Search Results (895)

Background/Objectives: Despite the long-standing history of liver transplantation (LT) in Spain, no multicenter study has reviewed national outcomes for LT in metastatic neuroendocrine tumors (NETs). In the current era of transplant oncology, auditing these results is essential to refine patient selection and improve long-term outcomes. Methods: This retrospective observational study analyzed data from 13 centers, including 91 patients who underwent LT for NET between 1995 and 2024. Patients were stratified into two groups: Milan IN (those meeting the Milan criteria) and Milan OUT (the remainder). Results: Recurrence occurred in 57.1% of cases, and overall mortality was 51.6%. Of the 91 patients, 71 (78.0%) were Milan IN and 20 (22.0%) were Milan OUT. Five-year overall survival was 71.0% in Milan IN and 58.0% in Milan OUT, with a statistically significant difference. The 5-year disease-free survival (DFS) rate was 58.8% in Milan IN and 36.3% in Milan OUT; this difference was not statistically significant. Conclusions: In conclusion, strict adherence to Milan criteria and incorporation of modern prognostic factors are critical to optimize long-term survival in LT for NET. While the overall outcomes in this historical cohort are modest, future improvements are expected through more rigorous selection and the potential use of bridging or downstaging therapies. Full article

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Anal squamous cell carcinoma (ASCC) is a rare malignancy of the lower gastrointestinal tract, with distant metastases typically involving the liver and lungs. Metastasis to the kidneys is uncommon, and only one prior case has been reported in the literature. Herein, we report a rare presentation of a patient with biopsy-confirmed metastatic ASCC presenting as bilateral renal lesions. We then provide a review of the literature for rare metastatic presentations of ASCC, highlighting all the cases described in the literature. Clinicians should maintain a high index of suspicion for unusual metastatic sites, perform targeted imaging and biopsy when indicated, and consider systemic therapies to optimize outcomes in rare metastatic presentations. Full article

Background/Objectives: For patients with advanced or metastatic clear cell renal cell carcinoma (RCC), combinations of immune checkpoint inhibitors (ICIs) and VEGFR-targeted tyrosine kinase inhibitors (TKIs) are standard first-line therapies. However, the clinical benefit of these regimens in patients with favorable IMDC risk remains unclear. Methods: We retrospectively analyzed 147 patients with favorable-risk metastatic RCC treated with first-line systemic therapy at the Samsung Medical Center between 2019 and 2023. Treatment regimens included TKI monotherapy (n = 110) or ICI–TKI combinations (n = 37). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated using Kaplan–Meier and Cox regression analyses. Results: At a median follow-up of 46.3 months, the overall median PFS was 20.1 months (95% CI, 14.5–25.7). Median PFS was 26.2 months with ICI–TKI combinations versus 17.0 months with TKI monotherapy (HR 1.32; 95% CI, 0.82–2.12; p = 0.25). In multivariate analysis, TKI monotherapy (HR 14.01; p = 0.002) and liver metastasis (HR 9.17; p < 0.001) were independent predictors of shorter PFS. ORR was significantly higher with combination therapy (68% vs. 46%; p = 0.01). Median OS was not reached in either group, with 3-year OS rates of 89% and 84%, respectively. Conclusions: The findings suggest that even within the favorable-risk population, clinical heterogeneity influences treatment outcomes, emphasizing the need for individualized therapy selection and refined prognostic models. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article

A 14-year-old spayed female Jindo dog presented with a firm, non-painful right-sided cervical mass. Computed tomography identified three distinct, separate masses thought to be arising from the right thyroid lobe; the largest measured 66.6 mm × 42.0 mm × 37.6 mm with an estimated volume of 56 cm³ and showed invasion into the right internal jugular vein. Multiple hepatic nodules were detected without evidence of pulmonary metastasis and regional lymph node involvement. Right thyroidectomy with resection of the invaded vein and partial liver lobectomy were performed. The histologic results confirmed all three masses as follicular-compact thyroid carcinomas, and the hepatic lesion as metastatic thyroid carcinoma. The dog recovered uneventfully, remained euthyroid, and showed no local recurrence over a 5-month follow-up. In human medicine, multifocality is common in papillary thyroid carcinoma and is associated with a high rate of recurrence. This report documents the first canine case of multifocal thyroid carcinoma, featuring macroscopic vascular invasion and an uncommon metastatic pattern in which the liver was affected in the absence of detectable pulmonary lesion. The presence of multifocal disease within a single canine thyroid lobe necessitates comprehensive cross-sectional imaging, meticulous surgical planning with vascular considerations, and long-term monitoring to optimize the prognosis of this carcinoma. Full article

Background and Objectives: This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. Materials and Methods: Eighty-eight metastatic NSCLC patients who were initiated on nivolumab between January 2022 and December 2024 were retrospectively analyzed. Body composition parameters were derived from baseline and 3-month ¹⁸F-FDG PET/CT scans at the L3 level, including psoas muscle index (PMI), skeletal muscle index (SMI), intramuscular adipose content (IMAC), and subcutaneous fat density (SFD). Treatment-related changes in body composition were evaluated, and survival analyses were performed using Kaplan–Meier estimates and Cox regression models. Results: Overall, 34.1% (n = 30) of patients were classified as sarcopenic. Median OS was significantly longer in non-sarcopenic patients (19 months vs. 5 months, p < 0.001). In univariate analysis, older age, higher comorbidity burden, liver metastasis, baseline sarcopenia, and adverse treatment-related changes in muscle and nutritional parameters were found to be associated with OS. In multivariate analysis, only unfavorable changes in skeletal muscle (ΔSMI; HR 3.39, p = 0.003) and subcutaneous fat radiodensity (ΔSFD; HR 2.45, p = 0.02) remained independent adverse prognostic factors. Baseline body composition parameters did not maintain their independence in multivariate models. Conclusions: Our study demonstrates that muscle loss or insufficient gain and unfavorable changes in subcutaneous fat radiodensity during nivolumab treatment more strongly predict overall survival compared to baseline measurements. These findings highlight the clinical importance of monitoring dynamic body composition throughout treatment, rather than static assessments, in NSCLC patients receiving immunotherapy. Full article

Uveal melanoma (UVM) is a rare cancer that represents the second most common melanoma (after the cutaneous) and the most common primary intraocular malignancy in adults. Despite recent advances in the understanding of UVM pathogenesis, its prognosis remains unchanged, with half of patients dying because of liver metastasis. Erythropoietin-producing human hepatocellular receptors (EPHs) constitute the largest known family of tyrosine receptors, and, along with their ligands, EFNs, regulate key physiological processes and are implicated in cancer pathogenesis. In this study, we used open-access web bioinformatics platforms to explore and analyze big datasets provided by The Cancer Genome Atlas (TCGA) UVM cohort of patients. We profiled the genomic alterations present in a subset of UVM patients, highlighting a likely pathogenic deep deletion of EPHA7. Survival analysis showed that overexpression levels of EPHA4, EPHA5, EPHA8, EPHB2, and EFNB2 are significantly associated with poor overall survival. Additionally, high expression levels of EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2 correlate with reduced progression-free interval and disease-free survival. Finally, we identified the EPHs (EPHA2, EPHA4, EPHA8, and EPHB4) and EFNs (EFNA1, EFNA3, EFNA4, and EFNB2) that are significantly overexpressed in the aggressive epithelioid histological subtype and revealed that the majority of EPHs/EFNs are overexpressed in metastatic disease. In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients. Full article

Sweet potato leaves (SPL) are increasingly recognized as a significant source of nutritionally and pharmacologically important bioactive compounds. This systematic review critically synthesizes current in vitro, in vivo, and preclinical data to evaluate the cancer preventive properties of SPL, with emphasis on their phytochemical composition, molecular mechanisms, and therapeutic relevance. A comprehensive literature search across major scientific databases (2015–2025), guided by PRISMA methodology, initially identified 29,416 records. After applying pre-specified inclusion and exclusion criteria and screening titles, abstracts, and full-texts, 38 eligible studies were included. The compiled evidence demonstrates that SPL contains high concentrations of phenolic acids, flavonoids, peptides, carotenoids, and dietary fiber, all of which contribute to diverse anticancer activities. Reported mechanisms include apoptosis induction, cell-cycle arrest, limitation of tumor propagation and metastatic activity, regulation of oncogenic pathways (PI3K/Akt, MAPK, NF-κB), modulation of inflammatory mediators, and suppression of angiogenesis. These effects were observed across multiple cancer models, including liver, colon, breast, lung, and prostate cancers. In addition, SPL represents a promising natural source of anticancer agents, significant gaps remain, particularly regarding standardized extraction procedures, phytochemical characterization, bioavailability, and human clinical validation. Overall, this review underscores SPL as a sustainable and underutilized plant resource with potential applications in functional foods, nutraceuticals, and adjunctive cancer therapy, while highlighting the need for mechanistic studies, pharmacokinetic investigations, and well-designed clinical trials to support future translational development. Full article

Background and Objectives: Urothelial carcinoma (UC) is one of the most prevalent and lethal cancers worldwide. Identifying and understanding the factors that influence treatment outcome is essential for improving therapeutic effectiveness and predicting patient response. The objective of this review is to estimate how clinical, biochemical, molecular and therapeutic factors impact the prognosis of patients with advanced urothelial carcinoma (aUC) and metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). Methods: A review was performed using PubMed, Scopus and Web of Science databases. All articles were published from 2013 to 2025 focusing on prognostic factors in locally advanced and metastatic urothelial carcinoma treated with ICIs. Results: Clinical prognostic factors for patients treated with ICIs include poor Eastern Cooperative Oncology Group (ECOG) performance status and the presence of liver or bone metastases, both associated with poor outcomes. Low hemoglobin levels and several biochemical markers, such as high neutrophil-to-lymphocyte ratio (NLR), elevated systemic immune-inflammation index (SII) and low serum sodium are also associated with reduced survival. Programmed cell death-ligand 1 (PD-L1) expression shows predictive relevance for ICI response. Concomitant use of antibiotics or proton pump inhibitors (PPIs) may diminish immunotherapy effectiveness. Additionally, sarcopenia and high lactate dehydrogenase (LDH) levels correlate with poorer clinical outcomes. Conclusions: Prognostic outcomes in aUC and mUC are influenced by a complex interaction of clinical, biochemical and molecular factors. Integrative prognostic models are essential to the guidance of personalized immunotherapeutic strategies and the improvement of patient outcomes in aUC and mUC. Full article

Background and Clinical Significance: Metastatic breast cancer is a major global health burden, with common metastatic sites including the bones, lungs, liver, and brain. Cardiac metastasis is rare and often clinically silent, leading to underdiagnosis. Recognizing cardiac involvement, even when asymptomatic, is important for understanding the full extent of disease and ensuring optimal patient care. Case Presentation: We report the case of a woman with advanced breast carcinoma who showed no clinical or imaging evidence of cardiac involvement throughout the course of her illness. Following her death from progressive metastatic disease, an autopsy revealed metastatic carcinoma infiltrating the myocardium and epicardium without gross cardiac abnormalities. Histological and immunohistochemical analysis confirmed the tumor’s origin from breast carcinoma. Conclusions: This case illustrates the potential for clinically occult cardiac metastasis in breast cancer and underscores the importance of pathological examination in detecting hidden metastatic sites. The absence of cardiac symptoms or imaging abnormalities highlights the diagnostic challenge of this rare manifestation and the need for greater awareness in managing advanced malignancies. Full article

Background: Colorectal cancer (CRC) frequently metastasizes to the liver (CRLM), where M2-polarized macrophages shape an immunosuppressive pre-metastatic niche. The molecular cues driving this polarization remain unclear. Methods and Results: Using integrated transcriptomics, patient cohorts, and mouse models, we investigated the role of tissue inhibitor of metalloproteinases-1 (TIMP1) in CRLM. TIMP1 was consistently overexpressed in CRC tissues and associated with poor overall survival. CRC cells secreted TIMP1 into the tumor microenvironment, where it induced M2-like macrophage polarization and increased the expression of immunosuppressive mediators such as CSF1 and IRF4. In vivo, TIMP1 overexpression enhanced, whereas its knockdown reduced, liver metastatic burden. Immune profiling and depletion experiments indicated that these pro-metastatic effects were largely macrophage-dependent. Mechanistically, TIMP1 engaged CD63/β1-integrin on macrophages, activating AKT/mTOR signaling and stabilizing the M2 phenotype. Conclusions: CRC-derived TIMP1 remodels liver macrophages via the CD63/β1-integrin–AKT/mTOR pathway to promote a hepatic pre-metastatic niche. Pharmacologic inhibition of this signaling axis with the integrin antagonist cilengitide suppressed macrophage M2 markers and liver colonization in mice, supporting TIMP1–integrin signaling as a potential therapeutic target. Full article

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a high rate of recurrence and a dismal prognosis. Studies have shown that pancreatic cancer stem cells (PCSCs) are a subpopulation that contributes to tumor progression, resistance to therapeutics, and metastasis, making them a key subpopulation to target for treatment. Gedunin (GD), a natural compound derived from Azadirachta indica (neem), has shown anticancer properties in pancreatic cancer cells, but its effects on PCSCs remains unclear. This study evaluated the effects of GD in pancreatic cancer stem cells, highlighting its impacts on tumor growth and progression and focusing on its impact on the sonic hedgehog (Shh) signaling pathway. Methods: Functional assays were performed to assess the effect of GD on the sphere-forming ability, colony formation, and self-renewal of PCSCs. Athymic mice xenograft models were utilized to evaluate the tumor suppression effect of GD in vivo. Furthermore, the anticancer effect of GD on PCSCs was assessed using both in vitro and in vivo limiting dilution assay. GD-induced changes in Shh signaling and key stem cell marker expressions in PCSCs were evaluated. Results: GD effectively inhibited tumor growth in xenograft models and reduced the percentage of PCSCs. GD was effective in decreasing PCSCs’ proliferative, self-renewal, and colony-forming capacity. GD decreased the protein expression levels of key Shh signaling markers Gli1 and Shh, stem cell markers SOX2, Nanog, and Oct4, metastasis-related proteins MMP-2, MMP-3, and MMP-9, and EMT markers Tgf1, Slug, Snail, and Twist in both PDAC cells and PCSCs. We demonstrated a significant decrease in the spheroid formation and self-renewal capacity of the (ALDH+) PCSC population following GD treatment in HPAC cells, indicating its potential antagonistic effects on PCSCs. GD was highly effective in reducing tumor volume, stemness, and metastasis in both early and late chemotherapy. In vivo limiting dilution assay using CD133+/LGR5+ PCSC xenografts demonstrated that GD reduces tumor growth, metastasis, and stemness associated with PCSCs by downregulating the expression of Shh and Gli1. GD treatment also reduced micrometastatic lesions in the lung, liver, and brain, as identified using H&E staining. Conclusions: The findings highlight GD’s potential as a promising therapeutic candidate for PDAC, with the ability to target both bulk tumor cells and PCSCs. By simultaneously suppressing tumor growth, stemness, and metastatic spread, GD may contribute to more effective treatment strategies and improved patient outcomes. Full article

Circulating tumor DNA (ctDNA) analysis offers a non-invasive approach to molecular profiling. While RAS mutations are well-established predictive biomarkers in metastatic colorectal cancer (mCRC), the prognostic value of their variant allele frequency (VAF) remains unclear. We retrospectively analyzed individual patient data with mCRC who underwent ctDNA testing using the FoundationOne^® Liquid CDx assay. The primary objective was to determine the optimal RAS VAF cutoff for overall survival (OS) prognostication. Between November 2020 and July 2024, 282 patients were enrolled. Among 265 eligible patients, 134 (50.6%) were ctRAS mutant, 25 (9.4%) ctBRAF^V600E mutant, and 106 (40.0%) were ctRAS/BRAF wild-type. A RAS VAF threshold of 5% yielded the highest prognostic discrimination for OS (HR = 2.41; 95% CI 1.65–3.55; p < 0.0001; C-index = 0.601). ctRAS-high mutant tumors (VAF ≥ 5%) were associated with synchronous metastatic disease, multiple metastatic sites, higher blood tumor mutational burden, and elevated tumor fraction. ctRAS-low mutant tumors (VAF < 5%) were more frequently metachronous, presented with a single metastatic site, and showed liver involvement. High RAS VAF in ctDNA is a strong and independent prognostic marker for OS in mCRC. Quantitative ctDNA profiling may enhance risk stratification and guide personalized management strategies. Full article