This case report describes a 77-year-old man with Barrett's esophagus and high grade dysplasia. He underwent endoscopic mucosal resection to remove the dysplastic tissue, followed by photodynamic therapy. His other medical issues included liver steatosis, benign prostate hypertrophy, hypercholesterolemia, and lower limb varicose veins. The document discusses Barrett's esophagus, endoscopic treatment options for high grade dysplasia, and follow-up after treatment.

1. 1
Case report

2. History
• 77 y/o man with longstanding history of reflux:
▫ Heartburn
▫ Regurgitation
• April 2010:
▫ Barrett‟s esophagus without dysplasia
▫ PPI 40mg bid
• Family history: negative
• Medical history:
▫ Hypercolesterolemia
▫ Benign prostatic hypertrophy
▫ Lower limbs varicose disease

3. 3
Physical Exam and Laboratory
• GI and systemic enquiry was negative
• Physical exam was normal.
• Laboratory: hypercolesterolemia
• Abdominal ultrasound:
▫ liver steatosis
▫ benign prostate hypertrophy

4. 4
First Step Diagnosis
• GERD/ Barrett Esophagus
• Liver Steatosis
• Benign Prostate Hypertrophy
• Hypercolesterolemia
• Lower Limb Varicose Disease

6. Barrett’s Esophagus
• Replacement of the lower
oesophageal squamous
mucosa by metaplastic
glandular epithelium
resulting from
gastroesophageal reflux
• Red (columnar) mucosa in
the esophagus; variable
length

7. Normal Cardiac Mucosa

8. • Endoscopy with biopsy is still the
gold standard for making the
diagnosis of Barrett's esophagus,
even though it is not 100%.
• Endoscopy defined the Barrett‟s
mucosal segment as 10 cm long;
partly circumferential
• Gastric antral ulcer of 9-10mm
• Helicobacter pylori positive
• Biopsies demonstrate goblet cells
• Biopsy showed multifocal HGD

9. Barrett’s esophagus
• 1.7% all endoscopies showed Barrett‟s 1
▫ 9.6% GERD also had Barrett‟s
• Barrett‟s patients develop adenocarcinoma at a
rate of ~ 0.5% per year 2
▫ 40 X increased incidence of cancer as compared to the general
population
• In the presence of high grade intraepithelial
neoplasia (HGIN), disease may progress at
rates >10% per year3
1 Phillips and Wong, Gastroenterol Clin North Am 1991
2 P. Sharma et al, Clinical Gastroenterol Hepatol 2006
3 Seewald S, Postgrad Med J 2007

10. Second Step Diagnosis
• Barrett Esophagus with High Grade Dysplasia
(HGD)
• Liver Steatosis
• Benign Prostate Hypertrophy
• Hypercolesterolemia
• Lower Limb Varicose Disease

11. What are the concerns with HGD?
• High risk of progression to cancer,
• High risk of coexisting cancer,
• Difficulty in differentiating HGD from
intramucosal cancer

12. 12
Metaplasia-Dysplasia Progression to Cancer

13. Age Adjusted Incidence of
Esophagogastric Adenocarcinoma In
White Males in USA 1974-1994
 Devesa S, Cancer 1998

14. 14
Riddell’s and Vienna classifications

15. Screening for Barrett’s
• Barrett‟s most common in older white males
with GERD
▫ Predictors: age > 40y, heartburn, long duration of
GERD sx (> 13 years), male gender; sensitivity of
heartburn is low
 Conio , Int J Cancer 2002;97:225-9
• 85% of EAC occurs in white males
▫ 3 studies show asymptomatic cases

16. Surveillance: No dysplasia
Documentation: Follow-up:
• 2 EGDs with biopsy • Every 3 years
within 1 year

17. Surveillance:Low-grade dysplasia
Documentation: Follow-up:
• Every year until no
• Repeat EGD and dysplasia X 2
biopsies within 6
months
• Expert pathologist
confirmation

18. Surveillance: High Grade Dysplasia
Documentation: Follow-up:
• Repeat endoscopy • Every 3 months or
within 3 months treatment based on
results and patient
• Expert pathologist factors
confirmation
• EMR (endoscopic
mucosal resection)
of all mucosal
irregularities

19. 19
Staging:
• CT chest/abdomen were normal
• The patient was subsequently referred for EMR

20. Potentially curative endoscopic therapies for
early stage esophageal carcinoma and Barrett’s
esophagus with high grade dyplasia
• Resective
▫ Edoscopic mucosal resection (EMR)
▫ Endoscopic submucosal dissection (ESD)
• Ablative
▫ Photodynamic therapy
▫ Radiofrequency ablation
▫ Argon plasma coagulation (APC)
▫ Others (laser therapy, multipolar
electrocoagulation, cryotherapy )

21. Indications for endoscopic mucosal
resection in Barrett’s esophagus
• High grade intraepithelial neoplasia
• Well or moderately differentiated T1 m
intramucosal cancer
• Absence of suspicious surrounding lymph nodes
by endoscopic ultrasound / CT

22. Depth of T1 carcinoma
 m1, m2, m3, and sm1
lesions could be treated
endoscopically if the
lesions are <30 mm,
well and moderately
differentiated, and
without lymphangitic
invasion
Conio M et al, Am J Gastroenterol
2006

23. Incidence of nodal metastasis for T1
adenocarcinoma of the esophagus
• M1, M2, M3, SM1: 0%
• SM2: 23%
• SM3: 69%
Buskens et al, Gastrointest Endosc 2004

24. Patient preparation
 patient‟s platelet counts and coagulation profile
◦ EMR is contraindicated if platelet count is less than 50,000
mm3 and/or international normalized ratio (INR) more
than 1.4.
 patients who are on aspirin (ASS) should stop taking
their medication 1 wk prior to EMR.
 oral anticoagulation such as warfarin should be switched
to low-molecular weight heparin (LMWH) injections and
the injection should not be administered on the day of
the procedure
 known gastroesophageal reflux disease should be treated
with a high-dose proton pump inhibitor at least for 2 wk
prior to EMR.

25. EMR
• En bloc
▫ maximum recommended diameter for en bloc
resection is 20 mm
• Piece-meal resection
▫ increases the complication rate,
▫ the histologic assessment of the margins is
difficult,
▫ the recurrence risk is higher

26. • Common EMR techniques
for Barrett‟s oesophagus:
A. Inject and cut technique
B. Simple snare resection
technique
C. Cap assisted EMR
D. EMR with ligation
• EMR strategies used for
Barrett‟s oesophagus:
▫ Localised EMR
▫ Circumferential EMR

27. Localised EMR Circumferential EMR
the area with HGIN and IMC is both the diseased area as well as all
targeted and resected underlying Barrett‟s mucosa is
completely resected
all of the four techniques „„simple snare resection‟‟ technique, the
„„inject and cut‟‟ technique, and
EMRL using the Duette Multiband
Mucosectomy Kit.
Local recurrence- 24.4% (Lopes CV, et Local recurrence- 9.52% (Giovanini M,
al Surg Endosc 2007) Endoscopy 2004)
Combined with PDT and APC Piecemeal resection is unavoidable
•One single setting is associated with
stricture formation
• Conditions for a complete resection
are most optimal in the first EMR
session.
•In further sessions fibrosis with scar
formation makes EMR more difficult

28. 1. Identify longitudinal/circumferential extent of
lesion, using chromoendoscopy if necessary
(methylene blue)
Chromoendoscopy (methylene blue): one flat lesion and
one exulcerated lesion

29. 2. Magnifying view: lesions with different grades
of dysplasia

30. 3. Lift the lesion (submucosal injection)
4. “Suck-and-ligate” technique: the lesion has been
aspirated into the variceal ligating device, then the
rubber band has been released

31. 5. Excision

32. Careful histopathologic examination of
endoscopic mucosal resection specimen is
critical to ensure appropriate staging

33. Postprocedure
• Most EMR procedures can be performed on an
outpatient basis.
• Patients are allowed soft diet after they are fully
awake and advised to continue on soft diet for 2
wk after every EMR session.
• Patients are continued on a high-dose proton
pump inhibitor.

34. Risks of EMR
• Procedural complications
▫ Perforation
▫ Stricture
▫ Bleeding
• Inadequate treatment
▫ Positive margins
▫ Untreated synchronous lesions
▫ Associated nodal disease

35. Reccurence
• 26 patients with BE and HGD/IMC
• Persistent endoscopic and histologic eradication
of BE at 28 months- 87.5%
• 2 patients –Barrett epithelium was detected
beneath the neosquamous epithelium 3 months
after EMR
Larghi A et al, Endoscopy 2007

36. Summary
• EMR- first line of therapy if there is any evidence of
HGD and /or an intra-mucosal ADC within a
Barrett‟s mucosa.
• EMR avoid the morbidity associated with
esophagectomy
• Patients must be carefully selected to assure early
stage disease without the potential for nodal
metastases
• Dysplasia and invasive carcinoma may be multifocal
• Even small tumors can be associated with nodal
metastases, particularly once the submucosa is
involved

37. Third Step Diagnosis
• Barrett‟s Esophagus with High Grade Dysplasia
(HGD) and Intramucosal Cancer treated with
EMR.
• Liver Steatosis
• Benign Prostate Hypertrophy
• Hypercolesterolemia
• Lower Limb Varicose Disease

38. Photodynamic Therapy

39. PDT
• Complimentary method in order to obtain a complete
eradication of the intestinal metaplasia.
• Can be used as a rescue procedure if the EMR results are
unsatisfactory (persistence of HGD on biopsy).
• Can also be used as an alternative to EMR in case of
diffuse HGD?
• No data in the literature
• Lack of tissue for histological assessment
• crucial for determining treatment adequacy,the ablation may
be incomplete, with remnant Barrett‟s mucosa post treatment
• the persistent Barrett‟s oesophagus will remain at risk for
progression to adenocarcinoma

40. PTD: two phases
Illumination
Injection

41. Balloon catheters Medlight

42. • PDT treatment was given to the distal 5 cms segment
in December 2010
• Patient tolerated the treatment well.
• Endoscopy did not reveal any areas of narrowing.
• He has been continued on Esomeprazole 40 mgm
bid.
• Follow up - March 2011

43. Removal of IM may be comparable to removal of
colon polyps in terms of cancer prevention and
avoidance of esophagectomy

45. When is Barrett’s mucosa truly eliminated ?
• 25 patients who had BE (~5cm length) eliminated by
PDT were followed for a period of~23 mo
• Results:
▫ 15/25 no recurrence
▫ 10/25 recurred in ~10 mo
▫ 8/10 no evidence of IM in the first set of bx,
▫ 2/10 had IM in the second sets of bx
▫ 6 pts - IM was detected in the third sets of biopsies.
• Recommendation :
▫ Absence of IM should only be accepted after min 3 neg sets
of biopsies.
Wang KK et al. Barrett‟s esophagus after photodynamic therapy: risk of cancer development during
long term follow-up. Gastroenterology 2004; 126 (suppl 2): A-50

46. PDT-complications
• For all ablative methods think of the residual
glands under the reepithelialised squamous
epithelium (“buried glands”)

47. Photodynamic therapy for ablation of high
grade dysplasia in Barrett's esophagus
* p<0.05 PDT plus omeprazole
omeprazole
HGD ablated 106/138 [77%] 27/70 [39%]*
Incidence of 13% (n=18) 28% (n=20) *
adenocarcinoma
Reduced risk of cancer
by 50% (did not
eliminate it)
Adverse events 94% 13% *
• Overholt BF et al, Gastrointest Endosc. 2005

48. EMR and PDT for Barrett’s Esophagus
with HGD
• 115 patients
– 96 with IMC
– 19 with HGD
• Results:
– Average follow=34±10 months
– Complete local remission in 98%
– Complication rate:9,5%
– 30% metachronous lesions in follow-up period; all but
one retreated endoscopically
May et al, Eur J Gastroenterol Hepatol 2002

49. PDT: T1 esophageal cancer
• Prospective cohort
• 80 (74 with EAC) patients
• 10 patients required 2nd treatment
• Five-year survival=97%
• No cancer related death
• Complete remission:
▫ PDT alone 90%
▫ PDT+EMR 95%
Cahlia et al, DDW 2005

50. PDT
• Avantages :
▫ Unifocal and multifocal lesions
▫ May be associated to other techniques
▫ Technique easy to perform
▫ Can be repeated in 48 hours
• Disadvantages :
▫ Photosensibility and strictures risk patient
education
▫ Pleural effusion
▫ Atrial fibrillation

51. Related issues - Chemoprevention
• NSAIDs
▫ OR for cancer - case control studies 0.57(0.47-
0.71)
▫ RCT of celecoxib: no benefit
• PPIs
▫ 2 retrospective cohort studies suggest benefit
 Large scale trials with aspirin and PPIs are
underway

52. Related issues: Reflux control in
Barrett’s Esophagus
• PPIs or surgery should be directed to symptom
control
• No convincing evidence that either PPIs or
surgery prevent EAC

53. Third Step Diagnosis
• Barrett‟s Esophagus with High Grade Dysplasia
(HGD) and Intramucosal Cancer treated with
EMR and PDT.
• Liver Steatosis
• Benign Prostate Hypertrophy
• Hypercolesterolemia
• Lower Limb Varicose Disease

54. Conclusions
• Screening commonly in high risk groups
• Surveillance now standard of care
• Dysplasia level still guides surveillance
protocols
• Endoscopic treatment now accepted as first line
approach to HGD and T1 cancer