BACKGROUND: This study aimed to evaluate the effectiveness of different tracers´ application techniques for sentinel lymph node (SLN) detection in women with endometrial cancer undergoing laparotomy. Additionally, potential risk factors for SLN detection failure were assessed. METHODS: We retrospectively analyzed data from 248 endometrial cancer patients who underwent abdominal surgery with SLN mapping between January 2020 and March 2024. Statistical analyses were conducted using the Wilcoxon rank sum test for continuous variables and either Pearson's chi-square test or Fisher's exact test for categorical variables, with a significance level set at p < 0.05. RESULTS: Group I + S consisted of 147 women with intracervical and subserosal tracers´application and group I + I included 101 women with intracervical and intrafundal application. Successful detection of SLN on both sides was achieved in 39.9% (99/248) of all patients, in 38.1% (56/147) in the I + S group and in 42.6% (43/101) in the I + I group, respectively. SLNs were identified in 32.7% (81/248) of all patients on only one side of the pelvis, in 31.3% (46/147) in the I + S and in 34.7% (35/101) in the I + I group, respectively. No SLNs were detected in 27.4% (68/248) of all subjects, comprising 30.6% (45/147) from the I + S and 22.8% (23/101) from the I + I group. Although the success rate of SLN detection was higher in the I + I group and on the right side of the pelvis regardless of the detection method, these differences were not statistically significant. An age exceeding 66.3 years was recognized as a critical risk factor for successful detection, other followed factors did not demonstrate a statistically significant impact on overall detection success. Additional significant risk factors were identified: depth of tumor myometrial invasion on the right side, history of pelvic surgery, and total tumor volume on the left side. CONCLUSIONS: The study did not reveal significant differences in SLN mapping success between the groups receiving intracervical + intrafundal and intracervical + subserosal tracers´applications among endometrial cancer patients treated via open surgery. Overall, older age emerged as the most critical risk factor for SLN detection failure, while other assessed factors did not show a statistically significant impact on overall detection success. TRIAL REGISTRATION: Institution University Hospital Královské Vinohrady, Prague, Czech Republic. REGISTRATION NUMBER: EK-VP-21-0-2023. Date of registration 7-JUN-2023. This study was retrospectively registered in compliance with the Declaration of Helsinki.

• Klíčová slova
• Detection failure, Detection success, Endometrial cancer, Laparotomy, Risk factors, Sentinel lymph node, Tracer application,
• MeSH
• biopsie sentinelové lymfatické uzliny * metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• nádory endometria * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sentinelová uzlina * patologie   diagnostické zobrazování   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

INTRODUCTION: Appendectomy for acute appendicitis is the most common surgical procedure performed during pregnancy. The primary treatment for acute appendicitis is emergency surgery, which can be particularly challenging due to altered anatomical conditions. Preoperative and postoperative care may require certain examinations due to pregnancy that are not standard within surgical practice or may be overlooked by the attending gynecologist. CASE PRESENTATION: A patient at 31 weeks of gestation presented to the obstetric clinic with an acute onset of acute appendicitis. After completing all necessary examinations and a thorough multidisciplinary evaluation, a successful laparoscopic appendectomy was performed. The subsequent hospitalization was complicated by the onset of uterine contractions, for which tocolysis was administered in combination with corticosteroid therapy to induce fetal lung maturity. CONCLUSION: In the presented case report, we demonstrate an example of the appropriate multidisciplinary approach with an analysis of the specific steps that should be taken to maximize the benefit for both the fetus and the mother, as well as the surgical team. In the discussion, we outline the steps that should be followed for patient benefit and forensic reasons.

• Klíčová slova
• Appendicitis, Laparoscopic surgery, Management, Minimally invasive surgery, Obstetrics, Pregnancy, Surgery,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The International Federation of Gynaecology and Obstetrics (FIGO) introduced a new staging system for endometrial carcinoma FIGO 2023 in June 2023. The new staging system differs significantly from previous versions by incorporating other non-anatomical parameters (histological type of tumour, tumour grade and the presence of massive lymphovascular space involvement as well as the molecular classification of the tumour). The FIGO 2023 staging system enhances the accuracy of prognostic assessments for patients at a specific stage with better options for targeted treatment. Another objective was to synchronise staging as much as possible with the European oncogynaecological ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma established in 2021. However, several changes are controversial. Routine molecular classification of endometrial carcinomas is not yet commonly available in most countries of the world. Another limitation of the FIGO 2023 staging system of endometrial cancer is the inclusion of variables whose definitions are still evolving, as well as variables that are subject to considerable interobserver variability in their assessment. Advantages, controversies, and limitations for clinical practice of the new FIGO 2023 endometrial cancer staging system are discussed.

Im Juni 2023 hat die Internationale Vereinigung für Gynäkologie und Geburtshilfe (FIGO) ein neues Staging-System für das Endometriumkarzinom – FIGO 2023 – eingeführt. Das neue Staging-System unterscheidet sich signifikant von früheren Versionen, da nun auch andere nicht anatomische Parameter (z. B. histologischer Tumortyp, Tumorgrad, ausgedehnter Befall des lymphatischen Raums sowie die molekulare Klassifikation von Tumoren) einbezogen wurden. Das FIGO-2023-Staging-System verbessert die prognostische Genauigkeit bei Patientinnen in einem bestimmten Tumorstadium mit einer besseren Auswahl an gezielten Behandlungsmöglichkeiten. Zweck des neuen Systems ist es auch, das FIGO-Staging weitmöglichst mit dem Staging der gynäkologisch-onkologischen Europäischen Leitlinien der ESGO/ESTRO/ESP, die im Jahre 2021 für das Management von Patientinnen mit Endometriumkarzinom aufgestellt wurden, in Einklang zu bringen. Allerdings werden mehrere Änderungen immer noch kontrovers diskutiert. So ist in den meisten Ländern der Welt die routinemäßige molekulare Klassifikation von Endometriumkarzinomen nicht allgemein üblich oder erhältlich. Eine weitere Einschränkung des FIGO-2023-Staging-Systems für das Endometriumkarzinom ist die Einbeziehung von Variablen, deren Definitionen noch im Entstehen begriffen sind, bzw. von Variablen, die eine erhebliche Interobserver-Variabilität aufweisen. Die Vorteile, Kontroversen und Einschränkungen des neuen FIGO-2023-Staging-Systems in der klinischen Praxis werden hier diskutiert.

• Klíčová slova
• ESGO, ESP, ESTRO, FIGO 2023, controversies, endometrial cancer, molecular classification, staging, staging system,
• Publikační typ
• časopisecké články MeSH

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC). PATIENTS AND METHODS: Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m2 weekly) or PTX. Primary endpoint was overall survival (OS). Exploratory post-hoc analyses assessed OS in pegylated liposomal doxorubicin (PLD)-naive patients. RESULTS: Between March 2019 and November 2021, 558 patients (ECOG PS 0, 60.2 %; median [range] age, 62 [22-91] years) were assigned TTFields+PTX (n = 280) or PTX (n = 278). 24.4 % had 4 + prior LOT. Median OS was 12.2 months with TTFields+PTX vs 11.9 months with PTX (HR, 1.01; 95 % CI, 0.83-1.24; p = 0.89). Grade ≥ 3 adverse events (AEs) were similar between treatment groups. Grade 1/2 device-related skin AEs occurred in 83.6 % of patients receiving TTFields therapy. In exploratory post-hoc analysis in PLD-naive patients, median OS was 16 months with TTFields+PTX (n = 113) vs 11.7 months with PTX (n = 88; nominal HR, 0.67; 95 % CI, 0.49-0.94; p = 0.03). CONCLUSIONS: No new safety signals were identified. TTFields+PTX did not significantly improve OS compared with PTX in the intent-to-treat population. An exploratory post-hoc analysis suggests a potentially favorable benefit-risk profile for TTFields therapy in PLD-naive patients.

• Klíčová slova
• Antineoplastic agents, Neoplasm drug resistance, Ovarian epithelial carcinoma, Ovarian neoplasm, Survival analysis,
• MeSH
• chemorezistence * MeSH
• dospělí MeSH
• elektrostimulační terapie metody   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory vaječníků * farmakoterapie   terapie   mortalita   patologie   MeSH
• paclitaxel * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• paclitaxel * MeSH

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

• MeSH
• adjuvantní chemoterapie MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• karboplatina aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria * genetika   farmakoterapie   terapie   patologie   radioterapie   MeSH
• oprava chybného párování bází DNA * MeSH
• paclitaxel aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• humanizované monoklonální protilátky * MeSH
• karboplatina MeSH
• paclitaxel MeSH
• pembrolizumab MeSH Prohlížeč

Tubal abortion is characterized by the extrusion of the foetus into the abdominal (peritoneal) cavity. It can either be a complete extrusion or incomplete with residual tissue remaining in the fallopian tube. It is a type of ectopic pregnancy that is difficult to determine the exact incidence of tubal pregnancies. Identifying cases of tubal abortions is crucial for individualized care since it can lead to a more conservative treatment approach. The diagnosis should be based on ultrasound imaging, b-hCG levels and visual conformation during exploratory surgery, either open or laparoscopic. The article describes the case of a 30-year old patient who presented with lower abdominal pain and was admitted for a suspected ectopic pregnancy. Ultrasound imaging showed a mass resembling a tubal pregnancy next to the uterus with b-hCG levels of 111.8 U/L. During laparoscopic surgery, a tubal abortion was detected in the pouch of Douglas (Rectouterine pouch). This finding led us to preserve both fallopian tubes. Histopathology confirmed our clinical findings. A conservative approach can be sufficient in case of tubal abortions, which can lead to preserved fertility and tubal functions.

• Klíčová slova
• abortion, ectopic pregnancy, hCG, laparoscopy, tubal abortion,
• MeSH
• dospělí MeSH
• laparoskopie MeSH
• lidé MeSH
• salpingektomie MeSH
• samovolný potrat etiologie   MeSH
• těhotenství tubární * chirurgie   diagnóza   diagnostické zobrazování   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal. METHODS: We isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism. RESULTS: The primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts. CONCLUSIONS: Analysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels.

• Klíčová slova
• Epithelial ovarian carcinoma, Metabolism reprogramming, Ovarian fibroblasts, Oxidative phosphorylation, Patient-derived cells, Unfolded protein response,
• Publikační typ
• časopisecké články MeSH

Impaired telomere length (TL) maintenance in ovarian tissue may play a pivotal role in the onset of epithelial ovarian cancer (OvC). TL in either target or surrogate tissue (blood) is currently being investigated for use as a predictor in anti-OvC therapy or as a biomarker of the disease progression, respectively. There is currently an urgent need for an appropriate approach to chemotherapy response prediction. We performed a monochrome multiplex qPCR measurement of TL in peripheral blood leukocytes (PBL) and tumor tissues of 209 OvC patients. The methylation status and gene expression of the shelterin complex and telomerase catalytic subunit (hTERT) were determined within tumor tissues by High-Throughput DNA methylation profiling and RNA sequencing (RNA-Seq) analysis, respectively. The patients sensitive to cancer treatment (n = 46) had shorter telomeres in PBL compared to treatment-resistant patients (n = 93; P = 0.037). In the patients with a different therapy response, transcriptomic analysis showed alterations in the peroxisome proliferator-activated receptor (PPAR) signaling pathway (q = 0.001). Moreover, tumor TL shorter than the median corresponded to better overall survival (OS) (P = 0.006). TPP1 gene expression was positively associated with TL in tumor tissue (P = 0.026). TL measured in PBL could serve as a marker of platinum therapy response in OvC patients. Additionally, TL determined in tumor tissue provides information on OvC patients' OS.

• Klíčová slova
• Ovarian cancer, Shelterin, Telomerase, Telomere length, Therapy response,
• Publikační typ
• časopisecké články MeSH

AIM: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. METHODS AND RESULTS: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the biological behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. CONCLUSION: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy.

• Klíčová slova
• FIGO, endometrial cancer, molecular classification, staging, update,
• MeSH
• lidé MeSH
• nádory endometria * patologie   klasifikace   terapie   diagnóza   MeSH
• staging nádorů * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer. METHODS: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative diagnostic biopsy and postoperative definitive histology. The data were statistically processed. RESULTS: Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative biopsy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/intermediate-risk group to intermediate-high/high-risk disease group. CONCLUSION: Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from diagnostic biopsies made in referring hospitals. Sentinel lymph node biopsy should be performed even in clinically low/intermediate-risk disease group.

• Klíčová slova
• endometrial cancer, sentinel lymph node detection, tumour grade, tumour stage,
• MeSH
• biopsie sentinelové lymfatické uzliny metody   MeSH
• lidé MeSH
• lymfadenektomie metody   MeSH
• lymfatické uzliny patologie   MeSH
• nádory endometria * chirurgie   patologie   MeSH
• prospektivní studie MeSH
• sentinelová uzlina * patologie   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH