Barrett's Columnar-lined Oesophagus Research Articles

Su1951 Over Expression of Cd55 and Loss of Dsc2 From Barrett's Columnar-Lined Esophagus Are Associated With Esophageal Adenocarcinoma Risk

activity of the lymph nodes described on the PET scan. Results: A total of 498 patients (median age 64, 84.13%males) with newly diagnosed esophageal cancer underwent complete EUS for initial staging at our center during 1999 to 2009. Adenocarcinoma was present in 440 patients and squamous cell cancer in 53 patients. The T stage distribution among 498 patients was T1 (including T1a, T1b and undifferentiated T1) was 91(18%), T2 was 59(12%), T3 was 317(64%), T4 was 14(3%) and T0 was 17(3%). There were 31 patients who underwent PET scan at another hospital and their report was not available. There were 170 lymph nodes that underwent FNA of which 96 lymph nodes (in 83 patients) were found to be positive for malignant cells. Among these, 72 lymph nodes (in 60 patients) were noted on the PET scan, 18 lymph nodes (in 18 patients) were not noted on the PET scan and 8 lymph nodes belonged to patients with no record of a PET scan either at our facility or outside. Among the 72 malignant lymph nodes noted on the PET scan, 12 lymph nodes were not FDG-avid. Table 1 shows the distribution of FNA positive lymph nodes and their detection on PET scan. FNA positive lymph nodes not noted on the PET scan were more commonly found below the diaphragm. Conclusion: EUS and PET scan are complimentary for esophageal cancer staging. The findings of PET scan should not limit an endosonographer in performing a complete lymph node survey.

The relationship between smoking and severe dysplastic disease in patients with Barrett’s columnar-lined oesophagus

The aim of this study was to examine the relationship between smoking and oesophageal high-grade dysplasia (HGD) or adenocarcinoma (AC) in a large cohort of patients with Barrett's columnar-lined oesophagus (CLO). A total of 1280 patients diagnosed with CLO and registered with the UK National Barrett's Oesophagus Registry were included. Data, including smoking habits, were collected from the patient's notes and development of HGD or AC noted. Analysis was performed with SPSS using logistic regression for calculation of odds ratios (ORs) for development of HGD/AC. Data on smoking habits were available in 956 (74.6%) patients. There was no significant difference between smokers and nonsmokers in mean age (P=0.877) or length of follow-up (P=0.359). There was a significant risk of HGD/AC in patients with any history of smoking compared with those who had never smoked (P<0.001, OR 2.81). Ex-smokers of 10 years or more remained at a significantly higher risk of HGD/AC compared with those who had never smoked (P=0.001, OR 3.37). Current smokers were not at a significantly higher risk of HGD/AC compared with ex-smokers (P=0.857) nor were those who smoked at least 20 a day compared with those who smoked fewer than 20 a day (P=0.632). In patients with CLO, smoking appears to be a significant risk factor for the development of severe dysplastic disease; however, we did not observe a dose-dependent effect of smoking on progression of disease.

PTU-207 Detection of dysplasia arising in Barrett's oesophagus is associated with better quality endoscopic technique

IntroductionBarrett's columnar lined oesophagus (CLO) is the pre-malignant lesion to oesophageal adenocarcinoma (OAC). The presence of dysplasia, when diagnosed in surveillance programmes, is an important marker of risk of progression...

Understanding Barrett's columnar lined oesophagus from the patients' perspective: qualitative analysis of semistructured interviews with patients

ObjectivesTo explore patients' views and perspectives on their experience of living with Barrett's columnar lined oesophagus (CLO) and being part of an endoscopic surveillance programme.DesignQualitative semistructured interviews.SettingDistrict General Hospital.Subjects22 men...

Lifetime risk of oesophageal adenocarcinoma in patients with Barrett's columnar-lined oesophagus registered with UK national Barrett's oesophagus registry

<h3>Introduction</h3> The annual rate of development of high-grade dysplasia or adenocarcinoma in Barrett9s columnar-lined oesophagus is 1.0%.12 This study uses data from the UK National Barrett9s Oesophagus Registry (UKBOR) and the Office of National Statistics to predict the average number of surveillance endoscopies and lifetime risk of development of high-grade dysplasia and adenocarcinoma. <h3>Methods</h3> Data on patient gender, age at columnar-lined oesophagus diagnosis and date of columnar-lined oesophagus diagnosis were collected for patients diagnosed between 1994 and 2008 from centres registering ≤20 patients with UKBOR. Patients were included if aged between 18 and 95 years at date of diagnosis. This yielded a total of 7877 patients from 36 centres in the UK. Life expectancy/years at risk was evaluated using age at diagnosis and predicted life years from life expectancy tables.3 Standard surveillance practice was modelled as a single endoscopy at diagnosis with 3 yearly surveillance for no dysplasia and 6 monthly follow-up endoscopy for low-grade dysplasia or indefinite changes for dysplasia (14.7% of diagnostic endoscopy findings and 19.6% of subsequent endoscopy findings). <h3>Results</h3> There were 5137 males, mean age 61.6 years at diagnosis and 2740 females, mean age 67.3 years at diagnosis. The mean predicted years of life (exposure time to the risk of developing malignancy in the metaplastic segment) were 23.1 and 20.7 years, respectively, and 22.2 years overall. This would predict that the lifetime risk of developing high-grade dysplasia or cancer would be between 1:4 and 1:5 and of adenocarcinoma would be between 1:7 and 1:8. The average number of surveillance OGDs during a patient9s lifetime using the above surveillance protocol is 9.8 per patient. <h3>Conclusion</h3> These data predict a significant lifetime risk of development of high-grade dysplasia or adenocarcinoma in patients diagnosed with Barrett9s oesophagus. The total burden of surveillance endoscopies excluding those for therapeutic interventions to the metaplastic segment or for follow-up of high-grade dysplasia, cancer or endoluminal treatment is 9.8 per patient.

Cost-Effectiveness of Endoscopic Screening Followed by Surveillance for Barrett's Esophagus: A Review

Screening interventions for Barrett's esophagus (BE) are appealing, but there is little supporting evidence. We reviewed health economics studies about BE endoscopic screening followed by, as required, endoscopic surveillance ("screening and surveillance" hereafter) to help inform the design and conduct of future research. Health economics studies about BE screening and surveillance were identified using electronic database searches and personal contact with authors of identified studies. No studies examined general population screening. Five US studies published between 2003 and 2007 examined the cost effectiveness of screening and surveillance (against no intervention) in patients with chronic gastroesophageal reflux disease (GERD). There was no randomized trial evidence to inform model construction. Assumptions about prevalence and transition probabilities between BE histologic subtypes and about surveillance and treatment protocols varied substantially between studies. Parameters such as potential BE diagnosis-related reduction in quality of life or increase in health care use, diagnostic accuracy, and infrastructural costs (for quality assurance) were considered either "optimistically" or not at all. Only 2 studies considered endoscopic treatments. No study considered the recently introduced radiofrequency ablation technique, or the potential for biomarker-based risk stratification of surveillance interval or duration. Current health economics evidence is likely to have provided optimistic cost-effectiveness estimates and is not sufficient to support introduction of endoscopic BE screening programs among GERD patients. The evidence does not adequately incorporate novel (endoscopic) treatments and the potential for (clinical, endoscopic, or biomarker-based) risk stratification of surveillance. Future research should aim to encompass both these factors.

Aspirin is not chemoprotective for Barrett's adenocarcinoma of the oesophagus in multicentre cohort

Barrett's columnar-lined oesophagus is the precursor lesion for oesophageal adenocarcinoma. The overall rate of progression to adenocarcinoma is 0.59% per annum. A large prospective multicentre trial is recruiting to assess the role of aspirin as a chemoprotective agent in prevention of development of cancer as well as cardiovascular protection in patients with Barrett's oesophagus. This retrospective analysis of the large UK National Barrett's Oesophagus Registry database seeks to analyse this question from within its large natural history study cohort. Multicentre UK retrospective cohort compared patients known to have been taking aspirin with those who did not take aspirin during the course of surveillance for columnar-lined oesophagus. End point was development of dysplasia or oesophageal adenocarcinoma. Analysis was undertaken using Cox's proportional hazard ratio. Total follow-up was 3683 patient-years. Eighty-six patients were taking aspirin, 650 were not taking aspirin (reference group). Numbers of patients developing all grades of dysplasia and adenocarcinoma were: 13 aspirin (15.1%) and 97 no aspirin (14.9%) (hazard ratio 0.723, 95% confidence interval 0.410-1.310, P = 0.294), high-grade dysplasia and adenocarcinoma: five aspirin (5.8%) and 25 no aspirin (3.8%) (hazard ratio 0.898, 95% confidence interval 0.340-2.368, P = 0.827) and adenocarcinoma: four aspirin (4.7%) and 16 no aspirin (2.5%) (hazard ratio 1.092, 95% confidence interval 0.358-3.335, P = 0.877). No significant difference was observed in hazard of developing dysplasia or adenocarcinoma between patients taking aspirin and those not taking aspirin during the course of follow-up of surveillance for columnar-lined oesophagus. In conclusion, no difference in risk of development of dysplasia or adenocarcinoma was observed between patients taking aspirin and those not taking aspirin in this large cohort.

The Outcome of Low-Grade Dysplasia in Barrett's Columnar-Lined Esophagus - A Large Cohort Study from the UK National Barrett's Oesophagus Registry

Introduction: The incidence of adenocarcinoma (AC) in columnar-lined esophagus (CLE) with low-grade dysplasia (LGD) has been variously reported as around between 0% and 12% per annum (p.a.) in small series. The fate of non-progressive LGD is also controversial. The aim of this study was to examine the population with LGD in CLE, the rate of development of high-grade dysplasia (HGD) and AC and also examine those patients who remained with LGD or reverted to non-dysplastic CLE in a large cohort from UK National Barrett's Esophagus Registry (UKBOR). Methods: Medical records of 283 patients with LGD in CLE from 7 UK centers registering with UKBOR were examined and data extracted on histological follow-up. Incidence data were modelled using an exact Poisson distribution. Results: 144 patients had 290 biopsies prior to LGD diagnosis (median time from CLE diagnosis to LGD 2.77 years, maximum 17.36 years). Of these, 141 patients (97.9%) had non-dysplastic CLE at diagnosis (including 18 [12.5%] with changes indefinite for dysplasia), 2 had HGD and 1 had AC (with LGD being biopsied at an urgent follow-up OGD); 3 patients had findings of HGD between initial diagnosis of ndCLO and LGD and 38 (26.4%) had findings of indefinite for dysplasia.217 had 535 biopsies after initial LGD diagnosis. 17 (11.8%) patients had biopsies of AC following LGD (including the patient with AC prior to LGD) and 12 developed HGD. 75 (34.6%) had persistent LGD for at least one further set of biopsies and 45 (20.7%) had LGD at their most recent set of biopsies, with the remaining patients having reverted to indefinite for dysplasia (37 patients, 17.1%) or non-dysplastic CLE (111 patients, 51.2%) at their most recent set of biopsies. The annual incidence of AC in LGD was 17/633.7 patient-years of follow-up (2.7% p.a. 95% confidence interval 1.6-4.3% p.a.). A further 12 patients developed HGD during follow-up, yielding a combined annual incidence of HGD and AC of 29/633.7 (4.6% p.a. 95% confidence 3.1-6.6% p.a.). Conclusion: In a large cohort of 243 patient s with LGD, 148 (68.2%) had reverted to non-dysplastic CLE or indefinite changes for dysplasia at final follow-up. Patients found to have LGD are at a significant risk of developing HGD and AC compared to those without dysplasia and should be followed-up closely to enable early detection of HGD/AC.

A surveillance programme for Barrett??s oesophagus in a UK general hospital

Surveillance programmes for oesophageal cancer in patients with Barrett's columnar-lined oesophagus have reported varying efficacies. To review the effectiveness of an endoscopic surveillance programme for patients with Barrett's oesophagus in a UK general hospital. Patients with Barrett's oesophagus (> or =3 cm histologically proven columnar-lined oesophagus) were identified from endoscopic and histological records and outcomes recorded when surveillance was performed with 2-yearly endoscopies and quadrantic biopsies at 3 cm intervals. One hundred and twenty-one patients (24%) entered the surveillance programme (mean age 60.2 years, 69.5% men, mean length of Barrett's mucosa 7.5 cm) of 505 patients identified with Barrett's oesophagus. Two hundred and five endoscopies were performed over a mean follow-up of 3.5 years. Five cases of high-grade dysplasia and two cases of adenocarcinoma were detected during the surveillance. One patient with high-grade dysplasia refused surgery and died of oesophageal carcinoma. The other six patients underwent oesophagectomy and five of the six resected specimens showed early (Tis to T2, N0) adenocarcinoma. All six patients remained well and tumour free at 24 months. No interval oesophageal cancers occurred. This surveillance programme for classical Barrett's oesophagus was effective with six cancers being detected early and treated. The detection rate was 1/71 patient-years of surveillance. Endoscopic workload was not excessive and no interval cancers occurred.

Barrett's oesophagus: effect of antireflux surgery on symptom control and development of complications.

Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO.

Role of salivary epidermal growth factor in the pathogenesis of Barrett's columnar lined oesophagus

Epidermal growth factor (EGF) is implicated in the regeneration of epithelial cells at the site of inflammation or ulceration in the gastrointestinal tract. Single parotid EGF concentration and production was studied in 64 patients with Barrett's columnar lined oesophagus (CLO), in 22 patients with severe reflux oesophagitis without columnar metaplasia and in 51 normal controls. In control patients, mean salivary EGF concentration was 2790 pg/ml (median 1450 pg/ml; range 450-16,500 pg/ml) and mean single parotid EGF production was 2550 pg/min (median 1750 pg/min; range 790-18,000 pg/min). Patients with severe reflux oesophagitis had a similar EGF concentration (mean 3112 pg/ml; median 1500 pg/ml; range 300-16,000 pg/ml) and production (mean 3100 pg/min; median 2200 pg/min; range 790-17,950 pg/min) to controls. Patients with CLO had a 62 per cent lower mean EGF concentration (mean 1197 pg/ml; median 640 pg/ml; range 233-4500 pg/ml) (P less than 0.001, Mann-Whitney U test) and a 60 per cent lower EGF production (mean 1254 pg/min; median 800 pg/min; range 170-3125 pg/min) (P less than 0.001, Mann-Whitney U test) than patients with severe reflux oesophagitis. A subpopulation with malignant change in CLO (n = 16) had a similar EGF concentration and production to the CLO group as a whole (mean 1240 and 1300 pg/min, respectively). Low salivary EGF levels are associated with Barrett's CLO but not with severe oesophagitis without columnar metaplasia. EGF levels do not identify those patients who will subsequently develop malignant change.

C-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus.

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.

Epithelial proliferation in Barrett's esophagus by proliferating cell nuclear antigen immunolocalization

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein to DNA polymerase δ and is an absolute requirement for cellular proliferation. Specialized-type Barrett's columnar-lined esophagus (CLE) is associated with adenocarcinomatous change. In the present study, the cellular proliferation of three histological types of CLE was assessed by semi-quantitative evaluation of PCNA immunolocalization in 93 biopsy specimens from 45 patients using the murine monoclonal PC10. Statistical comparison was performed by the Mann-Whitney U test. Luminal surface cell labeling was uncommon in all histological types other than specialized CLE where 25 of the 43 biopsy specimens had at least occasional luminal surface cell labeling. Mean crypt labeling score of 4.06 for specialized type exceeded that for junctional (mean, 3.12; P < 0.001) and fundic types (mean, 1.6; P < 0.001). Gland cell PCNA staining scores for specialized-type CLE (mean, 3.18) exceeded that of junctional (mean, 1.97; P < 0.001) and fundic (mean, 1.04; P < 0.001). Summated PCNA scores for specialized-type, mean of 8.29, exceeded junctional mean score of 5.45 (P < 0.001) and fundic mean score of 2.76 (P < 0.001). PCNA immunolocalization reveals a high proportion of cells in cycle in the specialized-type CLE and expansion of the proliferative compartment, which may explain the association of specialized-type CLE with malignancy.

Endoscopic Diagnosis of Early Primary Adenocarcinoma in Barrett's Columnar-Lined Esophagus

Endoscopic Diagnosis of Early Primary Adenocarcinoma in Barrett's Columnar-Lined Esophagus