Barrett's Segment Research Articles

Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation.

Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.

The use of a real-time computer-aided detection system for visible lesions in the Barrett’s esophagus during live endoscopic procedures: a pilot study (with video)

This pilot study evaluated the performance of a recently developed computer-aided detection (CADe) system for Barrett's neoplasia during live endoscopic procedures. Fifteen patients with a visible lesion and 15 without were included in this study. A CAD-assisted workflow was used that included a slow pullback video recording of the entire Barrett's segment with live CADe assistance, followed by CADe-assisted level-based video recordings every 2 cm of the Barrett's segment. Outcomes were per-patient and per-level diagnostic accuracy of the CAD-assisted workflow, in which the primary outcome was per-patient invivo CADe sensitivity. In the per-patient analyses, the CADe system detected all visible lesions (sensitivity 100%). Per-patient CADe specificity was 53%. Per-level sensitivity and specificity of the CADe-assisted workflow were 100% and 73%, respectively. In this pilot study, detection by the CADe system of all potentially neoplastic lesions in Barrett's esophagus was comparable to that of an expert endoscopist. Continued refinement of the system may improve specificity. External validation in larger multicenter studies is planned. (Clinical trial registration number: NCT05628441.).

Significance of Crypt Atypia in Barrett’s Esophagus: A Clinical, Molecular, and Outcome Study

The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry. In patients who had dysplasia in their baseline biopsy specimens, dysplasia was associated significantly with increasing grades of crypt atypia in the background nondysplastic Barrett's esophagus (P < .001). In a subset of patients without dysplasia at baseline (N= 149), a higher grade of crypt atypia was associated with longer Barrett's esophagus segment length (5.5 vs 3.3 cm; P= .0095), and a higher percentage of cells with 4N DNA content (3.67 ± 1.27 vs 2.93 ± 1.22; P= .018). Crypt atypia was associated with the development of any neoplasia (low-grade dysplasia and HGD/EAC). Although no significant association was noted between the grade of crypt atypia and increased 4N, aneuploidy, or progression to HGD/EAC, only patients with grade 2 or 3 crypt atypia showed increased 4N, aneuploidy, or progression to HGD/EAC. Patients with Barrett's esophagus likely develop dysplasia via a progressive increase in the level of crypt atypia before the onset of dysplasia, and these changes may reflect some alteration of DNA content.

Categorizing Risks within Barrett's Esophagus To Guide Surveillance and Interception; Suggesting a New Framework.

Barrett's esophagus is a precancerous condition that can progress in a stepwise manner to dysplasia and eventually esophageal adenocarcinoma (EAC). Once diagnosed, patients with Barrett's esophagus are kept on surveillance to detect progression so that timely intervention can occur with endoscopic therapy. Several demographic and clinical risk factors are known to increase progression toward EAC, such as longer Barrett's segments, and these patients are kept on tighter surveillance. While p53 IHC has been advocated as an adjunct to histopathologic diagnosis, use of this biomarker is variable, and no other molecular factors are currently applied. Given the new evidence available, it is time to consider whether other risk factors or tools could be applied in clinical practice to decide on closer or attenuated surveillance. In this commentary, we summarize the most relevant risk factors for Barrett's esophagus progression, highlight the most promising novel risk stratification tools-including nonendoscopic triage and commercial biomarker panels, and propose a new framework suggesting how to incorporate risk stratification into clinical practice.

Predictive factors of radiofrequency ablation failure in the treatment of dysplastic Barrett's esophagus

IntroductionRadiofrequency ablation (RFA) has become the recommended endoscopic treatment for flat dysplastic Barrett's esophagus. However, the outcomes of this treatment are variable across European countries. Our aim was to report the results of a French high-volume center, and to investigate factors associated with treatment failure. MethodsWe conducted a single-center retrospective study from a prospectively collected database from 2011 to 2020, including all consecutive patients treated with RFA for flat dysplastic Barrett's esophagus. The primary endpoint was the failure rate of esophageal radiofrequency treatment, defined as either persistence of intestinal metaplasia at the end of treatment, or neoplastic progression during RFA. Results96 patients treated with a median of four RFA sessions for a mean C5M6 Barrett's esophagus were included in the analysis. Complete eradication of intestinal metaplasia and dysplasia were achieved in 59% and 79% of patients, respectively, resulting in a treatment failure rate of 41%. Ten patients experienced neoplastic progression during treatment. We recorded 14% of post-RFA esophageal strictures, all successfully treated by endoscopic dilatation. Univariate analysis identified the length of Barrett's esophagus and the absence of hiatal hernia as predictive factors for treatment failure, however not confirmed in multivariate analysis. ConclusionIn our experience, RFA of flat dysplastic Barrett's esophagus had a 41% treatment failure rate. The length of the Barrett's segment might be associated with treatment failure. Although our results confirm a role for RFA in the management of dysplastic Barrett's esophagus, the treatment failure rate was higher than expected. This suggest that endoscopists, even in high-volume centers, should receive specific training in RFA.

S432 Fifty Percent Increase in Low-Grade Dysplasia Detection Using Probe-Based Confocal Endomicroscopy in a Metropolitan Veteran Cohort Undergoing Short Segment Barrett’s Esophagus Surveillance

Introduction: Seattle protocol (SP) is the standard method to biopsy Barrett’s esophagus. However, SP may miss dysplasia in all types of BE. Few studies have focused on pCLE in the diagnosis of dysplasia in short segment Barrett’s esophagus (SSBE). The primary aim of our study was to determine if pCLE was more effective in diagnosing dysplastic mucosa in patients undergoing surveillance endoscopy in SSBE. Methods: Patients undergoing surveillance endoscopy and diagnosed with SSBE between January 1, 2018 and January 1, 2021 at the VA Loma Linda Healthcare System (VALLHCS) were included. Patients who underwent pCLE were compared to those undergoing SP. Esophagogastroduodenoscopy (EGD) was performed using a high definition diagnostic upper endoscope (Olympus, Center Valley PA). All patients in both pCLE and SP group underwent high-definition white light examination (HD-WLE). All pCLE examinations were performed by two gastroenterologists (C.S.J.and N.S.) using GastroFlex UHD Confocal Miniprobe (Cellvizio, Mauna Kea Technologies). Age, sex, number of EGDs prior to a diagnosis of dysplasia, hiatal hernia length and pCLE findings were assessed. SSBE was defined using Prague criteria, circumference (C) ≤ 2cm and maximal length of Barrett's segment (M) ≤ 3cm. Two pathologists reviewed all biopsies with a diagnosis of dysplasia. Continuous variables were compared using a Fisher’s exact test with p≤0.05 as statistically significant. This study was approved by the institutional review board for VALLHCS. Results: Sixty-seven patients were identified as having SSBE. Sixteen patients underwent pCLE-targeted biopsies while 51 underwent SP. The mean age of the pCLE group was 64 years and 65.9 years for those who underwent SP. There was no difference in age, BMI, smoking status, statin, H2 blocker or PPI use in patients who underwent pCLE-targeted biopsies versus those who underwent SP. Low-grade dysplasia was detected in 17 patients (25.3%). Of these 17 patients, 11 were detected with pCLE, and 6 were detected with SP. The use of pCLE was significantly associated with detection of low-grade dysplasia (11/16, 68.7%) compared to (6/51, 11.7%) with a p-value of < 0.001. Conclusion: In a primarily male metropolitan veteran population, pCLE may be helpful in identifying low grade dysplasia in patients with SSBE. SP biopsy techniques may miss LGD during SSBE surveillance.

Barrett esophagus frequency and predictors of dysplasia or cancer in Barrett esophagus.

Identificating factors associated with an increased risk for dysplasia and cancer development among patients with Barrett esophagus would aid better patient care and improve risk stratification approaches. This study aimed at examining the frequency of Barrett esophagus and factors predicting the presence of dysplasia and cancer among patients with Barrett esophagus. Adult patients that underwent upper gastrointestinal endoscopic examination for gastroesophageal complaints were screened in this retrospective, cross-sectional study; and patients diagnosed with Barrett esophagus were included in the analysis. Frequency of dysplasia/cancer and its predictors were examined. Among 10,404 endoscopic examinations performed during the study period, 143 patients (1.4%) were diagnosed with Barrett esophagus. Among patients with Barrett esophagus, the frequency for high-grade dysplasia, low grade dysplasia, and adenocarcinoma was 2.8%, 2.1%, and 1.4%, respectively. On multivariate analysis, age ≥55 years (OR, 11.1 [95%CI: 2.0-61.4], p=0.006) and long segment Barrett esophagus (OR, 5.7 [95%CI: 1.2-27.8], p=0.031) emerged as significant independent predictors for dysplasia/cancer. Frequency of Barrett esophagus in our population seems to be different than figures reported from different geographical regions. Advanced age and long Barrett segment on endoscopic examination are associated with the presence of concomitant dysplasia/cancer on pathological examination. Larger studies with prospective methodology are warranted.

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

SummaryBackgroundEndoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.MethodsWe first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance.FindingsThe prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia.InterpretationCytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways.FundingMedical Research Council, Cancer Research UK, Innovate UK.

Longitudinal and Circumferential Distributions of Dysplasia and Early Neoplasia in Barrett's Esophagus: A Pooled Analysis of Three Prospective Studies.

INTRODUCTION:Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies.METHODS:This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded.RESULTS:A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half (P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere (P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002).DISCUSSION:In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.

Population-Based Prevalence of Gastrointestinal Abnormalities at Colon Capsule Endoscopy

The population prevalence of gastrointestinal (GI) disease is unclear and difficult to assess in an asymptomatic population. The aim of this study was to determine prevalence of GI lesions in a largely asymptomatic population undergoing colon capsule endoscopy (CCE). Participants aged between 50-75 years were retrieved from the Rotterdam Study, a longitudinal epidemiological study, between 2017-2019. Participants received CCE with bowel preparation. Abnormalities defined as clinically relevant were Barrett segment >3cm, severe ulceration, polyp >10 mm or ≥3 polyps in small bowel (SB) or colon, and cancer. Of 2800 invited subjects, 462 (16.5%) participants (mean age 66.8 years, female 53.5%) ingested the colon capsule. A total of 451 videos were analyzed, and in 94.7% the capsule reached the descending colon. At least 1 abnormal finding was seen in 448 (99.3%) participants. The prevalence of abnormalities per GI segment, and the most common type of abnormality, were as follows: Esophageal 14.8% (Barrett's esophagus <3 cm in 8.3%), gastric 27.9% (fundic gland polyps in 18.1%), SB abnormalities 33.9% (erosions in 23.8%), colon 93.3% (diverticula in 81.2%). A total of 54 participants (12%) had clinically relevant abnormalities, 3 (0.7%) in esophagus/stomach (reflux esophagitis grade D, Mallory Weiss lesion and severe gastritis), 5 (1.1%) in SB (polyps > 10 mm; n = 4, severe ulcer n = 1,) and 46 (10.2%) in colon (polyp > 10 mm or ≥3 polyps n = 46, colorectal cancer n = 1). GI lesions are very common in a mostly asymptomatic Western population, and clinically relevant lesions were found in 12% at CCE. These findings provide a frame of reference for the prevalence rates of GI lesions in the general population.

A predictive Bayesian network that risk stratifies patients undergoing Barrett's surveillance for personalized risk of developing malignancy.

BackgroundBarrett’s esophagus is strongly associated with esophageal adenocarcinoma. Considering costs and risks associated with invasive surveillance endoscopies better methods of risk stratification are required to assist decision-making and move toward more personalised tailoring of Barrett’s surveillance.MethodsA Bayesian network was created by synthesizing data from published studies analysing risk factors for developing adenocarcinoma in Barrett’s oesophagus through a two-stage weighting process.ResultsData was synthesized from 114 studies (n = 394,827) to create the Bayesian network, which was validated against a prospectively maintained institutional database (n = 571). Version 1 contained 10 variables (dysplasia, gender, age, Barrett’s segment length, statin use, proton pump inhibitor use, BMI, smoking, aspirin and NSAID use) and achieved AUC of 0.61. Version 2 contained 4 variables with the strongest evidence of association with the development of adenocarcinoma in Barrett’s (dysplasia, gender, age, Barrett’s segment length) and achieved an AUC 0.90.ConclusionThis Bayesian network is unique in the way it utilizes published data to translate the existing empirical evidence surrounding the risk of developing adenocarcinoma in Barrett’s esophagus to make personalized risk predictions. Further work is required but this tool marks a vital step towards delivering a more personalized approach to Barrett’s surveillance.

Within-patient phylogenetic reconstruction reveals early events in Barrett's Esophagus.

Barrett's Esophagus is a neoplastic condition which progresses to esophageal adenocarcinoma in 5% of cases. Key events affecting the outcome likely occur before diagnosis of Barrett's and cannot be directly observed; we use phylogenetic analysis to infer such past events. We performed whole‐genome sequencing on 4–6 samples from 40 cancer outcome and 40 noncancer outcome patients with Barrett's Esophagus, and inferred within‐patient phylogenies of deconvoluted clonal lineages. Spatially proximate lineages clustered in the phylogenies, but temporally proximate ones did not. Lineages with inferred loss‐of‐function mutations in both copies of TP53 and CDKN2A showed enhanced spatial spread, whereas lineages with loss‐of‐function mutations in other frequently mutated loci did not. We propose a two‐phase model with expansions of TP53 and CKDN2A mutant lineages during initial growth of the segment, followed by relative stasis. Subsequent to initial expansion, mutations in these loci as well as ARID1A and SMARCA4 may show a local selective advantage but do not expand far: The spatial structure of the Barrett's segment remains stable during surveillance even in patients who go on to cancer. We conclude that the cancer/noncancer outcome is strongly affected by early steps in formation of the Barrett's segment.

Deep learning algorithm detection of Barrett’s neoplasia with high accuracy during live endoscopic procedures: a pilot study (with video)

We assessed the preliminary diagnostic accuracy of a recently developed computer-aided detection (CAD) system for detection of Barrett's neoplasia during live endoscopic procedures. The CAD system was tested during endoscopic procedures in 10 patients with nondysplastic Barrett's esophagus (NDBE) and 10 patients with confirmed Barrett's neoplasia. White-light endoscopy images were obtained at every 2-cm level of the Barrett's segment and immediately analyzed by the CAD system, providing instant feedback to the endoscopist. At every level, 3 images were evaluated by the CAD system. Outcome measures were diagnostic performance of the CAD system per level and per patient, defined as accuracy, sensitivity, and specificity (ground truth was established by expert assessment and corresponding histopathology), and concordance of 3 sequential CAD predictions per level. Accuracy, sensitivity, and specificity of the CAD system in a per-level analyses were 90%, 91%, and 89%, respectively. Nine of 10 neoplastic patients were correctly diagnosed. The single lesion not detected by CAD showed NDBE in the endoscopic resection specimen. In only 1 NDBE patient, the CAD system produced false-positive predictions. In 75% of all levels, the CAD system produced 3 concordant predictions. This is one of the first studies to evaluate a CAD system for Barrett's neoplasia during live endoscopic procedures. The system detected neoplasia with high accuracy, with only a small number of false-positive predictions and with a high concordance rate between separate predictions. The CAD system is thereby ready for testing in larger, multicenter trials. (Clinical trial registration number: NL7544.).

External validation of a model to determine risk of progression of Barrett's oesophagus to neoplasia.

A risk prediction model containing sex, smoking history, Barrett's oesophagus length and presence of low-grade dysplasia was found to identify individuals at a higher risk of progression to oesophageal adenocarcinoma or high-grade dysplasia. To externally validate the model predicting risk of progression from Barrett's oesophagus to neoplasia and assess the predictive utility of additional factors. We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of Barrett's oesophagus (with intestinal metaplasia) between 1993 and 2005. The association between a points based model and risk of progression to high-grade dysplasia or oesophageal adenocarcinoma until 2010 was assessed using Cox Proportional Hazards model. Model performance was assessed using area under the receiver operating characteristics curves (AUROC), sensitivity and specificity. We identified 1198 individuals with Barrett's oesophagus of whom 54 progressed. The model discriminated reasonably well between progressors and nonprogressors, with an AUROC of 0.70 (95% CI 0.63-0.78). When categorised into low, intermediate and high risk groups, the AUROC was 0.68 (95% CI 0.61-0.74). Compared to using data on dysplasia and segment length for risk stratification, the model resulted in a net reclassification improvement of 20.9%. This external validation provides further evidence that a model based on sex, smoking, Barrett's segment length and baseline low-grade dysplasia may help to risk stratify patients after an initial diagnosis of Barrett's oesophagus. The model also performed better than the use of low-grade dysplasia status alone for risk-stratification.

Endoscopic therapy for Barrett's esophagus and early esophageal cancer: Where do we go from here?

Since Barrett’s esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett’s esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett’s patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett’s segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett’s esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett’s epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.

Is Barrett's-Associated Esophageal Adenocarcinoma a Clonal Disease?

In this study, we argue that the basic clonal unit that makes up the Barrett's segment is at the level of the gland. There is expansion of this clonal unit, the gland, by fission, and there is evidence that the Barrett's segment is itself a clonal proliferation. Barrett's esophagus arises from both goblet cell-containing metaplasia and non-goblet cell-containing metaplasia and may arise from a stable clone, but the genomic changes occurring are subject to selection, usually with little or no evolution, appearing indolent from the evolutionary perspective. Genomic changes leading to dysplastic phenotypes are selected, but without any single clone predominating within the segment.

Does anti-reflux surgery control Barrett’s oesophagus progression?

Controversy exists as to whether or not anti-reflux surgery can prevent the potential long-term complications of Barrett's oesophagus, in particular, dysplastic changes. Hence, literature was reviewed to find out effects of anti-reflux surgery on patients with Barrett's oesophagus. Data has been analysed using different electronic database including Ovid Medline, Scopus, Google Scholar and PubMed. Anti-reflux surgery is considered an effective option for rapid and long-term control of reflux symptoms. Most patients who were included in the studies had a satisfactory control of their symptoms after surgery. Successful procedures effectively abolished gastric reflux in the majority of patients. On the other hand, there were different patterns of Barrett's oesophagus segment progression after surgery regardless of the procedure's success. Many patients developed de novo Barrett's oesophagus, at the same time the intestinal metaplasia regressed in other patients, but the Barrett segment has remained unchanged in the majority of patients. Similarly, the pattern of dysplasia progression was different among patients. Surgery was effective in producing dysplasia regression in many patients, but it failed to prevent progression of columnar intestinal metaplasia into dysplasia in other patients. In conclusion the potential long-term complications of Barrett's oesophagus can develop after anti-reflux surgery. Therefore, long life follow- up, after surgery, is mandatory.

Cryotherapy and Radiofrequency Ablation for Eradication of Barrett's Esophagus with Dysplasia or Intramucosal Cancer.

Endoscopic ablation therapy has become the mainstay of treatment of Barrett's associated dysplasia and intramucosal cancer (IMC). The widely available techniques for ablation are radiofrequency ablation (RFA) and cryotherapy. Our aim was to compare eradication rates of metaplasia and dysplasia with both these modalities. Retrospective review of prospectively collected database of patients who underwent endoscopic therapy for Barrett's dysplasia or IMC from 2006 to 2011 was performed. Demographic features, comorbidities, and endoscopic data including length of Barrett's segment, hiatal hernia size, interventions during the endoscopy and histological results were reviewed. Among 154 patients included, 73 patients were in the RFA and 81 patients were in the cryotherapy group. There was complete eradication of intestinal metaplasia (CE-IM) in 81 (52.6%), complete eradication of dysplasia (CE-D) in 133 (86.4%), and persistent dysplasia or cancer in 19 patients (12.3%). Compared to RFA, cryotherapy patients were found to be older and less likely to have undergone endoscopic mucosal resection. On multivariate analysis, patients who underwent RFA had a threefold higher odds of having CE-IM than those who underwent cryotherapy (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.4-6.0, p = 0.004), but CE-D were similar between the two groups (OR 1.7, 95% CI 0.66-4.3, p = 0.28). Endoscopic therapy is highly effective in eradication of Barrett's associated neoplasia. Patients who underwent cryotherapy were equally likely to achieve CE-D but not CE-IM than patients who underwent RFA. Patient characteristics and preferences may effect choice of treatment selection and outcomes.

Does the treatment of proton pump inhibitors reduce dysplasia or adenocarcinoma development in Barrett's esophagus?

Besides reducing the reflux symptoms, the benefit of proton pump inhibitors (PPI) in the treatment of Barrett's esophagus (BE) is not exactly known. The data in the literature show that although the PPI treatment does not reduce the Barrett's segment length, it can reduce dysplasia or the development of early-stage adenocarcinoma (odds ratio (OR): 0.46). Therefore, treatments with PPI may be considered in patients with a diagnosis of BE and at a high risk of adenocarcinoma, even though they are not symptomatic.