Patient navigation has been proposed as a primary method of facilitating successful treatment and outcomes for cancer patients. In order to design a navigation program specific for HCC patients, the aims of this study were 3-fold: (1) to identify the needs of HCC patients, (2) to identify barriers to the successful treatment of HCC, and (3) to identify specific supports needed for the successful treatment of HCC.

In-depth qualitative interviews, lasting 60-90 minutes, were conducted with 42 individuals, including 14 patients, 7 caregivers, 8 advocates, 2 research coordinators, and 11 providers. The specialty of the provider participants included Hepatology, Transplant Surgery, Medical Oncology, Radiation Oncology, and Interventional Radiology. Advanced practice providers, social workers, and nurse navigators were also included. Patients, caregivers, and providers were recruited from 2 healthcare systems in South Florida. Advocates were recruited through collaboration with the Global Liver Institute and the Hepatitis B Foundation.

The interviews identified 5 overarching themes representing the navigation needs of HCC patients: (1) Education/Health Literacy, (2) Financial Resources, (3) Coordination of Care, (4) Emotional/Mental Health Management, and (5) Social Support. These overarching themes were composed of various subthemes, which further delineated the specific needs that patients and caregivers have in the context of their HCC treatment.

This study provides valuable insight into the needs of patients with HCC and their caregivers. Key stakeholders in the field of HCC provided valuable insights into the multidimensional needs of patients with HCC, identifying areas to target with high-quality interventions. To best meet the treatment needs of patients with HCC, successful navigation should include interventions targeted at addressing each of these areas of need.

Fluorescence in situ hybridization (FISH) is recommended as part of multimodality sampling in the evaluation of biliary strictures, but can be false negative in 40%-50% cases. The aim of this study was to comprehensively assess predictors of false-negative FISH in patients with biliary strictures.

Patients undergoing tissue sampling for biliary strictures from October 20 to February 22 were prospectively enrolled (NCT04572711). Procedural factors such as sampling techniques, order, and utilization of combination sampling were recorded. Results of an optimized pancreatobiliary FISH panel with locus-specific probes for 1q21, 7p12, 8q24, and 9p21 were reported per guidelines. Statistical analyses were performed using BlueSky Statistics v.10.3.1, R package v8.81.

Of 327 patients, 93 (28.5%) were diagnosed with malignancy. A false-negative pancreatobiliary fluorescence in situ hybridization (PB-FISH) was reported in 40 (43.1%) patients. A history of primary sclerosing cholangitis was associated with lower odds of having a false-negative PB-FISH (aOR=0.38, 95% CI=0.16-0.82, p=0.02), whereas a hilar stricture was associated with a significantly higher false-negative PB-FISH in those with cholangiocarcinoma (aOR=3.2 [1.4-7.9], p=0.009). Dilation of biliary strictures prior to brushing was not associated with a lower rate of false-negative PB-FISH.

In this prospective study, hilar strictures were more likely to have false-negative PB-FISH. Dilation of strictures did not affect PB-FISH performance. These results can help guide PB-FISH interpretation.

Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline BRCA1 mutation. The patient iPSC-MCs recapitulated the transcriptome, clinical genomic alteration, and tumorigenic ability of breast cancer cells. We also identified S100P as an oncogene downstream of mutated BRCA1 that promotes cancer cell stemness and tumorigenesis. Our study establishes a promising system of breast cancer for studying the mechanism of tumorigenesis and identifying potential therapeutic targets.

The relationship between genetic variation and CD8⁺ T cell receptor (TCR) repertoire usage in patients receiving immune checkpoint blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8⁺ TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-nucleotide oligomer usage from samples taken before and after ICB (n = 250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, while, at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with implications for understanding factors relating to therapeutic response and patient outcomes.

This study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1. Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1. Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.

Chimeric antigen receptor (CAR) T-cell therapy represents a groundbreaking approach to treating malignancies. This immunotherapy involves genetic modification of T cells to target and eliminate tumor cells, proving effective across various cancers. Its remarkable specificity, solid tumor infiltration, and durable responses highlight its potential to revolutionize cancer treatment. By targeting specific tumor antigens, CAR-T-cell therapy minimizes off-target effects and enables personalized treatment. Six CAR-T-cell therapies have been authorized, showing exceptional effectiveness, particularly for B-cell malignancies and multiple myeloma. However, challenges such as cytokine-release syndrome, neurotoxicity, and difficulties in targeting solid tumors due to issues like unreliable antigens, hypoxic tumor cores, and immunosuppressive environments complicate its application. Addressing these requires innovative strategies to enhance CAR-T cell efficacy and reduce toxicity. This review details CAR T-cell engineering, signaling pathways, clinical successes in B-cell malignancies, challenges in solid tumors, emerging strategies, and safety management.

UBE2C (Ubiquitin-conjugating enzyme E2C) has been confirmed to be closely associated with the progression of various cancers, but its specific role and clinical diagnostic and prognostic value in prostate cancer (PRAD) remain unclear. This study systematically assessed the expression characteristics, prognostic significance, and genetic mutations of UBE2C in cancer patients by integrating data from databases such as TCGA, GEO, cBioPortal, and COSMIC. Experimentally, we explored the biological functions of UBE2C in the occurrence and development of PRAD using various methods, including functional enrichment analysis, CCK8 cell proliferation assay, colony formation assay, Transwell migration and invasion assay, Edu staining, 3D tumor spheroid culture, cell cycle analysis, apoptosis detection, and xenograft tumor models. After knocking down UBE2C expression, the proliferation ability, migration and invasion ability of PRAD cells, as well as the growth of xenograft tumors, were all inhibited, and the cell cycle process and apoptosis were changed accordingly. These findings provide favorable experimental evidence and theoretical support for UBE2C as a novel molecular marker for prognosis assessment in solid tumors.

To compare the diagnostic performance of the Society of Radiologists in Ultrasound (SRU) and the 2022 Joint European Societies (JES) Guidelines regarding management at presentation of gallbladder polyps ≥ 7 mm.

All patients with ≥ 7 mm polyps reported on ultrasound scans at a hepatobiliary centre with eventual cholecystectomy over 20 years were retrospectively included. Four blinded radiologists reviewed selected images/clips. Shape and wall-thickening were used to categorize polyps. Imaging and relevant clinical features were used to derive guideline management into binary categories of no follow-up/follow vs refer-to-surgeon. Histological neoplastic polyps were defined as a positive outcome. Reliability, sensitivity, and specificity for both guidelines were tabulated.

One hundred thirty-five patients (mean age 51.9 years, 62 female [45.9%]) with a median polyp size of 12 mm (range 7-45) formed the study cohort. Twenty-eight out of one hundred thirty-five (20.7%) of patients had neoplastic polyps (1 low-grade dysplasia, 5 pyloric gland adenoma, 8 intracholecystic papillary neoplasm, 12 carcinoma in situ/carcinoma, 2 metastases). Pooled kappa values for SRUs and JES's polyp risk categorization were 0.70 (CI: 0.64-0.76) and 0.64 (CI: 0.57-0.71) for intra-observer and 0.41 (CI: 0.35-0.46) and 0.47 (CI: -0.40 to 0.53) for inter-observer agreement. SRU's low and indeterminate risk polyps had an odds ratio of 4.4 (p = 0.002) and 16.9 (p < 0.001) of being neoplastic compared to "very-low risk" polyps. Sensitivity, specificity and AUROC (CI) for SRU were 62% (43-80), 90% (85-95), 0.76 (0.66-0.86), and JES were 90% (79-100), 41% (32-49), 0.66 (0.58-0.73) respectively. The differences between the sensitivity and specificity of the two guidelines were significant (p = 0.002 and < 0.0001, respectively).

For ≥ 7 mm polyps, the SRU guidelines have significantly higher specificity with acceptable sensitivity, whereas the JES guidelines have significantly higher sensitivity with low specificity.

Question What are the diagnostic performances of the 2022 SRU and the JES guidelines for the management of ≥ 7 mm gallbladder polyps? Findings The SRU guidelines were significantly more specific but less sensitive than the JES guidelines. Clinical relevance For ≥ 7 mm polyps, the 2022 SRU guidelines would result in fewer surgical referrals and may be more applicable to the low-incidence populations of Europe and North America.

Histotripsy is the first noninvasive, nonthermal, and nonionizing focused ultrasound ablative therapy that effectively destroys targeted tissue. Histotripsy research began as an early preclinical prototype that eventually underwent small- and large-animal preclinical testing to ensure safe clinical translation to human use. Small-animal studies demonstrated the efficacy of histotripsy in destroying liver tumors and generating immune responses, while large-animal studies in human-sized livers further refined the technology for clinical translation. Preclinical studies revealed that histotripsy is a safe ablative modality that has tissue selectivity, meaning tissues of different structural composition have different thresholds for cavitation-induced destruction, with relative sparing of collagenous structures such as vessels and bile ducts. The noninvasive nature of histotripsy potentially allows for treatment of patients with coagulation abnormalities or those receiving anticoagulation therapy. Additional findings include the creation of well-defined treatment zones that are seen to rapidly resorb over time, a feature allowing for easier treatment response evaluation. This article reviews key observations and results from preclinical and early clinical histotripsy studies leading to U.S. Food and Drug Administration's approval for the treatment of liver cancer. A thorough understanding of the key findings and biologic effects of histotripsy in animal models will facilitate the clinical adoption of histotripsy. Keywords: Ultrasound, Ablation Techniques, Animal Studies, Abdomen/GI, Liver © RSNA, 2025.

This study evaluated diagnostic trends and the overall utility of cytology in feline patients through the analysis of a large, multicentric dataset from Portugal. A retrospective review of 3068 cytological cases from 130 veterinary practices was conducted, with samples categorised by anatomical location and lesion type. Diagnostic outcomes were statistically assessed, revealing an overall success rate of 66.20%. The highest diagnostic yields occurred in fluid samples (83.48%), glandular tissues (76.67%), and mucous membranes (75.81%), followed by organ-based samples (67.79%), miscellaneous tissues (66.98%), cutaneous/subcutaneous nodules (62.16%), and lymph nodes (57.93%). Neoplastic lesions showed age-associated prevalence, being more common in older cats, with epithelial and melanocytic lesions more frequent in females and round cell/mesenchymal lesions predominating in males. Non-diagnostic samples (33.80%) primarily resulted from insufficient cellularity or suboptimal quality, though no significant correlation existed between diagnostic success and clinical setting. This study underscores that cytology remains a fundamental diagnostic tool in feline medicine, particularly when combined with proper sampling techniques and complementary diagnostic methods, and reinforces its value in clinical decision-making, thereby supporting its broader utilisation in routine veterinary practice.