Update in Endoscopic Therapy for Upper GI Malignancies

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