1. Our Perspective on Endoscopic Resection for Colorectal Neoplasms 11-12 February, 2011, ROME Takahisa Matsuda, M.D, Ph.D National Cancer Center Hospital, Tokyo Endoscopy Division - Piecemeal EMR/ ESD - 3rd course on E NDOSCOPY IN GASTROINTESTINAL ONCOLOGY

3. National Cancer Center Hospital, Tokyo During Screening Colonoscopy…

4. How to Decide the “Therapeutic Plan”? - Endoscopic Treatment? Surgical Operation? EMR LN EMR Local resection without LN dissection Surgery Local resection with LN dissection Surgery LN

6. Importance of Estimation of SM Invasion Risk factors for lymph node metastasis in patients with submucosal cancer O We can predict only the “Depth of Invasion” X Lymphovascular invasion X P/D adenocarcinoma Vascular involvement (+) Submucosal deep invasion (+)

7. Pre-operative Endoscopic Depth Diagnosis Magnifying Colonoscopy Pit Pattern (Kudo’s) Classification Matsuda T, Fujii T, Saito Y, et al : Am J Gastroenterol, 2008 Endoscopic Treatment (EMR) Operation (OPE) No Treatment

8. & Demarcated area Irregular, distorted crypts 0.05% Crystal violet staining There is a strong relationship between this pattern and invasive cancer Demarcated area Irregular, distorted crypts Invasive pattern

9. Non-Invasive pattern Almost all the lesions of this pattern are intra-mucosal lesions (LGD or HGD)

10. LST-NG LST-NG IIa (< 5mm) LST-G IIa (5-10mm) LST (> 10mm) * LST: laterally spreading tumor; “Flat elevated lesion >10mm” Non-polypoid (Flat & Depressed) CRNs are Current Topic Clinically, it is very important “How to manage these LST lesions”. Flat Lesions

11. Relationship Between Lesion Size and Clinicopathological Findings － 1989 Flat early stage colorectal neoplasms, NCCH, 1998-2003 － Adenoma (LGD) M-SM Ca Size Pathology (HGD- Early Invasive ca) Location (C/A/T: D/S: R) 508:288:34 387:276:43 260:111:82 ( 61% :35%:4%) ( 55% :39%:6%) ( 57% :25%:18%) Total 1155:675:159 ( 58% :34%:8%) Matsuda T, Saito Y, et al : Dig Endoscopy, 2010 Flat Lesions < 5mm (830) 5-10mm (706) ≥ 10mm (453: 23% ) 828 (99.8%) 657 (93.1%) 203 (44.8%) 1688 (84.9%) 2 (0.2%) 49 (6.9%) 250 (55.2%) 301 (15.1%)

12. LST (Laterally spreading tumor) Saito Y, et al. Endoscopy 2001;33: 682-686. - Subclassification of LSTs - LST-granular (LST-G) uniform type LST-granular (LST-G) mixed type LST-nongranular (LST-NG) LST-G LST-NG

13. LST-NG 10mm - 20mm - 30mm - 12/246 (4.9%) 24/106 (22.6%) 11/33 (33.3%) Total 55/402 (13.7%) 0/115 (0%) 0/70 (0%) 1/31 (3.2%) 1/227 LST-G (uniform) LST-G (mixed) 4/72 (5.6%) 6/70 (8.6%) 9/65 (13.8%) 44/321 (0.4%) (13.7%) 40mm - 8/17 (47.0%) 0/13 (0%) 25/114 (21.9%) Relationship Between the Size of LSTs & the Rate of SM Invasion NCCH 1998-2006 Matsuda T, Saito Y, Conio M, et al : Gastroenterol Clin Biol, 2010

14. 16 (84%) 3 (16%) 19 Under the large nodule Under the depressed area 9 (27%) 23 (72%) 32 Multifocal Under the depressed area LST-G LST-NG The Area of SM Penetration Uraoka T, Saito Y, Matsuda T, et al. Gut. 2006. The extent of SM penetration of LST-G is easy to diagnose endoscopically. In contrast, the prediction of SM penetration of LST-NG is difficult.

15. EMR Strategy for LST LST-G En-bloc Resection 1 st; As large as possible LST-NG Endoscopic piecemeal resection (EPMR) is feasible for LST-granular type. In contrast, we should perform En-bloc resection for LST-non-granular type.

16. Treatment Strategy for Colorectal Neoplasms “ Based on the Lesion’s SIZE , MACROSCOPIC TYPE and Estimated DEPTH of INVASION ” SIZE DEPTH of Invasion 2cm 4cm SM ca 1000 µ m LAC (Laparoscopic Surgery) Open Surgery Conventional EMR Hot biopsy/ Polypectomy ESD EPMR M ca/ Adenoma Adv.ca (<5mm) (>5mm)

17. Rectum, 40mm, Is+IIa (LST-G: mixed type) Injected Solution: Glycerol , Snare: Snare master 25mm (OYMPUS), Scope: PCF240ZI (OLYMPUS) Procedure Time: 15 min EPMR (piecemeal EMR)

18. Hotta K, Saito Y, Matsuda T, et al. Int J Colorectal Dis. 2008 Local Recurrence Rate Size (mm) 10-19 20-29 30+ Total En-bloc Piecemeal Total 0.8% 0% 0% 0.7% (3/366) (0/65) (0/9) (3/440) 14.7% 21.7% 34.2% 23.5% (5/34) (13/60) (13/38) (31/132) 2.0% 10.4 % 27.7% 5.9% (8/400) (13/125) (13/47) (34/572)

19. A B C D E F G Recurrent Case: Rs, 50mm, Is+IIa (LST-G: mixed) A-C: Piecemeal EMR , W/D adenocarcinoma, pM (HGD) D-F: Follow-up CF (after 6M) -> Additional hot biopsy G: Follow-up CF (after 12M) -> No re-recurrence

20. Colorectal ESD Location: Ra, Size: 30mm, Macroscopic type: IIa+IIc

21. #10 -> O A ← Mapping and Panoramic View #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #12 #1

22. 800μm #5 SM Invasion Desmin

23. #4 SM Invasion

27. Endoscopic Mucosal Resection with Circumferential Incision

28. ■ ESD Using Several Knives under CO 2 Insufflations Ball tip B-knife IT knife CO2 insufflations COLORECTAL ESD PROCEDURE Zeon Medical Co. Olympus Co. Olympus Co. Colorectal ESD Olympus Co. Dual knife Water jet Scope Olympus Co.

30. CO 2 Insufflations System (OLYMPUS, UCR) CO2 Air

31. Virtual Colonoscopy Location: lower rectum (Rb) Size ： 60mm Macroscopic type ： 0-IIa (LST-G)

32. Conventional Endoscopy

33. Magnifying Endoscopy-NBI Capillary pattern: Type II (Sano’s classification)

34. Magnifying Chromoendoscopy Type IV/III L pit (Kudo’s classification) Non-invasive pattern

35. ESD Procedure

37. * All cases except one treated without surgery Saito Y, Uraoka T, Matsuda T et al. Gastrointest Endosc, 2010 Results of 500 Colorectal ESDs Macroscopic Type Is, IIa+IIc, IIc, SMT LST-G LST-NG Recurrent lesions 52 220 200 28 Location C: 35, Rt: 195, Lt: 130, R: 140 Size of Lesion (mean) 40  20mm (20-150mm) Procedure Time 90  73 (15-390) min. En-bloc Resection 88% Curative Resection 86% Complications Perforation Delayed Bleeding 13* (2.6%) 5 (1%) Histopathology Adenoma: 127, M-SM1: 315, SM2-: 55

38. National Cancer Center Hospital, Tokyo How often should we choose ESD? The Prevalence of Suitable Lesions for ESD

39. * LSTs: LST-G and LST-NG ** Definite indication: LST-NG lesion ≥20 mm § Relative indication: LST-G Mixed type [Is+IIa (LST-G)] ≥40 mm Matsuda T, Saito Y, Conio M, et al. Gastroenterol Clin Biol 2010 National Cancer Center Hospital, Tokyo, 1998-2006 The Prevalence of Suitable Lesions for ESD All Neoplastic Lesions ( n = 11,488) Early Colorectal Cancers ( n = 1,691) LSTs * 5.9% ( n = 674) 22.6% ( n = 382) Indication for ESD 2.3% ( n = 267) 12.1% ( n = 205) Definite indication ** for ESD 1.0% ( n = 115) 5.0% ( n = 85) Relative indication § for ESD 1.3% ( n = 152) 7.1% ( n = 120)

40. Endoscopic Depth Diagnosis is Important! All lesions are SM deep invasive cancer!

42. Thank you for your kind attention! Takahisa Matsuda M.D., Ph.D. National Cancer Center Hospital, Tokyo Endoscopy Division E-mail: tamatsud@ncc.go.jp