Endoscopic Mucosal Resection of Large Colon Polyps Chris Hamerski, MD Director of Luminal Oncology Interventional Endoscopy Services California Pacific Medical Center Assistant Professor of Medicine VA San Francisco

Giant: > 3 cm 176 polyps: 129 sessile, 47 pedunculated 24% bleeding rate: –58 procedural (immediately treated) –3 immediate post-procedure (endoscopically treated) –6 delayed (5 treated endoscopically, 1 managed conservatively) 16% (19/117) recurrence rate (18 successfully retreated) GIE 1996

“For technical reasons many large sessile polyps (>2 cm) cannot be completely or safely excised during colonoscopy, and the patient should be referred for primary surgical resection” Large polyps >2 cm usually contain villous tissue with high malignant potential, tend to recur after resection AJG 2000

GIE 2014

Concerns of EMR Coexistent malignancy –33-50% in early studies Safety Incomplete resection

Coexistent malignancy T1a T1b T2 T3

Dysplasia vs Cancer All adenomas are dysplastic –Low grade vs high grade –Carcinoma in situ, intramucosal carcinoma  outdated terms, should be designated HGD Cancer: invasion of dysplastic elements into the submucosa –Why this definition?  There are no lymphatics in the mucosa Lesions confined to mucosa have no chance of metastasis

Depth of Invasion Matters Misawa et al. Oncology Reports 2013

Risk of Lymph Node Metastasis Meta-analysis of 5 studies, 1213 patients –Sm1 (<1000 μm): 1.9% LNM –Sm2 or beyond: 14.6% Mou et al. Surg Endosc 2013

Polyp #1 Polyp #2Polyp #3

Polyp Assessment Paris classification Granular vs non-granular Kudo pit pattern

Paris Classification Laterally spreading tumor “Carpet lesion”

Granular vs Non-granular

IIa Granular IIa Non granular Is-IIa Granular IIa-IIc Non granular

Predictors of Submucosal Invasion Prospective study of polyps >2 cm –479 patients, 514 polyps, mean size: 35.6 mm SM invasion in 30/514 (6%) –IIa+c: 32% –Nongranular: 15% –Kudo V: 56% –IIa+c nongranular: 46% –IIa+c nongranular Kudo V: 56% –IIa granular: 1.4% Moss et al. Gastro 2011 Size does NOT predict SM invasion!!

Polyp #1 Polyp #2Polyp #3

EUS Staging

“Non-lifting sign” GIE /205 non-lifting: 83% invasive CA

NLS: Not Always Reliable False negatives: –10/26 polyps (38%) invading SM2 lifted (Kobayashi, Endoscopy 2007) False positives: –Prior resection attempt –Tattoo injection –Biopsies

Prior attempt causes NLS 199 polyps  30 with non-lifting sign (15%) –26 of these had undergone prior intervention 65%: partial resection 15%: tattoo into base 12%: biopsies only –4 without prior attempt: 50% had invasive cancer 24/26 resected (21 required APC for complete “resection”) –26% residual adenoma at f/u Diagnostic and Therapeutic Endoscopy 2013

14 studies, 1622 large polyps: mean residual adenoma rate: 25% GIE 2009

Risk Factors for Incomplete Resection – CARE Study 418 polyps (5-20 mm) resected by 11 endoscopists Incomplete resection rate (IRR): 10.1% Risk factors –SizeIRRRR mm13.4% mm23.3%4.0 –Morphology Flat12.4%1.8 –Histology SSA31%4.3 –Resection Piecemeal20.4%2.4 Pohl et al. Complete Adenoma Resection (CARE) Study, Gastro 2013

Risk Factors for Incomplete Resection in Large Polyps Australian study of 514 polyps >2 cm ResidualRR –Prior attempt25.5%2.9 –Size >4 cm41.0%3.0 –6 or pieces34.2%2.7 –High grade dys.27.1%1.6 –APC used39.5%2.3 Moss et al. Gastro 2011

21 polyps, mean size 26 mm Randomized to APC of edges vs no APC –APC: 1/10 recurrence –No APC: 7/11 recurrence GIE 2002

Why does prior attempt decrease EMR success?

Other Causes of Submucosal Fibrosis Retrospective study of 132 polyps >2 cm No manipulation (n=46) Biopsy only (n=44) Prior manipulation* (n=42) En bloc resection35%16%5% Residual on f/u8%41%54% *Prior manipulation includes tattoo, APC, snare “sampling” or resection attempt Kim et al. HPB 2011

Submucosal Injection EMR Saline Hyaluronic acid Hypertonic saline Hydroxypropyl methylcellulose Succinylated gelatin

SM Injection EMR Technique Soetikno et al. GIE 2003

Why Submucosal Injection? “Safety cushion” during resection –Reduced risk of perforation –Reduced risk of transmural thermal injury No clinical proof either are true!

n=6 swine model GIE 2002

Misguided SM Injection Injection into layer between circular and longitudinal muscle –Raises circular muscle –May result in snare capture of muscle Injection outside serosa –Local peritonitis/infection Longitudinal muscle Circular muscle Myenteric plexus Submucosa Serosa

SM injection through adenoma: risk factor for recurrence?

Needle tract tumor seeding after FNA of cholangiocarcinoma Heimbach et al. GIE 2015

Drawbacks of SM Injection May make snare capture of polyp more difficult –Increased SM tissue tension –Paradoxical flattening of polyp Narrows lumen, distorts native anatomy, displaces polyp Mucosal bleeding Repeat injections Cost, time

EUS of colon wall under water

60 patients with 62 large polyps (mean 34 mm) Median resection time 18 minutes 62/62 clinically successful –3 patients (5%) w/ delayed bleeding (no intervention required) Follow up colonoscopy in 54 patients (90%) –1 with residual adenoma (1.9%)

UEMR After Prior Resection Attempt 93 patients with prior resection attempt with scarring Technical success 96% –4 failed: all with 2 or more resection attempts and/or APC En bloc resection: 49% Clinical success on f/u: 97%

Appendiceal Orifice 27 attempted, 24 successful (89%) –4 referred to surgery (3 could not exclude extension into appendix, 1 invasive cancer) 2 post-polypectomy syndrome (7%) 10% residual adenoma on f/u

AO Resection Concerns Prior appendectomy? –Risk of appendicitis if intact Ability to exclude extension deep into orifice/appendix Increased perforation risk

UEMR Experience Author Technical success Median resection time (min) Mean F/U (months) Adverse events Residual at follow up Binmoeller (2012) 62/62 (100%) 1843 (5%)1/54 Wang (2013) 42/43 (98%)12.7NA1 (2.3%)NA Uedo (2013) 11/11 (100%) NA 0 Curcio (2015) 81/81 (100%) Sandhu (2015) 79/79 (100%) NA136/72 (8%) 6/48 (12.5%)

UEMR vs inject RCT Randomized, multicenter trial comparing standard injection EMR with underwater EMR Centers: –CPMC, UCLA, UC Irvine, Univ of Colorado, Univ of Virginia, Valduce Hospital (Italy) Outcomes: –Technical success, clinical success, resection time, complications

Underwater EMR Technical Steps Turn off air/CO2 Water immersion/exchange during insertion Careful inspection of polyp EUS (optional) APC marking of border (Forced APC, flow 0.8, 30W) Place snare around polyp – torque, crimp, suction as needed Cautery: –Standard: Dry cut 80W effect 5 –Scarred/giant/R colon: Autocut 80W effect 5 Piecemeal resection if not en bloc – avoid islands! Consider hot biopsy forceps (or coag forceps) cautery of vessels –Swift coag 60W effect 2

Management of Complications Acute bleeding: –Cautery (hot bx or coag forceps) –Clips –Epi injection Visible vessels –Cautery for vessels >1 mm Perforation –Clips, Ovesco, Apollo Overstitch Prophylactic clipping?

Hemostasis

Cardinal Sins Partial resection –“One chance to cure” Use of argon plasma coagulation Tattoo near the polyp –Question if tattoo really necessary? –If so, tattoo >5 cm away from polyp on opposite wall, limited volume (1 cc) Snare a large piece for pathology Multiple biopsies Referral to a surgeon prior to evaluation at an expert center

Extra Videos

Tattoo under polyp

Severe Scarring

Endoloop for Pedunculated Polyp

Take Home Points Size doesn’t matter. Paris classification, granular/non- granular, and Kudo pit pattern predict submucosal invasion All adenomas without submucosal invasion should be resected endoscopically Know your limitations – refer early if not able to resect on first try