Side Effects from Cancer Therapies and Perspective of 1044 Long-Term Ovarian Cancer Survivors-Results of Expression VI-Carolin Meets HANNA-Holistic Analysis of Long-Term Survival with Ovarian Cancer: The International NOGGO, ENGOT, and GCIG Survey.

The aim of this survey was to increase the knowledge on the characteristics and health concerns of long-term survivors (LTS; survival > 5 years) after ovarian cancer in order to tailor follow-up care. This international survey was initiated by the NOGGO and was made available to members of ENGOT and GCIG. The survey is anonymous and consists of 68 questions regarding sociodemographic, medical (cancer) history, health concerns including distress, long-term side effects, and lifestyle. For this analysis, 1044 LTS from 14 countries were recruited. In total, 58% were diagnosed with FIGO stage III/IV ovarian cancer and 43.4% developed recurrent disease, while 26.0% were receiving cancer treatment at the time of filling in the survey. LTS who survived 5-10 years self-estimated their health status as being significantly worse than LTS who survived more than 10 years (p = 0.034), whereas distress also remained high 10 years after cancer diagnosis. Almost half of the cohort (46.1%) reported still having symptoms, which were mainly lymphedema (37.7%), fatigue (23.9%), pain (21.6%), polyneuropathy (16.9%), gastrointestinal problems (16.6%), and memory problems (15.5%). Almost all patients (94.2%) regularly received follow-up care. Specialized survivorship care with a focus on long-term side effects, lifestyle, and prevention should be offered beyond the typical five years of follow-up care.

Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

GC-MS analysis of the composition of serum IgG glycans as a potential diagnostic marker of advanced endometriosis - Preliminary report.

BACKGROUND: Endometriosis is an immune-mediated inflammatory disease that causes the growth of endometrial-like tissue outside the uterus. Diagnostics of this disease are difficult, often invasive, and time-consuming, therefore non-invasive diagnostic methods and parameters are very desirable in endometriosis detection. OBJECTIVES: The study aimed to check whether there are any differences in the monosaccharide composition of N-glycans in serum IgG of women with advanced endometriosis and women with mild gynecological diseases. MATERIALS AND METHODS: The study material consisted of IgG samples isolated from blood sera derived from patients diagnosed with advanced endometriosis and women without endometriosis but with other gynecological diseases. To determine the monosaccharide composition of N-glycans in IgG, the gas chromatography-mass spectrometry (GC-MS) method was used. RESULTS: It was observed a significantly higher content of GlcNAc in the group of women with mild gynecological diseases, compared to the group of patients with advanced endometriosis (6.5 ± 5.2 and 4.5 ± 5.7; p = 0.0007704, respectively). In addition, the content of fucose was significantly higher in the group of women with mild gynecological diseases compared to women with advanced endometriosis (1.9 ± 0.5 and 1.7 ± 1.2; p = 0.000274, respectively). CONCLUSIONS: The content of GlcNAc and fucose in serum IgG may be useful markers differentiating patients with advanced endometriosis from women without endometriosis but with mild gynecological diseases.

Fast and reliable Sanger POLE sequencing protocol in FFPE tissues of endometrial cancer.

BACKGROUND: The new classification of endometrial carcinoma (EC) requires molecular interpretation of somatic polymerase epsilon (POLE) exonuclease domain mutations. The identification of pathogenic mutations within the POLE gene defines the important subtype of ultramutated tumours ("POLE-ultramutated") with specified prognostic and predictive utility. POLE somatic mutations are present in 7-12% of ECs, usually high-grade tumours with aggressive appearance. Molecular analysis of the POLE gene can be performed using a qPCR test, the Sanger sequencing method, a next generation sequencing (NGS) panel test and also in situ hybridisation (IHC) assay. We describe our current approach of identification of POLE mutations using Sanger sequencing technology, which is still the most robust, accurate and fast technique to sequence DNA. MATERIALS AND METHODS: We present a reliable protocol for Sanger sequencing of the entire sequence coding exonuclease domain of POLE - exons 9, 10, 11, 12, 13 and 14 (codons 268-491) with 5-10 nucleotides in exon/intron boundaries (reference sequences: NM_006231.4, NP_006222.2). RESULT: The protocol has been optimized for formalin-fixed, paraffin-embedded (FFPE) EC tissues. CONCLUSION: The method developed in our laboratory allows better diagnosis of patients with EC according to current standards.

Translational molecular research has established a novel clinical approach in endometrial cancer patients.

Endometrial cancer (EC) is the most common gynecological tumor in developed countries. Nowadays, molecular biomarkers have become increasingly important in the management of EC patients, helping in early detection, risk stratification, prognosis and response to the treatment, and qualification for novel immunotherapies, especially in EC patients with metastatic disease or recurrence. When EC tumor molecular profiling is combined with the standard histopathological features such as clinical stage, histologic grading and evaluation of lymphovascular space invasion, the final therapeutic outcome may bring benefits in terms of personalized and efficient management.

Advanced ovarian cancer imitating deep infiltrating endometriosis. Radical resection and reconstructive surgery of the anterior abdominal wall.

Endometriosis is a disease affecting approximately 10-15% of the female population of reproductive age [1]. A rare location is endometriosis in the scar after caesarean section - CSE (caesarean scar endometriosis) accounting for 0.5-1.0 % of all cases. Although endometriosis is usually a benign condition, its malignant transformation affects 0.7-1% of cases. In women diagnosed with ovarian cancer, foci of endometriosis are present in up to 30% of patients. This paper presents the case of a 36-year-old patient initially diagnosed with extensive endometriosis involving the anterior abdominal wall and the pelvis minor. After biopsy, a diagnosis of advanced low-grade serous ovarian cancer was established. The diagnostic methods used and the extent of surgery with reconstruction of the anterior abdominal wall were described.

O-Glycosylation Changes in Serum Immunoglobulin G Are Associated with Inflammation Development in Advanced Endometriosis.

Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly related to inflammatory processes with an immune basis. Our study aimed to analyze the O-glycosylation of native serum IgG and IgG isolated from sera of women with advanced endometriosis, without endometriosis but with benign gynecological diseases, and from a control group of healthy women, in the context of its utility for differentiation of advanced endometriosis from the other two groups of women studied. For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. The relative reactivities of isolated serum IgG O-linked glycans with specific lectins as well as the MPL/VVL O-glycosylation ratio were significantly higher in patients with advanced endometriosis and those with other gynecological diseases when compared to the control group of healthy women. We also showed significantly higher expression of PHA-L-reactive multi-antennary N-glycans in isolated IgG in the advanced endometriosis and the non-endometriosis groups in comparison to the control group. Additionally, significantly higher expression of Jacalin-reactive O-glycans in isolated IgG was observed in the non-endometriosis than in the advanced endometriosis group. The results of the ROC curve and cluster analysis additionally confirmed that the lectin-based analysis of isolated serum IgG O-glycosylation and the expression of highly branched N-glycans may help distinguish women with advanced endometriosis from healthy women. Moreover, the analysis of the expression of Jacalin-reactive i-IgG O-glycans may be helpful in differentiation between women with advanced endometriosis and patients with other gynecological diseases with an inflammatory background. In the case of non-endometriosis patients, the observed differences were most probably caused by increased expression of core 3 type O-glycans.

ATR-IR Spectroscopy Application to Diagnostic Screening of Advanced Endometriosis.

Endometriosis is one of the most common gynecological diseases among young women of reproductive age. Thus far, it has not been possible to define a parameter that is sensitive and specific enough to be a recognized biomarker for diagnosing this disease. Nonspecific symptoms of endometriosis and delayed diagnosis are impulses for researching noninvasive methods of differentiating endometriosis from other gynecological disorders. We compared three groups of individuals in our research: women with endometriosis (E), patients suffering from other gynecological disorders (nonendometriosis, NE), and healthy women from the control group (C). Partial least squares discriminant analysis (PLS-DA) models were developed based on selected serum biochemical parameters, specific regions of the serum's infrared attenuated total reflectance (FTIR ATR) spectra, and combined data. Incorporating the spectral data into the models significantly improved differentiation among the three groups, with an overall accuracy of 87.5%, 97.3%, and 98.5%, respectively. This study shows that infrared spectroscopy and discriminant analysis can be used to differentiate serum samples among women with advanced endometriosis, women without this disease, i.e., healthy women, and, most importantly, also women with other benign gynecological disorders.

The Alterations of Serum IgG Fucosylation as a Potential Additional New Diagnostic Marker in Advanced Endometriosis.

BACKGROUND: Endometriosis is an inflammatory disease leading to the growth of endometrial-like tissue outside of the uterus, which affects approximately 10% of young women of reproductive potential. The diagnosis of this disease is difficult, often invasive and time-consuming, therefore non-invasive diagnostic methods are strongly desirable in endometriosis detection. The aim of our project was to investigate whether any associations exist between the expression of serum IgG fucosylation and advanced stages of endometriosis. We were also interested in whether native serum IgG (s-IgG) fucosylation analysis, without prior IgG isolation, could provide a panel of parameters helpful in non-invasive diagnostics of advanced endometriosis. METHODS: IgG fucosylation was examined using a lectin-ELISA test with fucose-specific lectins: AAL and LCA, specific for core fucose α1,6-linked, as well as LTA and UEA which recognize α1,3- and α1,2-linked fucose, respectively. RESULTS: ROC curve and cluster analysis showed s-IgG reactivities with the panel of fucose-specific lectins AAL, LCA and LTA. CONCLUSION: s-IgG reactivity with the panel of fucose-specific lectins AAL, LCA and LTA can be taken into account as a useful diagnostic and clinical tool to differentiate women with advanced endometriosis. Moreover, it has been shown that the analysis of native IgG fucosylation directly in serum, without prior time-consuming, expensive IgG isolation, is sufficient to distinguish advanced stages of endometriosis from a control group of healthy women.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Is There a Balance in Oxidative-Antioxidant Status in Blood Serum of Patients with Advanced Endometriosis?

Can redox homeostasis indicators be potential non-invasive markers, crucial in the diagnosis and treatment of endometriosis? We checked if the differences in levels of serum oxidative-antioxidant balance parameters (TAS, FRAP, albumin, total bilirubin, uric acid, iron, SIRT3, SIRT5, SIRT6, telomerase, AOPP) are significant between patients with advanced endometriosis (E), healthy women (control group, C) and non-endometriosis women, but with other gynecological disorders (NE). The FRAP concentrations were significantly higher in E and NE group than in the control group (p = 0.015 and p = 0.017, respectively). The telomerase concentrations were significantly higher in the endometriosis group than in the control group (p = 0.004). Significantly higher concentrations of AOPP were observed in E (p < 0.001) and NE groups (p = 0.028) in comparison to the control subjects. Between stages III and IV of endometriosis, a significant difference existed only in concentration of iron (p = 0.013). There were no significant differences between the studied groups in the values of the remaining parameters. Based on the results of ROC curve analysis, we can conclude that the levels of serum FRAP, telomerase and AOPP may be taken into account as promising diagnostics markers that reflect the degree of oxidative stress accompanying advanced endometriosis.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis.

Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly associated with inflammatory processes. Serum concentrations of IL-1ß, IL-6, hs-CRP, IgG, YKL 40 and PRL, in comparison to the well-known CA 125 levels, were studied with the aim of identifying an additional noninvasive inflammatory marker or set of markers characteristic for endometriosis. The study group included 43 women with endometriosis (E), 35 women with benign gynecological disorders but without endometriosis (NE, non-endometriosis) as a comparative group, and a control group consisting of 18 healthy subjects (C). The serum concentrations of IL-1ß, IL-6, hs-CRP, YKL-40, PRL and CA 125 were significantly higher in the E group (median values: 0.41 pg/mL, 2.42 pg/mL, 2.33 mg/L, 79.30 ng/mL, 21.88 ng/mL and 68.00 U/mL, respectively) than in the control group (median values: 0.21 pg/mL, 0.98 pg/mL, 0.52 mg/L, 49.77 ng/mL, 12.08 ng/mL and 12.20 U/mL respectively), with the significance of p = 0.011, p < 0.001, p = 0.028, p = 0.005, p < 0.001 and p < 0.001, respectively. The IgG concentrations were significantly lower in the endometriosis group (median value: 1061.21 mg/dL) as compared to healthy women (median value: 1210.50 mg/dL; p = 0.025). Significant differences in concentrations of IL-6 (p = 0.040), hs-CRP (p = 0.007) and CA 125 (p < 0.001) were observed in stage III vs. stage IV of endometriosis. Significantly higher concentrations of IL-6 (p = 0.010), hs-CRP (p = 0.037) and PRL (p < 0.001) were observed in the NE group vs. the control group. Only CA 125 concentrations were significantly higher in endometriosis patients as compared to the non-endometriosis group (p < 0.001). The proposed panel of inflammatory markers, especially IL-6, PRL and CA 125, may become a useful tool to identify women with advanced endometriosis who could qualify for treatment.

Variability of serum IgG sialylation and galactosylation degree in women with advanced endometriosis.

Endometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Superparamagnetic iron oxide: a novel tracer for sentinel lymph node detection in vulvar cancer.

OBJECTIVES: Superparamagnetic techniques for sentinel lymph node (SLNs) biopsy in breast cancer is well recognized but remains novel in the literature in relation to early stage vulvar cancer. The aim of this study was to compare and validate SLN detection using a superparamagnetic iron oxide tracer and a magnetometer probe compared with the standard procedure with a radioisotope (99Tc-technetium 99) and a gamma probe, in patients with vulvar cancer. METHODS: Patients were included in the study with squamous vulvar tumors less than 4 cm in diameter and without suspicious groin lymph nodes on preoperative magnetic resonance imaging. Patients must have previously qualified for SLN biopsy with a radiotracer as the standard of care. The primary endpoint was the proportion of successful SLN detection with superparamagnetic iron oxide tracer versus 99Tc. The secondary endpoints were average number of SLNs retrieved per patient, proportion of SLNs detected (nodal detection rate), and proportion of pathologically positive results (malignancy rate) per patient and per node comparing both SLN detection methods. RESULTS: A total of 20 patients were included in the study. SLNs were found in all patients with both methods, resulting in similar average distributions (3.1/3.2 SLN per patient). The SLN detection rate per patient was 100% with both techniques. Nodal detection sensitivity was 98.5% for the superparamagnetic technique and 93.8% for the radiotracer. Percentage of metastatic lymph nodes detected was 100% with both tracers. The rate of lymph node positivity was 21.5% (14 lymph nodes with metastases) and for patients 45% (9 patients with nodal metastases). Additionally, SLN tainted brown due to superparamagnetic iron oxide nanoparticles in 19 of 20 patients. CONCLUSIONS: The use of superparamagnetic iron oxide tracer in patients with vulvar cancer seems reliable and not inferior to the standard approach with radiotracer.

Proteogenomic Characterization of Endometrial Carcinoma.

We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/ß-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.

Circulating Endometrial Cells: A New Source of Information on Endometriosis Dynamics.

The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis. The molecular characteristics of CECs could be supportive for an understanding of endometriosis pathogenesis and treatment decisions in the future. MATERIAL AND METHODS: Blood samples (n = 423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, CECs presence and characteristics were tested during menstrual cycle (MC) phases in 11 patients. CECs were enriched by size-based separation. RESULTS: CECs were present in 78.4% of the tested blood samples. In line with the revised American Fertility Society (rAFS) classification, CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate, and severe. Surprisingly, CECs negativity rate was also reported for severe disease in 21.1% of cases. The CECs captured during MC phases displayed different cytomorphology, including epithelial, stromal, and stem cell-like characteristics. The highest CECs numbers were detected in the mid-secretory phase of MC, which corresponds to uterine lining decidualization. CECs captured during mid-secretory periods expressed genes KRT18, NANOG, and VIM in higher amounts when compared to the proliferative phase of MC, where genes KRT19 and ESR1 were mostly elevated. GEA of the super-positive CECs samples (1000 CECs/8 mL PB) revealed high expression of genes KRT18, VIM, NANOG, and FLT1. The expression of these genes was also elevated in the endometriosis tissue samples and endometrioma. CONCLUSION: The panel of the identified CEC genes could be tested in a prospective manner to confirm the role of CECs in endometriosis pathogenesis and diagnostics.

Hysterectomy in Poland between 2011 and 2016. Changing trends in the surgical approach to hysterectomy.

OBJECTIVES: In Poland, approximately 35,000 women a year undergo hysterectomy. The surgical approach may vary depending on the indications and experience of the operator and advances in laparoscopic surgical techniques. The aim of the present study was to analyze trends in the use of various types of hysterectomy in Poland between 2011 and 2016. Summary values were given as numbers and percentages. Annual incidence of procedures and identify factors which influence these changes in gynecological practice. MATERIAL AND METHODS: Data on hysterectomy procedures performed between 2011 and 2016 in Poland acquired from the National Health Fund reports were extracted and analyzed. Summary values were given as numbers, percentages and rate ratios (RR). Annual incidence of procedures and identify factors that influence these changes in gynecological practice. RESULTS: Between 2011 and 2016, 215,744 women were treated by hysterectomy in inpatient settings. The total number of those procedures in analyzed period decreased by 11.5%; the incidence rate dropped by 2.15 per 100,000 women. A significant increase in laparoscopic procedures was observed (RR = 3.85; CI: 3.57-4.16; p < 0.001) along with a decrease in the number of abdominal operations (RR = 0.82; CI: 0.81-0.83; p < 0.001). CONCLUSIONS: Surgical technique advances, introduction of intrauterine systems and hormonal therapy, as well as recommendations of international institutions have brought about changes in the methods and frequency of hysterectomy. The laparoscopic approach has been gaining popularity since it is beneficial both for patients and public health system. However, the percentage of advanced minimally invasive hysterectomies is still low in Poland in comparison to other countries.

Correlation Between Disease Stage and the Presence of Viable Circulating Tumor Cells in Endometrial Cancer.

BACKGROUND/AIM: The presence of circulating tumor cells (CTCs) in the peripheral blood of patients with solid tumors is associated with a poor prognosis. However, there are limited data concerning the detection of CTCs in endometrial cancer (EC). The aim of this study was to evaluate the presence of CTCs in the peripheral blood of patients with EC. MATERIALS AND METHODS: Peripheral blood samples from 92 patients who underwent a surgical procedure were evaluated using MetaCell® separation technology for CTCs. RESULTS: CTCs were detected in 69 (75%) patients with EC. CONCLUSION: CTCs were detected in a higher percentage of patients than in other studies. The results showed that the technology applied in this study can efficiently capture viable tumor cells in the blood that can be cultured while maintaining their original phenotype. This paper discusses the first successful culturing of human circulating endometrial cancer cells for further downstream functional and molecular characterization.