Barrett’s Esophagus: Does that Z-line look irregular to you? Andrew Flynn, MD, PhD, FRCPC Sept 22, 2017

Disclosures None relevant.

Acknowledgments Dr. Cheryl Wright, PATH

Table of Contents Epidemiology Screening/diagnosis Surveillance/management Quiz!

But first... the case 50 y.o. man referred for Barrett‘s screening. 8 year history of heartburn, well controlled with daily pantoprazole. No dysphagia or other alarm symptoms. Otherwise healthy. Smokes occasional cigar. Social EtOH. Father and paternal aunt with esophageal adenocarcinoma.

Endoscopy

Barrett’s History Norman Barrett, 1950 “...in cases of congenital short oesophagus...the bare area is larger than usual.” Barrett initially thought the phenomenon was due to congenitally short esophagus.

Definition Metaplasia from normal stratified squamous epithelium to columnar epithelium with goblet cells (“intestinal metaplasia”). May or may not be associated with dysplasia. Replacement of one differentiated cell type with another. Goblet cells not found in stomach. Dysplasia = less differentiated.

Columnar epithelium more resistant to reflux-related damage. http://medcell.med.yale.edu/systems_cell_biology/gi_tract_lab.php

Pathogenesis? vs migration of stem cells from gastric cardia or circulation. Souza et al., 2008

Epidemiology Prevalence = 1.5% in general population, 15% in those with GERD RFs = older age, male, smoking, obesity, white ethnicity, FHx FHx Barrett’s or EAC.

So whats the problem 0.25% ~0.55% 4-8% Approximate annual risk. Conteduca et al., 2012

Could be worse! 10 year risk of EAC 17.5% 2.5% Earlier small studies severely over-estimated risk. Wani et al., 2011

Adeno vs squamous “Lower third” Barrett’s, GERD, smoking, obesity Incidence rising “Upper two thirds” Smoking, EtOH, dietary factors, caustic ingestion Incidence falling Not included: small cell carcinomas, sarcomas

Screening Points to keep in mind: > 90% of patients with EAC have never been diagnosed with BE 40% of patients with BE do not have a clinical history of GERD The majority of patients with BE will not die of EAC Meta-analysis of ~4200 patients. Most common cause of death in BE patients = CAD. Sikkema et al., 2010

Screening guidelines Consider screening patients with > 5 yrs heartburn or acid regurgitation, and 2 of: Age > 50 yrs Caucasian race Central obesity Smoking history History BE/EAC in first degree relative ACG Guideline 2015 Strong recommendation, moderate (male) or low (female) level of evidence. Male >> female. (Risk in female w/ GERD = risk in male w/o GERD.)

Diagnosis Columnar epithelium ≥ 1 cm above GEJ + biopsy demonstrating intestinal metaplasia. 4 quadrant biopsies every 2 cm > 3 cm = long segment Columnar epithelium = pink, velvety; squamous epithelium = pale, shiny. Longer mucosal inspection time & sufficient biopsies are predictors of increased dysplasia detection. Harrison et al., 2007

Prague Classification C1M4 Schoofs et al., 2017

8 weeks PPI bid Pointless to biopsy esophagitis. Patient had BE w/o dysplasia.

Imaging modalities Current recommendation: Goal: High-definition white light endoscopy Goal: Imaging modality to improve targeted biopsies VLE HD-WLE NBI Chromo CLE WLE, NBI, chromo, confocal laser endomicroscopy, volumetric laser endomicroscopy. Eluri and Shaheen, 2017 Leggett et al., 2016

Adherence to screening Analysis of 2245 surveillance cases in the community setting. #1 = adherence to screening based on BE length. #2 = detection of dysplasia depending on BE length. Abrams et al., 2009

Alternative screening options

Transnasal endoscopy Unsedated TNE using disposable Endosheath. Well tolerated (>95%) and cost effective. Not for surveillance (biopsy forceps too small to reliably detect dysplasia).

Cytosponge IHC done for Trefoil Factor-3. More sensitive/specific for long segment Barrett’s.

Surveillance/Management

Confirmed by 2nd (expert) pathologist No BE = no surveillance. Significant proportion (~75%) of LGD will be downgraded by expert pathologist. Remainder have high risk of progression. Could consider surveillance if elderly. vs Eluri and Shaheen, 2017

Radiofrequency ablation Thermal injury. Recommended post-EMR to reduce risk of subsequent dysplasia. Eluri and Shaheen, 2017

RFA results N = 127 patients. Risk of stricture = ~6%. Eradication in controls likely = sampling error. Shaheen et al., 2009

Recurrence post RFA Recurrence of intestinal metaplasia in patients who have undergone complete eradication of intestinal metaplasia (CEIM). Comparable whether EMR done or not. ~25% recurrence at 2-3 years (vast majority as NDBE), necessitating endoscopic follow-up. Pasricha et al., 2014

Death post RFA EAC Only 3% of ~5000 patients died. Most common cause of death = cardiac. EAC was 5th most common cause. Wolf et al., 2015

RFA for LGD? RCT of 136 patients. Study ended prematurely. Phoa et al., 2014

Map first, then biopsy abnormalities (nodularity, erosion, plaque, stricture), then 4 quadrant. Abnormalities are associated with higher rates of malignancy (risk = ~30% in patients with HGD on Bx).

Surveillance/Management (submucosal invasion) Esophagectomy ? Unfavorable histology = poor differentiation or lymphovascular invasion. Risk of nodal metastases in T1b is up to 22% (depends on sm1/2/3). ? = if sm1 (upper third of submucosa) + small + poor surgical candidate. Shaheen et al., 2015

EMR Band-ligation technique- one option. Benefit = staging + removal of dysplasia. Usually not recommended for complete resection due to high stricture rate. Sakai and Maluf-Filho, 2015

“Chemoprevention”? No PPI PPI Cohort study: 40 of 540 patients (7%) developed HGD or EAC. (Conflicting data.) No reduction in Barrett’s length with PPI. No role for bid PPI unless severe esophagitis. No role for anti-reflux surgery. No role for ASA or NSAIDs. PPI Kastelein et al., 2013

Summary Barrett’s esophagus (intestinal metaplasia) is common in older males with GERD Screening involves EGD with 4 quadrant biopsies every 2 cm Dysplasia is a significant risk factor for EAC RFA +/- EMR is effective at eradicating Barrett’s with/without dysplasia PPI therapy is recommended for Barrett’s

Back to the case Referred for EMR/RFA, but repeat biopsies showed at least T1b disease. CT/PET showed no metastases. Due for esophagectomy.

Quiz time!

Yes!

No! (EoE)

No!

No!

Yes!

No! (sloughing)

No!

Yes!

Yes/No (EAC)

What we’re trying to avoid 41 y.o. with 4 weeks progressive dysphagia, chronic heartburn.