| Background:Cervical cancer is the fourth most common cancer in women worldwide,with 85%of cases occurring in developing countries,where cervical cancer is a leading cause of cancer death in women.In recent years,the study of its incidence was younger,and even occurred in unmarried young women.At present,the treatment of cervical cancer in the domestic and foreign country is surgery combined with radiotherapy and chemotherapy,although this treatment prescription is rather mature,the ability of the patient’s fertility and normal tissue and organ function was impacted on varying degrees.With the incidence of cervical cancer shows younger trend,as well as the improvement of the quality of life,how to retain the reproductive function of young women is the common concern of doctors and patients.At present,all kinds of ablation technology,with the advantage of little injury and quicker recovery,increasing attention by doctors and patients.But the traditional variety of ablation techniques,such as radio frequency,microwave,focused ultrasound,freezing,laser,and so have some inherent shortcomings or deficiencies,the main performance of nerve vessels,bile duct,pancreatic duct,ureter,etc.Irreversible electroporation(IRE),as a non-thermal ablative technique,has been shown to be a more precise and complete method for the treatment of solid malignancies recently.The principle is that high-voltage electrical impulses are delivered to tissue in microseconds,it could lead to disruption of the lipid bilayer of the cell,which creates nano scale pores that allow molecules to exchange in and out of the cell,if permanent,it leads to cell programmed death,it is also called apoptosis.Nerve、vesse、bile duct、pancreatic duct、ureter and so on.which not only have cellular components,but also contains a lot of collagen fibers and other extracellular matrix,so they are minimal damage in the ablation process To date,there have been few preclinical and clinical research published for IRE,Related tissues and organs are involved in liver,pancreas prostate etc,however,lack of the relevant researches or reports to the tissues of uterine cervix.Objective:To research the satety of irreversible electroporatiog for cercvical tissues and the effectiveness of irreversible electroporation for cercvical transplantable tumor.Methods:PartⅠ:IRE ablation was performed in the cervices of 50 New Zealand rabbits,with one ablation lesion in eachanimal.Gross pathology,transmission electron microscopy,hematoxylin and eosin(H&E),Masson’s trichrome(Masson)stain,and terminal deoxynucleotidyl transferase dUTP nickend labeling(TUNEL)assays were performed at pre-set timepoints(0 h,12 h,1 d,2 d,4 d,7 d,14 d,and 28 d post-IRE).PartⅡ:2 rabbits were made tumor bearing ones,other 22 rabbits were separated into A and B group at random,eleven rabbits each group,which was implanted one or two pieces of 1mm~3 VX2 tumor fragment in rabbit cervix separately.The tumor size were compared in different times by ultrasound and CT examination,the metastasis situation and survival time were also comparedPartⅢ:A VX2 cervical transplantable tumor model was first made in 20 New Zealand rabbits.IRE ablation was performedfor the cervical cancers of 15 rabbits when the diameter of the tumor was about1.5–2.0cm.The control group(n=5)did not receive IRE ablation.The gross pathology,ultrasound,computed tomography,hematoxylin and eosin,terminal deoxynucleotidyl transferase dUTP nick end labeling assay and proliferating cell nuclear antigen immunohistochemical staining were performed to evaluate the efficacy of IRE on cervical cancer.Results:PartⅠ:All the rabbits tolerated the IRE ablation without serious complications.IRE caused complete cell death of the ablated cervixvia cell apoptosis.However,fast recovery of the cervixwas observed from 7d post-IRE,with the signs of collagenfibers hyperplasia,the disappearance of the necrotic cells and muscle fibers,and regeneration and extension of the cervicalepithelium.At 28 d post-IRE,the ablated cervices recovered to almost normal.PartⅡ:The success ratio of model establishment was 100%.The tumor presented as oval,hard and with rich blood vessels at surface in gross before 3weeks,and the pathological HE staining was consistent with the biological characteristics of squamous-cell carcinoma.Central necrosis and irregular growth occurred 4weeks after implanting.1 week after VX2 tumor fragment implanted,A and B group’s tumor sizes were(6±1.33)mm and(4.2±0.79)mm In 2 weeks,the tumor sizes were(10±1.83)mm and(8.2±1.55)mm.In 3 weeks,the tumor sizes were(21.4±3.03)mm and(19.5±2.68)mm..In 4 weeks,the tumor sizes were(39±2.45)mm and(33.4±3.34)mm.In 5 weeks,the tumor sizes were(45±4.06)mm and(37.9±3.07)mm..A and B group’s average survival time was(47.5±4.6)d and(53±5.2)d.In A group,we found 1 case of abdominal wall tumor in 2W by ultrasound examination(considered as tumor),1 case of axillary lymph node metastasis in 4w by CT examination.In A group,2 cases of liver metastases were found,and 1case in B group in 5w.PartⅢ:The tumors treated by IRE slightly increased in size during the first two days,but decreased gradually.IRE caused tumor cell death efficiently,mainly through cell apoptosis;however,it did not induce complete tumor ablation in our study.The tumor showed rapid progression in the control group.After IRE ablation,there was no side effect on the important organs of the whole body.Conclusion:1、Our study suggested that IRE might be an efficient and safe technology to treat cervical tissue,without causing serious cervical damage.Histopathology findings also showed the preservation of extracellular structures and the recovery of the ablated cervix.2、VX2 cervical transplantable tumor model in rabbits is established successfully by implanting tumor fragments,can use for the research of local treatment.3、The results suggested that IRE could eradicate rabbit VX2cervical transplantable tumors efficiently.However,the optimal IRE parameters remain to be determined.IRE ablation is a feasible treatment option for cervical tumors. |
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