Thermal and thermal damage responses during switching bipolar radiofrequency ablation employing bipolar needles: A computational study on the effects of different electrode configuration, input voltage and ablation duration.
- 作者列表："Cheong JKK","Ooi EH","Ooi ET
:Recent studies have demonstrated the effectiveness of switching bipolar radiofrequency ablation (bRFA) in treating liver cancer. Nevertheless, the clinical use of the treatment remains less common than conventional monopolar RFA - likely due to the lack of understanding of how the tissues respond thermally to the switching effect. The problem is exacerbated by the numerous possible switching combinations when bRFA is performed using bipolar needles, thus making theoretical deduction and experimental studies difficult. This article addresses this issue via computational modelling by examining if significant variation in the treatment outcome exists amongst six different electrode configurations defined by the X-, C-, U-, N-, Z- and O-models. Results indicated that the tissue thermal and thermal damage responses varied depending on the electrode configuration and the operating conditions (input voltage and ablation duration). For a spherical tumour, 30 mm in diameter, complete ablation could not be attained in all configurations with 70 V input voltage and 5 minutes ablation duration. Increasing the input voltage to 90 V enlarged the coagulation zone in the X-model only. With the other configurations, extending the ablation duration to 10 minutes was found to be the better at enlarging the coagulation zone.
: 最近的研究已经证明了开关双极射频消融 (bRFA) 治疗肝癌的有效性。尽管如此，该治疗的临床使用仍然不如传统的单极 RFA 普遍 -- 可能是由于缺乏对组织如何对转换效应做出热反应的理解。当使用双极针进行 bRFA 时，许多可能的开关组合加剧了这个问题，从而使得理论推导和实验研究变得困难。本文通过计算建模来解决这个问题，通过检查 X-、 C-、 U-、 N-定义的六种不同电极配置中是否存在治疗结果的显著变化,Z 和 O 模型。结果表明，组织热和热损伤响应因电极配置和操作条件 (输入电压和消融持续时间) 而异。对于直径为 30mm 的球形肿瘤，在输入电压为 70 v 、消融时间为 5 min 的情况下，所有配置均无法实现完全消融。将输入电压增加到 90 v，仅在 X-模型中扩大了凝血区。对于其他配置，将消融持续时间延长至 10 分钟被发现在扩大凝血区方面更好。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.