findings with other series. METHODS: All patients enrolled in the Cleveland Clinic Foundation's Barrett's esophagus registry from 1979 to 1995 were followed. Barrett's esophagus was defined as intestinal metaplasia anywhere in the tubular esophagus. The incidence of dysplasia and adenocarcinoma in these patients was recorded systematically. RESULTS: A total of 136 patients (91 male, 45 female) were followed in an endoscopic surveillance program for a mean of 4.2 yr and a total of 570 patient-years of follow-up. Thirty patients (22%) had short segment Barrett's esophagus. Two adenocarcinomas developed during follow-up, yielding an incidence of one per 285 patient-years of follow-up. Low grade dysplasia developed in 24 patients, whereas high grade dysplasia developed in four patients. CONCLUSIONS: Our study suggests that the incidence of adenocarcinoma in Barrett's esophagus is lower than initially thought. However, large multicenter studies are required to clarify the epidemiological and clinical factors related to the development of dysplasia and adenocarcinoma in Barrett's esophagus.

Adenocarcinoma↗

[Barrett's esophagus associated to caustic stenosis of the esophagus].

BACKGROUND: The esophageal stenosis secondary to the ingestion of caustic products is frequent in Brazil, mainly due to an attempt suicide. The Barrett's esophagus is consequence of the chronic gastroesophageal reflux. The literature consulted showed that are a rare association. CASUISTIC AND METHODS: From 1981 to 2000 were admitted and treated in the "Gastrocentro" State University of Campinas, SP, Brazil, 120 patients presenting caustic stenosis of the esophagus, and during the follow-up were found nine cases with Barrett's esophagus associated (7,5%). The time of caustic ingestion varied from 4 years to 54 years (mean 29 years), and they were four males and five females, eight whites and one black, with the mean age of 57,7 years (43 to 72 years). RESULTS: All the cases presented dysphagia and the flexible upper endoscopy showed stenotic areas and caustic esophagitis sequels. Three patients referred symptoms of gastroesophageal reflux, but hiatus hernia were found in only one case. The Barrett's esophagus was found in the middle third of the esophagus above the stenotic areas in three cases, and in the distal third in six cases. The dysphagia was treated with periodic esophageal dilatations. Two patients presenting severe symptoms of reflux were submitted to modified Nissen fundoplication by videolaparoscopy, with good results. CONCLUSIONS: The Barrett's esophagus in these patients could be associated to the caustic ingestion, because it is not situated in the distal third of the esophagus, as commonly found in reflux esophagitis. Its is very important the follow-up and biopsies of the Barrett's esophagus, due to the possibility of malignancy.

Adult↗

Recent advances in Barrett's esophagus: short-segment Barrett's esophagus and cardia intestinal metaplasia.

The recent rapid increase in the incidence of adenocarcinoma of the distal esophagus and the gastric cardia has generated significant interest in the premalignant lesion, Barrett's esophagus. The traditional definition of Barrett's esophagus included the presence of 3 cm or greater of columnar mucosa in the distal esophagus. Studies have clarified that intestinal metaplasia was not only the most common and distinctive type of epithelium detected within the columnar mucosa, but also the one with greatest malignant potential; therefore, Barrett's esophagus has come to be defined by the histological presence of intestinal metaplasia. Previous studies evaluating the association of esophageal adenocarcinoma with Barrett's esophagus have only included patients with traditional or long-segment Barrett's esophagus. However, recent studies have suggested that dysplasia and adenocarcinoma can also be associated with short-segment Barrett's esophagus (SSBE), ie, less than 3 cm of columnar mucosa. Data are also emerging regarding the significance of intestinal metaplasia detected in biopsy specimens obtained immediately below the gastroesophageal junction, ie, from the gastric cardia. However, the premalignant potential of cardia intestinal metaplasia (CIM) is unknown at this time. Although the exact incidence of adenocarcinoma in SSBE is not known, endoscopic surveillance of such patients, although controversial, appears to be prudent at this time. With the currently available information, routine biopsy of a normal-appearing squamocolumnar junction is not advocated. This review critically evaluates and summarizes recent data on SSBE and CIM.

Aged↗

Barrett's esophagus and adenocarcinoma of the esophagus and gastroesophageal junction.

Since 1985, 57 patients with adenocarcinoma of the esophagus and gastroesophageal (GE) junction have undergone surgical resection. In this group, 16 of the tumors arose in a Barrett's esophagus. There was a significant predilection toward white men above the age of 55 (15/16; 94%) in this subgroup. The mean proximal extent of abnormal columnar involvement was 5.4 cm above the gastroesophageal junction (range 2.5 to 11 cm). The mean location of the neoplasm centered in the distal esophagus 1.8 +/- 0.5 cm above the gastroesophageal junction. During the same time period, 30 patients with Barrett's esophagus were seen without associated adenocarcinoma. There were no statistical differences in the proximal extent of columnar involvement or the presence of reflux symptoms between the two groups. There were no significant differences in age, smoking history, and alcohol consumption between patients with benign or malignant Barrett's esophagus as compared to those with adenocarcinoma of the gastroesophageal junction not associated with Barrett's mucosa. The marked male predominance seen in the group with malignant Barrett's esophagus was in contrast to the benign cases (16/30; 53%) but was similar to the adenocarcinoma group, without recognized Barrett's esophagus (38/41; 93%). The mean location of the tumor in the latter was 0.9 +/- 1.2 cm above the gastroesophageal junction and was comparable to the location in the group with Barrett's adenocarcinoma. The 4-year survival rate of patients in the non-Barrett's adenocarcinoma group is approximately 30%. Of those with Barrett's adenocarcinoma, the present 4-year survival rate is 60%. The demographic and morphometric similarities between the Barrett's and non-Barrett's adenocarcinoma groups may be of primary importance in determining the true clinical prevalence of Barrett's adenocarcinoma. Our findings suggest that the sensitivity of endoscopic surveillance may be improved if biopsy specimens are concentrated within the distal 3 cm of the esophagus and the esophagogastric junction. Finally, the reason for the current difference in survival between the Barrett's and non-Barrett's adenocarcinoma groups is uncertain but may be related to endoscopic surveillance permitting earlier diagnosis and treatment.

Adenocarcinoma↗

Length of the esophagus in patients with gastroesophageal reflux disease and Barrett's esophagus compared to controls.

BACKGROUND: It is a current opinion among surgeons that the esophagus is shorter in patients with reflux disease and particularly in those with complicated Barrett's esophagus. However, objective evidence of this is scarce. Therefore we attempted to determine the occurrence and magnitude of this phenomenon among our patients. METHODS: One hundred ninety control subjects, 77 patients with severe erosive esophagitis, 74 with Barrett's esophagus, and 29 with complicated Barrett's esophagus (ulcer, stenosis) were grouped according to height. The length of the esophagus was determined by standard manometric study, measuring the distance from the crycopharingeal sphincter to the distal limit of the lower esophageal sphincter. Values were expressed in cm as the mean +/- SD. RESULTS: The esophageal length according to height was 1 to 2 cm shorter in patients compared to controls, but these differences were not significant. CONCLUSIONS: No differences were found between patients with progressive severity of the disease. This study confirms that the presence of a so-called "short esophagus" does not exist or is not relevant in our patients with gastroesophageal reflux disease, including those with complicated Barrett's esophagus.

Adult↗

Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates.

OBJECTIVE: To evaluate differences in clinical appearance and survival rates in patients operated on for adenocarcinoma in the distal esophagus with and without Barrett epithelium. DESIGN: Prospective clinical study. SETTING: University hospital, Sweden. PATIENTS: Fifty-four patients with adenocarcinoma in the distal esophagus with (n = 17) or without (n = 37) Barrett epithelium. INTERVENTION: Esophagectomy or total gastrectomy. MAIN OUTCOME MEASURES: Preoperative symptoms, endoscopic results, and histological findings; postoperative morbidity, mortality, and survival rates. RESULTS: The main indication for the endoscopic examination that revealed tumor in the group with Barrett esophagus was reflex-related symptoms in 6 patients (routine Barrett examination, n = 4; symptoms of reflux, n = 2), symptoms related to upper gastrointestinal tract bleeding in 6, and malignant symptoms in 5 (dysphagia, n = 4; weight loss, n = 1). In contrast, most patients in the cardia cancer group were admitted because of malignant symptoms (dysphagia, n = 26; epigastric pain, n = 9; and anemia, n = 2). Ten of 17 patients in the Barrett esophagus cancer group had tumors limited to the mucosa and submucosa only. In 1 patient the tumor grew into the muscular layer but not through it. In the remaining 6 patients the tumor did grow through the muscular layer and lymph node metastases were found. Wall penetration was found in 30 patients and metastases to lymph nodes in 29 patients in the cardia cancer group. The hospital mortality rate was 0 of 17 patients in the Barrett cancer group and 2 of 37 patients in the cardia cancer group. In the patients operated on for adenocarcinoma in the distal esophagus, a better long-term survival rate was seen in those with Barrett epithelium (50%) than in those without this metaplasia (10%) (log rank P = .005; X2 = 7.80). CONCLUSIONS: Concomitant Barrett epithelium improved the prognosis for patients with adenocarcinoma in the distal esophagus. Probably the reason for this was a higher rate of early-stage disease, because symptoms of gastroesophageal reflux and other benign disorders, not dysphagia, were most common in patients with adenocarcinoma without Barrett epithelium in the distal esophagus.

Adenocarcinoma↗

Multiple early esophageal cancers arising from Barrett's esophagus, and a review of cases of early adenocarcinoma in Barrett's esophagus in Japan.

A case of early esophageal adenocarcinoma arising in Barrett's esophagus is reported. Many cases of Barrett's esophagus, which is considered a premalignant condition, have been reported in Western countries, but few cases have been reported in Japan. The patient, a 53-year-old man with nausea and vomiting, was a drinker (four glasses wine/day for about 30 years), but did not smoke. He had had a hiatal hernia of the esophagus. Since endoscopic biopsies demonstrated an early adenocarcinoma in Barrett's esophagus, subtotal esophagectomy was performed. In the resected esophageal material, Barrett's esophagus was seen to extend for 12 cm. In addition to the cancer detected preoperatively as a 0-IIc lesion (1.5 cm in diameter), a 0-IIb lesion (1.5 cm in diameter) was also detected in the postoperative survey. Both lesions were well differentiated adenocarcinoma that had invaded only into the lamina propria mucosa. The 23 cases of early adenocarcinoma in Barrett's esophagus that have been reported in Japan were reviewed, and it was learned that the present case is the second of multiple early cancer arising in Barrett's esophagus so far reported in Japan.

Adenocarcinoma↗

Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus.

OBJECTIVES: The presence of a protective adherent mucus gel barrier against gastric reflux in the healthy esophagus is uncertain. The aim was to characterize the surface mucin composition and determine the extent of any adherent mucus gel layer on the normal esophagus, and compare this with that in Barrett's esophagus. METHODS: Isolated surface mucins were characterized by density centrifugation, gel filtration chromatography, and chemical composition. Adherent surface mucus was visualized in situ on unfixed and cryostat sections of mucosa and biopsies using a method that preserves mucus layer thickness. RESULTS: There was a complete absence of adherent mucus gel layers on normal human, pig, and rat esophagi. This was in contrast to the thick adherent mucous layer (median thickness = 100-200 microm) seen on the corresponding gastric mucosa. Small quantities of glycoprotein with a composition characteristic of a secretory mucin were isolated from the pig esophagus surface. The mucin, density range between 1.44 and 1.48 g x ml(-1), contained 80% carbohydrate and was rich in serine, threonine, and proline. The mucin fragmented into smaller glycoprotein units on proteolysis and partially on reduction. Cryostat sections from columnar-lined esophageal biopsies had a substantial adherent surface mucous layer (median thickness = 90 microm, interquartile range = 84-94 microm) staining for neutral mucins (gastric-type epithelium) and acidic mucins (intestinal metaplasia). CONCLUSIONS: A secretory mucin, with an analysis distinct from that of gastric or salivary mucin, is present in very small quantities on the esophageal mucosa and in amounts insufficient to form an adherent gel layer. It is unlikely that mucus has a role in protecting the normal esophagus against reflux. However, an adherent mucous layer was observed over columnar-lined esophagus, and this may protect against reflux.

Animals↗

Prevalence of intestinal metaplasia in the distal esophagus in patients endoscopically suspected for short Barrett's esophagus.

The clinical importance of Barrett's esophagus is related to its correlation to adenocarcinoma. The diagnosis is based on histologic demonstration of specialized intestinal metaplasia in the distal esophagus. The aim of this study was to assess the prevalence of intestinal metaplasia of the distal esophagus in a population submitted to gastroscopy not selected for reflux disease, and with columnar lined distal esophagus between 0.5 and 2 cm. Four biopsies in the distal esophagus were done in 224 patients undergoing routine gastroscopy. Patients were not selected for gastroesophageal reflux. Other clinical parameters were recorded to assess any possible association. In four Centers 224 patients received endoscopy with biopsies demonstrating specialized intestinal metaplasia in 21% of cases. No association was present among the patients with esophagitis or hiatal hernia, as well as with reflux symptoms. A significant association was present in over 70 (females), as well as with the presence of antral intestinal metaplasia demonstrated in 45 patients by gastric biopsies. No other significant associations were present. Biopsy samplings can diagnose the presence of intestinal metaplasia during endoscopy in patients endoscopically suspected for Barrett's esophagus: at present there is not clear evidence to promote this screening to achieve mortality reduction of esophageal adenocarcinoma.

Aged↗

A multigene expression panel for the molecular diagnosis of Barrett's esophagus and Barrett's adenocarcinoma of the esophagus.

In order to identify genes or combination of genes that have the power to discriminate between premalignant Barrett's esophagus and Barrett's associated adenocarcinoma, we analysed a panel of 23 genes using quantitative real-time RT-PCR (qRT-PCR, Taqman and bioinformatic tools. The genes chosen were either known to be associated with Barrett's carcinogenesis or were filtered from a previous cDNA microarray study on Barrett's adenocarcinoma. A total of 98 tissues, obtained from 19 patients with Barrett's esophagus (BE group) and 20 patients with Barrett's associated esophageal adenocarcinoma (EA group), were studied. Triplicate analysis for the full 23 gene of interest panel, and analysis of an internal control gene, was performed for all samples, for a total of more than 9016 single PCR reactions. We found distinct classes of gene expression patterns in the different types of tissues. The most informative genes clustered in six different classes and had significantly different expression levels in Barrett's esophagus tissues compared to adenocarcinoma tissues. Linear discriminant analysis (LDA) distinguished four genetically different groups. The normal squamous esophagus tissues from patients with BE or EA were not distinguishable from one another, but Barrett's esophagus tissues could be distinguished from adenocarcinoma tissues. Using the most informative genes, obtained from a logistic regression analysis, we were able to completely distinguish between benign Barrett's and Barrett's adenocarcinomas. This study provides the first non-array parallel mRNA quantitation analysis of a panel of genes in the Barrett's esophagus model of multistage carcinogenesis. Our results suggest that mRNA expression quantitation of a panel of genes can discriminate between premalignant and malignant Barrett's disease. Logistic regression and LDAs can be used to further identify, from the complete panel, gene subsets with the power to make these diagnostic distinctions. Expression analysis of a limited number of highly selected genes may have clinical usefulness for the treatment of patients with this disease.

Adenocarcinoma↗

In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: We studied the feasibility of endoscopic optical coherence tomography imaging in esophageal disorders, including Barrett's esophagus and Barrett-related adenocarcinoma. Optical coherence tomography is a high-resolution cross-sectional imaging technique with a resolution of almost 10 microm. PATIENTS AND METHODS: The mucosal architecture of reflux esophagitis (n = 9) and Barrett's esophagus (n = 9) including Barrett-related esophageal cancer (n = 6) was studied by optical coherence tomography imaging. RESULTS: In different stages of reflux esophagitis edema, fibrinoid deposits, or loss of the epithelial layer were observed. Optical coherence tomography images of Barrett's esophagus substantially differed from normal esophagus, reflux esophagitis, and esophageal carcinoma. A stratified structure of the mucosa was still preserved in Barrett's esophagus. However, images of Barrett-related cancer lacked the regular structure of the esophagus. CONCLUSIONS: The high consistency of the first optical coherence tomography findings, the resolution of up to 10 microm, and the distinct pattern of normal, inflammatory, premalignant and malignant tissues make optical coherence tomography a promising method for endoscopically obtained optical biopsy.

Adenocarcinoma↗