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

• Multiple potential origins for the metaplastic columnar epithelium have been proposed:
  • 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.
• These cells are believed to be responsible for the persistence of the metaplastic epithelium and its potential for malignant transformation.

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

• When Barrett’s oesophagus is complicated by structural or inflammatory changes, patients may present with:
  • 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

Strong risk factors that should be elicited 

• 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.

Weaker but still relevant historical risk factors

• 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

• Although not part of the physical exam per se, endoscopic visualisation constitutes the key 'clinical' examination modality:
  • 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

• When Barrett’s oesophagus is complicated by ulceration, stricture, or neoplasia, physical signs may reflect these secondary processes:
  • 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)

• Though not specific to Barrett’s, atypical reflux complications may yield observable findings:
  • 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

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.

Radiofrequency Ablation (RFA)

• 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

• Treated similarly to HGD—endoscopic resection of lesions followed by ablation if there is no submucosal invasion.
• Surveillance is 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

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.

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