A randomized comparison of methylene blue-directed biopsy versus conventional four-quadrant biopsy for the detection of intestinal metaplasia and dysplasia in patients with long-segment Barrett's esophagus

OBJECTIVES: Methylene blue (MB) selectively stains specialized intestinal metaplasia (SIM) and may assist in surveying a columnar-lined esophagus for Barrett's esophagus associated dysplasia. METHODS: This is a prospective, randomized crossover study comparing 4-quadrant random biopsies (4QB) versus MB-directed biopsies for the detection of SIM and dysplasia in 48 patients with long segment Barrett's esophagus (LSBE). Patients randomly underwent two endoscopies over a 4-wk time period with either 4QB or MB-directed biopsies as their first or second exam. Our aim was to correlate stain intensity with histology. RESULTS: The sensitivity of MB for SIM and dysplasia was 75.2% and 83.1%, respectively. The yield of 4QB for identifying nondysplasia SIM was 57.6% (523/917) and for dysplasia was 12% (111/917). Dark staining was significantly associated with histologic grade (P < 0.007). The final diagnosis was correct in 43 (90%) patients using MB and in 45 (94%) using 4QB. The 4QB technique missed dysplasia in 3 of 21 patients while MB biopsies missed dysplasia in 5 of 21 patients. The discordance between the two techniques was not significant (P= 0.727, McNemar's test). The mean number of biopsies taken during 4QB was 18.92 +/- 6.36 and with MB was 9.23 +/- 2.89 (P < 0.001). CONCLUSION: MB requires significantly fewer biopsies than 4QB to evaluate for SIM and dysplasia. Dark staining correlates more with HGD than LGD in our experience. While MB is not more accurate than 4QB, MB may help to define areas to target for biopsy during surveillance endoscopy in patients with LSBE.     

Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus

Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long‐segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P‐value 0.205). The rate of dysplasia detection in short‐segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high‐grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.     

Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short and long segment Barrett’s esophagus

Objective: Short segment Barrett’s esophagus (SSBE) is defined as the presence of specialized intestinal metaplasia (SIM) in the distal 2–3 cm of the esophagus. Although gastroesophageal reflux and heartburn is very common in these patients, the pathophysiology of the development of a short segment of SIM versus a longer segment of Barrett’s epithelium is not clear. The aim of this study was to assess the extent of gastroesophageal reflux in short versus long segments of SIM. Methods: Of 203 consecutive patients undergoing endoscopy with two biopsies performed just distal to the squamocolumnar junction, 28 patients were identified as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent esophageal manometry and 24-h dual pH monitoring, and the results were compared with 18 long segment Barrett’s esophagus (LSBE) patients and 15 patients with normal 24-h pH studies. Results: SSBE and LSBE patients were significantly older than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was significantly greater in SSBE patients compared with LSBE patients (12.3 ± 1.6 vs 5.2 ± 1.0 mm Hg, p < 0.0008). LSBE patients had a significantly lower distal esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm proximal to the LES, SSBE patients had significantly lower total 24-h pH scores, percent upright and percent supine reflux as compared with LSBE patients. Similarly, when measured at the proximal LES (0 cm), SSBE patients had significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03), whereas percent upright and percent supine reflux were not significantly different. Both LSBE and SSBE patients had a greater degree of GER measured at 5 cm above and just proximal to the LES when compared with normals. Conclusion: As a group, SSBE patients have more competent LES sphincters and less gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients with LSBE. These data indicate that the degree and length of acid exposure in the esophagus are important factors in the pathogenesis of SIM involvement of the esophagus.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.     

Losses of heterozygosity on chromosomes 9p and 17p are frequent events in Barrett's metaplasia not associated with dysplasia or adenocarcinoma

OBJECTIVE: Losses of heterozygosity (LOH) on chromosomes 9p and 17p frequently accompany malignant transformation of Barrett's esophagus (BE). They have been reported in adenocarcinoma, dysplasia, and adjacent metaplasia of patients with long-segment BE (LSBE). This study aimed to evaluate and compare the frequency of LOH on 9p and 17p in patients with long- and short-segment BE (SSBE) without dysplasia or adenocarcinoma. METHODS: Matched metaplasia and blood DNA were evaluated for LOH on chromosomes 9p and 17p in patients with a previous diagnosis of BE and no dysplasia or cancer. RESULTS: We included 18 patients (12 long-segment BE and six short-segment BE). The overall prevalence of LOH was 61% (10 of 18), with no significant difference between LSBE (58%) and SSBE (50%). The frequencies of LOH on 9p and 17p were similar (35% and 39%, respectively), with 18% of the patients showing losses at both chromosomes. CONCLUSIONS: LOH on 9p and 17p are highly frequent events in BE, even in the absence of dysplasia and adenocarcinoma. The presence of these abnormalities in non-neoplastic epithelium suggests they might be useful markers for risk stratification within endoscopic surveillance programs.     

Does this patient have Barrett's esophagus? The utility of predicting Barrett's esophagus at the index endoscopy

OBJECTIVES: Few studies have evaluated the ability of the endoscopist to predict the presence of Barrett's esophagus (BE) at index endoscopy. The goals of this study were to determine the operating characteristics of endoscopy in diagnosing BE, and to determine the clinical and endoscopic predictors of BE in suspected BE patients at the index endoscopy. METHODS: From September 1993 to October 1997, endoscopic reports were examined to identify patients with suspected BE. All esophageal pathology reports during the same period were evaluated for the presence of specialized intestinal metaplasia. RESULTS: During the study period, 4053 endoscopies were performed on 2393 patients. Eight percent of all procedures were performed for suspected or confirmed BE. Fifty-three patients were known to have BE and thus their reports were excluded from this analysis. Five hundred seventy of the remaining patients had esophageal biopsies performed, and were included in this analysis. Among these 570 patients, 146 were suspected to have BE on endoscopy, while 424 were not suspected to have BE at the time of endoscopy. There were no differences among the two groups in terms of gender, race, and dyspepsia as an indication for the endoscopy. However, suspected BE patients were slightly younger and were more likely to have heartburn, but were less likely to have dysphagia as an indication for the endoscopy. The sensitivity and specificity of the endoscopists' assessments were 82% (95% confidence interval [CI], 72-92) and 81% (95% CI, 78-84), respectively. The positive predictive value and the negative predictive value were 34% and 97%, respectively. The positive likelihood ratio was 4.32 (95% CI, 3.49-5.31) and the negative likelihood ratio was 0.22 (95% CI, 0.13-0.38). Univariate analysis showed that endoscopists diagnosed BE in those with long-segment BE (LSBE) more accurately than in those with short-segment BE (SSBE) (55% vs 25% p = 0.001; odds ratio [OR] = 3.63, 95% CI, 1.71-7.70). Barrett's esophagus was correctly diagnosed in 38.5% of white patients but in only 14.7% of black patients (p = 0.01; OR = 3.63, 95% CI, 1.31-10.13). Multivariable logistic regression identified only the length of the columnar-appearing segment (p = 0.002; OR = 3.33, 95% CI, 1.54-7.17) and race (p = 0.08; OR = 2.31, 95% CI, 0.88-6.03) to be associated with the presence of BE on biopsy. CONCLUSIONS: Barrett's esophagus is frequently suspected at endoscopy; SSBE was more frequently suspected than LSBE, but was correctly diagnosed only 25% of the time, versus 55% for LSBE. Endoscopists diagnosed BE with a sensitivity of 82% and a specificity of 81%. However, the positive predictive value was only 34%, whereas the negative predictive value was 97%. The length of the columnar-appearing segment is the strongest predictor of BE at endoscopy. Alternative methods are needed to better identify BE patients endoscopically, especially those with SSBE.     

Are ulcers a marker for invasive carcinoma in barrett''s esophagus? data from a diagnostic variability study with clinical follow-up

OBJECTIVES: We correlated follow-up information from 138 patients with Barrett's esophagus and varying degrees of dysplasia with the presence of ulcers. METHODS: A group of pathologist participants were asked to contribute patients' initial biopsy slides showing Barrett's esophagus (BE) without dysplasia and with epithelial changes indefinite for dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma. From the initial 250 cases used for a diagnostic reproducibility study, follow-up information was available for 138 patients. RESULTS: There were 44 cases submitted as BE, 22 as BE with epithelial changes indefinite for dysplasia, 26 as BE with LGD, 33 as BE with HGD, and 13 as BE with adenocarcinoma. Ulcers were present in 35/138 cases (25%), including 3/44 cases of BE without dysplasia (7%), 2/22 cases of BE with epithelial changes indefinite for dysplasia (9%), 0/26 cases of BE with LGD (0%), 10/33 cases of BE with HGD (30%), and 7/13 cases of BE with adenocarcinoma (54%). On follow-up, there were no invasive carcinomas detected among the BE without dysplasia group (median follow-up = 38.5 months). Adenocarcinomas were detected in 4/22 cases (18%) submitted as BE with epithelial changes indefinite for dysplasia at 19, 55, 60, and 62 months and in 4/26 cases (15%) of BE with LGD at 9, 9, 11, and 60 months. None of these carcinomas occurred in cases in which an ulcer was present in the initial biopsy specimen. Among the 33 HGD cases, 20 (60%) were found to have adenocarcinoma on subsequent resection specimens. The presence of an ulcer with HGD increased the likelihood of finding carcinoma in the resection specimen, as 8/10 biopsies (80%) of HGD patients with ulcers had carcinoma, compared to 12/23 biopsies (52%) of HGD patients without ulcers. All of the cases interpreted as adenocarcinomas on biopsy were found either to have invasive carcinoma on esophageal resection or to have metastases that were demonstrated in unresectable patients. CONCLUSION: If an ulcer accompanies HGD in a biopsy specimen from a patient with BE, it is likely that invasive carcinoma is also present at that time.     

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high‐grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low‐grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open‐label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2–3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE‐D) and complete eradication of all intestinal metaplasia (CE‐IM). Ninety‐six subjects with Barrett's dysplasia (67% HGD; 65% long‐segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow‐up endoscopy (mean duration 21 months). In patients with LGD, rate of CE‐D was 91% (21/23) and rate of CE‐IM was 61% (14/23). In HGD, CE‐D rate was 81% (46/57) and CE‐IM was 65% (37/57). In patients with short‐segment BE (SSBE) with any dysplasia, CE‐D was achieved in 97% (30/31) and CE‐IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non‐steroidal anti‐inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.     

The frequency of Barrett's esophagus in high-risk patients with chronic GERD

BACKGROUND: The reported frequency of Barrett's esophagus (BE) in patients with reflux symptoms varies from 5% to 15%. The exact frequency of long-segment BE (LSBE) (>3 cm) and short-segment BE (SSBE) (<3 cm) in patients with chronic symptoms of GERD is uncertain. The aim of this study was to determine the frequency of LSBE and SSBE in consecutive patients presenting for a first endoscopic evaluation with GERD as the indication. METHODS: Consecutive patients presenting to the endoscopy unit of a Veterans Affairs Medical Center for a first upper endoscopy with the indication of GERD were prospectively evaluated. Demographic information (gender, race, age), data on tobacco use and family history of esophageal disease, and body mass index (BMI) were recorded for all patients. Before endoscopy, all patients completed a validated GERD questionnaire. The diagnosis of BE was based on the presence of columnar-appearing mucosa in the distal esophagus, with confirmation by demonstration of intestinal metaplasia in biopsy specimens. All patients with erosive esophagitis on the initial endoscopy underwent a second endoscopy to document healing and to rule-out underlying BE. Patients with a history of BE, alarm symptoms (dysphagia, weight loss, anemia, evidence of GI bleeding), or prior endoscopy were excluded. RESULTS: A total of 378 consecutive patients with GERD (94% men, 86% white; median age 56 years, range 27-93 years) were evaluated. A diagnosis of BE was made in 50 patients (13.2%). The median length of Barrett's esophagus (BE) was 1.0 cm (range 0.5-15.0 cm). Of the patients with BE, 64% had short-segment BE (SSBE) (overall SSBE frequency 8.5%). The overall frequency of long-segment BE (LSBE) was 4.8%. A hiatal hernia was detected in 62% of the patients with BE. Of the 50 patients with BE (median age 62 years, range 29-81 years), 47 (94%) were men and 98% were white. Eighteen patients (36%) were using tobacco at the time of endoscopy; 23 (46%) were former users. The median body mass index (BMI) of patients with BE was 27.3 (overweight). There were no significant differences between patients with LSBE and SSBE with respect to age, gender, ethnicity, BMI, and GERD symptom duration. CONCLUSIONS: The frequency of BE in a high-risk patient group (chronic GERD, majority white men, age > 50 years) who sought medical attention is 13.2%, with the majority (64%) having SSBE. These data suggest that the frequency of BE in patients with GERD has not changed. The true prevalence of BE in the general population, including those who do not seek care, is undoubtedly lower, currently and historically. The majority of patients with BE are overweight and have a hiatal hernia. Demographic data for patients with LSBE and SSBE are similar, indicating that these are a continuum of the same process.     

Prevalence of Barrett's esophagus in asymptomatic individuals

BACKGROUND & AIMS: The incidence of esophageal adenocarcinoma in the western world has been linked to chronic heartburn, regurgitation, and the development of the premalignant epithelium of Barrett's esophagus (BE). However, up to 40% of esophageal adenocarcinomas occur in patients without prior reflux symptoms. We prospectively screened for the presence of BE in asymptomatic subjects older than 50 years of age undergoing screening sigmoidoscopy for colorectal cancer. METHODS: Subjects undergoing sigmoidoscopy for colorectal cancer (CRC) screening were invited to undergo upper endoscopy. Exclusion criteria included symptoms of gastroesophageal reflux disease (GERD) more than once a month, use of medications for GERD, or previous endoscopy. BE was classified as long-segment BE (LSBE), short-segment BE (SSBE), and microscopic specialized intestinal metaplasia of the esophagogastric junction (SIM-EGJ). RESULTS: Of 408 potential study candidates, 110 subjects were screened; 9 were women. The mean (+/-SD) age was 61 +/- 9.3 (range, 50-80) years, most of them (73%) Caucasian. Intestinal metaplasia (IM) extending above the EGJ was detected in 27 (25%) subjects; 8 (7%) had LSBE, and 19 (17%) had SSBE. Patients with BE were no more likely to be obese, consumers of tobacco or alcohol, report a family history of GERD, show association with toxic exposure, or use antacids more than once a month, compared with those without BE. CONCLUSIONS: BE was detected in 25% of asymptomatic male veterans older than 50 years of age undergoing screening sigmoidoscopy for CRC.     

Bile and acid reflux in long and short segment Barrett's esophagus, and in reflux disease

Gastroesophageal acid reflux (GER) is the primary risk factor for gastroesophageal reflux disease (GERD). In long segment Barrett's esophagus (LSBE) duodenogastroesophageal reflux (DGER) parallels acid reflux. The role of GER and DGER in short segment Barrett's esophagus (SSBE) remains to be determined. The aim of the present prospective study was to investigate the esophageal bile and acid reflux in patients with LSBE, SSBE and patients with GERD. Three groups of patients were studied: Patients with LSBE (n = 12), SSBE (n = 20) and patients with GERD without intestinal metaplasia (n = 33). Subjects underwent esophageal manometry and simultaneous 24-h pH and bile monitoring (Bilitec 2000). The thresholds for GER and DGER were a deMeester score > 14.7 and an absorbance value > 0.2 for 10.9% of total period, respectively. GER did not differ between the groups (p > 0.05). However, DGER differed between patients with LSBE, SSBE and GERD (14.7 vs 2.1 vs 2.1, respectively; p < 0.05). H. pylori status did not influence GER and DGER significantly. In contrast to patients with LSBE the DGER does not seem to play an important role in patients with SSBE and patients with GERD. This result indicates a different etiopathology of both long and short segment Barrett's esophagus.     

The Dose of Omeprazole Required to Achieve Adequate Intraesophageal Acid Suppression in Patients with Gastroesophageal Junction Specialized Intestinal Metaplasia and Barrett’s Esophagus

Background

The mainstay of medical therapy for Barrett’s esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown.

Aim

The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett’s esophagus (LSBE).

Methods

Patients with GEJSIM and Barrett’s esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated.

Results

A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526).

Conclusions

The majority of patients with Barrett’s esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett’s mucosa.     

Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors

OBJECTIVE: To assess the prevalence of and factors associated with squamous intraepithelial lesions and condyloma [human papillomavirus (HPV)-related lesions) in HIV-infected patients. DESIGN: A cross-sectional study in a tertiary-care university hospital conducted in 516 consecutive outpatients. INTERVENTION: A systematic examination for macroscopic HPV-related lesions through anoscopy with histological confirmation, evaluation of dysplasia and HPV typing. Sexual behaviours were assessed using a semi-directive questionnaire. RESULTS: Of 473 patients examined, (200 homosexual men, 123 heterosexual men, 150 women), 108 (23%) had histologically confirmed anal HPV-related lesions (36, 15 and 11% of the respective populations), including 51 (47%) with only endoanal localization. Among these 108 patients, histological dysplasia of grades I or II and grade III were noted in 59 and two patients, respectively, invasive endoanal cancer in one; three patients also had high-risk oncogenicity HPV without dysplasia. Independent identified associated factors of HPV-related condyloma were the number of incidents of sexual intercourse per month [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01-1.06], CD4 cell count below 200 x 10 cells/l (OR 3.22; 95% CI 1.37-7.60), history of anal HPV lesion (OR 4.57; 95% CI 2.13-9.81), and receptive anal intercourse (OR 2.30; 95% CI 1.11-4.77). The two latter factors remained associated with histological dysplasia (OR 2.82; 95% CI 1.38-5.76 for history of anal condyloma, and OR 4.29; 95% CI 2.18-8.44 for receptive anal intercourse). CONCLUSION: The high rate of condyloma and histological dysplasia seen argues for a systematic screening for these lesions in HIV-infected individuals.     

p53 protein overexpression in low grade dysplasia (LGD) in Barrett's esophagus: immunohistochemical marker predictive of progression

OBJECTIVES: The presence of low grade dysplasia (LGD) within Barrett's esophagus (BE) has a multitude of ramifications. Identification of markers that could risk stratify LGD would be of great clinical benefit. We aimed to prospectively evaluate the prognosis of the immunohistochemical overexpression of p53 protein in BE colocalized to LGD. METHODS: Consecutive BE patients in whom LGD was found had a repeat esophagogastroduodenoscopy within 8-12 wk per an ongoing prospective study. At each esophagogastroduodenoscopy, a therapeutic scope was used in conjunction with the Seattle Biopsy Protocol. Patients were observed until development of multifocal high grade dysplasia (mHGD), presence of an HGD dysplasia-associated lesion or mass (DALM) lesion, or frank adenocarcinoma. p53 protein overexpression was determined by computerized immunoquantitation using image analysis software on step serial-sectioned specimens of BE segment(s) harboring LGD. Kaplan-Meier survival curves were made on the ability of p53 staining colocalized to areas of LGD to predict progression to mHGD, HGD DALM, or cancer during prospective follow-up. RESULTS: Forty-eight BE patients with LGD were observed for a mean of 41.2+/-22.5 months. During this period, five of 48 patients progressed to mHGD with a focus in which intramucosal cancer could not be excluded (one), mHGD/DALM with one or more foci in which intramucosal cancer could not be excluded (two), cancer (one), or mHGD (one). Twelve had persistent LGD and 31 had regressed to no dysplasia. p53 staining was positive and colocalized to areas of LGD in 4/31 of patients that regressed, 3/12 that persisted, and 3/5 that progressed. Kaplan-Meier curves differed significantly between p53 positive and negative patients for outcome defined as progression of LGD. CONCLUSIONS: p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies.     

Barrett's esophagus: a new look at surveillance based on emerging estimates of cancer risk

OBJECTIVE: Surveillance of Barrett's patients is recommended, to detect dysplasia and early cancer. The reported risk for developing cancer varies substantially, however. Our previous analysis used an average cancer incidence of 1/75 patient-years (PY). Recent reports suggest that the risk may range from 1/251 to 1/208 PY in combined series of patients with long segment Barrett's esophagus (LSBE, >3 cm), and short segment Barrett's esophagus (SSBE), and up to 1% annually in patients with SSBE. Our goal was to consider these new estimates of cancer risk in a cost-utility analysis of surveillance of patients with Barrett's esophagus. METHODS: Using our previously published model, we incorporated an average of the recent estimates of cancer risk (0.4% annually, 1/227 PY), and our primary data on quality of life after esophagectomy. We included actual variable (direct) costs and used a discount rate of 5%. From the perspective of an HMO, the model evaluates surveillance every 1-5 yr and no surveillance, with esophagectomy performed if high grade dysplasia is diagnosed, and calculates the incremental cost-utility ratios for each strategy. RESULTS: The results suggest that, at our baseline, annual cancer risk surveillance every 5 yr is the only viable strategy. More frequent surveillance costs more and yields a lower life expectancy. The incremental cost-utility ratio for surveillance every 5 yr is $98,000/quality-adjusted life year (QALY) gained, comparable to the incremental cost-effectiveness ratios of accepted practices (heart transplantation and screening for tuberculosis in selected populations, $160,000/LY gained and $216,000/LY gained, respectively). CONCLUSIONS: Surveillance of Barrett's patients should extend life, with incremental cost-utility ratios that compare favorably with some accepted medical practices. Policy makers can compare the cost of surveillance to that of other accepted practices to determine their willingness to fund surveillance.     

The characteristics of Barrett's esophagus: an analysis of 4120 cases in China

Our objective was to investigate the endoscopic and clinico-pathological characteristics in patients with Barrett's esophagus (BE) in China. Using the terms 'Barrett's esophagus' and 'Barrett's esophagus, China' as key words, literatures published in Chinese and English journals were searched in Chinese data banks, as well as PubMed and ISI Web of Science from 1989 to 2007. An analysis was carried out with the standard inclusion and exclusion criteria. A total of 4120 cases were included in this study. BE was found in 2.44% of patients undergoing endoscopy for various symptoms of upper gastrointestinal tract diseases; the male : female ratio was 2.09 : 1, the average age of detection of BE was 53.15 years old, and 51% of patients with BE had typical symptoms for gastroesophageal reflux disease (GERD). The island-type BE was predominant (56.80%), and the occurrence of BE with special intestinal metaplasia (SIM) was 36.58%, but SIM was more common in tongue-type BE than island-type and circumferential-type BE (both P < 0. 001), as well as in long segment BE (LSBE) than in short segment BE (SSBE) ( P < 0. 001). A total of 46.39% of patients had Helicobacter pylori infection. The mean length of follow up was 2 years in 492 patiens. The incidence of adenocarcinoma was 0.61% patient-years of total follow up. In China, the endoscopic prevalence of BE is lower, but the average age of diagnosis is younger; a high proportion of H. pylori infection is found in patients with BE, and about half of the patients have no typical symptoms of GERD; the tongue-type BE and the LSBE are apt to SIM.     

食管末端及胃食管连接处的肠化生、异型增生和肿瘤发病情况

目的 了解我国人食管末端和胃－食管连接处的肠化生（IM）及异型增生和肿瘤的发病状况，齿状线（SCJ）位置和反流性食管炎（RE）的关系。方法 调查记录391例患者的症状，胃镜下RE的表现，并根据SCJ的位置分为3组，其中，胃镜下见齿状线上移≥3cm为A组，＜3cm为B组，齿状线和GEJ同一水平的为C组。每例患者均于齿状线远端活检送病理检查。结果 A，B，C，3组IM发生率分别为26.53%,33.85%,34.00%;IM的发生在40岁以后随着年龄增长逐渐增加，男女之间无差异；361例患者中共诊断异型增生12例（轻度7例，中重度5例），贲门癌16例，食管腺癌1例；A，B，C3组RE的发病率分别为57．14％，22．83％，12．00％。结论 1．胃镜下提示为LSBE，SSBE和GEJ三组间的IM发生率无显著差异；2．应重视食管末端及胃－食管连接处异型增生的诊断；3．贲门癌发病远高于食管腺癌。     

DNA abnormalities as marker of risk for progression of Barrett's esophagus to adenocarcinoma: image cytometric DNA analysis in formalin-fixed tissues

OBJECTIVES: To examine DNA content abnormalities in patients with Barrett's esophagus (BE) who progress to esophageal adenocarcinoma, using image cytometric DNA analysis (ICDA) of formalin-fixed tissues. METHODS: Studies were performed on archived biopsies of BE patients' undergoing endoscopic surveillance before developing adenocarcinoma. A comparison group consisted of BE patients' free of cancer during a follow-up period of over 9 yr. Tissue sections were analyzed for the degree of dysplasia and for DNA content abnormalities, using image cytometry. Additional patients were also analyzed in a cross-sectional study of 56 BE cases with and without dysplasia, including 12 cases of adenocarcinoma. RESULTS: Five patients developed adenocarcinoma during follow-up and earlier biopsies obtained before cancer diagnosis showed specialized intestinal metaplasia (SIM) followed by low-grade dysplasia (LGD) in one, SIM followed by high-grade dysplasia (HGD) in one, LGD in two, and HGD in one case. All five showed some DNA abnormality at baseline or in interval biopsies. In the comparison group, five of seven patients showed normal diploid DNA at baseline and on follow-up biopsies. One patient initially had diploid DNA, but developed aneuploidy 11 yr later. Another case initially had aneuploidy, but was diploid on follow-up. Overall, DNA abnormalities were found in 13% of cases with SIM without dysplasia, 60% with LGD, 73% with HGD, and 100% with adenocarcinoma. CONCLUSIONS: (i) Image cytometric DNA analysis is a useful method to examine DNA abnormalities in formalin-fixed tissues and may be more sensitive in predicting progression to adenocarcinoma than HGD. (ii) Histological dysplasia of any grade and DNA abnormalities, help identify BE patients at high risk for adenocarcinoma.     

The Risk Factors for Discrepancy After Endoscopic Submucosal Dissection of Gastric Category 3 Lesion (Low Grade Dysplasia)

Background

Treatment with endoscopic submucosal dissection (ESD) for gastric category 3 lesion (low grade dysplasia, LGD) diagnosed by endoscopic forceps biopsy (EFB) is controversial.

Aims

The purpose of the present study was to validate the use of ESD for gastric LGD diagnosed by EFB and to evaluate predictable factors for pathologic upgrade diagnosis to category 4 (high grade dysplasia, HGD) or 5 (early gastric cancer, EGC) lesions.

Methods

Between November 2008 and October 2011, a retrospective analysis of a prospective database was conducted at a single tertiary referral center. A total of 218 ESD procedures were carried out for gastric LGD lesions identified by EFB. The under-diagnosis rate by EFB and the predictable factors for upgrade diagnosis to category 4 or 5 lesions were analyzed.

Results

Pathologic discrepancy between EFB and surgical resection was 20.1 % (44/218). Thirty eight lesions (17.4 %) were diagnosed HGD or EGC by ESD. Gastric HGD lesions were 14 cases (6.4 %) and EGC lesions were 24 cases (23 mucosal and 1 submucosal cancer) (11.0 %). Multivariate analysis revealed that lesion diameter more than 1 cm (OR 3.496 [95 % CI 1.375–8.849]), surface redness (OR 6.493 [95 % CI 2.557–16.666]) and nodular surface (OR 2.762 [95 % CI 1.237–6.172]) were significant risk factors.

Conclusions

Endoscopic resection can be recommended if a LGD lesion has risk factors such as a size of 1 cm or greater, surface redness or surface nodulariy. For lesions without the risk factors, follow-up endoscopy may be recommended.     

The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression

OBJECTIVE: The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability. METHODS: A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens. RESULTS: Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and -0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2-84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2-43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists' diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p = 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p = 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed. CONCLUSIONS: A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.