Barrett's Esophagus and Barrett s Esophagus and Esophageal ...

Barrett’s Barrett s Esophagus and 

Esophageal Cancer Endoscopist 

Perspective 

Jack Leya, M.D. 

LUMC LUMC and and Hines Hines VA Hospital

Learning Objectives 

• Define Barrett’s Esophagus 

• Recognize g risk factors for Barrett’s 

esophagus and esophageal cancer 

• Recognize g natural history y of Barrett’s, , 

dysplasia and its progression to cancer 

• Discuss the role of endoscopic p management g 

of Barrett’s esophagus and early esophageal 

cancer

Case #1 

Pt 56 yow yowf, , cchronic o c G GERD, , oon PPI’s s for o >10y. 0y. Sy Symptoms p o s oof GGERD we well 

controlled but has occasional dysphagia. EGD done in outside hosp 

showed short segment Barrett’s. Biopsies reviewed by two 

independent pathologists showed Barrett’s with HGD and 

Intramucosal tumor. Patient was referred to LUMC for further 

managfement. 

PMH: HTN,hyperlipidemia,s/p PTCA. 

Meds: PPI, ASA, Plavix, Lopressor, Crestor, Lisinopril 

P.E. essentially normal… 

2009 

2010

Barrett’s Esophagus-? Congenital short esophagus

Barrett’s Esophagus 

• Probably a successful response to severe 

reflux 

• Usually; bad LES, hiatal hernia, 

compromised motility 

• Is it acid, or bile or both 

• Wh Why some develop d l Barrett’s B ’ 

• Why some (few) develop cancer

Barrett’s Barrett s Esophagus 

• Multiple definitions of Barrett’s have been used; 

three ttypes pes of columnar col mnar epithelia have ha e been 

described, gastric fundic type, gastric cardia and 

intestinal

Definition 

Definition: Specialized intestinal (columnar) 

epithelium in the esophagus is “Sine Sine Qua Non Non” 

Gastroenterology Vol.140, No. 3, 2011

Barrett’s Esophagus - Epidemiology 

Prevalence in GERD Patients 

Author 

S Spechler hl (1994) 

Weston (1996) 

Johnston (1996) 

Chalasani (1997) ( ) 

Hirota (1999) 

Average 

LSBE LSBE 

1% 

7% 

1% 

6% 

2% 

3.4% 

SSBE SSBE 

12% 

8% 

2% 

8% 

6% 

7.2% 

ALL BE 

13% 

15% 

3% 

14% 

8% 

10.6%


Endoscopic 

B Barrett’s tt’ 

Prevalence by Ethnicity 

10 

8 

6 

4 

2 

>50,000 

procedures; 

Overall BE 

prevalence: 6.6% 

(n=3357) 

0 

Caucasians Hispanic Asian African- 

s s A American i 

CORI Data, DDW 2001 

s


Risk Factors 

Increasing age 

Men 

Caucasians 

Longstanding GERD 

symptoms y p 

Conio M, et al. Int J Cancer 2002; 97:225 

Lieberman DA, et al. Am J Gastroenterol 1997; 92:1293

Acid and Pepsin Damage Tight Junctions 

Barrett’s Esophagus - Pathophysiology 

A Acid id and d Pepsin P i Damage D Tight Ti ht Junctions J ti 

Damaged 

junctions 

Increased 

paracellular 

permeability 

Widened 

Basal 

layer 

Tight 

junction j Acid 

cell 

junction j 

Tobey NA, et al. Am J Gastroenterol 2004; 

99:13 

Pepsin


% 

Endoscopic 

Barrett’s 

Duration of Reflux Symptoms and Risk of 

Barrett’s Esophagus 

25 

20 

15 

10 

5 

0 

< 1 year 1-5 yrs 5-10 yrs > 10 yrs 

Symptom 

duration 

Lieberman, et al. Am J Gastroenterol 1997; 92:1293


Bil Bile RReflux fl iis IIncreased d iin Barrett’s B tt’ 

% Time bilirubin 

absorbance 

0.14 0.14 0.14 

50 

40 

30 

20 

10 

0 

Control GERD Barrett’s 

p

The Role of H. pylori in Barrett’s 

Esophagus 

H. pylori py Infection is not more common in 


Th The inverse i relationship l ti hi between b t H. H pylori l i 

and adenocarcinoma is controversial 

-conflicting fli ti results lt from f different diff t studies t di of f 

Cag A+ 

“Protective” role regarding esophageal 

adenocarcinoma controversial because 

epidemiologic id i l i association i ti does d not t prove 

causation !


Potential Relationship 

Between H. pylori py and 


GERD is uncommon in regions of 

world where most people are 

colonized by H. pylori 

GERD and its sequelae sequelae are 

increasing g in countries where H. 

pylori prevalence is decreasing 

Peek RM and Blaser MJ, Nature Reviews Cancer 2002; 2:28


Al Alcohol h l Use U Does D NNot t IIncrease Ri Risk k of f 

Esophageal Adenocarcinoma 

Alcohol use Odds Ratio 95% CI 

Never 1.0 referent 

> 35 drinks per week 0.9 0.5-1.6 

> 70 g/w 0.6 0.3-1.1 0.3 1.1 

Gammon MD, et al. J Natl Cancer Inst 1997; 89:1277 

Lagergren J, et al. Int J Cancer 2000; 85:340

Endoscopic Evaluation 

• Short segment 3 cm. 

• Prague criteria Circmuferential (C) and 

Maximum extend (M) ( ) 

Sharma P, Dent J, Armstrong D, et al. Gastroenterology 2006;131:1392-1399


Patients 

(%) 

20 

15 

10 

5 

0 

PPrevalence l of f Dysplasia D l i and d 

Cancer in BE and CIM 

LSBE 

n = 40 

Hirota, et al. Gastroenterology 1999; 116:277 

SSBE 

n = 64 

Dysplasia 

Cancer 

CIM 

n = 47

NDBE Natural History

Barrett’s Esophagus - Surveillance 

Variable Progression Progression of of HGD HGD to Cancer – 

Adjusted for Referral Bias and Prevalence 

Cases 

Schnell, , et al. 

(n=75) 

Reid, et al. 

(n=76) 

Surveillance 

Period 

16% 7.3 7 77.3 3 years 

24% 5 years 

0% 10% 20% 30% 40% 50% 60% 70% 

Reid, et al. Am J Gastro 2000; 95:1669 

Schnell, et al. Gastro 2001; 120:1607

Barrett’s Esophagus - Screening 

American College of Gastroenterology 

Screening Guidelines 

Chronic GERD symptoms 

Male 

C Caucasian i 

Older age age g 

Sampliner RE, Am J Gastroenterol 2002; 97:1888

2005 Estimated US Cancer 

Deaths* 

Lung and bronchus 

Prostate 

31% 

10% 

Men 

295,280 

Women 

275,000 

27% 

15% 

Lung and bronchus 

Breast 

Colon and rectum 10% 

10% Colon and rectum 

Pancreas 6% 

6% Pancreas 

Leukemia 4% 

6% O Ovary 

Esophagus 4% 

4% Leukemia 

Liver and intrahepatic 

3% Non-Hodgkin 

bil bile d duct t 3% 

lymphoma 

Non-Hodgkin Lymphoma 3% 

3% Uterine corpus 

Urinary bladder 3% 2% Multiple p myeloma y 

Kidney 3% 

All other sites 24% 

2% Brain/ONS 

22% All other sites 

ONS=Other nervous system. 

Source: American Cancer Society, 2005.

Survival 

Stage Distribution and 5-year Relative Survival by Stage at 

Diagnosis for 

2001-2007, All Races, Both Sexes 

Stage at Diagnosis 

StageDistribution 

(%) 

5-year relative Survival 

(%) 

Localized (confined to primary site) 22 37.3 

Regional (spread to regional 

lymphnodes) 

32 18 18.44 

Distant (cancer has metastasized) 32 3.1 

Unknown (unstaged) 14 11 11.4 4 

Localized to the mucosa 83.0

Epidemiology: Adenocarcinoma 

• White men>8x white women 

• White men>5x African Americans 

• NNew cases iin the h US iin 2010 2010: 16 16,640 640 

• Deaths related do Esop Ca: 14, 500


GERD S Symptoms t and d Ri Risk k of f 


GERD symptoms 

Odds Ratio 

95% CI 

Esophageal adenocarcinoma 7.7 5.3-11.4 

Cardia adenocarcinoma 2.0 1.4-2.9 

E Esophageal h l squamous cancer 11 1.1 0719 0.7-1.9 

Lagergren, et al. N Engl J Med 1999; 340:825

Barrett’s Esophagus - Screening 

Esophageal 

Adenocarcinoma 

Odd Odds Ratio R ti 

GERD DDuration ti and d Ri Risk k of f 


20 

15 

10 

5 

0 

None 20 

Lagergren, et al. N Engl J Med 1999; 340:825 

Symptom Duration (Years)


Smoking Increases the Risk of 


Tobacco smoking OR 95% CI 

Previous smoker 2.0 1.4-2.9 

Current smoker 2.2 1.4-3.3 

42 years 2.4 1.5-3.7 

Gammon MD, et al. J Natl Cancer Inst 1997; 89:1277 

Lagergren J, et al. Int J Cancer 2000; 85:340


FFactors t Associated A i t d With Esophageal 

E h l 

Adenocarcinoma – Case Control Studies 

Risk Factor Magnitude of Association 

Odds Ratio 95% CI 

Ch Chronic i reflux fl symptoms 77 7.7 5311 5.3-11.4 4 

Body mass index 7.6 3.8-15.2 

Smoking: current smoker smoker 22 2.2 1433 1.4-3.3 

ex-smoker 2.0 1.4-2.9 

Prior cholecystectomy 1.3 1.0-1.8 

LES relaxing drugs 3.8 2.2-6.4 

Aspirin / NSAID use 0.4 0.2-0.6 

H. pylori Cag A positive 0.4 0.2-0.8

Incidence Rate of Esophageal 

Adenocarcinoma After Antireflux 

Surgery or Medical Therapy: Meta- 

analysis 

Antireflux Medical 

Medical 

Therapy in 

Surgery Therapy Last 5 Years 

(95% CI) (95% CI) (95% CI) 

Incidence Rate 3.8 5.3 4.3 

Incidence Rate (2.4-6.1) ( 3.6-7.8) (2.6-5.8) 

(cancer/1000 patient-years) 

From Corey KE et al. Am J Gastroenterol 2003;98:2390-4

Barrett’s Esophagus - Treatment 

Mortality from Esophagectomy is 

Related to Hospital Volume 

25 

20 

15 

10 

5 

0 

H Hospital it l Volume V l Per P Year Y 

Mortality (%) 

19 

Birkmeyer, et al. N Engl J Med 2003; 349:2117


Rationale for Ablation Therapy 

To To reduce the risk of cancer 

Avoidance Avoidance of esophageal 

resection 

Treatment Treatment of early y cancer 

Pacifico RJ, et al. Clinical Gastroenterology and Hepatology 2003; 1:252 

Scheiman JM, et al. Gastrointestinal Endoscopy 2003; 58:244


Techniques for Mucosal Ablation 

Mechanical 

Endoscopic mucosal resection (EMR) 

Th Thermal l 

Argon plasma coagulation 

Multi-polar Multi polar coagulation 

coagulation 

Radio-frequency ablation 

Lasers: Argon, Nd:YAG, KTP-YAG 

Cryoablation 

Photochemical 

Photodynamic therapy


Argon Plasma Coagulation is Safe 

and Reverses Barrett’s Esophagus 

10 studies (n=231) 

86% complete response 

(including HGD and cancer) 

8% had buried Barrett’s 

mucosa 

Complications are chest pain, 

strictures, fever 

Pereira-Lima JC, Am J Gastroenterol 2000; 97:279 

Kahaleh M, Endoscopy 2002; 34:950


Photodynamic Therapy 

Balloon 

Sodium 

Photoradiation Porfimer 

Laser


Photodynamic Therapy: Theory 

Photodynamic Therapy: Theory 

Photosensitizer + 

O 2 

Neoplastic p 

cells 

O 2


Long Long-Term Long Long-Term Term Follow-up Follow up After After PDT PDT and 

and 

Nd:YAG 

103 patients 

Mean follow-up 51 

months 

5% subsquamous 

subsquamous 

cancer 

5% subsquamous 

B Barrett’s tt’ mucosa 

without dysplasia 

100 

80 

60 

40 

20 

Overholt BF, Gastrointestinal Endoscopy 2003; 58:183 

0 

Successful 

Treatment (%) 

LGD HGD Cancer


Adverse Events Observed With 

Photodynamic Therapy 

100 

80 

60 

40 

20 

Photosensitivity 

Strictures 

Vomiting 

Constipation 

Chest pain 

Pyrexia 

0 

Adverse Events 

Wang and Nijhawan, Gastrointest Endosc Clin N Am 2000; 10:487

Radiofrequency 

Abl Ablation 

ti

Anatomy and 

RFA 

Targeted Epithelium 

Thickness ~500µm 

RFA 

Ablation depth 500-1,000µm 

Approximate EMR 

Depth 

Esophageal epithelium 

~500µm µ 

Lamina Propria 

Muscularis 

Mucosae 

Submucosa 

Muscularis Propria

Radiofrequency Ablation of Barrett’s Esophagus 

Shaheen NJ et al; NEJM, May 2009, Vol 360

Radiofrequency Ablation of Barrett’s Esophagus 

Shaheen NJ et al; NEJM, May 2009, Vol 360

halo

Cryo-Ablation 

Cryo Ablation

Dosimetry 

0.5 mm 

Am J Gastro 2006;101:S532. Cryo Spray Ablation 

(CSA) in the Esophagus: Optimization of Dosimetry. 

4 x 10 

3 x 20 

seconds = 

Lamina 

Propria to 

shallow 

SSubmucosal b l 

injury 

seconds = 

Submucosal 

injury 

CControlled by two variables: i 

– Primary: Length of tissue 

freeze time 

– Secondary: Repetitions of 

freeze–thaw cycles

CryoSpray Ablation Procedure 

Page 50

Results of CryoSpray Ablation for Esophageal 

HGD and IMCA in High Risk Risk, , Non-Surgical 

Non Surgical Patients 

Conclusions: Endoscopic cryotherapy ablation with low pressure liquid 

nitrogen spray is effective in HGD and IMCA in this heterogeneous group 

of high risk patients. 89% response rate for HGD was seen. 

66% response rate for Intra Intra-Mucosal Mucosal Cancer 

– Heterogeneous g population p p of very y sick p patients 

– 32 patients enrolled (71 years; 61 61-79 79 IQR) 

– 12 – IMCA 

– 20 – HGD 

– 27 – completed treatment 

– 5 – remain in treatment 

– Approximately pp y 2 y year follow up p 

– Prospective, single center (non (non-randomized) 

randomized) 

Dumot, John Adam et al. Results of CryoSpray Ablation for Esophageal HGD and IMCA in High Risk, Non-Surgical Non Surgical Patients. DDW 2008 

abstract. Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Safety and Tolerability of Endoscopic Cryotherapy 

Ablation in the Esophagus: A Multicenter Study 

• Prospective, IRB approved 

• 4 4 academic academic medical medical centers 

centers 

Conclusions – Endoscopic Cryotherapy Ablation: 

• Safe and well tolerated 

• Low rate of serious adverse events 

• Unique mechanism of action 

• 77 patients; 323 procedures 

• No side effects in 22 patients (29%); 155 

procedures (48%). 

• Mostly mild side effects overall 

• 1 SAE (1.3% / 0.31%) 

(Gastric perf, Marfan’s syndrome) 

• 3 Strictures 

Strictures 

(3.9% / 0.93%) 

Greenwald, Bruce D., Horwhat, J. David, Abrams, Julian A., Lightdale, Charles J., Dumot, John A.


Indications for for Endoscopic Endoscopic Mucosal 

Mucosal 

Resection (EMR) 

Raised lesions Suspicion Suspicion Suspicion of 

of 

Focal area of 

malignancy 

dysplasia dysplasia y p 


esophagus with 

dysplasia 

Ell C, Gastroenterology 2000; 118:670

Endoscopic Mucosal Resection 

(EMR) 

• Total of 349 patients 

• EMR done in 279 pts, PDT in 55 pts,APC in 2 pts 

• MMean f/ f/u period i d63 63.6 6months th 

• Complete response achieved 337 pts (96.6%) 

• Surgery was necessary in 13 pts (3.7%) (3 7%) 

• Metachronous lesions developed in74 pts (21.5%) 

• 56 died of not related disease. No deaths related to 

cancer 

O. Pech et al. Gut 2008;57 1200-1206


Mucosal Resection Caps

Step 1: Injection of Target Lesion 


Step 1: Injection of Target 

Lesion


Step p 3: Suction and Snare of Lesion 

Step 3: Suction and Snare 

of Lesion

Case presentation cont.

eus

emr

POST EMR

F/U EGD in six months 

• Pt asymptomatic on 

Pt asymptomatic on 

PPI’s BID

Collegium Novum, Jagiellonian University

Barrett's Esophagus and Barrett s Esophagus and Esophageal ...

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