1. Barrett’s Esophagus Dr. Robert Osterhoff, MD
Palo Alto Medical Foundation
Mills Peninsula Hospital
March 19th 2016

2. Objectives Background Examples and images Screening and Surveillance
Definitions: Learn the definition of Barrett's esophagus and gain some understanding of its pathophysiology and relationship to esophageal cancer
History of Barrett’s esophagus
The scope of the problem
Examples and images
What does Barrett’s look like
Prague classification
Short vs. Long segment
Screening and Surveillance
Understand the current indications and guidelines for Barrett's screening and surveillance
Explore some of the controversies
Treatment
Gain an understanding of methods of treatment for Barrett's esophagus and current standards of care, including risks of treatment and the impact on patients

3. Background…why do we care
The real issue is Esophageal cancer (EAC)
Accounts for approximately 1% of all cancers and 6% of cancers involving the gastrointestinal tract
By some estimates the incidence has grown 400% in the last years
The one year mortality is >85%
Barrett’s esophagus is a premalignant condition for EAC
It has been estimated that 5.6% of adults in the United States have Barrett’s esophagus.
Follows progression from metaplasiadysplasiacancer

4. Before we begin…Definitions
Metaplasia (Greek /(met″ah-pla´zhah)  change in type
A change or adaptation of one type of epithelium to another that is more likely to be able to withstand the stresses it is faced with
Dysplasia (Greek /(dis″pla´zhah) δυσ- dys-, "bad" or "difficult" and πλάσις plasis, "formation")
Abnormal growth or development of cells, tissue, bone, or an organ. Replacement of normal cells with those of another type, often maladaptive or premalignant
Low-grade vs. High-grade dysplasia
Carcinoma(Greek[kahr″sĭno´mah]  malignant new growth made up of epithelial cells tending to infiltrate surrounding tissues and give rise to metastatses
 Johns Hopkins Pathology Atlas. © Johns Hopkins University.

5. Barrett’s esophagus: simple definition
Barrett’s esophagus is a condition in which the lining of the esophagus changes, becoming more like the lining of the intestine.
It is a “precancerous
condition”

6. True Definition: Barrett’s esophagus
Barrett’s esophagus: The replacement of the normal stratified squamous epithelium of the esophagus by simple columnar epithelium with goblet cells .
Barrett's esophagus and esophageal cancer: An overview, Vincenza C. et. al Published online: May 17, 2012 Pages:   DOI:  /ijo

7. History Norman Rupert Barrett Allison and Johnstone
Esophageal surgeon who was born in Adelaide, Australia in 1903
Worked for most of his career as a surgeon at St. Thomas’ Hospital in London
First described the columnar metaplasia in 1950.
Allison and Johnstone
In 1953 described 7 patients who had reflux esophagitis involving an “esophagus lined with gastric mucous membrane associated with gastroesophageal reflux
An association with adenocarcinoma was made in 1975.

8. History (continued)
By the 1980s, it was well established that adenocarcinoma was associated with Barrett’s esophagus
Multiple strategies for diagnosis and treatment emerged in the 1990s
RFA developed and became widespread in early 200os along with some clinical guidelines

9. EAC: Scope of the Problem
1% of all cancer in the US
In 2012, there were an estimated 35,781 people living with esophageal cancer in the United States.
Rates are rising
National Cancer Institute; SEER database

10. Esophageal cancer represents 1.0% of all new cancer cases in the U.S.
EAC (continued)
Common Types of Cancer
Estimated New Cases 2015
Estimated Deaths 2015 1.
Breast Cancer (Female)
231,840
40,290 2.
Lung Cancer
221,200
158,040 3.
Prostate Cancer
220,800
27,540 4.
Colon Cancer
132,700
49,700 5.
Bladder Cancer
74,000
16,000 6.
Melanoma of the Skin
73,870
9,940 7.
NHL
71,850
19,790 8.
Thyroid Cancer
62,450
1,950 9.
Renal Cancer
61,560
14,080
10.
Endometrial Cancer
54,870
10,170 -
18.
Esophageal Cancer
16,980
15,590
Mean age at diagnosis=67
National Cancer Institute; SEER database

11. Barretts: Risk of progression
The risk of developing EAC in patients with NDBE was considered to be in the range of 0.1–3.5% per year
Several studies suggesting a risk of ~0.5% per year
A recent large study has shown that the risk may be as low as % per year
A cohort study of 11,028 patients from Denmark published in 2011 showed an incidence of only 1.2 per 1000 person-years
5.1 per 1000 person-years in patients with dysplasia.
1.0 per 1000 person-years in patients without dysplasia.

12. Diagnosis
Upper endoscopy identifies “salmon-colored mucosa” at the GE junction
Four quadrant random biopsies every 1-2cm with cold forceps from the abnormal area
Nodules or clearly abnormal areas should be targeted and removed by biopsy or EMR
Chromoendoscopy or narrow-band imaging used when available to enhance detection

13. Barrett’s examples
Atlas of Gastrointestinal endoscopy .

14. Prague classification
Developed by the Barrett’s Esophagus Subgroup of the International Working Group for the Classification of Reflux Oesophagitis (IWGCO)
Sharma, P. et al. The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria. Gastroenterology 131,  (2006).

15. Short segment vs. Long segment
Short segment = <3cm
Long segment = >3cm
New ACG Guideline: Diagnosis & Management of Barrett’s Esophagus November 2015 AJG Nicholas J. Shaheen, MD, MPH, FACG; et. Al.

16. Narrow band imaging Chromoendoscopy
El Salvador Atlas of Gastrointestinal endoscopy .

17. Screening: who to screen?
No recommendation to screen the general population
Patient selection is important
Longstanding reflux symptoms (>5 years)
Long-term PPI use
Numerous risk factors or Family history

18. Risk factors: for Barrett’s and EAC
Chronic GERD
Men ( 4 to 8 x vs. women)
Caucasian ( ~5x vs. African American)
Age <50
Tobacco
Obesity

19. Surveillance Guidelines
Waxman, et. al, Rev. esp. enferm. ig. vol.106 no.2 Madrid feb. 2014

20. Treatment
For many years, esophagectomy was the standard treatment for Barrett’s patients with high grade dysplasia or early cancer.
Esophagectomy is associated with a 40–50% risk of major complications and a mortality rate of 3–5%
Photodynamic therapy (PDT) offered an alternative outpatient endoscopic procedure that eliminates dysplasia and superficial cancer and reduces the length of Barrett’s mucosa
PDT utilizes the photochemical reaction between a photosensitizing drug (Porfimer sodium ), light and oxygen. Interaction of the three components results in production of free radicals that are highly cytotoxic, resulting in the ablation of illuminated tissue
APC equally effective based on studies in early 2000

21. Treatment Options (continued)
Radiofrequency ablation (RFA)
Endoscopic mucosal resection (EMR)
Endoscopic sub-mucosal dissection (ESD)
Argon plasma coagulation (APC)
Multipolar electrocoagulation (MPEC)
Laser ablation (using neodymium-yttrium aluminum garnet (Nd-YAG), potassium titanium phosphate),
Photodynamic therapy (PDT)
Cryotherapy

22. Radiofrequency Ablation (RFA)
In the year 2000, the founders of BÂRRX Medical, Inc. (scquired by Covidien and now Medtonic) developed an endoscopic device called the HALO360 System for treating Barrett's esophagus.
In 2001, the U.S. Food and Drug Administration cleared the HALO360 System for use in the ablation of bleeding and non bleeding sites in the gastrointestinal tract including Barrett's.
In January 2005, the Covidien Medical team conducted multi-center clinical trials to demonstrate the safety and efficacy of the system
Trials have been completed for all types of Barrett's tissue: intestinal metaplasia, low-grade dysplasia, and high-grade dysplasia
March 20, 2006 started a new landmark study comparing the effectiveness of the HALO Technology against a current standard of care for Barrett's (regular EGD surveillance and medical management of GERD)
April 21, 2006, the HALO90System (focal ablation device), was cleared by the FDA
2007 DDW, the current data was presented demonstrating that 98.4% of participants were Barrett's-free after one to two treatment sessions at 30 months.

23. RFA (continued)

24. RFA: technique Landmark determination with EGD
Cleaning of the esophageal wall to remove excessive mucus ( 1% acetylcysteine or water)
Esophageal sizing: a sizing catheter is connected calibrated, introduced over a guidewire and inflated to 4.3 psi (0.30 atm) to measure the inner esophageal diameter at various distances
Ablation catheter selection: Based on the esophageal inner diameter measurements. (all catheters are 165-cm long with a balloon in one of five outer diameters (18, 22, 25, 28, and 31 mm once inflated). The outer diameter of the ablation balloon should be smaller than the narrowest measured esophageal diameter. 
Ablation: The ablation catheter is then inflated to 3 psi. Upon activation, radiofrequency energy is for ~1.5 seconds, after which the balloon automatically deflates. Moving distally, the balloon is repositioned, allowing a small amount of overlap with the previous ablation zone (5 to 10 mm). Standard ablation regimen consists of two applications of 12 J/cm2 , 1.5 sec each with a cleaning phase in between.

25. RFA: post treatment care
After RFA, acid suppressive therapy is important to minimize patient discomfort and allow the esophagus to heal optimally.
Patients should limit to a liquid diet for 24 hours, then gradually advance to a soft and then normal diet at their own discretion.
Many patients require pain medicaiton. Tylenol is preferred first line over NSAIDs. Codiene or narcotics (vicodin/percocet) often used as well. Viscous lidocaine can be used as an adjunct.
Patients with severe chest pain and/or fever following their procedures may need prolonged observation or admission.
In rare cases, when there is a clear suspicion of severe complications, additional testing (eg, computed tomography) may be required.

26. RFA: potential complications
Chest pain occurs in the majority of patients who are treated and generally lasts for a few days.
In 1–2% of the patients, the pain has been more severe and longer lasting, and rarely, hospitalization for pain management is required.
The most common delayed complication has been the development of esophageal strictures. The exact incidence is not known, but in published series it has been in the range of 1%.
Perforations have occurred, but they are extremely rare and usually happened during insertion or removal of the ablation catheter.
Sharma VK, Wang KK, Overholt BF, et al. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc 2007; 65:

27. RFA: outcomes
Evidence from a number of well-designed studies, including RCT show that RFA is highly effective at removing Barrett's esophagus (BE) at both the endoscopic and histologic level with a favorable safety profile.
Overall, studies report complete eradication of intestinal metaplasia rates of 54 to 100 percent and complete eradication of dysplasia rates of 80 to 100 percent.
Long-term follow-up studies are still limited but the five-year follow-up data suggest that eradication is maintained in more than 90 percent of patients.
Shaheen NJ, Sharma P, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med 2009; 360:2277.

28. Role of PPIs Healing of esophagitis and control of reflux symptoms
Prevention of stricture formation and pain reduction after ablation
Reduces progression of Barrett’s mucosa and some studies have shown regression
Unclear effect on EAC rates or mortality
Peters , Ganesh S, Kuipers EJ, et al. (1999) Endoscopic regression of Barrett's oesophagus during omeprazole treatment: a randomised double blind study. Gut45:489–494.

29. Recap and Conclusions
Esophageal cancer is an important and growing problem
Barrett’s esophagus can lead to cancer, and progression may be preventable
Variation exists in screening and surveillance strategies
Good treatments are available, and carry minimal risk
Knowledge of EAC risk factors is important for individualized care

30. Ongoing Controversies
Who to screen and how often
Ablation of non-dysplastic Barrett’s
What about “buried glands”
What about those with “silent reflux”
Cost effectiveness?
More research is needed…

31. Thank You