Human Endogenous Retroviruses in Breast Cancer: Altered Expression Pattern Implicates Divergent Roles in Carcinogenesis.

INTRODUCTION: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. METHODS: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. RESULTS: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e. , AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. CONCLUSION: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis.

The Overexpressed MicroRNAs miRs-182, 155, 493, 454, and U6 snRNA and Underexpressed let-7c, miR-328, and miR-451a as Potential Biomarkers in Invasive Breast Cancer and Their Clinicopathological Significance.

INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-µm intervals/levels). SLNs from each site were submitted for central quality control. RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). CONCLUSION: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging. STUDY REGISTRATION: NCT02494063 (ClinicalTrials.gov).

Reproductive outcomes after fertility-sparing surgery for cervical cancer - results of the multicenter FERTISS study.

INTRODUCTION: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity. METHODOLOGY: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode. RESULTS: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001. CONCLUSION: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST.

Surgical treatment of recurrent gynecological malignancies.

OBJECTIVE: A comprehensive overview of surgical treatment of recurrent gynecological malignancies. Recurrent breast malignancies are not included in this review. METHODOLOGY: A review providing overview of surgical treatment options for recurrent malignancies of adnexa of the uterus (ovary, fallopian tube), uterine corpus, uterine cervix, and carcinoma of the vagina and vulva. CONCLUSION: Optimal surgical treatment for patients with recurrent cancer is based on multidisciplinary approach with stratification according to individual prognostic markers. These include patient's performance status, outcome of primary surgery, current extent of recurrence, and histopathological, molecular, and biochemical characteristics. Decision about choice of treatment should be individually discussed and evaluated by the multidisciplinary oncogynecological commission board.

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.

Therapeutical strategies for recurrent endometrial cancer.

OBJECTIVE: A comprehensive overview of therapeutical strategies for recurrent endometrial cancer with illustrative case report. METHODOLOGY: A review providing basic overview of therapeutical options for different forms of recurrent endometrial cancer including surgical treatment, systemic treatment and radiotherapy. It includes a case report presenting a treatment of patient with an endometrial cancer recurrence in the abdominal wall. CONCLUSION: Therapeutical strategies in patients with endometrial cancer recurrence include surgical treatment, radiotherapy and systemic treatment depending on previous therapy, type and site of recurrence or dissemination, performance status and wishes of the patient. Decision about choice of treatment should be individually discussed and evaluated by multidisciplinary oncogynecological commission board.

Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers.

BACKGROUND: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). METHODS AND RESULTS: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. CONCLUSIONS: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.

Vulvar carcinoma and its recurrences - principles of surgical treatment.

OBJECTIVE: A comprehensive overview of the surgical treatment of vulvar cancer, including recurrent forms. METHODOLOGY: A review work providing a basic overview of the pathogenesis, dia-gnosis and surgical treatment of vulvar cancer with a focus on the possibilities of treatment of its recurrences. It includes an illustrative case report presenting a patient with invasive squamous cell carcinoma of the vulva with iterative local recurrences and subsequent development of tumor triplicity and distant metastatic involvement. CONCLUSION: Surgical treatment remains the main modality of vulvar cancer therapy, even in the case of locally advanced or recurrent findings. In these cases, multidisciplinary cooperation of operational fields is necessary. The discipline of treated patients with participation in regular dispensary care plays an important role in the early detection of recurrences. (Chemo) radiotherapy remains a possible alternative to the surgical solution; in clinical practice, radiotherapy has an irreplaceable place in adjuvant therapy. Regional and distant recurrences are characterized by a poor  prognosis.

Change in the trend of surgical treatment and staging of lymph nodes in endometrial cancer - results of the Oncogynecology Center, Department of Gynecology and Obstetrics, University Hospital Brno and Masaryk University in the years 2012-2021.

INTRODUCTION: In the last decade, the view of endometrial cancer has shifted enormously, and the surgical approach or lymph node staging has changed significantly. We are presenting these changes with the University Hospital Brno Oncogynecology centers results in the years 2012-2021 in the actual national and European guidelines context. METHODS: The retrospective unicentric observational study, national and European guidelines review. RESULTS: In the observation period, 715 endometrial cancer patients were treated in our clinic, and 636 of them underwent surgical treatment (89%). Concerning lymph node staging, firstly, there is a clear trend of expanding lymphadenectomy to the paraaortic area, followed by the sentinel node bio-psy introduction in the years 2018-2019, and finally, the complete transition to this method as the main staging procedure in 2021, when this examination was performed in 73% of surgeries, even with high-risk cancers limited to the uterus. Within the sentinel node bio-psy expansion, a gradual decrease in laparotomy approach (maximum 41% in 2016, 18% in 2021), and blood loss (2012-2019 median 100 mL, with a decrease to 50 mL in 2020-2021) was evident. A hospitalization length stabilized at a median of 5-6 days. CONCLUSIONS: Surgical treatment of endometrial cancer has become a minimally invasive procedure for the majority of patients, the average blood loss and hospitalization length have decreased. Sentinel node bio-psy has become the preferred lymph node staging method.

Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.

OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Breast reconstruction in patients with BRCA mutation and breast cancer - our approach.

OBJECTIVE: Analysis of our approach to breast reconstruction after mastectomy in women with breast cancer and/or BRCA mutations. Oncoplastic surgery enables procedures that are sufficiently radical and with a very good cosmetic effect. With the development of genetic testing programs, the need for prophylactic procedures is also increasing. One-sided curative performance and at the same time prophylactic surgery on the other breast can be used. METHODS: We use the possibility of immediate breast reconstruction simultaneously with subcutaneous and skin-saving mastectomy. We solve the reconstruction either with an expander and in the second time by inserting a silicone implant, or directly by inserting the implant alone or in combination with the use of autologous tissue, depending on further oncological treatment (chemotherapy or radiotherapy). RESULTS: One-hundred and three reconstructive surgeries were performed on 58 women with breast cancer and/or BRCA mutations from April 2017 to May 2020. Of these, there were 52 immediate reconstructions for untreated tumors. A tissue expander was inserted in 27 women (46.6% of the group) with locally advanced tumors and the need for subsequent radiotherapy (18 immediate and 9 delayed reconstructions). Breast implants were used in 52 women (89.7% of the group) in a total of 80 implants. Breast reconstruction of own tissues was performed in 8 women, of which 5 operations had immediate reconstruction. Postoperative complications occurred in 11 women and 15 corrective procedures were performed (12.7% of operations). CONCLUSION: Breast reconstruction is a comprehensive set of techniques by which any patient can obtain a breast so that it does not depend on the epithelium. Patients with locally advanced disease who receive neoadjuvant chemotherapy and radiotherapy are at greater risk of complications. With the growing number of breast cancers, the demand for reconstructive procedures, especially immediate reconstructions, is increasing.

Poor outcome in hypoxic endometrial carcinoma is related to vascular density.

BACKGROUND: Identification of endometrial carcinoma (EC) patients at high risk of recurrence is lacking. In this study, the prognostic role of hypoxia and angiogenesis was investigated in EC patients. METHODS: Tumour slides from EC patients were stained by immunofluorescence for carbonic anhydrase IX (CAIX) as hypoxic marker and CD34 for assessment of microvessel density (MVD). CAIX expression was determined in epithelial tumour cells, with a cut-off of 1%. MVD was assessed according to the Weidner method. Correlations with disease-specific survival (DSS), disease-free survival (DFS) and distant disease-free survival (DDFS) were calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: Sixty-three (16.4%) of 385 ECs showed positive CAIX expression with high vascular density. These ECs had a reduced DSS compared to tumours with either hypoxia or high vascular density (log-rank p = 0.002). Multivariable analysis showed that hypoxic tumours with high vascular density had a reduced DSS (hazard ratio [HR] 3.71, p = 0.002), DDFS (HR 2.68, p = 0.009) and a trend for reduced DFS (HR 1.87, p = 0.054). CONCLUSIONS: This study has shown that adverse outcome in hypoxic ECs is seen in the presence of high vascular density, suggesting an important role of angiogenesis in the metastatic process of hypoxic EC. Differential adjuvant treatment might be indicated for these patients.

Ovarian Cancer: Differentially Expressed microRNAs in Tumor Tissue and Cell-Free Ascitic Fluid as Potential Novel Biomarkers.

Ovarian cancer is the deadliest gynecologic cancer. The large-scale microRNA (miRNA) expression profiling and individual miRNA validation was performed to find potential novel biomarkers for ovarian cancer. The most consistent overexpression of miRs-200b-3p, 135 b-5p and 182-5p was found in both ascitic fluid and tumors and suggests their potential as oncogenes. miR-451a was consistently underexpressed so may be a tumor suppressor. Results were inconsistent for miR-204-5p, which was overexpressed in ascitic fluid but underexpressed in tumor tissue. miR-203a-3p was generally overexpressed but this failed to be proved in independent sample set in tissue validation.

Added Value of Estrogen Receptor, Progesterone Receptor, and L1 Cell Adhesion Molecule Expression to Histology-Based Endometrial Carcinoma Recurrence Prediction Models: An ENITEC Collaboration Study.

OBJECTIVES: Endometrial carcinoma mortality is mainly caused by recurrent disease, and various immunohistochemical markers to predict recurrences have been studied. Loss of the estrogen receptor (ER) and progesterone receptor (PR) and the presence of the L1 cell adhesion molecule (L1CAM) are promising markers, but their combined value has not been studied. MATERIALS AND METHODS: Expression of ER, PR, and L1CAM was immunohistochemically determined in 293 endometrial carcinomas from 11 collaborating European Network for Individualized Treatment of Endometrial Cancer centers. Estrogen receptor, PR, or L1CAM staining was considered positive or negative when expressed by greater than or equal to 10% or less than 10% of the tumor cells, respectively. The association between these markers and clinicopathological markers, and their combined value in predicting survival were calculated, both in the entire cohort and in a selected groups of stage I endometrioid and low-risk stage I endometrioid carcinomas. RESULTS: Estrogen receptor and PR were negative in 19% and 28% of the cases, respectively, and L1CAM was positive in 18%. All 3 were associated with advanced stage, high-grade, nonendometrioid histology, lymphovascular space invasion (LVSI), and reduced disease-free survival. Only advanced stage, loss of PR, and LVSI were associated with reduced disease-free survival in multivariate analysis. A prognostic model including these 3 markers was superior to 1 including only the 3 immunohistochemical markers, which was superior to the traditional model. In both the stage I endometrioid and the low-risk stage I endometrioid groups, only loss of PR was associated with reduced disease-free survival. CONCLUSIONS: Loss of ER and PR, and the presence of L1CAM are associated with high risk characteristics, and loss of PR is the strongest predictor of recurrent disease. Although a combination of these 3 markers is slightly superior to the traditional histological markers, a prognostic model including stage, PR expression, and LVSI is the most promising model in the identification of high risk carcinomas. In the stage I endometrioid carcinomas, PR immunohistochemistry appears to be of additional value in predicting recurrences.

Vulvar cancer recurrence - an analysis of prognostic factors in tumour-free pathological margins patients group.

OBJECTIVES: To evaluate risk factors associated with the local recurrence of invasive squamous cell vulvar cancer in patient group with tumor-free pathological margins. MATERIAL AND METHODS: This is a retrospective analysis of 47 patients who underwent surgical treatment at University Hospital Brno, the Czech Republic between 2007 and 2014. 24 patients were classified as IB stage and three as II stage. A further 20 patients representing stage III showed the metastatic involvement of regional lymph nodes. Seven prognostic factors were analyzed in relation to local tumour recurrence: tumour size, margin distance, depth of invasion, lymphovascular space involvement (LVSI), midline involvement, metastatic lymph nodes and FIGO stage. RESULTS: All prognostic factors were found to be statistically significant with respect to the risk of local recurrence. The highest risk of local recurrence was observed for the depth of invasion > 5 mm (HR, 12.42 [95% CI; 3.44-44.84]) and for the presence of LVSI (HR, 10.83 [95% CI; 3.87-30.28]). The study also established a clear difference in the risk of local recurrence between patient groups with resection margin < 8 vs. ≥ 8 mm (HR, 4.91 [95% CI; 1.73-13.93; p = 0.003]. CONCLUSIONS: Tumour-free pathological margin of ≥ 8 mm is a major prognostic factor of local recurrence which can be influenced by the surgeon. A perfect knowledge of the extent of the disease prior to surgery supports adequately radical surgical trends. The emphasis is given on adequate radicality as well as on the reduction of overtreatment without worse-ning prognosis by simultaneously preserving the quality of life.

Brenner tumor of the ovary - ultrasound features and clinical management of a rare ovarian tumor mimicking ovarian cancer.

OBJECTIVES: To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures. MATERIAL AND METHODS: We retrospectively identified patients with histologically confirmed benign Brenner tumor of the ovary who were treated in our institution in 2003-2016, and for whom complete imaging, clinical, perioperative and histopathological data were available in the database. Ultrasound findings were drawn from images and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied. RESULTS: Twenty-three patients were identified, most postmenopausal and asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23 bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner tumors (16/23) contained solid components and revealed no or minimal blood flow by subjective color score upon Doppler examination (19/23, 83%). Calcifications with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors containing solid components. The complex appearance of the tumor misled the sonographers to describe the mass as malignant in 9 cases (39%), and frozen section was performed perioperatively. Surgery was performed via laparoscopy in 11 (48%) and via laparotomy in 12 (52%) cases. CONCLUSIONS: The complexity of the ultrasound picture, consisting of features like calcifications with acoustic shadowing, a poorly vascularized solid mass, and a left-sided localization could be signs of a benign Brenner tumor and could preop-eratively help to differentiate between benign and malignant tumor.

Modified posterior pelvic exenteration for advanced ovarian malignancies: a single-institution study of 35 cases.

INTRODUCTION: This study aimed to investigate the possible benefits of a complete cytoreduction in patients with advanced ovarian cancer and concomitant rectal invasion. Furthermore, we evaluated the morbidity associated with radical surgery. MATERIAL AND METHODS: A retrospective analysis examined 35 women who underwent radical surgery in the form of modified posterior pelvic exenteration. Descriptive statistics, Kaplan-Meier survival curves and log-rank test were used for statistical estimations. Surgical complications were analyzed using the Clavien-Dindo classification. RESULTS: The analysis of survival in relation to residual disease assessed according to Sugarbaker confirmed an optimistic prognosis in patients with optimal debulking with a mean disease-free survival period of 33.6 months in R0 patients, 19.6 months in R1 patients, and 14.3 months in R2 patients. A statistically significant difference in disease-free survival (p = 0.023) was observed between the R0 (without residual disease) and R1+2 (with residual disease) groups. Surgical complications occurred in 83% of patients, with early postoperative complications being most frequent (65.7%). While grade III-IV complications occurred in 37.7% of all patients, no cases of surgery-associated mortality occurred. CONCLUSIONS: Modified posterior pelvic exenteration is a highly effective method for achieving optimal debulking in cases of advanced ovarian cancer with the direct invasion of the rectum. Modified posterior pelvic exenteration does not delay the beginning of complementary chemotherapy. However, it is necessary to take into account surgery-related morbidity. As modified posterior pelvic exenteration represents an extremely invasive technique, the surgical plan and perioperative care should be personalized to address the individual medical and surgical conditions of each patient.

Predictors of quality of life in Czech female breast cancer survivors following treatment with special interest to coping strategies.

OBJECTIVES: This study examined the prognostic significance of breast cancer patients characteristics (coping strategies, BMI, age) and disease characteristics (stage of disease, relapse) with respect to quality of life (QoL) following treatment.Sample and settings: 120 breast cancer patients following treatment were recruited. Health-related QoL was assessed using the Czech version of FACT-B and SF-36; additionally, we used a life satisfaction questionnaire. Coping strategies were assessed using the SVF-78 method. In our sample of women, the average time from diagnosis to start of the study was 5.3 years. STATISTICAL ANALYSIS: Factors influencing QoL after treatment were analysed with univariate and multivariate linear regression. RESULTS: Overall negative strategy defined in SVF-78 (Flight tendency, Resignation and Self-accusation) was found to be associated with lower scores of most components of used QoL methods, while Resignation was found as the most negatively influencing strategy. Active problem confrontation (Situation control and Positive self-instruction) was associated with better QoL. More advanced stages and recurrence were related to a significant decrease in QoL for certain components only. CONCLUSION: Our findings suggest a significant predictive power of disease-related factors and of patients characteristics including coping strategies for QoL following treatment in Czech breast cancer survivors.Key words: breast cancer survivors - coping strategy - linear regression model - quality of life prediction - resignation.

L1CAM expression in endometrial carcinomas: an ENITEC collaboration study.

BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.