Concomitant ectopic Enterobius vermicularis infection in uterine cervical cancer.

BACKGROUND: Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making their caretakers a population at risk for the transmission of this helminth. It can occasionally affect extraintestinal organs and tissues, including the female genital tract. Infestation can be asymptomatic or manifest as different kinds of gynaecological disorders, such as pelvic inflammation mimicking tumours, abnormal uterine bleeding, or vaginitis. Diagnosis is made by identifying ova in the sample collected from the perineal skin using a transparent adhesive tape or microscopic examination of resected tissue. Mebendazole is the first-line medication and should also be administered to all household members. CASE PRESENTATION: We present a case of a patient who had undergone surgery for invasive cervical cancer with an accidental finding of E. vermicularis eggs in the cervix. CONCLUSIONS: Although not very common, infestation with E. vermicularis should be considered in differential diagnoses of various gynaecological disorders accompanied by histological findings of granulomatous inflammation.

Finding a Direct Method for a Dynamic Process: The DD (Direct and Dynamic) Cell-Tox Method.

The main focus of in vitro toxicity assessment methods is to assess the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division, or remain viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids, and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells, and liver sinusoidal endothelial cells to rifampicin, ibuprofen, and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds, as it considers the different cellular responses induced by toxic agents.

Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review.

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Gynaecological cancers and their cell lines.

Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape.

Endometrial cancer and its cell lines.

Endometrial cancer is one of the most common gynaecological malignancies worldwide. One type of research in this field is the growing of cell lines (CLs) and cultures, which can be used to explore the biological mechanisms of cancer. The purpose of this review is to offer an overview of the current literature and highlight the importance of correct CL studies. We carried out a literature analysis of more than 60 articles from the Pubmed, Medline databases that were almost exclusively published in indexed journals in the last 10 years as well as the primary originating scientific studies of specific CLs. We then summarized the newest findings and recommendations. Cell lines are becoming widely used as in vitro tumour models. Recent work has shown inconsistencies in nomenclature and culturing of CLs. Their genomic evolution leads to a high degree of variation across CL strains therefore it is of the utmost importance to recognize the variability within laboratory cancer models. Laboratories must adapt, incorporate additional characterisation techniques and view this situation as an opportunity to improve the reproducibility of pre-clinical cancer research. The authors offer a comprehensive literature review about endometrial cancer CLs, a review of the current literature and advice on culturing CLs.

Planned home birth in Slovenia-Are we ready?

Nowadays, women want a more intimate and familiar atmosphere during labour, which results in increased planned home birth rates. Every woman has the autonomy to decide where she will give birth; however, it is important that she is informed of risks and advantages beforehand. Home births can be distinguished between planned and unplanned home births. Planned home births can be conducted by professional birth attendants (licensed midwives) or birth assistants (doulas, etc). The rates of Slovenian women who decided to deliver at home are increasing year by year. Researches on home births still present discordant data about home birth safety. Their findings have shown that the main advantage of home birth is a spontaneous birth without medical interventions, especially in multiparous low-risk women. The main disadvantage, however, is a higher risk for neonatal death, in particular on occurrence of complications requiring a transfer to hospital and surgical intervention. Global guidelines emphasize careful selection of candidates suitable for home birth, well-informed pregnant women, education of birth attendants, and strict formation of transfer indications.

The passage of fluid into the peritoneal cavity during hysteroscopy in pre-menopausal and post-menopausal patients.

The present study aimed to determine the amount of fluid medium passing through the Fallopian tubes into the peritoneal cavity during a hysteroscopy. This was done to understand the pathophysiology of complications related to the hysteroscopy. Conducted in a general hospital setting, the study examined the fluid inflow-outflow during a hysteroscopy both in pre- and post-menopausal women. A hysteroscopy was performed vaginoscopically for both diagnostic and therapeutic procedures. The study involved 117 patients. 84 (71.8%) of them were pre-menopausal and 33 (28.2%) were classified as post-menopausal. The fluid volume difference in the peritoneal cavity prior to hysteroscopy was 26.0 ± 4.2 mL in the pre-menopausal and 7.7 ± 2.4 mL (p = .001) in the post-menopausal group. The pre-menopausal group's flow rate through the Fallopian tubes was 1.5 ± 0.2 mL/min. In the post-menopausal group, it was 0.4 ± 0.1 mL/min (p < .05). It was found that during the hysteroscopy in the pre-menopausal patients, more fluid flows through the Fallopian tubes and at a higher flow rate. Impact statement What is already known on this subject? The complications during a hysteroscopy (HSC) are usually fluid-related and can result in adverse events such as a fluid overload, the dissemination of malignant cells, or electrolyte misbalance. Currently, there is a poor understanding of how HSC fluid behaviour impacts on the pathophysiology of these adverse procedure effects. What do the results of this study add? There have been no quantitative studies of the behaviour of fluid inside the uterine cavity during HSC, which means a quantification of fluid inflow and absorption is required. Our study adds a quantitative understanding of fluid behaviour during HSC. It shows increased rates of fluid passage, as well as fluid speed, into the peritoneal cavity in pre-menopausal patients. What are the implications of these findings for clinical practice and/or further research? Due to the higher rates of fluid passage and speed in pre-menstrual patients, caution regarding the complications during hysteroscopy and further studies are needed on the impact of different fluid distribution.

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients.

BACKGROUND: The association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients. PATIENTS AND METHODS: A retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000-2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model. RESULTS: In univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83-4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low. CONCLUSIONS: uPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.

Incidence of positive peritoneal cytology in patients with endometrial carcinoma after hysteroscopy vs. dilatation and curettage.

BACKGROUND: The aim of the study was to compare the frequency of positive peritoneal washings in endometrial cancer patients after either hysteroscopy (HSC) or dilatation and curettage (D&C). PATIENTS AND METHODS: We performed a retrospective analysis of 227 patients who underwent either HSC (N = 144) or D&C (N = 83) and were diagnosed with endometrial carcinoma at the University Medical Centre Maribor between January 2008 and December 2014. The incidence of positive peritoneal cytology was evaluated in each group. RESULTS: There was no overall difference in the incidence of positive peritoneal washings after HSC or D&C (HSC = 13.2%; D&C = 12.0%; p = 0.803). However, a detailed analysis of stage I disease revealed significantly higher rates of positive peritoneal washings in the HSC group (HSC = 12.8%; D&C = 3.4%; p = 0.046). Among these patients, there was no difference between both groups considering histologic type (chi-square = 0.059; p = 0.807), tumour differentiation (chi-square = 3.709; p = 0.156), the time between diagnosis and operation (t = 0.930; p = 0.357), and myometrial invasion (chi-square = 5.073; p = 0.079). CONCLUSIONS: Although the diagnostic procedure did not influence the overall incidence of positive peritoneal washings, HSC was associated with a significantly higher rate of positive peritoneal cytology in stage I endometrial carcinoma compared to D&C.

Hypodontia phenotype in patients with epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is usually diagnosed in an advanced stage and the present clinical and diagnostic molecular markers for early OC screening are insufficient. The aim of this study was to identify potential relationship between the hypodontia and epithelial ovarian cancer (EOC). PATIENTS AND METHODS: A retrospective study was conducted on 120 patients with EOC treated at the Department of Gynaecologic and Breast Oncology at the University Clinical Centre and 120 gynaecological healthy women (control group) of the same mean age. Women in both groups were reviewed for the presence of hypodontia and the patients with EOC also for clinicopathological characteristics of EOC according to hypodontia phenotype. RESULTS: Hypodontia was diagnosed in 23 (19.2%) of patients with EOC and 8 (6.7%) controls (p = 0.004; odds ratio [OR] = 3.32; confidence interval [CI], 1.42-7.76). There was no statistically significant difference in patients with EOC with or without hypodontia regarding histological subtype (p = 0.220); they differed in regard to FIGO stage (p = 0.014; OR =3.26; CI, 1.23-8.64) and tumour differentiation grade (p = 0.042; OR = 3.1; CI, 1.01-9.53). Also, bilateral occurrence of EOC was more common than unilateral occurrence in women with hypodontia (p = 0.021; OR = 2.9; CI, 1.15-7.36). We also found statistically significant difference between the ovarian cancer group and control group in presence of other malignant tumours in subjects (p < 0.001). CONCLUSIONS: The results of the study suggest a statistical association between EOC and hypodontia phenotype. Hypodontia might serve as a risk factor for EOC detection.

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors.

BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. PATIENTS AND METHODS: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman's rank correlation, Mann Whitney U test and χ(2) test for statistical analysis. RESULTS: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). CONCLUSIONS: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.

Preoperative diagnosis of fallopian tube malignancy with transvaginal color doppler ultrasonography and magnetic resonance imaging after negative hysteroscopy for postmenopausal bleeding.

Primary fallopian tube carcinoma is a rare malignancy and is not often diagnosed preoperatively. We present a case of a 67-year-old woman who complained of postmenopausal vaginal bleeding. After a negative hysteroscopy, transvaginal ultrasound showed a well vascularized solid-cystic tumor in the adnexal region separate from the ovary. The presence of an adnexal mass was confirmed by MR imaging. Total abdominal hysterectomy with bilateral salpingoophorectomy, omentectomy and appendectomy, as well as pelvic and paraaortic lymphadenectomy was performed. The pathohistological diagnosis was poorly differentiated serous adenocarcinoma of the fallopian tube, FIGO stage IA. The patient was subsequently treated with platinum based adjuvant chemotherapy.

Isoform-Level Transcriptome Analysis of Peripheral Blood Mononuclear Cells from Breast Cancer Patients Identifies a Disease-Associated RASGEF1A Isoform.

Background: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.

Advances in Tumour-Infiltrating Lymphocytes for Triple-Negative Breast Cancer Management.

Triple negative breast cancer (TNBC) is a subtype of breast cancer which does not express or expresses a minimum amount of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) protein. TNBCs include a heterogenic group of cancers that are aggressive, grow rapidly and are associated with poor prognosis and overall survival, mainly attributed to a lack of effective therapeutic targets. For a long time, a major issue with predicting the outcome and prognosis of TNBCs was the lack of an accurate biomarker, a molecule that helps us objectively assess a patient's health status. In recent times, defining the presence of tumor-infiltrating lymphocytes (TIL) is becoming an indispensable method of determining a patient's prognosis. TILs are found in tumor tissue and the surrounding stroma and carry a prognostic value. Furthermore, they are known to improve the effect of systemic therapy. With the rise of immunotherapy, the role of TIL in this newer therapeutic option is a topic of increased importance. The goal behind this research article is a comprehensive review of the current literature on the importance of tumor-infiltrating lymphocytes in the prognosis of TNBC.

Identification of women with high grade histopathology results after conisation by artificial neural networks.

BACKGROUND: The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing conisation because of pathological changes on uterine cervix. PATIENTS AND METHODS: We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993-2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis. RESULTS: Bas eline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%. CONCLUSIONS: With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993-2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.

Advances in diagnostics and management of gestational trophoblastic disease.

BACKGROUND: Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). CONCLUSIONS: Patients with GTD are often asymptomatic, although vaginal bleeding is a common presenting symptom. With the advances in ultrasound imaging in early pregnancy, the diagnosis of molar pregnancy is most commonly made in the first trimester of pregnancy. Sometimes, additional imaging such as chest X-ray, CT or MRI can help detect metastatic disease. Most women can be cured, and their reproductive function can be preserved. In this review, we focus on the advances in management strategies for gestational trophoblastic disease as well as possible future research directions.

Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancer.

High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery.

Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer.

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

A Case of Stevens-Johnson Syndrome in Recurrent Late-Stage Ovarian Cancer Patient after Management of Chronic Pain with Elastomeric Pump.

(1) Background. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. (2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking, which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy, and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories, and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia, and in the following days she developed haemorrhagic vesiculobullous lesions on the facial skin and trunk. Stevens-Johnson syndrome was confirmed and ondansetron as a plausible leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. (3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens-Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.