Background: The perioperative period is critical in the long-term prognosis of breast cancer patients. The use of regional anesthesia, such as paravertebral block (PVB), could be associated with improvements in long-term survival after breast cancer surgery by modulating the inflammatory and immune response associated with the surgical trauma, reducing opioid and general anesthetic consumption, and promoting cancer cells death by a direct effect of local anesthetics. Methods: A systematic literature search was conducted for studies of patients who received PVB for breast cancer surgery. The Jadad score and Ottawa-Newcastle scale were used to assess the methodological quality of randomized controlled trial and observational retrospective studies, respectively. Only high-quality studies were considered for meta-analysis. The selected studies were divided into 3 groups to determine the impact of PVB on (a) recurrence and survival, (b) humoral response, and (c) cellular immune response. Results: We identified 100 relevant studies. The main outcome was to compare opioid consumption at the first 24 h after surgery. For secondary objectives, we aimed to compare pain scores after surgery, intraoperative opioid consumption, the incidence of PONV and block-related adverse events. Conclusions: Our study indicates that there are no data to support or refute the use of REGIONAL BLOCKS for reduction of cancer recurrence or improvement in cancer-related survival. However, its use is associated with lower levels of inflammation and a better immune response in comparison with general anesthesia and opioid-based analgesia.
Anesthetic techniques leading to cancer recurrence is a hypothesis that has been explored for more than a decade now. [1] Anesthesia management has a role to play in the surgical outcome. Volatile anesthetics and opioids when used for general anesthesia are considered unfavorable. Experimental and retrospective studies have shown that they could facilitate cancer recurrence. It has been demonstrated that opioids and volatile anesthetics inhibit the function of natural killer (NK) cells, thereby stimulating cancer cell proliferation by facilitating angiogenesis and tumor cell signalling pathways. Several retrospective data have tried to establish an association between the use of inhalational anesthetics and systemic opioids leading to cancer recurrence. [2,3] Anesthetic agents like thiopentone sodium and ketamine are also considered to have unfavorable effects on NK cells and the immune system. [4] Although this association has been studied (in-vitro studies), the association was never proven in humans convincingly. However, total intravenous anesthesia (TIVA) using propofol has been shown to have many desirable effects like preserving immunity and recurrence-free survival. [5]
The perioperative period after major oncological surgery leads to a cascade of events like immunosuppression, angiogenesis, extensive tissue handling, inflammation, and possible dissemination of cancer cells. This period is critical because if immunosuppression and angiogenesis are not obtunded by proper measures, there could be malignant cell proliferation, invasion, and eventually recurrence in the long run. [6,7,8]
Eligibility criteria for studies are defined based on PICOS standards (participants, interventions, comparisons, outcomes and study designs).
Inclusion criteria
Adult female patients aged 18–70 years with American Society of Anesthesiologists (ASA) physical status 1,2, and 3 scheduled for elective surgery for breast cancer were included in this study.
Exclusion criteria
Patients with other surgeries would be excluded, such as breast brachytherapy, radiofrequency ablation of liver tumors, lumbar surgery and thoracoscopic surgery.
Ultrasound (US)-guided ESPB was performed in the experimental group, and the control group was placebo or received no intervention. If the control group was included in the article which compared ESPB versus other type of nerve blocks, these articles would be included.
Pain scores (VAS/NRS) were significantly lower at all time-points (at 1, 6, 12, and 24 h after surgery) in patients receiving ESPB than that in the GA group, by a mean difference [95% CI] − 1.02 [− 1.73, − 0.31] (P < 0.01, I2 = 82%), − 0.92[− 1,83, − 0.01] (P = 0.05, I2 = 87%), − 0.76 [− 1.43, − 0.09] (P = 0.03, I2 = 89%), and − 0.59 [− 1.01, − 0.17) (P < 0.01, I2 = 88%), respectively
There were no statistically significant differences between the ESPB group and the GA group with regard to opioid consumption at 1 h postoperatively (MD: –0.32; 95% CI: − 0.83 to 0.20; P = 0.23] Patients receiving ESPB showed a significant reduction in morphine consumption compared with the GA group at 6 and 12 h postoperatively, by a mean difference [95% CI] − 2.71 [− 3.38, − 2.04] (P < 0.01, I2 = 0%), − 6.12[− 7.00, − 5.25] (P < 0.01, I2 = 0 ] respectively.
The incidence of PONV was significantly lower in patients receiving ESPB than that in the GA group (RR 0.59; 95%CI 0.45 to 0.78; p < 0.01)
Mortality among cancer patients is more commonly due to the effects of metastasis and recurrence as opposed to the primary tumour. Various perioperative factors have been implicated in tumour growth, including anesthetic agents and analgesia techniques. In this narrative review, we integrate this information to present a summary of the best available evidence to guide the conduct of anesthesia for primary cancer surgery.
Principal findings: There is conflicting evidence regarding volatile agents; however, the majority of studies are in vitro, suggesting that these agents are associated with enhanced expression of tumourigenic markers as well as both proliferation and migration of cancer cells. Nitrous oxide has not been shown to have any effect on cancer recurrence. Local anesthetic agents may reduce the incidence of cancer recurrence through systemic anti-inflammatory action in addition to direct effects on the proliferation and migration of cancer cells. Nonsteroidal anti-inflammatory drugs affect cancer cells via inhibition of cyclooxygenase 2 (COX-2), which leads to reduced resistance of the cancer cell to apoptosis and reduced production of prostaglandins by cancer cells. Nonsteroidal anti-inflammatory drugs also suppress the cancer cell growth cycle through effects independent of COX-2 inhibition. Opioids have been shown to inhibit the function of natural killer cells and to stimulate cancer cell proliferation through effects on angiogenesis and tumour cell signalling pathways. Supplemental oxygen at the time of surgery has a proangiogenic effect on micrometastases, while the use of perioperative dexamethasone does not affect overall rates of cancer survival
Current laboratory research suggests that perioperative interventions may impact recurrence or metastasis through effects on cancer cell signalling, the immune response, or modulation of the neuroendocrine stress response. Further evidence is awaited from prospective randomized-controlled trials. Meanwhile, with limited data upon which to make strong recommendations, anesthesiologists should seek optimal anesthesia and analgesia for their patients based on individual risk-benefit analysis and best available evidence on outcomes other than cancer recurrence
Funding– No source of funding
Conflict of interest – None declared
Ethical approval – The study was approved by the institutional ethics committee
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