Abstract 5589: The effect of morphine-based perioperative analgesia on circulating tumor cells dissemination in colorectal cancer patients
Authors: Stejskal Pavel , Srovnal Josef , Berta Emil , Rehulkova Alona , Večeřa Lubomír , Gabrhelik Tomas , Haiduk Filip , Maca Jan , Bruthans Jan , Michalek Pavel , Kourilova Pavla , Hajduch Marian 
Published: April 2023

Abstract
Purpose: Circulating tumor cells (CTCs) are primary or metastatic tumor cells shed into the bloodstream and are considered precursors of distant metastatic spread and can act as an independent prognostic and predictive biomarker. Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide and metastasis is the major cause of death. Previous studies showed poorer survival in CRC patients treated perioperatively with morphine in comparison to piritramide.
Patients and Methods: In total, 150 CRC stage I-III patients undergoing either radical or laparoscopic surgery were enrolled in this prospective multicentric randomized study (NCT03700411). Patients were randomized into three arms using different perioperative analgesia - morphine, piritramide, and epidural analgesia. Three peripheral blood samples were collected preoperatively, one day and one month after surgery respectively. To preserve the cellular content of specimens, Cell-Free DNA BCT® (Streck, Inc.) blood collection tubes were used. The CTCs were identified using CytoTrack CT11TM (2/C, Denmark), a semi-automated immunofluorescence microscopy detecting the pan-cytokeratin and EpCAM signals. The method recovery rate was analyzed using SW-480 cancer cell line by flow cytometry.
Results: The CTCs recovery rate of the method was 72% and the method was certified by ISO 15189. The analyses of CTC presence revealed the highest positivity rate in the samples collected from patients treated with morphine on the first day after surgery (51.4 %). Also, a significant increase in positivity (from 23.5 % for the perioperatively collected samples) compared to samples from patients treated with epidural analgesia (31.1 % to 33.3 %) and piritramide (44.2% to 41.0%) was observed. The CTC presence was lower in control samples collected after one month irrespective of the analgesia type. The highest positivity among the control samples was in those associated with morphine analgesia (32.1 % versus 25.7% for epidural and 25.0% for piritramide analgesia).
Conclusion: A significant increase in CTC levels was found in postoperative blood samples of CRC patients treated with morphine compared to piritramide and epidural analgesia. Enrollment in the study is ongoing.
Acknowledgments: This study was supported by the Ministry of Health of the Czech Republic (NV18-03-00470), Palacky University Olomouc (LF 2022_012), European Union - Next Generation EU (LX22NPO5102) and European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868).
Citation Format: Pavel Stejskal, Josef Srovnal, Emil Berta, Alona Rehulkova, Lubomír Večeřa, Tomas Gabrhelik, Filip Haiduk, Jan Maca, Jan Bruthans, Pavel Michalek, Pavla Kourilova, Marian Hajduch. The effect of morphine-based perioperative analgesia on circulating tumor cells dissemination in colorectal cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5589.