Search Results (3,321)

Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

Background: Patient survival after liver transplantation is lower in donor–recipient race mismatched patients for indications other than primary sclerosing cholangitis. Objectives: To determine if survival is lower after liver transplantation in donor–recipient race mismatched recipients with primary sclerosing cholangitis. Methods: The Organ Procurement and Transplantation Network database was analyzed for deceased donor adult liver transplant recipients with primary sclerosing cholangitis. Graft and patient survival by donor–recipient race were estimated using Kaplan–Meier survival method and compared using the log-rank test. Multivariable analysis was performed using Cox regression. Results: From 2002 to 2018, 5-year patient survival in White (n = 2223) and Black recipients (n = 491), was 89.8% and 87.1%, respectively. Five-year patient survival for the donor–recipient pairs, White–White (n = 1622), Black–Black (n = 110), Black–White (n = 335), and White–Black (n = 314) was 90.8%, 91.1%, 87.1%, and 86.0%, respectively, p = 0.026. In multivariable analysis, 5-year patient mortality was higher in Black recipients of White donors [HR 1.69, 95% CI 1.16, 2.45], compared to White recipients of White donors. Conclusions: Five-year patient mortality after deceased donor liver transplantation for primary sclerosing cholangitis is higher in Black recipients who received livers from White donors compared to matched White donors and recipients. Full article

Background/Objectives: Oral cancer resection often leads to maxillofacial defects and dentition loss, compromising patients’ quality of life. Implant-supported prosthetic rehabilitation offers a reliable solution to restore function, though factors such as bone reconstruction, radiotherapy, and timing of implant placement (immediate vs. delayed) may influence outcomes. This study aimed to evaluate long-term implant survival and rehabilitation timelines in oncologic patients, comparing two cohorts (2005–2014 and 2015–2024) to assess the impact of evolving clinical practices. Methods: A retrospective cohort study was conducted at Hospital General Universitario Gregorio Marañón (Madrid, Spain), including 304 patients who underwent ablative oral cancer surgery and subsequent implant-based rehabilitation between 2005 and 2024. Data on demographics, oncologic treatment, reconstruction, implant timing, and prosthetic rehabilitation were collected. Outcomes were compared using Kaplan–Meier analysis and appropriate statistical tests between the 2005–2014 (n = 122) and 2015–2024 (n = 182) cohorts. Results: A total of 2341 Ticare Implants^® were placed, supporting 281 prostheses. Implant placement during primary surgery increased from 41% to 71% (p < 0.001). The median time from surgery to prosthesis significantly decreased from 24 to 15 months (p < 0.001). Five-year implant survival was 95% in the early cohort versus 97% in the later cohort. Implant survival was comparable between irradiated and non-irradiated patients (~94–96%). Fixed prostheses became more frequent (92% vs. 79%, p = 0.002). Conclusions: Implant-supported rehabilitation in oncologic patients is highly feasible and durable, with improved timelines and functional outcomes associated with early implant placement and modern digital planning strategies. Full article

Background: Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic valve stenosis (AS). Balloon post-dilatation (PD) remains an important procedural step to optimize valve function by resolving incomplete valve expansion, which may lead to paravalvular regurgitation and other potentially adverse effects. There are only limited data on the predictors, incidence, and clinical impact of PD during TAVI. Methods: This retrospective, single-center study analyzed 585 patients who underwent TAVI (2016–2022). Pre-procedural evaluations included transthoracic echocardiography and CT angiography to assess key parameters, including the aortic valve calcium score (AVCS); aortic valve calcium density (AVCd); aortic valve maximal systolic transvalvular flow velocity (AV Vmax); and aortic valve mean systolic pressure gradient (AV MPG). We identified imaging predictors of PD and evaluated associated clinical outcomes by analyzing procedural endpoints (according to VARC-3 criteria) and long-term survival. Results: PD was performed on 67 out of 585 patients, with elevated AV Vmax (OR: 1.424, 95% CI: 1.039–1.950; p = 0.028) and AVCd (OR: 1.618, 95% CI: 1.227–2.132; p = 0.001) emerging as a significant independent predictor for PD in TAVI. Kaplan–Meier survival analysis revealed no significant differences in short- and mid-term survival between patients who underwent PD and those who did not. Interestingly, patients requiring PD exhibited a lower incidence of adverse events regarding major vascular complications, permanent pacemaker implantations and stroke. Conclusions: The study highlights AV Vmax and AVCd as key predictors of PD. Importantly, PD was not associated with increased procedural adverse events and did not predict adverse events in this contemporary cohort. Full article

Background: The importance of lymph node dissection (LND) at the time of radical cystectomy for urothelial carcinoma (UC) is widely accepted despite known risks. The therapeutic benefits of LND for variant subtype bladder cancer (VBC), a heterogenous and distinct set of diseases, are not well established. We aim to characterize the impact of LND on overall survival across VBC subtypes. Methods: The National Cancer Database was queried for all cases of variant subtype bladder cancer managed with radical cystectomy between 2004 and 2020, using the International Classification of Disease-O-3 morphological codes. The cases were stratified by receipt of individual variant subtypes. The primary outcome was overall survival associated with pathologic nodal status and receipt of nodal dissection. A Kaplan–Meier analysis and Cox proportional hazards analysis were used for survival analyses. Results: A total of 30,911 patients with VBC that were managed with radical cystectomy were included in our analysis. The pNx rates ranged from 33.1% in the micropapillary subtype, 42.2% in the sarcomatoid subtype, 68.4% in the squamous subtype, 48.9% in the adenocarcinoma subtype, and 56.2% in the neuroendocrine subtype. The median OS was higher in those that received a nodal dissection across subtypes but was statistically significant only for the squamous (71.0 [68.0 vs. 74.0] vs. 37.2 [33.6 vs. 40.9] months p < 0.001) and adenocarcinoma (45.9 [32.9 vs. 59.0] vs. 37.9 [28.6 vs. 47.1] months p = 0.037) subtypes. Using Cox proportional hazards regression, LN dissection was associated with improved OS for the squamous (0.50 (0.44–0.58) p < 0.001) and adenocarcinoma (0.65 [0.45–0.93) p = 0.030) subtypes. Conclusions: The role of LND across VBC subtypes is not clearly defined and warrants further investigation to develop a more risk-adaptive approach. We demonstrate heterogeneity with respect to the OS benefit associated with LND at the time of surgery. Among certain VBC subtypes, LND may not offer a significant therapeutic benefit, while LND in squamous and adenocarcinoma VBCs is correlated with improved survival. Full article

Background and Objectives: The Naples prognostic score (NPS), which incorporates inflammatory and nutritional indicators, is increasingly used as a prognostic score for various malignancies. Nonetheless, few studies have specifically evaluated the NPS as a prognostic factor for cervical cancer. This study aimed to assess the value of NPS at diagnosis as a predictor of cancer progression. Materials and Methods: This study included patients diagnosed with cervical cancer at Korea University Anam Hospital from January 2019 to December 2023. Patients with incomplete data or those who were lost to follow-up were excluded. The NPS was calculated based on laboratory results at the time of diagnosis, categorizing patients into the low-NPS group (NPS 0–1) and high-NPS group (NPS ≥ 2). Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Results: Out of 178 patients, 98 and 80 were categorized into the low-NPS and high-NPS groups, respectively. Kaplan–Meier survival analysis showed that the high-NPS group had significantly lower disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.02) rates than the low-NPS group. Multivariate Cox regression analysis identified the NPS as an independent prognostic factor for DFS (adjusted hazard ratio, 1.98; p = 0.017), but not for OS. Conclusions: This study demonstrated that the NPS measured at diagnosis may serve as a useful independent prognostic factor for cancer progression in patients with cervical cancer. Full article

Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs. partial thymectomy for early-stage thymoma. Methods: We identified patients diagnosed with WHO types A–B3 thymoma between 2010–2021 from a national hospital-based dataset. We excluded patients with stage II or higher disease, open resections and perioperative chemo-/radiation therapy. We stratified patients into total and partial thymectomy cohorts. We used propensity score matching to minimize confounding, Kaplan–Meier analysis to estimate survival, and Cox proportional hazards to identify associations. Results: Of 1598 patients with early-stage thymoma, 495 (31.0%) underwent partial and 1103 (69.0%) total thymectomy. Patients undergoing partial thymectomy were similar in sex (female 53.7% vs. 53.4%; p = 0.914), race (white 74.5% vs. 74.0%; p = 0.921), comorbidities (0 in 77.0% vs. 75.5%; p = 0.742), and tumor size (48.7 mm vs. 50.4 mm; p = 0.455) compared to total thymectomy. There were no differences in 30-day (0.8% vs. 0.6%, p = 0.747) or 90-day mortality (0.8% vs. 0.8%, p > 0.999), which persisted after matching. Moreover, 10-year survival was similar in both unmatched (p = 0.471) and matched cohorts (p = 0.828). Partial thymectomy was not independently associated with survival (aHR = 1.00, p = 0.976). Conclusions: In patients with early-stage thymoma, partial and total thymectomy were associated with similar short- and long-term outcomes. In light of recent attention to the role of the thymus gland, the results add important insights to shared decision-making discussions. Full article

Objective: Craniopharyngioma recurrence risk studies comparing gross total resection (GTR) vs. subtotal resection (STR) with radiotherapy (XRT) provide inconclusive or contradictory results. This may be an effect of the small group sizes and diversity in the approaches used. Currently, the endoscopic endonasal approach (EEA) is preferred in craniopharyngioma management. Here, we aimed to perform a meta-analysis comparing recurrence risk after GTR vs. STR plus XRT in patients treated with the EEA regimen. Methods: We performed a systematic literature search of original English language papers on craniopharyngioma management published in the PubMed, Web of Science, and Scopus databases up to 18 October 2023. Eleven articles included data on recurrence rate after EEA: GTR vs. STR with XRT. We extracted the year of publication, number of patients, surgical approach, extent of resection, and follow-up duration. We used meta-analysis for the odds ratio (OR) in fixed and random effects models and Egger’s and Begg’s tests to assess heterogeneity and publication bias. Follow-up duration and time to recurrence were additionally included in Kaplan–Meier curves with log-rank test analysis. Results: We observed a lower recurrence rate in patients after GTR (10%) as compared to STR with XRT (30%), OR = 0.299, p < 0.001. To increase data reliability, we limited our analysis to studies with at least five patients in each subgroup and also observed lower recurrence in patients after GTR (12%) as compared to STR with XRT (27%), OR = 0.376, p = 0.011. Survival analysis confirmed significant differences in recurrence-free survival percentages between these groups (p = 0.008). Conclusions: To date, this is the largest meta-analysis evaluating the recurrence risk in patients undergoing EEA for craniopharyngioma resection, comparing outcomes between those treated with GTR and those treated with STR plus XRT. The results suggest that GTR significantly reduces recurrence risk. Full article

Background: Overtime adversely affects physical and mental health, contributing to irritability, anxiety, reduced sleep, and even cardiovascular issues, ultimately lowering care quality and increasing turnover intentions. This study aimed to investigate whether prolonged overtime increases the risk of occupational burnout over time among healthcare workers. Methods: We conducted a four-year longitudinal observational study using secondary data from annual surveys (2021–2024) of healthcare workers at a medical university hospital in Taichung, Taiwan. Burnout was assessed using the personal burnout (PB) scale from the Copenhagen Burnout Inventory (CBI), with high PB levels (HPBL) defined as scores in the upper quartile of the 2021 baseline. Survival analysis utilizing the Kaplan–Meier method and Cox regression investigated burnout progression and the effects of overtime. Results: HPBL was defined as PB scores ≥45.83 (upper quartile in 2021). The proportions of HPBL were 30.28% (2021), 33.29% (2022), 36.75% (2023), and 32.51% (2024). Survival analysis confirmed that the risk of burnout increased over time, with the survival time estimated at 2.50 ± 0.03 years and lower survival probabilities observed among participants working overtime (Log-rank test, p < 0.0001). Multivariate logistics revealed overtime work, female gender, being a physician/nurse, and reduced sleep as independent risk factors for HPBL (OR = 3.14 for overtime, p < 0.001). These findings support the hypotheses on burnout progression and the impact of overtime. Conclusions: Overtime significantly heightens the risk of burnout, which worsens over time. Female sex, healthcare roles, obesity, and insufficient sleep are additional risk factors. Limiting overtime and proactive interventions are crucial to preventing burnout in healthcare workers. Full article

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

Background/Objectives: Alterations in DNA damage repair mechanisms can impair the therapeutic effectiveness of cisplatin. MicroRNAs (miRNAs), key regulators of DNA damage repair processes, have been proposed as promising biomarkers for predicting the response to platinum-based chemotherapy (CT) in non-small cell lung cancer (NSCLC). In this study, by using a bioinformatics approach, we identified six miRNAs, which were differentially expressed (DE) between NSCLC patients characterized as responders and non-responders to platinum-based CT. We further validated the differential expression of the selected miRNAs on tumor and matched normal tissues from patients with resected NSCLC. Methods: Two miRNA microarray expression datasets were retrieved from the Gene Expression Omnibus (GEO) repository, comprising a total of 69 NSCLC patients (N = 69) treated with CT and annotated data from their response to treatment. Differential expression analysis was performed using the Linear Models for Microarray Analysis (Limma) package in R to identify DE miRNAs between responders (N = 33) and non-responders (N = 36). Quantitative real-time PCR (qRT-PCR) was used to assess miRNA expression levels in clinical tissue samples (N = 20). Results: Analysis with the Limma package revealed 112 DE miRNAs between responders and non-responders. A random-effects meta-analysis further identified 24 miRNAs that were consistently up- or downregulated in at least two studies. Survival analysis using the Kaplan–Meier plotter (KM plotter) indicated that 22 of these miRNAs showed significant associations with prognosis in NSCLC. Functional and pathway enrichment analysis revealed that several of the identified miRNAs were linked to key pathways implicated in DNA damage repair, including the p53, Hippo, PI3K and TGF-β signaling pathways. We finally distinguished a six-miRNA signature consisting of miR-26a, miR-29c, miR-34a, miR-30e-5p, miR-30e-3p and miR-497, which were downregulated in non-responders and are involved in at least three DNA damage repair pathways. Comparative expression analysis on tumor and matched normal tissues from surgically treated NSCLC patients confirmed their differential expression in clinical samples. Conclusions: In summary, we identified a signature of six miRNAs that are suppressed in NSCLC and may serve as a predictor of cisplatin response in NSCLC. Full article

Background/Objectives: Eph receptor A5 (EphA5) is a receptor tyrosine kinase that is implicated in multiple malignancies, although its role in endometrial cancer (EC) remains unclear. The aim of this study was to investigate the clinicopathological significance of EphA5 expression in EC and explore its association with proliferative and metabolic markers. Methods: We retrospectively analyzed 75 EC tissue samples from treatment-naïve patients by using immunohistochemistry and H-score quantification. Associations between EphA5 expression and clinicopathological parameters were assessed through logistic regression analysis. Kaplan–Meier analysis was used to evaluate survival outcomes. Correlation analysis, stratified according to cancer stage, was used to explore biomarker interactions. Results: High EphA5 expression levels were significantly associated with elevated Ki-67 expression (adjusted odds ratio (aOR): 1.08 per 1-point H-score increase, p = 0.024) and decreased pAMPK expression (aOR: 0.89 per 1-point H-score increase, p = 0.024), indicating its involvement in proliferative and metabolic pathways. Paradoxically, patients with high EphA5 levels had significantly better overall survival probabilities (H-score > 105, log-rank p = 0.007). Stage-specific analyses suggested that EphA5 levels correlated with proliferation in early-stage disease and epithelial–mesenchymal transition in advanced stages. Conclusions: EphA5 may act as a context-dependent biomarker in EC. Despite its positive correlation with proliferation and negative association with metabolic stress signaling, high EphA5 expression levels were predictive of a favorable prognosis. Full article

Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, and overall survival (OS) in patients with DLBCL. Materials and Methods: This retrospective cohort study included 70 patients with DLBCL. Clinical characteristics, laboratory values, and metabolic parameters, including maximum standardized uptake value (SUVmax^liver and SUVmax), heterogeneity indices HI1 and HI2, and MTV were analyzed. Survival outcomes were assessed using Kaplan–Meier and log-rank tests. Receiver operating characteristic analyses helped evaluate the diagnostic performance of the selected biomarkers in predicting relapse and mortality. Univariate and multivariate logistic regression analyses were conducted to identify the independent predictors. Results: The mean OS and mean relapse-free survival (RFS) were 71.6 ± 7.4 and 38.7 ± 2.9 months, respectively. SUVmax^liver ≤ 22 and HI2 > 62.3 were associated with a significantly shorter OS. High lactate dehydrogenase (LDH) levels and HI2 > 87.9 were significantly associated with a reduced RFS. LDH, SUVmax^liver, and HI2 had a significant predictive value for relapse. SUVmax^liver and HI2 levels were also predictive of mortality; SUVmax^liver ≤ 22 and HI2 > 62.3 independently predicted mortality, while HI2 > 87.9 independently predicted relapse. MTV was not significantly associated with survival. Conclusions: Metabolic tumor burden and inflammation-based markers, particularly SUVmax^liver and HI2, are significant prognostic indicators of DLBCL and may enhance risk stratification and aid in identifying patients with an increased risk of relapse or mortality, potentially guiding personalized therapy. Full article