Sameer Zar - The Royal Marsden

The Royal Marsden 

Barrett’s Oesophagus 

and therapeutic 

endoscopic interventions 

Dr Sameer Zar 

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Barrett's oesophagus is a condition in which stratified 

squamous epithelium in the distal oesophagus is 

replaced by metaplastic columnar epithelium to a 

varying extent 

The condition develops as a consequence of chronic 

gastroesophageal reflux disease (GORD) 

It predisposes to the development of adenocarcinoma of 

the oesophagus

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Diagnosis of Barrett’s Oesophagus 

Diagnosis of Barrett’s oesophagus is based on 

two criteria 

– Endoscopic examination 

Location of squamocolumnar junction in relationship 

to the gastroesophageal junction 

– Histological confirmation 

Replacement of stratified squamous epithelium with 

intestinal metaplasia (columnar lined epithelium)

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Barrett’s Oesophagus - Diagnosis

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Clinical Features of Barrett’s Oesophagus 

No specific symptoms 

Symptoms related to reflux disease 

– Heartburn 

– Acid regurgitation 

– Retrosternal discomfort/pain 

– Dysphagia 

– Water brash 

– Odynophagia

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The Royal Marsden Change Presentation title and date in Footer dd.mm.yyyy 

Risk factors for Barrett’s 

Oesophagus

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Risk Factors Associated with Oesophageal 

Adenocarcinoma in Barrett’s Oesophagus 

Which of the following is not a risk factor for Barrett’s 

Oesophagus: 

1. Age 50 years or older 

2. Male sex 

3. White race 

4. Chronic GORD (>10yrs) 

5. Hiatus hernia 

6. H pylori infection 

Screening for Barrett’s should be considered in patients with 

multiple risk factors

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– Caucasian male disease 

– 40–100 x increased risk of oesophageal cancer 

– Annual progression rate 0.5%/year 

– Average age at diagnosis=55 

(Shaheen, Am J Gastro 2000) 

(Spechler, NEJM 1986)

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Cancer Risk in Barrett’s 

Oesophagus – Case for 

Screening and Surveillance


GORD - Metaplasia - Dysplasia - Carcinoma Model


Reflux is a Risk Factor for Adenocarcinoma 

of the Oesophagus 

Lagergren J et al, New Engl J Med 1999; 340: 825-31

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Incidence of Oesophageal Adenocarcinoma 

is on the rise in White Men 

Rate per 100,000 

4.5 

4 

3.5 

3 

2.5 

2 

1.5 

1 

0.5 

0 

1974 1978 1982 1986 1990 1994 1998


Oesophageal Cancer is a Lethal 

Disease 

Shaheen NJ et al. Am J Gastroenterol 2006; 101: 2128-38

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Cancer Risk in Barrett’s Oesophagus 

– Observational studies show that endoscopic 

surveillance can detect curable dysplasia in Barrett's 

– Asymptomatic cancers discovered during surveillance 

are less advanced than those found in patients who 

present with cancer symptoms


Surveillance Detects Cancer at Early Stage 

Barrett’s Barrett s Surveillance Surveillance associated associated with with better better cancer cancer stage and 

survival survival (Corley, (Corley, Gastro Gastro 2002) 

2002)


Oesophageal Adenocarcinoma 

Incidence rising rapidly 

6 Fold increase in last 3 decades 

Least studied and deadliest cancer worldwide 

5 year survival 10% 

Small number of cases 

Compare to Colorectal Cancer 

Population screening not feasible 

So Who should be targeted for surveillance?

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Surveillance of Barrett’s Oesophagus 

Barrett’s is a precursor lesion for Adenocarcinoma 

Progressive changes in Barrett’s segment offers a 

potential opportunity to intervene at an earlier stage 

to prevent progression to cancer 

Early detection of cancer improves survival

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Which of the following is not a risk factor for 

adenocarcinoma in Barrett’s Oesophagus: 

1. Family h/o Oesophageal cancer 

2. Family h/o Gastric cancer 

3. Alcohol 

4. Smoking 

5. Increased Body Mass Index 

6. Intra-abdominal distribution of body fat

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Which of the following is not a risk factor for Barrett’s 

Oesophagus: 

1. Length of Barrett’s segment (>8cm) 

2. Severity of reflux symptoms 

3. Frequency of reflux symptoms (>3 times/week) 

4. Ulceration or stricture in Barrett’s segment 

5. NSAIDs, Aspirin and COX -2 inhibitors 

6. Duodeno-gastro-oesophageal (Biliary) reflux

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Strategies to Manage Cancer Risk in 


Screening 

– General population 

– GORD patients 

Surveillance 

– Barrett’s oesophagus 

– Barrett’s oesophagus with risk factors

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Screening For Barrett’s Oesophagus 

General population 

– 1.6% of general population has Barrett’s 

Ronkainen J, Gastroenterology 2005; 129:1825. 

– 44 percent of patients lack "troublesome heartburn 

and/or acid regurgitation during the past three months 

GORD patient 

– 14% of adult population has weekly reflux symptoms 

(40% have monthly symptoms) 

– In patients with GORD symptoms, long-segment 

Barrett's oesophagus is found in 3 - 5 % and shortsegment 

Barrett's in 10 - 15 % 

Winters C Jr,. Gastroenterology 1987; 92:118. 

Spechler SJ. N Engl J Med 2002; 346:836.


Screening and Surveillance in Barrett’s 

Oesophagus 

Medical Society Recommendations for Screening and 

Surveillance 

Endorsement: BSG, ACG, ASGE 

No endorsement: AGA 

No Quality Trial Data of Natural History and 

Screening/Surveillance 

Observational data 

Computer simulation models

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Screening and Surveillance for Oesophageal 

Adenocarcinoma 

How many patients with early oesophageal 

adenocarcinoma can be potentially indentified 

through screening and surveillance? 

1 90-100% 

2 75% 

3 50% 

4 20-25% 

5 10%


Screening for Barrett’s Oesophagus 

>40% of patients diagnosed with oesophageal adeno- 

carcinoma have no history of heartburn 

Majority (>90%) Barrett’s pts will NOT develop 

adenocarcinoma 

Chak, Cancer 2006 

Barrett’s diagnosis negatively impacts Quality of Life 

Gerson, GI Endo 2007; Hur, Health Rel QoL 2007

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Screening and Surveillance for Oesophageal 

Adenocarcinoma


How to Improve Screening for Barrett’s 

Oesophagus 

>40% of patients diagnosed with oesophageal adeno- 

carcinoma have no history of heartburn 

Majority (>90%) Barrett’s pts will NOT develop 

adenocarcinoma 

Chak, Cancer 2006 

Barrett’s diagnosis negatively impacts Quality of Life 

Gerson, GI Endo 2007; Hur, Health Rel QoL 2007

How to Improve Screening for Barrett’s 

Oesophagus 

– Review guidelines for 

screening 

– Identify risk factors for Barrett’s 

– Heartburn / 4 weeks / most of the 

time – triggers endoscopy 

– Improve screening methods 

– Videocapsule 

– Cytosponge 

– Prescribing practices 

– Repeat prescriptions for PPI 

– Educating public, pharmacists

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How do Patients with Barrett’s Perceive 

their Cancer Risk?

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Management of Barrett’s 

Oesophagus


The current screening & surveillance 

practice for Oesophageal Adenocarcinoma?

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Managing Cancer Risk in Barrett’s Oesophagus 

The management of patients with Barrett's 

oesophagus involves three major 

components: 

– Treatment of the associated GORD 

– Endoscopic surveillance to detect dysplasia 

– Treatment of dysplasia

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How to Screen for Dysplasia in Barrett’s 

Oesophagus 

Endoscopic evaluation using white light 

endoscopy 

– Four-quadrant biopsy specimens be taken every 2 cm 

– Specific biopsy specimens of any mucosal 

irregularities 

– Four-quadrant biopsy specimens be obtained every 1 

cm in patients with known or suspected dysplasia

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Management of Barrett’s Oesophagus 

Management of patients with Barrett’s can be 

divided in three categories 

– Barrett’s oesophagus without dysplasia 

– Barrett’s oesophagus with Low Grade Dysplasia 

– Barrett’s with High Grade Dysplasia

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Barrett’s oesophagus 

– Risk of cancer 0.3 - 0.5% per year 

Shaheen. Gastroenterology 2000:119:333 

Barrett’s oesophagus with Low Grade Dysplasia 

– Probably 0.6 - 5% 

Barrett’s with High Grade Dysplasia 

– Risk of cancer 5-8% per year 

Spechler: Am J Gastroenterol 2005;100:927 

– 12% harbour invasive carcinoma at diagnosis 

– Lymph node metastases is

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Endoscopic surveillance is suggested for patients with 

Barrett's oesophagus using the following surveillance 

intervals: 

– No dysplasia: 2 to 5 years 

– Low-grade dysplasia: 6 to 12 months 

– High-grade dysplasia in the absence of eradication 

therapy: 3 months

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without Dysplasia 

Management of patients with Barrett’s who do 

not have dysplasia involves: 

– Treatment of reflux disease 

– PPI (H2 antagonists are inadequate) 

– Antireflux surgery 

– Surveillance endoscopy for dysplasia every 2-5 years 

– ?Chemoprevention

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without Dysplasia 

– In symptomatic patients, symptom control is an 

important objective of treatment 

– Many patients with Barrett’s have few or no 

symptoms due to the relative insensitivity of 

columnar mucosa to acid 

– Therefore, symptom control should not be 

interpreted as indicating suppression of oesophageal 

reflux

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PPI Dosing in Reflux Disease and Barrett’s 

Oesophagus 

If the patient requires a PPI to be given in doses higher 

than recommended, they are best given: 

1. Double dose once a day before breakfast 

2. Double dose once a day before dinner 

3. Before breakfast and before dinner 

4. Before breakfast and at bedtime

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Twice Daily dosing of PPI 

– Twice daily dosing of PPI has superior intra-gastric 

pH control over 24hrs compared to double dose 

taken before breakfast or before dinner alone 

Kuo et al; Am J Gastro 1996 

– Nocturnal intragastric pH control is superior with 

second dose taken before dinner vs. before bedtime 

Hatlebackk et al; A P & Th 1998

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Barrett’s Oesophagus with Low Grade 

Dysplasia 

– Darker Hyperchromatic 

– Cytological atypia 

– 2.7 – 3.4% per yr progress 

to HGD/Cancer over a 

mean follow up of 5-8 yrs

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Management of Barrett’s Oesophagus with 

Low Grade Dysplasia 

– Treatment of reflux disease 

– PPI (H2 antagonists are inadequate) 

– Anti-reflux surgery 

– Screening endoscopy for dysplasia every 6-12 months 

– ?Chemoprevention 

– ?Ablation/Surgery

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Barrett’s Oesophagus with High Grade 

Dysplasia 

– Cytological atypia 

– Loss of nuclear polarity 

– Crypts distorted with back- 

to-back glands 

– 25% progress to 

adenocarcinoma in 5 yrs 

– 12-17% may already harbour 

adenocarcinoma

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Management options in Barrett’s with High 

Grade Dysplasia

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Radiofrequency Ablation

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Radiofrequency Ablation 

– A bipolar device containing 60 separate 250-µm 

electrodes circumferentially oriented on the outer 

surface of a balloon for circumferential ablation in the 

esophagus 

– It delivers heat to the mucosa at a controlled depth 

(down to muscularis mucosae, with no involvement of 

the submucosa). 

– A related device (HALO90; Barrx) is designed for 

focal ablation.

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Barrx Halo

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Barrx Halo

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Endoscopic Mucosal 

Resection

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Endoscopic Mucosal Resection (EMR) 

– EMR is an endoscopic alternative to surgical resection 

of mucosal and submucosal neoplastic lesions 

– EMR involves snare resection of the dysplastic lesion 

– Two methods: Cap suction and Band ligation followed 

by snare resection 

– Lesion is excised rather than ablated – allows 

histological diagnosis and staging

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EMR for Barrett’s and High Grade Dysplasia

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Endoscopic Submucosal 

Dissection

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Endoscopic Submucosal Dissection (ESD) 

– Large oesophageal lesions are removed en bloc by 

dissecting through the submucosal plane 

– Specially designed needle-knives 

– Facilitated by submucosal injection of viscous 

substances such as hyaluronidate, which provide 

prolonged submucosal lifting 

– High level of endoscopic expertise required

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ESD for Barrett’s and High Grade Dysplasia

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Endoscopic Therapy in 

Oesophageal Cancer

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Endotherapy in Barrett’s with Oesophageal 

Cancer 

ESD or EMR 

– Early superficial cancer limited to mucosa 

Endoscopic palliation in advanced cancer 

– Oesopahgeal stent

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Oesophageal Stent to Relieve Dysphagia in 

Advanced Oesopahgeal Cancer


Primary Prevention 

- Surveillance Dietary factors (not proven): 

- Ample fruit and vegetables 

- Effect of dietary supplements not clear 

- Weight Gain and Obesity


Chemoprevention in Barrett’s Oesophagus 

(High Risk Patients) 

- Meta-analysis: Aspirin and NSAID use associated with 

decreased rate of adenocarcinoma [OR=0.5; 0.75] 

- Aspirin Chemoprevention in Barrett’s 

Cost-effective with or without Endoscopic surveillance 

- AspECT, Large RCT in the U.K. 

PPI & Aspirin’s Effect on BE EAC Progression 

5000 patient over 8 years (ongoing) 

Corley, Gastro 2003 

Hur, JNCL 2004


Conclusion 

- Screening for Barrett’s oesophagus should be targeted 

at high risk population 

- Surveillance for oesophageal adenocarcinoma in 

Barrett’s can detect dysplasia and early cancer 

- New endoscopic techniques offer an opportunity to 

intervene before the development of advanced 

oesophageal cancer

Sameer Zar - The Royal Marsden

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