Cervix-Online computer program: 27 years of hospital-based clinical registry for cervical cancer at the University Medical Centre Maribor.

BACKGROUND: Clinical registries are designed to collect quality data about the care for cancer patients in order to improve it. They gather data that are generated during diagnosis and cancer treatment and also post-treatment follow-up. Analysis of collected data allows an improvement in the quality of patient care and a comparison with other health care providers. The aim of the present article is to describe the current version and practice of hospital-based cervical cancer registry in UKC Maribor. MATERIALS AND METHODS: The first questionnaire for monitoring patients with cervical cancer was introduced at the Department of Gynecologic and Breast Oncology of the Maribor General Hospital in 1994. Since then, the principles for treating cervical cancer have been revised on several occasions. Therefore, based on our experience and new approaches to treatment, we have frequently amended the questionnaire content. It was redesigned into a form that is currently in use and transformed into a Cervix-Online computer program in 2014. RESULTS: Over the last 27 years, we have collected data on cervical cancer patients treated at the University Medical Centre Maribor and former Maribor General Hospital. The Cervix-Online computer program that was developed for this purpose enabled a rapid and reliable collection, processing and analysis of 116 different data of patients with cervical cancer, including general data, history, diagnostic procedures, histopathological examination results, treatment methods, and post-treatment follow-ups. CONCLUSIONS: The hospital-based cervical cancer registry with Cervix-Online computer program enables the collection of data to enhance diagnosis and the treatment of cervical cancer patients, the organization of day-to-day service, as well as the comparison of our treatment results with national and international standards. Incomplete or incorrect data entry, however, might pose a limitation of the clinical registry, which depends on several healthcare professionals involved in the diagnostic procedures, treatment, and follow-up of cervical cancer patients.

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.

Long term results of follow-up after HPV self-sampling with devices Qvintip and HerSwab in women non-attending cervical screening programme.

BACKGROUND: We are presenting the results of the Slovenian human papillomaviruses (HPV) self-sampling pilot study in colposcopy population of National Cervical Cancer Screening Programme ZORA for the first time. One-year and four-year follow-up results are presented for two different self-sampling devices. PARTICIPANTS AND METHODS: A total of 209 women were enrolled in the study at colposcopy clinic. Prior to the gynaecological examination, all women performed self-collected vaginal swab at the clinic; 111 using Qvintip and 98 using HerSwab self-sampling device. After self-sampling, two cervical smears were taken by a clinician; first for conventional cytology and second for HPV test. After that, all women underwent colposcopy and a cervical biopsy if needed. We compared sensitivity, specificity, and predictive values of cytology (at the cut-off atypical squamous cells of undetermined significance or more [ASC-US+]) and HPV test (on self- and clinician-taken samples) for the detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) after one and four years of follow-up. Hybrid Capture 2 (HC2) assay was used for all HPV testing. RESULTS: The mean age of 209 women was 37.6 years and HPV positivity rate 67.0% (140/209), 36.9 years and 70.3% (78/111) in the Qvintip group and 38.4 years and 63.3% (62/98) in the HerSwab group, respectively. Overall, percent agreement between self and clinician-taken samples was 81.8% (kappa 0.534) in the Qvintip and 77.1% (kappa 0.456) in the HerSwab group. In the Qvintip group, the longitudinal sensitivity, specificity, positive and negative predictive values were 71.8%, 75.0%, 83.6%, 60.0% for cytology; 83.1%, 51.3%, 75.6% and 62.5% for HPV test of self-taken samples and 94.4%, 57.5%, 79.8% and 85.2% for HPV test on clinician-taken samples. In the HerSwab group, the corresponding results were 71.7%, 46.7%, 61.3%, 58.3% for cytology; 75.0%, 47.7%, 62.9% and 61.8% for HPV test on self-taken samples and 94.3%, 44.4%, 66.7% and 87.0% for clinician-taken samples, respectively. CONCLUSIONS: The results confirm that HPV self-sampling is not as accurate as clinician sampling when HC2 is used. All HPV tests showed a higher sensitivity in detecting CIN2+ compared to cytology. Due to non-inferior longitudinal sensitivity of HPV self-sampling compared to cytology, HPV self-sampling might be an option for non-attenders to the National Cancer Screening Programme.

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.

Identification of novel diagnostic biomarkers in endometrial cancer using targeted metabolomic profiling.

PURPOSE: Endometrial cancer (EC) is the most common gynecological malignancy with high disease burden especially in advanced stages of the disease. Our study investigated the metabolomic profile of EC patient's serum with the aim of identifying novel diagnostic biomarkers that could be used especially in early disease detection. MATERIAL AND METHODS: Using targeted metabolomic serum profiling based on HPLC-TQ/MS, women with EC (n â€‹= â€‹15) and controls (n â€‹= â€‹21) were examined for 232 endogenous metabolites. RESULTS: Top performing biomarkers included ceramides, acylcarnitines and 1-methyl adenosine. Top 4 biomarkers combined achieved 94% sensitivity with 75% specificity with AUC 92.5% (CI 90.5-94.5%). Individual markers also provided significant predictive values: C16-ceramide achieved sensitivity 73%, specificity 81%, AUC 0.83, C22-ceramide sensitivity 67%, specificity 81%, AUC 0.77, hydroxyhexadecenoylcarnitine sensitivity 60%, specificity 96%, AUC 0.76 and 1-methyladenosine sensitivity 67%, specificity 81%, AUC 0.75. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. CONCLUSIONS: Using mass spectrometry targeted metabolomic profiling, ceramides, acylcarnitines and 1-methyladenosine were identified as potential diagnostic biomarkers for EC. Additionally, these identified metabolites may provide additional insight into cancer cell metabolism.

Identification of Novel Diagnostic Biomarkers in Breast Cancer Using Targeted Metabolomic Profiling.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women, with a high disease burden, especially in the advanced disease stages. Our study investigated the metabolomic profile of breast cancer patients' serum with the aim of identifying novel diagnostic biomarkers that could be used, especially for early disease detection. MATERIALS AND METHODS: Using targeted metabolomic serum profiling based on high-performance liquid chromatography mass spectrometry, women with BC (n = 39) and a control group (n = 21) were examined for 232 endogenous metabolites. RESULTS: The top performing biomarkers included acylcarnitines (ACs) and 9,12-linoleic acid. A combined panel of the top 4 biomarkers achieved 83% sensitivity and 81% specificity, with an area under the curve (AUC) of 0.839 (95% confidence interval, 0.811-0.867). Individual markers also provided significant predictive values: AC 12:0, sensitivity of 72%, specificity of 67%, and AUC of 0.71; AC 14:2, sensitivity of 74%, specificity of 71%, and AUC of 0.73; AC 14:0: sensitivity of 67%, specificity of 81%, and AUC of 0.73; and 9,12-linoleic acid, sensitivity of 69%, specificity of 67%, and AUC of 0.71. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. CONCLUSION: Using mass spectrometry-targeted metabolomic profiling, ACs and 9,12-linoleic acid were identified as potential diagnostic biomarkers for breast cancer. Additionally, these identified metabolites could provide additional insight into cancer cell metabolism.

Clinical features and their effect on outcomes of patients with triple negative breast cancer with or without lymph node involvement.

OBJECTIVE: Clinical and pathological characteristics of triple negative breast cancer (TNBC) treatment are required for escalation or de-escalation of treatment because of a lack of druggable targets. This study aimed to identify the factors affecting the risk of disease recurrence and disease-related death in patients with TNBC. METHODS: Patients with TNBC who were treated at the University Medical Centre Maribor between January 2010 and December 2017 were studied. Clinical and pathological data were analyzed using multivariate analysis and non-parametric tests. Subgroup analysis was performed to examine additional factors that affect 5-year overall survival (OS) and recurrence-free survival. RESULTS: Multivariate analysis showed that tumor size and the lymph node ratio (LNR) were significant risks in our population. Better discrimination of patients at risk of a shorter recurrence-free survival and OS was achieved by using the LNR. Only lymphovascular invasion was significant for predicting 5-year OS. CONCLUSION: For risk-based decision-making systems, the LNR is useful for discriminating between high- and low-risk patients with TNBC.

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.

Inquiry and computer program Onko-Online: 25 years of clinical registry for breast cancer at the University Medical Centre Maribor.

Background High-quality routine care data collected in the clinical registry play a significant role in improving the management of cancer patients. Clinical cancer registries record important data in the course of cancer diagnosis, treatment, follow-up and survival. Analyses of such comprehensive data pool make it possible to improve the quality of patients care and compare with other health care providers. Methods The first inquiry at the Department of Gynaecologic and Breast Oncology of the then General Hospital Maribor to follow breast cancer patients has been introduced in 1994. Based on our experience and new approaches in breast cancer treatment, the context of inquiry has been changed and extended to the present form, which served as a model for developing a relevant computer programme named Onko-Online in 2014. Results During the 25-year period, we collected data from about 3,600 breast cancer patients. The computer program Onko-Online allowed for quick and reliable collection, processing and analysis of 167 different data of breast cancer patients including general information, medical history, diagnostics, treatment, and follow-up. Conclusions The clinical registry for breast cancer Onko-Online provides data that help us to improve diagnostics and treatment of breast cancer patients, organize the daily practice and to compare the results of our treatment to the national and international standards. A limitation of the registry is the potentially incomplete or incorrect data input by different healthcare providers, involved in the treatment of breast cancer patients.

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.

Retained surgical needle and gauze after cesarean section and adnexectomy: a case report and literature review.

Although the incidence of retained surgical items (RSIs) is low, it is nevertheless an important preventable cause of patient injury that can ultimately lead to the patient's death and to subsequent high medical and legal costs. Unintentional RSI is the cause of 70% of re-interventions, with a morbidity of 80% and mortality of 35%. The most common RSIs are sponges or gauze (gossypiboma or textiloma), while retained surgical instruments and needles are rare. Perioperative counting of equipment and materials is the most common method of screening for RSIs, while a diagnosis can later be confirmed by the clinical appearance and by imaging studies. We present a rare case of a 43-year-old patient who was admitted to our hospital because of two retained needles following a cesarean section, despite several subsequent laparotomies. One needle had been removed previously, but in addition to the remaining needle, we also removed a retained gauze. The diagnosis of RSIs is extremely important, and safe surgical practices including the addition of new imaging technologies should be encouraged to detect RSIs.

Data on metabolomic profiling of ovarian cancer patients' serum for potential diagnostic biomarkers.

The data presented here are related to the research paper entitled "Metabolomic profiling suggests long chain ceramides and sphingomyelins as a possible diagnostic biomarker of epithelial ovarian cancer." (Kozar et al., 2018) [1]. Metabolomic profiling was performed on 15 patients with ovarian cancer, 21 healthy controls and 21 patients with benign gynecological conditions. HPLC-TQ/MS was performed on all samples. PLS-DA was used for the first line classification of epithelial ovarian cancer and healthy control group based on metabolomic profiles. Random forest algorithm was used for building a prediction model based over most significant markers. Univariate analysis was performed on individual markers to determine their distinctive roles. Furthermore, markers were also evaluated for their biological significance in cancer progression.

Metabolomic profiling suggests long chain ceramides and sphingomyelins as a possible diagnostic biomarker of epithelial ovarian cancer.

INTRODUCTION: Epithelial ovarian cancer (EOC) is a disease with a poor survival rate mostly due to its discovery in late stages. The aim of this study was to investigate the metabolomic profile of ovarian cancer with the intention of identifying and describing novel biomarkers with diagnostic potential. MATERIAL AND METHODS: Targeted serum metabolomic profiling was performed on 15 patients with ovarian cancer, 21 healthy controls and 21 patients with benign ovarian conditions, using HPLC-TQ/MS. RESULTS: Panel of 49 top performing biomarkers shows separation between EOC and controls with 87% specificity and 87% sensitivity with AUC of 93% (CI 90%-95%). Using only 5 top biomarkers, specificity of 80% and sensitivity of 83% was achieved on extended sample set. Most significant biomarkers belong to sphingolipid classes, especially long chain ceramides and sphingomyelins. Different concentrations of various fatty acid chain lengths ceramides and sphingomyelins are also implying their respective roles in cell proliferation and growth inhibition. CONCLUSION: Long chain ceramides and sphingomyelins may serve as a novel biomarker for epithelial ovarian cancer detection and may also offer insight into the role of sphingolipid metabolism in cell proliferation.

The value of ultrasound-guided surgery for breast cancer.

OBJECTIVE: An increasing number of breast-conserving surgeries (BCS) has lead clinicians to the dilemma how to provide patients with the best pathological, short-term and long-term outcomes, while at the same time improving the cosmetic outcome and the patients' quality of life. A proposed solution is the use of intraoperative ultrasound (IOUS) for lesion resection in palpable as well as non-palpable breast cancer. METHODS: This review identifies and compares evidence on palpation-guided/wire-guided vs. US-guided localization as well as stand-alone observational IOUS studies published between June 2001 and July 2017, indexed in Medline. A cornerstone of this review is the discussion on technology advancement as well as alternative IOUS approaches and their feasibility in treatment of patients with calcifications and multifocal lesions currently not treated with IOUS localization. RESULTS: In comparison to other available methods, IOUS provided in most studies better rates of clear margins, lower rates of re-excisions as well as better cosmetic outcomes. Currently, there is a lack of available multicenter data on method comparisons as well as several limitations to the use of IOUS. CONCLUSIONS: With a comparable follow-up rate of loco-regional recurrences and a higher reported long-term quality of life, IOUS should be a highly regarded method of localization in the planning of BCS.

Survival of Node-negative Breast Cancer Patients Treated at the University Medical Centre Maribor in the Period 2000-2009.

INTRODUCTION: Breast cancer is increasingly diagnosed in the early stages without regional nodal involvement. The aim of the present study was to determine the 5-year overall (OS) and breast cancer specific survival (BCSS) for patients with node-negative breast cancer treated at the University Medical Centre Maribor, and compare it with survival at the national level. METHODS: Medical records were searched for information on patients with lymph node-negative invasive breast cancer who received primary treatment at the University Medical Centre Maribor in the period 2000-2009. Information on all Slovenian node-negative breast cancer patients diagnosed in the same period was obtained from the Cancer Registry of Republic of Slovenia. Time trends in survival were assessed by comparing the periods 2000-2004 and 2005-2009. RESULTS: The 5-year OS and BCSS of patients treated in Maribor in the period 2000-2009 were 92.3% (95% CI, 90.5%- 94.1%) and 96.4% (95% CI, 95.2%-97.6%), respectively, and did not differ from the corresponding OS and BCSS for Slovenian patients. Although the improvement in OS for patients from Maribor diagnosed in the period 2005-2009 compared to 2000-2004 did not reach statistical significance (HR 0.73; 95% CI, 0.51-1.05; p=0.086), BCSS significantly improved over the same time periods (HR 0.53; 95% CI, 0.30-0.94; p=0.028). CONCLUSIONS: Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor is comparable to survival of corresponding patients at the national level. The rising number of long-term breast cancer survivors places additional importance on survivorship care.

Prognostic Role of HER2 Status and Adjuvant Trastuzumab Treatment in Lymph Node-Negative Breast Cancer Patients - a Retrospective Single Center Analysis.

BACKGROUND: The natural course of traditionally prognostically unfavorable human epidermal growth factor receptor 2 (HER2)-positive breast cancer has been changed by anti-HER2 therapy. It is not clear whether the prognosis for HER2-positive patients treated with adjuvant trastuzumab differs from that of HER2-negative patients. METHODS: We performed a retrospective study including patients with lymph node-negative invasive breast cancer treated at our institution in the period 2000-2009. Disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was applied to control for other clinically important variables. RESULTS: Median follow-up was 90-109 months. The 5-year DFS rates for HER2-negative patients, HER2-positive patients without adjuvant trastuzumab and trastuzumab-treated HER2-positive patients were 88.1% (95% confidence interval (CI) 85.6-90.6%), 73.1% (95% CI 64.3-81.9%) and 90.7% (95% CI 83.1-98.3%), respectively. No significant difference in DFS was observed between trastuzumab-treated HER2-positive patients and HER2-negative patients in multivariate analysis (hazard ratio 1.15; 95% CI 0.53-2.46; p = 0.728). There were no differences in OS among the 3 groups. CONCLUSION: Based on our results, the negative prognostic effect of HER2 positivity seen before targeted anti-HER2 treatment has completely disappeared in the era of routine trastuzumab administration in the adjuvant setting.

Treatment of vulvovaginal candidiasis: a review of the literature.

Vulvovaginal candidiasis (VVC) affects around three-quarters of all women during their reproductive age, although the exact incidence of VVC is difficult to determine because many patients are self-treated. The infections are divided into complicated and uncomplicated. Uncomplicated VVC is most effectively treated with local azoles. Oral treatment with a single dose of fluconazole is also effective for treating uncomplicated VVC. Treatment of complicated VVC is prolonged and most commonly consists of multiple doses of oral fluconazole or at least 1 week of local azoles. The role of probiotics in treating VVC is still disputed. This article presents a review of the literature on the various treatment options for VVC. Treatment for the most common pathogens that cause complicated VVC is also discussed.

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.

The role of intraoperative ultrasound in breast-conserving surgery of nonpalpable breast cancer.

OBJECTIVE: This retrospective study was undertaken to evaluate the role of intraoperative ultrasound in breast-conserving surgery of nonpalpable breast cancer. METHODS: The data about 125 patients with preoperatively diagnosed breast cancer operated with the help of intraoperative ultrasound between January 2009 and December 2012 were retrospectively analyzed. RESULTS: The mean volume of the excised tissue was 42.1 cm(3) (± 22.0 cm(3)). Immediate re-excision after ultrasound examination of the excised tissue was performed in 27 patients (21.6 %). Secondary procedure owing to positive histological margins was necessary only in four patients (3.2 %). CONCLUSIONS: Intraoperative ultrasound offers some advantages in comparison with other localization techniques for nonpalpable breast cancer surgery.