Mazmishvili Ketevan, Jayant Kumar, Janikashvili Nona, Kikodze Nino, Mizandari Malkhaz, Pantsulaia Ia, Paksashvili Natela, Sodergren Mikael H, Reccia Isabella, Pai Madhava, Habib Nagy, Chikovani Tinatin
Department of Immunology, Tbilisi State Medical University, 0186 Tbilisi, Georgia.
Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, DuCane Road, W120HS, UK.
J Cancer. 2018 Aug 6;9(17):3187-3195. doi: 10.7150/jca.25084. eCollection 2018.
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. 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. A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (=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 (=0.38). 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.
肝癌是一种致死率很高的肿瘤，在全球范围内发病率不断上升。这些肿瘤的特征是恶性细胞增殖、全身性免疫抑制和慢性炎症，其炎症标志物如中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）升高，以及T淋巴细胞上CD4+CD39+的过表达。研究概述了肝癌患者的免疫调节变化，这可能是生存率提高的合理原因。本初步研究的目的是了解射频（RF）能量和肝切除（非基于射频的设备；非RF设备）对NLR、PLR和CD4+CD39+ T淋巴细胞表达的可能免疫调节作用，并比较这些变化的程度。在本研究中，17例肝癌患者被前瞻性地分为治疗组：射频消融组（RFA组）和使用非RF设备的肝切除组（LR组）。在手术前一个月和手术后，从每位患者采集血样，并与年龄匹配的健康志愿者的血样进行组间比较。根据情况，使用曼-惠特尼U检验、麦克内马尔检验和威尔科克森秩和检验进行统计比较。RFA后，NLR从4.7±3.3降至3.8±1.8（P=0.283），而LR组则从3.5±2.8升至4.5±3.2（P=0.183）。同样，RFA后PLR从140.5±79.5降至137±69.2（P=0.386），而LR组从116±42.2升至120.8±29（P=0.391）。RFA组CD4+CD39+淋巴细胞从55.8±13.8显著降至24.6±21.1（P=0.03），而LR组从47.6±8.8显著升至55.7±33.2（P=0.38）。研究表明，NLR、PLR降低以及T淋巴细胞上CD4+CD39+表达降低是肝癌患者生存率提高的标志，我们的研究结果证实，应用RF能量后可诱导这些变化。此外，这可能是与非基于RF的肝切除技术相比，在不同研究中使用RFA或其他基于RF的设备观察到更好生存率的原因。然而，需要进一步的大规模研究来证实这些发现。
