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walker Update in Endoscopic Therapy for Upper GI Malignancies

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									Update in Endoscopic Therapy
 for Upper GI Malignancies
          Jon P Walker, MD MS
 The 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
    64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR

    Low Risk Group                 High Risk Group
•    N=35                          • N=29
•    Limited to mucosa      vs     • Some invasion of
•    Less than 2cm lesion             submucosa
•    97% achieved CR @12mos        • Greater than 2cm lesion
                                   • Poorly differentiated
                                   • 59% achieved CR @12mos



                                    Ell et al Gastroenterology 2000
       Endoscopic Mucosal Resection
    64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR

    Low Risk Group                 High Risk Group
•    N=35                          • N=29
•    Limited to mucosa      vs     • Some invasion of
•    Less than 2cm lesion             submucosa
•    97% achieved CR @12mos        • Greater than 2cm lesion
                                   • Poorly differentiated
                                   • 59% achieved CR @12mos



                                    Ell et al Gastroenterology 2000
     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 Therapy
                 Limitations
•   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 Ablation
Shaheen et al                  Ganz et al
NEJM 2009                      Gastointest Endosc 2006
• Evaluation of BARRX          • 22 patients w/ RFA for HGD
  therapy for eradication of   • 73% complete eradication
  Barretts dysplasia           • No stricture or serious
• 127 patients randomized to     adverse effects
  RFA vs sham
• 81% vs 19% total
  eradication of HGD
• 1.2% vs 9.3% development
  of cancer
• 6% stricture
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 Placement
Adler et al                       Bowers et al
Gastrointestinal Endoscopy 2009   Annals of Surgical Oncology 2009
• 13 patient w/ Polyflex stent    • 58 patients received stent,
  for neoadjuvant therapy           feeding tube or nothing
• No bleeding/perforation         • Statistically better outcome
• Chest pain 12/13 patients         in the stent group
                                      – Rate of interruption of chemo
• Dysphagia score from 3 to
                                      – Albumin level
  1.1, 0.8,0.9,1.0 on weeks
                                      – Weight loss
  1,2,3,4, respectively.
• Migration 6/13 patients at      • Migration rate: 24%
  some point
Esophageal Stent
    Polyflex
     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 Stents
 Other 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 – Uncovered
     Distal 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

								
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