| Lymph node metastasis has been recognized as an independent risk factor affecting the prognosis of patients with cervical cancer,which determines whether adjuvant radiotherapy is needed after surgery.The five-year survival rate of patients with lymph node metastasis decreased from 88-92%to 55-64%.It is important to properly assess the status of the lymph nodes.The treatment of early stage cervical cancer is mainly surgery.The standard operation is radical hysterectomy and bilateral pelvic lymphadenectomy.Due to the large scope of resection,the corresponding incidence of surgical complications is high,including lymphatic cysts,lymphedema and vessels,nerve damage,etc,affecting the quality of life of patients.The lymph node metastasis rate of early cervical cancer is only 27%(about 0%to 2%in IA,11.5%to 22%in IB,26.7%to 33%in IIA,and 39.2%to 63%in IIB).About 80-85%of patients experienced an "excessive" lymph node dissection.The sentinel lymph node(SLN)refers to the first site of the lymph node that receives the lymphatic return from the primary lesion.It is also the first site of metastasis.It can be considered that when there is no lymph node metastasis in SLN,there is no metastasis in other lymph nodes.Detection of SLN in breast,penile,and melanoma is the standard diagnostic procedure.If the SLN is negative,the complete lymph node dissection can be omitted.The blue dye,nuclides,combined method,nano-carbon(CNP),and indocyanine green(ICG)mapped in cervical cancer have been reported,the sensitivity is different,but in general,the feasibility of SLN technology in cervical cancer has been initially confirmed,but there are still many problems,such as the affect on the detection rate by choice of tracer,tumor size,clinical stage and lymph vessel vaginal invasion(LVSI).In addition,whether routine pathological examination is sufficient to accurately diagnose lymph node metastasis?In the case of routine pathological diagnosis of negative lymph nodes,there are still about 10%of patients with postoperative recurrence.Consider the existence of micrometastasis.Micrometastasis is currently defined as a lesion<2mm,which is difficult to diagnose by conventional pathological section.Therefore,it is currently recommended to perform ultrastaging on lymph nodes.Common methods for ultraging include serial section pathology,immunohistochemistry,PCR,flow cytometry and gene chip technology.Usually these methods need to be combined to increase the detection of positive rates.Common markers include cytokeratin(CKs),human papillomavirus(HPV),squamous cell carcinoma antigen(SCCAg).The ESGO-ESTRO-ESP guidelines had used serial section pathology as a postoperative pathology standard for cervical cancer.Noventa et al recommend the detection of HPV in lymph nodes as a molecular marker for micrometastasis.When intraoperative frozen sections is negative,HPV-DNA detection can be used to improve the accuracy of lymph node metastasis diagnosis.The CK19 mRNA can detect more micrometastasis than conventional intraoperative or histological permanent sections and has already been validated for intraoperative examination of SLNs in breast cancer patients.SCCAg is highly specific and can be used for the diagnosis of squamous cell carcinoma.Currently,it has been widely used in the diagnosis and disease monitoring of cervical squamous cell carcinoma.With the further study,it was found that SCCAg is not expressed in mesenchymal tissues,so it can be used to being molecular marker of lymph node micrometastasis in squamous cell carcinoma.This study intends to use CNP for early stage cervical cancer SLN mapping,explore the feasibility and safety,understand the factors affecting the detection rate of SLN.Further carry out research on lymph node micrometastasis,through serial sectioning pathological and detection of the expression of HPV in SLNs by RT-PCR.Two methods were used to detect the rate of micrometastasis,compared with conventional pathology to verify the value of these two methods for diagnosing micrometastasisPart ? Feasibility of sentinel lymph node mapping in cervical cancer and sensitivity to pelvic lymph node metastasis:a meta analysisObjective:Systematic evaluation of sentinel lymph node(SLN)technique for cervical cancer,clinical value in the diagnosis of lymph node metastasis.Methods:Our computer retrieved databases such as PubMed,Embase,Cochrane library,and Wanfang,and searched for the beginning of the database?October 2,2018,domestic and foreign research on SLN detection for early cervical cancer,through QUAD AS-2(Quality Assessment of Diagnostic Accuracy)Studies-2)Quality assessment of the literature,statistical analysis of the data using stata12.0 software,analysis of the accuracy of these studies to diagnose lymph node metastasis.Results:A total of 36 studies(3853 patients)were included.The total sensitivity was 0.91(95%C1 0.88-0.93),I2=0(95%Cl 0-100),and the ROC of the subject curve was 0.99(0.98-1.00).The combined detection rate was 97.1%(95%CI:96.5-97.8%),heterogeneity I2=90.8%(P=0.000),and the combined bilateral SLN detection rate was 69.2%(95%CI:62.8-75.5%),heterogeneity test I2=95.7%(P=0.000),high heterogeneity,subgroup analysis.Conclusion:SLN technology has high sensitivity for diagnosing lymph node metastasis of cervical cancer.The advantages of routine pathological examination and pathologic ultrastaging for diagnosis of lymph node metastasis need to be verified by a larger sample size.The choice of tracer and the size of the tumor are the main influencing factors of the bilateral detection rate.Part ? Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with cervical cancerObjective:To investigate the value of carbon nanoparticles in identifying sentinel lymph nodes in cervical cancer.Methods:From January 2014 to July 2016,116 patients with cervical cancer stage IA2-IIA2,based on the International Federation of Gynecology and Obstetrics(FIGO)2009 criteria,were included in this study.The normal cervix around the tumor was injected with a total of 1 ml of carbon nanoparticles(CNP)at 3 and 9 o'clock.All patients then underwent laparoscopic pelvic lymph node dissection and radical hysterectomy.The black-dyed sentinel lymph nodes were removed for routine pathological examination and immunohistochemical staining.Results:Among the 116 patients,111 patients had at least one SLN.The detection rate was 95.69%(111/116).A total of 496 SLNs were detected,with an average of 4.5 SLN per case.A total of 26 patients with lymph node metastasis and 82 positive lymph nodes,of which 66 were SLNs and 16 were nSLN.Sentinel lymph nodes were localized in the external lilac(47.97%),internal lilac(13.87%),obturator(26.59%),parametrial(1.16%),and common iliac(8.67%)regions.The sensitivity of the SLN detection was 81.8%,the specificity was 91.0%,the accuracy was 89.2%,and the negative predictive value was 95.3%and the false negative rate was 3.4%.Conclusions:Sentinel lymph nodes can be used to accurately predict the pathological state of pelvic lymph nodes in cervical cancer.The detection rates and accuracy of sentinel lymph node were high.CNP can be used to trace the sentinel lymph node in early cervical cancer.Part ? Preliminary study about pathological ultraging of sentinel lymph node in cervical cancerObjective:Up to 15%of patients with cervical cancer which were negative in lymph nodes developed recurrent disease.This might due to micrometastases that had not been diagnosed by conventional pathological examination.Pathological ultraging may have diagnostic value for micrometastasis.The pathological ultraging of serial sections is enhanced by pathological methods for micrometastasis.This study evaluated the true positive,true negative,and false negative of the serial section of SLN in early stage cervical cancer to compared the sensitivity with conventional pathology.Methods:It was a prospective study,we analyzed FIGO stage IA2-IIA2 100 patients with cervical cancer in the Affiliated Tumor Hospital of Guang Xi Medical University from August 01,2017 to August 01,2018.All the patients underwent surgical treatment.SLN was mapped with carbon nanoparticles(CNP),and pelvic lymphadenectomy was performed.SLN was identified during surgery,at least one SLN was detected successfully.The black-stained SLN was removed and then a comprehensive pelvic lymph node dissectionąpara-aortic lymphadenectomy were performed.SLN was sent to pathological examination alone,first stained with H&E.When SLNs were negative,serial sections were taken and detected by cytokeratin AE1/AE3 immunohistochemical staining to evaluate the micrometastasis.Non-sentinel lymph nodes(nSLN)were examined by H&E only.Results:In all,100 patients were evaluable.SLN were detected bilaterally in 71%of cases(n=71)and unilaterally in 29%(n=29).There are 27 patients with lymph nodes metastasis.Final lymph node status showed micrometastasis in 13 patients,macrometastasis in 14.Patients with optimal bilateral SN detection were more likely to have any metastasis detected 35.21%vs.6.9%;P=0.004)as well as micrometastasis detected in their SLN(13%vs.0%).SLN ultrastaging resulted in a low overall false-negative rate of 2.0%and no false-negative rate for patients with optimal bilateral mapping.The two patients with false negative were unilaterally detected,the metastatic lymph nodes were located on the opposite side of SLN detection,and LVSI was present.Sensitivity of SLN pathological ultrastaging was 97.26(95%CI:93.52%-101.01%)and accuracy was 99%,95%CI:9 7.05%-100.95%for the whole group.Conclusion:SLN ultrastaging can increase the detection rate of micrometastasis,and bilateral SLN detection substantially decreases the false negative rate of SLN ultrastaging and increases detection of micrometastasis.SLN mapping and pathological ultrastaging should become standard practice in the surgical management of early-stage cervical cancer.Part ? Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancerObjectives:The aim of this study was to investigate the DNA expression of human papillomavirus(HPV)in sentinel lymph nodes(SLN)in patients with cervical cancer(CC),as well as to compare the positive rate of SLNs metastasis detected by routine pathological examination,and to explore the value of HPV-DNA in the detection of CC lymph node micrometastasis.Methods:RT-PCR was used to evaluate the HPV DNA detection in all CC samples(FIGO stage IA2-IIA2).The consistency of HPV-DNA was compared between primary lesions and SLNs.The positive rates of HPV-DNA and pathological diagnosis of SLN metastasis were compared,and the relationship between the positive expression of HPV-DNA in SLNs and the clinical and pathological parameters of cervical cancer patients were analyzed.Results:A total of 345 sentinel lymph nodes were detected in 100 patients with IA2-IIA2 CC.The positive rates of RT-PCR and conventional histopathological detection of SLNs metastasis were 31.6%(109/345)and 12.8%(44/345),respectively(P<0.001).The positive expression of HPV-DNA in SLNs was related to the clinical stage and tumor diameter(P<0.05),and was not associated to patients' age,depth of cervical invasion,histological grade,lymphatic and vascular space invasion(LVSI)and SCCAg(P>0.05).Conclusion:The detection of HPV-DNA expression in pelvic lymph nodes of CC can be used to improve the detection rate of micrometastasis,guide the postoperative adjuvant therapy more accurately and improve the prognosis.Patients with positive HPV-DNA could need closer surveillance than those with negative HPV-DNA. |
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