T1 colonic carcinoma – Is endoscopic resection sufficient? HC Yip JHGR 21/7/2012

Colonoscopy – sigmoid colon:

Questions 1. Can we remove this lesion completely with endoscope? 2. If pathology confirms invasive carcinoma, is endoscopic resection sufficient? Do we need formal surgical resection?

Further endoscopic assessment of lesion Morphological assessment  Paris classification 2002 Pedunculated Sessile Polypoid Elevated, 0-IIa Flat, 0-IIb Depressed, 0-IIc Ulcer Non-polypoid Excavated SM invasive carcinoma

Lateral spreading tumor Lateral growth of lesions at least 10mm diameter Subtypes:  Granular (Homogenous / nodular mixed)  Non-granular (Flat elevated / pseudo- depressed) Deeper SM invasion  LST-G: low (6.6%)  LST-NG: high (30%) Uraoka et al, Gut 2006

Chromoendoscopy – pit pattern analysis Kudo classification Endoscopic resection Surgery Kudo S. et al. Gastrointest Endosc 1996; 44: 8-14

NBI endoscopy – vascular pattern analysis Sano Y. Clin. Gastroenterol. 2009

Decision of treatment Endoscopic assessment Benign Intramucosal carcinoma Endoscopic resection: ESD / EMR Superficial SM invasive CA Endoscopic resection +/- additional surgery Deep SM invasive CA Surgery Endoscopic assessment – not 100% accurate

Endoscopic resection Endoscopic mucosal resection (EMR) Endoscopic submucosal dissection (ESD)

Endoscopic Mucosal Resection Injection assisted EMR  “Inject and cut” (A)  “Inject, lift and cut” (B) Ligation assisted EMR (D)

Limitation of EMR Difficult for en-bloc resection for lesions > 20mm in size Piecemeal resection of large lesions  Possible local recurrence due to residual lesion Published rate of recurrence up to 27.2%  Inability to obtain complete specimen for detail pathological assessment

Endoscopic Submucosal Dissection First developed by Japanese endoscopists Dr. Ono, Dr. Gotoda since 2001 on gastric lesion

Indication of ESD Tanaka et al, GIE 2007 Indications for colorectal ESD recommended by the Colorectal ESD Standardization Implementation Working Group

Short term outcomes of ESD – Systemic review 2841 ESD treated lesions R0 resection rate: 88% Bleeding rate: 2% Perforation rate: 4% ESD is safe and effective, at least in expert hands Repici A et al. Endoscopy 2012

Long term outcomes of ESD for colorectal neoplasms 146 adenomas, 164 carcinomas Local recurrence rate: 2.0% Median FU 38.7 months 3 year overall survival: 97.1% 5 year overall survival: 95.3% Niimi K, Fujishiro M, Endoscopy 2010

Potential pitfalls for ESD Technically demanding  Tortuous structures – difficulty in maintaining scope position  Narrow lumen – difficulty in controlling the knife  Thin colonic wall – Increase risk of perforation Overall risk of perforation higher than EMR or EPMR

Questions 1. Can we remove this lesion completely with endoscope? 2. If pathology confirms invasive carcinoma, is endoscopic resection adequate? Do we need formal surgical resection?

Risk of recurrence after endoscopic resection alone Adequacy of local tumor control  Margin positivity Adequacy of regional tumor control  Lymphatic involvement  Need for further lymphatic clearance, i.e. formal colonic resection?

Adequacy of local tumor control Resection margin involved or less than 1mm Relapse rate 21–33% Most authors believe a resection margin of ≥ 2 mm is safe and the probability of residual disease or recurrent carcinoma is low Cooper HS et al, Gastroenterology 1995 L Bujanda et al, W. J. Gastroenterology 2010

Predictive factor of recurrence after endoscopic resection Multiple studies addressing the issue since 1980s

Haggitt classification Haggitt el al, Gastroenterology 1985 Main focus on pedunculated polyp Risk of LN metastases  Level 1-3: <1%  Level 4: 12-25% No subdivision of level 4 lesion Nivatvongs S et al, Dis Colon Rectum 1991

Japanese classification SM1 SM2 SM3 Kudo et al, Endoscopy 1993 Sakatani A et al, Stomach and Intestine 1991

Risk of LNM in SM1-3 carcinoma Level of invasion LNM positive or LR positive Neither LNM or LR SM1093P< SM2892 SM3926 Kikuchi et al, Dis Colon Rectum 1995

Journal of Gastrointestinal Surgery 2012

Meta-analysis papers selected 42 different histopathological features identified Sean C et al, J Gastrointestinal Surg 2012

Lymphatic invasion Vascular invasion Tumor Budding Differentiation at invasive front Sean C et al, J Gastrointestinal Surg 2012

Depth of SM invasion Kitajima et al, J Gastroenterology 2004 Haggitt 2

Kitajima et al, J Gastroenterology 2004

Conclusion Endoscopic resection adequate if  SM invasion <1000μm for non-pedunculated polyp  SM invasion <3000μm for pedunculated polyp in the absence of lymphatic invasion Kitajima et al, J Gastroenterology 2004

K Nakadoi et al, J Gastroenterology and Hepatology 2011 Well / mod. differentiated/papillary, absence of vascular invasion, grade 1 tumor budding

Japanese guidelines Submucosal carcinomas can be followed up:  Tumor-negative horizontal margin  Differentiated adenocarcinoma  Submucosal invasion of < 1000 μm  Absence of vascular invasion  Grade 1 (low grade) tumor budding Otherwise additional surgery with lymph node dissection recommended Japanese Society for Cancer of the Colon and Rectum. 2010

NCCN guidelines 2012 Favorable histological features:  Grade 1 or 2, no angiolymphatic invasion, negative margin of resection Controversy regarding endoscopic management of sessile malignant polyp

T1 colonic carcinoma – Is endoscopic resection sufficient? No direct comparison between endoscopic resection alone with formal surgical resection in prospective manner  Practically difficult to conduct Endoscopic resection alone should be safe in selected subgroup of patients with favorable histology and limited SM invasion Endoscopic resection also useful in accurate staging to predict need for additional surgery in marginal cases Need good liaison with dedicated pathologist to accurately identify the histological features that predict risk of lymph node metastases

Questions? Thank you Acknowledgement: Dr. SF Hon, PWH