BACKGROUND: Laparoscopic surgery (LS) is hypothesized to result in milder proinflammatory reactions due to less severe operative trauma, which may contribute to the observed clinical benefits after LS. However, previous systematic reviews and meta-analyses on the impact of LS on immunocompetence are outdated, limited and heterogeneous. Therefore, the humoral response after laparoscopic and open colorectal cancer (CRC) resections was evaluated in a comprehensive systematic review and meta-analysis.
METHODS: Included were randomized controlled trials (RCTs) measuring parameters of humoral immunity after LS compared to open surgery (OS) in adult patients with CRC of any stage. MEDLINE, Embase, Web of Science (SCI-EXPANDED), Cochrane Library, Google Scholar, ClinicalTrials.gov and ICTRP (World Health Organization) were systematically searched. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool. Weighted inverse variance meta-analysis of mean differences was performed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) using the random-effects method. Methods were prospectively registered in PROSPERO (CRD42021264324).
RESULTS: Twenty RCTs with 1131 participants were included. Narrative synthesis and meta-analysis up to 8 days after surgery was performed. Quantitative synthesis found concentrations to be significantly lower after LS at 0-2 h after surgery (IL-8), at 3-9 h (CRP, IL-6, IL-8, TNFα) and at postoperative day 1 (CRP, IL-6, IL-8, VEGF). At 3-9 h, IL-6 was notably lower in the LS group by 86.71 pg/ml (mean difference [MD] - 86.71 pg/ml [- 125.05, - 48.37], p < 0.00001). Combined narratively, 13 studies reported significantly lower concentrations of considered parameters in LS patients, whereas only one study reported lower inflammatory markers (for CRP and IL-6) after OS.
CONCLUSIONS: The increase in postoperative concentrations of several proinflammatory parameters was significantly less pronounced after LS than after OS in this meta-analysis. Overall, the summarized evidence reinforces the view of a lower induction of inflammation due to LS.

Colorectal cancer (CRC) is the third most common cancer worldwide. The main treatment options are laparoscopic (LS) and open surgery (OS), which might differ in their impact on the cellular immunity so indispensable for anti-infectious and antitumor defense. MEDLINE, Embase, Web of Science (SCI-EXPANDED), the Cochrane Library, Google Scholar, ClinicalTrials.gov, and ICTRP (WHO) were systematically searched for randomized controlled trials (RCTs) comparing cellular immunity in CRC patients of any stage between minimally invasive and open surgical resections. A random effects-weighted inverse variance meta-analysis was performed for cell counts of natural killer (NK) cells, white blood cells (WBCs), lymphocytes, CD4+ T cells, and the CD4+/CD8+ ratio. The RoB2 tool was used to assess the risk of bias. The meta-analysis was prospectively registered in PROSPERO (CRD42021264324). A total of 14 trials including 974 participants were assessed. The LS groups showed more favorable outcomes in eight trials, with lower inflammation and less immunosuppression as indicated by higher innate and adaptive cell counts, higher NK cell activity, and higher HLA-DR expression rates compared to OS, with only one study reporting lower WBCs after OS. The meta-analysis yielded significantly higher NK cell counts at postoperative day (POD)4 (weighted mean difference (WMD) 30.80 cells/µL [19.68; 41.92], p < 0.00001) and POD6-8 (WMD 45.08 cells/µL [35.95; 54.21], p < 0.00001). Although further research is required, LS is possibly associated with less suppression of cellular immunity and lower inflammation, indicating better preservation of cellular immunity.

Epidemiological evidence has highlighted a strong relationship between cardiorespiratory fitness and surgical outcomes; specifically, fitter patients possess heightened resilience to withstand the surgical stress response. This narrative review draws on exercise and surgical physiology research to discuss and hypothesise the potential mechanisms by which higher fitness affords perioperative benefit. A higher fitness, as indicated by higher peak rate of oxygen consumption and ability to sustain metabolic homeostasis (i.e. higher anaerobic threshold) is beneficial postoperatively when metabolic demands are increased. However, the associated adaptations with higher fitness, and the related participation in regular exercise or physical activity, might also underpin the observed perioperative benefit through a process of hormesis, a protective adaptive response to the moderate and intermittent stress of exercise. Potential mediators discussed include greater antioxidant capacity, metabolic flexibility, glycaemic control, lean body mass, and improved mood.

Radical gastrectomy is a mainstay therapy for patients with locally resectable gastric cancer (GC). GC patients who are candidates for radical gastrectomy will experience at least part of the following perioperative events: surgery, anesthesia, pain, intraoperative blood loss, allogeneic blood transfusion, postoperative complications, and their related anxiety, depression and stress response. Considerable clinical studies have shown that these perioperative events can promote recurrence and decrease the long-term survival of GC patients. The mechanisms include activation of neural signaling and the inflammatory response, suppression of antimetastatic immunity, increased release of cancer cells into circulation, and delayed adjuvant therapy, which are involved in every step of the invasion-metastasis cascade. Having appreciated these perioperative events and their influence on the risk of GC recurrence, we can now use this knowledge to find strategies that might substantially prevent the deleterious recurrence-promoting effects of perioperative events, potentially increasing cancer-free survival in GC patients.