1. Hospital of the University of Pennsylvania
Detection & Endotherapy of Barrett’s HGD & Early Adenocarcinoma: The Paradigm Shift
Gary W. Falk, M.D., M.S.
Professor of Medicine
Hospital of the University of Pennsylvania

2. Learning Objectives HGD-a historical perspective
Current data on optimal imaging for detection of early neoplasia
Current data on therapy of early neoplasia

3. Learning Objectives HGD-a historical perspective
Current data on optimal imaging for detection of early neoplasia
Current data on therapy of early neoplasia

4. The Problem HGD Intramucosal Ca
From Namasivayam V et al. Clin Gastroenterol Hepatol 2010;8:

5. HGD: The Old 0-70% risk of unsuspected cancer at esophagectomy
Debates centered on surgery vs. continued surveillance
PDT and APC problematic as alternative treatment strategies

6. Surgery for Esophageal Cancer
Technically demanding even in low risk patients
Problematic in high risk patients
Operative mortality
5-10% in low volume centers
0-2.5% for HGD/early cancer in expert hands 6

7. Surgery for Esophageal Cancer
Morbidity 30-50%
34% complication rate at Mayo Clinic*
Anastomotic leaks
Anastomotic strictures
Cardiopulmonary
Jejunostomy leaks
Prolonged recovery + impaired /QOL for 1st year
*Prasad G et al. Gastroenterology 2009;137: 7

8. From Bennett C et al. Gastroenterology 2012;143:336-46.
Operative Mortality In Surgical Series of Patients With HGD or Early Adenocarcinoma
From Bennett C et al. Gastroenterology 2012;143:

9. Risk of Lymph Node Metastases In HGD or Intramucosal Ca: Systematic Review
Lesion
Lymph Node Metastases
95% CI
HGD
Intramucosal Carcinoma
1.93%
Note esophagectomy mortality > 2% + morbidity
From Dunbar KB et al. Am J Gastroenterol 2012;107:

10. Long Term Survival Endoscopic Vs. Surgical Treatment of HGD
EMR preop
Note 13%
unsuspected
surgery
From Prasad GA et al. Gastroenterology 2007;132:

11. 11

13. Management Of HGD: BADCAT Consensus
Endoscopic therapy for HGD is preferred to surgery or surveillance
From Bennett C et al. Gastroenterology 2012;143:

14. Learning Objectives HGD-a historical perspective
Current data on optimal imaging for detection of early neoplasia
Current data on therapy of early neoplasia

15. Surveillance of Barrett’s Esophagus: White Light Endoscopy15

16. White Light Endoscopy Standard resolution
100, ,000 pixels
High resolution/high definition
600,000-1,000,000 pixels
TV Monitors
Standard-480 lines
HD-1080 lines
From Hassan MK & Wallace. ASGE Clinical Update 2009;16:1-4.

17. Methods of Detection of Dysplastic Barrett’s Esophagus
High Resolution
WLE
Indigo
Carmine
NBI
Acetic acid
From Curvers W et al. Gastroenterology 2008;134:670-9. 17

18. Methods of Detection of Dysplastic Barrett’s Esophagus
Enhanced imaging techniques preferred:
Image quality
Mucosal imaging
Vascular imaging
Enhanced imaging techniques did not improve:
Interobserver agreement for mucosal morphology vs. WLE
Yield for dysplasia/carcinoma vs. WLE
From Curvers W et al. Gastroenterology 2008;134:670-9. 18

19. Dysplasia Detection: The Challenge
Most patients never develop dysplasia
To detect 1 cancer will need to survey 200 average risk patients
Dysplasia & early cancer may be flat with no obvious endoscopic abnormality 19

20. From Abrams JA et al. Clin Gastro Hepatol 2009;7:736-42.
Adherence to Seattle Biopsy Protocol In Community Setting By Segment Length
From Abrams JA et al. Clin Gastro Hepatol 2009;7: 20

21. Adherence To Seattle Protocol Increases Dysplasia Detection
From Abrams JA et al. Clin Gastroenterol Hepatol 2009;7: 21

22. Inspection Time > 1 Minute Enhances Detection of HGD/Ca
Endoscopists who had an average Barrett's inspection time longer than 1 minute per centimeter of Barrett's esophagus detected more patients with an endoscopically suspicious lesion (P = .04). HGD/EAC, high-grade dysplasia/esophageal adenocarcinoma.
From Gupta N et al. Gastrointest Endosc 2012;76:531-8.

23. Correlation Between Inspection Time & Detection of HGD/Ca
From Gupta N et al. Gastrointest Endosc 2012;76:531-8.

24. Hemisphere Distribution of Early Cancer in Barrett’s Esophagus.
From Enestvedt BK et al. Gastrointest Endosc 2013;78:462-7.

25. Barrett’s Imaging 2014 Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

26. Barrett’s Imaging 2014 Detection Essentials
Clean mucosa
Carefully inspect with HDWLE for subtle surface irregularities
Vary insufflation & desufflation
Inspect distal segment in retrograde view
Add cap?
Look longer & biopsy less
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

27. Enhancements To Endoscopic Imaging
Chromoendoscopy
Magnification endoscopy
Narrow band imaging
Photodynamic diagnosis
Spectroscopy
Partial wave spectroscopy
Polarized scanning spectroscopy
Optical coherence tomography
Low coherence interferometry
Autofluorescence endoscopy
Confocal endomicroscopy
Molecular imaging 27

28. Barrett’s Imaging 2014 Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

29. Contrast Enhancement Optical Electronic post processing
Narrow band imaging
Illuminates tissue with special filters
Electronic post processing
Fuji intelligent chromoendoscopy (FICE)
I-Scan
Bottom line: image enhancement of mucosal microvasculature

30. Esophageal Surface Patterns With NBI
Circular
mucosal
Ridged/villous
mucosal
Absent
mucosal
Examples of the different oesophageal surface patterns seen during examination with narrow band imaging: (A) Circular mucosal pattern. (B) Ridged/villous mucosal pattern. (C) Absent mucosal pattern. (D) Irregular mucosal pattern. (E) Regular vascular pattern. (F) Irregular vascular pattern.
Irregular mucosal
Regular vascular
Irregular vascular
From Sharma P et al. Gut 2013;62:15-21.

31. Crossover Study of HD White Light Endoscopy Vs. NBI
HDWLE
NBI
P-value
IM detection
92% NS
Neoplasia detection [pt]
9 (7%)
12 (9%)
Visible lesions
22 (17%)
11 (4.9%)
< 0.01
Any dysplasia lesion
67 (21%)
81 (30%)
0.001
From Sharma P et al. Gut 2013;62:15-21.

32. From Sharma P et al. Gut 2013;62:15-21.
Crossover Study of HD White Light Endoscopy Vs. NBI: Detection of Patients With Dysplasia
HDWLE
NBI
Sensitivity
64%
53%
Specificity
100%
NPV
77%
73%
PPV
From Sharma P et al. Gut 2013;62:15-21.

33. Crossover Study of HD White Light Endoscopy Vs. NBI
All areas of HGD/Ca had irregular mucosal/vascular pattern
No areas with regular mucosal/vascular pattern had HGD/Ca
From Sharma P et al. Gut 2013;62:15-21.

34. Barrett’s Imaging 2014 Confocal Endomicroscopy
High quality images challenging to obtain
Expensive
Need for fluorescein
Relevance of real time decision making questionable
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

35. Volumetric Laser Endomicroscopy

36. Volumetric Laser Endomicroscopy
OCT technique
7-10 um resolution
In vivo 3D views of the esophagus
Wide field imaging technique with ability to visualize deeper mucosa
Now with marking laser for tissue acquisition

37. Volumetric Laser Endomicroscopy System
From Suter MJ et al. Gastrointest Endosc 2014 epub ahead of print

38. Volumetric Laser Endomicroscopy: Laser Markings
From Suter MJ et al. Gastrointest Endosc 2014 epub ahead of print

39. From Leggett C et al. Am J Gastroenterol 2014;109:298.
Volumetric Laser Endomicrosopy: Detection of Subsquamous Cancer After Ablation Ex Vivo
From Leggett C et al. Am J Gastroenterol 2014;109:298.

40. AGA Technical Review: Advanced Imaging Techniques & Dysplasia Detection
Unclear that any advanced imaging techniques provide additional clinically important information beyond that available by high resolution white light endoscopy
From Spechler SJ et al. Gastroenterology 2011;140:e18-52. 40

41. Learning Objectives HGD-a historical perspective
Current data on optimal imaging for detection of early neoplasia
Current data on therapy of early neoplasia

42. From Bennett C et al. Gastroenterology 2012;143:336-46.
BADCAT International Consensus For Management of Early Stage Adenocarcinoma
Endoscopic therapy preferred to surveillance of most patients with HGD
EMR of mucosal lesions followed by ablation of remaining at risk mucosa
Endoscopic therapy preferred to surgery of most patients with HGD
Low risk of lymph node metastases
Lower morbidity
Higher recurrence rate
Surgery remains an option if fails
From Bennett C et al. Gastroenterology 2012;143:

43. EMR Changes Diagnosis in HGD & Early Adenocarcinoma
From Moss A et al. Am J Gastroenterol 2010;105:

44. EMR Changes Diagnosis in HGD & Early Adenocarcinoma
From Moss A et al. Am J Gastroenterol 2010;105:

45. Safety of EMR in Barrett’s Esophagus at Mayo Clinic
N=681 patients undergoing 2,513 resections
Cap technique-77%
Band snare-18%
Complications
Perforation-0%
Bleeding-1.2%
Strictures-1%
From Tomizawa Y et al. Am J Gastroenterol 2013;108:

46. Factors Associated With Recurrence After EMR of Early Barrett’s Cancer (HGD/IMC)
From Pech O et al. Gut 2008;57:

47. Radiofrequency Ablation

48. From Shaheen NJ et al. NEJM 2009;360:2277-88.
Radiofrequency Ablation of Barrett’s Esophagus With High Grade Dysplasia
From Shaheen NJ et al. NEJM 2009;360: 48

49. From Shaheen N et al. NEJM 2009; 2009;360:2277-88.
RFA of Barrett’s Esophagus With High Grade Dysplasia: Histological Progression
From Shaheen N et al. NEJM 2009; 2009;360: 49

50. From Van Vilsteren FG et al. Gut 2011;60:765-73.
RCT Of Stepwise Radical EMR Vs. EMR + RFA for HGD/Early Adenoca in Barrett’s < 5 cm
SRER (N=25)
EMR + RFA (N=22)
CR HGD/Ca
100%
96%
CR IM
92%
Sessions to CR
2 [IQR 1-3]
3 [IQR 3-4]
Total sessions
6 [IQR 3-9]*
Acute complications
24%
14%
Strictures
88%*
From Van Vilsteren FG et al. Gut 2011;60:

51. AIM Dysplasia Trial: Durability of Epithelial Reversion Including Retreatment
All patients
LGD
HGD
CE-D
CE-IM
Year 2
101/106
(95%)
99/106 (93%)
51/52 (98%)
50/54 (93%)
48/54 (89%)
Year 3
55/56 (98%)
51/56 (91%)
4/14 with recurrent IM-subsquamous
5/119 (4%) treated patients had disease progression
From Shaheen N et al. Gastroenterology 2011;141:460-8.

52. Sustained Remission of HGD/IMC After EMR + RFA
5 yr dysplasia/IM free survival 90%
3 recurrent neoplasia
All seen on HDWLE
All managed endoscopically
Buried IM in 0.08% biopsies
From Phoa KN et al. Gastroenterology 2013;145:

53. Effectiveness of RFA: BETERNET Study
N=448 patients underwent RFA
Mean length cm
71% HGD/Ca
Median time to CRIM-22 mos
CRIM = no IM on 2 consecutive endoscopies in esophagus & GEJ
Only 56% achieved CRIM by 24 mos
71% with CRIM by 36 mos
From Gupta M et al. Gastroenterology 2013;145:79-86.

54. Predictors of CRIM: BETERNET Study
From Gupta M et al. Gastroenterology 2013;145:79-86.

55. Recurrence of IM After RFA: BETERNET Study
CRIM recurrence rate
Yr 1-20%
Yr 2-33%
22% of recurrences dysplastic
GEJ most common site of recurrent dysplasia
No factors predicted recurrence
From Gupta M et al. Gastroenterology 2013;145:79-86.

56. Efficacy of RFA For Eradication of IM & Dysplasia
From Kaimakliotis PZ et al. Current Opinion in Gastroenterology 2014 (In press)

57. RFA Durability
From Kaimakliotis PZ et al. Current Opinion in Gastroenterology 2014 (In press)

58. Safety of RFA: Systematic Review
Complication
% (95%CI)
Stricture
5% (3-7%)
Pain
3% (1-6%)
Bleeding
1% (1-2%)
From Orman ES et al. Clin Gastroenterol Hepatol 2013;11:

59. Subsquamous Cancer After RFA
(A) Low and (B) high power showing subsquamous adenocarcinoma (case 2).
From Titi M et al. Gastroenterology 2012;143:564-6.

60. Esophagectomy After Failed Endoscopic Therapy of HGD/IMC
Case series of N=15
Prior endoscopic therapy for HGD or IMC
EMR +/- RFA
Median EMR sessions-1 (0-3)
Median RFA session-3 (0-6)
Median attempt at endotherapy-13 mos
From Hunt BM et al. Dis Esoph 2014;27:362-7.

61. Pathology After Esophagectomy For Failed Endoscopic Therapy of HGD/IMC
From Hunt BM et al. Dis Esoph 2014;27:362-7.

62. Follow Up Protocol After Ablation
No standards exist
Seattle protocol of neosquamous segment + cardia
HGD/IMC
Q 3 mos X 1 yr
Q 6 mos X 1 yr
Annual
LGD

63. From Bennett C et al. Gastroenterology 2012;143:336-46.
BADCAT International Consensus For Management of Early Stage Adenocarcinoma
From Bennett C et al. Gastroenterology 2012;143:

64. Cryotherapy of Barrett’s Esophagus
From Johnston MH et al. Gastrointest Endosc 2005;62:842-8.

65. From Shaheen N et al. Gastrointest Endosc 2010 71:680-5.
Liquid Nitrogen Cryotherapy in 60 Barrett’s Esophagus HGD Patients: A Cohort Study
From Shaheen N et al. Gastrointest Endosc :680-5.

66. CryoBalloon Ablation
From Friedland S et al. Gastrointest Endosc 2011;74:182-8.

67. Summary
Careful high definition white light endoscopy remains cornerstone of detection of dysplasia
Adequate time
Attention to 12-6 o’clock hemisphere
Retroflexion into distal segment + cardia

68. Summary Narrow band imaging
Increases inspection time
Retrains white light eye
New generation equipment role to be determined
Other enhanced imaging techniques of uncertain clinical value

69. Summary EMR critical to adequate staging of dysplasia RFA
Effective in most but not all patients
Safe but not complication free
Durability promising but not perfect

70. Summary RFA is a commitment not a cure* No procedure is perfect*
*From Bergman JJ & Corley DA. Gastroenterology 2012;143:524-6.

72. Summary RFA is safe but not complication free
Any complication 4-7%
Stricture 5-9%
RFA is effective in most but not all patients…….it will sometimes fail!
The durability of RFA is unclear
Retreatment will be necessary in many
Ongoing reflux milieu remains
Meticulous ongoing surveillance is essential

73. UK RFA Registry: Complete Eradication at 12 Months
From Haidry RJ et al. Gastroenterology 2013;145:87-95.

74. UK RFA Study: Durability of RFA For Focal & 360 Ablation
From Haidry RJ et al. Gastroenterology 2013;145:87-95.

75. UK RFA Study: BE Length Vs. Success
From Haidry RJ et al. Gastroenterology 2013;145:87-95.

76. Cancer Risk After RFA For Barrett’s Neoplasia
From Haidry RJ et al. Gastroenterology 2013;145:87-95.

78. Cancer Free Survival After Endoscopic Therapy of T1a Mucosal Adenocarcinoma
From Prasad G et al Gastroenterology 2009;137:

79. Surgery For Intramucosal Carcinoma: Cleveland Clinic Experience
N=164 esophagectomy for IMC
Lymph node metastases-1 (0.6%)
Operative mortality
In hospital-3 (1.8%)
30 days-2 (1.2%)
6 mos-7 (4%)
95% survival at 6 mos
From Li Z et al. J Thorac Cardiovasc Surg 2013;145:

80. Surgery For Intramucosal Carcinoma: Cleveland Clinic Experience
Complications in 75 (46%)
Wound 22%
Cardiovascular 21%
Respiratory 20%
From Li Z et al. J Thorac Cardiovasc Surg 2013;145:

81. Survival After Endoscopic Therapy of T1a Mucosal Adenocarcinoma
From Prasad G et al Gastroenterology 2009;137:

82. From Prasad GA et al. Gastroenterology 2007;132:1226-33.
Long Term Cancer Free Survival Endoscopic Vs. Surgical Treatment of HGD
From Prasad GA et al. Gastroenterology 2007;132:

83. Methods of Detection of Dysplastic Barrett’s Esophagus
22 still images compared by expert & non-expert endoscopists
High resolution WLE
Indigo carmine chromoendoscopy
Acetic acid chromoendoscopy
NBI
From Curvers W et al. Gastroenterology 2008;134:670-9. 83

84. Components of Ideal Imaging Technology in Barrett’s Esophagus
Enhance detection of dysplasia/early cancer
Target biopsies to areas of interest
Decrease number of biopsies 84

85. Improving Recognition of Barrett’s Neoplasia
Cancer risk for a given patient low-0.5%/yr
To detect 1 cancer will need to survey 200 average risk patients!
Many studies done with high risk patients or with still images 85

86. From Gupta N et al. Gastrointest Endosc 2012;76:531-8.
Longer Barrett’s Inspection Time Associated With Higher Detection Rate of HGD/Ca
Inspection Time < 5 Minutes
Inspection Time > 5 Minutes
P-value
Visible lesion
32.4%
82.9%
<0.001
Final diagnosis HGD/Ca
22.5%
53.7%
0.002
# of visible lesions
0.51
1.95
<0.0001
# of areas with HGD/Ca
2.29
0.004
Mean BE length (cm)
3.3
4.4
0.11
From Gupta N et al. Gastrointest Endosc 2012;76:531-8. 86

87. Longer Inspection Time Increases Detection of HGD/Ca
From Gupta N et al. Gastrointest Endosc 2012;76:531-8.

88. Enhancements To Endoscopic Imaging
HD/High resolution white light
Chromoendoscopy
Magnification endoscopy
Narrow band imaging
Photodynamic diagnosis
Optical coherence tomography
Low coherence interferometry
Spectroscopy
Autofluorescence endoscopy
Confocal endomicroscopy
Molecular imaging 88

89. From Bennett C et al. Gastroenterology 2012;143:336-46.
BADCAT International Consensus For Management of Early Stage Adenocarcinoma
High resolution endoscope > 850,000 pixels should be used for surveillance
Targeted biopsies of suspicious lesions
4 quadrant biopsies at 1-2 cm intervals
From Bennett C et al. Gastroenterology 2012;143:

90. ASGE Barrett’s Esophagus PIVI on Barrett’s Esophagus Imaging
Thresholds for adoption for new imaging technology with targeted biopsies
Sensitivity > 90%
NPV > 98%
Specificity > 80%
From Sharma P et al. Gastrointest Endos 2012;76:252-4.

91. Barrett’s Imaging 2014 Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

92. Barrett’s Imaging 2014 Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

93. Narrow Band Imaging: Potential Advantages
Contrast enhancement without need for staining agents
User friendly
Wide area view + magnification capabilities
More suitable for detailed inspection than wide area view
Commercially available

94. Tandem NBI + HD WLE Vs. Standard WLE For Dysplasia Detection in Barrett’s Esophagus94

95. Tandem NBI + HD WLE Vs. Standard WLE For Dysplasia Detection in Barrett’s Esophagus
P-value
Dysplasia
37 (57%)
28 (43%)
Higher grade of histology
12 (18%)
<.001
Mean biopsy number
3/5 cases of HGD detected by NBI detected by HD WLE
From Wolfsen HC et al. Gastroenterology 2008;135:24-31. 95

96. Barrett’s Esophagus Imaging: The AMC Perspective
“Imaging attitude”
Spend time inspecting for subtle changes
Do not rush to biopsy
“Imaging eye”
Recognize subtle changes
From Curvers WL & Bergman JJ. Gastroenterology 2008;135: 96

97. Endomicroscopy of Barrett’s Esophagus
Intestinal metaplasia
Neoplasia
From Kiesslich R et al. Gastrointest Endosc 2007;66:150-3. 97

98. Molecular Imaging
Imaging of disease specific functional or morphologic alterations based on molecular fingerprint of single cells or whole tissue
Requires:
Knowledge of biomarkers of carcinogenesis
Appropriate imaging devices to detect markers

99. Molecular Probe Classes
From Goetz M et al. Gastroenterology 2010;138:

100. From Kang W et al. Optics Express 2010;18:17364-72.
Balloon Based OCT
High resolution cross sectional images from backscattered infrared light
Visualization of tissue architecture
Depth of 1-3 mm
Resolution of um
From Kang W et al. Optics Express 2010;18:

101. From Suter MJ et al. Gastrointest Endosc 2008;68:745-53.
Balloon Based OCT IM
HGD
From Suter MJ et al. Gastrointest Endosc 2008;68:

102. Tethered Capsule Endomicroscopy for Barrett’s Esophagus
Normal esophagus
Normal stomach
Barrett’s esophagus
From Gora MJ et al. Nature Medicine 2013;19:238–240.

103. Volumetric Laser Endomicroscopy: Laser Markings
From Suter MJ et al. Gastrointest Endosc 2014 epub ahead of print

104. Surveillance of Barrett’s Esophagus: AGA Medical Position Paper
White light endoscopy
Careful inspection remains standard of care
Strong recommendation
Moderate quality evidence
From Spechler SJ et al. Gastroenterology 2011;140:
104

105. Surveillance of Barrett’s Esophagus: AGA Medical Position Paper
4 quadrant biopsies Q2 cm if no dysplasia
Strong recommendation
Moderate quality evidence
Recommend against requiring:
Chromoendoscopy
Electronic chromoendoscopy
Advanced imaging techniques i.e. confocal endomicroscopy
From Spechler SJ et al. Gastroenterology 2011;140:
105

106. AGA Technical Review: Endoscopic Image Enhancement & Dysplasia Detection
Unclear that any image enhancing techniques add important information beyond that in careful high resolution white light inspection
From Spechler SJ et al. Gastroenterology 2011;140:e18-52.
106

108. From Bennett C et al. Gastroenterology 2012;143:336-46.
BADCAT International Consensus For Management of Early Stage Adenocarcinoma
Visible lumps or nodules with HGD suggest a more advanced lesion
EMR of lesions upgrades pathology in 40%
From Bennett C et al. Gastroenterology 2012;143:

109. Endoscopic Therapy of Barrett’s Esophagus: AGA Medical Position Paper
Eradication therapy recommended for confirmed HGD-not surveillance
Strong recommendation
Moderate quality evidence
EMR recommended for patients with dysplasia & visible lesion
From Spechler SJ et al. Gastroenterology 2011;140:

110. From Bennett C et al. Gastroenterology 2012;143:336-46.
BADCAT International Consensus For Management of Early Stage Adenocarcinoma
Risk of progression from HGD to adenocarcinoma is 6-19%/year in absence of mucosal abnormality
In the absence of visible lesions prevalence of unsuspected adenocarcinoma at surgery now 3%
From Bennett C et al. Gastroenterology 2012;143:

111. EMR of Early Cancer: Long-Term Wiesbaden Results of 100 Patients
The 2 deaths unrelated to cancer
From Ell C et al. Gastrointest Endosc 2007;65:3-10.
111

112. Paris Classification of Superficial Neoplastic Lesions
From Wani S et al. Clin Gastroenterol Hepatol 2012;10:

113. EMR Changes Biopsy Diagnosis
SMC
Vascular invasion
HGD
From Peters F et al. Gastrointest Endosc 2008;67:604-9.

114. Endoscopic Mucosal Resection
Images courtesy of Christian Ell

115. EMR Changes Biopsy Diagnosis
N=293 focal EMR
EMR changed diagnosis in 49% of lesions
Grade
Depth
Vascular invasion
EMR led to change in treatment plan in 30%
From Peters F et al. Gastrointest Endosc 2008;67:604-9.

116. Wiesbaden Low Risk Lesions Criteria
Diameter < 20 mm
Macroscopic type
I (polypoid)
IIa (flat & slightly elevated)
IIb (flat & level)
IIc (flat & depressed < 10 mm)
Differentiation: Well or moderate
Depth to mucosa
No invasion of lymph vessels or veins
From Ell C et al. Gastrointest Endosc 2007;65:3-10.
116

117. The Patient Understanding of ablation risks & benefits
Long term commitment
Continued surveillance
Touch up therapy
Failure rate
Lack of diagnostic certainty
Treatment vs. cure
117

118. RFA Baseline Quality Measures
High resolution endoscopy
Avoid surveillance if ongoing erosive esophagitis
Adequate inspection time
4 quadrant surveillance biopsies
2 cm if nondysplastic
1 cm if dysplastic
EMR capabilities
Expert pathology review of dysplasia

119. Safety of RFA: UNC Experience
*Hospitalizations due to bleeding
From Kim HP et al. Gastrointest Endosc 2012;76:733-9.

120. AIM Dysplasia Trial: Durability of Dysplasia Eradication Without Retreatment
Dysplasia free without retreatment:
HGD > 85%
LGD > 90%
From Shaheen N et al. Gastroenterology 2011;141:460-8.

121. AIM Dysplasia Trial: Durability IM Without Retreatment
IM remained eradicated in > 75% without retreatment
From Shaheen N et al. Gastroenterology 2011;141:460-8.

122. Durability of RFA for Dysplastic BE: Recurrence of Dysplasia
85% dysplasia median FU 393 days
No dysplasia recurrence for LGD
Dysplasia recurrence rate for HGD/Ca-4.2%/yr
Median time to recurrence-173 days
From Orman ES et al. Am J Gastroenterol 2013;108:

123. Durability of RFA for Dysplastic BE: Recurrence of Dysplasia
85% dysplasia median FU 393 days
No dysplasia recurrence for LGD
Dysplasia recurrence rate for HGD/Ca-4.2%/yr
From Orman ES et al. Am J Gastroenterol 2013;108:

124. Durability of RFA for Dysplastic BE: Recurrence of IM
80% remained free of IM
IM recurrence rate:
LGD-2.4%/yr
HGD-5.5%/yr
IMC-9.4%/yr
From Orman ES et al. Am J Gastroenterol 2013;108:

125. Durability of RFA for Dysplastic BE: Recurrence of IM
80% remained free of IM
IM recurrence rate:
LGD-2.4%/yr
HGD-5.5%/yr
IMC-9.4%/yr
From Orman ES et al. Am J Gastroenterol 2013;108:

126. Subsquamous HGD & Cancer After Successful Ablation
Case series of 3 patients with complete ablation after RFA for HGD
Subsquamous neoplasia in all 3
HGD
IMC
SMC
From Titi M et al. Gastroenterology 2012;143:564-6.

127. Persistent IM With Poor Reflux Control
N=37 underwent ablation after MII/pH on bid PPI
15/37 (41%) with incomplete response
Persistent IM after 2 ablations
35/37 with eventual complete response
Incomplete responders
Increased length (6 vs. 4 cm)
Increased hiatal hernia (3 vs.2.3 cm)
From Krishnan K et al. Gastroenterology 2012;143:

128. Persistent IM With Poor Reflux Control
From Krishnan K et al. Gastroenterology 2012;143:

129. Altered Barrier Function of Neosquamous Epithelium After RFA
From Jovov B et al. Am J Gastroenterol 2013;108:

130. Altered Barrier Function of Neosquamous Epithelium After RFA
Transepithelial resistance
Fluroscein Flux
From Jovov B et al. Am J Gastroenterol 2013;108:

131. Buried Glands Pre & Post RFA Detected by 3D OCT At GEJ
From Zhou C et al. Gastrointest Endsosc 2012;76:32-40.

132. Predictive Factors For Poor Response to Circumferential RFA
From Van Vilsteren F et al. Endoscopy 2013;45:

133. Predictive Factors For Poor Response to Circumferential RFA
From Van Vilsteren F et al. Endoscopy 2013;45:

134. Buried IM Post RFA Detected by 3D OCT At GEJ
From Zhou C et al. Gastrointest Endsosc 2012;76:32-40.

135. UK HALO Registry: Predictors of Response
Predictor of failure:
Length per 1 cm: OR [ ]
Predictor of success:
Each extra RFA session: OR [ ]
From Haidry RJ et al. DDW 2013

136. Remaining Concerns Buried IM/neoplasia Detection of buried IM
Follow up after ablation
Prediction of response
How to handle treatment failures

137. Grade of Dysplasia & Cancer Risk
Cancer Incidence
Cancer Risk IM
%/yr
Low
LGD
0.4-13%/yr
Intermediate
HGD
6-20%/yr
High
137

138. Dysplasia Detection: The Challenge
Many studies done with high risk patients or with still images
Biopsy protocols typically not followed especially for longer segments
138

139. Barrett’s Imaging 2014 Detection Essentials
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.

140. Recurrence of IM After RFA: BETERNET Study
CRIM recurrence rate
Yr 1-20%
Yr 2-33%
22% of recurrences dysplastic
GEJ most common site of recurrent dysplasia
No factors predicted recurrence
From Gupta M et al. Gastroenterology 2013 [Epub ahead of print]

141. RFA Complications
From Kaimakliotis PZ et al. Current Opinion in Gastroenterology 2014 (In press)

142. Subsquamous HGD & Cancer After Successful Ablation
Case series of 3 patients with complete ablation after RFA for HGD
Subsquamous neoplasia in all 3
HGD
IMC
SMC
Detection:
Surveillance biopsies of normal neosqaumous-2
Mucosal nodularity in 1/3
From Titi M et al. Gastroenterology 2012;143:564-6.

143. Patients With Invasive Ca Or + Lymph Nodes
From Hunt BM et al. Dis Esoph 2014;27:362-7.

144. Esophagectomy After Failed Endoscopic Therapy of HGD/IMC
Endoscopic therapy stopped:
Progression of disease
Failure to clear disease
Recurrence of disease after initial clearance
From Hunt BM et al. Dis Esoph 2014;27:362-7.

145. Endoscopic Therapy of Barrett’s Esophagus: AGA Medical Position Paper
Current literature on cryotherapy inadequate to recommend for LGD or HGD
From Spechler SJ et al. Gastroenterology 2011;140:

146. Barrett’s Imaging 2014 Chromoendoscopy
Options
Methylene blue
Indigo carmine
Acetic acid
Problems
Cumbersome
Questionable enhanced detection of early neoplasia
From Boerwinkel DF et al. Gastroenterology 2014;146:622-9.