Barrett’s Oesophagus

Gastro-oesophageal Reflux and Bile Exposure

• The fundamental aetiological factor in Barrett’s oesophagus is chronic gastro-oesophageal reflux disease (GORD), which leads to repeated mucosal injury in the distal oesophagus.
• It is not merely acid reflux that contributes to epithelial damage; a combination of acid and bile exposure is considered the most harmful. Evidence shows that more than 50% of patients with GORD exhibit abnormal bile levels in the oesophagus, and the highest levels are consistently found in those with Barrett’s oesophagus.
• Among patients with Barrett’s, approximately half with abnormal bile exposure in the oesophagus have normal gastric bile levels, suggesting an isolated oesophageal phenomenon.
• Mucosal injury is most frequent in those exposed to both acid and bile, less so in acid-only exposure, and least in bile-only exposure, highlighting the synergistic damaging effect of acid-bile reflux.

Anatomical and Functional Contributors

• Several anatomical and physiological features predispose GORD patients to develop Barrett’s oesophagus:
  • Hiatal hernia, which weakens the anti-reflux barrier.
  • Low lower oesophageal sphincter (LES) pressure, which reduces resistance to refluxate.
  • Delayed oesophageal acid clearance, leading to prolonged mucosal contact with refluxate.
  • Duodenogastric reflux, where bile enters the oesophagus, further potentiating epithelial damage.
    
    

Mechanisms of Mucosal Defence and Injury

• The oesophagus has intrinsic protective mechanisms:
  • A high-pressure LES zone supported by the diaphragm’s right crus.
  • Peristaltic clearance, gravity, and bicarbonate-rich secretions from salivary and submucosal glands.
  • Tight junctions between epithelial cells and lipid-rich intercellular spaces that restrict H+ entry.
• When overwhelmed, these defences fail:
  • Lower pH and prolonged exposure cause mucosal inflammation and epithelial necrosis.
  • This chronic injury is thought to trigger the metaplastic transformation to columnar epithelium.
    
    
    

Progression to Metaplasia

• Metaplastic columnar epithelium in Barrett’s oesophagus is likely an adaptive response to sustained injury, intended to resist further damage. However, this change introduces the risk of malignant transformation to adenocarcinoma.
• Columnarisation reduces GORD symptoms and stricture formation, paradoxically making the disease less symptomatic while increasing cancer risk.
  
  

Phenotypic Variation in Reflux Exposure

• Long-segment Barrett’s oesophagus (LSBE, >3 cm) and short-segment Barrett’s oesophagus (SSBE, <3 cm) exhibit different reflux profiles:
  • LSBE patients often have longer symptom duration, severe reflux (both supine and upright), and low LES pressure but reduced sensitivity to acid.
  • SSBE patients show shorter symptom duration, upright reflux only, normal LES pressure, and greater acid sensitivity.
    
    
    

Obesity and Lifestyle-Related Risk Factors

• Central obesity is an established independent risk factor for Barrett’s oesophagus, likely due to increased intra-abdominal pressure and its impact on reflux dynamics.
• The rising incidence of obesity correlates with increased rates of Barrett’s and oesophageal adenocarcinoma.
  
  

Medication-Related Risks: Oral Bisphosphonates

• Epidemiological evidence has linked oral bisphosphonate use—especially alendronate—with increased risk of Barrett’s oesophagus in patients with GORD.
• A case-control study in US veterans found a 2.33-fold increased risk overall, which rose to 3.29-fold in patients with active GORD symptoms.
• The risk was also significantly higher in users of proton pump inhibitors (PPIs), but no association was observed in those without GORD or PPI use.
  
  

Definition and Diagnostic Basis

• Barrett’s oesophagus is defined by the American College of Gastroenterology as a change in the oesophageal epithelium of any length that is visible endoscopically and confirmed histologically to contain specialised intestinal metaplasia (SIM) within the tubular oesophagus. This definition deliberately excludes intestinal metaplasia of the gastric cardia.
• Importantly, not all intestinal metaplasia is endoscopically visible, and even non-goblet columnar epithelium may undergo intestinalisation.

Initiating Mechanisms and Environmental Triggers

• The development of Barrett’s oesophagus is typically the result of a chronic insult—namely gastro-oesophageal reflux—that injures the squamous epithelium, prompting an aberrant healing response.
• Refluxate components, particularly acid and bile, create a pro-inflammatory, genotoxic environment that alters gene expression and promotes metaplastic transformation.
• Reflux exposure influences epithelial plasticity by altering transcription factor profiles—upregulating intestinal-promoting genes and downregulating those supporting squamous differentiation.
  
  
  

Stem Cell Origins and Persistence of Metaplasia

• Basal stem cells of the native squamous epithelium that undergo reprogramming after injury.
• Stem cells at the gastro-oesophageal junction, stimulated by reflux, which migrate proximally into the oesophagus.
• Submucosal gland neck stem cells, which emerge onto the surface after mucosal damage.
• Bone marrow-derived stem cells that home to the site of epithelial injury and undergo metaplastic differentiation.
  
  

Genetic and Molecular Drivers of Metaplasia

• The transcription factor Cdx2 (Caudal-type homeobox 2) is considered a central regulator of intestinal differentiation. Its aberrant expression is associated with the initiation of metaplasia.
• Other transcriptional changes are mediated by reflux-induced activation of cellular signalling cascades, including TGF-β, MAPK, and protein kinase C pathways.
• The cyclo-oxygenase-2 (COX-2) gene is commonly upregulated in Barrett’s epithelium and may contribute to both metaplastic maintenance and the angiogenic switch necessary for neoplastic progression.
• Evidence suggests that reflux suppression, especially through surgical means, may downregulate COX-2 expression in the oesophagus.
  
  

Progression from Metaplasia to Dysplasia and Carcinoma

• Persistent metaplasia in Barrett’s oesophagus carries a recognised risk of progression to adenocarcinoma. The process is driven by accumulating genetic abnormalities, including:
  • Loss of p53 tumour suppressor function, which promotes resistance to apoptosis.
  • Activation of cell surface pH regulators, such as sodium-hydrogen exchangers, facilitating downstream oncogenic signalling.
• Over time, these genetic and biochemical events lead to dysplasia, enhanced proliferation, loss of cell cycle control, and ultimately neoplastic transformation.
• The biological behaviour of the altered epithelium includes angiogenesis, frequently mediated by COX-2, enabling continued growth and survival of malignant clones.
  
  

Genetic Susceptibility and Familial Aggregation

• While familial cases have been reported, most Barrett’s oesophagus cases arise sporadically, and genetic predisposition is likely polygenic, involving normal genetic polymorphisms rather than single-gene mutations.
• The presence of 'multiplex' families with Barrett’s and oesophageal adenocarcinoma suggests that, in select individuals, inherited factors may play a larger role.
  
  
  

Prevalence in the General Population

• Barrett’s oesophagus is commonly identified during upper endoscopy in adults, particularly those aged 50 years and older, though it often remains undiagnosed due to its frequently asymptomatic nature.
• Estimates of population prevalence vary significantly due to differences in diagnostic criteria and population sampling:
  • In the United States, estimates range from 0.4% to over 20%, with a widely accepted approximation of 5.6% of adults being affected.
  • Globally, the prevalence is thought to be closer to 1%, though regional variability is notable.
    
    

Prevalence in Subpopulation

• Among individuals with gastro-oesophageal reflux disease (GORD), 2.3% to 15% may have Barrett’s oesophagus.
• Even among those without GORD symptoms, 1.2% to 5.6% have been found to have Barrett’s oesophagus, indicating the condition can develop silently.
• Autopsy studies and routine endoscopy suggest that a significant proportion of long-segment Barrett’s oesophagus (LSBE) cases are unrecognised in life.
  
  
  

Segment Length and Prevalence

• Short-segment Barrett’s oesophagus (SSBE) is considerably more prevalent than LSBE.
  • SSBE is found in 5% to 30% of individuals undergoing upper endoscopy, while LSBE is reported in only 0.3% to 2%.
  • A large study involving protocol biopsies at the gastro-oesophageal junction found specialised intestinal metaplasia in 13.2%, with 6.0% SSBE and 1.6% LSBE, and an additional 5.6% had intestinal metaplasia limited to the gastro-oesophageal junction.
    
    
    

Geographic and Ethnic Variation

• The prevalence is highest in White males, who make up over 80% of diagnosed cases in some series.
• Studies consistently report lower prevalence among Black, Hispanic, and Asian populations. However, a meta-analysis of 51 studies across Asia, encompassing over 450,000 individuals, found a pooled prevalence of 1.3%, mostly representing SSBE.
• In the UK and Sweden, population-based studies suggest a prevalence around 2%.
  
  

Demographic Risk Factors

• Barrett’s oesophagus most frequently presents in men aged 55–65 years, with a male-to-female ratio of approximately 3:1.
• Risk is elevated in individuals with:
  • Central or overall obesity
  • Smoking history
  • Alcohol intake
  • Caucasian ethnicity
  • Older age
    
    

Barrett’s in Children and Young Adults

• The condition is rare in children, particularly those under five years old. When it occurs, it is often in association with congenital anomalies such as oesophageal atresia, prior antireflux surgery, or oesophageal dilation.
• A study in adolescents aged 16–19 years treated for oesophageal atresia showed a correlation between Barrett’s and previous surgical interventions, histologic oesophagitis, and suspicious findings on endoscopy.
  
  

Malignant Potential

• Barrett’s oesophagus is a recognised premalignant condition, although the risk of progression to adenocarcinoma varies across studies.
• A systematic review estimated the annual incidence of progression to oesophageal adenocarcinoma at 6.3 per 1,000 person-years (95% CI: 4.7–8.4), with significant variability in study findings.
• Although Barrett’s oesophagus increases the risk of oesophageal adenocarcinoma, the annual risk of progression is relatively low, at 0.2% to 0.5%.
• The risk is influenced by the presence and grade of dysplasia, with long-segment cases posing a higher risk than short-segment or cardia-localised intestinal metaplasia.
  
  

Asymptomatic Nature of Barrett’s Epithelium

• The specialised intestinal metaplasia characteristic of Barrett’s oesophagus is histologically distinctive but does not itself produce symptoms.
• Consequently, most cases are detected incidentally during upper gastrointestinal endoscopy performed for other indications, most commonly in the context of gastro-oesophageal reflux disease (GORD).
  
  

Typical Presenting Symptoms

• The majority of patients with Barrett’s oesophagus are evaluated due to GORD-related symptoms, including:
  • Heartburn (pyrosis) – the most frequent complaint, reflecting acid reflux.
  • Regurgitation – the effortless return of gastric contents to the oropharynx.
• These symptoms are essential in the pathogenesis of Barrett’s oesophagus and commonly prompt diagnostic investigation.
  
  

Segment-Specific Symptom Associations

• Long-segment Barrett’s oesophagus (LSBE) is strongly associated with chronic, prominent GORD symptoms.
• Short-segment Barrett’s oesophagus (SSBE) may occur in the absence of classic GORD symptoms, and thus can be clinically silent.
  
  

Complication-Related Symptoms

• Dysphagia – indicating oesophageal stricture, motility disorder, or malignant transformation.
• Odynophagia – due to oesophageal ulceration.
• Gastrointestinal bleeding – uncommon, but may result from ulceration in metaplastic areas.
  
  

Atypical and Extragastrointestinal Manifestations

• A subset of patients may report symptoms not typically associated with reflux:
  • Chest pain – non-cardiac in nature.
  • Laryngitis, chronic cough, dyspnoea, wheezing, or a history of aspiration pneumonia – possibly indicating reflux-related airway irritation or microaspiration.
    
    

Key Risk Factors Identified in History

• Chronic GORD or documented acid-bile reflux – a requisite condition for the development of Barrett’s oesophagus.
• Male sex – men have nearly twice the risk compared with women.
• White ethnicity – the highest prevalence is observed among Caucasian individuals.
  Older age – prevalence increases significantly with advancing age.
  
  

• Family history – approximately 7.3% of individuals with Barrett’s oesophagus or oesophageal adenocarcinoma have a first- or second-degree relative affected.
• Obesity – particularly central adiposity, is linked with increased risk via its effects on intra-abdominal pressure and reflux.
• Smoking – associated with a higher prevalence, largely mediated by the enhanced risk of GORD in smokers.

General Considerations

• Barrett’s oesophagus is a histopathological diagnosis, and the metaplastic epithelium itself does not produce any unique clinical signs discernible on physical examination.
  Consequently, physical examination plays a limited role in the detection of Barrett’s oesophagus unless complications are present.
• The condition is most often suspected based on symptoms and confirmed through endoscopic and histological evaluation.
  
  

Endoscopic Finding

• Endoscopic visualisation may reveal a salmon-coloured, velvety mucosa replacing the normal pale squamous epithelium of the distal oesophagus.
• The Prague C & M classification is used to document the circumferential (C) and maximal (M) extent of the columnar-lined segment.
• Barrett’s oesophagus is frequently an incidental finding during endoscopy for unrelated indications, such as anaemia or dyspepsia.
  
  

Findings Associated with Complications

• Weight loss – may be observed in cases with significant dysphagia or underlying adenocarcinoma.
  Pallor – may indicate chronic blood loss from mucosal ulceration.
• Signs of dehydration or nutritional deficiency – can be seen in advanced cases with persistent dysphagia or odynophagia.
• Cervical lymphadenopathy or abdominal mass – rare, but may suggest metastatic disease from oesophageal adenocarcinoma.
  
  

Respiratory and Oropharyngeal Manifestations (GORD-Related)

• Hoarseness or laryngeal inflammation – suggestive of reflux laryngitis.
• Wheezing, reduced breath sounds, or signs of aspiration pneumonia – possible in reflux-related respiratory disease.
• Chronic cough – often present but typically without associated auscultatory findings unless concurrent infection exists.
  
  

Absence of Specific Abdominal or Oesophageal Signs

• On routine abdominal or chest examination, there are no specific findings that suggest Barrett’s oesophagus.
• Palpable abnormalities such as masses or organomegaly are typically absent unless malignancy has developed and disseminated.

Initial and Diagnostic Investigations

• Upper gastrointestinal (GI) endoscopy with biopsy is the gold standard for diagnosing Barrett’s oesophagus. It permits direct visualisation of the oesophageal mucosa and histological confirmation of specialised intestinal metaplasia (SIM).
  • On endoscopy, Barrett’s mucosa appears as salmon-coloured epithelium extending proximally from the gastro-oesophageal junction (GEJ), replacing normal squamous lining.
  • The Z-line is typically displaced proximally. Biopsies should be obtained from the abnormal segment for histological assessment.
  • The Prague C & M classification is used to document the circumferential (C) and maximal (M) extent of metaplastic change.
• Histological confirmation requires evidence of columnar epithelium. The presence of goblet cells confirms specialised intestinal metaplasia, the only subtype with recognised malignant potential.
  
  

Surveillance in Patients with Risk Factors

• Screening is considered in patients with multiple risk factors: male sex, age ≥50 years, chronic GORD, central obesity, White ethnicity, smoking, or a family history of Barrett’s oesophagus or oesophageal adenocarcinoma.
• Guidelines vary: U.S. practice requires intestinal metaplasia with goblet cells for diagnosis, while British guidelines also accept cardiac or oxyntocardiac-type mucosa.
  
  

Enhanced Endoscopic Imaging Modalities

• High-definition white light endoscopy (HD-WLE) with a systematic biopsy protocol remains standard.
• Narrow-band imaging (NBI) increases the visual contrast of mucosal and vascular patterns to identify dysplasia but has lower specificity for detecting SIM.
• Chromoendoscopy (e.g., using methylene blue or indigo carmine) and autofluorescence imaging have been investigated but are not routinely recommended.
• Confocal laser endomicroscopy (CLE) provides in vivo histological imaging. A meta-analysis reported a sensitivity of 89% and specificity of 75% per patient for neoplasia detection.
• Optical coherence tomography (OCT) and spectroscopy-based techniques offer additional non-invasive mucosal assessment but are still considered investigational.
  
  
  

Adjunctive and Emerging Investigations

• Barium swallow may be performed initially in patients with dysphagia to assess for stricture or mass lesions, though it cannot diagnose Barrett’s oesophagus.
• Endoscopic ultrasonography (EUS) is used when high-grade dysplasia or carcinoma is suspected, to evaluate depth of invasion and lymphadenopathy.
  Fluorescence in situ hybridisation (FISH) can detect genetic abnormalities (e.g., HER2, CMYC, ZNF217, CDKN2A) associated with dysplasia but is not routinely used.
• Capsule endoscopy can visualise mucosal changes but lacks tissue sampling capability, limiting its diagnostic role.
  
  

Non-Endoscopic Screening Techniques

• Cytosponge-TFF3 is a minimally invasive screening tool involving a gelatin capsule containing a sponge that samples oesophageal epithelium.
  • In large trials, it showed sensitivity up to 90% and specificity of 94% for Barrett’s segments ≥2 cm.
  • This method may enhance early detection in primary care but carries a notable false-positive rate.
• Other investigational tools include:
  • EsoCheck – a balloon-based sampling device evaluated for DNA methylation biomarkers.
  • EsophaCap – a variation on Cytosponge, assessed for molecular markers of intestinal metaplasia.
    
    

Limitations of Screening and Surveillance

• Not all patients with oesophageal adenocarcinoma meet traditional screening criteria, and up to 45% of such cases occur in unscreened individuals.
• While surveillance may detect early neoplasia, its impact on mortality is debated. Psychological and financial burdens of surveillance should be considered in shared decision-making.
  
  

Intestinal Metaplasia at the Gastro-Oesophageal Junction (GEJ)

• Definition: Presence of intestinal metaplasia at the Z-line when the Z-line and GEJ coincide.
• Challenge: Distinguishing between very short-segment Barrett’s oesophagus and gastric intestinal metaplasia due to chronic Helicobacter pylori gastritis.
• Histological indistinction: Intestinal metaplasia at the GEJ may appear identical to that in the distal oesophagus or stomach.
• Key points:
  • Biopsy mapping of the gastric antrum and body can help assess for chronic H. pylori-related gastritis.
  • In Western populations, intestinal metaplasia at the GEJ is more often related to GORD than to H. pylori.
  • The risk of progression to oesophageal adenocarcinoma is minimal, particularly compared to confirmed Barrett’s oesophagus.
    
    

Gastro-Oesophageal Reflux Disease (GORD)

• Symptoms: Heartburn, regurgitation, chest discomfort; similar to Barrett’s but without histological evidence of metaplasia.
• Endoscopy: May show erosive oesophagitis or a normal mucosa.
• Biopsy: No goblet cells or columnar-lined oesophageal epithelium.
• Differentiation: Barrett’s oesophagus requires histological proof of columnar epithelium with or without goblet cells in the oesophagus.
  
  

Eosinophilic Oesophagitis (EoE)

• Symptoms: Dysphagia, food impaction, chest pain—often confused with reflux.
• Endoscopy: May reveal linear furrows, rings, or white plaques.
• Biopsy: Shows eosinophilic infiltration (>15 eosinophils per high-power field); no evidence of intestinal metaplasia.
• Differentiation: Histological and endoscopic findings are distinct from Barrett’s oesophagus.
  
  

Oesophagitis (Non-specific)

• Causes: Infection, pill-induced injury, or chemical exposure.
• Symptoms: Odynophagia, dysphagia.
• Endoscopy: May show inflammation or ulceration.
• Biopsy: Reveals inflammatory changes without metaplasia.
• Differentiation: Lacks the glandular epithelium characteristic of Barrett’s oesophagus.
  
  

Gastritis

• Symptoms: Epigastric pain, bloating, nausea.
• Risk factors: H. pylori infection, NSAID use.
• Endoscopy: May reveal mucosal erythema or atrophy, often normal in distal oesophagus.
• Biopsy: May show intestinal metaplasia in the stomach but not within the oesophageal mucosa.
• Differentiation: Gastric intestinal metaplasia does not fulfil the criteria for Barrett’s unless located within the oesophagus.
  
  

Oesophageal Adenocarcinoma

• Symptoms: Dysphagia, weight loss, fatigue, anaemia, lymphadenopathy.
• Endoscopy: Nodularity, ulceration, mass lesion.
• Biopsy: Confirms malignancy.
• Differentiation: Often arises in a background of Barrett’s oesophagus but represents a distinct diagnosis requiring oncologic management.

Goals of Management

• The primary objectives in managing Barrett’s oesophagus are to reduce gastric acid reflux, prevent progression to dysplasia or adenocarcinoma, and eradicate metaplastic epithelium where indicated.
  
  

Non-Dysplastic Barrett’s Oesophagus

• Acid Suppression: Long-term proton pump inhibitor (PPI) therapy is standard, with evidence supporting reduced risk of progression to high-grade dysplasia or adenocarcinoma. High-dose PPIs may offer marginal mortality benefits but must be balanced against long-term risks.
• Anti-Reflux Surgery: Fundoplication may be offered to symptomatic patients unresponsive to PPIs. However, it is not recommended as a cancer-prevention strategy due to lack of evidence of risk reduction and surgical morbidity.
• Endoscopic Eradication: Routine endoscopic ablation is not recommended. The American Gastroenterological Association and NICE advise against its use in non-dysplastic cases due to the low progression risk.
• Surveillance:
  • Every 5 years for segments <3 cm.
  • Every 3 years for segments ≥3 cm.
    
    

Barrett’s Oesophagus with Low-Grade Dysplasia (LGD)

• Diagnosis Confirmation: LGD should be confirmed by at least two expert gastrointestinal pathologists due to inter-observer variability
• Management Options:
  • Surveillance: Acceptable for selected patients.
  • Endoscopic Eradication:
    • Radiofrequency ablation (RFA) is preferred and associated with reduced progression to cancer.
    • Visible lesions should be resected with endoscopic mucosal resection (EMR) prior to ablation.
• Guidelines:
  • NICE recommends RFA after diagnosis confirmed on two separate endoscopies.
  • Surveillance post-treatment is based on initial histology, typically every 6 to 12 months.
    
    
    

Barrett’s Oesophagus with High-Grade Dysplasia (HGD)

• Risk: HGD carries a 20–40% risk of concurrent adenocarcinoma.
• Treatment:
  • Endoscopic resection of visible lesions (EMR or endoscopic submucosal dissection [ESD]).
  • Followed by RFA to eradicate residual Barrett’s epithelium.
• Alternative:
  • Oesophagectomy may be reserved for selected patients with submucosal invasion, failed endoscopic therapy, or patient preference. However, it is associated with significant morbidity and mortality.
• Post-Treatment Surveillance: Required regardless of treatment modality due to risk of recurrence.
  
  

Intramucosal Carcinoma

• Approach: Treated similarly to HGD—endoscopic resection of lesions followed by ablation if there is no submucosal invasion.
• Surveillance: Tailored to histology and completeness of eradication.
  
  

Surveillance Protocols

• Standard Protocol (Seattle Protocol):
  • Four-quadrant biopsies every 2 cm for non-dysplastic cases.
  • Every 1 cm in patients with dysplasia.
  • Additional targeted biopsies of visible lesions.
    
    
• Advanced Techniques:
  • High-resolution endoscopy and virtual chromoendoscopy (e.g., narrow-band imaging) are recommended to improve dysplasia detection.
  • Wide-area transepithelial sampling with computer-assisted 3D analysis (WATS-3D) may improve yield when used with standard biopsy.
    
    
• Biomarker Use:
  • p53 Immunostaining: May assist in identifying high-risk patients.
  • Tissue Systems Pathology (e.g., TissueCypher): Predicts progression risk and may guide treatment decisions.
    
    

Chemoprevention

• PPIs:
  • Reduce inflammation and DNA damage from acid and bile reflux.
  • Associated with reduced progression risk (odds ratio ~0.47 in meta-analyses).
• Aspirin and NSAIDs:
  • May reduce cancer risk via COX-2 inhibition.
  • Not routinely recommended solely for cancer prevention due to bleeding risk.
• Combination Therapies:
  • Statins combined with NSAIDs may offer additional protective effects in reducing progression risk.
    
    

Endoscopic Therapy Options

• Radiofrequency Ablation (RFA):
  • High efficacy in eradicating dysplasia and intestinal metaplasia.
  • Recurrence occurs in up to 50% over 4–5 years, necessitating continued surveillance.
• Cryotherapy:
  • Effective in patients unfit for RFA or with tortuous oesophagus.
  • May result in fewer strictures than RFA, but long-term data are limited.
• Endoscopic Resection (EMR/ESD):
  • Preferred for visible or nodular lesions.
  • Provides histologic staging.
  • EMR is effective for focal disease; ESD allows en bloc resection but is technically demanding.
    
    
    

Oesophagectomy

• Reserved for:
  • Patients with submucosal invasion or failed endoscopic eradication.
  • Centres with high surgical volume achieve better outcomes.
• Risks:
  • Mortality varies by institutional experience.
    Long-term complications include dysphagia, reflux, and nutritional deficiencies.
    
    
    

Risk of Progression to Oesophageal Adenocarcinoma

• The most significant clinical concern in Barrett’s oesophagus is its potential to progress to oesophageal adenocarcinoma.
• While this progression remains relatively uncommon, it carries a serious prognosis and underlies the rationale for surveillance and treatment strategies.
  
  

Progression Rates Based on Histology

• Non-dysplastic Barrett’s Oesophagus:
  • Annual risk of progression to adenocarcinoma is estimated at ~0.5% per year.
  • Cumulative 5-year risk is approximately 2.7%.
• Low-Grade Dysplasia (LGD):
  • 5-year progression risk increases to 6.6%.
• High-Grade Dysplasia (HGD):
  • Carries a 5-year progression risk of approximately 30.6%, highlighting the need for endoscopic eradication.
    
    

Epidemiological Trends

• The incidence of oesophageal adenocarcinoma has been rising sharply over the past few decades:
  • In the US, oesophageal adenocarcinoma increased from 0.8–3.7% of oesophageal cancers in 1926–1976 to 54–68% by 1979–1992.
  • Data from the SEER program show a threefold increase in incidence from 1976–1978 to 1988–1990.
  • In Olmsted County, Minnesota, the incidence rose from 0.13 to 0.74 cases per 100,000 person-years between 1935–1971 and 1974–1989.
• The rate of diagnosed Barrett’s oesophagus among adults aged 45 to 64 years increased by 50% between 2012 and 2019, with a near doubling in the rate of oesophageal cancer during the same period.
  
  

Impact of Segment Length

• Long-Segment Barrett’s Oesophagus (LSBE; ≥3 cm):
  • Associated with the highest prevalence of dysplasia (20–35%) and the greatest individual risk of progression to adenocarcinoma.
  • Prevalence of adenocarcinoma is 7–15 times higher than in patients with short-segment Barrett’s oesophagus or intestinal metaplasia at the cardia.
    
    
    
• Short-Segment Barrett’s Oesophagus (SSBE; <3 cm) and cardia-specialised intestinal metaplasia (cardia-SIM):
  • Dysplasia prevalence: 6–8% (SSBE), 0–6% (cardia-SIM).
  • Despite lower individual risk, these groups are more numerous, and therefore account for a substantial absolute number of cancer cases.
    
    

Overall Prognostic Implications

• Barrett’s oesophagus significantly increases lifetime risk of oesophageal adenocarcinoma.
• However, most individuals with Barrett’s oesophagus do not progress to cancer, particularly in the absence of dysplasia.
• Risk stratification using histology, segment length, and clinical risk factors (e.g., age, sex, obesity, smoking history) is essential in guiding management and surveillance.
  
  
  
  

Development of Dysplasia and Adenocarcinoma

• The principal concern associated with Barrett’s oesophagus is its potential to evolve into oesophageal adenocarcinoma through progressive dysplastic changes.
  While the probability of malignancy is relatively low in patients without dysplasia, the likelihood increases with the presence of low- or high-grade dysplastic changes.
• Surveillance endoscopy plays a crucial role in detecting early neoplastic changes, often before symptoms arise.
• Endoscopic interventions—especially radiofrequency ablation (RFA)—have significantly reduced the progression of dysplasia to invasive cancer when applied early.
• The metaplasia-dysplasia-carcinoma sequence underlies the rationale for regular monitoring and early therapeutic intervention.
  
  

Oesophageal Stricture Formation

• Longstanding acid exposure in Barrett’s oesophagus can cause chronic inflammation, leading to fibrotic narrowing of the distal oesophagus.
• This structural complication frequently manifests as progressive dysphagia and may impact nutritional intake.
• Endoscopic balloon or bougie dilation is typically the initial treatment and may need to be repeated to maintain oesophageal patency.
  In a minority of resistant cases, especially those involving complex strictures, surgical correction may be warranted.
  
  

Impact on Quality of Life

• Beyond physical symptoms, Barrett’s oesophagus can negatively influence multiple aspects of a patient’s psychological and emotional wellbeing.
• The chronic nature of the condition, combined with the potential for malignant transformation, contributes to heightened anxiety and health-related distress.
• Quality of life assessments reveal that patients often report impairment in both general health measures and disease-specific concerns, including fear of cancer, uncertainty about prognosis, and procedural burden from repeated surveillance.
  These psychological effects are important to address within the broader context of long-term management and patient support.
  
  
  
  

1. Benaglia T, et al. Impact of the Cytosponge-TFF3 test on Barrett's oesophagus diagnosis in a primary care setting: a randomised controlled trial. Lancet. 2020;396(10247):333–344.
2. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991;265(10):1287–1289
3. Chandrasoma P, et al. Definition of histopathologic changes in gastroesophageal reflux disease. Am J Surg Pathol. 2000;24(3):344–351.
4. di Pietro M, et al. Accuracy and acceptability of esophageal cytosponge cell collection device for the detection of Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12(6):899–908.
5. di Pietro M, et al. Screening for Barrett's oesophagus: Are we finally ready? World J Gastroenterol. 2015;21(46):13023–13030.
6. El-Serag HB, Naik AD, Dubberke ER, et al. Clinical and psychosocial impact of Barrett’s esophagus diagnosis. Clin Gastroenterol Hepatol. 2010;8(1):60–65.
7. Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63(1):7–42.
8. Haggitt RC, Tryzelaar J, Ellis FH Jr, Colcher H. Adenocarcinoma complicating columnar epithelium-lined (Barrett's) esophagus. Am J Clin Pathol. 1978;70(1):1–5.
9. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365(15):1375–1383.
10. Jankowski JA, de Caestecker J, Love SB, et al. Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial. Lancet. 2018;392(10145):400–408.
11. Kadri SR, et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study. BMJ. 2010;341:c4372.
12. Moinova HR, Barnholtz-Sloan JS, Loparco C, et al. DNA methylation biomarkers for detection of Barrett’s oesophagus and esophageal adenocarcinoma. Gut. 2018;67(5):941–950.
13. Montgomery E, Bronner MP, Goldblum JR, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32(4):368–378.
14. NICE. Endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia or no dysplasia. Interventional procedures guidance [IPG496]. 2014.
15. Parasa S, Vennalaganti P, Gaddam S, et al. Development and validation of a tissue systems pathology test to predict progression in Barrett's esophagus. Clin Gastroenterol Hepatol. 2018;16(10):1587–1595.
16. Pera M, Cameron AJ, Trastek VF, et al. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology. 1993;104(2):510–513.
17. Qumseya BJ, Wani S, Gendy S, et al. Disease progression in Barrett’s low-grade dysplasia with radiofrequency ablation compared with surveillance: systematic review and meta-analysis. Am J Gastroenterol. 2017;112(6):849–865.
18. Shaheen NJ, et al. Diagnosis and management of Barrett’s esophagus: an update. Gastroenterology. 2016;150(3):S20–S25.
19. Sharma P, et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111(1):30–50.
20. Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2014;371(9):836–845.
21. Westerhoff M, et al. Intestinal metaplasia at the gastroesophageal junction: Barrett's esophagus or gastric intestinal metaplasia? Am J Surg Pathol. 2011;35(7):1034–1040.