Barrett's Esophagus Neoplasia Research Articles

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression.

Background and AimBarrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low‐grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high‐grade dysplasia/esophageal adenocarcinoma in patients with confirmed low‐grade dysplasia compared with those with downstaged low‐grade dysplasia from index presentation and referral. We analyzed risk factors for progression.MethodsWe analyzed consecutive patients with low‐grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006–October 2018). Biopsies were reviewed by at least two expert pathologists.ResultsOne hundred and forty‐seven patients referred with suspected low‐grade dysplasia were included. Forty‐two of 133 (32%) of all external referrals had confirmed low‐grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low‐grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non‐dysplastic Barrett's esophagus.ConclusionOur data show variability in the diagnosis of low‐grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low‐grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low‐grade dysplasia were significant risk factors for progression. It is important to differentiate these high‐risk subgroups so that decisions on surveillance/endotherapy can be personalized.

Artificial Intelligence in Surveillance of Barrett's Esophagus.

A study by Waterhouse and colleagues in a previous issue of Cancer Research describes the development and prospective validation of an artificial intelligence approach in conjunction with spectral imaging to enhance endoscopic detection of Barrett's esophagus-related neoplasia. The authors developed a novel spectral endoscope with external optics suitable for routine Barrett's esophagus surveillance with diffuse tissue reflectance to define multispectral data correlated with histopathology. A convolutional neural network was trained on the absis of the spectral signatures acquired as part of a small, prospective clinical trial to distinguish Barrett's esophagus from Barrett's esophagus neoplasia. The results from the study suggest the utility of artificial intelligence for diagnosis of Barrett's esophagus.See related article by Waterhouse et al., Cancer Res 2021;81:3415-25.

Wide-field endoscopic submucosal dissection for the treatment of Barrett's esophagus neoplasia.

Background and study aims Implementation of endoscopic submucosal dissection (ESD) for the treatment of Barrett’s esophagus neoplasia (BEN) has been hampered by high rates of positive margins and complications. Dissection with wider margins was proposed to overcome these problems, but was never tested. We aim to compare Wide-Field ESD (WF-ESD) with conventional ESD (C-ESD) for treatment of BEN. Patients and methods This was a cohort study of all ESDs performed in our center during 2011 to 2018. C-ESD was the only technique used before 2014, with WF-ESD used beginning in 2014. In WF-ESD marking was performed 10 mm from the tumor margin compared to 5 mm with C-E. Results ESD was performed in 90 cases, corresponding to 74 patients, 84 % male, median age 69. Of these, 22 were C-ESD (24 %) and 68 were WF-ESD (76 %). The en bloc resection rate was 95 vs 100 % (ns), the positive lateral margin rate was 23 % vs 3 % ( P < 0.01), the R0 rate was 73 % vs 90 %, and the curative resection rate was 59 % vs 76 % in the C-ESD and WF-ESD groups, respectively, (both P > 0.05). The procedure speed was 4.4 and 2.3 (min/mm) in the C-ESD and WF-ESD groups ( P < 0.01), respectively. WF-ESD was associated with less post-operative strictures, 6 % vs 27 % ( P = 0.01), with no local recurrence but no significantly reduced risk of metachronous recurrence (Hazard Ratio = 0.46, 95 %CI = 0.14–1.46), during a follow-up of 13.4 and 9.4 months in the C-ESD and WF-ESD cohorts, respectively. Conclusions WF-ESD is associated with a reduction in positive lateral margins, faster dissection, and lower stricture rates. Further prospective, multicenter studies are warranted to evaluate its role in clinical practice.

Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett’s esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75–83), 75% (CI, 71–79), and 81% (CI, 76–86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Corrigendum: Evaluation of a novel infra-red endoscopy system in the assessment of early neoplasia in Barretts esophagus: pilot study from a single center.

Corrigendum: Evaluation of a novel infra-red endoscopy system in the assessment of early neoplasia in Barretts esophagus: pilot study from a single center.

Endoscopic treatment for Barrett's oesophagus dysplasia and early cancer

Endoscopic treatment of early Barrett's oesophagus neoplasia is now proven to be a safe and effective alternative to oesophagectomy. An ideal candidate for endoscopic treatment should have dysplasia or carcinoma limited to the mucosa or superficial submucosa without lymphovascular invasion or poor differentiation. Two main types of endoscopic therapies are used: (1) endoscopic resection, which comprises of endoscopic mucosal resection or endoscopic submucosal dissection for removal of visible lesions en bloc and (2) endoscopic ablation utilising argon plasma coagulation, radiofrequency ablation or, more recently, cryotherapy. Although endoscopic resection is the cornerstone for Barrett's endotherapy, ablative techniques are complementary in achieving complete eradication of the columnar epithelium and dysplasia.

Please provide us with a reasonable definition for curative R0 resection in Barrett's esophagus neoplasia; which one should we choose?

A resection is considered to be R0 when the pathological examination confirms that the edges of the resected specimen are free of disease. A resection is curative when the patient is cured by the endoscopic treatment without need for further surgery or chemoradiation therapy. In the colon for example, the definition of the curative R0 resection is quite simple: a strict R0 is defined by an 'en bloc' specimen with normal mucosa on the edges when examined histologically. The treatment is considered to be curative if the resection is R0 with an invasion depth less than 1000 µm in the submucosa, without lymphatic or venous emboli, without budding, and with a differentiated carcinoma. The situation is far more complex in the neoplasia developed on Barrett’s esophagus (BE) since different degrees of neoplasia are possible with different prognosis and treatment strategies. At present, we do not have any consensus on the definition of R0 and curative resections for BE neoplasia (Fig. 1 a). This editorial aims to discuss various definitions of the R0 resection and their clinical impact. We shall also discuss the literature available to choose the best criteria to define resection curativeness. Fig. 1 Schematic representation of the different R0 resections. a Neoplasia representation; b Colon-like R0; c Intestinal metaplasia R0; d LGD or less R0; e HGD or less R0; f Flat components R0. IM, intestinal metaplasia; LGD, low grade dysplasia; ...

Long-term durability of radiofrequency ablation for Barrett's-related neoplasia.

Here, we examine data on the long-term durability of endoscopic therapy in patients with mucosal neoplasia in Barrett's esophagus. Short-term success is seen in most patients undergoing endoscopic therapy for Barrett's esophagus neoplasia, but long-term outcomes are only just becoming available. The incidence of esophageal adenocarcinoma (EAC) continues to rise with poor survival seen in the majority of patients. The only known precursor to EAC is Barrett's esophagus. Although the risk of progression from metaplastic Barrett's esophagus to neoplasia is low, surveillance is advocated as patients who progress to mucosal neoplasia carry a significantly higher risk of progressing to invasive EAC. Minimally invasive endoscopic therapy with endoscopic resection and radiofrequency ablation are now the gold standard treatments for patients with intramucosal neoplasia in Barrett's esophagus. After successful treatment, follow-up is still required as long-term durability is not 100% and recurrences are not rare. This review highlights the need for vigilant follow-up, but emphasizes the consensus that most patients have durable disease reversal.

Endoscopic eradication therapy for mucosal neoplasia in Barrettʼs esophagus

Endoscopic eradication therapy is frequently used to treat dysplasia and early cancers in Barrett's esophagus. This review addresses some of the recent developments in the field of endoscopic eradication therapy for Barrett's esophagus. Data on the effectiveness of Barrett's esophagus ablation programs have been published recently, with excellent results for dysplasia eradication. Studies describing long-term results have shed light on the durability of endoscopic ablation, with recurrence of Barrett's esophagus and neoplasia seen in some cases, particularly at the gastroesophageal junction. Risk factors for failed ablation include longer Barrett's esophagus segments and persistent gastroesophageal reflux. New developments include studies combining radiofrequency ablation (RFA) and endoscopic mucosal resection into a single endoscopic session, endoscopic submucosal dissection for Barrett's esophagus neoplasia, and a simplified RFA algorithm. New data on the cost-effectiveness of RFA have also been published, suggesting that RFA is cost-effective for both high-grade and low-grade dysplasia, but not for nondysplastic Barrett's esophagus. A systematic review has shown that lymph node metastases are rare (∼2%) with intramucosal adenocarcinoma, supporting the use of endoscopic eradication for that lesion. Research and clinical experience with the endoscopic therapies for Barrett's esophagus continue to grow. Proper patient selection and technique are critical for ensuring a good outcome. Endoscopic surveillance after any of the ablative therapies still appears to be necessary.

Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett's esophagus neoplasia

Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett's esophagus neoplasia

Update zum Barrett-Ösophagus und Barrett-Karzinom

The definition of Barrett esophagus is currently under discussion. It is now suggested that a distal esophagus coated with cylinder epithelium with cardia-fundus mucosa should also be classified as Barrett esophagus because the risk of cancer is significantly increased even without histological evidence of intestinal metaplasia with goblet cells. The results of recent epidemiological investigations imply that the cancer risk of cylinder cell metaplasia and low grade intraepithelial neoplasia in Barrett esophagus has previously been overestimated. The histological detection of dysplasia still remains the best biomarker for estimation of the risk of cancer of Barrett esophagus. Exact determination of invasion depth in the mucosa, respective submucosa is now established as prognostic marker for overall survival in Patients with early carcinomas and this classification is useful for therapy decisions (endoscopic versus surgical removal). In advanced Barrett carcinoma following neoadjuvant therapy the lymph node status (ypN) is a better prognostic factor than the ypT category. In metastasized tumors therapies targeting HER2/new, EGFR or c-Met have been investigated explicitly in Barrett carcinoma only in phase I/II studies, whereby the predictive value of appropriate molecular pathology investigations is not yet reliably established.

Endomicroscopy in the evaluation of Barrettʼs esophagus

Confocal laser endomicroscopy (CLE) can provide real-time, microscopic visualization of the gastrointestinal mucosa, allowing an endoscopic approach to the histologic evaluation of Barrett's esophagus and Barrett's esophagus-associated neoplasia. Both endoscope-based (eCLE) and probe-based (pCLE) CLE systems have been used to evaluate Barrett's esophagus and Barrett's esophagus-associated neoplasia. Criteria for distinguishing Barrett's esophagus with neoplasia from nondysplastic Barrett's esophagus have been developed and validated for both eCLE and pCLE. Several studies have shown excellent detection of Barrett's esophagus neoplasia by CLE, and the technique may be used to guide endoscopic therapy. Advanced endomicroscopy systems and peptides and antibodies that target neoplasia are in development. CLE has provided a new way of evaluating Barrett's esophagus and Barrett's esophagus-associated neoplasia and is being used to improve detection and management of neoplasia in Barrett's esophagus.

How should early neoplasia in Barrett esophagus be treated?

The appropriate management of patients with Barrett esophagus in whom early carcinoma or high-grade intraepithelial neoplasia has been detected continues to be a subject of controversy. For many years radical esophageal resection has been regarded as the treatment of choice, but the high morbidity and mortality rates associated with this procedure have led to less radical treatment strategies being advocated by many groups.

Correlation of histology with biomarker status after photodynamic therapy in Barrett esophagus

Currently, histology is used as the endpoint to define success with photodynamic therapy (PDT) in patients with high-grade dysplasia (HGD). Recurrences despite 'successful' ablation are common. The role of biomarkers in assessing response to PDT remains undefined. The objectives of the current study were 1) to assess biomarkers in a prospective cohort of patients with HGD/mucosal cancer before and after PDT and 2) to correlate biomarker status after PDT with histology. Patients who underwent PDT for HGD/mucosal cancer were studied prospectively. All patients underwent esophagogastroduodenoscopy, 4-quadrant biopsies every centimeter, endoscopic mucosal resection of visible nodules, and endoscopic ultrasound. Cytology samples were obtained by using standard cytology brushes. Biomarkers were assessed by using fluorescence in situ hybridization (FISH). The biomarkers that were assessed included loss of 9p21 (site of the p16 gene) and 17p13.1 (site of the p53 gene) loci; gains of the 8q24(c-myc), 17q (HER2-neu), and 20q13 loci; and multiple gains. Patients received PDT 48 hours after the administration of sodium porfimer. Demographic and clinical variables were collected prospectively. Patients were followed with endoscopy and repeat cytology for biomarkers. The McNemar test was used to compare biomarker proportions before and after PDT. Thirty-one patients were studied. The median patient age was 66 years (interquartile range [IQR], 56-73 years), and 28 patients (88%) were men. The mean Barrett segment length was 5 cm (standard error of the mean, 0.5 cm). Post-PDT biomarkers were obtained after a median duration of 9 months (IQR, 3-12 months). There was a statistically significant decrease in the proportion of several biomarkers assessed after PDT. Six patients without HGD after PDT still had positive FISH results for 1 or more biomarkers: of these, 2 patients (33%) developed recurrent HGD. In this initial study, histologic downgrading of dysplasia after PDT was associated with the loss of biomarkers that have been associated with progression of neoplasia in Barrett esophagus. Patients with persistently positive biomarkers appeared to be at a higher risk of recurrent HGD. These findings should be confirmed in a larger study.

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Barrett's esophagus is a useful model for the study of carcinogenesis, as the metaplastic columnar epithelium that replaces squamous esophageal epithelium is at elevated risk for development of adenocarcinoma. We examined telomere length and chromosomal instability (CIN) in Barrett's esophagus biopsies using fluorescence in situ hybridization. To study CIN, we selected centromere and locus-specific arm probes to chromosomes 17/17p (p53), 11/11q (cyclin D1), and 9/9p (p16 INK4A), loci reported to be involved in early stages of Barrett's esophagus neoplasia. Telomere shortening was observed in Barrett's esophagus epithelium at all histologic grades, whereas CIN was highest in biopsies with dysplastic changes; there was, however, considerable heterogeneity between patients in each variable. Alterations on chromosome 17 were strongly correlated with telomere length (r = 0.55; P < 0.0001) and loss of the 17p arm signal was the most common event. CIN on chromosome 11 was also associated with telomere shortening (r =0.3; P = 0.05), although 11q arm gains were most common. On chromosome 9p, arm losses were the most common finding, but chromosome 9 CIN was not strongly correlated with telomere length. We conclude that CIN is related to telomere shortening in Barrett's esophagus but varies by chromosome. Whether instability is manifested as loss or gain seems to be influenced by the chromosomal loci involved. Because telomere shortening and CIN are early events in Barrett's esophagus neoplastic progression and are highly variable among patients, it will be important to determine whether they identify a subset of patients that is at risk for more rapid neoplastic evolution.

Evaluation of an Endocytoscopy System in the Surveillance of Patients with Barrett Esophagus

Background: Biopsy surveillance for Barrett patients with increased risk for neoplasia is time consuming and subject to sampling error. Guided biopsy acquisition from neoplastic areas invisible to conventional endoscopy may increase effectiveness of surveillance examination. We assessed the potential role of Endocytoscopy using large scale magnification comparable to cytologic analysis in identifying neoplasia in Barrett esophagus. Methods: 82 biopsy specimens from 7 consecutive patients (6 men, mean age 58 years) who presented for Barrett surveillance without visible neoplastic lesions were enrolled into this prospective study. Markings along the Barrett segment were placed using Argon plasma coagulation. Endocytoscopy images with 1100 magnification (Olympus Corp. Hamburg, Germany) were collected immediately right to the marking. A biopsy was then carefully taken from that same spot to ensure that identical areas were scanned and biopsied. Biopsies were assessed according to WHO criteria of neoplasia. The major outcome included image quality parameters of endocytoscopy and identification of characteristic changes of dysplasia based on previously published criteria for Barrett cytology (Geisinger et al. Cancer 1992). Endocytoscopy images were randomized and individually reviewed by a pathologist and a gastroenterologist blinded to final diagnosis. Results: Adenocarcinoma was found in 4 (4.9%) of the biopsies, high-grade intraepithelial neoplasia in 14 (18.3%) and low-grade intraepithelial neoplasia in 5 (6.1%). The remaining biopsies showed either normal Barrett mucosa in 51 biopsies (62.2%) or no Barrett epithelium in 7 biopsies (8.5%). On average 9 images were reviewed per site. A general evaluation of images was not possible or poor in 22% and of moderate quality in 78%. None of the image sequences per site was graded as good or excellent. Staining was sufficient in 71%; however, image resolution was mostly graded as insufficient. Interpretable images to diagnose dysplasia were seen in only 4 to 41% depending on various cytologic criteria. Using only interpretable images staining was graded significantly better in nondysplastic areas than in dysplastic areas (p < 0.02). However, none of the characteristic changes of dysplasia were different when blindly comparing nondysplastic with dysplastic sites. Conclusion: Endocytoscopy lacks sufficient image quality to be currently of assistance in identifying areas of dysplasia in Barrett esophagus when using large scale magnification equivalent to cytology. Lower magnification might be superior and comparable to histologic architecture and has therefore to be tested using the same methodology.

High Resolution Chromoendoscopy with Acetic Acid for the Detection of Intestinal Metaplasia and Early Neoplasia in Barretts Esophagus - a Prospective Trial

Video capsule endoscopy has revolutionized direct endoscopic imaging of the gut.Small-bowel video capsule endoscopy (SBVCE) is now the first-line procedure for exploring the small bowel in case of obscure digestive bleeding and has also some room in case of Crohn's disease, coeliac disease and polyposis syndrome. In case of obscure digestive bleeding the main lesions are angioectasias, erosions/ulcerations and tumors. As for conventional optical endoscopy search was done for improving the detection and characterization of small-bowel lesions.The Fujinon Intelligent Chromoendoscopy (FICE) has been adapted on the software of the SBVCE (Given Imaging®/Medtronics). Although there are some conflicting results on the efficacy of FICE for detecting more lesions than with conventional light, it is now recognized that FICE – particularly the setting 1 – may enhance the delineation or characterization of lesions. The use of three-dimensional representation technique is now feasible but still needs further research.