Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Surgical trauma and anesthesia may modulate the tumor microenvironment and influence postoperative recurrence in colorectal cancer (CRC). Volatile anesthetics such as sevoflurane have been reported to exert anti-tumor effects in vitro, yet their clinical impact on CRC cell proliferation and dissemination remains unclear. Objectives: To determine whether sevoflurane anesthesia attenuates early tumor cell activity compared with total intravenous anesthesia (TIVA) through assessment of circulating tumor cells (CTCs), systemic inflammation, and tissue biomarkers of proliferation and apoptosis. Methods: In this prospective, single-center, randomized controlled study, 80 CRC patients undergoing radical resection were allocated to sevoflurane (Group A, n = 40) or TIVA (Group B, n = 40). Peripheral blood was collected pre-operatively and on post-operative days (POD) 1, 3 and 7 for enumeration of CTCs (CellSearch®) and quantification of IL-6, TNF-? and C-reactive protein (CRP). Resected specimens were immunostained for Ki-67, PCNA, Bax, Bcl-2 and caspase-3. Results: Baseline characteristics were comparable. CTC counts rose after surgery in both groups but remained lower in Group A at every time-point (POD 3: 3.2±1.4 vs 4.5±1.7, P = 0.001). Inflammatory markers peaked on POD 3 but were significantly lower in Group A (IL-6: 40.1±9.5 vs 51.3±10.7 pg mL-¹, P < 0.001). Ki-67 and PCNA positive rates were reduced, whereas Bax/Bcl-2 ratio and caspase-3 expression were elevated in Group A (all P < 0.05). One-month CEA and CA19-9 levels did not increase in Group A, while they rose significantly in Group B (CEA: 4.9 ± 1.3 vs 6.1 ± 1.6 ng mL-¹, P = 0.007). Conclusion: These findings support the hypothesis that volatile anesthetics may reduce short-term recurrence risk and warrant larger, longer-term trials to validate oncological outcomes.