Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

Relationship between Circulating Plasma Galectin-3 Levels and T-Cell Activation during Cervical Cancer Chemotherapy

Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+CD69+ cells in cervical cancer.

Relationship between the Expression of Telomerase and Human Papillomavirus Infection in Invasive Uterine Cervical Carcinoma

Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with human papillomavirus （HPV） infection. Histologically confirmed invasive cervical carcinomas and benign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol （TRAP）. The same cases were subjected to polymerase chain reaction （PCR） detection of HPV by using consensus primers and type-specific （HPV types 16 and 18） primers. Telomerase activity was detected in 40 of 45 （88.9%） invasive cervical carcinomas and 2 （all chronic cervicitis） of 50 （4%） benign cervical lesions. HPV was detected in 36 （24 HPV-16 and 4 HPV-18 cases） of 45 （80%） invasive cervical carcinomas and 20 （11 HPV-16 and 1 HPV-18 cases） of 50 （40%） benign cervical changes. There was a significant correlation between the expression of telomerase with histological grade （φ=0.44, P〈0.005）, but no correlation was found between telomerase expression and HPV-18 （P〉0.05）. Although larger sample studies are needed, there seems to be a clear association between telomerase upregulation and HPV status, mainly HPV-16 infection.

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

Objective: To identify the loss of heterozygosity (LOH) on chromosome 17p13 3 in ovarian cancer and cervical cancer Methods: The frequency of LOH on chromosome 17p13 3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ 22 Results: LOH on 17p13 3 was found in 12 of 24 (50 0%) ovarian cancers (including a borderline mucinous cystadenoma), 4 of 9 (44 4%) cervical carcinomas, and 1 of 13 (7 7%) non malignant gynecological diseases, which was cervical intraepithelial neoplasm III (CIN III) ( P< 0 01) Conclusion: These results show that LOH on 17p13 3 is associated with ovarian cancer and cervical cancer, suggesting that detection of LOH on 17p13 3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer

Expression and clinical significance of dendritic cell and transforming growth factor-beta 1 in cervical cancer

Objective:To explore the density and mature status of Dendritic cell(DC) in cervical cancer and correlation with the expression of transforming growth factor-beta 1(TGF-β1).Methods:Streptavidin-peroxidase(SP) immunohistochemistry methods were used to detect S-100 DC and the expression of TGF-β1 in 20 normal cervical tissues and 53 cervical cancer tissues without any sort of chemotherapy or radiation therapy prior to resection.Medical records were reviewed,clinicopathological variables were retrieved and used for analysis.Results:Two types of DC were observed under the microscope.The expression of DC in cervical cancer was significantly higher than that in normal tissues(23.34 cells/mm^2 vs 29.91 cells/mm^2,P<0.05),and significantly higher in early stage than that in advanced stage(P<0.05).The expression of TGF-β1 was significantly higher in cervical cancer than that in normal tissues (P<0.025).However,there was no correaction between TGF-β1 and lymph nodes metastasis.The index of DC in cervical cancer was negatively correlated to the expression of TGF-β1 in tumor cells (r=-0.8875,P=0.0001).Conclusion:Maturation of DC in cervical cancer is inhibited.The decreased number of DC and the higher expression of TGF-β1 are due to the failure of the immunity,these may play an important role in the development of the cervical cancer.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

Objective: To investigate the clinical significance of separate lateral parametrial lymph node dissection(LPLND) in improving parametrial lymph node(PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.Methods: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy(CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.Results: Compared with CRH group, the rate of laparoscopic surgery was higher(60.3% vs. 15.9%, P<0.001),and the blood transfusion rate was lower(19.0% vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases(96.7%) in the LPLND group, and 270 cases(11.6%) in the CRH group(P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group(median 3 vs. 1, P<0.001).The PLN metastases were detected in 25 cases(6.8%) in the LPLND group, and 18 cases(0.8%) in the CRH group(P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio(OR)=228.999, 95% confidence interval(95% CI): 124.661-420.664;P<0.001], but also for PLN metastasis identification(OR=10.867, 95% CI: 5.381-21.946;P<0.001).Conclusions: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.

Human Papillomavirus 16 E6,E7 siRNAs Inhibit Proliferation and Induce Apoptosis of SiHa Cervical Cancer Cells

Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results： HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs, which sustained at least 96 h by single dose siRNA. Furthermore, reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion： Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.

Limited energy parametrial resection/dissection during modified laparoscopic nerve-sparing radical hysterectomy

Objective: The aim of this study was to investigate the feasibility of using ultrasonic scalpel combined with vascular clip in parametrial management,called limited energy parametrial resection/dissection(LEPRD),in laparoscopic nerve plane-sparing radical hysterectomy(NPSRH),a modified nerve-sparing radical hysterectomy(NSRH); and to evaluate its effectiveness in pelvic autonomic nerve preservation.Methods: From July 2012 to January 2016,257 consecutive patients with stage IB1 to IIA2 cervical cancer who underwent NPSRH were included in this study.Patients were divided into three cohorts according to the different parametrial resection modality.The clinical,pathological and surgery-related parameters were compared between the three groups.Short-and long-term postoperative bladder functions were evaluated.Results: LEPRD was attempted in 94 patients,and was successful in 65(69.1%) patients(LEPRD group).The remaining 29(30.9%) patients required bipolar coagulation after failure of vascular clipping(combined modality group).Routine bipolar cautery was used in the other 163 patients during the parametrial resection(bipolar group).The blood loss in the LEPRD group was significantly lower than those in the other two groups(P<0.001).The rate of successful Foley removal on postoperative day 7 was significantly higher in the LEPRD group than in the bipolar group(P=0.022).The incidence of chronic voiding dysfunction was significantly lower in the LEPRD group than in the bipolar group(P=0.019).Conclusions: It is feasible to perform LEPRD in NPSRH for cervical cancers.This kind of limited energy surgical technique is associated with less blood loss,and leads to improved postoperative bladder function.

Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China

Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.

Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide

OBJECTIVE: To study the biological effect of arsenic trioxide (As2O3) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. METHODS: SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were established by transfecting SiHa cells with Bcl-2 expression vector. The sensitivities of SiHa and SiHa-Bcl2 cells to As2O3 were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. RESULTS: As2O3 inhibited the growth of SiHa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-Bcl2 cells partly resisted As2O3 induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c-myc gene expression. Nevertheless, As2O3 at a high concentration could still induce apoptosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightly inhibiting viral gene expression. CONCLUSION: As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As2O3 induced apoptosis, but the exact mechanism is unclear.

Identification of biomarkers for cervical cancer in peripheral blood lymphocytes using oligonucleotide microarrays

Background Oligonucleotide microarrays are increasingly being used to identify gene expression profiles that associated with complex genetic diseases. Peripheral lymphocytes communicate with cells and extracellular matrixes in almost all tissues and organs in human body, suggesting that the gene expression profiles in peripheral lymphocytes may reflect the presence of disease in the body. This study aimed to identify molecular biomarkers for cervical cancer in peripheral blood lymphocytes by using oligonucleotide microarrays. Methods Total RNA was extracted from peripheral blood lymphocytes of 24 early stage cervical cancer patients and 18 healthy controls. We used 22K Human Genome microarrays to profile peripheral blood lymphocytes from 4 early stage cervical cancer patients and compared their gene expression profiles with those from 3 healthy controls. Differentially expressed genes would be identified if they had adjusted P values of less than 0.05 and a groupwise average fold change greater than 1.5 or less than 0.67. Then the selected 5 genes were validated in the remaining 20 early stage cervical cancer patients and the 15 healthy controls by using real-time reverse-transcription polymerase chain reaction （RT-PCR）. Results Genes identified by the gene selection program expressed differently between the blood samples of the early stage cervical cancer patients and those of the healthy controls. To validate the gene expression data, 5 genes were analyzed by real-time RT-PCR. In three of the 5 identified genes, tenasin-c （TNC）, nuceolin （NCL）, and enolase 2 （EN02） showed a significant up-regulation in the blood samples of the early stage cervical cancer patients versus that of the healthy controls. Conclusions The up-regulation of TNC, NCL, and EN02 in peripheral blood may be used to identify novel blood biomarkers for detecting cervical cancer in a clinically accessible surrogate tissue, and thus to provide a possibility to develop a noninvasive and predictive diagnosis for the disease.

Age-specific effectiveness of primary human papillomavirus screening versus cytology in a cervical cancer screening program: a nationwide cross-sectional study

Background:Primary human papillomavirus(HPV)screening is recommended for the detection of cervical intraepithelial neoplasia(CIN)in the general pop-ulation;however,the triage for HPV-positive women remains a challenge.This study aimed to evaluate the age-specific effectiveness of primary HPV screening versus primary cytology screening for identifying optimal strategies for women of different ages.Methods:The dataset of the prevalence round screening was derived from the National Cervical Cancer Screening Program in China.Primary cervical screen-ing protocols included cytology only,HPV testing with cytology triage,and HPV testing with HPV-16/18 genotyping plus cytology triage.The primary outcomes were age-specific detection rate,colposcopy referral rate and positive predictive value(PPV)for CIN2+.Multivariate Poisson regression was used to evaluate the relativeeffectivenessofHPVtestingandcytologyaccordingtoagegroups.TheI 2 statisticwitharandom-effectmodelwasusedtotesttheheterogeneityinrelative effectiveness of HPV testing versus cytology between age groups.Results:This study included 1,160,981 women.HPV testing with HPV-16/18 genotyping plus cytology triage significantly increased the CIN2+detection by 36%(rate ratio[RR]:1.36,95%confidential interval[CI]1.21–1.54)for women aged 35-44 years and by 34%(RR:1.34,95%CI 1.20-1.51)for women aged 45-54 years compared with cytology only.HPV testing with cytology triage had simi-lar CIN2+detection rate compared with cytology only.The PPVs were substan-tially increased for both HPV testing groups.Among women aged 55-64 years old,HPV testing with HPV-16/18 genotyping plus cytology triage increased the colposcopyreferralrateby19%(RR1.19,95%CI1.10-1.29)comparedwithcytology only,butdidnotincreasetheCIN2+detection(1.09,0.91–1.30).Theeffectiveness ofHPVtestingwithcytologytriagedidnotchangeinolderwomen.Thebetween-age-group heterogeneity in the effectiveness was statistically significant for HPV testing with HPV-16/18 genotyping plus cytology triage versus cytology only.Conclusions:Our results suggested that the effectiveness of primary HPV screeningwithdifferenttriagestrategiesdifferedamongagegroups.HPVtesting with HPV-16/18 genotyping plus cytology triage could be used for women aged 35-54 years to detect more lesions,and HPV testing with cytology triage could balance the CIN2+detection and the number of colposcopies for women aged 55-64 years.Longitudinal data including both prevalence and incidence screen-ing rounds are warranted to assess age-specific triage strategies.

The delay, symptoms, and survival of Ivorian adolescent girls and young adults with uterine cervical cancer

Objective:To generate data on the nature and duration of cervical cancer symptoms,risk factors for delayed consultation,and diagnosis of adolescent and young adult groups in Cote d'Ivoire.Methods:This is a hospital-based cross-sectional study,conducted from July 2012 to May 2018,at the Department of Gynecology of the Yopougon teaching hospital in Cote d’Ivoire.The inclusion criteria were those who were under 40 years of age at the time of diagnosis with oral and written consent.Those whose information was more than 10%insufficient for the standards were excluded from the study.The survey files standardized anonymous pre-established data collected using medical records followed by phone calls.Results:The average age of the participants was 34±4.95 years with a minimum of 21 years.The mean parity per woman was 3.49±3.54.34.9%were HIV positive.The median patient delay was 122 days with a long delay in 84.62%of patients.The median time to total diagnosis was 209 days with a longer total delay in diagnosis of 87.18%.41%of patients honored their treatment,68.75%of which had received surgery,and 31.25%of which had received chemotherapy.The 5-year survival rate was 65%.Conclusion:The Ivorian health system must focus on primary and secondary prevention,the only guarantee to decrease the morbidity and mortality indicators linked to cervical cancer.

Immunomodulatory effects of astragalus polysaccharide on Human peripheral blood mononuclear cells co-cultured with cervical cancer cell lineImmunomodulatory effects of astragalus polysaccharide on Human peripheral blood mononuclear cells co-cultured with cervical cancer cell line

OBJECTIVE:To investigate immunomodulatory effects of Astragalus polysaccharides(APS)on the co-culture of peripheral blood mononuclear cells(PBMCs)with He La cervical cancer cell line.METHODS:To assess the proliferation of PBMCs,carboxyfluorescein succinimidyl ester(CFSE)-labeled PBMCs were co-cultured with He La cells and treated with different concentrations of APS.Supernatants of cell culture were collected for cytokines assay via enzyme-linked immunosorbent assay(ELISA).The impact of APS on the proliferation of PBMCs,induction of regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs)was carried out by flow cytometry.RESULTS:It was observed that APS could increase the proliferation of PBMCs co-cultured with He La cells(P<0.05).However,APS had no significant effects on the induction of Tregs and MDSCs in the co-culture assay(P>0.05).Furthermore,ELISA results demonstrated that APS could decrease IL-10 and TGF-βconcentration(P<0.05).CONCLUSION:The above-mentioned characteristics showed that APS might be able to modulate immune responses and improve anti-tumor effects through increasing the proliferation of PBMCs and decreasing inhibitory cytokines secretion as critical mediators of immune suppression in the tumor microenvironment.

Evaluation of pelvic visceral functions after modified nerve-sparing radical hysterectomy

Background Nerve-sparing radical hysterectomy （NSRH） was developed in an attempt to minimize complications after radical hysterectomy.Since 2008,a modified NSRH-nerve plane-sparing radical hysterectomy （NPSRH） has been developed at the Cancer Hospital,Chinese Academy of Medical Sciences.The aim of this study was to investigate the role of NPSRH in improving postoperative pelvic visceral dysfunctions.Methods Eighty-three patients with International Federation of Gynecology and Obstetrics （FIGO） stage IB1-IIA2 cervical cancer received NPSRH （the study group） from January 2008 to October 2012.One hundred and sixty-six patients who underwent conventional radical hysterectomy （CRH） were randomly selected as the control group.Age,pathological type and stage were matched between the two groups.The safety of surgery was assessed by duration of operation and blood transfusion rate.Postoperative short-term bladder function was analyzed by duration of catheterization.Long-term bladder,anorectal and sexual function were evaluated with questionnaires.Results Seventy-eight patients （94.0%） in the NPSRH group and one hundred and sixty patients （96.4%） in the CRH group completed the study.Median follow-up time was 31.9 months and 31.0 months respectively （P=0.708）.There was no significant difference between the two groups in terms of age,body mass index,FIGO stage,pathologic type,preoperative and postoperative therapy （P 〉0.05）.The blood transfusion rate shared no difference between two groups （P=0.364）.The operation time in the NPSRH group was significantly longer than CRH group （P 〈0.01）.But the duration of catheterization and hospitalization in the NPSRH group was significantly reduced compared with CRH group （P 〈0.01）.In addition,the incidence of long-term urinary frequency,urinary incontinence,urinary retention,straining to void,constipation and diarrhea was significantly lower in the NPSRH group （P 〈0.05）.However,there was no significant difference regarding sexual function （P 〉0.05）.Conclusions The current evidence indicated that NPSRH improved long-term bladder function compared to CRH.Moreover,it may improve long-term anorectal function as well.