Ultrasound finding of endometrial polyp and factors increasing risk of malignancy.

This article presents a comprehensive review of factors that increase the risk of malignancy in ultrasound findings of an endometrial polyp. We collected original studies, reviews, and meta-analyses that dealt with the topic of endometrial polyps and the risk of developing endometrial cancer. Each presumed risk factor was analysed individually. According to searched studies, abnormal uterine bleeding, old age, and body mass index are valid risk factors for developing endometrial cancer in endometrial polyps. Lynch syndrome patients are also in a high-risk group for endometrial cancer. On the other hand, the number of polyps, their size, diabetes mellitus, hypertension, and positive family history are factors with inconclusive results. There are either not enough data or different results among several studies.

Molecular testing of endometrial carcinoma in real-world clinical practice.

BACKGROUND: Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. MATERIALS AND METHODS: In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. RESULTS: A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8-36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. CONCLUSION: Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.

The amount of preoperative endometrial tissue surface in relation to final endometrial cancer classification.

OBJECTIVE: To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. METHODS: A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1-2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). RESULTS: The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm2 and 23.5 mm2 (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). CONCLUSION: The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer.

OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Is the finding of endometrial hyperplasia or corporal polyp an mandatory indication for biopsy?

OBJECTIVE: The aim of our study was to analyze a group of patients referred for endometrial biopsy. To evaluate the ultrasound finding of hyperplasia/polyp, the symptomatology of patients related to the result of definitive histology, to determine the severity of individual variables in connection with the detection of precancerosis/cancer. Due to the complexity of information identify women who are suitable for conservative approach. DESIGN: Unicentric retrospective observational study. SETTING: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno. METHODS: All patients over 50 years who underwent surgical endometrial biopsy at our department in the period of 2017-2018 (n = 754) were included. We were interested in reasons of indication, the age of patients at the time of the procedure and at the menopause, the presence of risk factors for development precancerosis/cancer (hypertension, diabetes mellitus, using of tamoxifen), number of deliveries and pregnancies, symptomatology, the description of ultrasound scans, the result of histology examination, peroperative and postoperative complications. RESULTS: Perimenopause - the median of endometrial thickness in both benign and malignant histology was 8 mm (p = 0.448), the median of the largest polyp dimension was 18 mm. All patients with precancerosis/malignancy were symptomatic with irregular/excessive bleeding, no carcinoma was found in polyp. Postmenopause - the median of endometrial thickness in benign histology was 7 mm versus 16 mm in precancerosis/malignancy (p < 0.001), the median of the largest polyp dimension was the same in both histologies (13 mm, p = 0.274). The risk of malignancy was more than threefold in bleeding versus asymptomatic patients with both hyperplasia and polyp (OR 3.39, 3.79). In asymptomatic patients the risk of cancer was similar for selected cut-offs (5, 8 and 12 mm), statistically significant only for 12 mm (OR 3.54), while in symptomatic patients the risk was high for all cut-offs, however with wide confidence intervals, statistically significant for cut-offs of 8 mm (minimum 3.58) and 12 mm (minimum 4.94). CONCLUSION: We have shown that symptomatology is a strong risk factor for the presence of precancerosis/malignancy in patients with endometrial hyperplasia or polyp. The thickness of the endometrium or polyp size in asymptomatic patients does not play a major role. Ultrasound alone does not have sufficient accuracy for detection or even screening of endometrial cancer. We recommend a conservative procedure, monitoring changes in the ultrasound scan and symptomatology of the patient over time.

Total laparoscopic hysterectomy - clinical comparison of the method using two types of uterine manipulators.

AIM OF THE STUDY: Comparison of two types of uterine manipulators used in total laparoscopic hysterectomy (TLH) and clinical evaluation of the method in patients in a two-year group supplemented by subjective evaluation. DESIGN: Prospective observational study. SETTING: Department of Gynecology and Obstetrics, Masaryk University, Faculty of Medicine and University Hospital Brno. MATERIAL AND METHODS: A group of patients operated in the years 2018-2019 by the TLH method using one of two types of uterine manipulators - Karl Storz HOHL (group No. 1) vs. plastic ring of Koh's manipulator (group No. 2). We compared surgical time (min), blood loss (ml), perioperative complications, length of hospital stay (days), early and late complications. We were interested in the possible influence of BMI, uterine on these parameters. Subjective evaluation of the method by patients took place before the procedure and 12 weeks after the operation with a standardized questionnaire. RESULTS: A total of 134 patients were enrolled in the study (75 in group 1 vs. 59 in group 2). The monitored parameters: age, BMI, operative time, blood loss and length of hospitalization did not differ statistically significantly. When comparing the individual groups with different manipulators, the total number of complications (mild difficulties, serious complications) was without statistical significance (p = 0.58), but the spectrum of symptoms was different in both groups. More than a third of the patients in the group were obese. There were more serious complications than non-obese ones, the performance was longer, however, for a small number it was statistically insignificant (p = 0.11). In patients with uterine surgery, we recorded more adhesiolysis. We did not show that previous surgery on the uterus was associated with a higher incidence of complications (p = 0.6). We did not notice any statistically significant difference in the subjective evaluation (p = 0.3). CONCLUSION: TLH is the dominant method of uterine removal in our workplace. In a group of 134 women, we did not show a statistically significant difference in the monitored parameters. The HOHL manipulator has proved to be more user-friendly due to its technical parameters and better clarity of the operating field. Subjective evaluation of the method was positive in patients.

The role of hormonal therapy in patients with uterine carcinoma.

OBJECTIVE: The aim of the study was to describe the role of hormonal therapy in the treatment of malignant uterine tumors, indications, the effect of the treatment and to verify its safety in our study cohort. We also present an overview of recent studies on that topic. DESIGN: Unicentric retrospective observational study and review of recent literature. SETTING: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno. METHODS: The results of recent relevant studies and reviews published in English until December 2017 were used for the review. The publications were searched using the PubMed server. All patients diagnosed in our oncogynecological center between 2010 and 2016 and who were treated hormonally - either in primary therapy or in relapse settings, were included in our study. We were interested in age, BMI, stage of disease, histological type and grade of tumor, occurrence of adverse effects, duration of survival, reasons for choosing hormonal therapy. Medroxyprogesterone-acetate or megestrol-acetate was used in the treatment. RESULTS: Between 2010 and 2016, 415 malignant tumors of the uterus were diagnosed in our oncology center. Recurrence of the disease occurred in 31 patients (8%), on average 16 months after primary treatment. Primary hormonal therapy was used in only 19 patients (5%), mostly because of contraindications of another treatment due to high age, comorbidities or obesity. Median age of patients was 83 years, mean BMI 41, median survival of patients who died was 8 months. Five patients (16%) were treated hormonally for the recurrence. Median survival from diagnosis of recurrence was 20 months. One patient (4%) experienced partial pulmonary embolism. CONCLUSION: Hormonal therapy plays an irreplaceable role in uterine cancer patients, especially in primary non-operable patients, in treatment of a relapse, or in a fertility-sparing procedure. This treatment option is safe, with minimal adverse effects.

Innovation and the growth of human population.

Biodiversity is sustained by and is essential to the services that ecosystems provide. Different species would use these services in different ways, or adaptive strategies, which are sustained in time by continuous innovations. Using this framework, we postulate a model for a biological species (Homo sapiens) in a finite world where innovations, aimed at increasing the flux of ecosystem services (a measure of habitat quality), increase with population size, and have positive effects on the generation of new innovations (positive feedback) as well as costs in terms of negatively affecting the provision of ecosystem services. We applied this model to human populations, where technological innovations are driven by cumulative cultural evolution. Our model shows that depending on the net impact of a technology on the provision of ecosystem services (θ), and the strength of technological feedback (ξ), different regimes can result. Among them, the human population can fill the entire planet while maximizing their well-being, but not exhaust ecosystem services. However, this outcome requires positive or green technologies that increase the provision of ecosystem services with few negative externalities or environmental costs, and that have a strong positive feedback in generating new technologies of the same kind. If the feedback is small, then the technological stock can collapse together with the human population. Scenarios where technological innovations generate net negative impacts may be associated with a limited technological stock as well as a limited human population at equilibrium and the potential for collapse. The only way to fill the planet with humans under this scenario of negative technologies is by reducing the technological stock to a minimum. Otherwise, the only feasible equilibrium is associated with population collapse. Our model points out that technological innovations per se may not help humans to grow and dominate the planet. Instead, different possibilities unfold for our future depending on their impact on the environment and on further innovation.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.

[Fertility preserving methods in women with breast cancer before gonadotoxic therapy]. / Zachování fertility u zen s karcinomem prsu pred gonadotoxickou lécbou.

OBJECTIVE: To present current options and own experiences with ovarian stimulation in young women with breast cancer before gonadotoxic therapy. DESIGN: Review article with own experiencies. METHODS: Literary search, analysis of own experiences with complex therapy in women with breast cancer planning pregnancy, definitions of stimulating protocols, using methods of assisted reproduction. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno. RESULTS: Embryo and oocyte cryopreservation are important methods of fertility preservation requiring controlled ovarian stimulation before the start of chemotherapy. Current studies demonstrante effectivenes of this special stimulating protocol and did not find negative side effects such a progression of the breast cancer. Since January 2016 to June 2016 we performed controlled ovarian stimulation and oocyte retrieval in three patients with breast cancer before chemotherapy. We used short stimulation protocol with recombinant FSH, GnRH agonists and letrozole and retrieved 13, 12 and 9 oocytes. We cryopreserved 8 and 6 embryos, one woman prefered freezing of 12 oocytes. During the stimulation estradiol level did not exceed 1,6 nmol/l. CONCLUSION: Neither the normal nor the cancerous cells in the breast react to the gonadotropins FSH, LH, nor to hCG. Conversely, there is a cellular proliferation and an increase in cancer cell lines with oestrogen receptors with exposure to oestrogen, and it is dose - dependent. The special stimulation protocol with FSH, GnRH agonists and letrozole is effective in gain of efficient amount of gamets with minimal increase of estradiole level. Current study reviews did not find higher risk of progression of breast cancer in association with ovarian stimulation. It is important to respect the recomendation of oncology committee and to effectively suppress the estradiol level.

[Postoperative administration of octreotide to reduce lymphorrhea, lymphocele, lymphedema and lymphatic ascites after lymphadenectomy in gynecological malignancies]. / Vliv pooperacního podání oktreotidu na redukci lymforey a následne vzniku lymfocyst, lymfedému a lymfatického ascitu po lymfadenektomii u gynekologických malignit.

INTRODUCTION: Octreotide is a synthetic analogue of natural somatostatin. Octreotide effect on lymphorrhea reduction in gynecological malignancies has only been assessed in case studies. DESIGN: Original work. SETTING: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno. METHODS: In 2014 there was a prospective, randomized, one-institution study. Patients underwent surgery including pelvic or pelvic and paraaortic lymphadenectomy for cervical, uterine and ovarian cancer. The informed consent was signed. Octreotide was evaluated in relation to diagnosis, surgery (laparoscopy versus laparotomy), pelvic and/or paraaortic lymphadenectomy, number of removed lymph nodes and their positivity, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, albumin, BMI, number of days with drains postoperatively, number of days in hospital, blood loss during surgery, time of surgery, total number of drains placed into abdominal cavity. In follow up period, within 1 year after surgery, we searched for lymphocele, lymph-edema of lower extremities and lymphatic ascites in relation to lymphorrhea. RESULTS: 44 patients (9 cervical, 19 endometrial and 16 ovarian cancer) were enrolled in two statistically comparable randomized groups. "Octreotide group", which paradoxically showed lymphorrhea of 4082 ml on average, (without 1992 ml, p = 0.001), needed drainage for more days (p = 0.001). The diagnosis had no influence on lymphorrhea in both groups (p = 0.966). The neoadjuvant chemotherapy was administered (p = 0.026), the more lymph nodes were removed (p = 0.018), the more days the drainage was in place (p < 0.001), the bigger the lymphorrhea; no relationship between lymphorrhea and age (p = 0.631), albumin level (p = 0.584), BMI ( p= 0.966) or number of positive nodes (p = 0.259), length of surgery (p = 0.206), blood loss (p = 0.494). Nor lymphedema (p = 0.404), nor lymphocele (p = 0.086), correlated with postoperative lymphorrhea. Lymphatic ascites was associated with lymphorrhea (p = 0.048). CONCLUSION: Octreotide did not reduce lymphorrhea and the incidence of lymphocele, lymphedema of lower extremities and lymphatic ascites within one year of follow-up period after surgery. According to our results, we do not recommend to administer the octreotide in oncogynecological patients after pelvic and/or paraaortic lymphadenectomy.

[Vascular anatomy and abnormalities of retroperitoneal pelvic and paraaortic area in relation to the radical oncogynecological surgery - individual experiences]. / Cévní anatomie aortopelvického retroperitonea a její abnormality v souvislosti s radikální onkogynekologickou operativou - vlastní zkusenosti.

OBJECTIVE: The overview of vascular anatomy and abnormalities of retroperitoneal pelvic and paraaortic area in relation to the radical oncogynecological surgery. DESIGN: Retrospective study. SETTING: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno. MATERIAL AND METHODS: The overview of visualized vascular anatomy of retroperitoneal pelvic, infrarenal suprapelvic and subhepatic area in relation to the radical oncogynecological surgery. Presentation of physiological vascular anatomy. Summary of the most common abnormalities and potential complications in terms of vascular injury. Basic management of these complications from the viewpoint of oncogynecologist. CONCLUSION: The perfect knowledge of vascular anatomy and its possible abnormalities has represented an absolute necessity for uncomplicated course and sufficient extent of radical surgery.

[Current FIGO staging classification for cancer of ovary, fallopian tube and peritoneum]. / Novinky ve FIGO stagingu karcinomu ovaria, tuby a peritonea.

INTRODUCTION: Pelvic high-grade serous carcinomas (HGSCs) include carcinoma of ovary, fallopian tube, and peritoneum. Five-year survival, irrespective of the stage, is between 35-40%. Most patients are diagnosed in advanced stages of the disease. The new revised and expanded dualistic model of ovarian carcinogenesis shows that type II tumors are composed for the most part of high-grade serous ovarian carcinoma, carcinosarcoma, undifferentiated carcinoma and can be further subdivided into morphologic and molecular subtypes. Many type II carcinomas develop from STIC predominantly in the distal portion of the fallopian tube and it is very likely the point of the origin of a significant subset of the pelvic high-grade serous carcinomas. OBJECTIVE: To provide an overview of major changes in our understanding of the origin of ovarian cancer, that led to the revision of FIGO (International Federation of Gynecology and Obstetrics) classification and its unification for the ovary, fallopian tube and peritoneum. We summarize the new classification, main changes compared to the former one and their clinical impact. METHODS: For this review, we have used the results of studies and review articles on the subject published in English up to October 2016. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords ("serous tubal intraepithelial carcinoma" or "high-grade serous ovarian carcinoma" or "FIGO ovarian cancer staging 2014"). We retrieved and assessed potentially relevant studies, and checked the reference lists of all papers of interest to identify additional relevant publications. CONCLUSION: The origin of most cases of pelvic HGSC (carcinoma of ovary, the fallopian tube, and peritoneum) is expected in the fallopian tube epithelium. The main changes in the revised FIGO classification for extrauterine pelvic serous carcinomas were subdivision of stages IC, III and IV and elimination of the stage IIC, based on new knowledge and prognostic data. A prerequisite for the proper treatment of patients is to perform adequate surgical and pathological staging, including determining the grade of carcinoma. These factors, coupled with appropriately performed operation with zero postoperative residuum (R0), are the most important prognostic factors for patients with carcinoma of the ovary, fallopian tube, and peritoneum.

Accuracy of ultrasound in prediction of rectosigmoid infiltration in epithelial ovarian cancer.

OBJECTIVE: To examine prospectively the accuracy of ultrasound in predicting rectosigmoid tumor infiltration in patients with epithelial ovarian cancer. METHODS: Patients referred for a suspicious pelvic mass between 2012 and 2014 were examined by ultrasound following the standard protocol for assessment of tumor infiltration. Of the 245 patients examined, 191 had proven ovarian cancer and underwent primary surgery and were included in the analysis. Patients with apparently benign or inoperable disease were excluded. Rectosigmoid infiltration was evaluated by histopathology or according to perioperative findings. Clinical, pathological and laboratory parameters were analyzed as factors potentially affecting the sensitivity and specificity of sonography. RESULTS: The sensitivity of ultrasound in detecting rectosigmoid infiltration in patients with ovarian cancer was 86.3%, with specificity of 95.8%, positive predictive value of 92.6%, negative predictive value of 91.9% and overall accuracy of 92.1%. CONCLUSION: Ultrasound is a highly accurate method for detecting rectosigmoid tumor infiltration in ovarian cancer patients, and thus, can be used for planning adequate management, including patient consultation, surgical team planning, suitable operating time and postoperative care. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Incidence of uterine sarcomas in West Bohemia, at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic.

OBJECTIVE AND SETTING: A retrospective review of women of the West Bohemian population was performed at the Department of Gynaecology and Obstetrics, University Hospital in Pilsen, Czech Republic from 1/2005 - 1/2017. METHODS: The following data was analysed: patients age, histological type, tumour size, FIGO stage, body mass index, previous irradiation, Tamoxifen usage, and other possible risk factors. A total number of 20 uterine sarcoma patients were detected in the period from 1/2005 to 1/2015, and these cases were followed until 1/2017. RESULTS: The histological types identified were: leiomyosarcoma in 12 cases, endometrial stromal sarcoma in 7 cases and one case of high-grade undifferentiated uterine sarcoma. This only patient diagnosed with high-grade undifferentiated uterine sarcoma showed distant metastases 12 months after the surgical treat-ment and died one month later. The whole group of uterine sarcoma patients regardless histological subtype reached two years in 50% of cases, with the median disease-free interval 18 months and the median follow up of 38 months. The diagnosis of sarcoma was already known in 25% of cases from dilatation and curettage histology. There were suspicious sonographic findings suggestive of sarcoma in 10% of cases. Multiparity was associated with 48.2% of endometrial stromal sarcoma cases. The leading clinical symptom was postmenopausal bleeding in 55% of patients. CONCLUSION: We confirmed uterine sarcomas to be rare malignancies, even in the Czech population with high uterine malignancy incidence. Uterine cold knife morcellation during the vaginal part of laparoscopically assisted vaginal hysterectomy didnt worsen the prognosis of our patients.

[Breast Cancer - Specifics of Gynecological Care and Counseling]. / Karcinom prsu - specifika gynekologické péce a poradenství.

BACKGROUND: This paper summarizes current knowledge about clinically important aspects of gynecological care in female breast cancer patients. Despite the overall positive acceptance of oral contraceptives and hormone replacement drugs, hormone therapy may raise fears of developing breast cancer. Specifics of gynecological care of fertile patients are discussed as these patients face ovarian failure when undergoing oncological treatment of breast cancer. Tamoxifen is used in adjuvant therapy of breast cancer, in metastatic breast cancer or as prophylaxis of breast cancer in high-risk patients. AIM: We aim to study the influence of hormonal treatment on breast cancer development in women with and without congenital predisposition. The main risk factors for developing breast cancer are family history, increased density of breast tissue, atypical hyperplasia of the breast and previous radiotherapy to the chest area. All these factors increase the relative risk of cancer more than four times. Contraceptives and hormone replacement therapy show generally less than two-fold or no increase at all (RR 0.96-1.6). We concentrate with safety of hormonal therapy in breast cancer patients after they finish breast cancer treatment in pre- and postmenopausal period. We discuss fertility-sparing methods for preservation of ovarian function due to oncological treatment. Those methods are cryopreservation of embryos, oocytes in metaphase II and ovarian tissue. Simultaneous administration of GnRH agonists may protect ovarian function before gonadotoxic chemotherapy. We describe in detail the effects of tamoxifen on gynecological organs in both pre- and postmenopausal women in relation to the potential risk of developing secondary malignancy. In premenopausal women, tamoxifen has no increased risk of cancer of the uterine body. In postmenopausal patients, the risk after five years of tamoxifen is increased 2-3 times. Transvaginal sonography is not the screening tool for detection of the pathology in the uterine cavity during tamoxifen therapy, and so we only recommend looking for symptoms. Hysteroscopy is the golden standard for the examination of the uterine cavity in symptomatic postmenopausal patients using tamoxifen. CONCLUSION: This paper summarizes the current knowledge in areas where oncological and gynecological cares for breast cancer patients mingle. It should lead to greater understanding and deepening cooperation between clinical oncologists and oncogynecologists for the benefit of our patients.Key words: adjuvant hormonal therapy - fertility preservation - GnRH analogs - contraceptives - endometrial hyperplasia - hormone replacement therapy - breast neoplasm - tamoxifenThis work was supported by the Czech Ministry of Health - RVO (FNBr, 65269705).The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 6. 6. 2016Accepted: 22. 7. 2016.

Supernatant versus exosomal urinary microRNAs. Two fractions with different outcomes in gynaecological cancers.

MicroRNAs (miRNAs) are key regulatory molecules implicated in fundamental cell processes. Recent investigations have been focused to investigate their diagnostic potential also in various body fluids. Plasma and serum are widely used for these purposes. Urinary miRNAs, as the easily available type of sample, have been explored particularly in urological diseases recently. However, we have shown previously that differential expression of urinary cell-free miRNAs may be observed also in gynaecological cancers, such as ovarian and endometrial cancers. In the present article, we focus on the differences in particular urine cell-free miRNA abundance among different samples including particularly ovarian and endometrial cancers and rare gynaecological diagnoses involved in the study. Using raw abundance miRNA expression data, we confirmed significant up-regulation of miR-92a in ovarian cancer, and significant down-regulation of miR-106b in endometrial cancers. As miR-21 appeared up-regulated in the endometrial cancer similarly as in the verification process, where also miR-106b resulted in significant down-regulation in ovarian cancer, these miRNAs may be good candidates for further evaluation as novel diagnostics. To find out why supernatant but not exosomal urine miRNAs fraction resulted in significant results in regards to de-regulation of expression, we performed a comparison of the same urine samples isolated by these two manners. We show that diagnostic potential of cell-free urinary miRNAs may depend on the urine fraction used for the isolation. While particular urinary miRNAs may be enriched, other may reveal unchanged or diminished expression in the exosomal fraction in comparison with supernatant fraction, giving differences also between cancer and control samples. More research will be needed to further explore which kind of cell-free samples would give better results for diagnostic purposes in various diagnoses using urinary samples and investigating cell-free miRNAs expression. Meanwhile, different urine fractions should be explored for their miRNA expression to establish novel diagnostic urinary miRNA markers.

[Radical fertility preserving surgery of gynaecological malignancies - five-year-old file]. / Radikální fertilitu zachovávající operacní výkony u gynekologických malignit - petiletý soubor.

OBJECTIVE: Analysis of radical fertility preserving surgery, oncogynaecological treatment including their pregnancy effort. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynaecology, Masaryk University and Faculty Hospital Brno. METHODS: The group of 13 patients in age fifteen to thirty-six, who underwent radical fertility preserving surgery of oncogynecological tumors (cervix, ovarium), 9 patients with ovarian cancer and 4 patients with carcinoma of cervix. RESULTS: Histology showed seven times ovarial epithelial carcinoma, twice nonepithelial ovarial carcinoma, twice spinocelular cervical carcinoma, one adenosquamous and one lymfoepithelioma like carcinoma. We reported lymphocele as the most often postoperative complication by five patients with ovarial carcinoma, lymphoedema of lower limbs in one case and one of them complicated by bilateral hydronephrosis. After surgery procedures of cervical carcinoma, there was a stenosis of cervical canal with postoperative correction. In one case there was provided vaginal revision of cervix followed by embolisation of uterine arteries because of heavy bleeding in early postoperative period. After two years follow up, there are 12 patients in remission. There were four patients with fertlity plan, two with ovarial carcinoma, two with cervical carcinoma. The first group describes two pregnancies - one misscariage and one spontaneus labour in the date of delivery. There were 4 pregnancies in two patients wit cervical carcinoma. One patient has an intrapartal cesarean section because of scarring of the cervix after the operation. Next patients has two labours in due date, three labours in 34-37th week of pregnancy and one misscariage in 23 week of pregnancy. One patient has ovarial cancer during pregnancy, so the radical fertility preserving surgery was done after delivery. CONCLUSION: Methods and procedures of surgery with fertility preserving goals in our oncogynecological centre are in concordance with actual knowledge of medicine and respect oncological safety of patients with malignancies, who currently wish for fertility preserving treatment. Presented group of patients is relatively small, but results of oncological treatment and fertility plan demonstrate right-fulness of this treatment.

New perspectives in diagnosis of gynaecological cancers: Emerging role of circulating microRNAs as novel biomarkers.

Early diagnosis is a prerequisite of the more successful treatment of cancer. In gynaecological cancers, such as ovarian, endometrial and cervical cancers, the recent efforts are aimed at finding novel diagnostic biomarkers to help reduce the worldwide health burden associated with these cancers. In this review, we focus on the recent research progress in circulating, particularly cell-free microRNAs expression achieved in ovarian, endometrial and cervical cancers showing an opportunity to find novel diagnostic biomarkers for these malignant diseases. With the onset of microRNAs investigations showing their diagnostic potential in many diseases, their role in gynaecological cancers has been examined as well. However, similarly as in many other diseases, the vast majority of research on microRNAs expression has been dealing with tissue samples and cell lines. Recently, as the novel approaches focused on cell-free microRNAs expression have emerged, several studies identified their potential diagnostic and prognostic value in gynaecological cancers using blood, serum/plasma or urine samples. More research will be needed to establish circulating and extracellular microRNAs as the novel diagnostic markers for gynaecological malignancies. Inconsistency of results across the studies due to technical and biological variation, and a low number of this kind of investigations are the main potential pitfalls remaining to be resolved.

[Incidence and therapy of lymphoceles after pelvic and paraaortic lymph node dissection - our file]. / Incidence a terapie lymfocyst po provedené systematické pánevní a paraaortální lymfadenektomii - vlastní soubor.

OBJECTIVE: Analysis of lymphocele´s incidence and therapy among the patients, who underwent systematic pelvic and paraaortic lymphadenectomy during the years 2010-2012 in Oncogynecological centre of Department of Gynecology and Obstetrics in Brno. DESIGN: Retrospective study. SETTING: Department of Gynecology and Obstetrics, Masaryk University Hospital Brno. METHODS: We retrospectively evaluated the file of 111 patients, who underwent pelvic and/or paraaortic lymphadenectomy during the years 2010-2012 in our clinic. These patients were observed for the incidence of lymphoceles proved by ultrasonography. We focused on the incidence of symptomatic lymphoceles from all detected lymphoceles in the file of patients and we searched for relation between their presence and the type of systematic lymphadenectomy (pelvic or paraaortic) and the type of gynecological tumor and we report their management. RESULTS: During the years 2010-2012 we provided 111 lymphadenectomies consisting of: 78 pelvic and 33 pelvic and paraaortic lymphadenectomies in our clinic. These patients were rewied for retrospective study. We reported 37 cases of lymphoceles (33.3%) detected by vaginal or transabdominal ultrasonography. Among all patients with lymphoceles, we observed 24 asymptomatic patients and 13 patients with clinical features. There were 11.7% symptomatic lymphoceles from overall count. Only these symptomatic patients underwent therapy including simple punction or surgery management. Among all patients with lymphoceles, we reported the presence of lymfoceles by 19 patients with ovarian cancer (51.4%), 12 patients with cancer of cervix (32.4%), 4 patients with cancer of uterus (10.8%), one patient with cancer of salpinx and one patient with cancer of peritoneum (both 2.7%). We did not register statistically important dependence of lymphocele´s incidence on the type of lymphadenectomy (pelvic and/or paraaortic) - difference of 4.31%. CONCLUSION: Asymptomatic lymphoceles do not represent such a risk for patients after lymphadenectomy such as lymphoceles with clinical symptoms, which need to be followed by therapy. We proved incidence of lymphoceles 33.3%. There were 11.7% symptomatic lymphoceles among all patients after systematic lymph-adenectomy. In the future, it is necessary to standardize the condi-tions, used to indicate systematic lymphadenectomy to ensure safety of the oncological procedure and at the same time not to increase postoperative morbidity of patients. Going forward the topic of lymphocel´s prevention and detection of their valid risk and protective factors requires further prospective studies divided into single types of gynecological malignant tumors. KEYWORDS: pelvic and paraaortic lymphadenectomy, lymphoceles, incidence.