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

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

One-step chromoendoscopy and structure enhancement using balsamic vinegar for screening of Barrett's esophagus

BACKGROUND AND STUDY AIMS: Screening for specialized columnar epithelium (SCE) within columnar lined esophagus (CLE) with standard video endoscopes is not reliable enough. Several methods to improve accuracy of predicting presence of SCE like chromoendoscopy with vital stains or structure enhancement with acetic acid have been introduced but data up to now remains controversial. The present prospective study was conducted to evaluate a combination of chromoendoscopy and acetic acid structure enhancement using the naturally brownish coloured balsamic vinegar during routine upper endoscopy. PATIENTS AND METHODS: Between March and July 2006 20 patients with macroscopic suspicion for SCE during routine endoscopy were included prospectively. Saline diluted balsamic vinegar (3%) was administered with a spraying catheter at the distal esophagus. After 1 minute the distal esophagus was evaluated for the presence of SCE according to the mucosal surface pattern (pattern I-II: round pits/circular pattern predicting gastric epithelium; pattern III-IV: ridged/villous pattern predicting Barrett's epithelium). Only HR-videoendoscopes without magnification were used. After presence or absence of SCE was defined by the endoscopist targeted biopsies of the CLE were performed. Histological results were compared with endoscopic findings. RESULTS: In 9 of 20 patients (13 male, 7 female; mean age 60.0 +/- 12.8 years) biopsy specimen revealed SCE within CLE on histology. Prediction of BM after balsamic vinegar staining was possible in all cases. Surface pattern I-II was found in 9 patients and pattern III-IV in 11 patients. Accuracy, sensitivity and specificity for BV staining predicting SCE were 90%, 100% and 82%, respectively. CONCLUSION: Chromoendoscopy with balsamic vinegar combines the advantages of chromoendoscopy and structure enhancement by acetic acid for detection of SCE. The reliability in predicting the presence of SCE was high in this prospective feasibility study.     

The magnified endoscopic view of cardia-type mucosa

BACKGROUND: The interpretation of magnification endoscopy regarding metaplasia of the esophagogastric junction (EGJ) is still controversial. Histology of areas endoscopically suspected of Barrett's esophagus often reveals only cardia-type mucosa (CTM). The aim of this study was to characterize the surface structure of CTM by magnification endoscopy, in comparison with specialized intestinal metaplasia (SIM) and gastric corpus mucosa. METHODS: Magnification endoscopy was performed in 52 patients with normal EGJ and 36 patients with columnar lined lower esophagus (CLE) on endoscopic examination. Biopsies for histology were obtained from EGJ and CLE segments. In cases with CLE, biopsies were targeted after methylene blue staining. RESULTS: A gyriform or oval pattern was observed in all patients at the normal EGJ, histologically representing CTM. These patterns of CTM were easily discernible from the small pits of corpus mucosa. A gyriform or villous pattern was dominant in CLE, both in areas with CTM and those with SIM. Methylene blue staining was more frequent in SIM than in CTM, but was of insufficient specificity for SIM. CONCLUSIONS: Although magnification endoscopy allows one to differentiate CTM from gastric corpus mucosa, a clear distinction from SIM is not possible. Auxiliary methods that complement magnification endoscopy, like methylene blue staining and acetic acid contrast enhancement, should be evaluated regarding the differentiation between CTM and SIM.     

ErbB2 without erbB3 expression in metaplastic columnar epithelium of Barrett's esophagus

BACKGROUND/AIMS: ErbB2 expression in esophageal adenocarcinoma has been shown to correlate with its clinicopathological features. However, expression levels for EGF receptor, erbB2 and erbB3 in specialized columnar epithelium (SCE) of Barrett's esophagus have yet to be determined. To investigate the relationship between EGF family receptors and Barrett's esophagus, we examined expression levels for EGF receptor, erbB2 and erbB3 in SCE of Barrett's esophagus. METHODS: 10 consecutive patients with short- and long-segment Barrett's esophagus, and 10 control subjects without organic esophago-gastric diseases were enrolled. Biopsy samples of Barrett's mucosa stained or not stained with methylene blue applied endoscopically were used for histological evaluation and Western blot analysis of EGF receptor, erbB2 and erbB3 proteins. RESULTS: Mean length of Barrett's esophagus was 2.6 cm (range 1-8 cm) and all tissue samples from methylene blue stained Barrett's mucosa consisted of non-dysplastic SCE. In the Barrett's group, Western blot analysis showed that EGF receptor and erbB2 were equally and strongly expressed in SCE and squamous epithelium; in contrast, erbB3 expression in SCE was considerably weaker. In control subjects, all proteins showed strong expression for all samples. Immunohistochemical analysis of SCE in Barrett's esophagus showed positive EGF receptor and erbB2 expression, and no erbB3 expression. CONCLUSIONS: ErbB2 is strongly expressed in both non-dysplastic SCE and squamous epithelium, whereas erbB3 expression is essentially limited to the squamous epithelium. .     

Surveillance of patients with Barrett's esophagus

Barrett's esophagus is a major complication of gastroesophageal reflux disease and is associated with 30-125 fold increased risk of developing carcinoma. Because of the rising incidence of esophageal adenocarcinoma the malignant potential of Barrett's esophagus has been generally recognized. The definition of Barrett's esophagus has evolved over the last decades. It is now accepted that "Long-Barrett-Segment" (LBS) is used when intestinal-type epithelium, characterized by the presence of goblet cells, is detected in the distal esophagus > 3 cm in length. The term "Short-Barrett-Segment" (SBS) is defined by intestinal metaplasia detection < 3 cm in length in the distal esophagus. Recently, there has been focus on microscopic Barrett's esophagus, so called "Ultra-Short-Barrett's esophagus", with histological evidence of intestinal metaplasia without endoscopic appearance.The most significant predictor of the risk of malignancy in patients with Barrett's esophagus is the presence of dysplasia. Guidelines for surveillance are based on the diagnosis of dysplastic lesions. New methods (e. g. Methylene blue staining, endoscopic fluorescence detection, OCT) to improve the recognition of Barrett's esophagus and especially enhance the detection of premalignant and malignant lesions are under evaluation. So far, the standard biopsy protocol for patients with LBS includes biopsies in the 4 quadrants every 1-2 cm, whereas the appropriate surveillance intervals are dependent on the grade of dysplasia. Whether surveillance in patients with SBS has to be similar to that in patients with LBS is unclear and needs further evaluation.     

Prevalence of Barrett's esophagus by endoscopy and histologic studies: a prospective evaluation of 306 control subjects and 376 patients with symptoms of gastroesophageal reflux

The classic endoscopic diagnosis of a Barrett's esophagus (BE) is based on the finding of > or =3 cm, of distal esophagus covered by specialized columnar epithelium. However, currently, it is based on the finding of intestinal metaplasia (IM) at the squamous-columnar mucosal junction, independent of its extent. The aim of this study was to determine the prevalence of Barrett's esophagus by endoscopic and histological findings in control subjects and in patients with symptoms of gastroesophageal reflux (GER). Three hundred and six control subjects and 376 patients with symptoms of gastroesophageal reflux were included in this prospective study. Patients with Barrett's esophagus were classified in three groups as follows. 1. Intestinal metaplasia at the cardia. When endoscopy showed non-Barrett's esophagus, but histological intestinal metaplasia was found. 2. Short-segment Barrett's esophagus. When <3 cm, was covered with tongues or finger-like or creeping substitution of distal esophagus. 3. Long-segment Barrett's esophagus. When > 3 cm, of distal esophagus was covered by specialized columnar epithelium. Two biopsies at the antrum, four biopsies at the squamous-columnar junction and one or two at the distal esophagus were taken. In control subjects, 1.6% showed histological IM at the esophagogastric junction. In patients with GER without esophagitis or with erosive esophagitis, IM was found in 18% and 10.7% respectively. 'Short-segment' Barrett's esophagus was three times more frequent than 'long-segment' Barrett's esophagus. Patients with Barrett's esophagus were significantly older than the other groups. The presence of complications or erosions, peptic ulcer or stricture were significantly more frequent among patients with 'long-segment' Barrett's esophagus (p < 0.0001). The prevalence of dysplasia was similar in all groups of patients with Barrett's esophagus. Complications such as ulcers, stricture and dysplasia were exclusively seen among patients with BE, whereas non-Barrett's patients did not exhibit these complications. In control subjects, IM can be found in a low percentage of cases. Among patients with symptoms of GER, the classic endoscopic diagnosis of a Barrett's esophagus can underestimate this condition in 80% of the cases. Patients with intestinal metaplasia at the cardia already present 17% of the cases with low-grade dysplasia. In all patients with symptoms of GER, systematic biopsies at the squamous-columnar junction should be taken.     

Crystal violet chromoendoscopy with mucosal pit pattern diagnosis is useful for surveillance of short-segment Barrett's esophagus

BACKGROUND: Because of a rapid increase in the incidence of Barrett's cancer, the appropriate surveillance method for Barrett's esophagus is of interest. Methylene blue chromoendoscopy has been reported to be an effective and inexpensive method to improve biopsy surveillance of Barrett's epithelium. However, the usefulness of this method in short-segment Barrett's esophagus cases is still controversial. AIMS: This study was undertaken to evaluate the abilities of crystal violet and methylene blue chromoendoscopy to detect potentially dysplastic Barrett's epithelium in cases with short-segment columnar-appearing epithelium of the esophago-gastric junction. PATIENTS AND METHODS: Four hundred patients with endoscopically suspected short-segment Barrett's esophagus were enrolled and randomly assigned to receive chromoendoscopy with 0.05% crystal violet, 0.1% crystal violet, 0.5% methylene blue, or 1.0% methylene blue. During crystal violet and methylene blue chromoendoscopy, biopsy specimens were obtained from stained and unstained columnar-appearing epithelium of the esophago-gastric junction, and the detection rates of Barrett's epithelium were evaluated. The value of pit pattern diagnosis was also evaluated as a possible way to detect dysplastic Barrett's epithelium. RESULTS: Chromoendoscopy with 0.05% crystal violet detected histologically confirmed Barrett's epithelium with the highest sensitivity (89.2%) and specificity (85.7%). Crystal violet clearly stained both dysplastic and nondysplastic Barrett's epithelia and made the surface pit pattern easy to observe without using magnifying endoscopy. CONCLUSIONS: The combination of crystal violet chromoendoscopy and pit pattern diagnosis is considered to be useful for the surveillance of short-segment Barrett's esophagus.     

Malignant degeneration of Barrett''s esophagus: the role of the Ki-67 proliferation fraction, expression of E-cadherin and p53

Barrett's columnar epithelium with dysplasia is the most important risk factor for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible for progression of columnar metaplasia to dysplasia and invasive carcinoma are mostly unknown. We investigated expression of the tumor suppressor gene p53, E-cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma sequence of esophageal adenocarcinoma. In 24 patients with R0-resected adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia, with and without dysplasia, and in squamous epithelium of the esophagus. No p53 immunoreactivity was seen in sections of normal squamous epithelium or columnar metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for mutated p53. The p53 expression correlated with the T-category (P = 0.048) and the N-category (P = 0.024). There was a significant decrease in the expression of E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia was similar to that seen in normal squamous epithelium of the esophagus. The Ki-67 proliferation fraction increased significantly from normal squamous epithelium to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a marked expansion of the proliferative component. There was no correlation between cell proliferation, E-cadherin expression and the tumor stage. In contrast to the alterations in the p53 expression, a decreased E-cadherin expression and the expansion of the proliferative component represent an early phenomenon in the malignant degeneration of Barrett's esophagus. This might aid in the early detection of esophageal adenocarcinoma.     

Use of Methylene Blue for Detection of Specialized Intestinal Metaplasia in GERD Patients Presenting for Screening Upper Endoscopy

The ability of randomly obtained biopsy specimens to identify intestinal metaplasia in the distal esophagus is low. Use of vital staining has been suggested, as stains are taken up by areas histologically identified as specialized intestinal metaplasia (SIM). This study evaluated the role of methylene blue (MB) staining for identification of SIM in GERD patients undergoing a screening endoscopy. Chromoendoscopy of the distal esophagus using 1% MB was performed on 52 GERD patients presenting for their first endoscopy. Biopsies were obtained from areas that were stained darkly, stained lightly, unstained, or macroscopically abnormal. In patients with no MB staining, four-quadrant biopsy of the distal esophagus was performed. Twenty-seven patients (52%) showed staining with MB, while 25 patients did not. Two hundred sixty-six biopsies were obtained. SIM was detected in 11 (21%) subjects (SIM+) but not in the remaining 41 (SIM–). One hundred sixty-five biopsies were unstained (25 SIM+, 140 SIM–) and 101 were stained (12 SIM+, 89 SIM–). The per-biopsy sensitivity and specificity of MB for detection of SIM were 32.4 and 85%, while the per-patient sensitivity and specificity were 63.3 and 51.2%. MB staining for detection of SIM in GERD patients without a macroscopic appearance suggestive of a columnar-lined esophagus is a poor screening tool for SIM.     

Methylene Blue Staining and Endoscopic Ultrasound Evaluation of Barrett's Esophagus with Low-Grade Dysplasia

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barrett's esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 ± 0.2 mm), nondysplastic Barrett's (2.6 ± 0.2 mm), and Barrett's with dysplasia (2.9 ± 0.3 mm) were similar. With staining, Barrett's mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barrett's were 68% and 85%, respectively. Barrett's with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barrett's (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.     

Value of endoscopic methylene blue and Lugol＇s iodine double staining and detection of GST-n and telomerase in the early diagnosis of esophageal carcinoma

AIM: To explore the expressions of GST-Pi and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue (MB) and Lugol's iodine double staining. METHODS: Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol's iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-Pi and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS: After MB and Lugol's iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology (P<0.005). The expression of GST-Pi and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-Pi and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium (P<0.005). The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased (P<0.025). Expression of GST-Pi was correlated with that of telomerase activity in dysplasia and carcinoma (phis = 0.4831, P<0.005; phis = 0.3031, P<0.025, respectively); but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION: The expression of GST-Pi and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol's iodine double staining and detection of GST-Pi and telomerase activity may contribute to the early diagnosis of esophageal carcinoma.     

Value of endoscopic methylene blue and Lugol''''s iodine double staining and detection of GST-n and telomerase in the early diagnosis of esophageal carcinoma

AIM: To explore the expressions of GST-n and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue (MB) and Lugol's iodine double staining. METHODS: Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol's iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-n and telomerase activity in specimens were examined by immunohis-tochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS: After MB and Lugol's iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology (P<0.005). The expression of GST-n and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-n and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium (P<0.005). The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased (P<0.025). Expression of GST-n was correlated with that of telomerase activity in dysplasia and carcinoma ((?)= 0.4831, P<0.005; (?)=0.3031, P<0.025, respectively); but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION: The expression of GST-n and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol's iodine double staining and detection of GST-n and telomerase activity may contribute to the early diagnosis of esophageal carcinoma.     

Is intestinal metaplasia a necessary precursor lesion for adenocarcinomas of the distal esophagus,gastroesophageal junction and gastric cardia?

Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed to arise in Barrett's esophagus with intestinal metaplasia. Whether adenocarcinoma can arise in columnar lined esophagus without intestinal metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate the relationship of size and stage of adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia to intestinal metaplasia and other types of columnar epithelium. Seventy-four patients who had esophagogastrectomy for adenocarcinomas in this region were examined histologically to assess the frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors without residual intestinal metaplasia were evaluated for the presence of other columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was present around all tumors. Residual intestinal metaplasia was present in 48 (65%) tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11 (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in all tumors that were less than 1 cm in maximum diameter and all intramucosal tumors. The prevalence of residual intestinal metaplasia decreased with increasing tumor size and stage. These data strongly support the contention that adenocarcinomas of this region, including those in the gastric cardia, arise in intestinal metaplastic epithelium. The absence of residual intestinal metaplasia in larger tumors is the result of tumor overgrowing the intestinal metaplasia from which it arose.     

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

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

Does methylene blue detect intestinal metaplasia in Barrett's esophagus?

BACKGROUND: Methylene blue has been used to selectively stain areas of specialized intestinal metaplasia in Barrett's esophagus. The sensitivity, specificity, and negative and positive predictive values for the detection of specialized intestinal metaplasia by methylene blue chromoendoscopy were determined in patients with Barrett's esophagus. METHODS: Thirty patients with Barrett's esophagus underwent endoscopy with biopsy specimens obtained from areas that stained positive and negative with methylene blue. Histopathologic findings were compared with methylene blue chromoendoscopy findings. RESULTS: Two hundred ninety-two biopsy specimens (mean 9.7/patient) were obtained: 203 from stained and 89 from unstained areas. Sensitivity, specificity, and negative and positive predictive values for detection of specialized intestinal metaplasia were, respectively, 72%, 46%, 22%, and 89%. Comparing 187 biopsy specimens from patients with long-segment Barrett's esophagus with 105 specimens from patients with short-segment Barrett's esophagus, the sensitivity, specificity, and negative and positive predictive values were, respectively, 77% versus 63% (p = 0.044), 79% versus 21% (p < 0.002), 28% versus 14% (p = 0.219), and 97% versus 73% (p < 0.002). The odds ratio for detection of specialized intestinal metaplasia in stained areas was 12.40 in long-segment and 0.45 in short-segment Barrett's esophagus. CONCLUSIONS: Data from this study confirm the value of methylene blue chromoendoscopy for detection of specialized intestinal metaplasia in long-segment Barrett's esophagus, but not in short-segment Barrett's esophagus.     

Accuracy of magnifying endoscopy with methylene blue in the diagnosis of specialized intestinal metaplasia and short-segment Barrett's esophagus in Japanese patients without Helicobacter pylori infection

BACKGROUND: The use of methylene blue chromoendoscopy in the diagnosis of specialized intestinal metaplasia in short-segment Barrett's esophagus is controversial. This study evaluated the use of magnifying endoscopy with methylene blue for this purpose. METHODS: A total of 30 patients (21 men, 9 women; median age 61 years, range 32-79 years) with short lengths of columnar-lined esophagus were enrolled in a prospective trial of magnifying endoscopy with methylene blue in which the appearance after methylene blue staining was used to target biopsy specimens. Patients were screened for Helicobacter pylori infection, and only those without infection were enrolled (because many Japanese patients have pan-gastritis caused by H pylori infection, and intestinal metaplasia distal to the squamocolumnar junction may be secondary to H pylori-induced gastritis). All biopsy specimens were stained with H and E; MUC2 immunostaining was used to identify specialized intestinal metaplasia. RESULTS: Thirty patients with short-segment columnar-lined esophagus underwent magnifying endoscopy with methylene blue. Ninety-three biopsy specimens were obtained, 33 from methylene blue-stained areas and 60 from unstained areas, each about 7 mm from the marginal edge of stained areas. Specialized intestinal metaplasia was confirmed in biopsy specimens from 28 of the 33 stained areas (sensitivity 84.8%); in biopsy specimens from 55 of the 60 unstained areas, specialized intestinal metaplasia was not found (specificity 91.7%). In magnified views of methylene blue-positive areas, a tubular, cavernous, or elliptical pattern was seen. Sixteen of 21 men (76.2%) and 3 of 9 women had specialized intestinal metaplasia, and short-segment Barrett's esophagus was diagnosed in these patients. Even in patients with less than 1 cm of columnar-lined esophagus, 8 of 10 stained areas contained specialized intestinal metaplasia (sensitivity 80%) and 23 of 24 unstained areas did not (specificity 95.8%). Six of 12 patients (50%) with less than 1 cm of columnar-lined esophagus had specialized intestinal metaplasia. In total, 19 of 30 patients had specialized intestinal metaplasia. CONCLUSIONS: Magnifying endoscopy with methylene blue selectively detects specialized intestinal metaplasia within short-segment columnar-lined esophagus.     

Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in patients affected by long-standing ulcerative colitis

AIM:To evaluate the diagnostic accuracy of confocal laser endomicroscopy(CLE) for the detection of dysplasia in long-standing ulcerative colitis(UC).METHODS:We prospectively performed a surveillance colonoscopy in 51 patients affected by long-standing UC.Also,in the presence of macroscopic areas with suspected dysplasia,both targeted contrasted indigo carmine endoscopic assessment and probe-based CLE were performed.Colic mucosal biopsies and histology,utilised as the gold standard,were assessed randomly and on visible lesions,in accordance with current guidelines.RESULTS:Fourteen of the 51 patients(27%) showed macroscopic mucosal alterations with the suspected presence of dysplasia,needing chromoendoscopic and CLE evaluation.In 5 macroscopically suspected cases,the presence of dysplasia was confirmed by histology(3 flat dysplasia;2 DALMs).No dysplasia/cancer was found on any of the outstanding random biopsies.The diagnostic accuracy of CLE for the detection of dysplasia compared to standard histology was sensitivity 100%,specificity 90%,positive predictive value 83% and negative predictive value 100%.CONCLUSION:CLE is an accurate tool for the detection of dysplasia in long-standing UC and shows optimal values of sensitivity and negative predictivity.The scheduled combined application of chromoendoscopy and CLE could maximize the endoscopic diagnostic accuracy for diagnosis of dysplasia in UC patients,thus limiting the need for biopsies.     

Barrett's esophagus: a review

Barrett's esophagus may be defined as a columnar epithelium-lined distal esophagus. As a frequently recognized complication of gastroesophageal reflux, Barrett's esophagus has become a diagnosis of general clinical concern. Factors governing the development of this complication in patients with gastroesophageal reflux are unknown but may be congenitally determined in part. When symptoms are present, they are due to the complications of reflux, such as esophagitis, stricture, ulcer, or bleeding. Barrett's esophagus may be suspected on the basis of results of a barium meal test, endoscopy, or isotope scanning. Iodine staining at endoscopy or manometrically guided biopsy helps to localize the abnormal mucosal segment. The diagnosis is proved by biopsy. The columnar epithelium of Barrett's esophagus has a malignant predisposition, and, once the diagnosis is made, periodic endoscopy, with biopsy and cytologic study, is indicated. The treatment of Barrett's esophagus is directed toward objective cessation of gastroesophageal reflux. In refractory cases, antireflux surgery improves symptoms and complications from reflux, but the columnar epithelium generally persists along with its malignant potential. It is not known whether effective antireflux treatment will lower the incidence of adenocarcinoma.     

Cell kinetic study on histogenesis of Barrett's esophagus using rat reflux model

BACKGROUND: To elucidate the histogenesis of Barrett's esophagus and esophageal adenocarcinoma, we designed a duodeno-gastric reflux model in which normal stomach function and normal nutritional status are retained. METHODS: Male Wistar rats were used in the experiment. The esophago-gastric junction was side-to-side anastomosed to a loop of jejunum about 3 cm distal to Treitz's ligament. The animals were not exposed to any known carcinogens during the experiment. Sequential morphological changes were studied for up to 50 weeks after surgery. Serial sections were made and stained with hematoxylin and eosin (H&E). In addition, immunohistochemical staining for bromodeoxyuridine (BrdU) was performed along with histochemical staining for mucins using paradoxical concanavalin A (ConA), galactose oxidase Schiff (GOS), and high-iron diamine-alcian blue (HID-AB). RESULTS: Severe esophagitis with squamous cell hyperplasia was noted in all animals after surgery. At week 20 after surgery, glandular metaplastic cells positive for ConA first appeared within the basal cell layer of esophageal squamous cell epithelium, and then GOS-positive cells and HID-AB goblet cells appeared. This is a characteristic of the specialized columnar epithelium of Barrett's esophagus. We detected esophageal adenocarcinomas in 1 out of 8 subjects at week 40 and in 3 out of 8 subjects at week 50 after surgery. CONCLUSIONS: Reflux of duodenal contents causes specialized columnar epithelium of Barrett's esophagus and esophageal adenocarcinoma. As part of the sequence of events leading to the development of Barrett's esophagus, pyloric-foveolar metaplasia was observed followed by the appearance of intestinal goblet cells. The pyloric-foveolar metaplasia appears to be associated with chronic mucosal damage and regeneration. This multiplastic cell lineage is referred to as 'gut-regenerative cell lineage' (GRCL).