Endoscopic Mucosal Resection (EMR): When, Where, and Charles J. Lightdale, MD Columbia University New York, NY Endoscopic Mucosal Resection (EMR) EMR developed for removal of sessile or flat neoplasms Flat lesions, benign or malignant Lesions confined to the superfical layers (mucosa and submucosa) of the GI tract ASGE Technology Committee. Gastrointest Endosc 2008;68:11-18 Endoscopic Mucosal Resection Developed in Japan for early gastric cancer: slightly raised, flat, or depressed lesions. Then extended to other flat GI lesions in the esophagus, duodenum, and colon Basic elements: marking, lifting, cutting Multiple techniques; still evolving Cuts through the submucosa 1
Human Esophagus Epithelium Lamina Propria Muscularis Mucosae Submucosa with esophageal glands G G EMR Muscularis Propria Early Esophageal Adenocarcinoma Risk of lymph node metastases: Tis (intraepithelial) 0 T1a (intramucosal) 2% T1b (submucosal) 25% Nigro, et al. J Thorac Cardiovasc Surg 1999;117:16-25 Stein, et al. Ann Surg 2000;232:733-742 Rice, et al. J Thorac Cardiovasc Surg 2001;122:1077-90 Hulscher, et al. N Engl J Med 2002;347:1662-1669 2
High-Grade Dysplasia Subgroups % Developing Cancer 100 90 80 70 60 50 40 30 20 13% 10 0 Flat Buttar et al. Gastroenterology 2001;120:1630-39 63% Nodular 3
EUS Staging of HGD and EC in BE T1m versus T1sm Accuracy = 41/48 patients = (85%) Overstaged 1 patient Understaged 6 patients Larghi et al. Gastrointest Endosc 2005;62:16-23 4
EMR Techniques INJECTION ASSISTED: Inject and snare (saline-assisted polypectomy) Inject, lift, and cut with snare (2-channel scope) CAP ASSISTED: inject, endoscopic suction, and snare LIGATION ASSISTED: Band and snare ENDOSCOPIC SUBMUCOSAL DISSECTION) (ESD) Inject and cut with free-hand knife for en-bloc resection 5
EMR in the Colon: Saline-Assisted Polypectomy Injection strategy: Flat polyps 1.5 cm Normal saline solution generally used If polyp not ulcerated, may inject into center Inject a few mm beyond polyp border Inject proximal edge of polyp to bring closer Snaring: deflate, retroflex prn, stiff, barbed, snares may help. Avoid snaring nl mucosa. Overhiser, Rex: Clin Gastroenterol Hepatol 2007;5:1076-1079 6
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EMR for HGD/Early Carcinoma in Barrett s Esophagus Outpatient procedure Major risk is bleeding, usually mild, < 5% Perforation is rare, < 1% Pathology specimen for evaluation of tumor depth and margins. Ell. Gastroenterology 2000;118:670-7. Nijhawan, Wang. Gastrointest Endosc 2000;52:328-32. ENDOSCOPIC MUCOSAL RESECTION m1 m2 m3 sm Epithelial layer Lamina propria Muscularis mucosae Submucosa 8
Good Risk Lesions For EMR in Early Esophageal Adenocarcinoma Non-ulcerated lesions, < 2.0 cm in diameter Invasion limited to mucosa No lympho-vascular invasion No poorly differentiated histology Ell et al. Gastrointest Endosc 2007;65:3-10. Non-Lifting Sign Lesion does not lift with injection, although the mucosa around the lesion lifts May be due to submucosal fibrosis or to submucosal tumor invasion Non-lifting sign is a containdication for EMR EMR should be stopped in the presence of a non-lifting sign EMR Fluids for Lifting Normal (0.9%) saline, may repeat 5-50 ml Dilute epinephrine, 1:100,000-1:200,000 Hypertonic dextrose( 20%) or saline(3%) Glycerol, albumin, autologous blood For ESD: Hyaluronic Acid, Hydroxypropyl methylcellulose (ophthalmic). For blue color add 1 drop of indigo carmine, methylene blue 9
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Results Cap MBM p N randomized 22 23 N resections 4 (2-8) 5 (3-9) ns Time (min) 50 29 0.04 Specimen size (mm) 21 18 0.01 Costs ( ) 322 240 0.01 Mild bleeding 12 9 ns Perforation 2 0 ns Pouw. Gastrointest Endosc 2008;67:AB75 Complete Removal of BE with EMR: Radical Sequential EMR Length of Barrett s segment is a major factor SSBE < 3 cm has best results Strictures >50% if >3.0 cm length or > ¾ circumference of lumen Longer segments: focal EMR + ablation Peters et al. Am J Gastroenterol 2006;101:1449-57. Larghi et al. Endoscopy 2007; 39:1086-91. Pouw et al. Endoscopy 2008;40:892-98. Prasad, et al. Gastroenterology 2007;132:1226-1233 11
100% RFA Complete Response Dysplasia (CR-D) HGD Cohort (n=43) 91% * 80% 80% * RFA Sham 60% * p<0.001 40% 20% 11% 12% 0% Intention to Treat Shaheen. N Engl J Med 2009;360:2277-2288 Per Protocol 100% Complete Response Intestinal Metaplasia (CR-IM) RFA in All Patients (n=101) 80% 77% * 83% * RFA Sham * p<0.001 60% 40% 20% 0% 0% 0% Intention to Treat Per Protocol Shaheen. N Engl J Med 2009;360:2277-2288 Prasad. Gastroenterology 2009;137:815-823 12
Randomized Trial: Complete Eradication of BE+HGD SR-EMR EMR+RFA (n = 25) (n = 22) Eradication 24(96%) 21(96%) Strictures 22(88%) 3(15%) p < 0.001 Mean sessions 6 3 p < 0.001 Van Vilsteren. Gastrointest Endosc 2009;69:AB133-134 Endoscopic Submucosal Dissection (ESD) for En Bloc Resection For larger lesions, usually > 2.0 cm Piecemeal resection for staging tumor depth (T), but not lateral resection margins. Lateral margin evaluation requires a single piece or en bloc resection Excellent results for ESD in initial studies from Japan in stomach, colon, esophagus. Lightdale. Endoscopy 2004;36:808-810. 13
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EMR vs. ESD Large gastric lesions > 2.0 cm: - EMR average time = 25.8 min - ESD average time = 84.0 min Perforation rates: - EMR = 0.3 0.5% - ESD = 4 10% Watanabe. Gastrointestinal Endosc 2006;63:776-782 EMR in T1a adenocarcinoma complicating Barrett s esophagus 100 patients, 144 resections No major complications; 11 mild bleeding Complete local remission in 99% after a maximum of 3 resections 11% recurred in 36.7 months, all successfully retreated with EMR Calculated 5-year survival = 98% Ell. Gastrointest Endosc 2007;65:3-10 15
Japanese Results: EMR/ESD in Upper GI Early Cancer Esophageal SCC T1a: 95% 5-year survival. Gastric cancer: 50% of gastric cancer (10,000 cases) are diagnosed at early stage. Complete resection in 73.9% with 1.4% bleeding and 0.5% perforation rate. ASGE Technology Committee. Gastrointest Endosc 2008;68:11-18 EMR in the Duodenum Ampullary adenomas: usually revoved using polypectomy technique: success 50-100%, recurrence 0-33%.; stent placement essential Malignant tumors need surgical resection. Non-ampullary adenomas: often flat and can be removed with EMR technique: complete removal in ~62%. ASGE Technology Committee. Gastrointest Endosc 2008;68:11-18 EMR/ESD in the Colon Widely used for large sessile lesions Often combined with APC ablation Recurrence rates 21-46% justifies close surveillance Treatment of superficial malignant polyps has been reported, but is controversial ESD for large colon lesions is technically difficult and controversial ASGE Technology Committee. Gastrointest Endosc 2008;68:11-18 16
Safety Bleeding in 5-10%, usually minor, sometimes delayed. Be prepared to treat bleeding with injection, multipolar coagulation, APC, clips Perforation in 0.3-0.5% Small perforations may be closed with clips EMR: Practical and Financial Considerations EMR/ESD: demanding, time consuming and not well reimbursed with no unique CPT code 43251/45385 (snare polypectomy EGD/colon Additional with 59 modifier: 43236/45381 (submucosal injection EGD/colon) 43258/45383 (adjunctive ablation EGD/colon) Alternative 22 modifier with documentation Consider negotiation with Medical Director of Payer 17
Future Research: EMR/ESD Improvements in instruments and techniques for better safety, efficacy, and efficiency Currently being tested: Combined saline Injection and cutting knife Balloon dissection of submucosa Optimal post-emr/esd surveillance intervals More comparative trials of EMR/ESD versus other ablative methods and surgery Conclusions: EMR A major advance in minimally invasive endoscopic therapy. Expands the potent combination of endoscopic surgery and surgical pathology for accurate diagnosis and staging. May be combined with ablation. Potentially curative for mucosal tumors and some submucosal tumors in the GI tract. 18