Study on influencing factors of positive peritoneal cytology and its relationship with prognosis in patients with endometrial cancer / 肿瘤研究与临床

Objective:To investigate the risk factors of positive peritoneal cytology (PPC) in patients with endometrial cancer and the impact of PPC on patients' prognosis.Methods:The clinicopathological data of 202 patients who underwent initial surgical treatment and were diagnosed with endometrial cancer by postoperative pathology at Qilu Hospital of Shandong University from January 2015 to December 2019 were retrospectively analyzed, and the peritoneal fluid of patients were sent intraoperatively for cytological liquid-based smear examination. Logistic regression was used to perform univariate and multivariate analyses of PPC in the whole group of patients and the early-stage patients; Univariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Kaplan-Meier method and compared by log-rank method, and multivariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Cox proportional hazards model.Results:Of 202 patients, 183 (90.6%) had negative peritoneal cytology (NPC) and 19 (9.4%) had PPC; 180 patients (89.1%) were stage Ⅰ-Ⅱ and 22 (10.9%) were stage Ⅲ-Ⅳ; 180 patients (89.1%) had early-stage endometrial cancer. Deep myometrial infiltration ( OR = 3.57, 95% CI 1.02-12.45, P = 0.046) and lymph node metastasis ( OR = 7.16, 95% CI 1.70-30.23, P = 0.007) were independent risk factors for PPC in patients with endometrial cancer; deep myometrial infiltration was an independent risk factor for PPC in patients with early-stage endometrial cancer ( OR = 6.22, 95% CI 1.22-31.73, P = 0.028). The 3-year PFS rates for the whole group of patients with PPC and NPC were 72.9% and 92.7%, and the difference was statistically significant ( P = 0.001); the 3-year PFS rates for early-stage patients with PPC and NPC were 82.5% and 96.2%, and the difference was statistically significant ( P = 0.002). PPC was an independent risk factor for PFS in the whole group of patients with endometrial cancer ( HR = 4.80, 95% CI 1.14-20.17, P=0.032); PPC was also an independent risk factor for PFS in patients with early-stage endometrial cancer ( HR = 8.85, 95% CI 1.96-39.93, P = 0.005). Conclusions:Deep myometrial infiltration is an independent risk factor for PPC, and PPC is an independent risk factor for PFS in patients with endometrial cancer. Routine cytological examination of peritoneal fluid is recommended in patients with endometrial cancer.

Recommendations on management of gynecological malignancies during the COVID-19 pandemic: perspectives from Chinese gynecological oncologists / 부인종양

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.

Recommendations on management of gynecological malignancies during the COVID-19 pandemic: perspectives from Chinese gynecological oncologists / 부인종양

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.

Evaluation of the accuracy of the right superior pulmonary vein sheath compression in the closure of atrial septal defect based on multi-layer perceptron by ultrasound / 中华超声影像学杂志

Objective:To evaluate the accuracy of measuring the siae of atrial septal defect(ASD) by transthoracic echocardiography(TTE) on " compression of right superior pulmonary vein sheath during operation" (compression-size) using multi-layer perceptron.Methods:From January 2016 to January 2019, 460 cases of ASD with soft margin, thin growth or central type with atrial septal tumor in the First Hospital Affiliated of Air Force Medical University were analyzed retrospectively. The age was (34.32±18.84)years, 129 males and 331 females. Preoperative TTE and intraoperative TTE were performed to measure the size of ASD and compression-size. With the final occluder size selected as the dependent variable, the preoperative and intraoperative ultrasound measurements were used as covariates, and all patients were randomly divided into training set, test set and verification set according to the proportion of 5∶2∶3, which were imported into multi-layer perceptron. Gradient descent method was used to optimize and adjust the weight, and 10 operations were carried out respectively, and the average value was calculated to evaluate the two ultrasound methods for blocking.Results:The mean values of ASD were (15.26±5.33)mm for preoperative, (23.83±6.39)mm for compression-size intraoperative TTE, and (25.14±6.55)mm for the occluder, respectively. The difference was statistically significant (χ 2=850.450, P<0.001). There were significant differences between the pairwise ( P<0.001). Ten times of multi-layer perceptron were used to obtain a training model for predicting the size of the occluder based on preoperative transthoracic ultrasound and TTE measurement after right upper pulmonary vein sheath compression. The average relative error of the model obtained by preoperative ultrasound measurement in the validation set was (16.55±0.02)%, and that of the model obtained by intraoperative ultrasound measurement in the validation set was (4.81±0.01)%. The difference between the two methods was statistically significant ( t=16.185, P<0.001). Conclusions:It is more accurate to measure the ASD size for selection of occluder by the use of the right superior pulmonary vein sheath compression and TTE, especially for ASD patients with soft margin, thin growth or atrial septal tumor.

Prevention and screening of cervical cancer:an achievement with significant social benefits / 肿瘤研究与临床

Cervical cancer is one of the most common gynecological malignancies, seriously threatening women's health. As early as 1878, Freund first used hysterectomy to treat cervical cancer. In 1898, Wertheim first proposed radical surgery for cervical cancer. With the continuous development of diagnosis and treatment technology, the etiology of cervical cancer has become increasingly clear. The various screening measures have been applied in early detection, early diagnosis and early treatment of cervical cancer. In recent years, the increasing promotion of human papillomavirus (HPV) vaccine has brought a new hope in the prevention and control of cervical cancer.

Prevention and screening of cervical cancer: an achievement with significant social benefits / 肿瘤研究与临床

Cervical cancer is one of the most common gynecological malignancies, seriously threatening women's health. As early as 1878, Freund first used hysterectomy to treat cervical cancer. In 1898, Wertheim first proposed radical surgery for cervical cancer. With the continuous development of diagnosis and treatment technology, the etiology of cervical cancer has become increasingly clear. The various screening measures have been applied in early detection, early diagnosis and early treatment of cervical cancer. In recent years, the increasing promotion of human papillomavirus (HPV) vaccine has brought a new hope in the prevention and control of cervical cancer.

Progress of aspirin in endometrial neoplasms / 肿瘤研究与临床

Obesity and exogenous hormone exposure are the well-established endometrial cancer risk factors, which are associated with chronic inflammation. Some evidences have shown that inflammation is potentially related to the increased risk of endometrial neoplasms. Aspirin is one of the most studied non-steroidal anti-inflammatory drugs, which can benefit the endometrial cancer patients with obesity. Although aspirin-related bleeding has to be considered prior to therapy, in most cases, the benefits of low-dose aspirin therapy substantially will exceed the risk. Aspirin and other non-steroidal anti-inflammatory drugs are expected to become effective new methods for the treatment of the tumors. This paper reviews the progress of aspirin in endometrial neoplasms.

Inhibitory effect of nigericin on human epithelial ovarian cancer cells and its mechanism / 肿瘤研究与临床

Objective To ascertain the specific activities of nigericin on inhibiting human epithelial ovarian cancer(EOC)cells,and to investigate the possible molecular mechanism of nigericin on cell migration and invasion.Methods Cell viability under different treatments of nigericin(0.312 5,0.625,1.25,2.5,5,10,20,40,80 μmol/L)on EOC A2780 and SKOV3 cell lines was examined by CCK-8 assay,with DMSO as a control.The human epithelial ovarian cancer cell lines A2780 and SKOV3 were treated with 5,10 or 20 μmol/L nigericin or with DMSO as a control.Transwell chambers was used to observe the impact of nigericin on migration and invasion of EOC cells.Western blot was used to detect the expressions of epithelial cell marker(E-cadherin),mesenchymal cell marker(Vimentin)and the epithelial-mesenchymal transition(EMT)-related transcription factors Slug,Snail,and Twist,as well as the expressions of proteins related to Wnt/β-catenin signaling pathway such as Gsk-3β,p-Gsk-3β and β-catenin under different concentration treatment of nigericin.Results CCK-8 assay showed that nigericin exhibited strong cytotoxicity on A2780 [ IC 50(16.19 ± 0.26)μmol/L,95％CI 1.077-1.341)] and SKOV3 [ IC50(11.87 ±0.21)μmol/L,95％CI 1.003-1.146] cell lines.Transwell chamber assay revealed that nigericin at different concentration(5,10,20 μmol/L)induced a remarkable reduction in the number of cells migrating through the membrane relative to the vehicle-treated controls in A2780 and SKOV3 cells [(121±9),(92±7),(59±5)/HP and(120.4±2.6),(91.8±5.5),(80.0±4.0)/HP,all P <0.05]; the invasive ability of A2780 and SKOV3 cells also inhibited [(61.2±3.7),(43.2±4.3),(23.6±2.1)/HP and(85.2±7.0),(65.2±4.6),(45.6±4.4)/HP,all P< 0.05].Western blot revealed that the increased expression of E-cadherin and decreased expression of Vimentin,Slug,Snail,Twist,p-Gsk-3β,β-catenin in EOC cells with the nigericin treatment at different concentration(5,10 and 20 μmol/L)showed concentration dependence(P < 0.05).Conclusion Nigericin may induce EMT by activating Wnt-β-catenin signaling pathway to promote the migration and invasion of EOC cells.

Research Progress of Fertility-sparing Management in Young Endometrial Cancer Patients Based on ESGO Recommendations / 中国微创外科杂志

[Summary] A more conservative approach for endometrial cancer ( EC ) is desirable in women who have requirement to preserve fertility, without compromising their survival .In this article, we tried to formulate clinical recommendations of preserving fertility based on suggestions of European Society of Gynaecological Oncology ( ESGO) in 2015 and relevant research progress .

Preparation of peri-epiphyseal fracture models in young rabbits：cross-epiphyseal plate internal fixation affects epiphyseal growth? / 中国组织工程研究

BACKGROUND:There are various therapies for children limb fractures involving the epiphysis or the metaphysis. According to the different methods, studies on the growth of the epiphyseal plate are a lot, most of which focus on the effects of Kirschner wires with different diameters or holow screw internal fixation on the development of epiphyseal plate. However, there are rare studies on the influence of cross-epiphyseal plate internal fixation on the growth of epiphyseal plate as wel as the influence level. OBJECTIVE:To prepare a peri-epiphyseal fracture model in young rabbits and to observe the effects of cross-epiphyseal plate implantation and removal on the growth of epiphyseal plate. METHODS: Traverse fracture models were made 5 mm above the right femoral distal epiphyseal plate of 60 young rabbits, and then fixed with suitable “L” steel plate and four screws across the epiphyseal plate and peri-epiphyseal fracture line. The left side served as control. Eight rabbits were kiled and observed at 2, 4, 8, 12 weeks after modeling, respectively, to take out the femoral specimens for measurement of femoral length, thickness of the epiphyseal plate, and number of mastocytes per unit column. Histopathology observation was done and changes in mastocytes and thickness of the epiphyseal plate were detected. Another seven rabbits were selected to remove the metal plate, continued to feed for 2 weeks and finaly executed to observe the above-mentioned indexes. RESULTS AND CONCLUSION: (1) There were significant differences in the above indexes between the plate and control groups at 4, 8, 12 weeks after modeling (P 0.05). These findings indicate that within 2 weeks after cross-epiphyseal plate internal fixation, proper pressue has no remarkable influence on the growth of epiphyseal plate; but after persistent internal fixation (> 4 weeks), the growth of epiphyseal plate can be partialy or completed retarded. (2) At 2 and 4 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length, thickness of the epiphyseal plate and mastocyte counting per unit column were improved to different extents, and there were no differences between the plate and control group (P > 0.05). At 8 and 12 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length and thickness of the epiphyseal plate were shortened, and the number of mastocytes per unit column was decreased obviously, which significantly differed from the control group (P < 0.001). These findings indicate that the chondrocytes in the proliferative and hypertrophy layers lose the differentiation and proliferation abilities, and the femoral length and epiphyseal plate thickness are difficult to recover.

Effects of 5-aza-2'-deoxycitydine on expression of RASSF1A gene in human ovarian cancer cell line / 国际肿瘤学杂志

Objective To investigate the effect of 5-aza-2'deoxycytidine (5-Aza-CdR) on proliferation and expression of RASSF1 A gene in human ovarian cancer cell line SKOV3 and 3AO.Methods SKOV3 and 3AO cells were treated with different concentrations (0.5,5,50 μmol/L) of DNA methyltransferase inhibitor 5-Aza-CdR.RT-PCR and Western Blot were adopted to detect expression of mRNA and protein of RASSF1A gene before and after treatment with 5-Aza-CdR respectively.Results Compared with control group,when the 5-Aza-CdR concentration was 0.5,5,50 μmol/L after drug treatment,human ovarian cancer cells could significantly inhibit tumor cell growth; SKOV3 and 3AO cells in control group were observed weaker expression of RASSF1A mRNA.After treated with 5-Aza-CdR,the expressions of RASSF1A mRNA were observed increased with the increase of the drug concentration.After treated with different concentration of 5-Aza-CdR,the expressions of RASSF1A mRNA treated with 0.5 μmol/L 5-Aza-cdR was lower than those treated with 5 and 50 μmol/L 5-Aza-cdR (t =-8.866,P =0.01 ; t =-12.256,P =0.000).However,expressions of RASSF1A mRNA treated with 5 and 50 μmol/L 5-Aza-cdR respectively showed no statistical significance (t =0.431,P =0.689).Expressions of RASSF1A protein treated with 0.5 μmol/L 5-Aza-cdR and 5 μmol/L 5-Aza-cdR didn't show statistically significant (t =-1.586,P =0.188).Conclusion Expressions of RASSF1A mRNA and protein in SKOV3 and 3AO cells were evidently enhanced.As one kind of methyltransferases inhibitors,5-Aza-CdR can inhibit ovarian cancer cell line SKOV3,3AO growth through the RASSF1A promoter methylation,and thus promote their apoptosis.

DNA double-strand break repair and ovarian cancer / 国际肿瘤学杂志

DNA double-strand break repair (DSBR) pathways are important repair pathways in human. DSBR pathways repair damaged DNA, maintain the integrity of the genetic information and therefore suppress cancer. More and more researches have indicated important roles of DSBR pathway genes in the development and treatment of ovarian cancer.

Methylation of RUNX3 gene in epithelial ovarian carcinoma / 中华检验医学杂志

Objective To access the role of methylated RUNX3 ggene in the carcinogenesis an progression of ovarian carcinoma.Methods Sample of 32 epithelial ovarian carcinoma tissues,32 para-carcinoma tissues,36 benign epithelial tumors and 10 normal ovarian tissues and 2 cell lines(3A0 and SKOV3),were collected and subject to methylation-specific PCR(MSP).Promoter methylation status of RUNX3 in two tumor cell lines were analyzed before and after 5-aza-2'deoxycytidine treatment.In addition. mRNA expression of RUNX3 were investigated by quantitative reverse transcription-PCR Results CpG island methylation of RUNX3 was observed in 53.1%(17 of 32)of epithelial ovarian cancer,and 37.5% (12 of 32)in corresponding noncancerous tissues,16.7% in benign epithelial tumors(6 of 36),and all celllines,but not in normal control tissues.The prevalence of RUNX3 gene CpG methylation in malignant was significantly higher than those in benign and normal tissues(X2=10.060,X2=8.925,P<0.05). Nineteen percent(6 of 32)of ovarian epithelial carcinoma expressed RUNX3 mRNA,while its expression Was present in 28% (9 of 32)corresponding noncancerous tissues and 72% (26 of 36)of benign ovarian tumor and 80% (8 of 10)of normal ovarian tissues.The RUNX3 promoter methylation was found in all cell lines tested.The ratio of expression of RUNX3 mRNA in ovarian epithelial carcinoma was significantly lower than those of normal and benign tumors(X2=19.443,X2=12.862,P<0.05).After 5-aza-2'deoxycytidine treatment,methylation was partially or completely reversed,and its mRNA expression was increased.The relationship between gene expression and promoter methylation was reversely correlated.Conclusions Our results suggest that promoter hypermethylation of RUNX3 genes is common in ovarian cancer. Therefore, hypermethylation of RUNX3 genes may be involved in the carcinogenesis of ovarian cancer and may serve as an early diagnostic marker for ovarian cancer. The close correlation between RUNX3 methylation of its mRNA suggests that methylation which can be reversed.Thus,it provides a new way for therapy of ovarian Cancer.

Expression of elastin,lysyl oxidase and elafin in the cardinal ligament of women with pelvic organ prolapse / 中华妇产科杂志

Objective To investigate expression of elastin,lysyl oxidase (LOX)and elafin in cardinal ligament of women with pelvic organ prolapse(POP) so as to determine their contributions to POP.Methods The cardinal ligament samples were obtained from 60 POP subjects and 60 non-POP control women undergoing hysterectomy.RT-PCR was used to verify the mRNA level of elastin,LOX and elafin.The protein concentration of the three genes was determined by western blotting technique,electrophoretic separation and quantification.Results The premenopansal and postmenopausal POP groups demonstrated significantly decreased expressions of elastin in cardinal ligament both in mRNA and protein levels than control group (mRNA 0.42±0.22,0.26±0.20 versus 0.79±0.30,0.63±0.23 ; protein 0.44±0.32,0.20±0.19 versus 0.89±0.27,0.78±0.25; P＜0.05).There was an identical tendency in the expression of LOX (mRNA 0.37±0.18,0.20±0.14 versus 0.65±0.22,0.53±0.20; protein 0.45±0.27,0.26±0.21 versus 0.85±0.39,0.69±0.31 ; P＜0.05).In POP group,the mRNA and protein levels of elastin and LOX in postmenopansal patients were significantly lower than premenopansal patients (P＜0.05).Inversely,POP group demonstrated an increased expression of elafin in cardinal ligament both in mRNA and protein levels than corresponding control group (mRNA 1.33±0.35,1.47±0.37 versus 0.62±0.25,0.55±0.24; protein 0.85±0.30,0.76±0.35 versus 0.21±0.15,0.29±0.22; P＜0.05). There was no significant difference in the expression of elafin between premenopansal and postmenopausal POP groups either in mRNA or protein levels(P＞0.05).There was a positive correlation between elastin and LOX both in mRNA and protein levels in POP group(r=0.9959,0.9708; P＜0.05),but there was no correlation between elastin and elafin(r=-0.0402,-0.0365;P＞0.05).Conclusions The results suggest that the decreased expression of elastin and LOX and the increased expression of elafin in the cardinal ligaments may contribute to POP.

Effect of 5-Aza-2’-deoxycytidine on cell apoptosis in ovarian cancer cell line and expression of HMLH1 as well as HMSH2 / 基础医学与临床

Objective To observe the effects of 5-Aza-2’-deoxycytidine(5-Aza-CdR)on cell proliferation and apoptosis in ovarian cancer cell line SKOV3 and the expression of mismatch repair gene HMLH1/HMSH2, and to investigate the potential mechanism of its antitumorigenesis. Methods Human ovarian cancer cell line SKOV3 was treated with 5-Aza-CdR(0.5, 5 and 50 ?mol/L), a specific demethylation agent for 3 d, and then cultured in RPMI-1640 medium for 7 d.The growth of cells was examined by MTT assay. The apoptosis was analyzed by flow cytometry. The expression of HMLH1 and HMSH2 mRNA was observed by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). Results SKOV3 cells treated with 5-Aza-CdR displayed a slow growth rate in comparison with that of the control cells, The apoptosis rates of each group were 10.59%?1.57%、17.52%?1.72%、34.10%?1.45%,respectively,which were markedly higher than that of control(P

Intestinal metastasis of ovarian cancer:clinical analysis of 64 cases / 中国现代普通外科进展

Objective:To retrospectively analyze the clinical features of intestinal tract metastatic tumors of ovarian cancer,and estimate the feasibility of resection and its relation to prognosis.Methods:64 patients with ovarian cancer associated with intestinal tract metastasis were brought into this clinical analysis.The extent of intestinal tract involvement was evaluated preoperatively.Cytoreduction was defined as the residual lesion less than 1 cm3,at the same time pelvic and paraaortic lymphadenectomy and/or biopsy were implied.Intestinal surgery included tumor stripping surgery and/or intestinal repair,intestinal resection or colostomy.Regular chemotherapy was administrated,postoperative complications as well as prognosis were evaluated.Results:54 cases (84.8%) had rectum/sigmoid colon metastasis,metatsis in other parts of colon were 26 cases,small intestinal metastasis were 18 cases,infiltration of serosal and superficial muscular layer were 47 cases,17 cases had deep muscular layer and mucosal infiltration.Epithelial cancer which had invaded intestinal mucosa were 4 cases (7.7%) ,no invading to intestinal mucosa was detected in germnoma.All the 64 patients were recepted surgical treatment,including tumor stripping surgery in 44 cases,intestinal resection in 20 cases,sigmoidal and rectal resection in 14 cases,and colonost omy in 6 cases.The optical cytoreduction was[FK(WB00018。142mmZQ1mm]achieved in 56 cases (87.5%),and post-chemotherpy regression rate was 58.9%,but the post-chemotherpy regression rate was only 12.5% in 8 patients who got partial resection;regular chemotherapy was finished in 49 cases,and the regression rate was 65.3%,but the regression rate was only 15.4% in those who couldn’t finish regular chemotherapy.Postoperative morbidity was 26.6%,and two patients died of postoperative peritonitis.Conclusion:Intestinal tract is the common metastatic site of ovarian cancer,tumor stripping and intestinal resection are not only feasible but also prerequisite for optimal cytoreduction,postoperative regular chemotherapy can improve prognosis of ovarian cancer.

Effects of 5-aza-2'-deoxycytidine on apoptosis of ovarian cancer cells and on expression of mismatch repair genes / 中国肿瘤生物治疗杂志

Objective:To observe the effect of 5-aza-2'-deoxycytidine on proliferation and apoptosis of ovarian cancer cell lines(SKOV3 and 3AO)and on expression of mismatch repair(MMR)genes(hMLH1 and hMSH2)in SKOV3 and 3AO cells.Methods:Human ovarian cancer cell lines SKOV3 and 3AO were treated for 3 d with 5-aza-CdR(0.5,5,50 ?mol/L),a specific demethylation agent,and then cultured in RPMI 1640 medium for another 7 d.The cells growth was observed by MTT assay before and after 5-aza-CdR treatment and the cell apoptosis was analyzed by flow cytometry.The expression of hMLH1 and hMSH2 mRNA was examined by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Results:5-aza-CdR(0.5,5,50 ?mol/L)obviously inhibited the growth of SKOV3 and 3AO cells compared in a concentration dependent manner.The apoptosis rates of SKOV3 cells were(10.59?1.57)%,(17.52?1.72)%,(34.10?1.45)% after treated with 0.5,5,50 ?mol/L 5-aza-CdR,respectively;and the apoptosis rates of 3AO cells were(11.11?2.21)%,(17.24?1.11)%,and(26.53?2.00)%,respectively,which were all markedly higher than those of control group(P