Columnar-lined Esophagus Research Articles

Risk factors of early proximal gastric carcinoma in Chinese diagnosed using WHO criteria.

The incidence of proximal gastric carcinoma (PGC) is rising worldwide for unknown reasons. Herein we compare the risk factors of early PGC with distal gastric carcinoma (DGC) in patients treated at a single tertiary hospital in China. Risk factors of 379 consecutive surgically resected early gastric carcinoma (EGC) diagnosed according to the 2010 World Health Organization criteria were studied by reviewing their medical records and esophagogastroduodenoscopy/biopsy findings and interviewing patients and family members for the patients' history of environmental toxin exposure (ETE), dietary habits, family (FCH) and personal cancer history (PCH) and survival. Differences between PGC (n = 115), DGC (n = 264) and age-matched and gender-matched controls (n = 225) were compared. Proportion of early PGC in all EGC patients was increased significantly (P < 0.05). The independent risk factors for both PGC and DGC identified by multivariate analysis were intake of preserved food and little fruit, and gastric mucosal intestinal metaplasia and atrophy (all P < 0.05). Advanced age (odds ratio [OR] 9.83, P < 0.01), PCH (OR 5.09, P < 0.05), a high body mass index (>24 kg/m(2) ) (OR 2.79, P < 0.01) and ETE (OR 2.31, P < 0.05) were independent risk factors for PGC, but not male gender, tobacco or alcohol abuse, hiatus hernia, gastroesophageal reflux disease or columnar-lined esophagus. In contrast, FCH (OR 2.34, P < 0.01) and Helicobacter pylori infection (OR 2.81, P < 0.001) were independent risk factors for DGC. Independent risk factors for PGC in Chinese patients differ from those of DGC or esophageal adenocarcinoma, supporting the classification of PGC as a separate gastric carcinoma entity in the Chinese populations.

Expression of SOX9 and CDX2 in nongoblet columnar-lined esophagus predicts the detection of Barrett's esophagus during follow-up

The diagnosis of Barrett's esophagus in the United States requires both endoscopically evident columnar-lined esophagus and the presence of goblet cells by histology. Currently, there is no consensus on how patients with nongoblet columnar-lined esophagus should be followed. In this study, we investigated whether biomarkers can be used to predict the detection of goblet cells in follow-up biopsies. Patients with nongoblet columnar-lined esophagus were identified. In 13 of these cases, goblet cells were detected in subsequent follow-up endoscopic biopsies (Barrett's group). Additionally, 26 cases that remained negative for goblet cells in follow-up biopsies served as controls. Immunohistochemistry for CDX2, SOX9, BMP4, SHH, and MUC2 was performed on the initial biopsies and graded independently by at least two pathologists in a masked manner. CDX2 was positive in the nongoblet columnar epithelium of 7/13 cases in the Barrett's group and in 4/26 controls (sensitivity 54%, specificity of 85%, odds ratio (OR) 6.4). Strong and diffuse immunoreactivity for SOX9 was detected in 10/13 cases in the Barrett's group and in 1/26 controls (sensitivity 77%, specificity 96%, OR 83.3). Combining CDX2 and SOX9 as a panel increased sensitivity to 85%, although the specificity decreased to 85% (OR 30.3). SHH, BMP4, and MUC2 expression showed no significant difference between the Barrett's and control groups. In patients with nongoblet columnar-lined esophagus, SOX9 and CDX2 may be useful in identifying a subset of patients who have a higher risk of being diagnosed for Barrett's esophagus (developing goblet cells) and need closer follow-up.

Su1725 Detection of Barrett's Esophagus in Columnar-Lined Esophagus by Using Narrow Band Imaging With Magnifying Endoscopy

Su1725 Detection of Barrett's Esophagus in Columnar-Lined Esophagus by Using Narrow Band Imaging With Magnifying Endoscopy

Is carcinoma in columnar-lined esophagus always located adjacent to intestinal metaplasia?: a histopathologic assessment.

Diagnostic criteria for Barrett esophagus in the United States and elsewhere, except the United Kingdom and Japan, include the presence of intestinal metaplasia with goblet cells. We analyzed high-grade dysplasia and adenocarcinoma in a complete series of sections of all interfaces between carcinoma in columnar-lined esophagus (CLE) and the adjacent mucosa, assessed them for the mucosal types present, and calculated the proportion of each mucosal type in each case. The materials were a consecutive series of 100 endoscopic resection cases, comprising a total of 1251 microscopic sections. After excluding cases in which intestinal-type or cardiac-type mucosa was not adjacent to CLE carcinoma, 70 cases remained, for which 885 sections were available. Whether the adjacent mucosa was primarily cardiac or intestinal in type was assessed, as were the patterns of immunostaining for HGM, MUC-2, and MUC-6. Twenty-four (34.3%) of the 70 CLE carcinomas were completely surrounded by cardiac-type mucosa, and 10 (14.3%) were completely surrounded by intestinal-type mucosa. In 13 (18.6%), the entire non-neoplastic mucosa of the endoscopic resection specimen comprised the cardiac type alone without any intestinal type, and only 3 (4.3%) comprised the intestinal type only, without any cardiac type. From these findings, we consider it unproven histogenetically that the background mucosa of CLE carcinoma is predominantly of the intestinal type. CLE carcinoma was not demonstrated to have a close relationship with CLE mucosa with intestinal metaplasia.

Hyperplasia of the submucosal glands of the columnar-lined oesophagus.

To evaluate the presence of multi-layered epithelium (ME) and to compare the distribution, size and morphology of the oesophageal submucosal glands (SMG) beneath reflux exposed metaplastic columnar mucosa with those of normal squamous epithelium in patients with columnar-lined oesophagus (CLO). In eight oesophageal resection specimens, the SMG of the metaplastic segments were significantly larger than those in the squamous segments of patients with CLO (0.81 versus 0.56mm(2) , P=<0.001). There was an accumulation of SMG close to the neosquamocolumnar junction (NSCJ), as indicated by a higher median frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm) and metaplastic segments (0.031 SMG/mm) (P=0.022). The frequency of ME was significantly higher in the metaplastic compared with the normal squamous segments (1/158mm and 1/341mm, respectively, P=0.028) and ME was found almost exclusively (96%) in direct connection with the excretory ducts of SMG. Hyperplasia of SMG in the metaplastic segment, accumulation of SMG near the NSCJ, the presence of ME in connection with the excretory ducts of SMG and metaplasia are all reflux-induced morphological changes, possibly induced by stimulation of progenitors in the excretory ducts of the SMG.

Current issues in Barrett's esophagus and Barrett's-related dysplasia

Surgical pathologists frequently encounter biopsies in patients with Barrett's esophagus (BE), defined as replacement of the normal stratified squamous epithelium of the distal esophagus by metaplastic columnar epithelium containing goblet cells. Thus, one of the primary roles of the pathologist is to definitively identify goblet cells, best done on routine stained sections. It has recently been questioned as to whether goblet cells should be absolutely necessary to render a diagnosis of BE, given immunohistochemical and flow cytometric similarities between columnar-lined esophagus with and without goblet cells. Once a diagnosis of BE is rendered, the pathologist must state, using a simple classification, whether the biopsy is negative for dysplasia or shows dysplasia (low-grade dysplasia or high-grade dysplasia). However, there are a number of known pitfalls in distinguishing dysplasia from reactive epithelium, and it can be similarly difficult to distinguish low-grade dysplasia from high-grade dysplasia. In addition, there are some cases in which the distinction of high-grade dysplasia from intramucosal adenocarcinoma can be challenging. All of these issues are summarized in this paper.

The changing role of the pathologist in the management of Barrett's oesophagus.

Pathological specimens from columnar-lined oesophagus (CLO) comprise a considerable proportion of the workload of gastrointestinal pathologists in Western countries. There remain controversies concerning the diagnostic role of pathology. More recently, in the UK at least, the diagnosis has been regarded as primarily an endoscopic endeavour, with pathology being corroborative and only diagnostic when endoscopic features are equivocal or when there are additional features that make the endoscopic diagnosis unclear. There is also recognition that demonstration of intestinalisation or 'goblet cells' is not paramount, and should not be required for the diagnosis. There have been notable changes in the management of CLO neoplasia: pathologists are centrally involved in its management. Pathological assessment of endoscopic mucosal resection (EMR) specimens provides the most useful means of determining the management of early neoplasia and of determining indications for surgery. This represents an extraordinarily rapid change in management, in that, <10years ago, laborious Seattle-type biopsy protocols were recommended, and high grade dysplasia was an indication for resectional surgery. Now, individual patient management is paramount: multi-professional meetings determine management after biopsy and EMR assessment. One significant change is that major resections are undertaken less often, in Western countries, for CLO neoplasia.

Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC. Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing. Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.

106 Random Biopsies in Endoscopically Normal Esophagus Improve Yield of Recurrent Intestinal Metaplasia After Successful Radiofrequency Ablation

Background: Radiofrequency ablation (RFA) treatment for dysplastic Barrett's Esophagus (BE) is associated with high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence of intestinal metaplasia (IM) in the esophagus is seen in approximately 25% of patients. The endoscopic findings associated with recurrence of IM are poorly described. Methods: We conducted a retrospective study of patients who underwent RFA for BE at University of North Carolina Hospitals between 2006 and 2013. Patients who achieved CEIM with at least two subsequent surveillance endoscopies were included. Patients were excluded if treated for non-dysplastic BE or invasive esophageal adenocarcinoma. Among patients with histologic evidence of recurrent BE during surveillance, we assessed the endoscopic findings associated with the recurrence. All patients had assessment of the distal esophagus by high-resolution white light and narrow band imaging, and all underwent regular biopsies according to a standard four-quadrant, q1cm procedure, as well as biopsy of endoscopically suspicious lesions. Endoscopic signs recorded included esophageal nodules (Paris classifications 0-Ip, 0-Is, 0-IIa), and areas suspicious for recurrent BE based on mucosal color changes. Statistical analysis was performed using SAS (version 9.3). Results: Of 302 patients, 178 met criteria for inclusion. These patients had 673 biopsy sessions (mean 3.8 sessions/pt). In total, 19 patients had histological recurrence of IM in the tubular esophagus (11%). Of these 19, only 5 (26%) had any endoscopic abnormality suggesting recurrence on endoscopy (table). The remaining 14/19 (74%, 95% confidence interval (CI): 49-91%) were found on routine surveillance biopsies. Of the 17 patients biopsied for a raised lesion or mucosal change suspicious for recurrent IM, only 5 (29%) actually had recurrence; 12 such biopsies were negative for recurrent IM. The median location for recurrent IM in targeted biopsies was 1 cm (Mean 2.5, S.D. 4.3) proximal to the top of the gastric folds; most (75%) specimens indicative of recurrence were from within 2 cm of the top of the gastric folds (figure). The odds ratio for recurrent disease in the setting of endoscopic signs was 17.7 (p < 0.001). Histologic grade was significantly higher for recurrence accompanied by endoscopic signs compared to those found on random biopsy (p = 0.016 for trend). Subsquamous recurrence was not identified in any biopsies regardless of endoscopic signs (95% CI: 0-23%). Conclusion: Histologic recurrence of IM following RFA was most common near the gastroesophageal junction. Subsquamous recurrence was not an important factor in recurrence. Most recurrences were found on routine, non-targeted biopsies, but endoscopic signs of recurrence including nodularity or apparent columnar-lined esophagus are associated with improved biopsy yield. Histology of Apparent and Non-Apparent Recurrence or Progression

Kritische Betrachtung neuer Konzepte zur endoskopischen Anatomie des ösphagogastralen Übergangs im Sinne des Denkens von Parmenides und Martin Heidegger

Current endoscopic anatomy interposes the gastric cardia between the tubular oesophagus and the proximal stomach. In contrast to that, recent evidence unfolds a different view. Using "PubMed" and "Scopus" searches, we examined if the novel understanding regarding the cardia goes in line with the concept of unfolding, as described by Heidegger based on the ancient didactic poetry of Parmenides. What has been taken as gastric cardia in fact represents reflux-damaged, dilated, columnar lined oesophagus (CLO): dilated distal oesophagus (DDO). Due to its macroscopic gastric appearance it cannot be discriminated from the stomach by endoscopy. Differentiation between DDE and proximal stomach requires the histopathology of measured multi-level biopsies obtained from the DDO and the proximal stomach. Cardaic, onxytocardiac mucosa and intestinal metaplasia (IM; Barrett's oesophagus) define CLO and thus the oesophageal location, while oxyntic mucosa (OM) of the proximal stomach verifies a gastric biopsy location. Endoscopically visible CLO and DDO define the morphological manifestation of reflux: the squamo-oxyntic gap (SOG). Biopsies obtained from the level of the diaphragmatic impressions allow differentiation between an enlarged hiatus with normal anatomic content (CLO; oesophagus) vs. hernia with abnormal content (OM; stomach). Non-dysplastic Barrett's oesophagus exists in 10 %-17 % of asymptomatic and in 20 %-100 % (with increasing CLO length) of reflux symptom-positive individuals (annual cancer risk: 0.2 %-0.7 %). These data justify biopsy of an endoscopically normal appearing squamocolumnar junction for the exclusion of Barrett's oesophagus and cancer risk. In the absence of contraindications, cancer risk-based therapy of dysplastic Barrett's oesophagus includes radiofrequency ablation (RFA) ± endoscopic resection. The perception of the cardia as reflux damaged DDO mirrors the concept of unfolding, as described by the interpretation of the didactic poem of Parmenides by Heidegger. Our data recommend to omit the term "cardia" and allocate morphology either to the oesophagus (CLO, DDO) or to the proximal stomach or indicate that allocation is impossible (i. e.. tumour-induced). Future studies will have to test the value of this novel concept for diagnosis, treatment of gastro-oesophageal reflux disease and cancer prevention.

Selected commentary to review on novel concepts of columnar lined esophagus

The focus of this review article is on the novel and challenging concepts that have emerged in the field of gastroesophageal reflux disease (GERD) and Barrett’s esophagus over the recent years. Lenglinger et al. (Wien Klin Wochenschr. 2013;125:577–590) have made an in-depth PubMed research on studies dealing with histopathology of nondysplastic columnar lined esophagus (CLE). The aim of the review is to summarize the current body of knowledge regarding the pathophysiology of nondysplastic CLE and its implications for the diagnosis and treatment of this pre-neoplastic condition.

Immunohistochemical/histochemical double staining method in the study of the columnar metaplasia of the oesophagus

Intestinal metaplasia in Barrett’s oesophagus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotypic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metaplasia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the histochemical features in cells that shows an aberrant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53, both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These findings suggest that some immunophenotypic changes are present in CLO and they can precede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition characterized by any extention of columnar epithelium. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology.

Barrett's oesophagus: Evidence from the current meta-analyses.

Guidelines have been published regarding the management of Barrett's oesophagus (columnar-lined oesophagus). These have examined the role of surveillance in an effort to detect dysplasia and early cancer. The guidelines have provided criteria for enrolment into surveillance and some risk stratification with regard to surveillance interval. The research basis for the decisions reached with regard to cancer risk is weak and this manuscript has examined the available data published from meta-analyses up to 25(th) April 2013 (much of which has been published since the guidelines and their most recent updates have been written). There were 9 meta-analyses comparing patients with Barrett's oesophagus to control populations. These have demonstrated that Barrett's oesophagus is more common in males than females, in subjects who have ever smoked, in subjects with obesity, in subjects with prolonged symptoms of gastro-oesophageal reflux disease, in subjects who do not have infection with Helicobacter pylori and in subjects with hiatus hernia. These findings should inform public health measures in reducing the risk of Barrett's oesophagus and subsequent surveillance burden and cancer risk. There were 8 meta-analyses comparing different groups of patients with Barrett's oesophagus with regard to cancer risk. These have demonstrated that there was no statistically significant benefit of antireflux surgery over medical therapy, that endoscopic ablative therapy was effective in reducing cancer risk that there was similar cancer risk in patients with Barrett's oesophagus independent of geographic origin, that the adenocarcinoma incidence in males is twice the rate in females, that the cancer risk in long segment disease showed a trend to be higher than in short segment disease, that there was a trend for higher cancer risk in low-grade dysplasia over non-dysplastic Barrett's oesophagus, that there is a lower risk in patients with Helicobacter pylori infection and that there is a significant protective effect of aspirin and statins. There were no meta-analyses examining the role of intestinal metaplasia. These results demonstrate that guidance regarding surveillance based on the presence of intestinal metaplasia, segment length and the presence of low-grade dysplasia has a weak basis, and further consideration should be given to gender and helicobacter status, ablation of the metaplastic segment as well as the chemoprotective role of aspirin and statins.

Risk factors associated with Barrett's epithelial dysplasia.

To elucidate risk factors associated with dysplasia of short-segment Barrett's esophagus (BE). A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital, Tokyo Women's Medical University, Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study. BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction. Dysplasia was classified into three grades - mild, moderate and severe - according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia. Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia. The prevalence of Helicobacter pylori (H. pylori) infection and the expression of p53 by immunohistological staining were also investigated. Histological examination classified patients into three types: specialized columnar epithelium (SCE) (n = 65); junctional (n = 38); and gastric fundic (n = 48). The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types (P < 0.01). The univariate analysis revealed that sex, H. pylori infection, body weight, p53 overexpression, and low diastolic blood pressure (BP) were associated with BE dysplasia. In contrast, body mass index, waist circumference, metabolic syndrome complications, and variables related to glucose or lipid metabolism were not associated with dysplasia. Multivariate logistic analysis showed that overexpression of p53 [odds ratio (OR) = 13.1, P = 0.004], H. pylori infection (OR = 0.19, P = 0.066), and diastolic BP (OR = 0.87, P = 0.021) were independent risk factors for epithelial dysplasia in BE patients with the SCE type. Overexpression of p53 is a risk factor for dysplasia of BE, however, H. pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.

Barrett's Esophagus Suspected at Endoscopy but No Specialized Intestinal Metaplasia on Biopsy, What's Next?

There are no guidelines regarding the best practice for when Barrett's esophagus (BE) is suspected but not confirmed by histology. The aim of this study was to examine the value of endoscopic follow-up for individuals with endoscopic only BE at index endoscopy. We performed a longitudinal study of patients diagnosed with suspected columnar lined esophagus (CLE) (suspected BE in the absence of histological confirmation of specialized intestinal metaplasia (IM)). We examined three possible outcomes (definite BE defined as CLE plus IM in targeted biopsies, suspected CLE, or no suspected CLE) on repeat endoscopy within 2 years after the index endoscopy and their predictors (clinical, demographic as well as endoscopists' identity). A total of 107 of 1,844 patients had suspected CLE (101 were <3 cm), and 80 underwent a repeat endoscopy within 2 years. Approximately, 71% (95% confidence interval (CI) 61.1-80.9%) had suspected CLE confirmed at repeat endoscopy and only 29% (95% CI 19.1-38.9%) had IM. The length of CLE on the index esophagogastroduodenoscopies was slightly longer among patients with definite BE on repeat endoscopy than those with suspected CLE and no IM or no CLE (1.6 cm (s.d. 1.3) vs. 1.5 cm (s.d. 1.4), and 1.4 cm (s.d. 1.2), respectively P>0.1). Patient demographics, body mass index, gastro-esophageal reflux disease symptoms, hiatal hernia, and endoscopists' identity were not significantly associated with the outcome on the repeat endoscopy. Most (71%) patients with suspected CLE remain negative for IM in the 2 years following the index endoscopy. The findings support withholding BE diagnosis for individuals with suspected CLE.

Barrett's esophagus is frequently overdiagnosed in clinical practice: results of the Barrett's Esophagus Endoscopic Revision (BEER) study

The published prevalence of Barrett's esophagus (BE) varies from 0.9% to 25%, in part because of differences in the endoscopic interpretation of the disease. We studied the accuracy of diagnosis in 130 patients previously labeled as having BE. Our aim was to determine the interobserver consistency of endoscopic findings and assess the percentage of patients with confirmed BE versus those with a revised diagnosis. Patients previously diagnosed with BE of any length and due for surveillance endoscopy were eligible for study. After intensive consensus anatomic and endoscopic review, study patients underwent endoscopy and biopsy by 1 of 3 endoscopists. BE was defined as any length of columnar-lined esophagus with goblet cells. Patients were photographed/videotaped for review by the other 2 endoscopists, and BE was either confirmed or revised. Eighty-eight patients (67.7%) had confirmed BE, and 42 (32.3%) had their diagnosis revised to no BE (95% confidence interval, 24.4%-41.1%) because there was no visible columnar-lined esophagus proximal to the gastric folds or no goblet cells were found on biopsy. BE length, site of previous endoscopy, age, sex, and hiatal hernia size were predictors of revision. All 3 endoscopists agreed on all confirmed BE cases and 38 of 42 of those revised. Retrospective analysis, possible sampling error. BE is overdiagnosed in clinical practice with important implications for patient care including increased costs, reduced insurability, and psychological stress. The true BE cancer risk may also be underestimated. This study suggests the need for a better definition of the gastroesophageal junction, stricter accountability for BE diagnosis, and improved endoscopic education.

Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.

A Cross-sectional Analysis of the Prevalence of Barrett Esophagus in Otolaryngology Patients With Laryngeal Symptoms

Populations at risk for esophageal adenocarcinoma remain poorly defined. Laryngeal symptoms can be secondary to laryngopharyngeal reflux (LPR) and can occur without associated gastroesophageal reflux symptoms such as heartburn and regurgitation. We sought to determine the prevalence of Barrett esophagus (BE) in otolaryngology patients with laryngeal symptoms±typical gastroesophageal reflux disease (GERD) symptoms. We performed a cross-sectional study of otolaryngology clinic patients who reported laryngeal symptoms. Symptoms, medications, and exposure histories were obtained. Unsedated transnasal endoscopy was performed. Suspected BE was biopsied and confirmed histologically. Risk factors and prevalence of BE were assessed. Two hundred ninety-five patients were enrolled [73% male, median age 60 y (interquartile range 51 to 68 y)]. The overall prevalence of BE was 11.8% (n=33). Antisecretory medication use was present in 56% (n=156) of patients at enrollment. Compared with patients without BE, patients with BE were more likely to be male (P=0.01) and to report occupational lung injury (P=0.001). Duration, but not severity of laryngeal symptoms, significantly increased the odds of BE (odds ratio, 5.64; 95% confidence interval, 1.28-24.83; for a duration of symptoms >5 y). Of patients with BE, 58% (n=19) had coexisting LPR and GERD symptoms and 30% (n=10) had only LPR symptoms. Presence and size of hiatal hernia and length of columnar-lined esophagus were significant risk factors for BE. Long-standing laryngeal symptoms are associated with the presence of BE in otolaryngology patients. Patients with chronic laryngeal symptoms and no identifiable ear, nose, or throat etiology for those symptoms may benefit from endoscopic screening regardless of whether typical GERD symptoms are present.

Review on novel concepts of columnar lined esophagus

Columnar lined esophagus (CLE) is a marker for gastroesophageal reflux and associates with an increased cancer risk among those with Barrett's esophagus. Recent studies fostered the development of integrated CLE concepts. Using PubMed, we conducted a review of studies on novel histopathological concepts of nondysplastic CLE. Two histopathological concepts-the squamo-oxyntic gap (SOG) and the dilated distal esophagus (DDE), currently model our novel understanding of CLE. As a consequence of reflux, SOG interposes between the squamous lined esophagus and the oxyntic mucosa of the proximal stomach. Thus the SOG describes the histopathology of CLE within the tubular esophagus and the DDE, which is known to develop at the cost of a shortened lower esophageal sphincter and foster increased acid gastric reflux. Histopathological studies of the lower end of the esophagus indicate, that the DDE is reflux damaged, dilated, gastric type folds forming esophagus and cannot be differentiated from proximal stomach by endoscopy. While the endoscopically visible squamocolumnar junction (SCJ) defines the proximal limit of the SOG, the assessment of the distal limit requires the histopathology of measured multilevel biopsies. Within the SOG, CLE types distribute along a distinct zonation with intestinal metaplasia (IM; Barrett's esophagus) and/or cardiac mucosa (CM) at the SCJ and oxyntocardiac mucosa (OCM) within the distal portion of the SOG. The zonation follows the pH-gradient across the distal esophagus. Diagnosis of SOG and DDE includes endoscopy, histopathology of measured multi-level biopsies from the distal esophagus, function, and radiologic tests. CM and OCM do not require treatment and are surveilled in 5 year intervals, unless they associate with life quality impairing symptoms, which demand medical or surgical therapy. In the presence of an increased cancer risk profile, it is justified to consider radiofrequency ablation (RFA) of IM within clinical studies in order to prevent the progression to dysplasia and cancer. Dysplasia justifies RFA ± endoscopic resection. SOG and DDE represent novel concepts fusing the morphological and functional aspects of CLE. Future studies should examine the impact of SOG and DDE for monitoring and management of gastroesophageal reflux disease (GERD).

Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus

Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus. To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma. A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo. Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit. Tissue from 62 patients was included in the study. Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically. Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma. ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated. Measurements were taken from ex vivo tissue. ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales.