Lymph Nodes In Cervical Cancer Research Articles

Equivalent dose in 2 Gy (EQD2) to pelvic lymph nodes using volume based prescription for three brachytherapy applicators - a dosimetric retrospective analysis.

BackgroundPelvic lymph node (PLN) metastasis has been included in the FIGO staging, so there is a need to determine the dose contribution from brachytherapy to ascertain the total delivered dose to the pelvic lymph nodes in cervical cancer. The aim of the study was to calculate the equivalent dose in 2 Gy (EQD2) of the pelvic lymph nodes (PLNs) based on volume prescription using three applicators.Materials and methodsForty-one patients who had undergone external beam radiotherapy followed by brachytherapy using tandem ovoids (TO), tandem ring (TR) and TO + free hand interstitial needles (TO + FH) applicators were taken for this study. 26 Gy in 4 fractions was prescribed to HRCTV. The external iliac node (ELN), internal iliac node (ILN) and obturator (OBT) were contoured and the median EQD2 of the lymph nodes was calculated.ResultsThe median bilateral EQD2 values of ELN were 1.55 Gy (TR), 1.75 Gy (TO), 1.9 Gy (TO + FH), of ILN these were 2.57 Gy (TR), 3.27 Gy (TO), 3.04 Gy (TO + FH), and of OBT these were 3.69 Gy (TR), 4.46 Gy (TO), 4.69 Gy (TO + FH), respectively. The total median EQD2 values of TR, TO and TO + FH were 52.71 Gy, 53.03 Gy, and 53.88–62.73 Gy, respectively.ConclusionOur study calculated the median EQD2 to the pelvic lymph nodes using three types of applicators in brachytherapy. This could serve as reference to decide on the EBRT boost dose while treating patients with enlarged pelvic lymph nodes.

Updating and Optimizing Anatomic Atlases for Elective Radiation of Para-Aortic Lymph Nodes in Cervical Cancer

PurposePrevious studies have proposed 2 different contouring guidelines for the prophylactic radiation of para-aortic lymph nodes (PANs) for locally advanced cervical cancer. Because PAN-mapping atlases in current literature are limited to small patient samples and nodal populations, we updated the PAN atlas with a large data set of positron emission tomography (PET)–positive PANs on PET/computed tomography (CT) from patients with cervical cancer. Methods and MaterialsWe identified 176 PET-positive PANs on pretreatment PET/CT of 47 patients with diagnosed International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer. PANs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). PAN clinical target volume (CTV) contours were drawn for all patients based on previously published guidelines by Takiar (CTV-T) and Keenan (CTV-K) and nodal volumetric coverage was assessed. ResultsWe identified 94 LPA nodes (54%), 71 AC nodes (40%), and 11 (6%) RPC nodes. CTV-T had improved nodal center coverage of 97.6% compared with 85.0% for CTV-K (P < .001). Nodal center coverage for CTV-K and CTV-T (with corresponding PAN) were 79 (84.0%) and 93 (99.0%) LPA nodes (P = .001), 64 (90.1%) and 68 (95.8%) AC nodes (P = .221), and 5 (45.5%) and 9 (81.8%) RPC nodes (P = .134), respectively. Additionally, our updated PAN atlas identified nodal centers anterior to the aorta and inferior vena cava that are not covered by CTV-T but covered by CTV-K due to the 10 mm anterior aortic expansion of CTV-K. ConclusionsWe have updated the PAN anatomic map of 176 PET-positive nodes from 47 patients and demonstrated that CTV-T has significantly better PAN coverage over CTV-K for posterior LPA and retrocaval regions for our data set. Additionally, we suggest a modification that includes a blend of CTV-T and CTV-K to provide optimal coverage for the mapped nodes anterior to the great vessels in our data set.

The invasion status of lymphovascular space and lymph nodes in cervical cancer assessed by mono-exponential and bi-exponential DWI-related parameters

To investigate whether mono-exponential and bi-exponential diffusion-weighted imaging (DWI)-related parameters of the primary tumour can evaluate the status of lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) in patients with cervical carcinoma preoperatively. Eighty patients with cervical carcinoma were enrolled, who underwent preoperative multi b-value DWI and radical hysterectomy. They were classified into LVSI(+) versus LVSI(-) and LNM(+) versus LNM(-) according to postoperative pathology. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) were calculated from the whole tumour (_whole) and tumour margin (_margin). All parameters were compared between LVSI(+) and LVSI(-) and between LNM(+) and LNM(-). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic performance of these parameters. f_margin and D∗_whole showed significant differences in differentiating LVSI(+) from LVSI(-) tumours (p=0.002, 0.008, respectively), while LNM(+) tumours presented with significantly higher ADC_margin than that of LNM(-) tumours (p=0.009). The other parameters were not independent related factors with the status of LVSI or LNM according to logistic regression analysis (p>0.05). The area under the ROC curve of f_margin combined with D∗_whole in discriminating LVSI(+) from LVSI(-) was 0.826 (95% confidence interval [CI]: 0.691-0.961), while ADC_margin in differentiating LNM(+) from LNM(-) was 0.788 (95% CI: 0.648-0.928). The parameters generated from mono-exponential and bi-exponential DWI of the primary cervical carcinoma could help discriminate its status regarding LVSI (f_margin and D∗_whole) and LNM (ADC_margin).

Validated limited gene predictor for cervical cancer lymph node metastases

Purpose: Recognizing the prognostic significance of lymph node (LN) involvement for cervical cancer, we aimed to identify genes that are differentially expressed in LN+ versus LN- cervical cancer and to potentially create a validated predictive gene signature for LN involvement.Materials and Methods: Primary tumor biopsies were collected from 74 cervical cancer patients. RNA was extracted and RNA sequencing was performed. The samples were divided by institution into a training set (n = 57) and a testing set (n = 17). Differentially expressed genes were identified among the training cohort and used to train a Random Forest classifier.Results: 22 genes showed > 1.5 fold difference in expression between the LN+ and LN- groups. Using forward selection 5 genes were identified and, based on the clinical knowledge of these genes and testing of the different combinations, a 2-gene Random Forest model of BIRC3 and CD300LG was developed. The classification accuracy of lymph node (LN) status on the test set was 88.2%, with an Area under the Receiver Operating Characteristic curve (ROC-AUC) of 98.6%.Conclusions: We identified a 2 gene Random Forest model of BIRC3 and CD300LG that predicted lymph node involvement in a validation cohort. This validated model, following testing in additional cohorts, could be used to create a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tool that would be useful for helping to identify patients with LN involvement in resource-limited settings.

Identification of Prognostic miRNA Signature and Lymph Node Metastasis-Related Key Genes in Cervical Cancer.

BackgroundmiRNAs and genes can serve as biomarkers for the prognosis and therapy of cervical tumors whose metastasis into lymph nodes is closely associated with disease progression and poor prognosis.MethodsR software and Bioconductor packages were employed to identify differentially expressed miRNAs (DEMs) from The Cancer Genome Atlas (TCGA) database. GEO2R detected differentially expressed genes (DEGs) in the GSE7410 dataset originating from the Gene Expression Omnibus (GEO). A Cox proportional hazard regression model was established to select prognostic miRNA biomarkers. Online tools such as TargetScan and miRDB predicted target genes, and overlapping DEGs and target genes were defined as consensus genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) function annotations were performed to discern the potential functions of consensus genes. STRING and Cytoscape screened key genes and constructed a regulatory network.ResultsA combination of four miRNAs (down-regulated miR-502 and miR-145, up-regulated miR-142 and miR-33b) was identified as an independent prognostic signature of cervical cancer. A total of 94 consensus genes were significantly enriched in 7 KEGG pathways and 19 GO function annotations including the cAMP signaling pathway, the plasma membrane, integral components of the plasma membrane, cell adhesion, etc. The module analysis suggested that CXCL12, IGF1, PTPRC CDH5, RAD51B, REV3L, and WDHD1 are key genes that significantly correlate with cervical cancer lymph node metastasis.ConclusionsThis study demonstrates that a four-miRNA signature can be a prognostic biomarker, and seven key genes are significantly associated with lymph node metastasis in cervical cancer patients. These miRNAs and key genes have the potential to be therapeutic targets for cervical cancer. Among them, two miRNAs (miR-502 and miR-33b) and two key genes (PTPRC and CDH5) were first reported to be potential novel biomarkers for cervical cancer. The current study further characterizes the progression of lymph node metastasis and mechanism of cervical tumors; therefore, it provides a novel diagnostic indicator and therapeutic targets for future clinical treatments.

Value of integrated PET-IVIM MR in assessing metastases in hypermetabolic pelvic lymph nodes in cervical cancer: a multi-parameter study.

To evaluate the value of integrated multi-parameter positron emission tomography-intravoxel incoherent motion magnetic resonance (PET-IVIM MR) imaging for pelvic lymph nodes with high FDG uptake in cervical cancer, and to determine the best combination of parameters. A total of 38 patients with 59 lymph nodes with high FDG uptake were included. The imaging parameters of the lymph nodes were calculated by PET-IVIM MR, and the differences between lymph nodes diagnosed by postoperative pathology as metastasis versus non-metastasis were compared. We used the receiver operating characteristic (ROC) curve and logistic regression to construct a combination prediction model to filter low value and similar parameters, in order to search the optimal combination of PET/MR parameters for predicting pathologically confirmed metastatic lymph nodes. The correlation between diffusion parameters and metabolic parameters was analyzed by Spearman's rank correlation. The maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total metabolic tumor volume (MTV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), diffusion-related coefficient (D), and perfusion-related parameter (F) showed significant differences between the metastatic and non-metastatic groups (p < 0.05). The combination of MTV, SUVmax, and D had the strongest predictive value (area under the ROC 0.983, p < 0.05). SUVmax, SUVmean, and TLG weakly correlated with F (R = - 0.306, - 0.290, and - 0.310; p < 0.05). The combination of MTV, SUVmax, and D may have a better diagnostic performance than PET- or IVIM-derived parameters either in combination or individually. No strong correlation exists between diffusion parameters and metabolic parameters. • Integrated PET-IVIM MR may assist to characterize lymph node status. • The combination of MTV, SUVmax, and D may have a better diagnostic performance than PET- or IVIM-derived parameters either in combination or individually for the assessment of pelvic lymph nodes with high FDG uptake. • No strong correlation exists between diffusion parameters and metabolic parameters in pelvic lymph nodes with high FDG uptake.

Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

The aim of the present study was to investigate the expression of human papillomavirus (HPV) DNA in sentinel lymph nodes (SLN) in patients with early-stage cervical cancer (CC). In addition, the present study compared the positive rate of SLNs metastasis detected by routine pathological examination, and investigated the value of HPV-DNA in the detection of early CC lymph node micrometastasis. Reverse transcription-quantitative PCR (RT-qPCR) was used in order to evaluate the HPV DNA detection in all CC samples [International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA2]. The consistency of HPV-DNA was compared between primary lesions and SLNs. The positive rates of HPV-DNA were compared with pathological diagnosis of SLN metastasis, and the association between the positive expression of HPV-DNA in SLNs and the clinical and pathological parameters of patients with cervical cancer were analyzed. A total of 345 sentinel lymph nodes were detected in 100 patients with IA2-IIA2 CC. The positive rates of RT-qPCR 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 associated with the clinical stage and tumor diameter (P<0.05), but not with patients' age, depth of cervical invasion, histological grade, lymphatic and vascular space invasion (LVSI), squamous cell carcinoma antigen (SCCAg) (P>0.05). The detection of HPV-DNA expression in pelvic lymph nodes of early CC may be used to improve the detection rate of micrometastasis, guide the postoperative adjuvant therapy more accurately and improve prognosis. Patients with positive HPV-DNA would require closer surveillance than those with negative HPV-DNA.

The variable impact of positive lymph nodes in cervical cancer: Implications of the new FIGO staging system

ObjectiveThe 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer changed from a clinical system to a clinical/pathologic/radiologic system with stages IIIC1 and IIIC2 indicating positive pelvic and para-aortic lymph nodes, respectively. We evaluated the National Cancer Database (NCDB) for the impact on survival of lymph node metastases (LNM). MethodsThe NCDB from 2004 to 2015 was queried for patients with cervical cancer, yielding 115,819 patients. Patients with FIGO IVB (22,569), non-adeno/squamous cell histologies (5,909), unknown nodal status (60,695), or unknown survival time (9,473) were excluded. Survival was compared using Cox proportional hazard model based on nodal status. Univariate (UVA) and multivariate analyses (MVA) were done for the overall cohort, followed by UVA by individual stage. ResultsIn 17,173 eligible patients, LNM negatively affected survival (UVA IIIC1 Hazard Ratio [HR] 2.0, p < 0.001, IIIC2 HR 3.9, p < 0.001, MVA IIIC1 HR 1.36, p < 0.001, IIIC2 HR 2.14, p < 0.001). In T1B, the effect of IIIC2 was most pronounced (HR 5.38, p < 0.001 versus HR 1.5 p = 0.001 for IIIC1 disease). In T3, the effect of LNM was markedly less: (HR 1.7, p < 0.001 for IIIC2 versus HR 1.2 p = 0.02 for IIIC1). Within T1B, there was no difference in survival for IIIC1 for the smaller T stages (IB1-2). ConclusionIn this study, LNM negatively affects prognosis in cervical cancer. The impact on survival varies by T stage with the greatest effect seen in stage T1B with IIIC2 disease.

Dose Response Relationship and Prognostic Factors of Nodal Control Rate of Metastatic Lymph Nodes in Cervical Cancer

In contrast to excellent local control in definitive aim radiation therapy (RT) of cervical cancer, control rate of metastatic lymph nodes remains insufficient. Therefore, radiation boost to metastatic lymph nodes has been attempted, but little is known about the optimal dose and prognostic factors of regional nodal control. In this study, we retrospectively investigated the dose response relationship of metastatic lymph nodes as well as prognostic factors of nodal control, and attempted to propose optimal dose for individual metastatic lymph nodes. We identified 90 patients (295 lymph nodes) who received definitive aim RT for node positive cervical cancer between 2013 and 2017. Total prescribed dose to each metastatic lymph node was converted to 2 Gy equivalent dose (EQD2, α/β = 10 Gy). Each node was tracked individually from initial diagnosis to any recurrence in the same specific node. Any tumor or treatment factors predictive of nodal control were searched. In addition, we attempted to stratify risk groups in order to find optimal dose for nodal control in a certain risk group. The median number of metastatic lymph nodes per patient was 2 (range, 1-14). Regarding total lymph nodes, the most common pathology was squamous cell carcinoma (85.6%) followed by adenocarcinoma (8.9%) and others (5.6%). The mean nodal volume at initial diagnosis was 5.0 ± 9.2 mL, and the mean total prescribed dose in EQD2 for each node was 55.0 ± 6.8 Gy. With median follow up of 25 months (range, 3-57 months), 32 nodal failures occurred, and 2-year nodal control rate was 89%. In multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) higher than 3.0 (p<0.001), para-aortic nodes (vs. pelvic nodes, p=0.013), larger initial nodal volume (p<0.001) and lower total dose (HR 0.90 for increase of 1 Gy in EQD2; 95% CI 0.85-0.95; p<0.001) were identified as risk factors for poor nodal control. Each node was stratified into two risk groups; low risk group with none or one risk factor, and high risk group with two or three risk factors. For risk group analysis, initial nodal volume was dichotomized (≤ 5.3 mL or > 5.3 mL). ROC curve analysis showed that 53.1 Gy and 62.0 Gy was the optimal cut-off dose for predicting nodal control rate in low and high risk group, respectively. In low risk group, doses higher than 53.1 Gy showed significantly superior nodal control rate (p=0.050) with 2-year nodal control rate of 99% (vs. 93% for ≤ 53.1 Gy). In high risk group, doses equal to or higher than 62.0 Gy showed superior nodal control rate with marginal significance (p=0.053) with 2-year nodal control rate of 80% (vs. 62% for < 62.0 Gy). Our data demonstrated that nodal control depends on the prescribed dose to lymph node, NLR, location of lymph node, and initial nodal volume. Therefore, these factors should be considered to enhance nodal control at the stage of treatment plan.

Indocyanine green can stand alone in detecting sentinel lymph nodes in cervical cancer

ObjectivesThe effectiveness of indocyanine green (ICG) dye for detecting sentinel lymph nodes (SLNs) in cervical cancer compared with other tracers is unknown. This study aimed to assess the validity of ICG dye in detecting SLNs in cervical cancer preoperatively.MethodsWe performed a literature search for identifying eligible articles from PubMed database using the search terms “cervical cancer”, “sentinel lymph node”, “indocyanine green”, “blue dyes”, “human serum albumin”, and “technetium-99 radiocolloid”. We performed a meta-analysis. Comparison of the overall, bilateral, and unilateral detection rates of the different tracers was the primary goal. Comparison of the false-negative rate among the tracers was the secondary goal.ResultsOnly eight retrospective studies including 661 patients were included. ICG versus combinations of three other tracers showed significantly higher bilateral and unilateral detection rates, but no difference in the overall rate of detecting SLNs. ICG had a higher bilateral detection rate than blue dye and technetium-99. Absorbing human serum albumin into ICG as a lymphatic tracer did not show a difference in detection rate compared with ICG alone.ConclusionsICG is superior and better than other tracers, and absorbing human serum albumin as a lymphatic tracer is not required in patients with cervical cancer.

Cervical Injection of Methylene Blue for Identification of Sentinel Lymph Nodes in Cervical Cancer

Cervical Injection of Methylene Blue for Identification of Sentinel Lymph Nodes in Cervical Cancer

Risk of micrometastases in non-sentinel pelvic lymph nodes in cervical cancer

ObjectiveA high sensitivity of sentinel lymph nodes (SLN) for pelvic lymph node (LN) staging has been repeatedly shown in patients with cervical cancer. However, since only SLN are evaluated by pathologic ultrastaging, the risk of small metastases, including small macrometastases (MAC) and micrometastases (MIC), in non-SLN is unknown. This can be a critical limitation for the oncological safety of abandoning a pelvic lymphadenectomy. MethodsThe patients selected for the study had cervical cancer and were at high risk for LN positivity (stage IB–IIA, biggest diameter≥3cm). The patients had no enlarged or suspicious LN on pre-operative imaging; SLNs were detected bilaterally and were negative on intra-operative pathologic evaluation. All SLNs and all other pelvic LNs were examined using an ultrastaging protocol and processed completely in intervals of 150μm. ResultsIn all, 17 patients were enrolled into the study. The mean number of removed pelvic LNs was 30. A total of 573 pelvic LNs were examined through ultrastaging protocol (5762 slides). Metastatic involvement was detected in SLNs of 8 patients (1× MAC; 4× MIC; 3× ITC) and in non-SLNs in 2 patients (2× MIC). In both cases with positive pelvic non-SLNs, there were found MIC in ipsilateral SLNs. No metastasis in pelvic non-SLNs was found by pathologic ultrastaging in any of the patients with negative SLN Side-specific sensitivity was 100% for MAC and MIC. There was one case of ITC detected in non-SLN, negative ipsilateral SLN, but MIC in SLN on the other pelvic side. ConclusionsAfter processing all pelvic LNs by pathologic ultrastaging, there were found no false-negative cases of positive non-SLN (MAC or MIC) and negative SLN. SLN ultrastaging reached 100% sensitivity for the presence of both MAC and MIC in pelvic LNs.

The relationship among the expressions of vascular endothelial growth factor-C and its receptor and the cervical cancer growth and lymph node metastasis

Objective To study the relationship between the expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-2 (KDR) in cervical carcinoma and the formation of cervical cancer and lymph node metastasis. Methods We selected 72 cervical carcinoma tissues, their corresponding adjacent tissues and 36 normal cervical tissues which have been resected in the Maternal and Child Health Care Hospital of Baoji of Shaanxi Province from January 2010 to December 2013. The mRNA and protein expressions of VEGF-C and KDR were examined by semi-quantitative PCR and enzyme linked immunosorbent assay in these tissues. The relationships between the expressions of VEGF-C and KDR and the formation of cervical cancer and lymph node metastasis were analyzed. Results The mRNA levels of VEGF-C in 72 cases of cervical cancer tissues and its corresponding adjacent tissues were 4.67±1.05 and 2.02±0.65, which were significantly higher than those in normal cervical tissues (0.36±0.06), with significant differences (t=2.247, P=0.025; t=1.379, P=0.027). The protein levels of VEGF-C in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 68.30±17.10 and 48.20±12.70, which were significantly higher than those in normal cervical tissues (18.40±10.70), with significant differences (t=4.357, P=0.016; t=6.337, P=0.012). The mRNA levels of KDR in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 3.52±0.95 and 1.92±0.87, which were significantly higher than those in normal cervical tissues (0.72±0.36), with significant differences (t=3.127, P=0.023; t=1.214, P=0.028). The protein levels of KDR in 72 cases of cervical cancer tissues and their corresponding adjacent tissues were 47.20±15.60 and 38.60±11.30, which were significantly higher than those in normal cervical tissues (16.40±9.40), with significant differences (t=3.667, P=0.020; t=0.986, P=0.032). The expression level of VEGF-C protein in 72 cases of cervical cancer tissues was not correlated with age (χ2=0.54, P=0.17), tissue type (χ2=0.34, P=0.25), depth of invasion (χ2=5.39, P=0.08), pathological grade (χ2=0.78, P=0.11), but was correlated with tumor size (χ2=22.34, P=0.02), clinical stage (χ2=32.14, P=0.01) and lymph node metastasis (χ2=15.58, P=0.03). The expression level of its receptor KDR was correlated with tumor size (χ2=13.78, P=0.04), tissue type (χ2=32.74, P=0.01), pathological grade (χ2=13.72, P=0.04), depth of invasion (χ2=10.27, P=0.04), clinical staging (χ2=20.25, P=0.02) and lymph node metastasis (χ2=19.52, P=0.02), but was not correlated with age (χ2=4.17, P=0.09). Conclusion The expression levels of VEGF-C and KDR are correlated with the growth, invasion and metastasis of cervical cancer, which are good indicators of the lymph node metastasis. Key words: Uterine cervical neoplasms; Lymphatic metastasis; Vascular endothelial growth factor C

Characterization of long non-coding RNA expression profiles in lymph node metastasis of early-stage cervical cancer.

Pelvic lymph node metastasis (PLNM) is an independent prognostic parameter and determines the treatment strategies of cervical cancer. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the process of tumor biological functions. This study aimed to mine lymph node metastasis-associated lncRNAs and investigate their potential pathophysiological mechanism in cervical cancer lymph node metastasis. We applied the lncRNA-mining approach to identify lncRNA transcripts represented on Affymetrix human genome U133 plus 2.0 microarrays from Gene Expression Omnibus (GEO) and then by validation in clinical specimens. The biological role and molecular mechanism of these lncRNAs were predicted by bioinformatic analysis. Subsequently, a receiver operating characteristic (ROC) curve and survival curve were conducted to evaluate the diagnostic and prognostic value of candidate lncRNAs. In total, 234 differentially expressed lncRNAs were identified to significantly associate with pelvic lymph node metastasis in early-stage cervical cancer. Our qRT-PCR results were consistent with the mining analysis (P<0.05). The functional enrichment analysis suggested that these lncRNAs may be involved in the biological process of lymph node metastasis. The ROC curves demonstrated satisfactory discrimination power of MIR100HG and AC024560.2 with areas under the curve of 0.801 and 0.837, respectively. Survival curve also indicated that patients with high MIR100HG expression had a tendency of poor prognosis. This is the first study to successfully mine the lncRNA expression patterns in PLNM of early-stage cervical cancer. MIR100HG and AC024560.2 may be a potential biomarkers of PLNM and these lncRNAs may provide broader perspective for combating cervical cancer metastasis.

4: Use of methylene blue for detection of sentinel lymph nodes in cervical cancer

4: Use of methylene blue for detection of sentinel lymph nodes in cervical cancer

Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in cervical cancer.

ObjectiveA causal relationship between removal of circumflex iliac nodes distal to the external iliac nodes (CINDEIN) and lower leg edema has been recently suggested. The aim of this study was to elucidate the incidence of CINDEIN metastasis in cervical cancer.MethodsA retrospective chart review was carried out for 531 patients with cervical cancer who underwent lymph node dissection between 1993 and 2014. CINDEIN metastasis was pathologically identified by microscopic investigation. After 2007, sentinel lymph node biopsy was performed selectively in patients with non-bulky cervical cancer. The sentinel node was identified using 99mTc-phytate and by scanning the pelvic cavity with a γ probe.ResultsTwo hundred and ninety-seven patients (55.9%) underwent CINDEIN dissection and 234 (44.1%) did not. The percentage of International Federation of Gynecology and Obstetrics stage IIb to IV (42.4% vs. 23.5%, p<0.001) was significantly higher in patients who underwent CINDEIN dissection than those who did not. CINDEIN metastasis was identified in 1.9% overall and in 3.4% of patients who underwent CINDEIN dissection. For patients with stage Ia to IIa disease, CINDEIN metastasis was identified in 0.6% overall and in 1.2% of patients who underwent CINDEIN dissection. Of 115 patients with sentinel node mapping, only one (0.9%) had CINDEIN detected as a sentinel node. In this case, the other three lymph nodes were concurrently detected as sentinel lymph nodes.ConclusionCINDEIN dissection can be eliminated in patients with stage Ia to IIa disease. CINDEIN might not be regional lymph nodes in cervical cancer.

MicroRNA‑10a enhances the metastatic potential of cervical cancer cells by targeting phosphatase and tensin homologue.

Cervical cancer is one of the leading causes of cancer‑related mortality worldwide. Previously, the upregulation of microRNA (miR)‑10a has been identified in human cervical cancer. The present study firstly demonstrated that miR‑10a was markedly upregulated in primary tumor tissues in patients with positive lymph node metastasis (LN+) compared with negative (LN‑) by quantitative polymerase chain reaction. miR‑10a mimics markedly enhanced cervical cancer cell migration and invasion abilities, and accordingly the miR‑10a inhibitor suppressed those functions. Furthermore, these data suggested that the phosphatase and tensin homologue (PTEN) was inhibited by miR‑10a through an miR‑10a binding site within the 3'‑untranslated region of PTEN at the posttranscriptional level, and that miR‑10a mimics promoted nuclear translocation of β‑catenin. Therefore, it was concluded that the overexpression of miR‑10a contributes to metastasis in cervical cancer by targeting PTEN. miR‑10a may therefore be used clinically as a molecular marker for patients with cervical cancer lymph node metastasis.

Clinical feasibility and diagnostic accuracy of detecting micrometastatic lymph node disease in sentinel and non-sentinel lymph nodes in cervical cancer: outcomes and implications

Lymph node (LN) micrometastatic disease has come to prominence since ultrastaging was shown to improve the quality of LN procedures in epithelial cancers. The aim of the study was to evaluate the feasibility and diagnostic usefulness of detecting micrometastases in sentinel (SLN) and non-sentinel LNs (nSLN) in cervical cancer Twelve consecutive patients with cervical cancer stages IA to IIA, classified according to the Union for International Cancer Control (UICC) and divided into two groups: A (7) and B (5), with and without SLN procedure with methylene blue dye, who underwent radical hysterectomy and lymph nodes removal, were recruited for the study. All LNs were evaluated in hematoxylin-eosin (HE) staining and immunohistochemically (IHC) in ultrastaging with anti-cytokeratin AE1/AE3 antibodies. A detailed analysis was performed with regard to the technical and histopathological aspects of the procedure. More LNs could be extracted and studied in group A as compared to group B (210 vs. 70, mean 30 vs. 14, respectively p < 0.0005). A total of 13 SLNs were extracted, and the identification rate was 71% (5/7 in group A). One micrometastatic LN was found in each of the groups (16% cases), but the preliminary classification of the advancement stage was changed only in 1 case from the labeled nodes group (group A--from pN0 with HE to pN1 with IHC). Presence or absence of metastases in SLN(s) should not be sufficient amount of information for a surgeon or an oncologist, who ought to have data about all of the removed lymph nodes (sent to ultrastaging). In order for the surgery to be performed properly it is vital to ensure that SLNs were removed. Assessment of the N status ought to be taken into consideration in the classification according to the International Federation of Gynecology and Obstetrics (FIGO).

PO-0886: Alternatives to the PTV concept for dose escalation of pelvic lymph nodes in cervical cancer

PO-0886: Alternatives to the PTV concept for dose escalation of pelvic lymph nodes in cervical cancer

Robotic-assisted dissection of bulky lymph nodes in cervical cancer.

The resection of bulky lymph node metastases, which may provide a therapeutic benefit, has been proposed in several studies based on laparotomy and laparoscopy. There is no published study in the literature examining the resection of bulky lymph node metastases using a robotic technique. In this report, we presented a patient with cervical cancer who underwent robotic-assisted dissection of bulky lymph nodes. The robotic-assisted operation time was 255 minutes, and the mean console time was 215 minutes. The estimated blood loss was 70 mL. The number of lymph nodes retrieved was 28, and the number of the dissected paraaortic lymph nodes was 13. The number of the lymph node metastases was eight. The bulky lymph nodes which are difficult to be eradicated with standard radiation therapy can be resected with robotic-assisted surgery and successful resection of the lymph nodes can improve the treatment strategy. This minimal invasive technique is safe and feasible for bulky lymph node dissection.