1. Advanced Endoscopy Techniques
Jayant P.Talreja, M.D.
Gastrointestinal Specialists, Inc.
Bon Secours St. Mary’s Hospital

2. Acknowledgements Christopher Thompson, MD Marvin Ryou, MD
William Brugge, MD
David Forcione, MD
Brigham & Women’s Hospital
Massachusetts General Hospital
Harvard Medical School
Boston, MA

3. Objectives Discuss the endoscopic management of Barrett’s Esophagus
EUS-guided placement of fiducials
Endoscopic management of bariatric surgery complications

4. Case Presentation #1 HPI:
53 year old male with 8 month history of reflux symptoms
Marginal benefit with omeprazole daily
Despite lifestyle modifications – avoiding dietary triggers, late meals
No alarm symptoms – no dysphagia, weight loss
Presented for outpatient EGD

6. Barrett’s esophagus
In 1957 Norman Barrett, British thoracic surgeon, described the “lower esophagus lined by columnar epithelium.”
Barrett’s esophagus is now defined as “metaplastic change from squamous to columnar-lined epithelium (including the presence of goblet cells), visible endoscopically and confirmed histologically.”
Barrett’s esophagus results from the reflux of gastric acid and bile salts into the esophagus, and may be viewed as an adaptive response in which stratified squamous epithelium is replaced by potentially acid-resistant columnar epithelium.
O’Donovan M, Fitzgerald R. Diag Histopath 2012
Noffsinger N. Atlas Nontumor Path. AFIP. 2007

7. Evolution of Barrett’s and Cancer
Injury
Acid & bile reflux
nitrous oxide
Genetics
Gender, race,
? other factors (cox-2)
Accumulate Genetic
Changes
Kountourakis P, et al. Gastrointest Cancer Res 2012
Ong CA, et al. World J Gastroenterol, 2010

8. Barrett’s Prevalence Estimates
1.6% of general adult population (3.8 M)
Ronkainen J, et al. Prevalence of BE… Gastroenterology 2005;129:
5.6% of general US adult population (13.1M)
Hayeck TJ, et al. The Prevalence of BE in the US (model)…Dis Esophagus 2010;23:451-7.
6.8% of persons over age 40 (8.3 M)
Rex DK, et al. Screening for Barrett’s... Gastroenterology 2003;125:
For final bullet point (“25% of persons without GERD…”), derived conservative calculation by using following assumptions:
# of people who are >50 years old = 121,757,429 x 2/3 = 81,171,619
Source:
Assume 80% of individuals >50 years old do not have GERD = 81,171,619 x .8 = 64,937,295
Source: Standards of Practice Committee et al. Role of endoscopy in the management of GERD. Gastrointest Endosc Aug;66(2):
Assume 25% of individuals >50 years old without GERD have BE = 64,937,295 x .25 = 16,234,323
Source: Gerson LB, Shetler K, Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals. Gastroenterology 2002;123:461-7.

9. U.S. Cancer Incidence General Population Cancer Incidence
HGD Cohort Cancer Incidence
Multiple
Esophageal Adenocarcinoma
3.0 per 100,000
(0.003%)
6,600 per 100,000
(6.6%)
2,200X
General Population Cancer Incidence
Polyp Cohort Cancer Incidence
Multiple
Colorectal Cancer
45 per 100,000
(0.045%)
580 per 100,000
(0.58%)
13X
(accessed July 2, 2013)
Surveillance, Epidemiology and End Results (SEER)
Wani S, et al. Am J Gastroenterol 2009
Winawer SJ, et al. N Engl J Med 1993
Risk multiple for developing cancer conferred by HGD or polyp versus risk of that cancer in the general U.S. population

10. U.S. Cancer Incidence General Population Cancer Incidence
LGD Cohort Cancer Incidence
Multiple
Esophageal Adenocarcinoma
3.0 per 100,000
(0.003%)
1,700 per 100,000
(1.7%)
560X
General Population Cancer Incidence
Polyp Cohort Cancer Incidence
Multiple
Colorectal Cancer
45 per 100,000
(0.045%)
580 per 100,000
(0.58%)
13X
(accessed July 2, 2013)
Surveillance, Epidemiology and End Results (SEER)
Wani S, et al. Am J Gastroenterol 2009
Winawer SJ, et al. N Engl J Med 1993
Risk multiple for developing cancer conferred by LGD or polyp versus risk of that cancer in the general U.S. population

11. U.S. Cancer Incidence General Population Cancer Incidence
ND-BE Cohort Cancer Incidence
Multiple
Esophageal Adenocarcinoma
3.0 per 100,000
(0.003%)
330 per 100,000
(0.33%)
110X
General Population Cancer Incidence
Polyp Cohort Cancer Incidence
Multiple
Colorectal Cancer
45 per 100,000
(0.045%)
580 per 100,000
(0.58%)
13X
(accessed July 2, 2013)
Surveillance, Epidemiology and End Results (SEER)
Desai TK, et al. Gut 2012
Winawer SJ, et al. N Engl J Med 1993
Risk multiple for developing cancer conferred by NDBE or polyp versus risk of that cancer in the general U.S. population

13. Case Presentation #1
Diagnostic EGD – by Prague Criteria the Barrett’s appearing mucosa was measured at C5M6
Top of the gastric folds seen at 40 cm
Circumferential extent of Barrett’s terminated at 35 cm
Maximum extent of Barrett’s terminated at 34 cm
Prague Criteria – C5M6
Biopsies taken with cold forceps
Current consensus guidelines – 4 quadrant biopsies every 2 cm
Directed biopsies at abnormal appearing regions (i.e. nodules)
This patient had a total of 4 specimen jars – biopsies taken every 2 cm and directed biopsies at nodular region

14. Case Presentation #1
Biopsies of nodular region show high grade dysplasia
Remaining biopsies show intestinal metaplasia consistent with Barrett’s esophagus
Follow up discussion with patient about significance of these findings and options for the next step in management
What can we offer this patient?
Endoscopic mucosal resection
Radiofrequency Ablation

15. Endoscopic Mucosal Resection
endoscopic technique designed to remove targeted superficial tissue
Indicated for nodular dysplasia and superficial T1a adenocarcinoma
Distinct advantage is availability of larger tissue specimens
EMR for HGD and EAC is successful in 91-98% of T1a cancers
Complications include bleeding, perforation, and stricture formation
For final bullet point (“25% of persons without GERD…”), derived conservative calculation by using following assumptions:
# of people who are >50 years old = 121,757,429 x 2/3 = 81,171,619
Source:
Assume 80% of individuals >50 years old do not have GERD = 81,171,619 x .8 = 64,937,295
Source: Standards of Practice Committee et al. Role of endoscopy in the management of GERD. Gastrointest Endosc Aug;66(2):
Assume 25% of individuals >50 years old without GERD have BE = 64,937,295 x .25 = 16,234,323
Source: Gerson LB, Shetler K, Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals. Gastroenterology 2002;123:461-7.

16. Endoscopic Mucosal Resection
For final bullet point (“25% of persons without GERD…”), derived conservative calculation by using following assumptions:
# of people who are >50 years old = 121,757,429 x 2/3 = 81,171,619
Source:
Assume 80% of individuals >50 years old do not have GERD = 81,171,619 x .8 = 64,937,295
Source: Standards of Practice Committee et al. Role of endoscopy in the management of GERD. Gastrointest Endosc Aug;66(2):
Assume 25% of individuals >50 years old without GERD have BE = 64,937,295 x .25 = 16,234,323
Source: Gerson LB, Shetler K, Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals. Gastroenterology 2002;123:461-7.

17. Case Presentation #1
EMR of nodular region completed during subsequent endoscopy
If initial biopsies had shown intramucosal carcinoma, staging radial EUS would be performed prior to EMR to ensure submucosal preservation
Post-procedure recommendations:
Clear liquid diet for 24 hours
Soft solid diet for 72 hours
PPI
Carafate
Consider liquid oxycodone
Avoid non-essential NSAID’s for 14 days
Hold Plavix for additional 5-7 days
Restart ASA if CAD
Repeat EGD in 2 months

18. Case Presentation #1
Repeat EGD in 2 months shows well healed EMR resection site with no residual nodularity
Next step is to proceed to radiofrequency ablation (RFA)
An electrode mounted on a balloon catheter or over the scope is used to deliver heat energy directly to the diseased lining of the esophagus.
The energy delivered results in high temperature heating (ablation) of the Barrett’s lining.
This tissue sloughs off over 48 to72 hours following the procedure.
Over a period of six to eight weeks, this tissue is replaced by normal (squamous) lining.

19. Ablation Effect on Natural History
NDBE
LGD
HGD
Natural History
(53 studies)
0.6%
1.7%
6.6%
After Ablation
(65 studies)
0.16%
Polyp
0.58%
0.06%
NNT=45
NNT=13
NNT= 4
NNT= 38
Progression risk expressed as “Per-patient-per-year” (%) risk of developing EAC
NNT calculated on 5-year basis (number needed to treat to avoid one cancer over 5 years)
Wani S. Am J Gastro 2009
Winawer SJ. NEJM 1993

23. Proprietary Properties of RFA Lead to a Precise Ablation Depth
Mechanisms
Tightly spaced electrodes (250 µm apart)
Proven pre-set energy & power densities
Generator turns off when a pre-determined resistance level in the ablated tissues is reached (mean of 0.3s)
Ganz, Gastrointest Endosc, 2004
Dunkin, Surg Endosc 2006
Smith, Surg Endosc 2007

24. Case Presentation #2 HPI:
64 year old male with 6 month history of progressive dysphagia
Unintentional weight loss of 12 pounds
Longstanding smoker
No significant reflux symptoms
Presented for outpatient EGD

26. Bx: adenocarcinoma

27. Background Esophageal Cancer: Resectability rate: 60%-90%
Worldwide 5th most common cause of cancer related death
In US 4th leading cause of cancer mortality
Resectability rate: 60%-90%
Neo-adjuvant chemoradiation commonly used
5-year overall survival rate of resectable disease: 10% - 25%

28. Background
Advances in XRT (IMRT, IGRT, PET-based planning), particularly in esophageal CA
However, these advances only as effective as the accuracy with which target is known
Esophagus represents cancer site affected by one of the widest ranges of inter-observer variability in tumor delineation1
Endoscopic clipping has improved definition of gross tumor volume during XRT sim2
1 Njeh CF. J Med Phys. 2008
2 Pfau PR. J Clin Gastro. 2005

29. Clinical Need Accuracy & Precision of Tumor Delineation
Current paradigm entails:
Baseline PET CT (FDG activity, bony landmarks, surgical hardware)
Endoscopy report (distance from incisors)
Challenges of the current paradigm:
Dynamic movement of viscera
Respiratory variations & cardiac cycle
Body habitus changes over treatment

30. Solution: Paint the Target
Fig 1: Fiducial marking proximal mass
Fig 2: PET shows optimal fiducial positioning