1. Management of Barrett’s oEsophagus
Joint Hospital Surgical Grand Round
United Christian Hospital
Dr C Leung

2. Definition
A change in the normal squamous epithelium of the oesophagus to specialized intestinal metaplasia
Normal eso squamous mucosa
Intestinal metaplasia (goblet cells)
Playford RJ. New British Society of Gastroenterology guidelines for the diagnosis and management of Barrett’s esophagus
Gut 2006;55:442-3

3. Background Prevalence Premalignant condition 1.6-5.6%
10-15% in patients with reflux symptoms
Premalignant condition
30-40 fold increased risk of oesophageal CA
Difficult to truly know prevalence as many barretts individual are asymptomatic and never be evaluated

4. Etiology Combined acid and bile reflux
> 50% of patients with GERD had abnormal levels of acid and bile in the oesophagus
Barrett’s esophagus patients have the highest level
Fein M. Br J Surg 2006; 93:
Mucosal injury most common in mixed acid and bile exposure. Followed by acid alone and uncommon for bile alone (P<0.001)

5. Pathogenesis

6. Risk of Adenocarcinoma
0.25 to 0.4% per year
Nondysplasic : 3.86/1000 person years
Low-grade dysplaia: 7.66/1000 person years
High-grade dysplasia
Occult carcinoma: 30%-40% of patients
14.1/100 person years
Sharma P. Clin Gastroenterol Hepatol 2006; 4:
Buttar NS. Gastroenterology 2001; 120:

7. Endoscopic Evaluation
Prague classification
the maximal length (M) (including tongues) of Barrett esophagus
length of the circumferential Barrett segment (C)
For future endoscopic comparison
Salmon color epithelium projected into tubular esophagus (projection can be tongues of tissue/ circumferential involvement of mucosa)
Sharma P. Gastroenterology 2006; 131:

8. Biopsies Seattle protocol
4 quadrant jumbo bx at 1cm intervals throughout whole length of Barrett’s
Separate target bx of any irregularities (nodules/erythema/ erosions)
Reid BJ. Am J Gastroenterol 2000; 95:
-4 quadrant jumbo biopsies at 1 cm intervals throughout length of Barrett's esophagus (and inclusive of any neosquamous re-eepithelialized tissue growth and cardia)
irregularities (tiny nodules, patches of friability/erythema, erosions, ulcers, strictures, or regions appears fixed and or poorly distensible)
Currently, white light high definition endoscopy and chromoendoscopy help in localizing lesions

9. Treatment rationale Removal of diseased mucosa, not entire organ
Prevent disease progression to adenoCA
Tx rationale barrett mucosal disease before it progress to CA / crossing submucosa–removal of disease mucosa suffix

10. Treatment Options Cant reduce CA risk resection Anti-reflux treatment
-PPI
-Fundoplication
+/- surveillance
Endoscopic
ablation
Photodynamic therapy (PDT)
Multipolar electrocoagulation
Argon Plasma Coagulation
Radiofrequency ablation (RFA)
Cryoablation
resection
EMR/ ESD
Esophagectomy
Symptomatic control
Cant reduce CA risk
HGD / Tis , T1a adenoCA
Role of endoscopic ablation in non-dysplastic/ low grade dysplasia is less clear
Multifocal, extensive HGD/ persistent HGD despite ablation/ ? CA

11. Acid Suppression with Surveillance
Acid suppression will not eliminate risk of adenocarcinoma/ consistent regression of Barrett’s
Degree of dysplasia
Surveillance OGD interval
Non-dysplastic
3-5 year
Low grade dysplasia
6-12 months
High grad dysplasia
Interval 3 months (if patient not receive invasive therapy)
No reliable data on tx length
-some keep patients on PPI indefinitely. Supra-therapeutic dose (for control of GERD) solely for chemoprevention is not warranted
Optimal frequency of surveillance has not yet been determined, most recommend as above chart
adenoCA discovered while screening for Barretts are early stage lesions and have a gd prognosis (5 year suvival >85%)
? Duration and dosage of PPI (indefinite)
?optimal frequency of surveillance

12. Anti-reflux Surgery
Fundoplication eliminates acid and bile reflux in > 90% of patients with Barrett’s oesophagus
Meta-analysis: 15.4% of patients undergone surgery will have regression of Barrett’s vs. 1.9% medically managed patients
Swedish Cohort study showed that RR of adenocarcinoma in patients undergone surgery was 14.1 vs. 6.3 for medical treatment
Reduce risk of adenoCA ?
Mixed evidences so far
Meta-analysis found no difference between fundoplication and medical treatment in prevention of adenocarcinoma
Oelschlager BK. Ann Surg 2003; 238:
Chang EY. Ann Surg 2007; 246:
Lagergren J. Gastroenterology 2010; 138:

13. PPI vs fundoplication
Surgery can definitely treat reflux-related symptoms, but its role in protection against adenocarcinoma should be cautious
Effectiveness in eliminating reflux symptoms
Co- morbidities
Patient’s choice/ compliance
Medications S/E

14. Photodynamic Therapy
Injecting a light-sensitizing drug into patient, then expose the portion of oesophagus to a specific wavelength
Found NOT effective in eliminating Barrett’s
‘Buried glands’: a layer of normal-appearing squamous epithelium is present but under this layer, Barret’s metaplasia still present
Stricture
Phototoxicity
Stricture esp in long segment
Menon D. BMC Gastroenterol 2010; 10: 111.

15. Argon Plasma Coagulation
Systemic review: more effective than PDT, 3- month complete eradication 80%
Less complications like stricture or bleeding
Odynophagia 10%
Li YM. Dig Dis Sci 2008; 53:

16. Radiofrequency Ablation
One of the best studied method
Applies bipolar electrical energy to mucosal surfaces, 10J for 1 second  mucosa is ablated to submucosal level
Balloon based radiofrequency device for circumferential ablation
RFA advantage : treat larger surface area than other thermal techniques, also true for focal disease
(contact technique but not point technique)

17. Radiofrequency ablation
Need standardized FU as complete ablation with single treatment in only 70% of patients
FU OGD 3 months and 1 year, if not complete ablated  repeat RFA

18. Radiofrequency ablation
Shaheen NJ (2009): Multicentre RCT
Can eliminate Barrett’s oesophagus with high grade dysplasia and reduce risk of oesophageal carcinoma
Wani S (2009): Meta-analysis
Reduction in carcinoma progression in high-grade dysplasia
Shaheen NJ (2011): Long term results
3 years follow-up: complete eradication persist in 96% patients with high-grade dysplaia
Adenocarcinoma occurred in one per 181 patient-years of follow-up

19. Radiofrequency ablation
Promising results
S/E : esophageal stricture, GIB, chest pain
Sustaintially lower than those in photodynamic therapy
Long term data needed

20. Cryoablation
Endoscopically directed spray of liquid nitrogen at -196oC
Complete eradication of high grade dysplasia occurs in 68-97% of patients
Not well studied as RFA
? Treat patient refractory to RFA
Dumot JA. Gastrointest Endosc 2009; 70:
Shaheen NJ. Gastrointest Endosc 2010; 71:

21. Endoscopic Mucosal Resection
when a visible nodule is present or only a short segment of Barrett’s is seen
substantial tissue for pathologist
treat Tis or T1a adenocarcinoma
Can combined with RFA
Usually visible nodule has higher chance of ca
Endoscopic resection followed by thermal ablation should be treatment of choice
EUS to determine pass thro submucosa
Thro submucosa,risk of LN met >20%
EMR ~2 cm size specimen in each attempt while ESD can remove specimen en bloc regardless of size
With submucosal invasion, 20% risk of LN met
If confined to mucosa ,<1% LN met

22. Endoscopic therapy
No single endotherapy achieve complete eradication without complications
Recurrence
For mucosal lesion
Buried metaplasia

23. Esophagectomy
‘gold standard’ for high grade dysplasia and early adenocarinoma
20-40% of patients harbour early adenocarcinoma in HGD (old data)
Mortality can be as low as 1% in high vol centre
Significant morbidity
For multifocal , too extensive HGD / intractable HGD /suspicious of carcinoma
Traditionally esophagect gold standard for early ca and HGD
Old data show 20-40% occult CA in HGD. Only 12 % in Jennifer Chennat at el 20101(gastrointest enodoscopy clin N AM 21 (2011)
Vagal sparing esophagectomy , laparoscopically
Ablation or resection not suitable for multifocal/ too extensive disease
After esophagect, life long reflux/ regurg/ aspiration
With potential early and long term cx and magnitude of procedure, usu discourage patient from doing esophagect
Esophagect is a 1 shot procedure
Surgery vs ablation for high grade/ early CA
No RCT yet . All non randomized trails - all no significant difference in survival

24. Summary Barrett’s esophagus metaplasia LGD HGD
Anti-reflux +surveillance OGD every3-5 year
Anti-reflux+OGD every 6-12 months
Repeat bx confirmed HGD
Send to expert pathologist
HGD –procedure shift from esophagectomy to endoscopic ablative /resection
Flat HGD – ablation + PPI
Nodular HGD EMR/ ESD +PPI
Ablative therapy for metaplasia w/o dysplasia ? (non dysplastic barretts develop CA at only 0.5% per year, no study established that endoscopic ablation decreases risk)
Also need surveillance OGD afterwards as we dunnno the chance of buried metaplasia and regrowth of barretts (review stuart et al surg oncol clin N AM ) similar for LGD- not much evidence on tx by ablative therapy, more outcome needed to support recommendation. Some have Spontaneous regression
Intractable HGD/ suspicious of carcinoma – esophagectomy
Some study on cost perspective- HGD most cost effective tx by RFA, EMR cost preferred than esophagectomy for early BE
Endotherapy (ablative/EMR/ESD)
If persist/ ? CA then esophagectomy

25. Take Home Messages Barrett’s esophagus is a pre-malignant condition
Diagnosis relies on both endoscopic and histological findings
Management should be based on risks stratification
Emerging evidence on the use of endoscopic therapy
Treatment should be individualized
Risk stratification (no dysplasia/ LGD/ HGD)
When to treat : currently no evidence for ablation in non dysplastic/ LGD - surveillance +PPI
Surgery vs ablation equally effective – the best mx depends on patient characteristics , preference, local expertise. Multiple comorbities- endoscopic tx

26. Acid Suppression Without Surveillance
Screening for Barrett’s oesophagus has not been shown to improve mortality from adenocarcinoma
Economic model suggests that the adverse effects related to screening outweigh benefit of early detection of adenocarcinoma
American Gastroenterological Association Chicago Workshop concluded that although surveillance can detect curable neoplasia but may not prolong survival
Doesn’t change much of surveillance practice, even in US
Garside R. Health Technol Assess 2006; 10:
Attwood SE. J Gastrointest Surg 2008; 12:
Sharma P. Gastroenterology 2004; 127: