Pathological Study Of Wilm's Tumor After Preoperative Transcather Arterial Chemoembolization

BackgroundWilm's tumor is one of the most common malignant renal tumors in children.Current histological diagnosis and riskadapted therapies are based on the studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale Oncologie Pediatrique(SIOP)in Europe and the Children's Oncology Group(COG)in America.The SIOP studies largely focus on the issue of preoperative therapy and have shown the effectiveness of preoperative chemotherapy,whereas the COG studies start with primary surgery.Dramatic improvements in survival have occurred as the result of advances in histological methods of diagnosis and surgical management,irradiation and chemotherapy.The technique of preoperative transcatherter arterial chemoembolization(TACE)in Wilm's tumor has been applied widely in China.The aim of TACE procedure is to reduce tumor vascularity with a resultant decrease in tumor mass improved tumor contours, easier nephrectomy and minimal intraoperative bleeding,and the risk of intraoperative malignant cell spillage into the bloodstream that results in the metastasis will be greatly reduced.TACE is also useful in differential the diagnosis.The previous studies about TACE mostly focus on the development of imaging and clinical temporary therapeutic effect,while the contributions in histological methods of diagnosis and improved staging have few been reported.This paper studies the change of morphologic characteristics and histological staging systems for Wilm's tumor with treatment of TACE,trying to find out the histological influencing factors to the prostecdtive efficacy.Apoptosis is a form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area.Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells,unnecessary cells,and unhealthy cells.The biomedical scientists have paid wide attention to the apoptosis because of its considerable effect and potential medicative significance. Proliferating cell nuclear antigen(PCNA)seldom exists in G₀ stage of cell and mostly in proliferative or invert cells.It is an important index to the activity of cell proliferation.Expression of PCNA plays a significant role in the emergence and development of Wilm's tumor.The immunohistochemical Monoclonal Antibody method to estimate the express of PCNA has a high specificity.The histological structure can be keep up and the distribution of single proliferative cell can be observed at the same time.It has been a popular research topic of tumors.Therefore,there is an important practical significance for study on the variance of apoptosis and PCNA index of the post-TACE Wilm's tumor cells to explain the potential mechanism of therapeutic effect. ObjectiveTo evaluate the effect of TACE on the histopathological classification and morphologic distinctive characteristics of the Wilm's tumors.Study on the apoptosis and proliferating cell nuclear antigen(PCNA)expressed by nephroblastoma cells in order to discuss the mechanism of growth retardation and apoptosis of tumor cells by TACE.To discuss the potential prognostic factors of Wilm's tumor and explore the relationship of the long-term survival by TACE and the grade of different histopathological classification.Methods(1)The general clinical situation of 84 patients of Wilm's tumor were reviewed and analyzed at the same period.The patients were divided into TACE group,chemotherapy group and operation group by different therapies.(2)The excisional tumor specimens were compared and the ratio of neoplasm liquefaction necrosis was counted in different groups.(3)Morphologic characteristics of each tumor tissue were observed and histopathological classification was made according to the revised SIOP working classification of Wilm's tumor.(4)Study on 28 Wilm's tumor tissues suffering from fine-needle biopsy before TACE and the excisional tumor tissues after TACE.(5)Morphologic characteristics of the tumors' cells and interstitial substance in each group were also observed and propotional staging were undertaken.(6)The areas of cellular necrosis were observed and compared.(7)According to the random principle,15 tumor tissues in each group were choiced out.The effect on cell apoptosis and proliferation after TACE were learned using TENUL method to estimate the apoptosis index of tumor cell and the immunohistochemical Monoclonal Antibody method to estimate the index and class of PCNA.(8)The follow-up information was collected.The Cox's regression analysis model was used to anolysis the dependablity of every prognostic influencing factors and the long-term survival in different histological staging of TACE group.Results(1)In general,the mean age of 84 cases was 3.07±2.38 years old,with equal sex ratio and 69.0%of children being diagnosed before the age of 3 years.There are no statistical disparation in diagnostic age,gender and the operating technique,so the influence of these factors to the research can be ruled out.(2)In the 42 cases of the TACE group,the average tumor volume was 3370.60±3775.22cm³ and the average ratio of the tumor and the kidney was 47.89±17.52%,which had no statistical difference between each group(P＞0.05).The average ratio of neoplasm liquefaction necrosis was 62.91±14.61%,higher than the operation group's 3.05±3.25%(P＜0.05),but seemed no statistical difference with chemotherapy group(P＞0.05).(3)Base on the morphologic characteristics,three groups were discerned in the SIOP schemes.In the TACE group,there were 14 cases in the low-risk stage,20 cases in the intermediate-risk stage and 8 cases in the high-risk stage,which seemed no statistical difference with the opertion and chemotherapy group(P＞0.05).(4)The comparative study of the fine-needle biopsy tissue and and the excisional tumor tissues found that tumor cell necrosis was seldom observed in stromal type relatively(1/6),while it was prominent observed in other types especially in blastemal type(5/7).(5)The microstructure features of the TAGE group found that X₃ and X₄ degeneration was observed in 29 cases out of 42(69.05%),which was significantly higher than the operation group's 15.00%(3/20,P＜0.05) and had no statistical difference with chemotherapy group's 45.45% (10/22,P＞0.05).The average thickness of fibrous envelopes was 3.39±0.77mm,which was significantly higher than the operation group's 1.56±1.13mm.The atresia of medium-sized vessels were found in 40 cases out of 42(95.24%),which was significantly higher than the chemotherapy group and operation group(P＜0.05).Moreover the residue of flavescent lipiodol emulsion was seen in all eases.Obvious spumose rhagiocrine cells(37/42)and lymphocyte(40/42)infiltration can be observed.The hyperplasy of interstitial fibrous tissue were found in 32 cases out of 42cases,showing statistical significance with the chemotherapy group and operation group(P＜0.05).(6)The microscopic examination found that cellular necrosis was observed in all cases in TACE group.The average ratio of the necrosis area was 73.15±11.55%(ranged from 45%to 94.25%),showing statistical significance with the chemotherapy group's 64.72±8.28%and operation group's 2.87±2.31%(P＜0.01).(7)The average apoptosis index(AI)in the TACE group was 7.29±5.1 and 7.64±5.9 in chemotherapy group,which was significantly higher than the operation group(P＜0.05).AI of the SIOP intermediate-risk tumors was significantly higher than that of the high-risk tumors.The average PCNA-LI in the TACE group was 22.25±18.55,which was significantly lower than the operation group(P＜0.05).There were no statistical significance among the different series of SIOP type.However,there was still no statistical difference between the TACE group and the chemotherapy group in the AI and PCNA-LI.In TACE group,the AI and PCNA-LI had a negative correlation(P＜0.01)and the coefficient correlation was -0.972.(8)Multivariable analysis revealed significant prognostic factors as follow: age,the way of treatment,clinical stage and SIOP pathological type of the tumor.In TACE group,the median survival time was 142 months and mean survival time was 122.23 months.The survival rate of 2 years was 80.95%,which was significantly higher than the operation group and had no statistical difference with chemotherapy group.The only significant prognostic factor in TACE group was SIOP pathological type of the tumor.In the high-risk tumors,the mean survival time was 26 months and had no significant prognostic factors.Conclusion(1)The preoperative TACE used in Wilm's tumor is effective in inducing cell death,resulting in quick liquefaction necrosis in a large area.The necrosis and atresia of vessels in the tumor are occurred rapidly and the degeneration of the tumor cells is intensified, accompaning with the hyperplasy of interstitial fibrous tissue and the form of fibrous envelopes.The residue of flavescent lipiodol emulsion and the obvious spumose rhagiocrine cells infiltration will contribute to the death of tumor cell.(2)The sensitivity of TACE is related to different pathological types.(3)The preoperative TACE has more efficiency on inducing tumor cell apoptosis and restraining cell proliferation,leading to the objective of anti-tumor.(4)The preoperative TACE can improve the patient's survival rate effectively.The prognosis in the TACE group is concerned with the SIOP pathological types of the tumor closely.In the high-risk tumors, patients have a bad survival rate and need a better consummate treatment.