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Original article
Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression
  1. F Kastelein1,
  2. S H van Olphen1,2,
  3. E W Steyerberg3,
  4. M C W Spaander1,
  5. M J Bruno1
  6. on behalf of the ProBar-study group
    1. 1Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
    2. 2Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
    3. 3Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
    1. Correspondence to Florine Kastelein, Department of Gastroenterology and Hepatology, Erasmus Medical Center, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands; f.kastelein{at}rdgg.nl.

    Abstract

    Objective Endoscopic surveillance for Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage and survival of patients with neoplastic progression.

    Design 783 patients with BO of at least 2 cm were included in a multicentre prospective cohort and followed during surveillance according to the American College of Gastroenterology guidelines. Cases of high-grade dysplasia and OAC were identified during follow-up. OAC staging was performed according to the 7th UICC-AJCC classification. Survival data were collected and crosschecked using death and municipal registries. Data from patients with OAC in the general population were obtained from the Dutch cancer registry. We compared survival of patients with BO with neoplastic progression during surveillance with those of patients without neoplastic progression and patients with OAC in the general population.

    Results 53 patients with BO developed high-grade dysplasia or OAC during surveillance. Thirty-five (66%) were classified as stage 0, 14 (26%) as stage 1 and 4 (8%) as stage 2. OAC was diagnosed at an earlier stage during BO surveillance than in the general population (p<0.001). Survival of patients with BO with neoplastic progression was not significantly worse than those of patients without neoplastic progression and similar to survival of patients with stage 0 or stage 1 OAC in the general population.

    Conclusions OAC is detected at an earlier stage during BO surveillance than in the general population with good survival rates.

    • BARRETT'S OESOPHAGUS
    • OESOPHAGEAL CANCER
    • SURVEILLANCE
    • BARRETT'S CARCINOMA
    • BARRETT'S METAPLASIA

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    Significance of this study

    What is already known on this subject?

    • Endoscopic surveillance is recommended for Barrett's oesophagus (BO) to detect oesophageal adenocarcinoma (OAC) at an early stage.

    • Over the past years there has been a major shift in the treatment of patients with high-grade dysplasia and early OAC using endoscopic techniques.

    • Previous studies have investigated the impact on survival in patients with BO undergoing endoscopic surveillance with conflicting results.

    What are the new findings?

    • Endoscopic surveillance of patients with BO of at least 2 cm enables the detection of OAC at an earlier stage than in the general Dutch population.

    • The survival of patients with BO with neoplastic progression during surveillance was not significantly worse than those of patients with BO without neoplastic progression.

    • The survival of patients with BO with neoplastic progression during surveillance was similar to the survival of patients with stage 0 or stage 1 OAC in the general population.

    How might it impact on clinical practice in the foreseeable future?

    • These results support current guidelines recommending endoscopic surveillance in patients with BO of at least 2 cm.

    Introduction

    Barrett's oesophagus (BO) is a premalignant condition in which patients have an increased risk of developing oesophageal adenocarcinoma (OAC) with an estimated incidence of 0.1–0.5% per year.1–4 The development of OAC in BO is a gradual process, in which metaplastic epithelium without dysplasia evolves to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and eventually OAC under the influence of oesophageal acid exposure.5 ,6 Once a patient has developed OAC the prognosis is poor with a 5-year survival of less than 20%.7–9 Endoscopic BO surveillance is therefore recommended to detect OAC at an early stage, when curative treatment is still feasible.10 ,11 Current guidelines recommend endoscopic surveillance every 3–5 years in patients with non-dysplastic BO, every 6–12 months in patients with LGD and (endoscopic) treatment in patients with established HGD or OAC.10 ,11 A major drawback of endoscopic surveillance is that it is an invasive and expensive procedure which is subject to interobserver variation, sampling error and variation in protocols. However, endoscopic surveillance is the only screening test available for BO. Over the past years there has been a major shift in the treatment of patients with BO with neoplastic progression with the introduction of endoscopic mucosal resection (EMR) and ablation techniques such as radiofrequency ablation (RFA), photodynamic therapy (PDT) and argon plasma coagulation.12 Endoscopic treatment is effective, less burdensome, associated with low morbidity and mortality rates, and may improve survival.13 Although oesophagectomy is still the mainstay for advanced OAC, oesophagectomy is nowadays complemented by neoadjuvant chemotherapy or chemoradiotherapy.14 Chemotherapy, oesophageal stenting and brachytherapy have been added to the palliative treatment of OAC.15

    Recently, the value of endoscopic BO surveillance has been under discussion given the overall low incidence of neoplastic progression and lack of evidence that endoscopic surveillance reduces the risk of advanced OAC and improves survival.16–18 These key questions have been evaluated in case-control studies, population-based studies and small prospective cohort studies with conflicting results.12 ,18–32 Although most studies suggest that endoscopic surveillance enables the detection of early OAC with good survival, some other studies reported no effect on mortality.18 Furthermore in most studies patients were included independent of BO length. However the risk of neoplastic progression is much lower in patients with short BO.33 ,34 The aim of the present study was to evaluate the impact of endoscopic surveillance of patients with BO of at least 2 cm according to current guidelines, on tumour stage and survival of patients with OAC.

    Methods

    Study design

    We conducted a large multicentre prospective cohort study in 3 academic and 12 regional hospitals throughout the Netherlands (see online supplementary appendix 1). Between November 2003 and December 2004, 783 consecutive patients were included with known or newly diagnosed BO with a maximum length of at least 2 cm according to the Prague (Circumferential and maximal BO length) criteria.35 The endoscopic diagnosis was confirmed by the presence of intestinal metaplasia and patients with HGD or OAC in the past or at the index endoscopy were excluded. Endoscopic surveillance was performed according to guidelines of the American College of Gastroenterology.11 Patients without dysplasia underwent upper endoscopy with biopsy sampling every 3 years and patients with LGD every year. All endoscopic procedures were performed by experienced gastroenterologists, according to a standardised protocol. At each endoscopy targeted biopsies were taken from mucosal abnormalities and quadrant biopsies were taken every 2 cm from the most distal part to the most proximal part of the BO epithelium, according to the Seattle protocol.36 Most patients are still under surveillance.

    Histology

    Biopsy specimens were fixed with buffered formalin and embedded in paraffin, according to standard procedures. From each biopsy set 4μm thick sections were cut and stained with H&E to assess the presence of BO and define the grade of dysplasia. After examining all biopsies, the highest degree of abnormality was reported for each endoscopy. Slides were first graded by a local pathologist and then by an expert pathologist for second opinion. When the local and expert pathologists disagreed on the grade of dysplasia, the slides were reviewed by a second expert pathologist. Pathologists were blinded to the diagnosis of each other and a final diagnosis was made only if at least two pathologists agreed on the grade of dysplasia. If there was disagreement, a panel of expert pathologists reviewed the slides and a final diagnosis was made based on consensus agreement.

    Neoplastic progression

    Neoplastic progression was defined as the development of HGD or OAC after inclusion in the study. The diagnosis was made only if at least two pathologists, including an expert pathologist, agreed on the presence of HGD or OAC. Patients with neoplastic progression were treated according to the guidelines of the American College of Gastroenterology. Patients with HGD received intensive endoscopic surveillance or were treated as early OAC with EMR, ablation techniques or a combination of both depending on local expertise. Patients with advanced OAC received oesophagectomy with or without neoadjuvant chemoradiotherapy.11 OAC staging was performed according to the 7th (International Union Against Cancer and American Joint Committee on Cancer) classification. The stage of the primary tumour was based on histological assessment of biopsies, EMR specimens or resection specimens, whichever was available. The highest tumour stage was reported for each patient. After endoscopic or surgical treatment surveillance was resumed. During follow-up occurrence of complications, recurrence and metastasis was recorded.

    Survival

    Survival data were collected from all patients included in the study. Since surveillance intervals were up to 3 years and some patients dropped out of surveillance, survival was cross-checked using death registries and municipal administrations. When a patient was deceased, the cause of death was obtained from the attending gastroenterologist or general practitioner. Survival data from patients with OAC in the Netherlands, independent of cause of death and stratified by age, gender, stage and year of diagnosis, were obtained from the Dutch cancer registry over the same time period.7 Data on cause of death in the general population, stratified by age, gender and year of death, were obtained from the Dutch central statistical office.37

    Statistical analysis

    The incidence rate of neoplastic progression was calculated by dividing the number of patients with HGD or OAC by the total person-years of follow-up. χ2 tests were used to compare OAC stage at diagnosis in patients with BO undergoing surveillance and patients with OAC in the general population. Survival of patients with BO with and without neoplastic progression during surveillance was compared in Cox proportional-hazards models adjusted for age and gender, whereby neoplastic progression was modelled as a time-dependent variable. Follow-up time was defined as the time from inclusion in the study to death or 1 January 2014, whichever came first. When no information was available from death or municipal registries, follow-up time was defined as the time from inclusion in the study to the last surveillance endoscopy. Cox-regression models were used to calculate HRs and 95% CIs. In addition, survival of patients with different OAC stages in the general population was evaluated and compared with survival of patients with neoplastic progression during BO surveillance. To adjust for lead time bias, which is the time between the detection of preclinical OAC during surveillance and the moment OAC becomes symptomatic, we estimated the sojourn time for OAC from the difference in mean age at OAC diagnosis between patients with BO undergoing surveillance and patients with OAC in the general population. To adjust for length time bias, which refers to the detection of less aggressive OAC during surveillance, we performed sensitivity analyses in which we only included patients with OAC. The 5-year cumulative survival was estimated using survival tables and Kaplan-Meier curves. In addition, we evaluated cause of death in patients with BO and in individuals with similar age and gender in the general population. Two sided p<0.05 was considered to be statistically significant. Data were analysed using SPSS Statistics V.20.0 (Chicago, Illinois, USA).

    Results

    Patient characteristics

    Seven hundred and eighty-three patients (73% male, median age 61 years) were included and followed during surveillance with a median duration of 7 years (IQR 4–8 years) and a total 4556 person-years of follow-up (table 1). The majority of patients (72%) was already known with BO before inclusion in the study. At baseline, patients had a median BO length of 4 cm (IQR 2–6 cm), 78 (10%) patients were diagnosed with oesophagitis and 117 (15%) with LGD.

    Table 1

    Characteristics of patients with Barrett's oesophagus and patients with OAC in the general population

    Neoplastic progression

    After a median follow-up of 3 years 53 patients (83% male, median age 68 years) developed HGD or OAC with an incidence rate of 1.2 per 100 person-years (IQR 0.9–1.5), which was stable over time (figure 1). The incidence rate was 0.3 per 100 person-years (IQR 0.2–0.6) for OAC (all stages) and 0.1 per 100 person-years (IQR 0.02–0.2) for advanced OAC (at least stage 2). Thirty-five patients (66%) developed HGD, 12 (22%) T1a OAC, 2 (4%) T1b OAC, 2 (4%) T2 OAC and 2 (4%) T3 OAC. In two patients with T2 OAC, metastases were found in regional lymph nodes (N1). In none of the other patients lymph node metastases were found (N0). At the time of diagnosis, there was no evidence of distant metastases in any of the patients (M0). Thirty-five patients (66%) were classified as stage 0 disease, 14 (26%) as stage 1 and 4 (8%) as stage 2. OAC stage at diagnosis did not significantly change over time. Three patients (75%) with stage 2 OAC were previously diagnosed with LGD, for which they received annual surveillance. The remaining patient was never diagnosed with dysplasia and received surveillance every 3 years. Two patients (50%) with LGD at inclusion were diagnosed with stage 2 OAC at the first follow-up endoscopy 1 year later.

    Figure 1

    Cumulative incidence of neoplastic progression during Barrett surveillance. HGD and OAC, is ··· HGD, — OAC (all stages), ··· advanced OAC (at least stage 2). HGD, high-grade dysplasia; OAC, oesophageal adenocarcinoma.

    In the Netherlands, 8855 patients (81% male, median age 68 years) were diagnosed with OAC between 2004 and 2012 according the Dutch cancer registry data.7 One per cent of patients was classified as stage 0 disease, 14% as stage 1, 16% as stage 2, 23% as stage 3 and 46% as stage 4. OAC was diagnosed at a significantly earlier stage in the population undergoing BO surveillance than in the general population (p<0.001) (figure 2).

    Figure 2

    Stage of oesophageal adenocarcinoma at the time of diagnosis in patients with Barrett's oesophagus undergoing surveillance (▪) and in the general Dutch population (▪) (p<0.001).

    Treatment

    During surveillance 10 patients were diagnosed with focal HGD without mucosal abnormalities for which they received intensive surveillance. Although the initial diagnosis of HGD was confirmed by expert pathologists, in none of these patients HGD was confirmed during further follow-up. Therefore it was chosen to refrain from endoscopic treatment and follow a policy of watchful waiting. The remaining 25 patients with HGD received endoscopic treatment. Two patients were treated with PDT, 11 with EMR, 7 with EMR followed by PDT and 5 with EMR followed by RFA. One patient developed a stenosis after EMR for which dilatation was performed and one patient had a perforation for which a stent was placed. Five patients had recurrence of HGD or early OAC during follow-up for which they were treated successfully with EMR and RFA. Of the 12 patients with T1a OAC 2 were treated with EMR, 7 with EMR followed by PDT and 2 with EMR followed by RFA. One patient died prior to treatment, one patient developed a stenosis for which dilatation was performed and two patients had recurrence for which they were treated successfully with EMR and RFA. The remaining six patients with T1b, T2 or T3 OAC were treated with transhiatal oesophagectomy, which in two patients was complemented by neoadjuvant chemoradiotherapy. Two patients developed postoperative anastomotic leakage. One patient died due to postoperative complications and two patients due to advanced OAC after a median follow-up of 2 years (figure 3).

    Figure 3

    Treatment of patients with neoplastic progression detected during surveillance. *One patient died prior to treatment of a cause not related to Barrett's oesophagus, all patients with local recurrence were successfully treated with EMR and RFA. HGD, high-grade dysplasia; OAC, oesophageal adenocarcinoma; PDT, photodynamic therapy; EMR, endoscopic mucosal resection; RFA, radiofrequency ablation; THE, transhiatal oesophagectomy.

    Survival

    Of all 53 patients with neoplastic progression during surveillance, 12 patients (23%) (83% male, median age 73 years) died after a median follow-up of 2 years (IQR 1–4 years). The all cause 5-year survival of patients with neoplastic progression during surveillance was 74% (95% CI 60% to 87%) and was similar for patients in academic and regional hospitals. The 5-year survival was 80% for patients with stage 0 disease (n=35), 68% for stage 1 (n=14) and 33% for stage 2 (n=4). Of the remaining 730 patients with BO in the cohort, 100 patients (14%) (76% male, median age 78 years) died after a median follow-up of 7 years (IQR 3–8 years). The all cause 5-year survival of patients with BO without neoplastic progression was 94% (95% CI 92% to 96%). Of the 8855 patients with OAC in the general population, 6352 patients (72%) (81% male, median age 71 years) died after a median follow-up of 7 months (IQR 3–15 months). The all cause 5-year survival of patients with OAC in the Netherlands was 17% (95% CI 16% to 18%). The 5-year survival was 62% for patients with stage 0, 65% for stage 1, 30% for stage 2, 14% for stage 3 and 3% for stage 4 (figure 4).

    Figure 4

    Cumulative survival of patients with Barrett's oesophagus with neoplastic progression during surveillance and patients with different stages of oesophageal adenocarcinoma (OAC) in the general population. Barrett's oesophagus with neoplastic progression during surveillance, ··· OAC stage 0, — OAC stage 1, ··· OAC stage 2, — OAC stage 3, ··· OAC stage 4.

    The overall survival of patients with BO with neoplastic progression during surveillance was only slightly (and not statistically significant) worse than those of patients with BO without neoplastic progression during surveillance (HR 1.8, 95% CI 0.9 to 3.3), and similar to those of patients with stage 0 or stage 1 OAC in the general population (HR 0.8, 95% CI 0.3 to 1.8 and HR 0.7, 95% CI 0.4 to 1.2, respectively).

    Lead and length time bias

    To adjust for lead time bias we estimated the sojourn time for OAC based on the difference in mean age at OAC diagnosis in patients with BO undergoing surveillance and patients from the general population (2.2 years). After adjusting for lead time bias, the all cause 5-year survival of patients with neoplastic progression during BO surveillance was 72% and the overall survival was still similar to those of patients with stage 0 or stage 1 OAC in the general population (HR 0.8, 95% CI 0.4 to 1.7 and HR 0.9, 95% CI 0.5 to 1.6, respectively). To adjust for length time bias we performed separate analyses for patients with BO with at least stage 1 OAC. The all cause 5-year survival of patients with OAC during BO surveillance was 62% and the overall survival was still similar to those of patients with stage 0 or stage 1 OAC in the general population (HR 0.9, 95% CI 0.3 to 2.4 and HR 0.9, 95% CI 0.4 to 2.1, respectively).

    Cause of death

    Of the 783 patients with BO, 112 patients (14%) died after a median follow-up of 6 years. The majority of patients died due to malignancies (36%) or cardiovascular diseases (29%). Four per cent of patients died due to OAC after a median follow-up of 2 years. Of all 53 patients with BO with neoplastic progression during surveillance, 12 patients (23%) died after a median follow-up of 2 years. Two patients (17%) died due to cardiovascular diseases, four (33%) due to pulmonary diseases, and six (50%) due to malignancies, among which three (25%) due to OAC (table 2). The cause of death for patients with BO in our cohort was comparable with those of individuals with similar age and gender in the general population.

    Table 2

    Cause of death in patients with Barrett's oesophagus and the general population

    Discussion

    The results of this large multicentre prospective cohort study suggest that OAC is detected at an earlier stage during surveillance than in the general population, independent of age, gender and year of diagnosis, and that endoscopic treatment leads to good survival.

    Surveillance is a process of periodic testing in patients at high risk for a certain disease. Key elements in the effectiveness of surveillance are whether disease is detected at an early and curable stage and whether survival is improved. In the present study we showed that OAC was detected at a significantly earlier stage during endoscopic BO surveillance than in the general population. Of all patients with neoplastic progression during BO surveillance, 92% was diagnosed with early OAC (stage 0 or stage 1), compared with 15% in the general population. These results are in line with those of previous retrospective and small prospective studies, which reported early OAC in 60–95% of patients with BO with neoplastic progression during surveillance and 10–40% of patients with OAC in the general population.18 ,20 ,22 ,24–26 ,28 ,31 In two previous studies surveillance failed to detect early OAC.7 ,11 One of the major shortcomings of those studies was that patients were not under strict surveillance, which is crucial for the detection of HGD or early OAC.

    In contrast to most previous studies, patients with early OAC in the present study received endoscopic treatment instead of oesophagectomy, according to current guidelines. Since the majority of patients was diagnosed with early OAC, most patients were treated endoscopically and only 12% needed oesophagectomy. After endoscopic treatment six (17%) patients had complications and seven (19%) had recurrence of HGD or OAC for which they received additional endoscopic treatment. None of the patients with early OAC died due to OAC or its treatment.

    The overall 5-year survival was 74% in patients with OAC during BO surveillance and 17% in patients with OAC in the general population. Although it is difficult to compare survival of both groups due to different types of bias, including lead time bias and length time bias, this large difference seems clinically relevant. The results correspond to those of previous retrospective and small prospective studies, which report an overall 5-year survival of 65–100% in patients with OAC during surveillance and 0–30% in patients with symptomatic OAC.6 ,10 ,14 ,16 ,17 ,20 ,24 ,37 ,38 The majority of patients undergoing BO surveillance died due to cardiovascular diseases or malignancies and only 4% due to OAC, which was comparable to cause of death in individuals with similar age and gender in the general population. One in four patients with OAC during surveillance died due to OAC or its treatment. Unfortunately, no information was available on cause of death in patients with OAC in the general population. Since the cause of death in patients undergoing BO surveillance was comparable to those of individuals in the general population, it is likely that excess mortality in patients with OAC in the general population is caused by OAC itself or its treatment. This idea is supported by data from the Surveillance, Epidemiology, and End Results database, which shows that approximately half of patients with OAC in the USA dies due to OAC or its treatment.39

    The present study shows that OAC is detected at an early stage during BO surveillance, but the cost-effectiveness of BO surveillance is still controversial. Several recent studies among which one of our own study group, have shown that BO surveillance may be cost-effective with intervals of 5 years for patients with non-dysplastic BO and 3 years for LGD.40 ,41 Although surveillance intervals were shorter in the current study, a minority of patients still developed advanced OAC. With prolongation of surveillance intervals, the risk of interval carcinomas will increase thereby limiting the protective effect. To improve the cost-effectiveness of endoscopic BO surveillance identification of additional risk factors is needed.38 ,42 ,43 Another possibility to improve cost-effectiveness would be a less invasive screening test.

    Our study has several strengths including the large sample size and long prospective follow-up. Consecutive patients with BO were included presenting at the endoscopy unit of 3 academic and 12 regional hospitals throughout the Netherlands, resulting in a cohort that should be representative for the Dutch BO population. This is also supported by the annual incidence rate of OAC during follow-up of 0.3%, which corresponds to incidence rates reported in previous studies.1 ,3 ,4 There were strict criteria for BO diagnosis and inclusion in the study, such as a BO length of at least 2 cm, presence of intestinal metaplasia in biopsies, and no presence or history of HGD or OAC. In addition, there was a stringent follow-up scheme and a standardised endoscopy and biopsy protocol. All biopsies were reviewed by at least two pathologists to obtain a diagnosis based on consensus. Surveillance and treatment of patients with neoplastic progression was performed according to current guidelines, which include endoscopic treatment modalities and neoadjuvant chemoradiotherapy for advanced OAC. Survival data were collected prospectively and were crosschecked using death registries and municipal administrations.

    Our study also has some limitations. Studies evaluating the effect of surveillance may be subject to lead time bias and length time bias.44 When improved survival is based on earlier detection during surveillance rather than postponement of death this is called lead time bias. Length time bias refers to the fact that surveillance enables the detection of less aggressive disease with a mild course and thereby better survival. Thus even in the absence of a true effect of surveillance it may improve survival due to lead time bias and length time bias. Lead time bias is unlikely to affect the results of our study since improved survival was seen until 10 years after diagnosis, while the median survival of patients with symptomatic OAC was only 11 months. To consider lead time bias and length time bias as much as possible we performed additional analyses in which we estimated the sojourn time for OAC based on difference in mean age at OAC diagnosis and excluded patients with HGD, which had no major effect on the results.

    Unfortunately we were unable to adjust for differentiation grade, since this information was not available for the majority of patients with OAC in the general population.

    Despite our efforts to consider different types of bias as much as possible, we cannot exclude uncontrolled confounding. A randomised controlled trial would be the ideal way to investigate the effect of endoscopic BO surveillance on survival. Although not impossible, it would be difficult to perform such a trial since only a small proportion of patients with OAC is previously known with BO. An alternative would be to perform an observational study including patients with BO undergoing surveillance and patients with BO not under surveillance. Unfortunately, all patients participating in our prospective study received endoscopic surveillance and as a result we were only able to compare our data with those of patients with OAC in the general population.

    We compared the pathological stage and survival of patients with neoplastic progression during BO surveillance with those of patients with OAC in the general population based on data from the Dutch cancer registry. Since patients are included in this registry based on clinical or pathological diagnosis of cancer, there is under-reporting of HGD. However, since most patients were diagnosed with advanced OAC we assume this is not a major source for bias.

    During surveillance 10 patients with BO were diagnosed with focal HGD without mucosal abnormalities and although this diagnosis was confirmed by expert pathologists, in none of these patients HGD was confirmed during further follow-up. An important question is whether this is the result of misclassification or is a reflection of the natural history of focal HGD, since this may result in overtreatment of patients with focal HGD.

    Unfortunately, the Dutch cancer registry provides no information on previous participation in surveillance. It is therefore possible that some patients in the control group had previous surveillance, which may result in an underestimation of the surveillance effect. In addition the registry provides no information on cause of death in patients with OAC.

    Finally, we only included patients with BO of at least 2 cm in the study and therefore our results cannot be applied universally to all patients with BO. Since longer BO length is associated with a higher risk of neoplastic progression we believe that our cohort is representative for the patients who are most likely to benefit from surveillance.

    In conclusion, this study suggests that regular endoscopic surveillance of patients with BO enables the detection of OAC at an early and curable stage when endoscopic treatment is still feasible and leads to good survival. The results of this study therefore support current guidelines recommending endoscopic surveillance in patients with BO.

    References

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    Supplementary materials

    • Supplementary Data

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    Footnotes

    • MCWS and MJB contributed equally.

    • Abstract has been presented at the United European Gastroenterology week 2014.

    • Collaborators The ProBar-study group: K Biermann; H Geldof; H van der Valk; PCJ ter Borg; RWM Giard; RJF Felt; GA Meijer; J Alderliesten; R Heinhuis; F ter Borg; JW Arends; JJ Kolkman; J van Baarlen; TG Tan; B den Hartog; AJP van Tilburg; LGJB Engels; W Vos; FTM Peters; A Karrenbeld; BE Schenk; F Moll; R Loffeld; M Flens; H van Roermund; F Lockefeer.

    • Contributors FK: conception and design, acquisition of data, data analysis, statistical analysis, interpretation of data and writing of manuscript. SHvO: acquisition of data, data analysis, interpretation of data and critical revision of manuscript. EWS: conception and design, data analysis, statistical analysis, interpretation of data and critical revision of manuscript. MCWS: conception and design, data analysis, interpretation of data and critical revision of manuscript. MJB: conception and design, interpretation of data and critical revision of manuscript. All authors listed have contributed substantially to the design, data collection and analysis, and editing of the manuscript.

    • Competing interests None declared.

    • Ethics approval The study protocol was approved by the Institutional Review Boards of the Erasmus University Medical Center, as well as those of all participating hospitals.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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