Search Results (2,449)

Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) has emerged as a major global etiology of chronic liver disease. However, the prognostic impact of MASLD in patients with non-B, non-C HCC (NBNC-HCC) following curative resection remains poorly defined. This study aimed to evaluate the prognostic significance of histologic SLD and MASLD-related components in this growing patient population. Methods: We retrospectively reviewed consecutive patients with NBNC-HCC receiving curative-intent hepatectomy between 2014 and 2023, excluding those with viral hepatitis or significant alcohol use. MASLD was defined as hepatic steatosis (≥5%) combined with at least one cardiometabolic risk factor (obesity, type 2 diabetes, dyslipidemia, or hypertension). Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards models were used to identify independent prognostic factors. Results: 169 (61.7%) patients fulfilled MASLD criteria. The MASLD group showed significantly better RFS (p = 0.039) and OS (p = 0.016). Notably, after multivariate adjustment, histologic SLD remained independently associated with reduced mortality (HR 0.55, 95% CI 0.32–0.93; p = 0.027), while MASLD status was attenuated. Subgroup analysis revealed that this survival benefit was most pronounced in non-cirrhotic patients (p = 0.027 for OS). Patients with MASLD also exhibited lower liver-related mortality (p = 0.028). Conclusions: Steatotic liver disease was independently associated with improved survival in NBNC-HCC patients undergoing curative hepatectomy, particularly in non-cirrhotic individuals. Given the increasing prevalence of MASLD, incorporating hepatic steatosis, metabolic components, and fibrosis status into risk stratification may help improve postoperative management in this distinct subgroup. Full article

Background and Objective: Transurethral resection of bladder tumor (TURBT) is the standard for non-muscle-invasive bladder cancer (NMIBC), yet recurrence rates remain high. This study evaluates the safety, tolerability, and efficacy of neoadjuvant intravesical mitomycin C (neoMMC) before TURBT in reducing recurrence and improving surgical outcomes. Methods: This randomized phase III trial enrolled patients with primary or recurrent NMIBC. Participants were randomized 1:1 to a neoadjuvant group receiving two instillations of MMC (day −14 and −7) before TURBT, or a control group undergoing standard TURBT without neoadjuvant treatment. The primary endpoint was 12-month recurrence-free survival (RFS). Secondary endpoints included surgical quality (complete resection, cauterization only, absence of residual tumor) and safety. Exploratory endpoints included histopathologic response and time to recurrence. Key Findings and Limitations: Among 95 patients (48 neoMMC, 47 controls), baseline characteristics were balanced. After a median follow-up of 19.4 months, recurrences occurred in 9 StA and 4 NeoA patients, with one progression to MIBC in the NeoA arm. RFS did not differ significantly between groups at 12 or 18 months. Neoadjuvant MMC was well tolerated, with only grade 1–2 AEs. Exploratory microbiota analyses suggested that neoadjuvant MMC modulated urinary microbial diversity and was associated with a microbiota profile more similar to that observed in non-recurrent patients. Limitations include single-center design and relatively short follow-up. Conclusions and Clinical Implications:Neoadjuvant intravesical MMC before TURBT was feasible and well tolerated in patients with NMIBC, with no unexpected safety signals. In this prematurely terminated and underpowered trial, no significant improvement in RFS was observed. Larger adequately powered studies are needed to clarify the oncologic efficacy of this approach. Full article

Radiomics involves the extraction of quantitative information from medical images and can offer valuable insights into the management of rectal cancer (RC). We aim to systematically review the current literature on radiomics’ role in the prediction of lymph nodes and distance metastases, local recurrence and survival outcomes in rectal cancer. Method: This systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and principles. We systematically searched PubMed, Cochrane, Google Scholar, and ResearchGate databases to identify the relevant articles. Result: After searching 3327 articles, only 50 articles were included after assessing the quality using a radiomics quality score (QRS) and finding a mean score of 14.74. Only eight studies used CT radiomics, with the rest based on MRI radiomics. Only three of the included studies are prospective, with the others being retrospective cohort studies and 14 having external validation. Most of the included studies concluded that radiomic models alone or combined models achieve better outcome predictions when compared with clinical and subjective analysis. Conclusions: Radiomics offers significant promise as a non-invasive tool for predicting lymph node status, distant metastasis (DM), recurrence, and survival outcomes in rectal cancer. There is a need for more robust prospective studies with cost benefit analysis for implementation into clinical practice. Full article

Objectives: Percutaneous Patent Foramen Ovale (PFO) closure has become a standard treatment for secondary prevention following cryptogenic stroke. This study aims to compare the long-term clinical outcomes and stroke recurrence rates between the Amplatzer PFO Occluder and other commercially available devices, including Occlutech, Cardiofix, and Biostar. Methods: This retrospective study included 130 consecutive patients who underwent percutaneous PFO closure due to PFO-related stroke. The participants were divided into two groups: the Amplatzer group (n = 90, 69%) and the Other Devices group. Primary endpoints were Major Adverse Cardiovascular Events (MACE) defined as stroke recurrence, new-onset atrial fibrillation (AF), and mortality during the follow-up period. Results: The average follow-up period was 2200 days (median 1739 days, interquartile range: 1062–2616 days). No statistically significant differences were observed between the groups regarding baseline characteristics such as age, hypertension, or diabetes. The Amplatzer and other device groups showed similar rates for MACE, atrial fibrillation, and stroke recurrence. Kaplan–Meier analysis demonstrated no significant difference in event-free survival between the groups. This study demonstrates that the Amplatzer PFO Occluder and other commercial devices provide comparable long-term safety and efficacy profiles in patients undergoing PFO closure for cryptogenic stroke. Regardless of the device type used, long-term stroke recurrence rates remain low in both groups. Full article

Objective: To characterize the frequency, timing, patterns of first distant metastasis, and post-metastatic survival in uterine sarcoma using population-based registry data. Methods: This study included all patients diagnosed with uterine sarcoma between 2000 and October 2025 in the regional cancer registry of Saxony-Anhalt, Germany. Patients with carcinosarcoma were excluded. Metastatic disease was classified as primary (present at diagnosis or ≤3 months) or metachronous (>3 months). Metastatic patterns were analyzed based on the first metastatic presentation only. Overall survival (OS), recurrence-free survival (RFS), and post-metastatic OS were estimated using Kaplan–Meier methods. RFS was defined as the interval from confirmed tumor-free status after primary therapy to first recurrence or death, and was restricted to patients who achieved tumor-free status (n = 114). Multivariable Cox regression analyses for OS and RFS were performed with administrative censoring at 5 years. Results: A total of 155 patients with uterine sarcoma were included. During follow-up, 54 patients (34.8%) were diagnosed with metastatic disease, of whom 30 (55.6%) presented with primary metastatic disease. Lung was the most frequent site of first metastasis, followed by bone, peritoneum, and liver; 43.4% of metastatic patients had multiple synchronous metastatic sites at first presentation. Median time to first metastasis was short, with several metastatic sites showing median values of zero months, reflecting the high proportion of primary metastatic disease. Median post-metastatic OS was 12 months. Advanced FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage and failure to achieve tumor-free status after primary therapy were independently associated with worse OS, whereas histologic subtype was not. Conclusions: In this population-based cohort, metastatic disease occurred in more than one-third of patients with uterine sarcoma and was frequently present at diagnosis. Lung metastases predominated as the first site of distant spread, and post-metastatic survival was poor. These findings underscore the importance of comprehensive staging at diagnosis and highlight the aggressive metastatic behavior of uterine sarcoma in real-world practice. Full article

Background/Objectives: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is increasingly being used to avoid abdominal incisions; however, its mid-term oncological safety in endometrial cancer remains unclear. Methods: This single-center retrospective cohort study included patients with International Federation of Gynecology and Obstetrics (FIGO) clinical stage IA endometrioid endometrial carcinoma undergoing simple hysterectomy between January 2014 and December 2023. Patients were treated with either total laparoscopic hysterectomy (TLH) or vNOTES. Patients who underwent lymph node assessment were excluded. Follow-up assessed mid-term oncological outcomes. Recurrence-free survival (RFS) was evaluated using the Kaplan–Meier method and compared between the groups, and Cox proportional hazards models were used to identify prognostic factors for RFS. Results: In total, 130 patients were included: 109 underwent TLH and 21 vNOTES. The median follow-up period was 48 and 33 months in the TLH and vNOTES groups, respectively. Postoperative adjuvant therapy was more frequent in the vNOTES group. The operative time was significantly shorter with vNOTES. Postoperative complications were low and similar between the groups. The 3-year RFS was 92.8% and 94.4% in the TLH and vNOTES groups, respectively, without a significant difference (p = 0.874). Lymphovascular space invasion was significantly associated with worse RFS, whereas surgical approach was not significantly associated with RFS. Conclusions: No statistically significant difference in mid-term RFS was observed between vNOTES hysterectomy and conventional TLH in this highly selected low-risk cohort. However, the study was underpowered and subject to residual confounding; therefore, these findings should be considered preliminary and hypothesis-generating. Full article

Background/Objectives: Malignant PEComa is a rare sarcoma subtype and usually represents PEComa-NOS (not otherwise specified), one of the several entities of the PEComa family. Surgery is the primary treatment for localized disease; chemotherapy is used mainly for metastatic or unresectable cases. Radiotherapy (RT) may be considered in selected cases; however, its role remains unclear due to the rarity of the disease and limited radiotherapy-specific studies. Methods: This is a descriptive literature review of a limited number of reports on RT use in PEComa. Descriptive statistics were used to summarize reported case characteristics and outcomes. Results: We identified 28 publications reporting 33 cases. In neoadjuvant settings, there was a significant local response to RT in one case. In other neoadjuvant cases, although quantitative response assessments were not reported, most showed no recurrence during follow-up, with the longest follow-up at 34 months, suggesting that a possible benefit in local disease control may exist. In the adjuvant setting, some reports described prolonged disease-free survival following RT, though the lack of direct comparisons between surgery with versus without RT and heterogeneous follow-up periods limit definitive conclusions. In selected metastatic cases, palliative RT achieved notable local responses, potentially contributing to durable local control. Conclusions: In conclusion, although the only available data on RT in PEComas come from case studies with overall heterogeneous management approaches, RT has shown some potential as a therapeutic option across neoadjuvant, adjuvant, and palliative settings, warranting further dedicated clinical studies. Full article

Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) into a manageable disease, and discontinuation has become a feasible goal for many patients. However, molecular relapse after TKI cessation remains a challenge. This study investigated factors influencing molecular relapse-free survival (MRFS) in a real-world cohort of CML patients undergoing TKI discontinuation, focusing on clinical, molecular, and immune-related variables. Traditional prognostic tools, such as the Sokal score, showed limited capacity to predict relapse risk in this context. Instead, total treatment duration and depth of molecular response emerged as critical predictors, with longer therapy and deeper remission associated with improved outcomes. A key novel finding was the prognostic relevance of cytokine profiles, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). These cytokines were strong predictors of relapse in a decision tree model that achieved high specificity and positive predictive value in an independent validation cohort. Notably, lower IL-6 and MCP-1 levels were associated with increased relapse risk, suggesting reduced immune surveillance may contribute to recurrence. Integrating cytokine signatures with molecular markers improved prognostic accuracy, supporting immune biomarkers as complements to established clinical parameters. These findings underscore the complexity of relapse mechanisms and the need for individualized risk assessment when considering TKI discontinuation. Full article

Objective: The optimal adjuvant therapy for intermediate-risk endometrial cancer remains controversial. Although radiotherapy is commonly used in Western countries, chemotherapy is preferred in Japan; however, its real-world outcomes remain limited. This study evaluated the survival and safety outcomes of three-cycle adjuvant chemotherapy in patients with intermediate-risk endometrial cancer. Methods: We retrospectively analyzed patients who underwent primary surgery for endometrial cancer at a university hospital between 2008 and 2019. Low- and intermediate-risk patients defined by the 2013 Japan Society of Gynecologic Oncology recurrence risk classification were included. Intermediate-risk patients were classified as receiving chemotherapy (Int-Chemo+) or not (Int-Chemo−). The primary endpoint was disease-free survival (DFS); secondary endpoints included cancer-specific survival (CSS), adverse events, and treatment completion. Results: Among 232 patients, 161 were low-risk and 71 intermediate-risk; 49 intermediate-risk patients received platinum-based combination chemotherapy. The 5-year DFS rates were 92.8% (95% CI, 88.6–96.9) in the low-risk group, 89.4% (95% CI, 80.7–98.2) in the Int-Chemo+ group, and 73.5% (95% CI, 53.5–93.6) in the Int-Chemo− group (log-rank p = 0.005). DFS differed between the Int-Chemo+ and Int-Chemo− groups (HR 0.232, 95% CI 0.062–0.867), whereas the DFS outcomes of the Int-Chemo+ group were numerically similar to those of the low-risk group. CSS did not differ significantly among groups (p = 0.052). Treatment completion was 93.8%, and grade ≥ 3 adverse events were mainly hematologic, without severe late toxicities. Conclusions: Three cycles of adjuvant platinum-based combination chemotherapy for intermediate-risk patients may be associated with improved DFS, while maintaining a high treatment completion rate and manageable toxicity. Full article

Background: Clinical target volume (CTV) delineation in glioblastoma remains debated, particularly in the era of modern chemoradiation and image-guided radiotherapy. Whether reduced CTV margins can preserve oncological outcomes without increasing marginal or out-of-field failures remains uncertain. We evaluated the association of the gross tumor volume (GTV)-to-CTV margin with survival, patterns of failure, and its interaction with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Materials and Methods: We retrospectively analyzed a single-center cohort of patients with glioblastoma treated with conventionally fractionated chemoradiation (58–60 Gy in 29–33 fractions). Patients were categorized into two predefined margin groups: <1.5 cm and 1.5 cm. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and patterns of failure. Survival was assessed using Kaplan–Meier estimates and Cox regression, including an interaction term with MGMT status. Results: Among 102 eligible patients, 95 were included in the margin-based OS analysis. Reduced margins (<1.5 cm; applied range 1.0–1.4 cm) were not associated with worse OS, either overall or within MGMT subgroups. No significant differences were observed in PFS or recurrence patterns, with overlapping distributions and no increase in marginal or out-of-field recurrences. MGMT methylation and gross total resection were independently associated with improved survival, while no statistically significant interaction between margin and MGMT status was detected. Conclusions: In this retrospective exploratory cohort, reduced GTV-to-CTV margins were not associated with a clear signal of worse survival or less favorable recurrence patterns. These findings are consistent with the oncological adequacy of margins around 15 mm and justify cautious prospective evaluation of whether further reduction can be achieved safely, including formal assessment of toxicity, neurocognitive outcomes, and quality of life. Full article

Ubiquitin-specific protease 13 (USP13) is a deubiquitinating enzyme that stabilizes phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a well-established tumor suppressor involved in PI3K/AKT signaling. This study aimed to evaluate the relationship between USP13 immunohistochemical staining intensity and clinicopathological factors associated with prostate cancer progression. USP13 staining was scored as grade 0 (negative), 1 (weak), 2 (moderate), or 3 (strong) in 242 prostate cancer tissues and 22 adjacent non-neoplastic control tissues. Higher USP13 grades were exhibited by adjacent non-neoplastic tissues than prostate carcinoma. In comparison, lower USP13 grades were observed in 88.6% of the neoplastic regions (p < 0.001). No differences in PSA level, Gleason’s score, disease stage, involvement of either the seminal vesicle or lymph nodes, surgical margin positivity, biochemical or clinical recurrence rates, or overall survival statistics were found. Cox proportional hazards modeling showed no significant association between USP13 expression and biochemical recurrence-free survival or overall survival. Kaplan–Meier analysis demonstrated no statistically significant differences in survival outcomes according to USP13 expression, although a descriptive trend was observed. USP13 immunohistochemical staining distinguished malignant prostate tissue from adjacent non-neoplastic tissue in tissue microarrays. However, USP13 expression was not independently associated with pathological aggressiveness or survival outcomes in this cohort. Full article

Inter-individual variability in outcomes following radiotherapy-based treatment remains a major challenge in head and neck squamous cell carcinoma (HNSCC). Osteopontin (OPN) and its receptor CD44 are key mediators of tumor progression, hypoxia-related treatment resistance, and metastatic dissemination. In this exploratory, hypothesis-generating study, we investigated selected functional polymorphisms in OPN (SPP1) and CD44 genes, together with pretreatment plasma OPN levels, in relation to overall survival (OS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MFS) in 242 HNSCC patients treated with curative-intent radiotherapy alone (RT) or combined with chemotherapy (RT + CT). In individual multivariable models, the OPN rs11730582 C and CD44 rs13347 T variants were associated with improved survival outcomes, while elevated OPN levels correlated with shorter OS. In full multivariable models, rs11730582 C and high OPN levels remained independent predictors of OS in the entire cohort. In the RT + CT subgroup, high OPN independently predicted worse OS, whereas rs13347 T was associated with better MFS. In the RT subset, rs11730582 CC independently predicted longer OS. These findings suggest that both germline variability within the OPN-CD44 signaling axis and circulating OPN levels are associated with treatment outcomes in HNSCC patients receiving radiotherapy-based regimens. Given the exploratory design, further validation in independent cohorts is warranted. Full article

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: Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly aggressive pediatric central nervous system (CNS) malignancies. AT/RT of the lateral ventricle is an exceptionally rare subgroup, with only 11 reported cases. SMARCB1 inactivation is the primary molecular feature of AT/RT. Current consensus is to classify AT/RT based on methylation and molecular profiles into the following subgroups: AT/RT-TYR, AT/RT-SHH, AT/RT-MYC, and a potentially distinct SMARCA4-deficient subtype. AT/RT-MYC exhibits high levels of CD8⁺ tumor-infiltrating lymphocytes, indicating immunogenic potential. Case presentation: We report three pediatric cases presenting with intracranial hypertension and seizures. Diagnosis was confirmed via histopathology and molecular profiling. Interventions included gross total resection, chemotherapy, radiotherapy, and combined immune checkpoint inhibitors (pembrolizumab and ipilimumab). Outcomes varied from rapid progression to 3-year recurrence-free survival. A cohort of 14 pediatric patients with lateral ventricle AT/RT, comprising 3 institutional cases and 11 cases identified from the PubMed database, was evaluated through a narrative synthesis. Conclusions: These advancements highlight the crucial role of molecular subtyping in tailoring personalized treatments, including epigenetic modifiers and immune-based regimens. However, clinical validation is essential to establish standardized protocols. Integrating genomic, epigenetic, and immune microenvironment profiling may enhance risk assessment and treatment precision, ultimately improving survival and quality of life in pediatric patients. Full article