Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky, University and University Hospital in Olomouc, Olomouc, Czech Republic.
Ringerike Hospital, VVHF, Honefoss, Norway.
BMC Anesthesiol. 2023 Feb 28;23(1):64. doi: 10.1186/s12871-023-02007-1.
Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet.
We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development.
The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies.
NCT03700411, registration date: October 3, 2018.
recruiting.
阿片类药物和硬膜外镇痛是围手术期镇痛的主要手段，但它们对癌症复发的影响尚不清楚。基于回顾性数据，我们发现结直肠癌手术后癌症复发与术后早期循环肿瘤细胞（CTC）的数量有关。此外，吗啡而非哌替啶术后镇痛会增加 CTC 的存在并缩短癌症特异性生存时间。硬膜外镇痛对 CTC 的影响尚未研究过。
我们计划在四个中心招募 120 名患者参与这项前瞻性随机对照试验。所有参与中心的伦理委员会均批准了研究方案。接受根治性开腹结直肠癌手术的患者被随机分为硬膜外、吗啡和哌替啶组进行围手术期镇痛。主要结局是手术前、术后第 2 天和术后 2-4 周外周血中 CTC 的数量差异。CTC 的数量通过分子生物学方法测量。围手术期护理标准化，并记录相关数据。如果可行，次要结局将是癌症组织中各种受体亚型的表达和活性。我们计划进行 5 年的随访，以观察转移的发展情况。
有利于降低癌症复发率的围手术期镇痛方式将降低发病率/死亡率。为了确定这种技术，具有长期随访期的试验似乎并不理想。鉴于复杂的肿瘤治疗策略，这种试验可能无法将围手术期镇痛的影响与其他因素分开。我们认为，术后早期 CTC 的存在/动态变化可能是各种围手术期干预对癌症复发影响的敏感标志物。重要的是，它不受长期因素的影响，并且微创。分析癌症组织中的阿片类药物/大麻素受体亚型将有助于深入了解潜在机制，并促进治疗的个体化。我们不知道是否有任何类似的正在进行的研究。
NCT03700411，注册日期：2018 年 10 月 3 日。
招募中。
