Search Results (105)

Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes—bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances—demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform. Full article

Background/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy in developed countries, yet no clinically validated noninvasive screening biomarker exists. Fatty acid metabolic reprogramming is a hallmark of cancer that produces measurable changes in systemic free fatty acid (FFA) profiles. We aimed to identify serum FFAs altered in EC and evaluate their potential as early diagnostic biomarkers. Methods: Gene expression of fatty acid metabolic enzymes in EC tissues was assessed using public databases. Serum levels of 19 FFAs were quantified by gas chromatography–mass spectrometry in 72 patients with EC and 84 healthy donors. A two-variable diagnostic model was constructed using logistic regression and validated in an independent dataset. Results: Multiple fatty acid metabolic enzymes involved in de novo synthesis were upregulated in EC tissues as early as stage I, while enzymes mediating fatty acid uptake and release were downregulated. Serum levels of palmitoleic acid, oleic acid and dihomo-γ-linolenic acid were significantly elevated, whereas arachidic acid and arachidonic acid were significantly decreased in patients with EC from stage I onward. A diagnostic model combining palmitoleic acid and arachidonic acid achieved an area under the receiver operating characteristic curve of 0.9674, with a sensitivity of 91.3% and specificity of 96.4% in the validation dataset, including for stage I disease, and was independent of body mass index, age, metastasis status, and family history. Conclusions: Serum FFA profiling represents a promising noninvasive strategy for early EC detection, with the potential to complement existing diagnostic methods. Full article

Endometrial cancer is the most common gynecologic malignancy in developed countries and remains challenging in terms of risk stratification, treatment monitoring, and early detection of recurrence. Liquid biopsy provides a minimally invasive approach for the dynamic assessment of tumor-derived biomarkers and may complement tissue-based diagnosis and molecular classification. This narrative review summarizes current evidence on circulating biomarkers in endometrial cancer, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating microRNAs, and tumor-educated platelets, with attention to validity, applicability, and implementation barriers. Among these biomarkers, ctDNA currently has the strongest evidence base, especially for longitudinal monitoring, prognostic stratification, molecular residual disease assessment, and early detection of relapse in high-risk or recurrent disease. However, its sensitivity remains limited in early-stage, low-volume, and low-shedding tumors. CTCs, EVs, microRNAs, and platelet-derived signatures are promising but still largely investigational. Artificial intelligence may support multimodal biomarker validation, although clinical adoption will require external validation, locked algorithms, standardized workflows, and prospective utility trials. Overall, liquid biopsy represents a promising adjunct to tissue-based diagnosis and molecular classification in endometrial cancer, particularly for monitoring and follow-up. Prospective studies are now needed to demonstrate whether liquid-biopsy-informed decisions can improve outcomes or safely reduce overtreatment. Full article

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification—diet, physical activity, sleep, and stress regulation—remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification. Full article

Background: Unscheduled bleeding in postmenopausal women on hormone replacement therapy (HRT) represents a common but poorly characterised clinical challenge. Whilst endometrial cancer affects approximately 9% of women with unexplained postmenopausal bleeding, existing evidence in HRT users is largely restricted to women under 60 years and short-duration regimens, leaving a critical evidence gap in contemporary all-age clinical practice. Whether the same investigative urgency is warranted for HRT users experiencing unscheduled bleeding as for women with unexplained postmenopausal haemorrhage remains unresolved. Objectives: To determine the diagnostic yield of endometrial cancer and hyperplasia amongst postmenopausal women presenting with unscheduled bleeding whilst on HRT, and to explore potential associations with HRT regimens and clinical risk factors. Methods: This retrospective observational study analysed 343 postmenopausal women presenting with unscheduled bleeding whilst on HRT at a single tertiary centre between September 2023 and February 2024. All patients underwent transvaginal ultrasound and endometrial sampling according to institutional protocol. Descriptive statistics were used to characterise outcomes, with exploratory analyses of potential risk factors. Given the symptomatic and selected nature of this cohort, all proportions represent the diagnostic yield within an investigated population rather than population-level incidence estimates. Results: Amongst 343 women (mean age 56.2 ± 7.4 years), nine cases (2.6%) of endometrial abnormalities were identified: four malignancies (1.2%), four endometrial hyperplasia without atypia (1.2%), and one complex atypical hyperplasia (0.3%). Only five cases (1.5%) required surgical intervention. All four endometrial cancers were Stage IA (FIGO 2009; three Grade 1, one Grade 2; no LVSI), corresponding to Stage IA2mNSMP under FIGO 2023. None required adjuvant therapy. Strikingly, 88.9% of all abnormal cases occurred within two years of HRT initiation, with no endometrial pathology identified amongst the 45 women using systemic HRT for more than five years—a temporal pattern not previously reported. Conclusions: In this retrospective all-age NHS cohort, the diagnostic yield of endometrial cancer was 1.2% in HRT users with unscheduled bleeding, with only 1.5% requiring surgical intervention. All cancers were early-stage (FIGO 2009 Stage IA; FIGO 2023 Stage IA2mNSMP) and required no adjuvant therapy. A previously unreported temporal clustering of pathology within the first two years of HRT initiation generates a hypothesis that early unscheduled bleeding may unmask pre-existing rather than HRT-induced endometrial abnormalities. These observations are hypothesis-generating and should not be interpreted as evidence of endometrial safety. These findings apply specifically to symptomatic women presenting for investigation and cannot be generalised to asymptomatic HRT users. Prospective validation in larger cohorts with baseline endometrial assessment is required before any clinical conclusions can be drawn. What This Study Adds: (1) A real-world cancer detection proportion of 1.2% in an all-age contemporary NHS cohort. (2) A previously undescribed temporal pattern with pathology clustering within two years of HRT initiation and no pathology in long-term users (n = 45), generating a testable hypothesis about pre-existing versus HRT-induced disease. (3) Dual FIGO 2009/2023 staging demonstrating that molecular classification added no treatment-discriminatory value in this early-detection context. Full article

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries. Sentinel lymph node (SLN) mapping has emerged as a less invasive alternative to systematic lymphadenectomy and is increasingly incorporated into surgical staging algorithms. Vaginal natural orifice transluminal endoscopic surgery (vNOTES) provides transvaginal access to the retroperitoneum and may facilitate SLN mapping while potentially reducing postoperative morbidity, including lower extremity lymphedema (LEL). Objective: This study aimed to evaluate the feasibility of vNOTES hysterectomy with bilateral salpingo-oophorectomy (BSO) and retroperitoneal SLN mapping and to report early postoperative lymphedema outcomes in patients with newly diagnosed endometrial cancer. Methods: This retrospective cohort study included 113 patients who underwent vNOTES-assisted hysterectomy with BSO and SLN mapping using methylene blue dye at a tertiary referral center between January 2022 and January 2023. Lymphedema was evaluated using the Gynecologic Cancer Lymphedema Questionnaire at 6 and 12 months postoperatively, supported by clinical examination. Descriptive statistical analyses were performed to summarize clinical characteristics and symptom profiles. Results: The mean patient age was 55.0 ± 10.5 years and the mean BMI was 30.94 ± 2.54 kg/m². Endometrioid adenocarcinoma was the most common histological subtype (75.5%), and most tumors were grade 1 (57.1%). SLN mapping was successful in 102 of 113 patients (overall detection rate 90.3%), with bilateral detection in 79.6% and unilateral detection in 10.6% of cases. Limb swelling was reported in 4.1% of patients, while only one patient (1.0%) met the criteria for self-reported mild lymphedema. No clinical signs of inguinal lymphedema were detected. Conclusions: vNOTES hysterectomy combined with retroperitoneal SLN mapping was associated with a low incidence of postoperative lower extremity lymphedema in this single-arm cohort. These findings suggest that vNOTES-assisted SLN mapping may represent a feasible minimally invasive approach for nodal assessment in selected patients with endometrial cancer. Prospective comparative studies are required to confirm these findings and to evaluate long-term oncologic and lymphatic outcomes. Full article

Background/Objectives: High-grade endometrial cancer (EC) is associated with poor outcomes, particularly in populations with a high burden of aggressive histologies. There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management. Methods: In this study, we evaluated the feasibility and clinical relevance of monitoring circulating tumor DNA (ctDNA) by tracking somatic TP53 mutations using a routine next-generation sequencing (NGS) assay already implemented in diagnostic practice. Results: Among 21 patients with high-grade EC carrying TP53 mutations in the primary tumor, ctDNA was detectable in over 75% during follow-up. Baseline ctDNA detection strongly correlated with advanced disease: none of the FIGO I tumors were ctDNA-positive at diagnosis, whereas 73% of FIGO > I tumors showed detectable ctDNA. Patients with ctDNA detected at baseline had significantly poorer outcomes, with a 2-year recurrence-free survival (RFS) of 18% versus 60% and a 2-year overall survival (OS) of 40% versus 78%. Longitudinal monitoring revealed that postoperative persistence or reappearance of ctDNA was consistently associated with disease progression, often preceding radiological relapse. Conversely, early ctDNA clearance (at M4–M8) was associated with more favorable clinical trajectories. Conclusions: These findings highlight the potential role of ctDNA as a real-time molecular marker of minimal residual disease and tumor dynamics. Our results demonstrate that TP53-based ctDNA tracking using a standard NGS panel is feasible, sensitive, and clinically informative in high-grade EC. This approach may contribute to improving prognostic stratification and enabling more personalized, responsive clinical management, particularly in high-risk populations. Full article

Background: Minimally invasive hysterectomy with sentinel lymph node (SLN) mapping is standard for early-stage endometrial cancer, but comparative real-world data on robot-assisted (RAH) versus conventional laparoscopy (TLH) remain limited. This study aimed to compare the two techniques in a real-world clinical setting. Methods: We retrospectively reviewed medical records of 140 patients with FIGO stage I endometrial cancer who underwent RAH or TLH at Semmelweis University between January 2022 and December 2024. We analyzed patient demographics, sentinel lymph node (SLN) detection rates, conversion rates, operative time, pathological characteristics. Results: Baseline demographic and oncologic characteristics were comparable. SLN detection was significantly higher in the RAH group compared to TLH (98% vs. 90.2%, p = 0.04). Conversion to laparotomy occurred in 0% of RAH cases versus 11.5% of TLH cases (p = 0.0024). Conclusions: In a standardized ICG-guided SLN mapping setting, RAH achieved higher SLN detection and markedly lower conversion rates than TLH, without differences in operative time or key pathological parameters. Full article

Background/Objectives: With the rising incidence of obesity-related endometrial cancer, there is renewed interest in physiologic, low-cost approaches to identify women with hormonally active endometrium who may benefit from early preventive interventions. The progesterone challenge test (PCT), an established clinical tool for evaluating amenorrhea, has been previously proposed as a method to detect endometrial pathology. This study systematically evaluated the diagnostic accuracy of the PCT for detecting endometrial hyperplasia, intraepithelial neoplasia, and carcinoma in asymptomatic postmenopausal women to determine its potential role as a physiologic marker of endometrial cancer risk. Methods: A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. MEDLINE, EMBASE, EBM Reviews, and CINAHL were searched from inception to 20 January 2025, along with ClinicalTrials.gov and grey literature. Eligible studies prospectively evaluated the PCT with endometrial biopsy as the reference standard. Data extraction and risk-of-bias assessment were performed in duplicate. Risk of bias was assessed using QUADAS-2. Pooled sensitivity, specificity, and predictive values were estimated using hierarchical summary receiver operating characteristic models. Results: Nineteen studies (n = 3902) met the inclusion criteria. The pooled sensitivity and specificity of the PCT for detecting endometrial pathology were 95% (95% CI 86–100%) and 87% (76–96%), respectively. The positive predictive value was 32% (95% CI, 16–50%) and the negative predictive value was 100% (100–100%). When endometrial proliferation was included in the target condition, sensitivity decreased to 82%, but positive predictive value increased to 70%. Conclusions: The PCT shows high diagnostic accuracy for identifying estrogen-driven endometrial pathology in asymptomatic postmenopausal women. Re-evaluating this simple, physiologic test as a functional risk-stratification tool could inform precision prevention strategies for endometrial cancer. Full article

Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [¹⁸F]FDG PET/MRI’s diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [¹⁸F]FDG PET/MRI before surgery (2018–2024). Histology, immunohistochemistry, and patients’ follow-up (mean FU time: 3.13y) were used as the reference standard. [¹⁸F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [¹⁸F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman’s correlations, Fisher’s exact test, ROC-AUC analysis, Kaplan–Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [¹⁸F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm³ showed increased probabilities of recurrence (p < 0.001). Conclusions: [¹⁸F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence. Full article

Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and may offer a rapid alternative. Methods: In this prospective single-centre study, 63 women (median age 62 years) undergoing primary surgery with sentinel lymph node biopsy (SLNB) for endometrial, cervical, vulvar, or early ovarian carcinoma were enrolled. A total of 172 SLNs were excised, submerged in coupling gel, and scanned ex vivo using a 9 MHz linear probe. Results: A total of 172 SLNs underwent SWE (mean 2.7 nodes/patient). Endometrial primaries accounted for 58% of nodes, mostly retrieved by robotic-assisted surgery (71.8%). Node dimensions were significantly larger in malignant lesions for sonographic (long-axis: 13.02 ± 3.31 mm vs. 10.80 ± 3.28 mm; p = 0.002) and pathological long-axis measurements (11.45 ± 2.83 mm vs. 9.75 ± 2.61 mm; p = 0.004). Mean SWE velocities were similar between groups (1.381 ± 0.307 vs. 1.343 ± 0.236 m/s; p = 0.541). Histopathology identified metastases in 18% of SLNs, comprising macrometastases (7%), micrometastases (5%), and isolated tumour cells (6%). Conclusions: Although ex vivo SWE is rapid, reproducible, and integrates seamlessly into the sterile field, stiffness measurements alone lack sufficient discriminatory power for SLN staging in gynaecological cancers. Future research should focus on three-dimensional SWE, advanced radiomic analyses, and machine-learning algorithms to improve the detection of low-volume metastatic disease. Full article

Background/Objectives: Currently, no non-invasive detection method for endometrial cancer (EC) is recommended in clinical practice worldwide. This study aimed to evaluate the clinical value of detecting DNA methylation of CDO1 and CELF4 (CDO1m/CELF4m) in exfoliated cervical cells for the detection of EC in women with suspected endometrial lesions. Methods: A total of 2164 patients scheduled for hysteroscopic surgery due to suspected endometrial lesions at the Obstetrics and Gynecology Hospital of Fudan University between July 2023 and May 2024 were prospectively enrolled. Preoperative exfoliated cervical cells were collected for dual-gene methylation testing. Clinical data and endometrial thickness measured by transvaginal sonography (TVS) were recorded. Hysteroscopic histopathological diagnosis served as the gold standard to evaluate the performance of methylation testing alone and in combination with TVS. Results: This study included 2164 patients, comprising 33 EC cases, 31 cases of endometrial intraepithelial neoplasia (EIN), and 2100 cases of non-endometrial lesions, with mean ages of 51.7 ± 6.4, 49.5 ± 8.9, and 44.7 ± 9.8 years, respectively (p < 0.001). For EC detection, CDO1m/CELF4m positivity showed a sensitivity of 93.94% (95% CI: 79.77–99.26%), specificity of 96.7% (95% CI: 95.92–97.47%), positive predictive value (PPV) of 31.0% (95% CI: 25.96–36.53%), and negative predictive value (NPV) of 99.90% (95% CI: 99.63–99.98%). For EIN detection, the sensitivity was 83.87%, specificity 97.95%, PPV 37.68%, and NPV 99.76%. Combining TVS with DNA methylation detection further improved the sensitivity and NPV for both EC and EIN detection. Conclusions: DNA methylation detection in exfoliated cervical cells demonstrates high sensitivity and specificity for EC detection. The combination with TVS further enhances sensitivity and NPV, offering a simple and non-invasive triage strategy for patients with suspected endometrial lesions. This study was registered in China Clinical Trial Registry (ChiCTR2200055991) on 30 January 2023. Full article

Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates the SLN detection rates, perioperative outcomes, and 12-month oncologic outcomes oncologic results of retroperitoneal vNOTES mapping in presumed early-stage EC. Materials and Methods: This single-center retrospective cohort study analyzed consecutive patients undergoing retroperitoneal vNOTES staging (hysterectomy, BSO, and SLN mapping) for presumed EC between February 2023 and January 2024. Eligible patients had radiologically uterine-confined disease and were candidates for transvaginal surgery. Following cervical methylene blue injection, SLN mapping was executed via the retroperitoneal vNOTES route. Mapped and suspicious nodes were excised, with side-specific lymphadenectomy performed for failed mapping per algorithm. While perioperative outcomes were assessed for the full cohort, oncologic analyses (FIGO 2023 staging, nodal metastasis) were restricted to patients with confirmed carcinoma. Results: Of 98 patients (median age 54; BMI 31 kg/m²), final pathology confirmed carcinoma in 78 (73 endometrioid, 5 serous) and EIN in 20. Bilateral SLN mapping succeeded in 87.8% (86/98), necessitating side-specific lymphadenectomy in the remaining 12.2%. The obturator fossa was the predominant nodal basin (43.9%). Within the carcinoma cohort (n = 78), 57.7% were Grade 1 and 74.4% FIGO Stage I. Nodal metastases (FIGO IIIC1) were identified in 12.8% (10/78), all prompting adjuvant therapy. At a median follow-up of 12 months, no disease recurrences were observed. The complication rate was 6.1% (5.1% Clavien–Dindo ≥ III), with no conversions required. At 12-month follow-up, no recurrences were detected, though the absence of systematic lymphadenectomy precluded formal sensitivity analysis. Conclusions: Retroperitoneal vNOTES represents a feasible and safe strategy for SLN mapping in early-stage EC, demonstrating high bilateral detection with minimal morbidity. However, reliance on methylene blue and limited follow-up necessitate caution. Broader implementation requires validation through prospective, comparative trials utilizing indocyanine green and long-term oncologic surveillance. Full article

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary cancer syndrome significantly increasing the risk of colorectal cancer (CRC) and various extracolonic cancers, including endometrial, ovarian, and gastric cancers. LS results from germline pathogenic variants (GPVs) in DNA mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, and PMS2, leading to microsatellite instability (MSI). This review explores the multifaceted aspects of LS, covering clinical presentation, genetic underpinnings, and emerging therapeutic strategies. The discussion explores the importance of identifying at-risk individuals, facilitating personalized cancer surveillance and prevention strategies. Molecular insights into distinguishing between sporadic and LS-associated cancers are also examined, with a focus on somatic testing methods, including MSI and immunohistochemistry (IHC). The gynecological cancer risks, particularly those related to endometrial and ovarian malignancies, are addressed, underscoring the need for early detection and risk-reducing interventions. Recent advancements in the management of colorectal and other LS-related cancers are highlighted, with particular attention to the growing role of immunotherapy, including immune checkpoint inhibitors, and immunoprevention strategies. With ongoing advances in our understanding of LS, opportunities for earlier detection, more effective prevention, and innovative treatments continue to expand. This narrative review adopts a multidisciplinary approach to provide a comprehensive understanding of LS, from its genetic basis to current clinical and therapeutic practices, with the ultimate goal of improving patient outcomes and enhancing the quality of care. Full article

Background/Objectives: Endometrial hyperplasia (EH) is a pathology of the uterus, which is a pathological overgrowth of the endometrial glands associated with the risk of progression to endometrial cancer (EC). The purpose of this study was to conduct a retrospective comparative analysis of the medical and social characteristics of women with endometrial hyperplasia (EH) across two time periods (2016–2017 and 2023–2024) in Almaty, the largest city in Kazakhstan. Methods: A retrospective comparative analysis included 376 women (188 per period) with histologically confirmed EH treated in public and private healthcare facilities. Data were extracted from electronic medical systems (Damumed, Avicenna). Group differences were evaluated using the χ² test, Fisher’s exact test, and Mann–Whitney U test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated; significance was set at p < 0.05. Results: The proportion of postmenopausal women increased from 22.3% to 37.8% (OR: 2.11, 95% CI: 1.34–3.32, p < 0.001), and self-referrals to private clinics rose from 17.6% to 37.2% (OR: 2.79, 95% CI 1.73–4.49, p < 0.001). Women with higher education became more prevalent (from 26.1% to 43.6%, OR: 2.19, 95% CI: 1.42–3.39, p < 0.001), along with an increase in endocrine and metabolic disorders such as thyroid disease (from 4.8% to 12.2%, OR: 2.77, 95% CI: 1.25–6.16) and overweight status (from 51.6% to 65.4%, OR: 1.78, 95% CI: 1.17–2.69, p = 0.020). Asymptomatic cases were more frequently detected (from 18.6% to 28.2%, OR: 1.72, CI: 1.06–2.79, p = 0.028), and diagnostic approaches shifted from blind curettage (78.2% vs. 47.3%, OR: 0.25, CI: 0.16–0.39, p < 0.001) toward hysteroscopy with biopsy (from 21.3% to 53.7%, OR: 4.30, CI: 2.73–6.75, p < 0.001). Conclusions: Over seven years, the clinical and socio-demographic composition of women with EH in Almaty has changed toward older, more educated, and metabolically burdened populations, with broader access to minimally invasive diagnostic methods. The findings describe observable structural changes and risk group patterns, emphasizing the importance of prospective, registry-based, and molecularly oriented studies to refine clinical strategies for prevention and early detection. Full article