1. Advance in Endoscopic Submucosal Dissection (ESD)
Tommy Siu-man Yip
Department of Surgery
North District Hospital

2. Background
Endoscopic submucosal dissection (ESD) first described in 1988 to treat early gastric cancer; now expanded to locations throughout GI tract
Enables en bloc removal of larger and potentially deeper lesions with a curative intent than can be accomplished with EMR

3. Introduction of ESD procedures & devices

4. ESD steps during resection
1) Marking of perimeter of lesion with cautery
2) Injection of lifting agent into submucosa around the perimeter of lesion
3) Incision of mucosa and circumferential cut around lesion with an eletrosurgical knife
4) Injection of submucosa beneath lesion and dissection until complete resection of specimen
5) Hemostasis and vessel coagulation

5. Knives
A: ITKnife. B: ITKnife2. C: ITKnife nano. D: HookKnife. E: TTKnife. F: DualKnife G: FlexKnife. H: HybridKnife I type. I: HybridKnife T type

6. Hemostatic forceps
Coagrasper hemostatic forceps: Colonic forceps (left) and gastric forceps (right)

7. Cap
A transplant distal attachment uniformally applied to the tip of endoscope
Maintain visualization by keeping the resected flap of mucosa off the endoscope lens
Many caps feature drainage holes to allow egress of water and blood

8. Dyes Better characterize the surface of lesion
Clearer demarcation of borders
Better recognition of tissue planes during dissection by coloring the injectate for submucosal lifting
E.g Indigo carmine, methylene blue, Lugol’s iodine

9. Injection agents Drug Des Devel Ther. 2008; 2: 131–138.
Normal Saline (NS) Solution
Commonly used, but fluid cushion not long-lasting
Hypertonic Saline Solution
Hypertonic solution
Dextrose Water (DW)
Cheaper hypertonic solution, but likelihood of tissue damage in concentrations ≥20%
Hyaluronic Acid (HA)
Produces and maintains long-lasting fluid cushion, but high cost and limited availability
Fibrinogen Mixture (FM)
High viscosity and reasonable cost, but risk of virus transmission
Hydroxypropyl Methylcellulose (HPMC)
Produces long-lasting fluid cushion, inexpensive and readily available, but detailed toxicity testing necessary
Drug Des Devel Ther. 2008; 2: 131–138.

10. Endoscopes Influenced by a number of considerations
Auxillary water channel with flushing pump for water-jet effect to maintain visualization
Two instrument channels
Allow dual instrument use
Choice of channel for optimal working angle
Extra channel for suctioning
? High definition ? High magnification
? Multi-bending endoscope

11. Gas insufflation Carbon dioxide (CO2)
Absorbed across the intestines rapidly
Less prolonged luminal distension and less patient discomfort
Reduce the likelihood of tension pneumoperitoneum in case of perforation

12. Sedation
From moderate sedation (eg. midazolam), deep sedation (eg. propofol) or general anesthesia (GA)
GA for upper GI lesions
Potential for reflux and aspiration of secretion or blood
Moderate to deep sedation for colorectal ESD
Conscious sedation may facilitate changes in posture to use gravity as counter-traction

13. Complications of ESD
Bleeding
Perforation
Stricture

14. Bleeding Coagulation by ESD knife / hemostatic forceps
Delayed bleeding more common in gastric ESD (4.5%, up to 15.6%)
PPI +/- mucosal protective agent
Urgent surgery

15. Perforation 2.3-10% in oesophageal ESD 4.5% for gastric ESD
4.8% in colorectal ESD
Most amendable by clip closure
Gastric ESD
≤1cm defect: Primary clip closure
Larger defect: “omental patch” method
NG tube, TPN, antibiotics
Urgent surgery

16. Stricture 12-17% after oesophageal ESD
Highest risk if resection >75% circumference of oesophagus
Management
Prophylactic serial dilatation
Intralesional / topical steroid application
Prophylactic placement of SEMS

17. Advance in ESD Problems to be tackled Dissection
Traction
Ease of dissection of submucosal plane
Prevention of Complications

18. Advance in ESD Problems to be tackled Dissection
Traction
Ease of dissection of submucosal plane
Prevention of Complications

19. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

21. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

22. Enable release and regrasping of the lesion with the forceps if the traction is not sufficient

23. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

24. A – medical ring
B – Spring-assisted ESD, stainless steel ? Safety
Not applicable for lesions in pylorus or cardia, where space is limited

25. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

27. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

28. Thicker, heavier and more difficult to manipulate
Since grasping forceps or outer sheath move synchronously with the endoscope, making it difficult to control the traction direction and to cut the submucosal layer of larger lesions

29. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

30. Master and slave transluminal endoscopic robot (MASTER)
-forward viewing therapeutic endoscope with 2 operating channels
-The slave manipulators controlled the end effectors which included a monopolar diathermy “L” shaped hook and a grasper
-Complicated configuration and fixed instruments
Anubiscope – An endoscopic surgical platform with two working channels, for surgical instruments with articulated tip allowing four degrees of freedom
Master and slave transluminal endoscopic robot (MASTER)

31. Traction for ESD Methods for traction Traction Other advantages
Other disadvantages
Push
Control of direction
Control of Tension
Clip-with line ✘ ✔
Simple, easy
Percutaneous
Regrasping
Invasive
External forceps
Regrasping, no need of assistant to hold the forceps
Care of mucosal damage
Internal traction
Easy
Roll back of mucosa
Outer-route
Synchronous movement of forceps and scope, small distance between forceps and knife
Double-channel-scope
Synchronous movement of forceps and scope
Double-scope
Interference of scopes, double manpower
Robot-assisted
More complicated, difficult hemostasis for massive bleeding

32. Advance in ESD Problems to be tackled Dissection
Traction
Ease of dissection of submucosal plane
Prevention of Complications

33. Chemical dissection Mesna (sodium 2-mercaptoethanesulfonate)
Thiol compound
Dissolve disulfide bonds in connective tissue between anatomical planes
Evaluated in a double-blind, randomized, placebo-controlled trial of 101 patients undergoing gastric ESD
Submucosal dissection time was 18.6 minutes in the mesna group and 24.6 minutes in the placebo group (P=0.13)
However, multivariate regression analysis found use of mesna to be highly correlated with submucosal dissection time
Gastrointest Endosc 2014;79:

34. Cook Medical’s submucosal lifting gel
consist of a proprietary combination of known biocompatible components
safe and effective for a durable submucosal cushion without resulting in tissue damage in animal models

35. Advance in ESD Problems to be tackled Dissection
Traction
Ease of dissection of submucosal plane
Prevention of Complications

36. Endoscopic suturing of ESD defects
Overstitch endoscopic suturing device
Evaluated in a retrospective, single-center study of 12 patients (4 lesions in stomach, 8 lesions in colon; mean lesion size, 42.5 ± 14.8 mm) over a period of 8 months in
Technically feasible and fast (mean closure time, 10.0 ± 5.8 minutes per patient)
Patients discharged home on the same day after the procedure
No immediate or delayed adverse events observed

37. Endoscopic tissue shielding method
Polyglycolic acid (PGA) sheet & fibrin glue
Evaluated in a prospective, single-arm, pilot study in 10 patients with colorectal tumours in 2012 in a single tertiary centre in Japan
Mean tumor size 39.7 ± 15.2mm
Mean procedure time 18.7 ± 15.9 minutes
No procedure-related adverse events occurred
Upon colonoscopy 9 to 12 days after ESD, the PGA sheets were still fixed on the whole defect in 8 patients
Gastrointest Endosc 2014;79:151-5.

38. Conclusion
ESD is an effective treatment modality for premalignant and early-stage malignant lesions of stomach, oesophagus and colorectum
ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures
Additional refinements in the technique, instruments, devices and training would be necessary to further reduce the higher risk of complications and longer procedure times

39. END

40. General indications for ESD
Oesophageal ESD:
Endoscopic signs of early lesions or echo endoscopic examination confirming tumor limited to the mucosa or up to the superficial submucosa (Sm1)
Histological confirmation of squamous cell carcinoma or high grade intraepithelial neoplasia restricted to the mucosa (M1 and M2).
Lesions with M3 or Sm1 invasion without lymphatic and vascular involvement, no larger superficial size (< 2.5 mm)
No signs of LN metastases

41. Gastric ESD INTRAMUCOSAL CANCER SUBMUCOSAL CANCER
Differentiated adenocarcinoma- No lymphatic-vascular invasion
- Irrespective of tumor size without ulcer findings
- Tumor less than 3 cm in size with ulcer findings
- Superficial submucosal invasion, < 500 μm (Sm1)
- Differentiated adenocarcinoma
- No lymphatic-vascular invasion
- Tumor less than 3 cm in size
Undifferentiated adenocarcinoma- No lymphatic-vascular invasion
- No ulcer findings
- Tumor less than 2 cm in size

42. Colorectal ESD:
≥2cm lesions in which en bloc resection by snare EMR difficult
LST-NG type particularly pseudo-depressed lesion
Kudo V pit pattern
Cancer with submucosal infiltration
Mucosal lesion with fibrosis
Local residual early cancer after endoscopic resection
Sporadic localized tumours in chronic inflammation such as UC