Sage Journals: Discover world-class research

Abstract

Barrett’s esophagus is the precursor lesion for esophageal adenocarcinoma. Screening and surveillance of Barrett’s esophagus are undertaken with the goal of earlier detection and lowering the mortality from esophageal adenocarcinoma. The widely used technique is standard esophagogastroduodenoscopy with biopsies per the Seattle protocol for screening and surveillance of Barrett’s esophagus. Surveillance intervals vary depending on the degree of dysplasia with endoscopic eradication therapy confined to patients with Barrett’s esophagus and confirmed dysplasia. In this review, we present various novel techniques for screening of Barrett’s esophagus such as unsedated transnasal endoscopy, cytosponge with trefoil factor-3, balloon cytology, esophageal capsule endoscopy, liquid biopsy, electronic nose, and oral microbiome. In addition, advanced imaging techniques such as narrow band imaging, dye-based chromoendoscopy, confocal laser endomicroscopy, volumetric laser endomicroscopy, and wide-area transepithelial sampling with computer-assisted three-dimensional analysis developed for better detection of dysplasia are also reviewed.

Keywords

Barrett’s esophagus cytosponge dysplasia esophageal adenocarcinoma gastroesophageal reflux disease screening surveillance trefoil factor unsedated transnasal endoscopy

Introduction

Barrett’s esophagus (BE) is a well-established premalignant stage of esophageal adenocarcinoma (EAC) and is defined as an extension of salmon-colored mucosa into the tubular esophagus extending ⩾1 cm proximal to the gastroesophageal junction (GEJ) with biopsy confirmation of intestinal metaplasia (IM).¹ The incidence of EAC in patients with BE is 0.3–0.6% per patient-year.¹ The estimated prevalence of BE in the general population is 1–2%.^2,3 As most patients with BE are asymptomatic, these rates likely underestimate the true prevalence of the disease. Esophagogastroduodenoscopy (EGD) with biopsy is the gold standard for the diagnosis and surveillance of BE. As there is an increasing incidence of EAC in the Western world, efforts focusing on the screening and surveillance of BE are of paramount importance. In this review, we examine the current strategies for the screening and surveillance of BE and recent advances in the field.

Screening

Should we screen for BE? Pros and cons

The rationale for screening for BE is early identification of patients who are at increased risk of developing EAC and timely intervention with the goal of decreasing mortality. Despite a lack of randomized controlled trials (RCTs), indirect evidence suggests that screening leads to detection of EAC at earlier stages, better outcomes and increase in 5-year survival rates from 17% to 74%.⁴

The current screening strategies are inadequate as more than 90% of patients diagnosed with EAC do not have a prior diagnosis of BE and over 40% of patients with EAC do not have prior gastroesophageal reflux disease (GERD) symptoms.⁵ It must be noted that even if all patients with chronic GERD are screened, a huge number of patients with BE (probably more than two-thirds) will remain undiagnosed because many among them do not have chronic GERD. Better targeting of the candidates for BE screening is necessary in order for a screening strategy to be useful. Sedated EGD (sEGD) cannot be used for large-scale screening of general population as it is expensive and has a very low yield owing to the small absolute risk of EAC in GERD patients. In addition, some studies with a long-term follow-up show no difference in survival.^6,7 To address these limitations and to improve efficiency, novel techniques have been described but are yet to prove their ability to replace sEGD.

Who should we screen?

Guidelines of major societies recommend against screening of the general population and instead recommend screening patients with multiple risk factors for BE^1,8–13 (Table 1). Chronic GERD is the most common risk factor for BE [odds ratio (OR) of 2.9; 95% confidence interval (CI) 1.86–4.54, p = 0.0001] and has a stronger association for long segment BE (OR 4.92; 95% CI 2.01–12.0; p = 0.30).¹⁴

Table 1.

Screening guidelines for Barrett’s esophagus^*.

General population	AGA,⁸ ACG,¹ ASGE,⁹ BSG,^10,11 ESGE¹²	Not recommended.
General population	Australian¹³	One-time screening in a 50-year-old male with GERD.
Risk factors (chronic GERD (>5 years), white race, age > 50 years, obesity, male gender, smoking, hiatal hernia, family history of BE/EAC)	AGA	Screen patients with multiple risk factors
	ACG	Screen high-risk individuals (⩾2 risk factors). If negative pathology for suspected BE, repeat EGD in 1–2 years. If esophagitis (Los Angeles classification B/C/D) is seen, then repeat EGD after PPI therapy for 8–12 weeks.
	ASGE	Screen patients with >1 risk factor. No further screening after the first EGD is negative.
	BSG	Screen patients with chronic GERD and ⩾3 risk factors. If positive family history in at least one first-degree relative with BE/EAC, then screen patients with <3 risk factors.
	ESGE	Screen patients with chronic GERD and multiple risk factors.
	Australian	Consider age, gender, history of GERD, central adiposity, smoking history, family history of BE/EAC.

All guidelines recommend that biopsy is taken using Seattle protocol (four quadrant biopsy every 2 cm or every 1 cm in cases of known/suspected dysplasia).

Other risk factors for BE include male gender, increasing age, white race, central obesity, cigarette smoking, and family history of BE/EAC. Studies have shown that BE is twice as likely in men than women with the ratio increasing to 4:1 in patients younger than 50.¹⁵ Men develop BE about 20 years earlier than women.¹⁵ BE is usually diagnosed in sixth to seventh decade of life with a steep increase in prevalence from 2.1% in third decade to 9.3% in sixth decade and plateau thereafter.¹⁶ In a large study of 280,075 procedures, white subjects were most likely to have suspected BE (5.0% in white, 2.9% in Hispanic, 1.8% in Asian/Pacific islander, 1.5% in black; p < 0.0001).¹⁷ Waist circumference is also an independent risk factor for BE after adjustment for other risk factors (for every 5 cm increase, OR 1.14; 95% CI 1.03–1.27, p = 0.02).¹⁸ This association persists even after adjustment for body mass index (BMI) and GERD symptoms.¹⁹ Having ever-smoked is also associated with an increased risk of BE compared with non-GERD controls (OR 1.44; 95% CI 1.20–1.74) and population-based controls (OR 1.42; 95% CI 1.15–1.76).²⁰ Family history of BE has been identified as another potential risk factor for BE. BE is more common in first- or second- degree relatives of patients with BE compared to controls (24% versus 5%, p < 0.005) and the presence of family history of BE/EAC was strongly associated with BE (OR 12, 95% CI 3.3–44.8).²¹ Even though these factors increase the relative risk of BE, the absolute risk of EAC remains low. In a prospective cohort of 355,034 subjects, a scoring system was developed using age, sex, smoking, body mass index, and history of esophageal conditions or treatments. The five-year risk of EAC was 0.16% for individuals with scores above the threshold and 0.02% for individuals with scores below the threshold.²²

How to screen?

Careful visual inspection during EGD and four quadrant biopsies at every 1–2 cm interval using Seattle protocol and biopsy of any mucosal irregularities in salmon-colored mucosa above the GEJ is the gold standard method for BE screening.²³ Standard brush cytology for detection of BE was also evaluated. Cytology has high diagnostic accuracy for high-grade dysplasia (HGD)/EAC (sensitivity 90%), moderate sensitivity for BE (60% versus 92%) and low sensitivity for low-grade dysplasia (LGD) (20% versus 97%) compared with histology.²⁴ The addition of brush cytology complements histology and increases cost without improvement in diagnostic yield.²⁵

Standard sEGD is expensive and associated with a small risk of complications such as cardiopulmonary events, aspiration, bleeding, perforation, and indirect patient-related costs. Therefore, sEGD is not an ideal tool for screening of large populations and there exists a need for alternative, cheap, widely available, and an accurate method of screening.^26,27 Several modalities were developed and the current evidence is presented in the following.

Unsedated transnasal endoscopy (uTNE) is performed with an ultrathin endoscope using topical anesthesia obviating the need for sedation. Compared with sEGD, the sensitivity of uTNE for detection of columnar lined esophagus was 98% and of IM was 91% and specificity was 100%.²⁸ Procedure time ranged from 3.7 ± 1.8 min to 5.5 ± 1.7 min and the mean recovery time was quicker in uTNE compared with sEGD (18.5 versus 67.3 min; p < 0.001).^29–31

When compared with sEGD, uTNE was safer with fewer procedure- and sedation-related complications and high acceptability with willingness to undergo repeat procedure in up to 93.2%.^32,33 Minor complications (2.8%) included minimal choking, gagging, anxiety, nasal pain, sore throat, and minor epistaxis.^28,29,34 No serious adverse events were reported.^29,30,34 In a RCT, differences in mean costs for sEGD versus hospital-based uTNE was US$1386.72 (95% CI 1291.79–1486.07).³⁵ In addition, endoscopes with disposable sheaths such as EndoSheath^® technology (Vision-Sciences Inc., Orangeburg, New York) reduce cost by eliminating need for disinfection and nonphysician providers can be trained to perform the procedure. Better acceptance and affordability allow consideration for uTNE as a screening test for BE for patients seen in the office.²⁹

Cytosponge is a mesh surrounded by gelatin capsule attached to a string passed transorally.³⁶ Five minutes after swallowing, the capsule dissolves in the proximal stomach, expanding the mesh to a sphere of 3 cm. The sample containing cytological specimen is stained with Trefoil Factor3 (TFF3) which is a biomarker for IM.

Three large-scale trials were undertaken to utilize cytosponge and TFF3 to develop an improved screening method for BE.^36–38 In a prospective study of 504 patients with a prescription for acid suppressants, cytosponge with TFF3 had a sensitivity of 73.3% (95% CI 44.9–92.2%) and specificity of 93.8% (95% CI 91.3–95.8%) for detecting BE ⩾1 cm of circumferential length.³⁷ In a case-control study of 1110 GERD patients with or without BE comparing cytosponge and TFF3 with sEGD, sensitivity was 79.9% which increased to 89.7% when the device was swallowed twice and specificity was 92.4%.³⁶ BE Trial 3 (BEST3) is in the process of determining its efficacy and cost-effectiveness in primary care.³⁸ A cost-effectiveness analysis with cytosponge using microsimulation models calibrated for US Surveillance, Epidemiology, and End Results Program (SEER) data on EAC incidence and mortality was determined.³⁹ Screening GERD patients with cytosponge and following up positive results with EGD for confirmation reduced cost by 27–29% when compared with screening by EGD alone. In addition to TFF3, cytosponge sample can be used for detection of other additional biomarkers for BE such as TFPI2, TWIST1, ZNF345, and ZNF569, which can further improve the sensitivity.⁴⁰

A qualitative study showed high acceptability and comfort level in patients undergoing cytosponge procedure.⁴¹ Visual analog scale determined favorable acceptability (p < 0.001) in 93.9–99% patients.^36,37 Brief episodes of sore throat and site abrasion with oozing blood was noted in 16.7% of patients, which resolved without any intervention.³⁶ Cytosponge with TFF3 appears promising over endoscopy and can be utilized in the primary care clinic if applicable to the general population. Ongoing large-scale studies will guide further decisions.

A similar technology called a sponge on string device (EsophaCap, Capnostics, Doylestown PA) has been evaluated in pilot studies where it was swallowed and withdrawn in 98% of subjects and provided abundant DNA yield for the evaluation of BE markers.⁴²

In an earlier study, a prototype nonendoscopic balloon with spikes on the surface was passed transorally in patients with BE presenting for surveillance sEGD. Balloon cytology was positive in 52 of 63 (83%) patients with BE, in 6 of 8 patients with EAC, 2 of 2 patients with HGD, and 2 of 8 patients with LGD.⁴³ Balloon cytology was six-fold cheaper than sEGD, but only 49% of patients found it more tolerable. Recently, a swallowable nonendoscopic encapsulated balloon device with textured surface was developed.⁴⁴ In 86 patients who swallowed nonendscopic balloon, a biomarker panel consisting of CCNA1 DNA methylation and VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. As a nonendoscopic screening technique, the balloon sampling device was well tolerated and efficient.⁴⁴

Esophageal capsule endoscopy (ECE) is a noninvasive unsedated imaging technique that allows visualization of the esophagus using wireless or tethered cameras without obtaining a biopsy. In a meta-analysis of nine studies including 618 patients, the pooled sensitivity and specificity for diagnosis of BE were moderate, 77% and 86%, respectively.⁴⁵ ECE is safe and 80% preferred ECE to sEGD; however, it was not more cost-effective than sEGD (Table 2).^46,47

Table 2.

Screening techniques.

Technique	Availability	Cost
Sedated esophagogastroduodenoscopy (esophagoscopy, flexible, transoral, with biopsy single or multiple)	Commercially available	US$2149.37⁵⁶
Unsedated transnasal endoscopy (uTNE)	Commercially available	Hospital based, mean cost: US$976.38.⁵⁶ Mobile research van based, mean cost: US$497.92.⁵⁶
Cytosponge + TFF3	Not available	Low cost³⁹
Balloon cytology	Not available	Low cost
Esophageal capsule endoscopy	Commercially available for detection of esophagitis, varices but not FDA approved for use in BE	Cost of capsule US$450 and with physician interpretation US$785.⁵⁷
Liquid biopsy	Not available	-
Electronic nose (Aeonose)	Not available
Oral microbiome	Not available	-
Narrow band imaging	Commercially available	Available in Olympus endoscopes and processors
Chromoendoscopy (acetic acid staining)	Commercially available	Acetic acid with 100 ml costing approximately £5 (US$6.53) and 5–8 ml is needed per patient⁵⁷
Confocal laser endomicroscopy	Commercially available	Console: US$182,000GastroFlex UHD probe cost US$9200⁵⁸
N Vision Volumetric Laser Endomicroscopy	Commercially available	Console: US$249,000US$1195 for catheter and US$145 for inflation device*
Wide area transepithelial sampling with computer-assisted three-dimensional analysis (WATS^3D)	Commercially available	The average reimbursement by third party insurance plans for this overall analysis is ~US$600/case (includes cost of materials, shipment and interpretation).*

From manufacturer.

A liquid biopsy utilizes a blood sample for detection of circulating microRNAs (miRNAs) in the blood, which are dysregulated and expressed in tissue-specific patterns in cancer. In a recent study of 41 patients with BE and 15 controls, a panel of 4 circulating miRNAs (miRNA-95-3p, -136-5p, -194-5p, and -451a) distinguished BE from controls with sensitivity and specificity of 78% and 86%, respectively.⁴⁸ In a recent meta-analysis, increased expression of miR-192, -194, and -215 and decreased expression of miR-203 and -205 was found in BE tissue when compared with normal controls.⁴⁹ However, assays with sufficient sensitivity and specificity need to be developed before these markers can be recommended for clinical use.

Exhaled volatile organic compounds (VOC) are products of metabolism which can be detected in the breath by ‘electronic nose’ devices and which may be altered in different disease states. In a recent study of 66 patients with BE compared with 56 patients without BE, the electronic nose distinguished the two groups with 82% sensitivity, 80% specificity, and 81% accuracy with an area under receiver operating characteristic curve (AUROC) of 0.79.⁵⁰ A study on 81 patients with EAC versus gastric cancer versus no controls identified 12 VOCs of which 8 were significant predictors for EAC compared with normal subjects. The AUROC to detect EAC from normal controls was 0.97.⁵¹ As these are noninvasive tests, the patient acceptance rate is very high but needs to be validated in larger studies.

Oral microbiome is another area of research as dysregulation and alteration of the microbiome have been reported in several diseases. There appears to be a higher risk of EAC with Tannerella forsythia and Lactobacillus fermentum, and lower risk with fewer number of genus Neisseria and species Streptococcus pneumoniae.^52,53 The efficiency of cytosponge as a sampling tool in retrieving microbiome DNA when compared with endoscopic methods found >10 times increased quantity (p < 0.0001).⁵⁴ However, the diagnostic accuracy and application for the general population, feasibility, and cost-effectiveness are yet to be determined.

Surveillance

Currently, surveillance involves early detection of dysplasia by high-definition white light endoscopy (WLE) with random four-quadrant biopsies every 2 cm (or every 1 cm if dysplasia is known or suspected) followed by biopsy of mucosal irregularity (nodules, ulcers, or visible lesions). Shared medical decision involving risks, benefits, limitations, and importance of adherence to periodic endoscopies along with the possibility of endoscopic therapy or surgery needs to be discussed with patient before enrolling in surveillance. The risk of EAC in BE depends on the degree of dysplasia. The annual risk of EAC with nondysplastic BE (NDBE) is estimated to be 0.33%, 0.54% in LGD, and 7% in HGD.¹ It should be noted that confirmed LGD by expert pathologists have higher rates of progression than those downstaged. In one study, the risk of HGD/EAC with LGD confirmed by expert pathologists was 9.1% per patient-year whereas for those downstaged to NDBE or indefinite for dysplasia, it was 0.6% and 0.9% per patient-year respectively.⁵⁴ Other factors known to be associated with neoplastic progression of BE are age (OR 1.47, 95% CI 1.01–1.05), male sex (OR 2.16, 95% CI 1.84–2.53), smoking (OR 1.47, 95% CI 1.09–1.98), and length of BE segment (OR 1.25, 95% CI 1.16–1.36).⁵⁵ How-ever, all societies recommend surveillance intervals taking into consideration the degree of dysplasia only (Table 3).^1,8–13

Table 3.

Surveillance guidelines for BE^*.

NDBE	AGA	Surveillance every 3–5 years.
	ACG
	ASGE
	BSG	If length <3 cm without IM/dysplasia→ repeat EGD.If repeat EGD is negative → discharge from surveillance.If repeat EGD is IM positive → surveillance every 3–5 years.If length ⩾3 cm → surveillance every 2–3 years.
	ESGE	<1 cm → no surveillance,⩾1 cm → and <3 cm surveillance every 5 years,⩾3 cm → and <10 cm surveillance every 3 years⩾10 cm → refer to BE expert center.Continue surveillance till at least 75 years of age.
	Australian	Short segment (<3 cm): repeat EGD in 3–5 years.Long segment (⩾3 cm): repeat EGD in 2–3 years.
IND	AGA	-
	ACG	Repeat EGD after PPI therapy for 3–6 months. If repeat EGD shows IND, then surveillance every 12 months.
	ASGE	Additional pathology review, dose escalation of PPI therapy and repeat EGD with biopsy.
	BSG	Repeat EGD after PPI therapy in 6 months. If repeat shows NDBE, then follow NDBE protocol.
	ESGE	Repeat EGD after PPI therapy for 6 months. If repeat shows IND or NDBE, then follow NDBE protocol.
	Australian	Repeat EGD after PPI therapy for 6 months. If repeat shows NDBE/LGD/HGD/EAC, then follow respective protocols. If repeat shows IND → repeat EGD in 6 months.
LGD	AGA	Surveillance every 6–12 months.
	ACG	EET is recommended for confirmed LGD without life-limiting comorbidity or alternatively, surveillance every 12 months.
	ASGE	Repeat EGD in 6 months to confirm the diagnosis. Then surveillance every year with EET in select patients.
	BSG	Repeat EGD in 6 months. If repeat shows LGD, then EET is recommended or alternatively, surveillance every 6 months.
	ESGE	Repeat EGD in 6 months. If repeat shows NDBE, then repeat EGD every year until two consecutive results show NDBE. Then follow NDBE protocol. If repeat shows LGD, then EET is recommended.
	Australian	Repeat EGD every 6 months until two consecutive results show NDBE. Then follow a less-frequent follow-up schedule.
HGD	AGA	EET or, alternatively, surveillance every 3 months.
	ACG	EET is recommended for confirmed HGD without life-limiting comorbidity.
	ASGE	EET or alternatively, surveillance every 3 months.
	BSG	EET.
	ESGE	EET. If biopsies show NDBE, then repeat EGD in 3 months.
	Australian	EET or alternatively surveillance every 3 months.

All guidelines recommend confirmation of dysplasia by expert gastrointestinal pathologists.

ACG, American College of Gastroenterology; AGA, American Gastroenterological Association; ASGE, American Society for Gastrointestinal Endoscopy; BE, Barrett’s esophagus; BSG, British Society of Gastroenterology; EAC, esophageal adenocarcinoma; EET, Endoscopic eradication therapy; EGD, esophagogastroduodenoscopy; ESGE, European Society of Gastrointestinal Endoscopy; GERD, gastroesophageal reflux disease; HGD, high-grade dysplasia; IND, indefinite for dysplasia; IM, intestinal metaplasia; LGD, low-grade dysplasia, NDBE, nondysplastic Barrett’s esophagus; PPI, proton pump inhibitor.

Studies show a survival advantage in patients with BE undergoing surveillance endoscopy. In a cohort study of about 30,000 patients with BE followed for over 5 years, patients diagnosed with EAC during surveillance, were detected at an earlier stage (stage 0 to 1: 74.7% versus 56.2; p < 0.001), survived longer (median 3.2 versus 2.3 years; p < 0.001), and had lower cancer-related mortality (34.0% versus 54.0%, p < 0.0001) compared with those not in surveillance.⁵⁹ Despite these advantages of earlier detection of EAC with surveillance, the current approach is invasive, time-consuming with concerns of lead and length time bias affecting the improvement in mortality.^60,61 The natural course of progression in BE is unknown, and when compared with other cancers, EAC is relatively rare.⁶² The cost–benefit analysis calculated per life-year gained compared with other cancer programs is expensive, and the overall survival of patients appears similar to age and gender-matched individuals.⁶³

Therefore, various advanced imaging technologies have been proposed to maximize efficiency and diagnostic yield of the current surveillance model. In a meta-analysis on 843 patients, advanced imaging techniques increased diagnostic yield of dysplasia/EAC by 34% (95% CI 0.13–0.56; p = 0.0001) when compared with WLE with random four-quadrant biopsy.⁶⁴ Whereas ASGE endorses the use of advanced imaging, AGA, ACG, BSG do not recommend routine use.⁹ Most of the currently available techniques rely on the ability of endoscopist to detect the abnormalities.

ASGE released criteria for the preservation and incorporation of valuable endoscopic innovations (PIVI) for advanced imaging techniques. An imaging technique can replace random four-quadrant biopsy if their per-patient sensitivity is ⩾90%, specificity is ⩾80%, and negative predictive value (NPV) is ⩾98% for detecting HGD/EAC. The techniques evaluated for PIVI included chromoendoscopy by using acetic acid and methylene blue, narrow-band imaging (NBI), and confocal laser endomicroscopy (CLE). Targeted biopsies with acetic acid chromoendoscopy, NBI, and endoscope-based CLE meet these thresholds.⁶⁵

Dye-based chromoendoscopy utilizes chemicals such as methylene blue, indigo carmine, and acetic acid to provide wide-field imaging and mucosal enhancement during endoscopy.⁶⁵ Methylene blue and indigo carmine do not meet ASGE PIVI standards, and mixed reports in studies prevent routine use. A meta-analysis on acetic acid chromoendoscopy found high diagnostic accuracy for HGD/EAC (sensitivity 92% and specificity 96%).⁶⁶ Chromoendoscopy is simple, inexpensive, and improves detection rates. However, there is high interobserver variability owing to a lack of classification, unequal distribution of dye over the mucosa, and increased procedure time making this technique uncommon.^65,67,68

Virtual chromoendoscopy involves advanced imaging of surface patterns without the use of dyes. NBI, available on Olympus endoscopes, allows real-time wide-field imaging using narrow wavelength range of light (filtering white into blue and green) in identifying early neoplastic lesions from irregular mucosal and subsurface vascular patterns.⁶⁵ Recognition of the mucosal and vascular patterns guides imaging targeted biopsies leading to fewer total biopsies and reduced cost of surveillance.⁶⁹ Barrett’s International NBI Group (BING) developed NBI classification to be more user-friendly than earlier classifications and has a good inter-observer agreement (κ = 0.681).⁷⁰ A meta-analysis showed pooled sensitivity, specificity, and NPV of 94.2%, 94.4%, and 97.5%, respectively.⁷¹ Similar virtual chromoendoscopy techniques include I-Scan (Pentax), flexible spectral imaging color enhancement (FICE, Fujinon), and blue light imaging (Fujinon), which accentuate specific areas by wavelength and improve the detection of dysplasia in BE.⁷²

CLE allows in vivo histological assessment by 1000 times magnification using an integrated endoscope or probe insertion to obtain confocal images after exogenous fluorescein administration. Probe-based CLE has high specificity for detecting dysplasia and cancer (98%), low sensitivity (67%), and substantial inter-observer agreement (κ = 0.6) and aids in real-time therapeutic decision making.⁵⁸ Endoscope-based CLE is no longer in use despite meeting ASGE PIVI standards (pooled sensitivity, specificity, and NPV of 90.4%, 92.7%, and 98.3%, respectively).⁷¹ CLE is expensive,⁷³ requires a correlation between imaging and histology, administration of intravenous fluorescein which increases sampling error from extravasation of fluorescein and near-field imaging. Probe-based CLE can be used to image only limited areas and cannot be used to image the entire esophagus.⁷³

Volumetric laser endomicroscopy (VLE) is an optical frequency domain imaging technique that provides high-resolution real-time cross-sectional images using a 3.7 mm probe located within the balloon that helically scans 360° circumference of esophageal surface up to 3 mm in depth.⁶⁵ A total length of 6cm is scanned starting 1 cm distal to the GEJ and moving proximally from distal end of the balloon.⁶⁵ The sizes of currently available balloons are 14, 17, and 20 mm.⁷⁴ VLE is sensitive in identifying mucosal lesions that are invisible under standard WLE, thus allowing targeted biopsy of dysplastic/cancerous lesions.⁷⁵ The novel VLE laser marking system further enables direct in vivo marking of suspicious areas for targeted biopsy.⁷⁶ Imaging features of VLE found to be independently predictive of BE neoplasia included lack of layering, higher surface than subsurface signaling, and irregularly dilated glands/ducts. Recently, a software upgrade called Intelligent Real-time Image Segmentation™ (IRIS) artificial intelligence has become available, which displays the three most common esophageal image features and colorizes the image to aid review. Sensitivity and specificity of VLE for dysplasia detection are 86% and 88%, respectively, and diagnostic accuracy is 87%.⁷⁷ A recent study reported incremental yield of dysplasia with laser marked targets in VLE (33.7%) when compared with random biopsies (5.7%), Seattle protocol biopsies (19.6%), and VLE without laser marking (24.8%).⁷⁸ The rate of overall yield of dysplasia compared to Seattle protocol was statistically higher (OR 2.1; p = 0.03). Another study demonstrated very high inter-observer agreement overall (esophageal mucosa, gastric mucosa, nonneoplastic BE, and neoplastic BE; κ = 0.81) and strong agreement for nonneoplastic BE and neoplastic BE (κ = 0.66 and 0.79, respectively).⁷⁹ The learning curve for VLE users after a brief training session of 31 novice clinicians showed that 71% were able to achieve interpretation competency during 96-slide review and half of the physicians achieved competency at 65 images. The median accuracy overall was 95%, 90% for nonneoplastic BE, and 96% for neoplastic BE.⁸⁰ VLE provides a large field of view and is fast requiring only 60–90 seconds for a complete scan.⁶⁵ Minor mucosal lacerations were reported in 2% of patients with the 25 mm balloon and hence it was discontinued.⁸¹ An upcoming development is computer-aided detection of early Barrett’s neoplasia using an algorithm for automated analysis of ex vivo VLE images where a full scan including 1200 frames is analyzed in less than a minute.⁸² This technology had a considerably high detection rate when compared with manual reads (AUROC 0.95 versus 0.81, respectively) thereby demonstrating a future potential to assist endoscopists in the early detection of neoplasia with VLE.

Wide area transepithelial sampling with computer-assisted three-dimensional analysis (WATS^3D) uses esophageal brush biopsy that procures wide-area, full-thickness transepithelial tissue sample. In the laboratory, computer-assisted analysis synthesizes up to 100 two-dimensional optical slides into a single three-dimensional image for pathology review. Multicenter randomized trials or double-blinded crossover studies have been underway since 2010 evaluating the efficiency of WATS^3D in the diagnosis of BE/dysplasia as an adjunctive to the Seattle protocol biopsies.^83–86 A study on 160 patients with BE, using WATS^3D in conjunction with biopsy yielded an additional 23 cases (14.4%; 95% CI 7.5–21.2%) of HGD/EAC compared with biopsy alone.⁸⁷ The inter-observer agreement among pathologists in the diagnosis of dysplasia using WATS^3D was very high with a κ = 0.95 for HGD/EAC and κ = 0.74 for LGD and indefinite for dysplasia (IND).⁸⁸ The main advantage of this technique lies in large tissue sample size although it adds an additional 4.5 min to procedure time.⁸⁷ Even though glandular changes are better detected by WATS^3D than with cytology, architectural changes cannot be detected as in histology and this leads to overestimation of dysplasia by WATS^3D.⁸⁹ Furthermore WATS^3D has been studied as an adjunctive to random biopsy without a direct comparison with surveillance biopsies per Seattle protocol. Only WATS-positive HGD/EAC slides were reviewed by two expert pathologists instead of all cases as only latter can give an idea of false-negative and false-positive rates. Studies on larger patient cohorts with longer follow up are needed before WATS^3D is generalizable to community population.

Role of artificial intelligence

On the horizon is the use of artificial intelligence which will allow auto-analysis of medical images to detect dysplastic lesions within BE (computer-aided detection). Several studies have been performed in past the few years using WLE, high-definition WLE, and NBI images to automatically detect areas of abnormality within BE segment. These studies are based on use of mainly support vector machines and neural networks with other techniques such as k-nearest neighbors (k-NN), k-statistics, and decision trees.⁹⁰ The main limitations of the currently proposed techniques are the limited number of images these studies are based on, inordinate amount of time needed to process the images, and, finally, the accuracy.

Post-ablation surveillance

Endoscopic eradication therapy (EET) of BE is highly effective with eradication rates of up to 78% for metaplasia and 91% per dysplasia, but with recurrence rates of 4.8/100 person-years for IM and 2/100 person-years for dysplasia.^91,92 Therefore, close surveillance is recommended after successful eradication of BE. ACG recommends surveillance every 3 months for the first year following complete eradication of intestinal metaplasia (CEIM), every 6 months in the second year, and annually thereafter for patients with HGD or IMC.¹ In patients with LGD before ablation, endoscopic surveillance is recommended every 6 months in the first year following CEIM and annually thereafter.¹ A recently published model based on US RFA registry and UK national Halo registry recommends surveillance at 1 and 3 years after CEIM for LGD and 0.25, 0.5, and 1 year for HGD or IMC.⁵⁶ Discontinuing surveillance is not recommended after multiple negative examinations as recurrences have been reported several years after EET. Another concern is the presence of subsquamous BE (buried BE) developing beneath the endoscopically normal appearing post-ablative epithelium, which cannot be adequately sampled by biopsy forceps. The clinical significance of subsquamous BE is not known but likely carries a low risk of progression as subsquamous EAC is infrequent.⁶⁷

In conclusion, although there are clear-cut guidelines on the screening and surveillance of BE, the current strategies are inadequate as more than 90% of patients diagnosed with EAC do not have a prior diagnosis of BE. The alternative nonendoscopic methods of screening that are in development may make screening available to the wider population while reducing the costs. Based on current evidence, uTNE is suitable for mass screening for BE. Cytosponge and Esocheck nonendoscopic balloon are being validated in larger studies before they can be implemented for clinical use. For better detection of dysplasia during surveillance, NBI is useful for recognition of subtle lesions as it is fast, easy to use, and accurate. VLE and WATS^3D are commercially available and have high dysplasia detection rates and have potential for future use. Further studies are needed to evaluate their efficacy in decreasing EAC mortality rates and also to develop better biomarker panels for risk stratification of BE patients.

Footnotes

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

ORCID iD

Prashanthi N. Thota

References

Shaheen

Falk

Iyer

et al . ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111: 30–50; quiz 51.

Hayeck

Kong

Spechler

et al . The prevalence of Barrett’s esophagus in the US: estimates from a simulation model confirmed by SEER data. Dis Esophagus 2010; 23: 451–457.

Boeckxstaens

El-Serag

Smout

AJPM

et al . Symptomatic reflux disease: the present, the past and the future. Gut 2014; 63: 1185–1193.

Kastelein

van Olphen

Steyerberg

et al . Impact of surveillance for Barrett’s oesophagus on tumour stage and survival of patients with neoplastic progression. Gut 2016; 65: 548–554.

Lagergren

Bergström

Lindgren

et al . Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340: 825–831.

Anderson

Murray

Murphy

et al . Mortality in Barrett’s oesophagus: results from a population based study. Gut 2003; 52: 1081–1084.

Eckardt

Kanzler

Bernhard

Life expectancy and cancer risk in patients with Barrett’s esophagus: a prospective controlled investigation. Am J Med 2001; 111: 33–37.

American Gastroenterological Association; Spechler

Sharma

et al . American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology 2011; 140: 1084–1091.

Evans

Early

Fukami

et al . The role of endoscopy in Barrett’s esophagus and other premalignant conditions of the esophagus. Epub ahead of print 2012. DOI: 10.1016/j.gie.2012.08.004.

10.

Fitzgerald

di Pietro

Ragunath

et al . British society of gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 2014; 63: 7–42.

11.

di Pietro

Fitzgerald

. Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett’s oesophagus with low-grade dysplasia. Gut 2018; 67: 392–393.

12.

Weusten

Bisschops

Coron

et al . Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Epub ahead of print 2017. DOI: 10.1055/s-0042-122140.

13.

Whiteman

Appleyard

Bahin

et al . Australian clinical practice guidelines for the diagnosis and management of Barrett’s esophagus and early esophageal adenocarcinoma. J Gastroenterol Hepatol 2015; 30: 804–820.

14.

Taylor

Rubenstein

JH.

Meta-analyses of the effect of symptoms of gastroesophageal reflux on the risk of Barrett’s esophagus. Am J Gastroenterol 2010; 105: 1730–1737.

15.

van Blankenstein

Looman

CWN

Johnston

et al . Age and sex distribution of the prevalence of Barrett’s esophagus found in a primary referral endoscopy center. Am J Gastroenterol 2005; 100: 568–576.

16.

Rubenstein

Mattek

Eisen

Age- and sex-specific yield of Barrett’s esophagus by endoscopy indication. Gastrointest Endosc 2010; 71: 21–27.

17.

Wang

Mattek

Holub

et al . Prevalence of complicated gastroesophageal reflux disease and Barrett’s esophagus among racial groups in a multi-center consortium. Dig Dis Sci 2009; 54: 964–971.

18.

Kubo

Cook

Shaheen

et al . Sex-specific associations between body mass index, waist circumference and the risk of Barrett’s oesophagus: a pooled analysis from the international BEACON consortium. Gut 2013; 62: 1684–1691.

19.

Singh

Sharma

Murad

et al . Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11: 1399–1412.e7.

20.

Andrici

Cox

Eslick

GD.

Cigarette smoking and the risk of Barrett’s esophagus: a systematic review and meta-analysis. J Gastroenterol Hepatol 2013; 28: 1258–1273.

21.

Chak

Lee

Kinnard

et al . Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. Gut 2002; 51: 323–328.

22.

Kunzmann

Thrift

Cardwell

et al . Model for identifying individuals at risk for esophageal adenocarcinoma. Clin Gastroenterol Hepatol 2018; 16: 1229–1236.e4.

23.

Levine

Haggitt

Blount

et al . An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology 1993; 105: 40–50.

24.

Saad

Mahood

Clary

et al . Role of cytology in the diagnosis of Barrett’s esophagus and associated neoplasia. Diagn Cytopathol 2003; 29: 130–135.

25.

Alexander

Jones

Smith

et al . Usefulness of cytopathology and histology in the evaluation of Barrett’s esophagus in a community hospital. Gastrointest Endosc 1997; 46: 318–320.

26.

Offman

Fitzgerald

RC.

Alternatives to traditional per-oral endoscopy for screening. Gastrointest Endosc Clin N Am 2017; 27: 379–396.

27.

Sami

Iyer

PG.

Recent advances in screening for Barrett’s esophagus. Curr Treat Options Gastroenterol 2018; 16: 1–14.

28.

Jobe

Hunter

Chang

et al . Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett’s esophagus: a randomized and blinded comparison. Am J Gastroenterol 2006; 101: 2693–2703.

29.

Peery

Hoppo

Garman

et al . Feasibility, safety, acceptability, and yield of office-based, screening transnasal esophagoscopy (with video). Gastrointest Endosc 2012; 75: 945–953.e2.

30.

Wilkins

Gillies

RA.

Office-based unsedated ultrathin esophagoscopy in a primary care setting. Ann Fam Med 2005; 3: 126–130.

31.

Sami

Dunagan

Johnson

et al . A randomized comparative effectiveness trial of novel endoscopic techniques and approaches for Barrett’s esophagus screening in the community. Am J Gastroenterol 2015; 110: 148–158.

32.

Shariff

Bird-Lieberman

O’Donovan

et al . Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett’s esophagus. Gastrointest Endosc 2012; 75: 954–961.

33.

Thota

Zuccaro

Jr. Vargo

II et al . A randomized prospective trial comparing unsedated esophagoscopy via transnasal and transoral routes using a 4-mm video endoscope with conventional endoscopy with sedation. Endoscopy 2005; 37: 559–565.

34.

Saeian

Staff

Vasilopoulos

et al . Unsedated transnasal endoscopy accurately detects Barrett’s metaplasia and dysplasia. Gastrointest Endosc 2002; 56: 472–478.

35.

Moriarty

Shah

Rubenstein

et al . Costs associated with Barrett’s esophagus screening in the community: an economic analysis of a prospective randomized controlled trial of sedated versus hospital unsedated versus mobile community unsedated endoscopy. Gastrointest Endosc 2018; 87: 88–94.e2.

36.

Ross-Innes

Debiram-Beecham

O’Donovan

et al . Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett’s esophagus: a multi-center case–control study. PLoS Med 2015; 12: e1001780.

37.

Kadri

Lao-Sirieix

O’Donovan

et al . Acceptability and accuracy of a non-endoscopic screening test for Barrett’s oesophagus in primary care: cohort study. BMJ 2010; 341: c4372.

38.

Barrett’s ESophagus Trial 3. MRC cancer unit, https://www.mrc-cu.cam.ac.uk/research/rebecca-fitzgerald/clinical-studies/BEST3 (accessed 22 April 2018).

39.

Heberle

Omidvari

Ali

et al . Cost effectiveness of screening patients with gastroesophageal reflux disease for Barrett’s esophagus with a minimally invasive cell sampling device. Clin Gastroenterol Hepatol 2017; 15: 1397–1404.e7.

40.

Chettouh

Mowforth

Galeano-Dalmau

et al . Methylation panel is a diagnostic biomarker for Barrett’s oesophagus in endoscopic biopsies and non-endoscopic cytology specimens. Gut. Epub ahead of print 30 October 2017. DOI: 10.1136/gutjnl-2017-314026.

41.

Freeman

Offman

Walter

et al . Acceptability of the cytosponge procedure for detecting Barrett’s oesophagus: a qualitative study. BMJ Open 2017; 7: e013901.

42.

Iyer

Taylor

Johnson

et al . Highly discriminant methylated DNA markers for the non-endoscopic detection of Barrett’s esophagus. Am J Gastroenterol 2018; 113: 1156–1166.

43.

Falk

Chittajallu

Goldblum

et al . Surveillance of patients with Barrett’s esophagus for dysplasia and cancer with balloon cytology. Gastroenterology 1997; 112: 1787–1797.

44.

Moinova

LaFramboise

Lutterbaugh

et al . Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus. Sci Transl Med 2018; 10: eaao5848.

45.

Bhardwaj

Hollenbeak

Pooran

et al . A meta-analysis of the diagnostic accuracy of esophageal capsule endoscopy for Barrett’s esophagus in patients with gastroesophageal reflux disease. Am J Gastroenterol 2009; 104: 1533–1539.

46.

Ramirez

Akins

Shaukat

Screening of Barrett’s esophagus with string-capsule endoscopy: a prospective blinded study of 100 consecutive patients using histology as the criterion standard. Gastrointest Endosc 2008; 68: 25–31.

47.

Rubenstein

Inadomi

Brill

J V

et al . Cost utility of screening for Barrett’s esophagus with esophageal capsule endoscopy versus conventional upper endoscopy. Clin Gastroenterol Hepatol 2007; 5: 312–318.

48.

Bus

Kestens

Ten Kate

FJW

et al . Profiling of circulating microRNAs in patients with Barrett’s esophagus and esophageal adenocarcinoma. J Gastroenterol 2016; 51: 560–570.

49.

Mallick

Patnaik

Wani

et al . A systematic review of esophageal microRNA markers for diagnosis and monitoring of Barrett’s esophagus. Dig Dis Sci 2016; 61: 1039–1050.

50.

Chan

Zakko

Visrodia

et al . Breath testing for Barrett’s esophagus using exhaled volatile organic compound profiling with an electronic nose device. Gastroenterology 2017; 152: 24–26.

51.

Kumar

Huang

Abbassi-Ghadi

et al . Mass spectrometric analysis of exhaled breath for the identification of volatile organic compound biomarkers in esophageal and gastric adenocarcinoma. Ann Surg 2015; 262: 981–990.

52.

Peters

Pei

et al . Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Res 2017; 77: 6777–6787.

53.

Elliott

DRF

Walker

O’Donovan

et al . A non-endoscopic device to sample the oesophageal microbiota: a case-control study. Lancet Gastroenterol Hepatol 2017; 2: 32–42.

54.

Yamamura

Baba

Nakagawa

et al . Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res 2016; 22: 5574–5581.

55.

Krishnamoorthi

Singh

Ragunathan

et al . Factors associated with progression of Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 16: 1046–1055.e8.

56.

Cotton

Haidry

Thrift

et al . Development of evidence-based surveillance intervals after radiofrequency ablation of Barrett’s esophagus. Gastroenterology 2018; 155: 316–326.e6.

57.

Gerson

Lin

OS.

Cost-benefit analysis of capsule endoscopy compared with standard upper endoscopy for the detection of Barrett’s esophagus. Clin Gastroenterol Hepatol 2007; 5: 319–325.e3.

58.

Shah

Lippman

Kohli

et al . Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett’s esophagus. Endosc Int Open 2018; 06: E414–E420.

59.

El-Serag

Naik

Duan

et al . Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett’s oesophagus. Gut 2016; 65: 1252–1260.

60.

Lochhead

Chan

AT.

Screening and surveillance for Barrett esophagus. JAMA Intern Med 2015; 175: 159.

61.

Saxena

Inadomi

JM.

Effectiveness and cost-effectiveness of endoscopic screening and surveillance. Gastrointest Endosc Clin N Am 2017; 27: 397–421.

62.

Esophageal Cancer. Cancer stat facts, https://seer.cancer.gov/statfacts/html/esoph.html (accessed 14 March 2018).

63.

Jung

Talley

Romero

et al . Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett’s esophagus: a population-based study. Am J Gastroenterol 2011; 106: 1447–1455.

64.

Qumseya

Wang

Badie

et al . Advanced imaging technologies increase detection of dysplasia and neoplasia in patients with Barrett’s esophagus: a meta-analysis and systematic review. Clin Gastroenterol Hepatol 2013; 11: 1562–70.e1–2.

65.

Kandel

Wallace

MB.

The role of adjunct imaging in endoscopic detection of dysplasia in Barrett’s esophagus. Gastrointest Endosc 2017; 27: 423–446.

66.

Coletta

Sami

Nachiappan

et al . Acetic acid chromoendoscopy for the diagnosis of early neoplasia and specialized intestinal metaplasia in Barrett’s esophagus: a meta-analysis. Gastrointest Endosc 2016; 83: 57–67.e1.

67.

Mansour

El-Serag

Anandasabapathy

Barrett’s esophagus: best practices for treatment and post-treatment surveillance. Ann Cardiothorac Surg 2017; 6: 75–87.

68.

Chedgy

Subramaniam

Kandiah

et al . Acetic acid chromoendoscopy: improving neoplasia detection in Barrett’s esophagus. World J Gastroenterol 2016; 22: 5753.

69.

Pascarenco

Coroş

Pascarenco

et al . A preliminary feasibility study: narrow-band imaging targeted versus standard white light endoscopy non-targeted biopsies in a surveillance Barrett’s population. Dig Liver Dis 2016; 48: 1048–1053.

70.

Sharma

Bergman

JJGHM

Goda

et al . Development and validation of a classification system to identify high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophagus using narrow-band imaging. Gastroenterology 2016; 150: 591–598.

71.

Thosani

Abu Dayyeh

Sharma

et al . ASGE Technology Committee systematic review and meta-analysis assessing the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance. Gastrointest Endosc 2016; 83: 684–98.e7.

72.

de Groof

Swager

A-F

Pouw

et al . Blue-light imaging has an additional value to white-light endoscopy in visualization of early Barrett’s neoplasia: an international multicenter cohort study. Gastrointest Endosc. Epub ahead of print 9 November 2018. DOI: 10.1016/j.gie.2018.10.046.

73.

Chauhan

Abu Dayyeh MPH

Bhat

et al . Confocal laser endomicroscopy. Gastrointest Endosc 2014; 80: 928–938.

74.

NvisionVLE® Imaging System. NinePoint Medical, http://www.ninepointmedical.com/nvisionvle-imaging-system/ (accessed 3 December 2018).

75.

Jain

Fatima

Jain

et al . Volumetric laser endomicroscopy for Barrett’s esophagus: looking at the fine print. J Gastrointestin Liver Dis 2017; 26: 291–297.

76.

Swager

A-F

de Groof

Meijer

et al . Feasibility of laser marking in Barrett’s esophagus with volumetric laser endomicroscopy: first-in-man pilot study. Gastrointest Endosc 2017; 86: 464–472.

77.

Leggett

Gorospe

Chan

et al . Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc 2016; 83: 880–888.

78.

Alshelleh

Inamdar

McKinley

et al . Incremental yield of dysplasia detection in Barrett’s esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol. Gastrointest Endosc 2018; 88: 35–42.

79.

Trindade

Inamdar

Smith

et al . Volumetric laser endomicroscopy in Barrett’s esophagus: interobserver agreement for interpretation of Barrett’s esophagus and associated neoplasia among high-frequency users. Gastrointest Endosc 2017; 86: 133–139.

80.

Trindade

Inamdar

Smith

et al . Learning curve and competence for volumetric laser endomicroscopy in Barrett’s esophagus using cumulative sum analysis. Endoscopy 2018; 50: 471–478.

81.

Wolfsen

Sharma

Wallace

et al . Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett’s esophagus (with videos). Gastrointest Endosc 2015; 82: 631–640.

82.

Swager

A-F

van der Sommen

Klomp

et al . Computer-aided detection of early Barrett’s neoplasia using volumetric laser endomicroscopy. Gastrointest Endosc 2017; 86: 839–846.

83.

Thoguluva Chandrasekar

Vennalaganti

Sharma

. Management of Barrett’s esophagus: from screening to newer treatments. Rev Gastroenterol Mex 2016; 81: 91–102.

84.

Fennerty

MB.

Endoscopic diagnosis and surveillance of Barrett’s esophagus. Gastrointest Endosc Clin N Am 2003; 13: 257–267.

85.

Anandasabapathy

Sontag

Graham

et al . Computer-assisted brush-biopsy analysis for the detection of dysplasia in a high-risk Barrett’s esophagus surveillance population. Dig Dis Sci 2011; 56: 761–766.

86.

Johanson

Frakes

Eisen

Computer-assisted analysis of abrasive transepithelial brush biopsies increases the effectiveness of esophageal screening: a multicenter prospective clinical trial by the EndoCDx Collaborative Group. Dig Dis Sci 2011; 56: 767–772.

87.

Vennalaganti

Kaul

Wang

et al . Increased detection of Barrett’s esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial. Gastrointest Endosc. Epub ahead of print 2017. DOI: 10.1016/j.gie.2017.07.039.

88.

Vennalaganti

Naag Kanakadandi

Gross

et al . Inter-observer agreement among pathologists using wide-area transepithelial sampling with computer-assisted analysis in patients with Barrett’s esophagus. Am J Gastroenterol 2015; 110: 1257–1260.

89.

Canto

Montgomery

Wide-area transepithelial sampling with 3-dimensional cytology: does it detect more dysplasia or yield more hype?

Gastrointest Endosc 2018; 87: 356–359.

90.

de Souza

Palm

Mendel

et al . A survey on Barrett’s esophagus analysis using machine learning. Comput Biol Med 2018; 96: 203–213.

91.

Orman

Shaheen

NJ.

Systematic reviews and meta-analyses efficacy and durability of radiofrequency ablation for Barrett’s esophagus: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013; 11: 1245–1255.

92.

Fujii-Lau

Cinnor

Shaheen

et al . Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: a systematic review and meta-analysis. Endosc Int open 2017; 5: E430–E449.

Barrett’s esophagus: novel strategies for screening and surveillance

Abstract

Keywords

Introduction

Screening

Should we screen for BE? Pros and cons

Who should we screen?

How to screen?

Surveillance

Role of artificial intelligence

Post-ablation surveillance

Footnotes

Funding

Conflict of interest statement

ORCID iD

References