To the best of our knowledge, this is the first retrospective study to compare the efficacy and safety of EUS-guided multimode ablation and conventional chemotherapy for untreated PDAC. According to the data, after multimode EUS-RFA treatment, the tumor size was significantly reduced after undergoing multimode EUS-RFA, with an average tumor volume reduction of 38.1% (P = 0.005). The tumor size was not significantly changed in Group B (P = 0.389). A statistically significant difference was observed in tumor size between Group A and Group B after treatment (P = 0.022). Conventional therapy did not appear to have a significant therapeutic effect on PDAC. This may be due to the fact that it is focused on improving patients' quality of life, with the aim of improving clinical benefit rates such as controlling local cancer tissue invasion, lesion spread, and maximizing life expectancy . Obviously, compared with conventinal EUS-RFA, multimode EUS-RFA is more effective in reducing tumor volume and prolonging median lifetime. Although conventional chemotherapy can also relieve pain, patients can experience adverse side effects at the same time. In fact, compared to traditional EUS-RFA , multimode EUS-RFA has advantages in prolonging survival and the occurrence of complications.
In this study, we used the HTP to perform EUS-guided multimode ablation. Compared with the traditional probe, HTP is a bipolar probe that combines RFA with cryogenic cooling. Many previous studies have confirmed that the RFA is feasible for pancreatic cancer and can achieve the purpose of prolonging survival which is similar to our result[9, 17–19]. However, the reason that hinders the further promotion of RFA in the clinical treatment of pancreatic cancer is the serious complications and higher mortality caused by the use of RFA. The treatment of pancreatic cancer with RFA may be accompanied by some adverse reactions, such as pancreatitis caused by heat injury and destruction of peripancreatic structures, etc. Therefore, some scholars suggest that radiofrequency ablation needs to be used at the correct temperature and at a proper distance from important structures.
Since HTP has cryogenic cooling function, there would be less thermal damage due to the use of HTP for ablation. Besides, the EUS guidance with color Doppler coupling can provide precise positioning of target lesions and predict a certain area of ablation. Consequently, compared with traditional RFA treatment, the incidence of RFA-related complications when undergoing EUS-guided multimode ablation can be reduced. In Group A, in 2 of the 10 cases, intraoperative bleeding at the puncture point occurred but was relieved by endoscopic application of hemostatic agents. No severe adverse events related to RFA were observed in all patients.
The internal carbon dioxide in HTP probe internal use carbon dioxide for cooling can prevent overheating electrode surface in a longer time, increasing the resistance , current and extend the time , so more radio frequency energy can be applied to the tumor tissue, resulting in more ablation. Freeze makes cell dehydration and protein denaturation which is easier to thermal damage, contributing to the shortest possible time to achieve maximum size technically. Compared with conventional radiofrequency ablation systems (30 ± 60 W), less power input (16 W) is required to achieve the same ablation results, and therefore less collateral damage is expected [12–14]. He et al and Liu et al found that Cryo-thermal treatment created an acute inflammatory environment to initiate a systemically cascading innate and adaptive anti-tumor immunity, which as more permissive for tumor eradication and inhibited metastasis in the long term..
The above reasons explain that compared with traditional RFA, performing RFA with HTP can prolong the survival of patients with pancreatic cancer and reduce the incidence of adverse events. Besides, the therapeutic effect of pancreatic cancer is not ideal when performed RFA with cryoprobe alone. Wu et al  reported 25% of fatal hemorrhagic complications after intraoperative treatment of pancreatic head tumors by Cool-Tip RF probe. Therefore, we believe that HTP, a probe that combines thermal ablation and cooling functions, may be more suitable for the treatment of pancreatic cancer.
This conclusion is similar to that of Arcidiacono et al . Compared with their study, patients enrolled in this study did not undergo neoadjuvant chemotherapy before undergoing EUS-guided multimode ablation. This indicated that for patients with PDAC, if HTP was used for treatment, the neoadjuvant chemotherapy may not be necessary. This could reduce the pain and financial burden of patients undergoing chemotherapy.
There are several limitations in this study. First of all, the sample size is insufficient and this study is a single- center retrospective study which may bias the outcomes. The ablation model and parameters have not yet been standardized which may also bias the outcomes. Finally, due to the lack of cases, we cannot obtain enough samples from our center to conduct comparative studies on the therapeutic effect among traditional RFA, EUS-guided multimode ablation, and undergoing conventional chemotherapy alone for pancreatic cancer patients. We will pay attention to this aspect in future research.