Advance in Endoscopic Submucosal Dissection (ESD)

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.

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

21. Traction for ESD

23. Traction for ESD

25. Traction for ESD

27. Traction for ESD

29. Traction for ESD

30. 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

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;79:756-64.

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 2012-13 • 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

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