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Update in Endoscopic Therapy for Upper GI Malignancies
Jon P Walker, MD MSThe Ohio State University Medical Center
October 8th, 2010
Disclosure
• No financial disclosures to report• Will discuss off-label usage of a product.
Overview
• Endoscopic management of high grade dysplasia
• Endoscopic management of superficial malignancies
• Maintenance of Luminal Patency
Management of High Grade Dysplasia and Superficial Malignancy
• Surgical management (resection)– First consideration– Surgical candidate?
• Radiofrequency ablation– BARRX
• Photodynamic therapy• Endoscopic mucosal resection
– Nodule– Clearing of focal area of dysplasia
Management of High Grade Dysplasia and Superficial Malignancy
• Endoscopic therapy for superficial malignancy only!– No seriously…really superficial malignancy.– T1sm vs T1m very important– Mucosal involvement 5-8% LN involvement– Submucosal involvement 25-40% LN involvement
Endoscopic Mucosal Resection• Procedure
– Submucosal injection of saline/epinephrine/dye– Banding of the lesion; snare resection of the lesion
• Benefit: Both staging & resection– Planning of next step in treatment– Inaccuracy of EUS staging
• EUS 29% accurate for T1 tumors & 45% accurate for T2 tumors. (Zuccaro et al Am J Gastroenterol 2005)
• Recent studies showing accuracy 70-80%
• Risks– Bleeding, perforation, chest pain, stricture
• Follow up ablative therapy
Endoscopic Mucosal Resection
Endoscopic Mucosal Resection
Courtesy Todd Baron MD; Dave Project.org
Endoscopic Mucosal Resection
• 68y/o WM with recent EGD for epigastric pain.• EGD: Approx 1cm sessile lesion in setting of
short segment Barretts esophagus• Biopsy: high grade dysplasia with at least
intramucosal adenocarcinoma• Multiple medical problems. Considered poor
candidate for elective esophagectomy• EUS: T1m lesion; No lymphadenopathy
Endoscopic Mucosal Resection
Endoscopic Mucosal Resection
Endoscopic Mucosal Recection
• Follow up pathology: HGD w/ intramucosal carcinoma.
• No evidence of lymphovascular invasion• No evidence of submucosal invasion• Scheduled for subsequent Barrett’s ablation
Endoscopic Mucosal Resection
• 75y/o WM with recent EGD for anemia• Demonstrated 1.5cm distal esophageal lesion• Biopsy revealed high grade dysplasia w/ at
least intramucosal carcinoma• Poor surgical candidate for elective
esophagectomy• EUS: T1m lesion. No lymphadenopathy• EMR performed
Endoscopic Mucosal Resection
Endoscopic Mucosal Resection
Endoscopic Mucosal Resection
• Pathology: Well-differentiated adenocarcinoma with foci of submucosal invasion.
• Surgical options offered.
Endoscopic Mucosal Resection
Low Risk Group• N=35• Limited to mucosa• Less than 2cm lesion• 97% achieved CR @12mos
High Risk Group• N=29• Some invasion of
submucosa• Greater than 2cm lesion• Poorly differentiated• 59% achieved CR @12mos
64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR
Ell et al Gastroenterology 2000
vs
Endoscopic Mucosal Resection
Low Risk Group• N=35• Limited to mucosa• Less than 2cm lesion• 97% achieved CR @12mos
High Risk Group• N=29• Some invasion of
submucosa• Greater than 2cm lesion• Poorly differentiated• 59% achieved CR @12mos
64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR
Ell et al Gastroenterology 2000
vs
Endoscopic Mucosal Resection• Follow up to prior study• 100 patients• Low risk • 37 months follow up• 99% local remission at 12 months• 11% metachronous lesion• Approx 50% ablative therapy of non-dysplastic
Barretts
Ell et al Gastrointest Endoscop 2007
Ablative Therapies
• Laser• Argon Plasma Coagulation• Bipolar Electric Coagulation• Cryotherapy• Photodynamic Therapy• Radiofrequency Ablation
Ablative Therapies
• Laser• Argon Plasma Coagulation• Bipolar Electric Coagulation• Cryotherapy• Photodynamic Therapy• Radiofrequency Ablation
Photodynamic Therapy• Nonthermal ablative therapy• Administration of photosensitizing agent followed by
focal exposure of lesion to specific wavelength of light• Overholt et al Gastrointest Endoscopy 2003
– 105pts w/ HGD or Superficial Cancer– 78% eradication w/ HGD; 44% w/ cancer
• Overholt et al Gastrointest Endoscopy 2005– Similar findings w/ HGD
• Recurrence rate of up to 20%
Photodynamic TherapyLimitations
• Chest pain• Odynophagia• Cutaneous Photosensitivity• Stricture
– 27-40% stricture formation reported– Risk factors for stricture
• Prior EMR• Prior stricture• Number of applications• Usually treatable with dilations
Radiofrequency Ablation
• Topical focal application of radiofrequency ablation.
• Superficial uniform thermal therapy over wide-field
• Application by 360 or 90 degree delivery system
• Most frequent complication:chest pain
• Stricture rate: 0-8%
Radiofrequency AblationShaheen et alNEJM 2009• Evaluation of BARRX
therapy for eradication of Barretts dysplasia
• 127 patients randomized to RFA vs sham
• 81% vs 19% total eradication of HGD
• 1.2% vs 9.3% development of cancer
• 6% stricture
Ganz et alGastointest Endosc 2006• 22 patients w/ RFA for HGD• 73% complete eradication• No stricture or serious
adverse effects
Factors to Consider When Offering Endoscopic Therapy
• HGD only• Early Cancer within the mucosa only• Visible lesion less than 20mm• Well-differentiated to moderate• No lymph node involvement• No mets on CT• Patient desire to avoid surgery and compliance
with endoscopic follow-up
Sarah Rodriguez Esophageal Cancer 2009
Luminal Access
• Stent placement– Polyflex stent placement– Metal stents
• Uncovered stent placement• Partially covered stent placement• Fully covered stents
• Photodynamic therapy• Laser therapy – Argon Beam Coagulation• Brachytherapy
Stent Placement
Stent Placement
Stent Placement
• Issues to keep in mind– Chest pain– Migration– Palliation
• Will stent really improve current diet
– Tolerance for endoscopy– Reflux
Plastic Stent Placement
• Polyflex stent - silicone• Removability• Temporary• Easy placement• Bridge to surgery• Difficult to assemble• Bulky (poorly tolerated)• Migration
Polyflex Stent PlacementAdler et alGastrointestinal Endoscopy 2009
• 13 patient w/ Polyflex stent for neoadjuvant therapy
• No bleeding/perforation• Chest pain 12/13 patients• Dysphagia score from 3 to
1.1, 0.8,0.9,1.0 on weeks 1,2,3,4, respectively.
• Migration 6/13 patients at some point
Bowers et alAnnals of Surgical Oncology 2009
• 58 patients received stent, feeding tube or nothing
• Statistically better outcome in the stent group– Rate of interruption of chemo– Albumin level– Weight loss
• Migration rate: 24%
Esophageal StentPolyflex
Metal Stent Placement – Partially Covered
• Primarily esophageal• Permanent placement
– Epithelialization– Complication:better get them out early
• Primarily palliation– Luminal access– Fistula
• Decreased tumor ingrowth– Overgrowth or Undergrowth– Re-stent if needed
Metal Stent – Fully Covered
• New product• Minimal migration• Minimal epithelialization• Permanent• ?Removable• Easy to place• Bridging therapy
– Radiaton is the issue– Removability is the issue
Stent Placement
Esophageal Stent Full-covered
Esophageal StentsOther roles in esophageal malignancy
• Sticture patency maintenance– Post-radiation– Post-ablative therapy of high grade dysplasia– Post-operative anastomotic stricture
• Post-operative anastomotic leaks– Requires removable/temporary stent
• Fistulas– Tracheoesophageal fistula– Secondary to tumor or radiation therapy
• Determination of stent type– Condition duration– Patient prognosis– Luminal diameter– Location of defect
Metal Stent - Uncovered
• Primarily palliation• Distal stomach and
small bowel• Must consider biliary
access prior to placement
• Tumor ingrowth factor
Duodenal Stent
Distal Gastric/Proximal Duodenal Tumors
• Gastric outlet obstruction• Options
– Surgical Gastrojejunostomy (GJJ)– Endoscopic intraluminal stent placement
• Dutch SUSTENT Study Group– Long term multicenter trial comparing palliative measures for GOO
secondary to malignant obstruction• Stent placement for palliation better than GJJ in patients with
life expectancy less than 2 months• GJJ better if longer survival anticipated
– Jeurnink Gastrointestinal Endoscopy, 2010– Jeurnink Journal of Gastroenterology, 2010
Metal Wall Stent – UncoveredDistal Small Bowel
Distal Small Bowel Obstruction
Time is shortening. But every day that I challenge this cancer and survive is a victory for me.Ingrid Bergman