Advanced Endoscopic Therapyfor Pancreatic Cancer

Nathan Landesman, D.O.

Flint Gastroenterology Associates

February 28, 2015

Disclosures

• None

Emerging Role of Endoscopyin 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

Therapeutic EndoscopicInterventions

• Fiducial Placement– Delineates extent of malignancy

– Quantifies respiratory-associated tumor motion

Therapeutic EndoscopicInterventions

• 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

Therapeutic EndoscopicInterventions

• Fiducial Placement Technique

– Placement of at least 3 markers is preferred to “triangulate” the malignancy

– > 4 markers to “box-in” the lesion is ideal

Therapeutic EndoscopicInterventions

• 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

Therapeutic EndoscopicInterventions

• Fiducial Placement Safety/Efficacy

– < 7% migration rate is likely overstated

• Decompression of gastroduodenal obstruction

• Decompression of biliary obstruction

Therapeutic EndoscopicInterventions

• Fine Needle Injection (FNI)

– Activated lymphocytes/Oncolytic viruses

– Viral vectors (“Gene Therapy”)

– Ink marking of small lesions

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

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

Gastroduodenal Obstructionin Pancreatic Cancer

• Uncovered metal prosthesis of varying lengths

• Avoid coverage of major papilla if possible– APC laser-assisted fenestration

• Surgical bypass

Biliary Obstructionin 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.

Biliary Obstructionin 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

Biliary Obstructionin 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.

Biliary Obstructionin 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

Biliary Obstructionin 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.

Biliary Obstructionin 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

Biliary Obstructionin Pancreatic Cancer

• EUS-guided drainage for difficult cases

– Transgastric

– Transduodenal

– Rendezvous• IR assistance