Accuracy of Intraoperative Frozen Section in the Diagnosis of Ovarian Neoplasms

Objective: The aim of the work is to evaluate the accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms in Zagazig University. Design: A prospective cross sectional cohort study. Method: This study was performed between March 2011 and March 2012, on 50 patients presented with ovarian mass. Gross examination of the tumor removed was done by inspection and palpation. The specimen was then cut with a sharp knife into two halves. The most appropriate area thought to be representative of lesion was chosen. The number of sections frozen was depended on the type and size of the tumor. Seven to eight μm sections were obtained and stained with hematoxylin-eosin. The specimens were then fixed in formalin. Paraffin blocks of the sections were processed in the routine way and sections were stained with hematoxylin and eosin (H and E). The diagnosis obtained by intraoperative frozen section based on cellularity and cell morphology was compared with final histopathological diagnosis in terms of diagnostic sensitivity, to differentiate between benign and malignant lesions. Assessment of the overall accuracy of the intraoperative diagnosis was classified as concordant or discordant. Results: There was no statisticaly significant differencre in the studied patients as regard the clinical data, macroscopic and intraoperative picture, while there was statisticaly significat association as regard the laterality of the ovarian masses. The validity of frozen section in the diagnosis of benign tumour was 100% with 100% accuracy, specificity, positive predictive value, negative predictive value, while sensitivity & negative prediction for borderline tumour and specificity & positive prediction of malignant tumour were 100%, specifecity for borderline tumours was 95% while the positive predictive value was 33.3% with 96% accuracy for both malignant and borderline tumours. Conclusion: Intraoperative frozen section is accurate for rapid diagnosis of ovarian tumors. It can help surgeons avoid under-treatment or overtreatment of patients. Our study was designed prospectively using a small number of patients. The door is open to larger studies using a larger number of patients to be performed in order to substantiate our results.

卵巢-附件报告和数据系统超声2022版(O-RADS US v2022)及其联合恶性风险指数4鉴别附件良、恶性肿瘤

目的观察卵巢-附件报告和数据系统超声2022版(O-RADS US v2022)及其联合恶性风险指数4(RMI4)鉴别附件良、恶性肿瘤的价值。方法回顾性分析126例手术病理诊断为附件肿瘤患者,根据O-RADS US v2022将1~3类归为良性病变、4~5类归为恶性病变,以450为RMI4分类的临界值,基于二者进行联合分类。以病理结果为金标准,绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估单一O-RADS US v2022、RMI4及其联合鉴别附件良、恶性肿瘤的效能。结果126例附件肿瘤中,良性94例、恶性32例。O-RADS US v2022鉴别附件良、恶性肿瘤的敏感度、特异度、准确率及AUC分别为78.13%、80.85%和80.16%、0.795,RMI4分别为71.88%、84.04%和80.95%、0.780;二者联合的特异度及准确率(93.62%、92.06%)均高于单一O-RADS US v2022(χ^(2)=7.322、5.967,P=0.007、0.015)或RMI4(χ^(2)=4.625、5.331,P=0.032、0.021),而敏感度及AUC(87.50%、0.906)差异均无统计学意义(P均>0.05)。结论O-RADS US v2022能有效鉴别附件良、恶性肿瘤,联合RMI4可提高鉴别特异度及准确率。

机会性输卵管切除术对卵巢储备的短期影响:基于GRADE证据分级系统的随机对照试验荟萃分析

背景机会性输卵管切除术(OS)可以作为卵巢癌(OC)的一级预防手段,但由于卵巢与输卵管拥有同源血供系统,OS可能会引起卵巢功能的损害,从而增加卵巢老化和更年期提前的风险。目的基于GRADE证据分级系统,评价OS对卵巢储备的短期影响。方法于2022年9月,检索中国知网、万方数据知识服务平台、维普网、PubMed、Web of Science、Scopus,获取评估OS对卵巢储备短期影响的文献,检索时限均为建库至2022-09-10。由2名研究者独立筛选文献并提取数据,使用Jadad量表评价文献质量,Stata 17.0软件用于数据处理与荟萃分析,GRADEpro 3.2软件用于评估荟萃分析结果的证据质量。结果共纳入9项随机对照试验(RCT),包含482例患者,其中OS组238例、non-OS组244例。Jadad风险评估量表结果显示所纳入的RCT均为高质量文献。荟萃分析结果表明:相对于non-OS组,OS组抗苗勒氏激素(AMH)(WMD=-0.07,95%CI=-0.28~0.13,P=0.13)、卵泡刺激素(FSH)(WMD=-0.03,95%CI=-1.65~1.59,P=0.24)、黄体生成素(LH)(WMD=-0.39,95%CI=-1.62~0.83,P=0.08)、雌二醇(E2)(WMD=3.08,95%CI=-4.26~10.43,P=0.35)手术前后的变化差异无统计学意义(P>0.05)。GRADEpro软件对荟萃分析的结果显示,AMH的研究为高质量证据,FSH的研究为中等质量证据,E2和LH的研究为低质量证据。结论在短期内因良性疾病接受OS的未绝经女性的卵巢储备功能指标与未接受OS的女性无明显差异。已完成生育的绝经前女性通过OS来预防OC是合理的,但是这个结论仍有待于更长随访时间、设计更严谨且样本量更大的RCT来验证。

合成MRI在O-RADS MRI 3~5分卵巢附件肿物良恶性鉴别中的价值

目的探索合成MRI(synthetic MRI,syMRI)对卵巢-附件影像报告和数据系统(Ovarian-Adnexal Reporting and Data System,O-RADS)MRI 3~5分的卵巢附件占位良恶性鉴别的效能。材料与方法回顾性分析在2021年8月至2023年6月期间于我院就诊的100例盆腔占位患者病例及影像资料,共计附件肿块126例,所有占位的O-RADS MRI评分均为3~5分。以手术病理或至少1年的随访结果为诊断标准。所有患者均在3.0 T MRI扫描仪上进行盆腔MRI扫描,包括syMRI及扩散加权成像(diffusion-weighted imaging,DWI)序列。在附件区病灶的实性成分的最大层面勾画感兴趣区,以获得syMRI定量参数[T1、质子密度(proton density,PD)、T2^(*)、R2^(*)]及表观扩散系数(apparent diffusion coefficient,ADC)值。采用独立样本t检验或Mann-Whitney U检验比较各参数的差异,通过logistic回归分析建立syMRI及syMRI+ADC诊断模型,采用受试者工作特征(receiver operating characteristic,ROC)曲线比较各参数及模型的诊断效能,DeLong检验比较各模型ROC曲线下面积(area under the curve,AUC)的差异。结果入组100例患者共126个病灶,其中良性55例,恶性71例。T1、T2^(*)、R2^(*)及ADC值在两组间差异有统计学意义(P<0.05),其鉴别卵巢附件良恶性病变的AUC分别为0.739[95%置信区间(confidence interval,CI):0.652~0.826]、0.780(95%CI:0.698~0.862)、0.783(95%CI:0.699~0.866)及0.674(95%CI:0.576~0.772)。syMRI及syMRI+ADC模型的AUC分别为0.860(95%CI:0.791~0.929)及0.879(95%CI:0.818~0.940),二者之间差异无统计学意义,均高于ADC值(P<0.05)。结论syMRI在鉴别O-RADS MRI 3~5分卵巢附件病变的良恶性中具有很好的效能。

TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

The diagnostic value of multiple tumor markers in malignantovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

O-RADS对卵巢良恶性肿瘤诊断的效能并分析卵巢恶性肿瘤发生的影响因素

目的探讨卵巢-附件报告和数据系统(O-RADS)对卵巢良恶性肿瘤诊断的效能,并分析卵巢恶性肿瘤发生的危险因素。方法回顾性分析病理确诊为卵巢肿瘤的417例患者的临床资料,以病理结果为金标准,将患者分为恶性组和良性组,对两组临床资料进行比较,同时依据超声图像特征和O-RADS对患者进行分类,绘制受试者工作特征(ROC)曲线,分析O-RADS诊断效能。结果单因素及多因素分析示,囊壁厚度≥3 cm、有实性成分、血流评分3~4分、腹水、腹膜结节是卵巢恶性肿瘤发生的危险因素(P<0.05)。与O-RADS 5类归为卵巢恶性肿瘤相比较,以O-RADS 4~5类归为卵巢恶性肿瘤作为诊断依据,其诊断的灵敏度、准确率及曲线下面积均显著升高(χ^(2)=6.28~18.84,P<0.05)。结论O-RADS分类能够较好地鉴别诊断卵巢良恶性肿瘤,当O-RADS 4~5类视为卵巢肿瘤恶性高风险时,诊断效能最好。

A Case of Low-Grade Appendiceal Mucinous Neoplasm of Its Difficultly to Distinguish from a Right Ovarian Tumor Due to Postmenopause

We here present a rare case of appendiceal tumor mimicking ovarian tumor in menopause woman. The patient was a 56-year-old woman, G1P1, who presented to our hospital with a right adnexal cyst diagnosed at another hospital. Transvaginal echocardiography showed a cyst in the right adnexal region, and pelvic contrast-enhanced MRI revealed a small cyst in the same region. The left ovary was atrophic and identifiable. It was unclear whether the cyst was contiguous with the gastrointestinal tract. Blood tests showed no elevation of tumor markers. We considered its possibility of a gastrointestinal origin, but since right normal ovary was not found, we thought the tumor was of ovarian origin and decided on a laparoscopic resection of the right adnexa. Intraoperatively, we observed atrophied bilateral normal ovaries, and the pelvic tumor was contiguous to the appendix. Surgeons performed a laparoscopic appendectomy after consultation with us. After resection we searched the abdominal and pelvic cavities, but found no obvious disseminated lesions. The histological diagnosis was low-grade appendiceal mucinous neoplasm (LAMN), a rare benign tumor of the appendix. Appendiceal tumors can be difficult to differentiate from right ovarian tumors due to their close anatomic location in the pelvis. It is possible to determine whether the tumor is of ovarian or appendiceal origin by identifying normal ovaries and the location of the feeding vessels into the tumors. In our case, there were no lesions other than the appendix, but LAMN can metastasize to the ovary, cause pseudomyoxoma peritonei, or be an overlapping tumor with an ovarian tumor. If an appendiceal tumor is diagnosed after surgery for ovarian tumor, the intra-abdominal cavity should be searched for metastasis or dissemination, and a thorough search for ovarian lesions should be performed with the possibility of an overlapping tumor in mind.

程序性死亡因子受体-1抑制剂联合化疗和贝伐珠单抗一线治疗RAS突变MSS型晚期结直肠癌的疗效观察

目的评估程序性死亡因子受体-1(PD-1)抑制剂联合化疗和贝伐珠单抗一线治疗大鼠肉瘤病毒(RAS)基因突变、微卫星稳定(MSS)型晚期结直肠癌病人的疗效及安全性。方法2021年6月至2022年6月徐州医科大学附属医院收治的67例RAS基因突变MSS型晚期结直肠癌病人分为两组,观察组(n=32)行PD-1抑制剂联合化疗和贝伐珠单抗,对照组(n=35)行化疗联合贝伐珠单抗,观察两组的治疗效果及不良反应。结果观察组和对照组的客观缓解率(ORR)分别为78.1%和51.4%(P<0.05),疾病控制率(DCR)分别为96.9%和77.1%(P<0.05);观察组中位无进展生存期(mPFS)较对照组延长,分别为12.9个月和11.2个月,差异有统计学意义(P<0.05)。观察组的不良反应率高于对照组(90.6%比88.6%),差异无统计学意义(P>0.05),但均可控制,且未发生致死性事件。结论PD-1抑制剂联合化疗和贝伐珠单抗一线治疗RAS基因突变MSS型晚期结直肠癌初步显示疗效显著,此类病人在常规贝伐珠单抗联合化疗的基础上可以考虑加用PD-1抑制剂。

Hp、RASAL2、CDH1及TP53对胃癌前病变与早期胃癌的鉴别诊断价值

目的探讨幽门螺杆菌(Hp)、RAS蛋白激活样因子2(RASAL2)、钙黏蛋白1(CDH1)及肿瘤抑制基因P53(TP53)对胃癌前病变与早期胃癌的鉴别诊断价值。方法选取2021年6月至2023年6月收治的早期胃癌52例,根据1:1选例原则另选取同期胃癌前病变52例、胃炎52例,分别纳入胃癌组、癌前组、胃炎组。比较3组及不同病理特征的早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率,比较胃癌组Hp阳性、阴性患者RASAL2、CDH1、TP53阳性表达率,采用Spearman相关分析探讨各指标阳性表达与早期胃癌患者部分病理特征的相关性,采用受试者工作特征(ROC)曲线分析联合检测对早期胃癌及胃癌前病变的鉴别诊断价值。结果3组Hp、CDH1、TP53阳性表达率胃癌组>癌前组>胃炎组,RASAL2阳性表达率胃癌组<癌前组<胃炎组,差异有统计学意义(P<0.05,P<0.01)。胃癌组Hp阳性患者CDH1、TP53阳性表达率高于Hp阴性患者,RASAL2阳性表达率低于Hp阴性患者(P<0.05,P<0.01);早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率在肿瘤浸润深度及淋巴结转移方面比较差异有统计学意义(P<0.05,P<0.01)。Hp、CDH1、TP53阳性表达与早期胃癌肿瘤浸润深度、淋巴结转移均呈正相关,RASAL2阳性表达与之呈负相关(P<0.01)。ROC曲线分析结果显示,Hp、RASAL2、CDH1、TP53联合诊断胃癌前病变的曲线下面积(AUC)为0.904(95%CI:0.846,0.945),联合诊断早期胃癌的AUC为0.894(95%CI:0.819,0.946)。结论Hp、CDH1、TP53在早期胃癌组织中阳性表达率较高,RASAL2阳性表达率较低,联合检测对胃癌前病变及早期胃癌具有一定鉴别诊断价值,可作为临床鉴别诊断胃癌前病变、早期胃癌的辅助指标。

微RNA-196a-1-3p靶向Ras响应元件结合蛋白调控胆管癌细胞增殖的机制研究

目的探讨转化生长因子β(TGF-β)调控人胆管癌细胞系RBE细胞增殖的关键微RNA(miRNA)及其潜在的机制。方法该研究起止时间为2020年1月至2022年1月。磷酸盐缓冲液(PBS)处理为对照组,TGF-β处理为TGF-β组,TGF-β抗体处理为抗体组。检测三组RBE细胞的增殖水平。miRNA高通量测序检测三组RBE细胞的miRNA调控变化,并进行miRNA模拟物过表达筛选鉴定受TGF-β调控的影响RBE细胞增殖水平的关键miRNA。miRNA数据库(miRDB)在线分析miRNA的潜在底物,并通过小干扰RNA(siRNA)敲低筛选鉴定影响RBE细胞增殖水平的关键底物。结果相比于对照组,TGF-β组RBE细胞的增殖水平上升(1.62±0.07比2.35±0.09,P<0.05),抗体组RBE细胞的增殖水平下降(1.62±0.07比1.11±0.08,P<0.05)。过表达微RNA-196a-1-3p(miR-196a-1-3p)时,RBE细胞的增殖水平下降(P<0.05)。敲低Ras响应元件结合蛋白(RREB1)时,RBE细胞的增殖水平下降(P<0.05)。过表达miR-196a-1-3p后,RBE细胞中RREB1的信使RNA(mRNA)和蛋白水平下降(P<0.05)。敲低miR-196a-1-3p后,RBE细胞中RREB1与SMAD家族蛋白3(SMAD3)的相互作用增加。敲低SMAD3后,RBE细胞的增殖水平下降(P<0.05)。与仅敲低SMAD3相比,敲低SMAD3的同时过表达RREB1的RBE细胞的增殖水平无显著变化,并且同时敲低SMAD3和miR-196a-1-3p的RBE细胞的增殖水平无显著变化。结论TGF-β能够通过miR-196a-1-3p/RREB1/SMAD3轴促进RBE细胞增殖;miR-196a-1-3p和RREB1可作为潜在的治疗胆管癌的靶标,为针对该靶标的新药研发奠定了基础。

Effect of WFDC 2 silencing on the proliferation,motility and invasion of human serous ovarian cancer cells in vitro

Objective:To investigate effect and possible mechanisms of silencing human WFDC2（HE4） gene on biological behavior changes as cell proliferation,apoplosis,movement and invasion of human serous ovarian cancer cell line SKOV3.Methods:Lentiviral WFDC2 gene sequence of small interfering siRNA was stablely transfected into SKOV3 identified by Q-PCR and western-blot. Obtained SKOV3 stable strains with silenced HE4 were measured by proliferation,apoplosis, migration,and invasion.Results:Gene sequencing showed that the oligonucleotides were successfully inserted into the expected site.After silencing HE4 in the SKOV3,proliferation was significandy inhibited（P【0.05）.G0/G1 phase was arrested by the cell cycle（P【0.01） and capacity of the migration and invasion decreased significandy（P【0.01）.Slight early apoptosis ratio and no change of late apoplosis were found without change of Caspase-3 or Bcl-2 protein.Proteins involed in ERK pathway as phosphorylated protein as p-EGFR,p- ERK decreased and protease protein involved in tissue remoding as matrix metalloproteinases MMP-9,MMP-2 and cathepsin B decreased compared with control group.Conclusions:HE4 gene plays an important role in regulating proliferation,apoptosis,migration,invasion of serous ovarian cancer cells by ERK pathway and protease system.Its role in apoptosis needs to be further explored,and it may be a potential target for serous ovarian cancer.

Relationship between the Expression of Connexin43 and Bystander Effect of Suicide Gene Therapy in Ovarian Cancer

The relationship of connexin43 (Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro was explored and the effect of all-trans retinoic acid (RA) on the expression of Cx43 and bystander effect investigated. The Cx43 expression was detected by flowcytometry, Western blot, and immunofluorescence in two ovarian tumor cell lines OVCAR3, CaOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than that in CaOV3 (P<0.05). The expression of Cx43 was detected in OVCAR3 by flowcytometry and Western blot, but it could not be detected in CaOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluoresence staining showed that Cx43 protein of OVCAR3 was located on membrane surface, whereas CaOV3 in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be enhanced by RA in ovarian cancer.

Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin A in cisplatin--inducedhuman epithelial ovarian cancer resistant cell line 3Ao/cDDP

Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.

Establishment and validation of a nomogram to predict the risk of ovarian metastasis in gastric cancer: Based on a large cohort

BACKGROUND Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer.The pathogenesis of ovarian metastasis is incompletely understood,and the treatment options are controversial.Few studies have predicted the risk of ovarian metastasis.It is not clear which type of gastric cancer is more likely to metastasize to the ovary.A prediction model based on risk factors is needed to improve the rate of detection and diagnosis.AIM To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features.METHODS A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center,and patients with distant metastasis other than ovary and peritoneum metastasis were excluded.Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression.Independent risk factors were chosen to construct a nomogram which received internal validation.RESULTS Ovarian metastasis occurred in 83 of 1696 female patients.Univariate analysis showed that age,Lauren type,whether the primary lesion contained signet-ring cells,vascular tumor emboli,T stage,N stage,the expression of estrogen receptor,the expression of progesterone receptor,serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer(all P<0.05).Multivariate analysis showed that age<50 years,Lauren typing of non-intestinal,gastric cancer lesions containing signet-ring cell components,N stage>N2,positive expression of estrogen receptor,serum carbohydrate antigen 125>35 U/mL,and a neutrophil-to-lymphocyte ratio>2.16 were independent risk factors(all P<0.05).The independent risk factors were constructed into a nomogram model using R language software.The consistency index after continuous correction was 0.840[95%confidence interval:(0.7740.906)].After the internal self-sampling(Bootstrap)test,the calibration curve of the model was obtained with an average absolute error of 0.007.The receiver operating characteristic curve of the obtained model was drawn.The area under the curve was 0.867,the maximal Youden index was 0.613,the corresponding sensitivity was 0.794,and the specificity was 0.819.CONCLUSION The nomogram model performed well in the prediction of ovarian metastasis.Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination,to ensure early detection and treatment.

超声O-RADS分类联合超声造影及血清CA125和HE4检测诊断绝经后卵巢肿物的应用价值

目的探讨卵巢-附件影像报告和数据系统(Ovarian-Adnexal Reporting and Data System,O-RADS)分类联合超声造影及血清糖类抗原125(carbohydrate antigen 125,CA125)和人附睾分泌蛋白4(human epididymis protein 4,HE4)在诊断绝经后卵巢肿物中的应用价值。方法回顾性分析2021年1月至2022年3月在本院收治并经病理证实的76例绝经后妇女卵巢肿物患者。患者术前均行常规超声、超声造影及血清CA125和HE4检查,以病理诊断为金标准,采用受试者工作特征(receiver operating characteristic,ROC)曲线分析常规超声O-RADS分类联合超声造影及血清CA125和HE4指标对绝经后卵巢肿物的诊断价值。结果76例绝经后卵巢肿物病理诊断良性55例,恶性21例。超声O-RADS分类诊断敏感度、特异度和准确度分别为71.4%、76.4%和75.0%。超声造影显示,卵巢恶性肿物始增时间和达峰时间均低于良性肿物,峰值强度高于良性肿物(均P<0.05)。超声O-RADS分类、超声造影联合血清CA125和HE4检测诊断卵巢良恶性肿物的敏感度、特异度、准确度和曲线下面积(area the under curve,AUC)分别为85.7%、92.7%、90.8%和0.892,高于单一检测技术(均P<0.05)。结论超声O-RADS分类、超声造影联合血清CA125和HE4检测可提高绝经后卵巢肿物的诊断效能。

Synchronous Mucinous Borderline Tumor of the Ovary and Low-Grade Appendiceal Mucinous Neoplasm

We present a rare case of synchronous mucinous borderline tumor of the ovary and low-grade appendiceal mucinous neoplasm (LAMN). We performed a left adnexectomy to diagnose the left ovarian borderline malignancy and an ileostomy because of the swollen appendix during the operation. It was diagnosed as left ovarian mucinous borderline malignancy and LAMN. LAMN causes peritoneal dissemination, ovarian metastasis, and peritoneal pseudomyxoma. The appendix and ovary are close to each other anatomically and can metastasize if there is a tumor in either. For ovarian mucinous tumors, it is necessary to search the gastrointestinal tract, especially the appendix, as the primary lesion. For appendix tumors, it is necessary to search for the ovary. Since LAMN may be associated with borderline ovarian malignancies, as in this case, there is a possibility of the duplication of tumors when searching for ovarian mucinous tumors as the primary tumor and if ovarian tumors are found. Since LAMN and mucinous ovarian tumors have similar histological features, immunohistochemical staining is useful for their differentiation because they show different immunostaining patterns.

Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro

Objective:To address how genistein sensitizes the chemotherapy-resistant ovarian carcinoma cells and promotes apoptosis in the respect of cell cycle and the regulation of survivin expression in the process.Methods:Ovarian SKOV-3 carcinoma cell line was treated with genistein or cisplatin either alone or in combination.Cell viability was showed by MTT method.Cell cycle and apoptosis were detected by flow cytometry.Survivin mRNA and protein were revealed by RT-PCR and immunocytochemistry,respectively.Results:Genistein could reduce the cell viability in a dose-dependent manner,while cisplatin did so at a much higher level.In contrast,if the two agents were treated in combination,half growth inhibition(IC50) value for cisplatin was reduced remarkably and the effect was synergistic as analyzed by isobologram.In particular,the reduced cell viability was exhibited by a switch in cell cycle progression,as the cells were arrested in G2/M phase and the G0/G1 phase-fraction was significantly decreased.The reduced cell viability appeared to involve apoptosis,based on our results from flow cytometry and Hoechst 33258 staining.In the meanwhile,genistein performed the inhibitory effect on cisplatin-induced survivin expression.Conclusion:Genistein can sensitize ovarian carcinoma cells to cisplatin therapy with the inhibition of survivin expression as the potential mechanism.

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.