Search Results (20,608)

Steatotic liver disease (SLD) is characterised by profound metabolic reprogramming, yet no single biomarker reliably distinguishes disease entities, stages or sex-specific risk profiles. By integrating serum metabolomic signatures as a liquid biopsy with tumour-associated CSC marker profiles in a sex-stratified analytical framework, we aimed to identify biologically meaningful differences and improve strategies for early, presymptomatic detection of SLD progression and HCC. The present study focuses on a targeted panel of 12 strongly dysregulated serum metabolites as candidate biomarkers of disease progression, quantified by NMR-based metabolomics and ELISA and complemented by CSC marker staining. We combined these NMR-based metabolomic ‘liquid biopsy’ data with circulating tumour-associated biomarkers, MELD-based risk assessment and tissue-level CSC marker expression across MetALD, MASLD, immune-mediated and cancerogenic liver disease, HCC and healthy controls. Female MetALD patients showed the second highest mortality after HCC, with lower survival than male cancer patients, despite MELD 3.0 assigning ~50% higher scores in women. MetALD mortality clustered with GP73, CD44, metabolomics and AA/3HB ratio, indicating a distinct, high-risk female phenotype. Integrating liquid-based metabolomic profiling, AA/3HB redox assessment, CSC markers and MELD 3.0 into sex-sensitive diagnostic pathways may improve early detection and risk stratification of alcohol-associated SLD, especially in women. Full article

Previous studies have shown that, after postoperative recovery from upper and lower gastrointestinal surgery for cancer, patients use peculiar modalities to describe their health. The purpose of this study is to determine how upper and lower gastrointestinal cancer surgery is considered by patients when they set their health. A structured interview was developed and 47 consecutive patients were interviewed postoperatively. Answers were analyzed through M.A.D.I.T., a quantitative and qualitative methodology that allows for the detection of discursive processes comprising the text, beyond thematic analysis. Four dimensions have been analyzed: representation of the postoperative period in daily life; use of resources; participation in achieving the clinical objective after hospital discharge; and continuing to respect the surgeons’ indications. A corpus of 2374 text occurrences was analyzed. Without differences between types of surgery, surgical patients described the time after surgical intervention as a critical scenario. Patients expressed their personal opinions, expecting normality after surgery and having difficulty envisioning the future: their representation of inflexibility in the postoperative period prevented them from finding new coping strategies. Overall, across all four dimensions, participants used stabilization discursive modalities in more than 50% of cases, representative of a situation bound within strict ties and personal theories. When defining their health, cancer surgery patients tend not to consider their condition as a new and different one from before; they imagine that they will be able to fully resume their previous habits. However, this can risk undermining the achievement of the clinical objective. Thus, during early surgical consultations, as well as in surgical recovery, exploring differences after surgery and solutions could help patients in their engagement with surgical outcomes and consequences. Full article

CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment. Full article

Background: Soft-tissue sarcomas (STSs) are rare and heterogeneous malignancies with generally poor and unpredictable prognosis. Tertiary lymphoid structures (TLSs) have been identified as favorable prognostic indicators in several cancer types, yet their role in STS remains poorly defined. This study investigates the prognostic relevance of TLS presence, maturity, location and density in resected STSs. Methods: We retrospectively analyzed 219 cases of primary STS surgically resected at the Bergonié Institute (France) between 1990 and 2020. TLSs were assessed for presence, spatial distribution, semi-quantitative density and degree of maturity using CD20 and CD23 immunohistochemistry, categorizing tumors as fully mature TLS-positive (fmTLS⁺) or -negative (fmTLS⁻). RNA sequencing was performed on 126 formalin-fixed paraffin-embedded samples to characterize immune microenvironment profiles. Survival outcomes—including overall survival (OS), time to locoregional progression (TTLRP), and time to distant progression (TTDP)—were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Results: The presence of fmTLS was significantly associated with improved 5-year OS (p = 0.012) and cause-specific survival (p = 0.006). Unexpectedly, fmTLS⁺ tumors showed a higher rate of local recurrence (22.9% vs. 8.1%, p = 0.002). On multivariate analysis, high-density fmTLS⁺ tumors conferred a 2.68-fold increased risk of locoregional progression (95% CI: 1.28–5.59, p = 0.009). Transcriptomic profiling confirmed a significant correlation between fmTLS⁺ status and a high-immune phenotype (Φ = 0.30, p < 0.001). Conclusions: STSs with fmTLS are associated with improved OS but increased risk of local recurrence. These findings support fmTLS as a dual prognostic biomarker and highlight the need for tailored surveillance and adjuvant strategies in fmTLS⁺ patients. Full article

Survivors of primary gastric lymphoma (PGL) face a significantly elevated and persistent risk of developing second primary malignancies (SPMs), with gastric adenocarcinoma representing the most frequent SPM and standardized incidence ratios reaching up to 16-fold above the general population. This excess risk persists for decades after initial treatment and is associated with increased cause-specific mortality compared to matched primary cancers. Among patients with PGL, approximately 5% develop gastric cancer (with two-thirds being metachronous), and nearly 15% harbor precancerous lesions including atrophic gastritis, intestinal metaplasia, and dysplasia. Beyond gastric malignancies, survivors also experience elevated rates of extra-gastric SPMs, particularly digestive system tumors (43%), respiratory cancers (21%), and urinary tract malignancies (13%). Key risk factors include treatment with immunochemotherapy or radiotherapy, advanced age, male sex, advanced stage at diagnosis, ulcerative-type lymphoma morphology, and persistent Helicobacter pylori (HP) infection. Patients receiving combined chemoradiotherapy demonstrate the highest SPM risk, particularly for gastric and pancreatic cancers. These findings underscore the critical importance of lifelong, risk-adapted surveillance strategies integrating both hematology and gastroenterology follow-up. Annual endoscopic surveillance is recommended for high-risk patients, with intervals adjusted according to lymphoma histology, HP status, and the presence of precancerous gastric lesions. Mandatory HP eradication with confirmation of response is essential for reducing gastric cancer risk. Future research priorities include prospective, standardized studies to better quantify SPM risk, validation of molecular and microbiological biomarkers for individualized risk stratification, and development of predictive models to enable personalized surveillance protocols and improve long-term outcomes in this vulnerable population. Full article

Ovarian cancer (OC) remains one of the most lethal gynaecological malignancies, which is mainly due to late diagnosis, high frequency of metastasis, and the risk of developing resistance to systemic therapy. In recent years, exosomes—small extracellular vesicles (EVs) secreted by cancer cells and components of the tumour microenvironment (TME)—have been identified as potential mediators of OC progression. Exosomes participate in intercellular communication and enable the transfer of RNA, proteins, and lipids. These vesicles may modulate the immune response, promote angiogenesis, remodel the extracellular matrix, and drive epithelial–mesenchymal transitions. Exosomes also appear to play a role in the development of drug resistance via direct transfer of resistance factors or indirect modification of TME. In this review article, we summarise current knowledge on the biological role of exosomes in OC pathogenesis. We also discuss their possible diagnostic, prognostic, and therapeutic relevance. The properties and composition of exosomes make them promising noninvasive liquid biomarkers and convenient carriers for anticancer drugs. However, to fully exploit their potential, further large-scale preclinical and clinical studies are required, which should focus primarily on standardising research methods and assessing the safety and efficacy of exosome-based diagnostic and therapeutic methods. Full article

Background and Clinical Significance: The coexistence of synchronous urologic malignancies may present diagnostic and therapeutic challenges, particularly when symptoms are minimal or nonspecific. This case illustrates the role of multimodal diagnostic correlation in identifying a second primary urologic malignancy during the evaluation of incidental PSA elevation. Case presentation: Case Presentation: We report the case of a 56-year-old male presenting with minimal lower urinary tract symptoms who underwent stepwise diagnostic evaluation including PSA (prostate specific antigen), free PSA, urinary SelectMDx RT-PCR testing (reverse transcription polymerase chain reaction), multiparametric MRI (magnetic resonance imaging), transrectal biopsy and inflammatory biomarker assessment. PSA was 17.69 ng/mL with a free PSA ratio of 6.56%. SelectMDx indicated a 90% probability of prostate cancer and a 65% risk of Gleason ≥ 7 disease. mpMRI demonstrated two suspicious lesions without extracapsular extension. Biopsy confirmed acinar adenocarcinoma Gleason 7 (3 + 4), Grade Group 2. Persistent post-biopsy hematuria led to additional imaging that revealed bladder wall thickening, and cystoscopy confirmed multifocal carcinoma in situ. Radical cystoprostatectomy with orthotopic ileal neobladder reconstruction was performed. Conclusions: This case illustrates the importance of diagnostic vigilance and multimodal correlation in a minimally symptomatic patient, particularly when persistent clinical findings are not fully explained by the initial diagnosis. The findings should be interpreted as illustrative and cannot be generalized beyond the single-case context. Full article

Background/Objectives: Trastuzumab emtansine (T-DM1) is widely used in Human Epidermal Growth Factor Receptor2 (HER2)-positive metastatic breast cancer; however, outcomes vary, and reliable prognostic markers remain limited. We developed the CALA index as a composite biomarker integrating CA15-3, lactate dehydrogenase (LDH), and albumin. This study aimed to evaluate the prognostic value of the CALA index in metastatic breast cancer treated with T-DM1. Methods: This multicenter retrospective study included 168 patients treated with T-DM1 across four tertiary centers. The CALA index was calculated using pretreatment levels of CA15-3, LDH, and albumin. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value, and patients were stratified into groups accordingly. Survival outcomes and independent risk factors were assessed using Kaplan–Meier and Cox regression analyses. Results: The median overall survival (OS) was 26 months (95% CI: 21.3–30.7). ROC analysis identified an optimal CALA cutoff value of 118.3. Patients with CALA ≤ 118.3 demonstrated significantly longer OS compared with those with CALA > 118.3 (log-rank p = 0.006), with 1- and 3-year OS rates of 81.2% and 43.2% versus 69.8% and 22.7%, respectively. In univariate analysis, CALA > 118.3 was associated with worse OS (HR: 1.699; 95% CI: 1.151–2.506; p = 0.008), and this association remained significant in multivariate analysis (HR: 1.671; 95% CI: 1.088–2.565; p = 0.019). Conclusions: The CALA index was associated with overall survival in metastatic breast cancer treated with trastuzumab emtansine and may serve as a practical tool for risk stratification. Full article

Background: Persistent lymph node metastases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer indicate poor response to treatment. This study evaluated the long-term prognosis of patients with residual nodal disease following neoadjuvant RCT and total mesorectal excision (TME) in comparison with patients who underwent upfront TME without adjuvant radiotherapy. Methods: Consecutive patients with rectal adenocarcinoma and histopathologically confirmed lymph node metastases after TME were identified from the prospectively maintained database of the colorectal unit at Dresden-Friedrichstadt General Hospital. Patients with distant metastases, in-hospital mortality, or postoperative radiotherapy were excluded. The two groups were comprehensively compared regarding patient-, tumor-, and treatment-related characteristics. Cumulative local recurrence, time to recurrence, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method. Results: Between 1996 and 2021, 155 eligible patients were identified, including 101 patients in the RCT group and 54 in the upfront surgery group. Baseline characteristics were largely comparable, except for a higher median age (70.5 vs. 64 years, p < 0.001) and a higher proportion of lymphovascular invasion (36.0% vs. 15.2%, p = 0.004) in the upfront surgery group. Ten-year local recurrence rates were similar between groups (21.0% [95% CI: 10.4–31.6] vs. 20.8% [95% CI: 8.5–33.1], p = 0.609). No significant differences were observed in time to recurrence or cancer-specific survival. Overall survival was lower in the upfront surgery group, most likely reflecting the substantially higher age of these patients. Conclusions: Despite more intensive treatment, patients with a persistent ypN-positive category have outcomes no better than untreated patients with node-positive disease after TME, indicating a biologically high-risk subgroup. Non-response is therefore a sign of a negative selection. These patients may lose the opportunity for optimal local tumor control during prolonged neoadjuvant treatment, underscoring the urgent need for reliable predictive markers to identify non-responders and guide individualized treatment strategies. Full article

Prostate cancer (PCa) is one of the most common malignancies in men and remains a major cause of cancer-related death worldwide. Radiotherapy is a well-established treatment modality for PCa, offering clinical outcomes comparable to surgical approaches. In recent years, stereotactic body radiotherapy (SBRT), characterized by the delivery of high radiation doses in a limited number of fractions, has been increasingly adopted as a standard approach in the treatment of prostate cancer, due to its favorable efficacy and toxicity profile. CyberKnife (CK) is one of the most commonly used hypofractionated radiotherapy techniques. This preliminary study aimed to evaluate and compare the radiation dose delivery and treatment time of CK-based SBRT using two different collimation systems: the multileaf collimator (MLC) and the IRIS variable aperture collimator, a dynamic device that adjusts its opening to simulate different circular field sizes. A total of 19 patients with low-to-intermediate-risk PCa were selected and treated at the Radiation Oncology Department of the National Cancer Institute IRCCS Fondazione G. Pascale in Naples between January 2024 and January 2025. For each patient, two treatment plans were generated—one with the IRIS collimator and one with the MLC. The results demonstrated that the use of the MLC significantly reduced treatment time while maintaining dosimetric quality comparable to IRIS-based plans. These findings support the clinical benefit of MLC implementation in prostate SBRT with the CK system. Full article

Background/Objectives: Pancreatic cancer (PC) should be diagnosed in its early stages. Therefore, it is necessary to identify high-risk individuals of PC. Methods: Between 2001 and 2017, 1542 PC cases were diagnosed at two tertial care institutions. Of these, 117 cases had undergone abdominal contrast-enhanced computed tomography (CE-CT) 1–10 years before PC diagnosis and were classified as the PC group. Meanwhile, 43,102 cases underwent abdominal CE-CT for close examination of non-pancreatic diseases in the same period, of which 1170 were randomly selected. Of these, 117 cases were matched to the PC group with the propensity score and designated the non-PC group. Pancreatic volumetry was performed using the 3D image analysis system for abdominal CE-CT in both groups and various measurements were compared. In PC group, CE-CT taken 1–10 years before the onset of PC was analyzed. Results: After propensity score matching, baseline characteristics did not significantly differ between the two groups. The whole pancreatic volume/body surface area (BSA) (p = 0.014), volume of main pancreatic duct (MPD) plus cystic lesion/BSA (p < 0.001), volume of pancreatic parenchyma/BSA (p = 0.002), ratio of cross-sectional areas (p = 0.033), and MPD diameter/BSA (p < 0.001) significantly differed between the two groups. In subgroup analysis of patients without cystic lesions, the whole pancreatic volume/BSA, volume of MPD/BSA, volume of pancreatic parenchyma/BSA, ratio of cross-sectional areas, and MPD diameter/BSA significantly differed between the two groups. Conclusions: Pancreatic volumetry could identify patients at high risk of PC. Full article

Apitherapy is a complementary therapeutic approach based on the use of bee-derived products, particularly bee venom (BV), also known as apitoxin. Bee venom is a complex mixture of biologically active compounds, including peptides, enzymes, and biogenic amines, that exhibit diverse pharmacological activities. Major bioactive constituents such as melittin, apamin, adolapin, and phospholipase A2 have attracted increasing scientific interest due to their anti-inflammatory, antioxidant, antimicrobial, analgesic, and immunomodulatory properties. This review provides a comprehensive overview of the biological effects and therapeutic potential of bee venom in the management of chronic diseases, particularly diabetes, cancer, and neurological disorders. Evidence from experimental and clinical studies suggests that BV and its components can modulate multiple molecular pathways associated with oxidative stress, inflammation, apoptosis, and immune responses. These mechanisms contribute to potential benefits in glycemic control, tumor suppression, neuroprotection, and pain management. Additionally, bee venom has been investigated for its capacity to influence signaling pathways involved in cellular proliferation and survival, highlighting its potential as a complementary strategy in the treatment of complex diseases such as neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Despite these promising therapeutic effects, the clinical use of BV remains limited due to safety concerns, particularly the risk of allergic reactions, systemic toxicity, and anaphylaxis. Recent advances in drug delivery systems and nanotechnology may help improve the safety and efficacy of BV-based therapies by enabling targeted delivery and controlled dosing. Overall, bee venom represents a promising source of bioactive compounds with potential applications in translational and integrative medicine; however, further well-designed clinical trials and mechanistic studies are necessary to establish its safety, efficacy, and long-term therapeutic value. Full article

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy in which radiotherapy plays a uniquely central role compared with other gastrointestinal cancers. Definitive chemoradiotherapy (dCRT) is widely used as a curative treatment; however, a substantial proportion of patients develop residual or recurrent disease, creating a complex clinical scenario that requires tailored salvage strategies. Salvage esophagectomy offers the potential for long-term survival but remains technically demanding and is associated with significant morbidity because of radiation-induced tissue damage. Less invasive local therapies, such as endoscopic submucosal dissection and photodynamic therapy, may provide effective treatment in selected patients, although their indications are limited by tumor characteristics and post-radiation fibrosis. In addition, immune checkpoint inhibitors have demonstrated promising efficacy in advanced ESCC and may represent a potential therapeutic option in the salvage setting. For patients who are not candidates for curative treatment, palliative esophageal stenting remains an important option for symptom relief, although prior radiotherapy may increase the risk of treatment-related complications. Given the diversity of available treatment modalities and their associated risks, a multidisciplinary and individualized treatment approach is essential. Further prospective studies are warranted to optimize treatment algorithms and improve outcomes in patients with ESCC after dCRT. Full article

To address the problems of easy cracking and the difficulty in balancing construction schedule and structural quality in the construction of ultra-long concrete slabs, this paper takes the ultra-long floor slab project of an inpatient building in the Science City Campus of Chongqing University Cancer Hospital as the research object, and conducts research on temperature and crack control in the construction of the alternative bay method. The key structural mechanical parameters are determined through theoretical calculation. The temperature and deformation changes during the whole process of concrete pouring are tracked by combining on-site monitoring and finite element simulation, and the effects of different construction parameters are compared and analyzed. The results show that when the alternative bay method is adopted, the overall temperature distribution of the floor slab is uniform, and there are obvious differences in deformation at different positions. The center of the first-poured slab has smaller deformation, the beam side has larger deformation, the later-poured slab has larger overall deformation, and tensile deformation occurs on both sides of the construction joint. Reasonably dividing the pouring blocks, optimizing the pouring sequence and extending the pouring interval can significantly reduce the tensile deformation of concrete and alleviate stress concentration. This study confirms that the alternative bay method can effectively reduce the risk of temperature-induced cracking in ultra-long floor slabs and provide technical reference for seamless construction of similar above-ground structures. Full article

Sex differences influence cancer incidence, treatment response, and susceptibility to cardiovascular toxicity. Males exhibit higher rates and poorer outcomes in most non-sex-specific cancers, while females more frequently experience treatment-related adverse events, including cancer therapy-related cardiac dysfunction. Biological factors such as hormonal status, genetic polymorphisms, immune responses, and pharmacokinetics contribute to these disparities. In cardio-oncology, women—particularly premenopausal or with specific genotypes—may be at increased risk for cardiotoxicity after treatment with anthracyclines, immune checkpoint inhibitors or radiotherapy. Clonal hematopoiesis and certain germline genetic variants such as single nucleotide polymorphisms (e.g., RARG rs2229774, HAS3 rs2232228) are emerging as potential sex-informed biomarkers for predicting cardiotoxicity risk. Despite growing evidence, sex remains insufficiently integrated into clinical trials and guideline development in cardio-oncology. This review highlights the importance of sex-specific surveillance, prevention, and multi-omic risk stratification to advance precision cardio-oncology and support better outcomes for patients across the cancer care continuum. Full article