IS ALCOHOL FREE ABLATION EFFECTIVE AND SAFE FOR TREATMENT OF PRE-CANCEROUS PANCREATIC CYSTS?
- Graduate Program:
- Public Health Sciences
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- May 14, 2018
- Committee Members:
- Thomas Allen Lloyd, Thesis Advisor
- Pancreatic Cancer Prevention; Chemotherapy; Mucinous Pancreatic Cysts
- Background: Approximately 15% of precancerous pancreatic cysts will develop into pancreatic cancer. Endoscopic Ultrasound (EUS)-fine needle infusion is a new technique to deliver drugs and ablate these pre-cancerous pancreatic cysts. EUS ablation is typically followed with ethanol lavage followed by infusion of the chemotherapeutic agent, paclitaxel, and has been shown to be an effective treatment for ablation of mucinous precancerous cysts. This procedure is associated with 3–10% adverse events after treatment, and it has been hypothesized that these adverse events are linked to the inflammatory effects of alcohol. Our research focused on elucidating whether alcohol is required for effective ablation, whether removing alcohol from the ablation decreases the rate of adverse events, and whether this novel multi-drug chemotherapeutic mixture of Paclitaxel and Gemcitabine (Drug cocktail) is more effective and can increase the rate of ablation compared to paclitaxel alone. Method: Between November 2011 and December 2016, we conducted a single-center, prospective, randomized, and double-blinded study. Forty-six patients with pre- cancerous cysts were randomized into this study and 39 underwent treatment. All patients were randomized to either the control arm which included EUS-guided pancreatic cyst lavage with an 80% ethanol lavage followed by a drug cocktail (or to the experimental arm, namely normal saline lavage followed by the same chemotherapeutic cocktail. The primary outcomes were the rates of complete ablation 12 months after the procedure and rate of serious and minor adverse events within 30 days after the procedure. Results: Of the 39 patients who received treatment, 23 (59%) were male and 16 (41%) were female. The majority of cysts were located in the head and body of the pancreas (48.7% of the cysts for both locations) and the mean cyst diameter was 2.5 cm. Fourteen (67%) patients underwent EUS ablation in the saline lavage arm had a complete response, defined as ≥ 95% reduction in cyst volume, after 12 months. In the alcohol arm, eleven (64%) of patients had a complete response after 12 months (CI= -0.38-0.24, p=0.01). Serious adverse events occurred in 6% of patients in the alcohol arm and 0% in the trial group. Minor adverse events occurred in 22% of patients in the control group and 0% in the alcohol-free group. The overall rate of complete ablation in both groups was 64% after 12 months. Conclusion: In this prospective, randomized study we demonstrated that alcohol is not required for effective ablation. Moreover, removing alcohol from the EUS ablation of a pancreatic cyst significantly reduced the number of adverse events in patients who underwent this procedure. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve the rate of complete ablation compared to previous studies which used alcohol followed by paclitaxel alone.