1. Esophageal ESD
National Cancer Center Hospital, Tokyo
Endoscopy Division
Ichiro Oda, MD

2. Agenda
 Introduction
 Indication of Endoscopic resection for esophageal SCC
 ESD for esophageal SCC

3. Incidence and Mortality
Esophageal cancer
 It is the eighth most common cancer
worldwide, accounting for 462,000 new cases in
2002.
 It is the sixth most common cause of cancer
related death (386,000 deaths).
 Squamous cell carcinoma (SCC) is the most
common histological type worldwide.
Japan
Adenocarcinoma 1-2%
SCC 92-93%
Others 5-6%
Muto M, et al. J Clin Oncol 2010;28:1566-72.

4. Risk Factors for SCC in Esophagus
 Alcohol
 Smoking
 Male
 over 50ys
 History of Esophageal Cancer
 History of Head and Neck Cancer
 Family history
 Achalasia
Casteｌｌsague X, et al , Cancer 82:657-664,1999
Aggestrup S, et al. Chest 102:1013‐ 1016,1992
T. Yoshida , et al. The GI Forefront (Japanese Journal) vol3 (2) 118-122,2007

5. Risk Factors for SCC in Esophagus
 Prevalence of drinkers and smokers in Japanese
men is so high.
 35.7% of men drink every day
 43.3% are current smokers in 2004
 Aldehyde dehydrogenase-2 (ALDH2) genotype
determines an individual’s blood acetaldehyde
concentration.
 Acetaldehyde has been established as a carcinogen in
experimental animals and is also suspected of playing
a critical role in cancer development in humans.
Yokoyama T, et al. Cancer Epidemiol Biomarkers Prev 2008;17:2846-54.

6. Risk Factors for SCC in Esophagus
 Recent study shows that inactive ALDH2 is a very
strong risk factor for esophageal SCC in alcohol
drinkers.
 Alcohol flushing is a marker of inactive ALDH2.
Yokoyama T, et al. Cancer Epidemiol Biomarkers Prev 2008;17:2846-54.

7. Agenda
 Introduction
 Indication of Endoscopic resection for esophageal SCC
ESD for esophageal SCC

8. Indications for endosopic resection
 Depth of tumor invasion
 Mucosal defect (luminal circumference)

9. Relationship Between Depth of Invasion and Lymph Node
Metastasis in Superficial Esophageal Cancer
m1 m2 m3 sm1 sm2 sm3
EP
LPM
MM
SM
Frequency of Lymph Node Metastasis
0% 0% 10〜15% 40〜50%
Definite Indication
Relative Indication
Definite Non-indication

10. M2

11. SM2

12. Mucosal defect >3/4 luminal circumference
Require
balloon
dilatation
Mucosal defect
>3/4 luminal
circumference
develop stenosis

13. Stenosis
Stenosis +ve Stenosis -ve
n=11 n=54
< 1/2 2 40
Circumferental
> 1/2 4 13
extention
> 3/4 5 1 < 0.0001
Longitudinal diameter (mm) 45.0±15.9 31.5±13.6 0.0062
Circumferental diameter (mm) 37.2±8.6 26.8±9.7 0.0020
Ono S, Fujishiro M, et al. Gastroint Endosc 2009

14. Agenda
 Introduction
 Indication of Endoscopic resection for esophageal SCC
ESD for esophageal SCC

15. Endoscopic resection modalities
 Endoscopic mucosal resection (EMR)
 Strip biopsy
 EMR with cap
 EMR with ligating device
 EEMR tube
 etc
 Endoscopic submucosal dissection (ESD)

16. EMR
Strip Biopsy EMR with a cap-fitted
scope (EMRC)
Tada M, et al. Endoscopy 1993 Inoue H et al. Gastrointest Endosc. 1993
• Technically simple
• Low en-bloc resection rate
• Difficult to resect large lesions

17. EMRC
SCC, m1, , 1cm, ly0, v0, cut end(-)

18. Piecemeal resection of EMRC
• Difficult to en-bloc resect for large lesions

19. Disadvantage of piecemeal resection
Piecemeal resection
 is difficult to evaluate the
histological curability.
 has a risk of local
recurrence tumor.

20. Local recurrence after EMR
National cancer center East, Japan
Katada et al. GIE 2005;61:219-25
116 consecutive patients with a total of 165
squamous-cell carcinom
Retrospective study
Local recurrence: cancer was detected at the site
of the EMR scar
Median follow-up: 35 months (12-110 months)
Method of EMR: 157 strip biopsy, 8 EEMR tube
Local recurrence rate: 20% (33/165 lesions)

21. Predictors of local recurrence after EMR
~Univariate analysis~
No. Local rec (%) p Value
Tumor size <20 88 13 (14.8)
(mm) 0.07
≧20 77 20 (26.0)
Tumor location Upper 22 1 (4.5)
0.03
Middle+lower 143 32 (22.4)
Depth of invasion m1+m2 128 23 (18.0)
0.2
m3 37 10 (27.0)
No.resection en-bloc 38 1 (2.6)
<0.001
Piece meal 127 32 (25.2)
Multiple LVLs Without 78 13 (16.7)
<0.01
With 38 15 (39.5)
LVL: Lugol-voiding lesion Katada et al. GIE 2005;61:219-25

22. Predictors of local recurrence after EMR
~Multivariate logistic regression analysis~
Variables Odds ratio (95% CI) p Value
Tumor size (≧20mm vs. <20mm) 1.2 (0.5-2.8) 0.7
Tumor location (Middle+lower vs. Upper) 3.1 (0.4-26.2) 0.2
Depth of invasion (m3 vs. m1+m2) 1.5 (0.6-3.8) 0.3
No. resection (piecemeal vs. en-bloc) 8.4 (1.0-69.7) 0.01
Multiple LVLs (with vs. without) 3.1 (1.1-8.5) 0.03
Katada et al. GIE 2005;61:219-25

23. For reducing the local recurrence
 En-bloc resection seems to be the ideal for
reducing the local recurrence rate.
 However en-bloc resection is technically
difficult for larger lesions by conventional EMR.
ESD
(Endoscopic Submucosal Dissection)

24. ESD for early gastric cancer

25. ESD One-Piece Resection Rate
NCCH, 2000-2003
Upper (n=176) 97% (170)
Location Middle (n=431) 97% (418)
Lower (n=426) 98% (419)
≦ 20 (n=719) 98% (706)
Size, mm 21-30 (n=176) 97% (171)
>30 (n=138) 95% (131)
Ulcer + (n=243) 97% (236)
- (n=790) 98% (772)
Total (n=1,033) 98% (1,008)
Oda I, et al. Digestive Endoscopy 2005

26. ESD in the esophagus

27. ESD procedures
 Marking
 Injection
 Initial incision
 Mucosal incision
 Submucosal dissection

28. Marking Needle knife or Dual knife
anal
lesion
FORCED COAG; 20W
onal

29. Initial incision Needle knife or Dual knife
anal
lesion
onal
ENDO CUT; 80W, Effect 3

30. Mucosal incision IT knife 2 or Dual knife
anal
lesion
onal
ENDO CUT; 80W, Effect 3

31. Submucosal dissection IT knife 2 or Dual knife
anal
lesion
onal
ENDO CUT; 80W, Effect 3

32. Mucosal inicision IT knife 2 or Dual knife
anal
lesion
onal
ENDO CUT; 80W, Effect 3

33. Submucosal dissection IT knife 2 or Dual knife
anal
lesion
onal
ENDO CUT; 80W, Effect 3

34. ESD (Video)

35. Results of esophageal ESD
Ono S, et al. Gastroint Endosc 2009

36. Our series: EMR vs ESD for Lesions >2cm
EMR (88) ESD (44) P
One-piece resection 22 (25) 41 (93) 0.0001
Curative resection
(EP-LPM/ly-/v-/ce-) 13 (15) 15 (34) 0.01
Local recurrence 2 (2) 0 (0) NS
(); % NS; not significant

37. Perforation during Esophageal ESD

38. Subcutaneous & Mediastinal Emphysema
Induced by Perforation during Esophageal ESD
Air insufflation CO2 insufflation
Nonaka S, Oda I, et al, Surg Endosc 2010

39. Conclusions
 Noninvasive SCCs (m1) and intramucosal
invasive SCCs limited to the lamina propria
mucosae (m2) are definite indications for
endoscopic resection with curative intent.
 ESD has an advantage for archiving en-bloc
resection of large superficial esophageal SCC.