Nonsteroidal anti-inflammatory drug with a local anesthetic compared to nonsteroidal anti-inflammatory drug alone significantly reduce the pain associated with vaginoscopic office hysteroscopy.

INTRODUCTION AND OBJECTIVES: Pain is the most common cause of office hysteroscopy (OH) failure. There is no consensus on alleviation of pain during OH. The aim was to compare the effectiveness of pain-relieving methods during OH. STUDY DESIGN: A prospective randomized open-label trial included women subjected to OH. All women received 100 mg of ketoprofen intravenously pre-procedure. Women were randomly assigned to 3 arms: A) no local anesthesia, B) infiltration anesthesia with 20 ml of 1% lidocaine solution, C) paracervical block with 20 ml of 1% lidocaine solution. Karl Storz Bettocchi® rigid hysteroscope with a 5 mm operative sheath was used. Intensity of pain in numeric rating scale (NRS), intensity of cervical bleeding, frequency of vasovagal episodes, and failure rate were compared. RESULTS: The study involved 201 women, 67 in each arm. NRS value during OH was higher in arm A than in B and C (6.3 vs. 5.1 vs. 5.0; p = 0.01). NRS value after OH did not differ and in all arms pain was imperceptible (p = 0.007). Cervical bleeding was more frequent in arm B than in A and C (76.1% vs. 33.4% vs. 35.9%; p < 0.0001), but its intensity did not differ from the other arms (p = 0.3). Vasovagal episode was most common in arm B (p = 0.048). There was no difference in the failure rate between the arms (p = 0.08). CONCLUSIONS: The paracervical block, albeit technically the most laborious, has proven to be the most beneficial for the patient in terms of overall comfort and for the surgeon regarding feasibility.

Association of Membranous WNT-1 and Nuclear mTOR with Endometrial Cancer Grade.

Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1-3 and FIGO stages I-IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB-IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms.

CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion.

BACKGROUND: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1-3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer.

Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.

Metastatic and non-metastatic sentinel inguinofemoral lymph nodes in vulvar cancer show an increased lymphangiogenesis.

INTRODUCTION AND OBJECTIVE: Lymph node involvement is a strong predictor of disease recurrence and patient survival in vulvar cancer. The aim of the study was to evaluate the feasibility of sentinel lymph node (SLN) screening, the incidence of skip metastases, and lymph node lymphangiogenesis. MATERIAL AND METHODS: Fifty-five patients participated in this prospective, single centre study. A double SLN screening method was employed using radiocolloid (technetium-99 sulfur colloid) and 1.0% Isosulfan Blue. Immunohistochemistry, using a mouse monoclonal antibody against D2-40, was used to evaluate lymphatic vessel density (LVD). All calculations were performed using STATISTICA software v. 10 (StatSoft, USA, 2011); p < 0.05 was considered significant. RESULTS: Using both methods of SLN detection, 100% accuracy was achieved, and skip metastases were diagnosed in only one woman (1.82%). Peri-tumour median LVD was significantly increased compared with matched intra-tumour samples (p < 0.001), while median LVD was significantly lower in negative, compared with positive SLN, regardless of whether matched non-SLN were negative (p < 0.001) or positive (p = 0.005). Metastatic SLN exhibited significantly higher median LVD compared with matched negative non-SLN (p = 0.015), while no significant difference in median LVD was detected between positive SLN and matched positive non-SLN. However, negative SLN had a significantly higher median LVD compared with matched negative non-SLN (p = 0.012). CONCLUSIONS: SLN detection is a safe and feasible procedure in vulvar cancer. In patients without nodular involvement, SLN, compared with non-SLN, exhibited significantly higher median LVD, which may be an indication of its preparation to host metastases, and thus requires further investigation.

SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

BACKGROUND: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. METHODS: SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. RESULTS: The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. CONCLUSIONS: There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.

[The influence of age, place of living, education and number of earlier pregnancies on attendance of pregnant women to screening tests--questionnaire study]. / Wplyw wieku, miejsca zamieszkania, wyksztalcenia i Iiczby wczesniejszych ciaz na zglaszalnosc ciezarnych do badan przesiewowych- badanie ankietowe.

UNLABELLED: The aim of this study was to assess attendance at the screening programme in pregnancy and the influence of age, number of past pregnancies, level of education and place of residence on the attendance. MATERIAL AND METHODS: Our study was performed on the basis of an anonymous questionnaire handed out 543 women aged 16-45, on the third day of their puerperal, in one of the five obstetric wards in southern Poland. The questionnaire contained questions about participation in recommended for pregnant women screening tests such as: fasting blood glucose level measurement, oral glucose tolerance test, blood type test, measurement of hepatitis B surface antigen and antibodies to VDRL, Rubella, Toxoplasma gondii, hepatitis C virus at least once during pregnancy. RESULTS: The highest attendance rate was related with blood type test, whereas the lowest was related with measurement of antibodies to hepatitis C virus (95.6% vs 22.7%, p < 0.001). A very low percentage of pregnant patients measured Rubella antibodies (29.1%). A larger proportion of the respondents checked antibodies against Toxoplasma gondii (41.6%). The attendance at fasting blood glucose level was 66.9 % and at oral glucose tolerance test was 63.7%. The attendance according as age, place of living, number of past pregnancies and level of education was described in detail. CONCLUSION: Despite current recommendations of Polish Gynecological Society and the ordinance of polish Minister of Health the percentage of women participating in screening tests during pregnancy is still insufficient. Age, place of residence and education remain strong factors influencing attendance at the screening programme in pregnancy.

Analysis of RCAS1 immunoreactivity within hydatidiform mole cells and decidual cells according to the applied therapeutic strategy: surgery or surgery followed by chemotherapy.

INTRODUCTION: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. METHODS: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULT: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. CONCLUSION: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.

[The value of three-dimensional multiplanar (MPV) and volume contrast imaging (VCI) in the ultrasound evaluation of endometrial pathology]. / Wartosc trójwymiarowego obrazowania wieloplaszczyznowego (MPV) i kontrastowego (VCI) w ultrasonograficznej ocenie patologii blony sluzowej jamy macicy.

The aging of the women population as well as widespread use of the ultrasound leads to an increased detection of abnormal endometrial characteristics. The aim of this study was to assess the value of three-dimensional ultrasound viewing options: multi-planar view (MPV) and volume contrast imaging (VCI) in the endometrial evaluation. 147 women, referred for endometrial sampling, because of bleeding or an abnormal endometrial two-dimensional ultrasound image were enrolled in the study. Before dilation and curettage, all patients underwent three-dimension ultrasound scans for endometrial thickness measurements and endometrial-myometrial junction assessment. Ultrasound results and the presence of abnormal vaginal bleeding were compared with pathological diagnosis. Sensitivity, specificity, negative predictive value, and positive predictive value for abnormal vaginal bleeding, irregular endometrial-myometrial junction and endometrial thickness were established. Logistic regression model was used to assessed the relationship between the characteristics and the incidence of endometrial pathology. For each of the independent variables odds ratios were calculated. Sensitivity, specificity of the endometrial thickness cut-off 11 mm were 73.8%, 74.4%, for 10.5 mm 76.2%, 69.8% respectively. The irregular endometrial-myometrial junction reached 70.5% sensitivity and 93% specificity. Odds ratios for 10,5 mm cu-off value of the endometrial thickening and irregular E-M junction were calculated: 4.10 [95% CI: 1.14-14.74] and 36.07 [95% CI: 7.10-183.27]. The negative predictive value of any of these parameters did not exceed 70%. The combination of 3D ultrasound parameters and the occurrence of abnormal vaginal bleeding has reached only 53% sensitivity. In the case of connection of two of these three indices, increased sensitivity of 76.9% and specificity of 82.4%. In an unselected group of women in terms of menopausal status and symptoms endometrial thickness measured and the evaluation of endometrial-myometrial junction using 3D ultrasound is less value in predicting the occurrence of endometrial cancer than in 2D and the endometrial volume calculation.

Prevalence of HPV-DNA in Pap smears containing ASC and AGC performed within Population Programme of Prophylaxis and Early Detection of Early Cervical Cancer.

AIM: to assess the incidence of HPV -DNA in women with ASC/AGC compared to patients with normal Pap smears. MATERIAL AND METHODS: The study group consisted of 242 women (207 ASC and 35 AGC cases). The control group counted 200 age-matched women with negative Pap smears. Cervical samples collected from all the participants were tested for the presence of HPV-DNA using the Hybrid Capture-2 test. RESULTS: Total HPV infection was significantly higher in the study than in the control group (43.0% vs.14.0%) (p=0.005). There was no difference in the incidence of HPV -DNA between ASC and AGC groups. Prevalence of HPV-DNA ASC-H was significantly higher in ASC-US group (83.3% vs. 40.5%) (p=0.004). HPV positive endometrial AGC significantly outnumbered HPV positive endocervical AGC (88.9% vs. 26.9%) (p=0.003). Similar trends were observed for the high-risk type of HPV (p<0.001). CONCLUSIONS: The significant difference in HPV -DNA incidence between the study and control groups suggests that HPV plays a role in the development of ASC and AGC. The implementation of HPV testing in all women diagnosed with ASC or AGC can lead to tailored therapeutic management and more careful follow-up care.