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Dr.TimWiyule Mutafya
COSECSA General surgery resident
Kamuzu Central Hospital, Malawi
20/7/2023
 Barrett's Esophagus is an acquired metaplastic condition in which
healthy squamous epithelium is replaced by specialized intestinal columnar
epithelium.
 Occurs in 10-15% of patients with GERD.
 Prevalence of 0.9-10%(2%) in general adult population
 Male 3x > Female
 Age >50yrs
 Definition has evolved over past 100 years.
 1906,Tileston, a pathologist, described several patients with "peptic ulcer of the esophagus" in
which the epithelium around the ulcer closely resembled that normally found in the stomach.
 1950, Barrett supported the view that this ulcerated, columnar-lined organ was, in fact, the
stomach tethered within the chest by a congenitally short esophagus.
 1953, Allison and Johnstone argued that the columnar organ was more likely esophagus, because
the intrathoracic location, lacked peritoneum and had all layers of esophagus.
 1957, Barrett agreed and suggested that the condition that bears his name be referred to as
"lower esophagus lined by columnar epithelium.“
 1976, Paull et al used manometric guidance for their biopsies demonstrated distinctive type of
intestinal metaplasia the investigators called "specialized columnar epithelium." This specialized
intestinal metaplasia (SIM), complete with goblet cells, has become the sine qua non for the
diagnosis of Barrett esophagus.
 The most significant morbidity associated with Barrett esophagus is the
development of adenocarcinoma in the esophagus.
 0.5% annual rate of neoplastic transformation.
 factors affecting transformation
 Length of area affected
 Biomarkers
 Dysplasia
 None 0.5 - 2%
 Low grade  7 – 10 %
 high grade  22 - 40%
Bhat S et al Natl Cancer Inst. 2011 Jul 6;103(13):1049-57
5-year survival without treatment is About 14%
Combination of LOH at 17p with p53 inactivation, LOH at 9p, tetraploidy and aneuploidy, COX -2
Expert Rev Gastroenterol Hepatol. 2008;2(5):653-663.
No screening programs in SSA
 High pressure Antireflux barrier
 Lower esophageal sphincter (LES)
 Extrinsic compression of the diaphragm
 Clearing mechanism
 Gravity
 Bicarbonate secretion from esophageal and salivary glands
 Peristalsis
 Epithelial defense factors to resist acid entry into intercellular 
spaces
 Thick epithelial layer
 Tight junctions
 Lipid-rich intercellular space
 Gastroesophageal reflux
disease
 Erosive esophagitis
 Peptic stricture
 Hiatal hernia
 Smoking
 has a synergistic effect
with GERD
 Central obesity
 Family history
Normal LES
1.Resting Pressure = 13mmhg
2.Length = 3-4cm
3.Position = 2-3cm
Defect LES
1. LES mean resting pressure < 6 mm Hg,
2. LES length < 2 cm, or
3. LES intra-abdominal segment length < 1 cm
Lower esophageal
sphincter
• Prolonged exposure of the esophagus to the refluxate can
erode the esophageal mucosa, promote inflammatory cell
infiltrate, and ultimately cause epithelial necrosis.
• This chronic damage is believed to promote the replacement
of healthy esophageal epithelium with the metaplastic
columnar cells of Barrett esophagus, the cellular origin of
which remains unknown.
• This likely is an adaptive response of the esophagus, which, if
not for the increased risk of cancer, would have been
beneficial. GERD symptoms and strictures are less common in
the columnarized segment
Fitzgerald RC
Molecular basis of Barrett’s oesophagus
and oesophageal adenocarcinoma
Gut 2006;55:1810-1820.
chronic history of gastroesophageal reflux;
• Pyrosis (heartburn)
• Acid regurgitation
• Dysphagia.
• Sometimes no any symptoms.
The features of GERD in relation to length of affected esophagus
1. Long-segment Barrett esophagus (LSBE, >3 cm)
2. Short-segment Barrett esophagus (SSBE, < 3 cm)
GERD in LSBE
• Longer duration of reflux symptoms
• When undergoing 24-hour esophageal pH
monitoring, they have severe, combined patterns of
reflux (supine and erect)
• Reduced LES pressures
• Patients also tend to be less sensitive to direct acid
exposure
GERD in SSBE
• Shorter duration of symptoms
• Patients are more sensitive to acid exposure
• Normal LES pressures
• Only upright reflux on 24-hour esophageal pH testing
1. Esophagogastroduodenoscopy
2. Ultrasonography
3. Histologic findings
4. Fluorescence in situ hybridization(FISH)
 The procedure of choice for the diagnosis of Barrett esophagus
 Sensitivity and specifity of endoscopy for detection of Barrett's esophagus is 100% and 84.13%
(CI 95%:78.53-89.09%), respectively. [Asghar, S. 2014]
 Diagnostic criteria
 Presence of columnar lined epithelium ≥1 cm above the proximal margin of the gastric folds
 Long segment > 3cm
 Short segment < 3 cm
 Ultrashort segment <1cm with microscopic demonstration of metaplasia
• Stratifies severity of Barrett’s esophagus according to
endoscopic findings
• The assessment of the circumferential (C) and
maximum (M) extent of the endoscopically visualized
BE segment as well as endoscopic landmarks
• Excludes pockets or areas of metaplasia, but only
the length of the large segments
The presence of specialized intestinal metaplasia in the esophagus confirms the diagnosis.
• When high-grade dysplasia or cancer is found on surveillance endoscopy, endoscopic
ultrasonography (EUS) is advisable to evaluate for surgical resectability.
 Identifies chromosomal abnormalities
 FISH detects aneusomy in Barrett esophagus to 9p12 (CDKN2A), 17q11.2-12 (HER2),
8q24.12-13 (CMYC), and 20q13.2 (ZNF217) appears to be able to detect.
 non-detection of aneusomy did not rule out dysplasia.
 In a study consisting of 20 cases of Barrett esophagus,
 significant increases in HER2, CMYC, and ZNF217 copy number were found in dysplastic
mucosa compared with non-dysplastic mucosa.
https://www.qxmd.com/r/25735914
These have prognostic factors important in surveillance too
1. Turn and suction biopsy
2. Biopsy all mucosal irregularities(erosions , ulcers)
3. Low grade
• Four quadrant biopsies 2cm from BE- in separate
containers
4. High grade dysplasia
• Four quadrants every 1cm
ACG surveillance guidelines 2014
These are aimed to reduce risk GERD
• weight reduction if overweight
• Stop smocking
• Avoid alcohol
• Remain upright 3hrs post meal
• Sleep in left lateral position
Proton pump inhibitors inhibit gastric acid secretion by inhibition of the H+/K+ ATPase
enzyme system in the gastric parietal cells
• 1st line instead of an H2-receptor antagonist due to the relative acid insensitivity of patients
with Barrett esophagus
• Omeprazole, esomepzole, pantoprazole
Indications for medical therapy in Barrett esophagus—control of symptoms and healing of esophageal mucosa
H2 receptor blockers
• reversible competitive blockers of histamine at H2 receptors in the gastric parietal cells, where
they inhibit acid secretion
• Cimetidine, Ranitidine, Famotidine
In patients without dysplasia, H2 blockers had lower risk of progression to High grade dyspalsia/Cancer.
Official journal of the American College of
Gastroenterology | ACG109:S28-S29, October 2014
COX-2 causes  proliferation and  apoptosis
COX-2 inhibitors decrease proliferation and induce
apoptosis in both Barrett's epithelial and adenocarcinoma
cells
Selective COX-2 inhibitors
Ablative therapy
• Photodynamic Therapy
• Laser AblationArgon Plasma Coagulation (APC)
• Multipolar Electrocoagulation (MPEC)
• Heater Probes,Various Forms Of Lasers
• Endoscopic Mucosal Resection (EMR)
• Cryotherapy
Surgical resection
• esophagectomy
No adequate date to
justify use without
dysplasia
PRE POST
Photodynamic therapy
Endoscopic mucosal resection
• Transhiatal approach in 4 phases
1. Right thoracic incision to mobilize the stomach
2. Widening of esophageal hiatus to mobilize mediastinal
esophagus
3. Cervical incision to mobilize cervical esophagus and upper
mediastinum dissection is performed.
4. Esophagus is resected and stomach tube created
• Stomach serves a s conduit to make an esophagogastric
anastomosis.
• Indicated for BE with severe dysplasia
Advantages
• Excellent visualization of organs
• Allows performance two field lymphadenopathy
• Lower leakge rate
• Less likely to injure recurrent laryngeal nerve
Perioperative complications
• Hemorrhage
• Tracheobronchial and (Recurrent laryngeal) vagus nerve injury 5-10%
• Chylothorax
Postoperative
• Dysphagia
• Anastomotic leak
• Diaphragmatic hernia
• Delayed emptying of condult
Factors to consider.
• Prevalence of condition in the region
• Protocol feasibility(cost, accuracy, acceptability)
• Availability of resources)
• Impact on clinical outcome indicators- survival,QUALY
• Patient compliance
• Workload at the facility
Any hope for surveillance in Malawi?
 https://www.researchgate.net/publication/289956551_Sensitivity_and_specificity_of_endoscopy_in_diagnosis_for_Barrett's_esophagus
 Bhat S, Coleman HG,Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients:
results from a large population-based study. J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57. doi: 10.1093/jnci/djr203. Epub 2011 Jun 16.
Erratum in: J Natl Cancer Inst. 2013 Apr 17;105(8):581. PMID: 21680910; PMCID: PMC3632011.
 Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study - PMC (nih.gov)
 Shaheen, Nicholas J. MD, MPH1; Falk, Gary W. MD, MS2; Iyer, Prasad G. MD, MS3; Souza, Rhonda F. MD4;Yadlapati, Rena H. MD, MHS (GRADE
Methodologist)5; Sauer, Bryan G. MD, MSc (GRADE Methodologist)6;Wani, Sachin MD7. Diagnosis and Management of Barrett's Esophagus:
An Updated ACG Guideline.The American Journal of Gastroenterology 117(4):p 559-587, April 2022. | DOI:
10.14309/ajg.0000000000001680
 Sharma P, Dent J, Armstrong D, Bergman JJ, Gossner L, HoshiharaY, Jankowski JA, Junghard O, Lundell L,Tytgat GN,Vieth M.The
development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria. Gastroenterology. 2006
Nov;131(5):1392-9. doi: 10.1053/j.gastro.2006.08.032. Epub 2006 Aug 16. PMID: 17101315.
 My MediNotes: PRAGUE CRITERIA - For Endoscopically Suspected Oesophageal Columnar Metaplasia / Barrett’s Oesophagus
(medinotable.blogspot.com)
 Barrett Esophagus Treatment & Management: Approach Considerations, Barrett Esophagus Screening and Surveillance, Ablative Therapy
for Barrett Esophagus (medscape.com)
 Fitzgerald RC Molecular basis of Barrett’s oesophagus and oesophageal adenocarcinoma Gut 2006;55:1810-1820
 selective cox 2 inhibitor drugs - Bing images

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Barret's Esophagus.pdf

  • 1. Dr.TimWiyule Mutafya COSECSA General surgery resident Kamuzu Central Hospital, Malawi 20/7/2023
  • 2.  Barrett's Esophagus is an acquired metaplastic condition in which healthy squamous epithelium is replaced by specialized intestinal columnar epithelium.  Occurs in 10-15% of patients with GERD.  Prevalence of 0.9-10%(2%) in general adult population  Male 3x > Female  Age >50yrs
  • 3.  Definition has evolved over past 100 years.  1906,Tileston, a pathologist, described several patients with "peptic ulcer of the esophagus" in which the epithelium around the ulcer closely resembled that normally found in the stomach.  1950, Barrett supported the view that this ulcerated, columnar-lined organ was, in fact, the stomach tethered within the chest by a congenitally short esophagus.  1953, Allison and Johnstone argued that the columnar organ was more likely esophagus, because the intrathoracic location, lacked peritoneum and had all layers of esophagus.  1957, Barrett agreed and suggested that the condition that bears his name be referred to as "lower esophagus lined by columnar epithelium.“  1976, Paull et al used manometric guidance for their biopsies demonstrated distinctive type of intestinal metaplasia the investigators called "specialized columnar epithelium." This specialized intestinal metaplasia (SIM), complete with goblet cells, has become the sine qua non for the diagnosis of Barrett esophagus.
  • 4.  The most significant morbidity associated with Barrett esophagus is the development of adenocarcinoma in the esophagus.  0.5% annual rate of neoplastic transformation.  factors affecting transformation  Length of area affected  Biomarkers  Dysplasia  None 0.5 - 2%  Low grade  7 – 10 %  high grade  22 - 40% Bhat S et al Natl Cancer Inst. 2011 Jul 6;103(13):1049-57 5-year survival without treatment is About 14%
  • 5. Combination of LOH at 17p with p53 inactivation, LOH at 9p, tetraploidy and aneuploidy, COX -2 Expert Rev Gastroenterol Hepatol. 2008;2(5):653-663.
  • 7.  High pressure Antireflux barrier  Lower esophageal sphincter (LES)  Extrinsic compression of the diaphragm  Clearing mechanism  Gravity  Bicarbonate secretion from esophageal and salivary glands  Peristalsis  Epithelial defense factors to resist acid entry into intercellular spaces  Thick epithelial layer  Tight junctions  Lipid-rich intercellular space
  • 8.  Gastroesophageal reflux disease  Erosive esophagitis  Peptic stricture  Hiatal hernia  Smoking  has a synergistic effect with GERD  Central obesity  Family history
  • 9. Normal LES 1.Resting Pressure = 13mmhg 2.Length = 3-4cm 3.Position = 2-3cm Defect LES 1. LES mean resting pressure < 6 mm Hg, 2. LES length < 2 cm, or 3. LES intra-abdominal segment length < 1 cm Lower esophageal sphincter
  • 10. • Prolonged exposure of the esophagus to the refluxate can erode the esophageal mucosa, promote inflammatory cell infiltrate, and ultimately cause epithelial necrosis. • This chronic damage is believed to promote the replacement of healthy esophageal epithelium with the metaplastic columnar cells of Barrett esophagus, the cellular origin of which remains unknown. • This likely is an adaptive response of the esophagus, which, if not for the increased risk of cancer, would have been beneficial. GERD symptoms and strictures are less common in the columnarized segment
  • 11. Fitzgerald RC Molecular basis of Barrett’s oesophagus and oesophageal adenocarcinoma Gut 2006;55:1810-1820.
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  • 13. chronic history of gastroesophageal reflux; • Pyrosis (heartburn) • Acid regurgitation • Dysphagia. • Sometimes no any symptoms. The features of GERD in relation to length of affected esophagus 1. Long-segment Barrett esophagus (LSBE, >3 cm) 2. Short-segment Barrett esophagus (SSBE, < 3 cm) GERD in LSBE • Longer duration of reflux symptoms • When undergoing 24-hour esophageal pH monitoring, they have severe, combined patterns of reflux (supine and erect) • Reduced LES pressures • Patients also tend to be less sensitive to direct acid exposure GERD in SSBE • Shorter duration of symptoms • Patients are more sensitive to acid exposure • Normal LES pressures • Only upright reflux on 24-hour esophageal pH testing
  • 14. 1. Esophagogastroduodenoscopy 2. Ultrasonography 3. Histologic findings 4. Fluorescence in situ hybridization(FISH)
  • 15.  The procedure of choice for the diagnosis of Barrett esophagus  Sensitivity and specifity of endoscopy for detection of Barrett's esophagus is 100% and 84.13% (CI 95%:78.53-89.09%), respectively. [Asghar, S. 2014]  Diagnostic criteria  Presence of columnar lined epithelium ≥1 cm above the proximal margin of the gastric folds  Long segment > 3cm  Short segment < 3 cm  Ultrashort segment <1cm with microscopic demonstration of metaplasia
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  • 17. • Stratifies severity of Barrett’s esophagus according to endoscopic findings • The assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualized BE segment as well as endoscopic landmarks • Excludes pockets or areas of metaplasia, but only the length of the large segments
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  • 20. The presence of specialized intestinal metaplasia in the esophagus confirms the diagnosis.
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  • 23. • When high-grade dysplasia or cancer is found on surveillance endoscopy, endoscopic ultrasonography (EUS) is advisable to evaluate for surgical resectability.
  • 24.  Identifies chromosomal abnormalities  FISH detects aneusomy in Barrett esophagus to 9p12 (CDKN2A), 17q11.2-12 (HER2), 8q24.12-13 (CMYC), and 20q13.2 (ZNF217) appears to be able to detect.  non-detection of aneusomy did not rule out dysplasia.  In a study consisting of 20 cases of Barrett esophagus,  significant increases in HER2, CMYC, and ZNF217 copy number were found in dysplastic mucosa compared with non-dysplastic mucosa. https://www.qxmd.com/r/25735914 These have prognostic factors important in surveillance too
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  • 27. 1. Turn and suction biopsy 2. Biopsy all mucosal irregularities(erosions , ulcers) 3. Low grade • Four quadrant biopsies 2cm from BE- in separate containers 4. High grade dysplasia • Four quadrants every 1cm ACG surveillance guidelines 2014
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  • 31. These are aimed to reduce risk GERD • weight reduction if overweight • Stop smocking • Avoid alcohol • Remain upright 3hrs post meal • Sleep in left lateral position
  • 32. Proton pump inhibitors inhibit gastric acid secretion by inhibition of the H+/K+ ATPase enzyme system in the gastric parietal cells • 1st line instead of an H2-receptor antagonist due to the relative acid insensitivity of patients with Barrett esophagus • Omeprazole, esomepzole, pantoprazole Indications for medical therapy in Barrett esophagus—control of symptoms and healing of esophageal mucosa
  • 33. H2 receptor blockers • reversible competitive blockers of histamine at H2 receptors in the gastric parietal cells, where they inhibit acid secretion • Cimetidine, Ranitidine, Famotidine In patients without dysplasia, H2 blockers had lower risk of progression to High grade dyspalsia/Cancer. Official journal of the American College of Gastroenterology | ACG109:S28-S29, October 2014
  • 34. COX-2 causes  proliferation and  apoptosis COX-2 inhibitors decrease proliferation and induce apoptosis in both Barrett's epithelial and adenocarcinoma cells Selective COX-2 inhibitors
  • 35. Ablative therapy • Photodynamic Therapy • Laser AblationArgon Plasma Coagulation (APC) • Multipolar Electrocoagulation (MPEC) • Heater Probes,Various Forms Of Lasers • Endoscopic Mucosal Resection (EMR) • Cryotherapy Surgical resection • esophagectomy No adequate date to justify use without dysplasia
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  • 40. • Transhiatal approach in 4 phases 1. Right thoracic incision to mobilize the stomach 2. Widening of esophageal hiatus to mobilize mediastinal esophagus 3. Cervical incision to mobilize cervical esophagus and upper mediastinum dissection is performed. 4. Esophagus is resected and stomach tube created • Stomach serves a s conduit to make an esophagogastric anastomosis. • Indicated for BE with severe dysplasia
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  • 42. Advantages • Excellent visualization of organs • Allows performance two field lymphadenopathy • Lower leakge rate • Less likely to injure recurrent laryngeal nerve Perioperative complications • Hemorrhage • Tracheobronchial and (Recurrent laryngeal) vagus nerve injury 5-10% • Chylothorax Postoperative • Dysphagia • Anastomotic leak • Diaphragmatic hernia • Delayed emptying of condult
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  • 44. Factors to consider. • Prevalence of condition in the region • Protocol feasibility(cost, accuracy, acceptability) • Availability of resources) • Impact on clinical outcome indicators- survival,QUALY • Patient compliance • Workload at the facility
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  • 46. Any hope for surveillance in Malawi?
  • 47.  https://www.researchgate.net/publication/289956551_Sensitivity_and_specificity_of_endoscopy_in_diagnosis_for_Barrett's_esophagus  Bhat S, Coleman HG,Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57. doi: 10.1093/jnci/djr203. Epub 2011 Jun 16. Erratum in: J Natl Cancer Inst. 2013 Apr 17;105(8):581. PMID: 21680910; PMCID: PMC3632011.  Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study - PMC (nih.gov)  Shaheen, Nicholas J. MD, MPH1; Falk, Gary W. MD, MS2; Iyer, Prasad G. MD, MS3; Souza, Rhonda F. MD4;Yadlapati, Rena H. MD, MHS (GRADE Methodologist)5; Sauer, Bryan G. MD, MSc (GRADE Methodologist)6;Wani, Sachin MD7. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline.The American Journal of Gastroenterology 117(4):p 559-587, April 2022. | DOI: 10.14309/ajg.0000000000001680  Sharma P, Dent J, Armstrong D, Bergman JJ, Gossner L, HoshiharaY, Jankowski JA, Junghard O, Lundell L,Tytgat GN,Vieth M.The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria. Gastroenterology. 2006 Nov;131(5):1392-9. doi: 10.1053/j.gastro.2006.08.032. Epub 2006 Aug 16. PMID: 17101315.  My MediNotes: PRAGUE CRITERIA - For Endoscopically Suspected Oesophageal Columnar Metaplasia / Barrett’s Oesophagus (medinotable.blogspot.com)  Barrett Esophagus Treatment & Management: Approach Considerations, Barrett Esophagus Screening and Surveillance, Ablative Therapy for Barrett Esophagus (medscape.com)  Fitzgerald RC Molecular basis of Barrett’s oesophagus and oesophageal adenocarcinoma Gut 2006;55:1810-1820  selective cox 2 inhibitor drugs - Bing images