A prospective, randomized, double-blind, placebo controlled trial on the efficacy of ethanol celiac plexus neurolysis in patients with operable pancreatic and periampullary adenocarcinoma

Harish Lavu, Harry B Lengel, Naomi M Sell, Joseph A Baiocco, Eugene P Kennedy, Theresa P Yeo, Sherry A Burrell, Jordan M Winter, Sarah Hegarty, Benjamin E Leiby, Charles J Yeo, Harish Lavu, Harry B Lengel, Naomi M Sell, Joseph A Baiocco, Eugene P Kennedy, Theresa P Yeo, Sherry A Burrell, Jordan M Winter, Sarah Hegarty, Benjamin E Leiby, Charles J Yeo

Abstract

Background: Ethanol celiac plexus neurolysis (ECPN) has been shown to be effective in reducing cancer-related pain in patients with locally advanced pancreatic and periampullary adenocarcinoma (PPA). This study examined its efficacy in patients undergoing PPA resection.

Study design: There were 485 patients who participated in this prospective, randomized, double-blind placebo controlled trial. Patients were stratified by preoperative pain and disease resectability. They received either ECPN (50% ethanol) or 0.9% normal saline placebo control. The primary endpoint was short- and long-term pain and secondary endpoints included postoperative morbidity, quality of life, and overall survival.

Results: Data from 467 patients were analyzed. The primary endpoint, the percentage of PPA patients experiencing a worsening of pain compared with preoperative baseline for resectable patients, was not different between the ethanol and saline groups in either the resectable/pain stratum (22% vs 18%, relative risk [RR] 1.23 [0.34, 4.46]), or the resectable/no pain stratum (37% vs 34%, RR 1.10 [0.67, 1.81]). In multivariable analysis of resected pancreatic ductal adenocarcinoma (PDA) patients, there was a significant reduction in pain in the resectable/pain group, suggesting that surgical resection of the malignancy alone (independent of ECPN) decreases pain to a significant degree.

Conclusions: In this study, we demonstrated a significant reduction in pain after surgical resection of PPA. However, the addition of ECPN did not synergize to result in a further reduction in pain, and in fact, its effect may have been masked by surgical resection. Given this, we cannot recommend the use of ECPN to mitigate cancer-related pain in resectable PPA patients.

Trial registration: ClinicalTrials.gov NCT00806611.

Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Intraoperative ethanol celiac plexus neurolysis procedure with injection of 50% ethanol into the celiac nerve plexus. A 20 mL volume injection was performed on each side of the aorta. (Reprinted courtesy of the artist, Jennifer Brumbaugh.)
Figure 2
Figure 2
Ethanol celiac plexus neurolysis study design and flowchart.
Figure 3
Figure 3
Survey response as a function of time.
Figure 4
Figure 4
Average pain scores over time by preoperative pain in the subgroup of resectable, pancreatic ductal adenocarcinoma patients (using estimates from multivariate analysis) (*p

Figure 5

FACT-Hep total scores over time…

Figure 5

FACT-Hep total scores over time by pain and treatment group in resectable patients.…

Figure 5
FACT-Hep total scores over time by pain and treatment group in resectable patients. Blue line, pain/ethanol; red line, pain/saline; green line, no pain/ethanol; purple line, no pain/saline.

Figure 6

Kaplan-Meier survival estimates; resectable stratum.

Figure 6

Kaplan-Meier survival estimates; resectable stratum.

Figure 6
Kaplan-Meier survival estimates; resectable stratum.
Figure 5
Figure 5
FACT-Hep total scores over time by pain and treatment group in resectable patients. Blue line, pain/ethanol; red line, pain/saline; green line, no pain/ethanol; purple line, no pain/saline.
Figure 6
Figure 6
Kaplan-Meier survival estimates; resectable stratum.

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