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
• Chemotherapy, Adjuvant MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   administration & dosage   adverse effects   MeSH
• Carboplatin administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Endometrial Neoplasms * pathology   drug therapy   mortality   therapy   MeSH
• DNA Mismatch Repair * MeSH
• Paclitaxel * administration & dosage   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Endometrial carcinomas (EC) of no special molecular profile (NSMP) represent the largest molecular category of EC, comprising a mixture of tumors with different histology and molecular profiles. These facts likely point to different tumor biology, clinical outcomes, and targeted therapy responses within this molecular category. The PIK3CA is currently the only targetable kinase oncoprotein directly implicated in EC carcinogenesis. Investigating a unique single-institution cohort, we attempted to stratify NSMP ECs based on the presence of the PIK3CA pathogenic mutation. Those cases were further analyzed for other well-established-associated oncogenic driver gene mutations. Histological and clinical variables were also correlated in each case. Altogether, 175 ECs were prospectively tested by a limited custom NGS panel containing ARID1A, BCOR, BRCA1, BRCA2, CTNNB1, KRAS, MLH1, MSH2, MSH6, NRAS, PIK3CA, PMS2, POLD1, POLE, PTEN,and TP53 genes. We identified 24 PIK3CA mutated cases in the group of 80 NSMP ECs, with another co-occurring mutation in at least one oncogenic driver gene (CTNNB1, PTEN, ARID1A, KRAS, BCOR, PMS2) in 19 cases. In conclusion, a limited NGS panel can effectively test EC tissue for specific pathogenetically relevant oncogene mutations. The NSMP EC category contains 30% of the PIK3CA mutated cases. Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.

• MeSH
• Molecular Targeted Therapy MeSH
• Adult MeSH
• Class I Phosphatidylinositol 3-Kinases * genetics   antagonists & inhibitors   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• DNA Mutational Analysis MeSH
• Biomarkers, Tumor * genetics   MeSH
• Endometrial Neoplasms * genetics   pathology   drug therapy   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Patient Selection MeSH
• High-Throughput Nucleotide Sequencing * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later. Immunohistochemically, the tumor cells showed diffuse nuclear expression of beta-catenin, confirming the activation of the beta-catenin pathway. Our case represents only the 4th reported case of CTNNB1-rearranged endometrial stromal tumor with extensive whorling. The biological nature of uterine tumors characterized by whorled morphology and rearrangement of CTNNB1 is not yet clear, which underscores the importance of genetic profiling for accurate diagnosis and potential targeted therapies in malignant cases.

• MeSH
• beta Catenin * genetics   MeSH
• Endometrial Stromal Tumors * pathology   genetics   diagnosis   MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• Gene Rearrangement MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   analysis   MeSH
• Neoplasm Proteins MeSH
• Endometrial Neoplasms * genetics   pathology   diagnosis   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10-15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients.

• MeSH
• Cytokines metabolism   immunology   MeSH
• Endometriosis * immunology   therapy   pathology   etiology   MeSH
• Endometrium immunology   pathology   MeSH
• Humans MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

INTRODUCTION: This was a single-center pilot study that sought to describe an innovative use of 4DryField® PH (premix) for preventing the recurrence of intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis in patients with Asherman's syndrome (AS). MATERIAL AND METHODS: Twenty-three patients with AS were enrolled and 20 were randomized (1:1 ratio) to intrauterine application of 4DryField® PH (n = 10) or Hyalobarrier® gel (n = 10) in a single-blind manner. We evaluated IUAs (American Fertility Society [AFS] score) during initial hysteroscopy and second-look hysteroscopy one month later. Patients completed a follow-up symptoms questionnaire three and reproductive outcomes questionnaire six months later. RESULTS: The demographic and clinical characteristics, as well as severity of IUAs, were comparable in both groups. The mean initial AFS score was 9 and 8.5 in the 4DryField® PH and Hyalobarrier® gel groups, respectively (p = .476). There were no between-group differences in AFS progress (5.9 vs. 5.6, p = .675), need for secondary adhesiolysis (7 vs. 7 patients, p = 1), and the follow-up outcomes. CONCLUSION: 4DryField® PH could be a promising antiadhesive agent for preventing the recurrence of IUAs, showing similar effectiveness and safety to Hyalobarrier® gel. Our findings warrant prospective validation in a larger clinical trial. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN15630617.

• MeSH
• Tissue Adhesions prevention & control   MeSH
• Adult MeSH
• Gels * MeSH
• Gynatresia prevention & control   MeSH
• Hysteroscopy * methods   MeSH
• Single-Blind Method MeSH
• Hyaluronic Acid administration & dosage   MeSH
• Humans MeSH
• Uterine Diseases prevention & control   surgery   MeSH
• Pilot Projects MeSH
• Recurrence MeSH
• Secondary Prevention methods   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Prevalence detekce izolovaných nádorových buněk a mikrometastáz v sentinelové uzlině stoupá díky jejich podrobnému zpracování formou ultrastagingu. Předkládaná práce poskytuje aktuální přehled literatury od ledna roku 2019 do září roku 2024 se zaměřením na nízkoobjemové postižení regionálních uzlin, jeho prevalenci, prognózu a souvislost s molekulární klasifikací. Přítomnost mikrometastáz je aktuálně považována za metastatické postižení lymfatických uzlin, avšak s lepší prognózou než makrometastázy, dle toho je volen i terapeutický postup společný pro obě tyto kategorie uzlinového postižení. Naopak přítomnost izolovaných nádorových buněk není v rámci Mezinárodní federace gynekologie a porodnictví (FIGO) 2023 stagingu považována za uzlinové postižení a neovlivňuje doporučený terapeutický postup, protože doposud nebyly prokázány signifikantní prognostické důsledky jejich přítomnosti.

Due to the implementation of sentinel lymph node ultrastaging, the prevalence of isolated tumor cells and micrometastases have increased. This literature review comprises of articles published between January 2019 and September 2024 aiming at low-volume metastases in regional lymph nodes, their prognosis, and links to molecular classification. Micrometastases are currently considered as having metastatic lymph node involvement; however, they have a better prognosis than macrometastases. Accordingly, therapy is tailored. In contrast, isolated tumor cell presence is not considered metastatic involvement according to International Federation of Gynecology and Obstetrics (FIGO) 2023 staging and does not affect the therapeutic procedure because their significant prognostic importance has not been proven so far.

• Keywords
• nízkoobjemové postižení uzlin,
• MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Neoplasm Metastasis diagnosis   pathology   MeSH
• Neoplasm Micrometastasis MeSH
• Endometrial Neoplasms * diagnosis   epidemiology   complications   MeSH
• Prognosis MeSH
• Sentinel Lymph Node * pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

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.

• MeSH
• Sentinel Lymph Node Biopsy * methods   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Endometrial Neoplasms * surgery   pathology   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sentinel Lymph Node * pathology   diagnostic imaging   surgery   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Úvod a cíl studie: Uterinní NK (uNK) buňky jsou specializovanou subpopulací NK (natural killer) lymfocytů nacházejících se v endometriu. Hrají klíčovou roli v regulaci imunitní odpovědi a v procesu implantace embrya. Cílem této studie je retrospektivní analýza výsledků léčby metodou in vitro fertilizace (IVF) v souboru žen, které podstoupily imunofenotypizaci uNK buněk a na základě výsledků tohoto vyšetření byly, nebo nebyly léčeny imunomodulační terapií. Metody: Studie zahrnovala 122 pacientek, které podstoupily imunofenotypizaci uNK buněk v období od dubna do prosince 2023. Imunofenotypizace byla provedena metodou průtokové cytometrie. Pacientky byly roztříděny do čtyř skupin dle fenotypu uNK buněk: normální nálezy, nízké absolutní a relativní počty uNK (LOW-IMMUNE profil), nízké počty uNK v kombinaci s nežádoucím posunem směrem k cytotoxickému uNKdim imunofenotypu (MIXED-IMMUNE profil) a normální počty uNK, ale nežádoucí posun v poměru cytotoxických a regulačních uNK s cytotoxickým fenotypem (OVER-IMMUNE profil). Byly hodnoceny výsledky embryotransferu a výskyt potratů do ukončeného 12. týdne těhotenství v jednotlivých skupinách. Výsledky: Nejvyšší míra dosažení klinické gravidity byla nalezena v léčené skupině OVER- -IMMUNE (70 %), následované skupinou MIXED-IMMUNE (60 %). Skupina LOW-IMMUNE se od neléčené NORMAL skupiny signifikantně nelišila (p = 0,205). Nedostatečná imunitní aktivace (LOW-IMMUNE profil) byla signifikantně nejčastěji sdružena s prvotrimestrální těhotenskou ztrátou (p < 0,0001). Závěr: Tato studie přináší nové poznatky o potenciálu imunofenotypizace uNK buněk a následné imunomodulační terapie v léčbě poruch plodnosti. Ačkoli výsledky naznačují možné klinické přínosy, je zapotřebí dalšího výzkumu k potvrzení těchto zjištění a k objasnění mechanizmů, které vedou ke zlepšení výsledků léčby technikami asistované reprodukce.

Introduction and objective: Uterine NK (uNK) cells, a specialized subpopulation of natural killer (NK) lymphocytes located in the endometrium, play a crucial role in regulating the immune response and in the process of embryo implantation. This study aims to retrospectively analyze the outcomes of in vitro fertilization (IVF) treatment in a cohort of women who underwent uNK cell immunophenotyping with subsequent immunomodulatory therapy applied based on the results. Methods: The study included 122 patients who underwent uNK cell immunophenotyping between April and December 2023. Immunophenotyping was performed using flow cytometry. Patients were categorized into four groups according to their uNK cell phenotypes: normal findings, low absolute and relative numbers of uNK cells (LOW-IMMUNE profile), low numbers of uNK cells combined with the shift towards the cytotoxic uNKc dim immunophenotype (MIXED-IMMUNE profile), and normal numbers of uNK cells, but an undesirable shift in the ratio of cytotoxic to regulatory uNK cells towards the cytotoxic uNK dim phenotype (OVER-IMMUNE profile). Embryo transfer outcomes and the occurrence of miscarriages up to the 12th week of pregnancy were evaluated in each group. Results: The highest clinical pregnancy rate was observed in the treated OVER-IMMUNE group (70%), fol lowed by the MIXED-IMMUNE group (60%). The LOW-IMMUNE group did not differ significantly from the untreated NORMAL group (P = 0.205). Insufficient immune activation (LOW-IMMUNE profile) was significantly associated with first-trimester pregnancy loss (P < 0.0001). Conclusion: This study provides new insights into the potential benefits of uNK cell immunophenotyping and subsequent immunomodulatory therapy in treating fertility disorders. While the results indicate possible clinical advantages, further research is necessary to confirm these findings and elucidate the mechanisms leading to improved outcomes in assisted reproductive techniques.

• Keywords
• uterinní NK buňky, imunofenotypizace lymfocytů, opakované selhání implantace,
• MeSH
• Killer Cells, Natural MeSH
• Endometrium cytology   MeSH
• Fertilization in Vitro * MeSH
• Abortion, Habitual MeSH
• Immunophenotyping MeSH
• Immunomodulation MeSH
• Humans MeSH
• Flow Cytometry methods   MeSH
• Retrospective Studies MeSH
• Infertility, Female * MeSH
• Check Tag
• Humans MeSH
• Female MeSH

Minimally invasive surgery is the method of choice in endometrial cancer. Experience in procedures assisted by a robotic system is growing rapidly. One of the new bipolar ones is a Vessel Sealer, with sealing and cutting function. The aim of the study was to compare robotic surgery assisted with the da Vinci X system with use of the Vessel Sealer or without it. The study included 25 patients with high-risk endometrial cancer after completed pelvic and paraaortic lymphadenectomy with mean age 60.07 ± 10.67 (range 34.69-83.23) years divided into two groups: one with use of the Vessel Sealer; the second one only with monopolar scissors and subdivided by one-site versus dual docking. Duration of the operation was significantly associated with previous surgery (p < 0.005). Use of the Vessel Sealer was associated with lower blood loss during surgery (p < 0.05). The number of removal pelvic lymph nodes was higher in case of Vessel Sealer with no relation to BMI. Experience in robotic surgery allowed for shortened operation time and led to better outcomes. The Vessel Sealer used in robotic surgery appears to reduce blood loss during surgery and operation time, especially in the case of previous surgery, however, it increases costs of the procedure.

• MeSH
• Operative Time MeSH
• Adult MeSH
• Blood Loss, Surgical prevention & control   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision * methods   MeSH
• Endometrial Neoplasms * surgery   pathology   MeSH
• Robotic Surgical Procedures * methods   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. METHODS: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. RESULTS: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. CONCLUSIONS: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

• MeSH
• Adult MeSH
• Carcinoma, Endometrioid * pathology   metabolism   surgery   mortality   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor metabolism   MeSH
• Tumor Suppressor Protein p53 * metabolism   biosynthesis   MeSH
• Endometrial Neoplasms * pathology   metabolism   surgery   mortality   MeSH
• Prognosis MeSH
• Receptors, Progesterone * metabolism   biosynthesis   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Grading MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH