Diagnosis And Treatment Of Lymph Node Metastasis In Endometrial Cancer

CHARPTER1 SYSTEMATIC EVALUATION OF THE EFFICACY AND SAFETY OF SYSTEMATIC LYMPH NODE DISSECTION FOR EARLY ENDOMETRIAL CARCINOMAAND THE PROGNOSIS OF LYMPH NODE METASTASISObjective To systematically evaluate the efficacy and safety of standard surgery and systematic lymph node dissection for stage I endometrial carcinoma,pelvic lymph node dissection and pelvic and para-aortic lymph node dissection,as well as the prognostic analysis of lymph node metastasis.Methods This study “Endometrial cancer,pelvic lymphadenectomy,Para aortic lymphadenectomy”,“Endometrial carcinoma,pelvic lymph node cleaning technique,the lymph node by abdominal aorta” as the main key words,Computer retrieval for nearly 10 years(January 1,2008,solstice,January 1,2019)PUBMED,Cochrane library,China biomedical literature database,WIPO Chinese SCI-tech journal database,CNKI database,wanfang database.Manual retrieval of relevant literature including the meeting summary.Languages are limited to English and Chinese.Standard surgical group adopted the uterusdouble appendix resection and postoperative adjuvant therapy,the experiment group USES the uterus double appendix resection and pelvic lymph nodes were performed the lymph node or supplement line by abdominal aorta surgery plus postoperative adjuvant therapy,we will be divided into subgroup analysis in control group: the uterus double appendix resection and pelvic lymph nodes were performed and the whole uterus double appendix resection and pelvic lymph node cleaning and the lymph node by the abdominal aorta,the quality evaluation of the literature of into after extraction of available data,quality evaluation,using RevMan 5.3 software for Meta-analysis.The five-year survival rate and recurrence rate of the standard surgery group and the lymphatic dissection group were compared.Postoperative complications: lower limb edema,lymphocyte,deep vein thrombosis,intestinal obstruction,ureteral fistula were used as the efficacy observation indexes.The RR values of each study were calculated and their significance was discussed.Results There were 2 clinical randomized controlled trials and 20non-randomized controlled trials,a total of 10050 patients met the inclusion criteria.Meta analysis results showed that there was no significant difference in5-year overall survival between the standard surgery group(no lymphadenectomy group)and the lymphadenectomy group [RR=0.98,95%CI(0.84,1.14),P=0.82].There was also no significant difference in recurrence rates[RR=0.98,95%CI(0.69,1.39),P=0.90].Pelvic lymphadenectomy group and pelvic + para-aortic lymphadenectomy group: the 5-year overall survival rate of pelvic lymphadenectomy group was lower than that of pelvic + para-aortic lymphadenectomy group [RR=0.87,95%CI(0.83,0.92),P<0.00001].Pelvic +para-aortic lymphadenectomy reduced the recurrence rate [RR=2.44,95%CI(1.81,3.28),P<0.00001].Postoperative wound infection rate in thelymphadenectomy group was lower than that in the standard surgery group[RR=0.56,95%CI(0.32,0.98),P=0.04],while postoperative complications of lower limb edema [RR=6.15,95%CI(1.11,34.00),P=0.04],thrombosis[RR=3.35,95%ci(1.80,6.25),P=0.0001] and lymphocele [RR=10.96,95%CI(1.95,61.41),P=0.006] in the lymphadenectomy group were higher than that in the standard surgery group.There was no significant difference in ileus[RR=1.57,95%CI(0.79,3.09),P=0.20] and ureteral injury [RR=1.53,95%CI(0.50,4.65),P=0.46].There was no significant difference between pelvic lymphadenectomy group and pelvic + para-aortic lymphadenectomy group with postoperative complication such as ileus [RR=0.41,95%CI(0.06,2.61),P=0.34],thrombosis [RR=0.93,95%CI(0.28,3.10),P=0.90],lymphocele [RR=0.83,95%CI(0.61,1.12),P=0.22],lower limb edema [RR=1.02,95%CI(0.66,1.58),P=0.92] and ureteral injury [RR=1.26,95%CI(0.44,3.57),P=0.67].Conclusions Systematic pelvic lymphadenectomy is not recommended for patients with early endometrial cancer.If lymph node dissection is considered,pelvic and para-aortic lymph node dissection is recommended.Although a large number of literatures have been included,the quality of the studies is not very high.Systematic lymphadenectomy for early endometrial cancer requires large-scale prospective studies,so as to make more scientific clinical decisions for gynecologist.CHARPTER2 RESEARCH ON CLINICAL CHARACTERISTICS AND PROGNOSIS IN ENDOMETRIAL CANCER PATIENTS WITH LYMPH NODE METASTASISObjective:To analyze the clinical characteristics and prognosis of endometrial cancer patients with lymph node metastasis in the real world,so as to provide reference for lymph node dissection in patients with endometrial cancer.Methods:To extract the electronic medical data of 1219 patients with endometrial malignancy were treated by our hospital based on hospital information system(HIS): a large integrated warehouse of electronic medical records(EMR).Then,made a mean and rate descriptive analysis,and survival analysis for the general characteristics,clinical symptoms,testing index and pathological manifestations,operation related problems.Result:(1)Lymph node metastasis rate was 9.8%,para-aortic lymph node metastasis rate was 19.2%,abdominal aorta + pelvic lymph node metastasis rate was 56.7%,pelvic lymph node metastasis rate was 24.2%.The metastasis rate of abdominal aorta + pelvic lymph node was significantly higher than that of pelvic or para-aortic lymph node alone.(2)The average age of endometrial cancer patients with lymph node metastasis was 52.74 years old,ranging from 23 to 73 years old.(3)The first symptoms of endometrial cancer patients with or without lymph node metastasis were mainly irregular vaginal bleeding,and the proportion of postmenopausal patients was higher than that of non-menopausal patients.(4)When do gynecologic examination for endometrial cancer patients,the proportion of vagina and the side of the uterus involvement is low,but the patients with lymph node metastasis in the ratio of vagina and the side of the uterus involvement,HPV detection,TCT,CRP value?10ng/ml,G3,postoperative pathological includes cervical invasion,lymphatic vascular invasion,muscular infiltration depth > 1/2 were higher than in patients without lymph node metastasis.(5)The proportion of CA125 ?35 U/ml in endometrial cancer patients with lymph node metastasis was higher than that of CA125 < 35 U/ml.(6)The median number of dissected lymph node in pelvic lymphadenectomy group was 17,ranging from 1 to 51,among which the median of dissected lymph node in patients with lymph node metastasis and non-metastasis was 20,17,ranging from 1 to 40,and 1 to 51,respectively.The median number of dissected lymph nodes in para-aortic lymphadenectomy group was 6 and the range was 1-29,among which the median number of dissected lymph nodes in patients with and without lymph node metastasis was 3and 6,and the range was 1-21 and 1-29,respectively.(7)According to the survival and prognosis analysis of relevant clinicopathological in endometrial cancer patients with lymph node metastasis,it was found that there was no statistically significant difference in the overall survival rate between the three groups of patients with pelvic and para-aortic lymph node metastasis,patients with pelvic lymph node metastasis alone,and patients with para-aortic lymph node metastasis alone.Among endometrial cancer patients with lymph node metastasis,CA125 value,lymphangitic infiltration,cervical involvement and tissue differentiation showed no significant difference in prognosis.(8)COX regression analysis showed that the expression of CA125 was an independent prognostic factor affecting OS.Conclusion:(1).The lymph node metastasis rate of endometrial cancer is low.The lymph node positive rate is related to tissue differentiation,lymphangitic infiltration,cervical invasion,muscle infiltration depth > 1/2,and CA125.(2).The metastasis rate of pelvic and para-aortic lymph node is higher than pelvic lymph node alone or para-aortic lymph node alone.(3).There was no statistically significant difference in the overall survival rate between the three groups of patients with pelvic and para-aortic lymph node metastasis,patients with pelvic lymph node metastasis alone,and patients with para-aortic lymph node metastasis alone.CHARPTER 3 BIOINFORMATICS ANALYSIS OF GENES RELATED TO ENDOMETRIAL CANCER WITH LYMPH NODES METASTASISObjective To investigate the potential genes associated with lymph nodes metastasis in endometrial cancer(EC)through microarray data analysis and bioinformatics methods.Methods We screen m RNA expression profiling chip data related to lymph node metastasis of EC from the GEO database,analyze m RNA expression profiling by array,search for differentially expressed genes,and combine biological process annotation,biological signaling pathway enrichment,text mining and protein/gene interactions to analyze again,to search for signaling pathways and genes associated with lymph node metastasis in endometrial cancer.Results GSE2109 and GSE39099 accession were obtained in the GEO database,and eight signaling pathways(type I interferon,interferon-gamma-mediated,PI3K-Akt?Rap1?TGF-beta?c GMP-PKG?Wnt and Ras)were found though the signaling pathways enrichment of common differentially expressed genes.Regulate the14 differentially expressed genes in these signaling pathways.Among them,11 genes were associated with lymph node metastasis of EC and formed a protein interaction network.PI3K-Akt signaling pathway may be an important signaling pathway for lymph node metastasis of EC.VEGFC and IRS1 may be the important candidate genes related to the regulation of lymph node metastasis in EC.Conclusion We found that eight signaling pathways and 11 differentially expressed genes were identified to be associated with lymph node metastasis in endometrial cancer by bioinformatics analysis.CHAPTER 4 STUDIES ON THE EXPRESSION OF MULTIPLE RELATED PROTEINS IN LYMPH NODE METASTATIC TISSUE OF ENDOMETRIAL CARCINOMASECTION1 THE RELATIONSHIP BETWEEN RELATED GENES AND CLINICAL FACTORS AND PROGNOSIS OF ENDOMETRIAL CARCINOMA WAS ANALYZED BY TCGAObjective The clinical database was used to further analyze the expression and prognosis of 8 genes related to endometrial carcinoma.Methods The above genes datas were in endometrial cancer for conducted mining from TCGA database data by bioinformatics,so as to understand the expression of relevant genes in endometrial cancer and their prognostic relationship.Result(1)The up-regulated genes in endometrial cancer include CA125,CK19 and e IF4 E.The down-regulated genes were VEGF-C,IRS1,FGFR1,ANGPT1,LPAR4,IFNA1 and IL7.(2)There was no significant difference in PRLR expression between endometrial carcinoma and normal tissue.Each gene was clinically analyzed for endometrial cancer.For example,it was associated with body weight,age,postmenopausal and pathological types.From the pathological types,we found that the expression of CA125,e IF4 E,IL7,LPAR4 and VEGF-C in endometrial adenocarcinoma was significantly higher than that of in serous adenocarcinoma.(3)CK19 gene expression in endometrioid adenocarcinoma was significantly lower than that in serous adenocarcinoma.IRS1,FGFR1 and ANGPT1 were not significantly different among pathological types.(4)According to K-M analysis of public clinical data,we found that the survival rate of LPAR4 with low expression level was significantly higher than that with high expression level,while there was no significant difference in others 9 genes(CA125,CK19,e IF4 E,vegf-c,IRS1,FGFR1,ANGPT1,IFNA1 and IL7).(5)Lymph node tssue microarray of endometrial carcinoma was successfully completed.Conclusion Through analysis,we finally targeted 8 genes(CA125,CK19,vegf-c,CD44V6,IRS1,FGFR1,ANGPT1 and e IF4E)as immunohistochemical validation genes,laying a foundation for clinical decisions on lymph node dissection.SECTION 2 THE EXPRESSION AND SIGNIFICANCE OF RELATED PROTEINS IN ENDOMETRIAL CANCER WITH LYMPN NODES METASTASIS WERE STUDIED BY TISSUE MICROARRAY TECHNIQUEObjective To explore new important tumor markers for preoperative evaluation to lymph node metastasis in endometrial carcinoma.Methods Through the application of tissue microarray technology in endometrial carcinoma with lymph node metastasis pathological tissue to verify the expression of the above eight tumor markers(CA125,CK19,VEGFC,CD44V6,IRS1,FGFR1,ANGPT1,EIF4E)in immunohistochemistry,Spearman rank correlation analyzes the correlation of eight proteins,ROC analyzes showed that combined CK19,VEGFC,IRS1 and EIF4 E proteins to detect the sensitivity and AUC area of lymph node metastasis,and K-M method analyzes the 5-year overall survival rate.Result(1)Immunohistochemistry showed that CK19 and EIF4 E proteins were highly expressed in the intimal tissues of lymph node metastasis(56.14%,52.63%).IRS1 protein was highly expressed in positive lymph node tissues(70.18%).VEGFC was highly expressed in both positive lymph node tissue and intimal tissue of lymph node metastasis(54.39%,61.40%).(2)EIF4E protein had a moderate negative correlation with CA125,and a moderate positive correlation with CD44v6,CK19,IRS1,ANGPT1,VEGFC,and FGFR1.CK19 was moderately negatively correlated with IRS1 and VEGFC(r=-0.366,P=0.001).There was a significant positive correlation between IRS1 and VEGFC(r=-1.000,P=0.001).In other words,patients with positive IRS1 expression may have a high positive VEGFC expression.(3)ROC analysis showed that the sensitivity and specificity of detecting lymph node metastasis in endometrial cancer by combining IRS1,VEGFC,CK19 and EIF4 E proteins expression were 0.778 and 0.825(AUC=0.887,95% ci0.681-0.922,P=0.001).(4)There was no statistically significant difference in 5-year survival rate between the IRS1 negative group and IRS1 positive group in endometrial cancer tissues and positive lymph node tissues(P > 0.05),and also was no statistically significant difference in 5-year survival rate between the VEGFC negative group and the VEGFC positive group in endometrial cancer tissues and positive lymph node tissues(P > 0.05).Conclusion Through analysis,we think that the combined expression of IRS1 and VEGFC proteins may be a potential marker for the prediction of lymph node metastasis in endometrial cancer,laying a foundation for the clinical decision of lymph node dissection.