Search Results (3,283)

Background/Objectives: Total neoadjuvant therapy (TnT) has emerged as a treatment option for locally advanced rectal cancer. Few studies have evaluated specifically the use of chemotherapy and short-course radiation therapy (SCRT) in obtaining a complete clinical response (cCR) or near-complete clinical response (nCR) and offering non-operative management (NOM). This phase II study sequences FOLFOX followed by SCRT with the primary aim of evaluating the rate of cCR or nCR. Methods: Treatment-naïve adults with non-metastatic clinical T2-3N0 or T1-3 with N1-2a rectal adenocarcinoma deemed candidates for total mesorectal excision (TME) were eligible for this open-label, single-arm clinical trial. This trial evaluated TnT with 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) followed by SCRT. The primary endpoint was the rate of cCR or nCR. Those with cCR or nCR after TnT were offered NOM and close surveillance; all others underwent TME. Secondary endpoints included 1-year disease-free survival (DFS), overall survival (OS), and R0 surgical resection rate. Results: Twelve patients of a planned 40 were enrolled with a median follow-up duration of 4.1 years. The study was closed early after results of the OPRA trial suggested a benefit of sequencing radiation prior to chemotherapy when seeking organ preservation. Four of the twelve patients (33%, 95% CI = (9.9%, 65.1%)) achieved cCR or nCR after TnT and underwent NOM; one patient had local regrowth 5.5 months after the completion of TnT and underwent TME. All four were free of disease at time of analysis. The 1-year DFS was 100%. The median OS was not reached. All surgical resections were R0 with no local recurrence after TME. Conclusions: This paper suggests that TnT with FOLFOX followed by SCRT is a safe and effective approach for treating locally advanced rectal cancer. This approach can be considered in select patients. The 33% of patients offered NOM is lower than the published 74% in OPRA, however, suggesting that chemotherapy followed by SCRT may not be the most optimal approach if organ preservation is the primary treatment aim. Full article

Background and Objectives: Intraperitoneal onlay mesh (IPOM) reduces ventral/incisional hernia recurrence but raises concern for adhesions and infection, particularly when the operative field is not strictly clean. We aimed to determine how contamination severity modulates the peritoneal response to intraperitoneal polypropylene mesh. Materials and Methods: In a prospective, randomized, blinded rat study, 60 male Wistar rats were allocated to three groups (n = 20/group) and evaluated at postoperative day (POD) 4 and POD 8 (n = 10/timepoint): A, clean mesh placement; B, small-bowel resection with end-to-end anastomosis without spillage (“potentially septic”); and C, mesh placement followed by intraperitoneal inoculation with Escherichia coli and Staphylococcus aureus (“controlled contamination”). The primary outcome was adhesion severity (Van der Ham scale, 0–3). Secondary outcomes included semi-quantitative histological scores (0–4) for neutrophil infiltration, fibroblast proliferation, neoangiogenesis, and collagen deposition. Prespecified non-parametric analyses were applied. Results: All animals completed follow-up; no pre-sacrifice deaths occurred. Adhesion severity showed no statistically significant differences between Groups A and B at either timepoint (mean POD4: 0.3 vs. 0.6; POD8: 0.4 vs. 0.8; p > 0.05). In contrast, Group C demonstrated markedly higher adhesion scores (mean POD4: 2.3; POD8: 2.4; both p < 0.001 vs. Groups A and B), with a substantially greater proportion of grade 2–3 adhesions. Histological parameters paralleled these findings: at both POD4 and POD8, Group C showed significantly higher neutrophil, fibroblast, neoangiogenesis, and collagen scores compared with Groups A and B (all p < 0.001). No statistically significant within-group temporal differences were observed between POD4 and POD8. Conclusions: In this experimental model, intraperitoneal polypropylene mesh demonstrated similar early biological response patterns in clean and controlled contamination settings, whereas established intra-abdominal sepsis was associated with a marked escalation of inflammation, fibroproliferation, and adhesion formation. These findings suggest that selective use of synthetic intraperitoneal mesh may be considered when contamination is controlled, while caution is warranted in frankly septic environments. Full article

Breast-conserving therapy, consisting of lumpectomy followed by adjuvant radiotherapy, is the standard of care for early-stage breast cancer, providing oncologic outcomes equivalent to mastectomy while preserving breast anatomy and quality of life. Radiotherapy remains a cornerstone of treatment across disease stages, significantly reducing local recurrence rates and improving long-term survival. Advances in radiotherapy techniques—including conventional fractionation, hypofractionation, tumor-bed boost delivery, and regional nodal irradiation—have optimized oncologic efficacy while inducing a broad spectrum of time-dependent morphological changes in breast tissue. Accurate imaging surveillance is therefore essential to distinguish expected post-radiotherapy changes from tumor recurrence and to avoid unnecessary diagnostic or therapeutic interventions. This review provides a comprehensive overview of contemporary breast radiotherapy protocols, their impact on post-treatment imaging appearances, and current recommendations for imaging surveillance. Characteristic findings across mammography, ultrasound, magnetic resonance imaging, and nuclear medicine modalities are discussed, with emphasis on their temporal evolution from acute inflammatory changes to chronic fibrosis, fat necrosis, and architectural distortion. Recognition of these imaging patterns, together with integration of radiotherapy-related parameters into image interpretation, is crucial for accurate diagnosis, early detection of recurrence, and informed clinical management of breast cancer survivors. Full article

Background: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis primarily affecting small and medium-sized vessels. The typical presentation commonly includes upper and/or lower respiratory tract and renal involvement. GPA has a particularly strong association with proteinase-3 (PR3) ANCA. Though well defined, GPA may be clinically difficult to recognize, particularly in early disease. Initial presentations may include nonspecific symptoms, including but not limited to fatigue, fever, and sinus congestion or sinusitis, which may be mistaken for infection. Though initial ANCA testing is useful, it is not definitive as early stages of disease may be negative, thus delaying diagnosis; Clinical Significance: This case highlights the importance of including GPA in the differential diagnosis of patients with unremitting upper or lower respiratory and constitutional symptoms despite negative ANCA testing. Though atypical, GPA cases may lack renal involvement and even have negative ANCA serologies, leading to a delay in diagnosis and increased morbidity. ANCA positivity can be as low as 60% in limited GPA cases, and less than 20% of individuals have renal involvement at presentation. If GPA suspicion is high, repeat testing and biopsy are warranted; Case Presentation: A woman in her 50s initially presented to the emergency department with recurrent/persistent fever with nonspecific sinus symptoms that remained unresolved despite multiple outpatient treatments and tests. Infectious work-up was negative. She was found to have multiple pulmonary nodules on various scans. Initial testing on admission was unremarkable or nondiagnostic, including anti-neutrophil cytoplasmic antibody (ANCA) serologies. The patient’s hospital course was complicated by acute hypoxic respiratory failure with distributive shock during bronchoscopy. Repeat serological testing was positive for PR3-ANCA, and lung biopsy demonstrated necrotizing granulomatous vasculitis consistent with a diagnosis of granulomatosis with polyangiitis (GPA). The patient demonstrated clinical improvement with avacopan, glucocorticoids, and rituximab; Conclusions: The diagnosis of GPA should be suspected in all patients with nonspecific constitutional symptoms along with clinical evidence of upper/lower respiratory tract involvement, regardless of renal function. Physicians with a strong suspicion of an autoimmune disease, such as GPA, should utilize a thorough clinical history, physical exam, and other labs in the setting of a negative autoimmune marker and/or negative imaging. Clinical judgment is required to not rule out GPA despite a negative workup when other more serious causes have been excluded, as the diagnosis may be life-threatening. Full article

Background/Objectives: Squamous cell metaplastic breast carcinoma (SCMBC) is a rare and aggressive breast cancer subtype with limited imaging and prognostic data. This study aimed to characterize the multimodal imaging features, clinicopathological profiles, and prognostic outcomes of SCMBC in a single-center cohort. Methods: We retrospectively analyzed 22 patients with histopathologically confirmed SCMBC treated between January 2012 and May 2025. Clinicopathological profiles, multimodal imaging features, and prognostic outcomes were collected and evaluated. Results: All patients were female (median age 64.5 years; range, 34–82). The majority (59.1%) presented with clinical stage II disease. Axillary lymph node metastasis was present in eight (36.4%) patients at diagnosis, with one case of distant lung metastasis. The mean tumor diameter was 4.24 cm (range, 2.1–11.8). MRI findings (n = 13) included heterogeneous internal structure, a low mean apparent diffusion coefficient (ADC) value of 0.98 × 10⁻³ mm²/s, and frequent necrosis (92.3%). Pathologically, 54.5% of tumors were high-grade, and 81.8% exhibited a triple-negative phenotype. After a median follow-up of 34 months, the 5-year overall survival (OS) rate was 64.3%, while the 3-year disease-free survival (DFS) rate was 42.1%. The recurrence/metastasis rate was 22.7% (5/22), and all five deaths occurred in this subgroup. Conclusions: SCMBC is characterized by suggestive multimodal imaging features, a predominant triple-negative phenotype, and a high risk of early recurrence. Given the exploratory nature of this single-center study with a limited sample size, these findings require validation in larger, prospective cohorts. Early radiological identification and aggressive personalized treatment strategies may improve outcomes for patients with this aggressive disease. Full article

Background/Objectives: High-risk prostate cancer patients undergoing radical prostatectomy remain at significant risk of biochemical recurrence and metastasis. Immediate adjuvant external beam radiotherapy (EBRT) has been proposed to improve outcomes, but its role compared to observation remains debated due to potential toxicity and uncertain overall survival benefit. To evaluate the efficacy and safety of immediate adjuvant EBRT versus observation following radical prostatectomy in men with high-risk prostate cancer. Methods: A meta-analysis was conducted according to PRISMA guidelines. We sought to include both randomized controlled trials (RCTs) and observational studies published between 2005 and 2025; however, no observational studies meeting the predefined criteria were identified. Therefore, only RCTs comparing immediate adjuvant EBRT with observation in patients with adverse pathological features and undetectable postoperative PSA were included. Primary outcomes were biochemical recurrence-free survival (BCR-FS), metastasis-free survival (MFS), and overall survival (OS). Secondary outcomes included toxicity and quality of life (QoL). Data were pooled using Mantel–Haenszel and inverse variance methods, and heterogeneity was assessed with I² statistics. Results: Four RCTs (n = 1987) met the inclusion criteria. Adjuvant EBRT significantly improved progression-free survival (PFS) (HR = 0.38; 95% CI: 0.20–0.74; p = 0.004) and metastasis-free survival (HR = 0.70; 95% CI: 0.54–0.92; p = 0.01). However, OS benefit was not statistically significant (HR = 0.88; 95% CI: 0.59–1.32; p = 0.55). Heterogeneity was substantial for some outcomes (I² up to 71%). Adjuvant EBRT was associated with higher genitourinary and gastrointestinal toxicity compared to observation. Conclusions: Immediate adjuvant EBRT after radical prostatectomy improves PFS and MFS in high-risk prostate cancer but does not confer a clear OS advantage. Treatment decisions should be individualized, balancing disease-control benefits against toxicity risks. Observation with early salvage RT remains a reasonable alternative in selected patients. Full article

Background/Objectives: Ovarian function suppression (OFS) is part of endocrine therapy treatment for high-risk premenopausal women with hormone receptor-positive (HR+) breast cancer (BC). Incomplete OFS may occur and compromise treatment efficacy. Methods: We conducted a retrospective single-center cohort study of premenopausal patients with HR + BC treated with OFS therapy at the Centre des maladies du sein (CMS) of the CHU de Québec (Québec, Canada). Ovarian function suppression failure was defined as either biochemical failure (estradiol (E2) levels within the premenopausal range according to local immunoassays used) or clinical failure (return of menstrual bleeding). Patients’ characteristics, treatment specifics and side effects, timing and type of OFS failure, recurrence, and mortality were analyzed. Results: Among 208 included patients, 17 (8.2%) experienced at least one episode of OFS failure during a median follow-up of 62.6 months. Most failures occurred early, with 76.2% occurring within the first year of treatment. No significant differences were observed between patients with and without OFS failure regarding age, body mass index (BMI), or prior chemotherapy exposure. Patients with OFS failure had a significantly younger age at first pregnancy and higher rates of active smoking. No BC recurrence or death occurred among patients with OFS failure. Treatment-related side effects were common, and 23.0% of OFS regimens were discontinued due to adverse effects. Conclusions: In this study, OFS failure occurred in fewer than 10% of premenopausal patients. Younger age at first pregnancy and active smoking may be associated with OFS failure, but further data are needed to validate these exploratory associations. These findings reinforce the need for larger prospective studies to better assess OFS failure and develop standardized monitoring strategies to optimize treatment efficacy. Full article

Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI. Full article

Non-muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates and necessitates lifelong cystoscopic surveillance, underscoring the need for minimally invasive biomarkers to improve early detection and risk stratification. Therefore, this study aimed to investigate the role of trimethylamine-N-oxide (TMAO) and its precursors as diagnostic biomarkers for NMIBC. A total of 50 male patients with NMIBC (25 pTa and 25 pT1) were included in this study. Additionally, 52 age-matched healthy individuals were included as controls. Serum TMAO and its dietary precursors were quantified using liquid chromatography–tandem mass spectrometry. Group differences were analyzed using nonparametric tests, associations were assessed using Spearman’s correlation, and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Multivariate logistic regression was performed to identify independent predictors, and a composite risk score was generated. Serum TMAO, carnitine, and choline levels were significantly higher in patients with NMIBC than in controls (p ≤ 0.0001), whereas betaine showed a nonsignificant trend toward higher levels (p ≥ 0.05). The pathological stage (pTa vs. pT1) showed the strongest correlation with TMAO levels. The ROC analysis revealed that TMAO had the highest individual diagnostic accuracy (area under the curve [AUC] = 0.875, 95% confidence interval [CI] 0.812–0.939), whereas carnitine and choline provided complementary diagnostic performance. In multivariate models, TMAO, carnitine, and choline remained independent predictors of NMIBC (p ≤ 0.0001). A composite risk score integrating all four metabolites demonstrated excellent discriminatory capacity (AUC = 0.958, 95% CI 0.926–0.991). The TMAO metabolic axis can be used as a minimally invasive biomarker panel for NMIBC. Further large, prospective, multicenter studies integrating metabolomic and microbiome profiling are needed to validate the findings. Full article

Stress fractures (SFs) are a common overuse injury in athletes and represent the severe end of the bone stress injury (BSI) continuum. They result from repetitive mechanical loading exceeding the bone’s capacity for adaptation and are associated with impaired performance, prolonged time away from sport, and risk of recurrence if not appropriately managed. This narrative review provides a clinically oriented synthesis of current evidence on the epidemiology, pathophysiology, risk factors, diagnosis, management, and prevention of SFs in athletes. Particular emphasis is placed on modifiable contributors, including training load errors, neuromuscular fatigue, and low energy availability within the framework of Relative Energy Deficiency in Sport (RED-S). Diagnostic evaluation is discussed using a stepwise clinical approach integrating history, physical examination, targeted laboratory assessment, and imaging, with magnetic resonance imaging (MRI) as the reference standard for early detection and severity grading. Management is presented through a risk-based framework combining MRI severity and anatomical site classification to guide treatment decisions and return-to-sport pathways. While most low-risk SFs respond to conservative strategies, high-risk lesions require closer monitoring and, in selected cases, early surgical consideration. This review proposes a practical clinical framework to support decision-making in athletes with suspected or confirmed SFs, aiming to improve early diagnosis, optimize management, and reduce recurrence risk in sports medicine practice. Full article

Introduction: Non-muscle-invasive bladder cancer (NMIBC) represents approximately 78% of newly diagnosed bladder cancers and is characterized by high recurrence rates and variable progression risk. While transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains standard management, optimal treatment of high-risk and Bacillus Calmette-Guerin (BCG)-unresponsive disease remains controversial. Radiotherapy (RT), particularly in combination with chemotherapy, has been explored as a bladder-preserving alternative. Material and Methods: We conducted a narrative review of published literature evaluating the role of definitive RT in high-risk NMIBC, with emphasis on T1 disease. Retrospective series, prospective trials, meta-analyses, and contemporary guideline recommendations were examined. For each included study, we extracted data on the extent of TURBT (maximal vs. incomplete/non-specified), use and type of concurrent chemotherapy, radiotherapy technique (3D-conformal, IMRT, or proton), treatment volume (bladder only vs. whole pelvis), and dose/fractionation schedule. Results: Early studies evaluating RT alone demonstrated modest complete response rates. More recent approaches incorporating maximal TURBT followed by concurrent chemoradiotherapy report improved outcomes, with complete response rates of approximately 80–88% and 5-year overall survival comparable to surgical series. The phase II NRG/RTOG 0926 trial in recurrent high-risk T1 disease after intravesical therapy failure demonstrated an 81% complete response rate and favorable bladder preservation outcomes. Meta-analytic data suggest 5-year recurrence-free survival around 54% and overall survival near 70%, although evidence remains limited and largely non-randomized. Advances in image-guided and hypofractionated RT may further improve therapeutic outcomes while limiting toxicity. Conclusions: while definitive chemoradiotherapy is a promising option for selected patients, it remains investigational and should be considered only in those who are unfit for or decline radical cystectomy. Prospective randomized studies are needed to better define its role in contemporary management. Full article

Background: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and remains a major health concern due to its high recurrence and mortality rates. Recent studies suggest that anesthetic agents, including ketamine, may have direct effects on cancer cell viability and apoptosis. Objective: This study aimed to investigate the in vitro effects of ketamine on the HT-29 human colorectal adenocarcinoma cell line, focusing on its cytotoxic and pro-apoptotic potential. Material and Methods: HT-29 cells were treated with ketamine for 24 h. Cell viability was evaluated using the MTT assay. Apoptosis rates were determined by flow cytometry with Annexin V-FITC/7-AAD staining. Furthermore, quantitative PCR (qPCR) was performed to assess the expression levels of key genes associated with proliferation and apoptosis. GeneQuery™ Human Basal Cell Carcinoma qPCR Array Kit (GQH-BCC-GK015-C) was used for qPCR analysıs. Molecular docking simulations were performed to investigate the potential molecular interactions between ketamine and three target proteins: the N-methyl-D-aspartate (NMDA) receptor, epidermal growth factor receptor (EGFR), and casein kinase 1 delta (CSNK1D). To ensure robustness of predictions, two independent docking methods were employed. Results: Ketamine significantly reduced cell viability in a dose-dependent manner, with an IC₅₀ value of approximately 1.05 µM. Flow cytometry analysis demonstrated a marked increase in early apoptosis (23.9%) in treated cells. These findings suggest that ketamine exhibits potential anti-proliferative and pro-apoptotic effects on HT-29 colorectal cancer cells. Conclusions: These findings suggest that ketamine exhibits potential anti-proliferative and pro-apoptotic effects on HT-29 colorectal cancer cells in vitro. Further studies are warranted to elucidate the underlying molecular mechanisms and potential clinical implications. Full article

Background: Vitamin D is a secosteroid that exerts immunomodulatory and anti-proliferative effects through the vitamin D receptor (VDR). Because HER2-targeted therapies substantially improve prognosis in HER2-positive breast cancer and introduces a new mechanism of immunotherapy, we hypothesized that successful correction of vitamin D deficiency would be associated with improved disease-free survival (DFS) in patients treated with curative intent. Methods: We performed a retrospective interventional cohort study of patients with early-stage HER2-positive breast cancer treated at Cancer Treatment Centers of America Midwestern Regional Medical Center from 2008 to 2014. Eligible patients had baseline vitamin D deficiency (25-hydroxyvitamin D or D25 < 30 ng/mL), received trastuzumab-based therapy, and had ≥12 months follow-up. Patients received vitamin D3 supplementation (typically 2000–10,000 IU/day) with doses adjusted based on D25 level follow-up. Responders were defined as having achieved a mean D25 ≥ 30 ng/mL during the first year; non-responders remained <30 ng/mL DFS was analyzed using Kaplan–Meier and Cox models. Results: Of 196 patients, 129 (65.8%) were vitamin D-deficient at baseline. Among these, 76 (60.3%) achieved repletion while 50 (39.7%) remained deficient. Three did not have D25 follow-up obtained. Thirty-one DFS events occurred but no deaths. Responders demonstrated numerically improved outcomes (3-year DFS 90% vs. 85%). Non-responders had a 1.7-fold higher hazard of recurrence, and those who achieved the highest D25 levels (>50 ng/mL) had the most favorable DFS trends, suggesting a dose response. Conclusions: Failure to correct a vitamin D deficiency was associated with a 1.7-fold higher recurrence risk, although the relationship did not achieve statistical significance. A similar effect size was reported in another retrospective cohort of HER2-positive breast cancer that did achieve statistical significance, and a doubling of pCR rates was seen in two recently completed RCTs in 2025, with benefits particularly seen in the triple-negative and HER2-positive subtypes. Prospective trials evaluating optimized vitamin D repletion in HER2-positive breast cancer are warranted. Full article

Background: Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic adjuvant potential of selected essential oil components against clinically relevant respiratory bacteria and to determine whether planktonic synergistic interactions translate into early-stage antibiofilm efficacy. Thymol, eugenol, trans-cinnamaldehyde, and terpinen-4-ol were tested against Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. Methods: Minimum inhibitory concentrations were determined by broth microdilution. Synergistic interactions with clinically relevant antibiotics were assessed using the checkerboard method and fractional inhibitory concentration index (FICI) analysis. Selected combinations were further evaluated in a 6 h crystal violet-based early-stage biofilm model. Gram-positive strains generally exhibited higher susceptibility to the tested components than Gram-negative bacteria. Results: Synergistic interactions (FICI ≤ 0.5) were most frequently observed between β-lactam antibiotics and phenolic components, particularly thymol and trans-cinnamaldehyde. Strong synergy was detected for vancomycin-eugenol against MRSA and for amoxicillin/clavulanic acid–cinnamaldehyde against M. catarrhalis. Importantly, synergistic combinations translated into significantly enhanced inhibition of early biofilm formation, increasing inhibition rates by 15–40% compared to antibiotic monotherapy (p < 0.05). Selected essential oil components enhanced the antibacterial activity of clinically relevant antibiotics and effectively potentiated early-stage biofilm inhibition. Conclusions: These findings support further investigation of phytochemical-antibiotic combinations as potential adjunct strategies in respiratory infection management. Full article

Background: POLE-mutated endometrial carcinomas are associated with exceptionally favorable outcomes, forming the basis for treatment de-escalation in early-stage disease. Nevertheless, rare adverse clinical courses have been reported. This study describes an unusual case of late metastatic recurrence in a POLE-mutated tumor and provides a review of similar cases in the literature. Methods: We present a detailed clinical, radiological, pathological, and molecular description of a patient who developed metastatic recurrence 16 years after initial surgery. A systematic literature search was conducted to identify reports of recurrence, progression, or cancer-related death in POLE-mutated endometrial carcinoma, with extraction of recurrence patterns, genomic features, treatment, and outcomes. Results: The patient experienced sequential pulmonary, cerebral, and leptomeningeal metastases despite harboring a canonical POLE hotspot mutation, proficient mismatch repair status, wild-type TP53, no additional known driver mutation beyond PTEN alterations. The literature review identified a small number of similarly adverse cases. Reported recurrences were heterogeneous, though distant and occasionally central nervous system involvement were noted. Conclusions: While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients. Full article