Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer

Abstract

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes.Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate.Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38).Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings.

A Systematic Review and Meta-Analysis Comparing Liver Resection with the Rf-Based Device Habib™-4X with the Clamp-Crush Technique

“…The exact reasons are not explicitly well defined, but could be explicable after the systemic and local immunomodulatory effect generated following the application of radiofrequency energy over tumour mass, causing T-cells’ infiltration into the tumour microenvironment [ 83 ].…”

Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation

“…According to meta-analysis performed by Ding et al, increased density of tumour infiltrating lymphocytes (TILs) have been significantly associated with improved survival [78]. Additionally, studies have outlined positive immunomodulatory change following the application of RF in terms of Tregs, CD8+ T-cells, TGF-β, IFNγ, IL-10, IL-17, respectively [79][80][81][82].…”

“…immunomodulatory change following the application of RF in terms of Tregs, CD8+ T-cells, TGF-β, IFNγ, IL-10, IL-17, respectively [79][80][81][82].…”

Positive Immuno-Modulation Following Radiofrequency Assisted Liver Resection in Hepatocellular Carcinoma

“…The debris produced following RF-induced coagulative necrosis during liver resection generates tumour antigens and chemokines, which enticed the immunoprotective infiltrates, macrophages, neutrophils, DCs, and NK cells. DCs activate the nuclear factor kappa-light-chain-enhancer of the activated B cells (NF-κβ) pathway, which stimulates CD8 + and CD4 + T lymphocytes and promote a systemic immune response also known as the “in-vivo dendritic cell vaccine effect” [27,28,29,30]. A strikingly dense CD3 + T cell infiltration has been demonstrated by studies at tumour locations following radiofrequency ablations (RFA), consistent with the local antitumor immune response.…”

“…Consequently, resections have to be as conservative as achievable in the ablation of non-tumoural hepatic parenchyma. [30,34,35,36]. Qiu et al (2017) [37] have outlined the benefits of a liver resection with Habib TM 4X and demonstrated significantly less morbidity, mortality and better survival than with the conventional clamp-crush technique.…”