Primary primitive neuroectodermal tumor of the cervix confirmed with molecular analysis in a pregnant woman: A case report and literature review.

Primary primitive neuroectodermal tumor (PNET) in the female tract is rare. Recently, a case of cervical PNET was diagnosed in our hospital. A 29-year-old pregnant woman presented with a cystic-solid cervical mass at the 7th week of gestation. The mass grew rapidly during follow-up and ruptured at the 22nd week. A biopsy was performed on the mass. Pathological examination revealed a malignant neoplasm composed of small cells which exhibited positive immunohistochemical (IHC) staining for CD99, SYN, and FLI1. Fluorescence in situ hybridization (FISH) displayed the presence of EWS-FLI1 fusion gene resulting from the chromosomal translocation t (11;22, q24;q12), which confirmed the diagnosis of cervical PNET. The reverse transcription-polymerase chain reaction (RT-PCR) results showed type 2 EWS-FLI1 fusion occurred in this tumor, suggesting a poor prognosis. The patient underwent surgical resection and was given adjuvant chemotherapy followed by pelvic radiotherapy. PNET arising from the genital tract, especially in the uterine cervix, is very rare and presents a diagnostic challenge. FISH and RT-PCR analysis are helpful for the diagnosis of such a tumor at an unusual site, as in the present case.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Effect of body mass index on the assisted reproductive outcome of frozen-thawed embryo transfer in patients with polycystic ovary syndrome / 中华妇产科杂志

Objective:To investigate the effect of body mass index (BMI) on clinical pregnancy and neonatal outcomes in patients with polycystic ovary syndrome (PCOS) during frozen-thawed embryo transfer.Methods:A total of 650 patients with PCOS who received routine in vitro fertilization or intracytoplasmic sperm injection treatment for frozen-thawed embryo transfer from June 2014 to June 2019 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively analyzed. According to BMI, PCOS patients were divided into group A (18.5≤BMI<23 kg/m 2, n=253), group B (23≤BMI<25 kg/m 2, n=167), and group C (BMI≥25 kg/m 2, n=230). The general information, clinical pregnancy outcomes, pregnancy complications, the incidence of macrosomia and low-birth-weight infants were compared in the three groups, and the influencing factors of neonatal birth weight were analyzed. Results:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate all showed downward trend with the increase of BMI, but the differences were not statistically significant (all P>0.05). The live birth rate in group C [47.0% (108/230)] was significantly lower than those in groups A and B, with statistical significance ( χ2 =7.43, P=0.024). The late miscarriage rate was higher in group C [9.4% (13/139)] than in groups A and B ( χ2 =7.66, P=0.022). The birth rates of macrosomia in groups B [22.2% (16/72)] and group C [21.1% (16/76)] were significantly higher than that in group A, and the difference was statistically significant ( χ2 =14.15, P=0.001). There was no statistically significant difference in the incidence of gestational diabetes between the three groups ( χ2 =3.81, P=0.149). The incidence of hypertension disorders complicating pregnancy increased with the increase of BMI, and the difference was not statistically significant ( P>0.05). Regression analysis showed that macrosomia was significantly associated with maternal pre-pregnancy BMI and gestational weeks, and the risk of macrosomia increased by 15% (95% CI: 3%-28%) for every increase in maternal BMI. Conclusions:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of PCOS patients in frozen-thawed embryo transfer cycles show downward trend with the increase of BMI. Obese patients with PCOS have a significant increase in late miscarriage rate and a significant decrease in live birth rate. The incidence of hypertension disorders complicating pregnancy in PCOS patients in the obese group has an increasing trend, and the birth rate of macrosomia has increased significantly. Therefore, it is recommended that obese women with PCOS lose weight scientifically before pregnancy to improve pregnancy and neonatal outcomes.

Research progress on ultrasound image-guided brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Brachytherapy is an integral part of radiotherapy treatment for cervical cancer. With the rapid development of medical imaging technology, three-dimensional (3D) imaging modality has been applied in the brachytherapy for cervical cancer. After computed tomography (CT) and magnetic resonance imaging (MRI), 3D ultrasound has been gradually applied to guide the brachytherapy for cervical cancer due to its superior soft tissue imaging characteristics, economy, high efficiency and convenience. In this article, the research progress on the application of ultrasonography in brachytherapy was summarized according to literature review, aiming to provide reference for subsequent research.

Research progress on ultrasound image-guided brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Brachytherapy is an integral part of radiotherapy treatment for cervical cancer.With the rapid development of medical imaging technology,three-dimensional (3D) imaging modality has been applied in the brachytherapy for cervical cancer.After computed tomography (CT) and magnetic resonance imaging (MRI),3D ultrasound has been gradually applied to guide the brachytherapy for cervical cancer due to its superior soft tissue imaging characteristics,economy,high efficiency and convenience.In this article,the research progress on the application of ultrasonography in brachytherapy was summarized according to literature review,aiming to provide reference for subsequent research.

Relationship between factors of gross tumor volume and locoregional failure of radical intensity-modulated radiation therapy for esophageal carcinoma / 中华放射肿瘤学杂志

Objective Investigate the relationship between gross tumor volume (GTV)-related factors including GTV-T volume,the maximum thickness of the esophageal lesion plane and GTV-T volume/length(GTV-T volume divided by the length of the lesion calculated by the number of GTV-T layers) and the locoregional failure of radical intensity-modulated radiation therapy (IMRT) for esophageal carcinoma.Methods A total of 133 patients with esophageal cancer undergoing radical IMRT were enrolled.The factors related to GTV-T including GTV-T volume,the maximum thickness of the esophageal lesions,GTV-T volume/length were calculated.The relationship between GTV-T related factors and local recurrence of tumors was retrospectively analyzed.Results There was positively linear association between the locoregional failure rate of GTV-T and the volume of GTV-T.The volume of GTV-T tumor was 36 cm3,the maximum wall thickness was 2.5 cm,and the GTV-T volume/length was calculated as 5.3 cm2.These critical values could be utilized to predict the risk of locoregional failure of IMRT for esophageal carcinoma.Conclusions The GTV-T factors can be adopted to predict the local control and the risk of locoregional failure of radical IMRT for esophageal carcinoma to certain extent.

Prognosis and staging of primary bone lymphoma:an analysis of 40 patients / 中华放射肿瘤学杂志

Objective To retrospectively analyze the treatment outcomes and prognostic factors for primary bone lymphomas ( PBL) . Methods Forty patients with PBL who were admitted to our center from 1964 to 2014 were enrolled as subjects. In those patients, 10 were treated with chemotherapy alone, 10 with radiochemotherapy, 10 with postoperative chemotherapy, 9 with postoperative radiochemotherapy, and 1 with surgery alone. The median radiation dose was 36 Gy. The Kaplan?Meier method was used to calculate survival rates . The log?rank test was used for survival difference analysis and univariate prognostic analysis . Results The follow?up rate was 100%. The 3?year sample size was 36. In all patients, the 1?and 3?year overall survival rates were 60% and 42%, respectively, while the 1?and 3?year disease?free survival rates were 45%and 34%, respectively. The univariate analysis showed that no pathological fracture at diagnosis, normal lactate dehydrogenase level, an International Prognostic Index score of ≤1, early clinical stage ( stageⅠE ) , complete response after initial treatment, no less than 6 cycles of chemotherapy, a radiation dose of≥40 Gy, no progression outside radiation field after radiotherapy, and grade<3 bone marrow suppression during the treatment were prognostic factors for survival ( P=0. 027, 0. 037, 0. 000, 0. 016, 0. 000, 0. 000, 0. 022, 0. 014, and 0. 030). Conclusions The incidence of PBL is low. Comprehensive treatment can achieve satisfactory outcomes. As a PBL staging system, Ann Arbor has limitations. The staging of PBL should be based on local bone destruction and metastasis.

The clinical value of HPV E6/E7 mRNA and HPV DNA in early screening of cervical cancer / 天津医药

Objective To analyze the differences of positive detection rate and copy number of human papillomavirus (HPV) DNA and E6/E7 mRNA between different grades of cervical lesions, and evaluate their clinical values in early screen?ing of cervical cancer. Methods The cervical exfoliated cell samples from 154 women undergoing biopsy examination and 32 objects undergoing hysterectomy (control group) were collected in Tianjin Central Hospital of Gynecology Obstetrics in 2014. According to the pathological results of cervical biopsy, 154 samples were divided into low-grade squamous intraepi?thelial lesion group (LSIL, n=51), high-grade squamous intraepithelial lesion group (HSIL, n=71), and squamous cell carci?noma group (SCC, n=32). HPV DNA was tested with hybrid capture technology, and E6/E7 mRNA was detected with fluores?cence quantitative hybridization. Immunohistochemistry was performed by detecting E6/E7 protein in all patients after sur?gery or cervical biopsy. Results Combined results of HPV DNA and E6/E7 mRNA demonstrated that the positive detection rate was significantly lower in control group than that of all levels of lesion groups (P 10 000 E6/E7 were significantly increased in high-grade squamous intraepithelial lesion group. Immunohistochemical results showed that the positive detection rate of E6/E7 was significantly lower in control group than that of all levels of lesion groups (P<0.05). The positive rate of E6/E7 was significantly higher in the high-grade squa?mous intraepithelial lesion group than that of low-grade group (P<0.05). Conclusion HPV infection is closely related to cervical abnormalities, which is one of effective measures for early screening of cervical cancer. The negative result of HPV DNA is very helpful to exclude the cervical abnormality, whereas the positive detection of mRNA has great value in predict?ing the disease. Combined results of positive detection and copy number make a comprehensive evaluation for the risk of cer?vical lesions.

Incidence and risk factors of human papilloma virus type 16 infection / 天津医药

Objective To investigate the incidence and risk factors of human papillomavirus type 16 (HPV16) infec?tion among women through health screenings in Tianjin urban area. Methods A total of 2 000 women from Tianjin urban area were recruited for this study, and potential risk factors were investigated by questionnaire as well as by collecting cervi?cal exfoliated cells from the participants. HPV type was examined using polymerase chain reaction and pyrosequencing tech?nology, then the risk factors of HPV16 infection were examined by chi square test and the multiple factor logistic regression analysis. Results Among those 2 000 women who received health screenings, a total of 271 cases were HPV positive (13.55%). HPV16 accounts for the most common human papillomavirus types (39.5%, 107/271) while HPV58 account for 15.13%(41/271)and HPV18 account for 9.59% (26/271). Factors related to HPV16 infection were investigated include smoking history, initial age of sex (>25 years old or not) , number of pregnancies (≥2 or not), number of sexual partners (≥2 or not) and contraception measures (condom or other ways) with χ2=6.268,8.540,4.951,7.123,6.053,5.019, respectively. (P < 0.05). Age, alcohol intake, education level and previous gynecologial examination did not differ significantly among HPV16 positive patients compared to those with negative HPV. Multiple factor Logistic regression model analysis showed that the independent factors were smoking history and initial age for sex(≤25 years old)(P<0.05). Conclusion HPV16 is the most common type of cervical infection among women in Tianjin urban area. Changing inappropriate sexual behavior and smoking cessation are effective measures to prevent HPV16 infection and reduce incidence of cervical cancer.

The Analysis of HPV Genotypes and Related High Risk Factors in 459 Women of Annual Health Examination / 天津医药

Objective To investigate the cervical human papillomavirus (HPV) infection, genotypes and related high risk factors in 459 women of annual health examination. Methods A total of 459 cervical cytology specimens were de-tected with nest PCR and pyrosequencing methods. Questionnaires were collected simultaneously and the risk factors of HPV infection were analyzed. Results The detection rate of HPV-positive samples was 17.9%. Seven kinds of high-risk genotypes of HPV were found. The detection of HPV 16 was the most common (9.8%), followed by HPV58 (7.0%) and HPV18 (5.2%). The detection rates of simplex infection, dual infections and multiple infections were 9.6%, 4.8%and 1.5%respectively. The risk factors for HPV infection included alcohol consumption,income 1, frequency of sexual activity>4 times/month and cervical erosion (P<0.05). Conclusion HPV DNA genotyping can provide important reference for HPV screening at early time and the application of HPV vaccines, which also provide sig-nificant evidence for the prevention, diagnosis and treatment of cervical cancer at early stage for the high risk population.

Relationship between the methylation of L1 3' and long control region gene of HPV16 DNA and it's pathogenicity / 中华妇产科杂志

Objective Quantifiably and located measure the methylation rate of 21 cytosinephosphate-guanosine (CpG) sites in the 3' region of L1 gene and long control region (LCR) gene of HPV16 DNA in asymptomatic patients,cervical intraepithelial neoplasia (CIN) patients,and cervical cancer patients.To analysis the relationship between HPV16 methylation and it's pathogenicity.Methods Chosen 30 cases with HPV16 positive in each group.Firstly,extract DNA from the remaining cells of liquid-based cytology specimen and bisulfite treatment DNA,then amplify the 3' region of L1 gene and LCR gene,test the methylation rate of 21 CpG sites of HPV16 DNA in three groups.Results All of the 5 CpG sites in E6/E7 promoter (31,37,43,52,58) were hypomethylation in cervical cancer group (21.86％,28.15％,21.37％,26.15％,15.48％,respectively),hypermethylation in asymptomatic group,and middle-methylation in CIN group,in which there were significant difference among three groups (all P ＜0.01).The CpG site in 7032,7091,7136 of the 3' region of L1 gene was also different methylated among three groups (all P＜0.01).Hypermethylation was found in cancer group (18.89％,27.72％),hypomethylation was found in asymptomatic group (2.71％,6.95％) in 7032 and 7091.In 7136,the highest methylation was detected in CIN (66.45％),the lowest in asymptomatic (34.85％),middle in cancer group (46.43％).Conclusion The methylation status of CpG sites in the 3' region of L1 gene and E6/E7 promoter of HPV16 is significant different among three groups,which is likely to anticipate the pathogenesis of CIN and cervical cancer.

Primary Fallopian Tube Carcinoma: A Retrospective Clinical Analysis of 40 Patients / 中国肿瘤临床

Objective: To investigate the clinical features and survival factors of primary fallopian tube car-cinoma. Methods: We used Kaplan-Meier survival analysis, single factor analysis and multivariate analysis to evaluate the prognostic factors of 40 patients diagnosed with primary fallopian tube cancer. Results: The aver-age age of the patients was 51 years and all of them received surgery. There were 29 (72.5%) stage Ⅰ or Ⅱ patients, 11 stage Ⅲ or Ⅳ patients. Thirty-one (77.5%) patients were diagnosed with poorly differentiated tu-mors and 22 (55%) patients had serous adenocarcinoma. Thirty-seven patients received PAC/PC or TC che-motherapy after surgery. Six patients (15%) had recurrences within 23 to 56 months after surgery. The medi-an survival of Ⅰ～Ⅱ and Ⅲ～Ⅳ stage patients was 79 and 35 months, respectively. The total 5-year survival was 58% and 0 (P=0.005). Univariate and multivariate analysis showed that stage (Ⅰ～Ⅱ vs. Ⅲ-Ⅳ), grade (G_1+G_2 vs. G_3), residual disease after surgery (none, <1cm vs. >1cm) were significant factors affecting surviv-al. In accordance with the formula to calculate the half-life of CA125 and compare preoperative serum CA125 with the value at 3 weeks after surgery (T_(1/2)>3 week, T_(1/2)<3 week), the 5-year survival was 78% and 50%, re-spectively (P=0.036). Conclusion: Special attention should be paid to the joint screening of primary fallopian tube cancer in clinical practice in order to avoid misdiagnosis. The consecutive measurements of serum CA-125 level may have significant value as a prognostic indicator for patient survival.

E-cadherin promoter methylation and demethylation in epithelial ovarian carcinoma cells / 中华妇产科杂志

Objective To investigate the cytidylyl phosphate guanosine(CpG) islands methylation status of E-cadherin (E-cad) promoter region in human ovarian carcinoma cell lines (ES-2,3 AO, SKOV3 ), and the effect of 5-azacytidine-2 '-deoxycytidines (5-Aza-CdR ) on the cell proliferative ability, invasion and the expression of E-cad protein. Methods Methylation specific PCR(MSP) was used to detect CpG islands methylation status of E-cad promoter region in ES-2,3AO and SKOV3 cell lines. After treated with different concentrations of 5-Aza-CdR, morphological changes of cell lines were observed under microscope. The proliferative ability was evaluated by methyl thiazolyl tetrazolium(MTT) assay. E-cad protein expression was detected by western-blot and cellular invasion was investigated by 24-well matrigel invasion chambers. Results Hypermethylatian status of CpG islands of E-cad promoter region was observed in ES-2 and SKOV3 cell lines, but not in 3AO cell lines. After treated with 5-Aza-CdR (0.1,1.0,10.0 μmol/L), ES-2 and SKOV3 cell lines displayed morphological evidence of differentiation. 5-Aza-CdR was found to decrease proliferation as evidenced by cell growth curve , to increase the level of E-cad protein expression (P ＜ 0.01 ), and effectively inhibit the ability of cell invasion(P ＜0.01 ). Conclusions CpG hypermethylation is an important mechanism of E-cad gene inactivation in ES-2 and SKOV3 cell lines. 5-Aza-CdR be found to inhibit proliferation and invasion, and increase the expression of E-cad probably by the inhibition of hypermethylation.

Sentinel Lymph Node Detection in Endometrial Cancer and Clinical Significance of Micrometastases / 中国肿瘤临床

Sentinel lymph node (SLN) detection in endometrial cancer is still in the exploration stage. But a good many studies have confirmed the feasibility of SLN detection in patients with early endometrial cancer. Higher detection rate of SLN can be achieved by the combination of blue dye and radiocolloid. Compared with intracervical injection, more injections at different sites of the uterine corpus and hysteroscopic injection may improve SLN detection rate and para-aortic SLN detection rate. SLN detection rates are also related to some other factors such as the amount of tracers, the interval between injection and detection, and the depth of myometrium invasion. Serial-step section of SLN combined with immunohistochemistry staining with anti-cyto-keratin may improve the detection of micrometastasis (MM) in SLN. SLN procedure can detect MM which cannot be found by traditional pathological techniques. The ultrastaging will allow better stratification of patients at intermediate risk and can provide valuable informaiton for the selection of adjuvant therapy, thus decreasing the recurrent rate.