NaK Alloy-induced Ablation Therapy On Pancreatic Cancer Mice

Objective: Cancer is a significant public health problem,an approximate 14 million new cancer cases and 8 million cancer-related deaths occurred every year throughout the world.Finding the best treatment approach according to the tumor stage is of vital importance.As a minimally invasive alternative with low morbidities,thermal ablation is being widely applied in eradication of the tumor.Our group proposed the Na K alloy ablation therapy.It based on thermal chemical reaction between the alkali metal fluid and the tissue water to release plenty of heat in the target tissue.In previous studies,some fundamental mechanisms related to the anti-tumor effects of sodium and the preliminary applications in tumor treatment have been disclosed.With an extremely small amount of liquid NaK alloy,a significant temperature increase can be obtained at the targeted tissue,which immediately results in a strong thermal ablation effect.Meanwhile,lots of OH-was generated,and the resulted alkaline environment could inhibit tumor growth.The reaction in the tissue produces a large amount of hydrogen during the exothermic chemical process,which could cause mechanical cell structure collapsing.Reactants such as Na and K will be mostly absorbed for they work as the most basic element of the body.The aim of this paper is to evaluate the in vivo treatment effect of the liquid alkali alloy ablation on early stage tumor and advanced stage tumor.Temperature responses,pathology assessments and the tumor volume changes were measured during the percutaneous Na K alloy injection.Methods:Panc02 tumor cells were injected into 21 female C57BL/6 mice.Each mouse was injected with 0.2ml Panc02 tumor cell suspension of 1×107 cells/ml.The tumor volumes were measured once every two days.The mice were randomly divided into three groups: early tumor group(ET,the average tumor volume is about 150mm3),advanced tumor group(DT,the average tumor volume is about 550mm3),control group(DT,the average tumor volume is about 550mm3).1 The mice in the early tumor group received the NaK alloy ablation on the 18 th day after tumor cell inoculation.About 15 uL Na K alloy was injected into the center of the tumor.A thermal couple and an infrared camera recorded the dynamic temperature change.After ablation experiment,two mice in the early tumor group were chosen randomly to make pathological sections.2 On the 25 th day after tumor cell inoculation,the mice in develop tumor group received the NaK alloy ablation.About 15 uL NaK alloy was injected into the center of the tumor.A thermal couple and an infrared camera recorded the dynamic temperature change.After ablation experiment,two mice in the advanced tumor group were chosen randomly to make pathological sections.3 The mice in control group received no ablation.On the 25 th day after tumor cell inoculation,the mice in control group received an injection of 15 uL saline.The injection process was performed under the monitoring of thermal couple and an infrared camera.After the saline injection,two mice in the control group were chosen randomly to make pathological sections.After an observation of 17 days,all of the remaining mice were executed.The tumors were cut off to calculate the weight and the tumor inhibition rates.Results:1 Thermal responseThe curve measured by thermal couple depicted the temperature change near the center of the injection region.The initial body temperature of the mouse was about 33°C(t<0).When the alkali metal was injected to the center of tumor(t=0),the temperature increased sharply from 33°C to 85°C within two seconds.The highest temperature maintained less than one second and then followed by a slow decrease until returning the initial temperature.The result showed that the temperature could maintained above 42°C for about 50 seconds in each injection.Besides,the infrared images captured by the infrared camera revealed the release of heat energy during the ablation process.The thermographs at t=-5,2,10,20,50,90 s were given as the monitor of the detailed skin temperature distribution.The red region showed the increase temperature.When the NaK alloy was injected,the red region received the largest area.The yellow region demonstrated that the basic temperature of mice keep stable.With the decrease of temperature,the red area became smaller and smaller.The distribution of heat was concentrated on the injection area,and the shape of high temperature region coincided with the tumor.2 Histological evaluationsThe injection region of early stage cancer proved the typical sign of coagulative necrosis.The nucleus of tumor cell was dissolved and necrotic,and the tumor cell structure was completely disappeared.It demonstrated incomplete necrosis of the tumor tissue in marginal ablation area in the developing tumor treatment mouse.The top left of the section depicted the integrated tumor cell structure with pleomorphic neoplastic cell nuclei,while the bottom right revealed the thermal injury.The tumor cells were deformed and necrotic and their nuclei had become pyknotic.In the control group,the cell structure was integrated and consistent with the high-density of cells and abundant nuclei chromatin.3 The volume of tumorFor the early stage tumor group,on the 18 th day,the average tumor volume was about 180mm3 before the treatment,while the volume decreased to 33mm3 on the 24 th day after the alkali metal ablation therapy.For the mice in the advanced tumor treatment group,after received the alkali metal ablation treatment,the tumor volume gradually decreased.During the following days,the injection region began to scab and the volume decreased slowly to 260mm3.Since the developing tumor were out-of-shape and infiltrated into adjacent organs before the treatment,it was difficult for a thorough ablation of the malignant cells.As a result,the volume increased gradually at the late period of the experiment.In the end of experiment,the average volume was about 560mm3.The tumor increased exponentially and rapidly in the control group in the beginning twenty days.Then from the 20 th day,the tumor growth rate declined.In the end,the tumor could grow up to about 3300mm3.4 The tumor inhibition rateThe weight of the tumor in three groups was measured at the end of the experiment.The mean tumor weight in early treatment mice was 0.21 g,and the tumor inhibition rate was 88.5%(P<0.05).The mean tumor weight in advanced tumor group was 0.58 g,and the tumor inhibition rate was 67.6%(P<0.05).Conclusions:1 Only an extremely small amount Na K alloy will generate a powerful reaction.The distribution of heat energy is concentrated on the tumor.Typically coagulate necrosis can be seen in the injection region.2 Liquid NaK alloy ablation could serve as an anticancer approach.For the early stage tumor,it provides a nearly entire ablation.For the advanced tumor,the tumor burden will be alleviated after this cytoreductive surgery.