1. Advanced Endoscopic Therapy for Pancreatic Cancer Nathan Landesman, D.O. Flint Gastroenterology Associates February 28, 2015

2. Disclosures None

3. Emerging Role of Endoscopy in Pancreatic Cancer Therapeutic –Fiducial Placement –Fine Needle Injection (FNI) Palliative –Celiac Plexus Neurolysis (CPN) –Relief of Obstruction Gastroduodenal Biliary Shifting emphasis from ERCP-based approach to EUS-guided modalities

4. Therapeutic Endoscopic Interventions Fiducial Placement –Delineates extent of malignancy –Quantifies respiratory-associated tumor motion

5. Therapeutic Endoscopic Interventions Fiducial Placement Technique –19 or 22 gauge delivery system –Loaded retrograde after stylet withdrawal –Needle tip sealed with sterile bone wax –Lesion accessed and fiducial deployed by stylet or sterile water injection

6. Therapeutic Endoscopic Interventions Fiducial Placement Technique –Placement of at least 3 markers is preferred to “triangulate” the malignancy –> 4 markers to “box-in” the lesion is ideal

7. Therapeutic Endoscopic Interventions Fiducial Placement Safety/Efficacy –Prior studies reported technical failure with 19 gauge delivery system in the pancreatic head and/or altered anatomy –Newer trials report 88-97% success with only minor complications Equipment malfunction Pain (Pancreatitis) Bleeding/Infection Migration

8. Therapeutic Endoscopic Interventions Fiducial Placement Safety/Efficacy –< 7% migration rate is likely overstated Decompression of gastroduodenal obstruction Decompression of biliary obstruction

9. Therapeutic Endoscopic Interventions Fine Needle Injection (FNI) –Activated lymphocytes/Oncolytic viruses –Viral vectors (“Gene Therapy”) –Ink marking of small lesions

10. Gene Therapy Delivery Vector –Viral vs Non-viral Delivery Route –Intravascular vs Intratumoral Tumor Targeting –Gene Mutation/Transcriptional/Transductional Therapeutic Systems –Virotherapy/Suicide Genes/Correction

11. Celiac Plexus Neurolysis (CPN) Bupivacaine and absolute alcohol 74-88% effective –Head lesions may respond more favorably –Single/Multiple Sites +/- Fenestrated needles Side Effects: –Bleeding/Infection –Diarrhea –Pain –Hypotension –Paralysis

12. Gastroduodenal Obstruction in Pancreatic Cancer Uncovered metal prosthesis of varying lengths Avoid coverage of major papilla if possible –APC laser-assisted fenestration Surgical bypass

13. Biliary Obstruction in Pancreatic Cancer Role of pre-operative biliary decompression in resectable pancreatic head tumors –van der Gaag NEJM 1/14/10 reported “serious complication” rate of 39% and 74% in 2 arms from biliary intervention Pancreatitis Bleeding Biliary contamination Pancreatic fistula/leak –Post-op complication rates did not differ significantly.

14. Biliary Obstruction in Pancreatic Cancer Is plastic stenting for pancreatic cancer still relevant in 2015? GIE review (Wang) –Plastic stents 15-40x cheaper than metal –Historically there was believed to be a cost advantage in using plastic stents if: Diagnosis of malignancy was not established Patients expected to live < 3-6 months Patients undergoing operative resection < 3 months

15. Biliary Obstruction in Pancreatic Cancer Is plastic stenting for pancreatic cancer still relevant in 2015? –Patency of 10 French plastic biliary stents becomes an issue after 8 weeks with larger caliber stents failing to increase patency duration –Plastic stents > 7 cm length are associated with higher occlusion (and migration) rates.

16. Biliary Obstruction in Pancreatic Cancer Multiple studies have demonstrated superior patency of metal stents, which overrides cost savings of plastic stenting –More frequent ERCPs –More frequent hospitalizations for occluded stents –Possible sequelae of migrated plastic stents

17. Biliary Obstruction in Pancreatic Cancer 2014 NCCN Guidelines on Pancreatic Adenocarcinoma –Short metal stent should be considered effective first-line therapy for palliation (uncovered) or bridge to surgery (covered) in borderline resectable, non-metastatic patients assigned to neoadjuvant therapy.

18. Biliary Obstruction in Pancreatic Cancer Covered vs Uncovered metal biliary stents –Comparable patency –Higher migration risk of covered stents –Higher cholecystitis and sludge risks of covered stents –Fragmentation risk with covered stent removal

19. Biliary Obstruction in Pancreatic Cancer EUS-guided drainage for difficult cases –Transgastric –Transduodenal –Rendezvous IR assistance