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. 2023 Feb 5;43(3):365–386. doi: 10.1002/cac2.12408

FIGURE 6.

FIGURE 6

Perioperative opioid treatment promotes CTC formation in BC patients receiving robot‐assisted laparoscopic radical cystectomy, (A‐E) The numbers of total epithelial CTCs (A), total mesenchymal CTCs (B), total double‐positive CTCs (C), total CTCs (D), and total CTC clusters (E) in BC patients receiving surgery under GA or a combined GA + E, measured pre‐surgery, immediately after surgery, 3rd day post‐surgery, and 1 month post‐surgery, respectively. Patients in the GA + E group received only a very small amount of MORA during anesthesia induction, whereas patients in the GA group received continuous perioperative doses of MORAs, (F) Fold changes of the different types of CTCs at indicated time points. When CTC count = 0 pre‐surgery but > 0 at the other three time points, the Log2(fold change) was defined as 10. Similarly, when CTC count > 0 pre‐surgery but = 0 at the other three time points, the Log2(fold change) was defined as ‐10. Change trends of patients whose post‐surgery blood samples were missing are not shown. The decline trends of CTCs in the GA + E group were significantly more pronounced than those in the GA group in most cases, (G) Before surgery, patients with higher tumor stages (III and IV) had significantly more total CTCs compared to those diagnosed with lower tumor stages (I and II), (n = 13‐22 in A‐G, mean ± SD) *P < 0.05, **P < 0.01, ***P < 0.001; ns, not significant, (H) Schematic model showing the mechanisms how a MORA facilitates the formation of CTCs leading to increases in tumor metastases in BC, Abbreviations: CTC, circulating tumor cell; BC, bladder cancer; GA, general anesthesia; E, epidural anesthesia; MORA, μ‐opioid receptor agonist; MOR, μ‐opioid receptor; EMT, epithelial‐mesenchymal transition.