Background: Contrast-enhanced ultrasound (CEUS) has become the preferred method for many clinicians in evaluating focal liver lesions (FLLs) initially identified through standard ultrasound. However, in clinical practice, certain lesions may deviate from the typical enhancement patterns outlined in EFSUMB guidelines. Methods: This study aims to assess FLLs that remained inconclusive or misdiagnosed after CEUS evaluation, spanning eight years of single-center experience. Following CEUS, all FLLs underwent secondary imaging (CT, MRI) or histopathological analysis for diagnostic confirmation. Results: From the initial 979 FLLs, 350 lesions (35.7%) were either inconclusive or misdiagnosed by CEUS, with hepatocellular carcinoma (HCC) and liver metastases constituting the majority of these cases. The most frequent enhancement pattern in inconclusive lesions at CEUS was hyper-iso-iso. Factors such as advanced liver fibrosis, adenomas, and cholangiocarcinoma were significantly associated with higher rates of diagnostic inaccuracies. Conclusions: Advanced liver fibrosis, adenomas, and cholangiocarcinoma were significantly associated with increased diagnostic challenges, emphasizing the need for supplementary imaging techniques.

Background and Aims: Elastography can provide information regarding tissue stiffness (TS). This study aimed to analyze the elastographic features of hepatocellular carcinoma (HCC) and the factors that influence intratumoral elastographic variability in patients with liver cirrhosis. Methods: This prospective study included 115 patients with liver cirrhosis and hepatocellular carcinoma evaluated between June 2016–November 2019. A total of 88 HCC nodules visualized in conventional abdominal ultrasound (US) met the inclusion criteria and underwent elastographic evaluation. Elastographic measurements (EM) were performed in HCC and liver parenchyma using VTQ (Virtual Touch Quantification), a point shear wave elastography (pSWE) technique. In all patients, we performed contrast-enhanced ultrasound (CEUS), and the final diagnosis of HCC was established by contrast-enhanced-CT or contrast-enhanced-MRI. Results: The mean VTQ values in HCCs were 2.16 ± 0.75 m/s. TS was significantly lower in HCCs than in the surrounding liver parenchyma 2.16 ± 0.75 m/s vs. 2.78 ± 0.92 (p < 0.001). We did not find significant differences between the first five and the last five EM, and the intra-observer reproducibility was excellent ICC: 0.902 (95% CI: 0.87–0.950). However, the tumor size, heterogeneity, and depth correlated with higher intralesional stiffness variability (p < 0.001). Conclusions: VTQ brings additional information for HCC characterization. Intra-observer reproducibility for both HCC and liver parenchyma was excellent. Knowing the stiffness of HCC’s might endorse an algorithm-based approach towards focal liver lesions (FLLs) in liver cirrhosis.

Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC). Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous. Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22–735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a “butyrate-rich” baseline profile was 44% (95% CI 35–54) versus 21% (95% CI 15–29) in controls (I² = 18%). Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment.

Pancreatic ductal adenocarcinoma (PDAC) remains a high-burden disease worldwide with increasing incidence, poor prognosis, and high mortality. Complete surgical resection is the only potentially curative treatment; however, due to a lack of symptoms in the early stages, most patients have advanced disease when diagnosed. Type 2 diabetes mellitus (T2DM) is a significant health concern characterized by hyperglycemia, insulin resistance, and impairment in insulin secretion. T2DM is linked with PDAC, sharing a complex bidirectional relationship. Therefore, dual causality between the two diseases represents significant challenges in practice, distinguishing existing T2DM as a PDAC risk factor from newly onset, potentially pancreatic cancer-related diabetes (PCRD). Evidence showed that new-onset diabetes (NOD) may serve as a biomarker for early diagnosis of PDAC, and several risk prediction models were developed to identify high-risk patients for further intervention. Although early PDAC detection is important, widespread screening is not currently recommended for T2DM patients due to a lack of cost-effective, efficient screening modalities. However, further risk stratification in diabetic patients is warranted to support a targeted screening strategy with economic viability. Diabetes confers ≈2-fold PDAC risk overall, with the highest relative risk in the first 2–3 years after diagnosis. Strategies using clinical signs (age ≥50–60 years, unintentional weight loss, rapid HbA1c escalation/insulin initiation) and predictive risk scores (e.g., ENDPAC) can triage NOD patients for magnetic resonance imaging/computed tomography (MRI/CT) and endoscopic ultrasound (EUS). A targeted screening approach may allow early diagnosis that could improve the prognosis of PDAC patients. This narrative review aims to synthesize current evidence linking T2DM and PDAC; delineate risk factors within diabetes populations; appraise predictive models and biomarkers for differentiating PCRD from typical T2DM; outline pragmatic, risk-adapted screening strategies, especially for NOD, and identify additional areas where further research is needed.

Backg round: Shear-wave elastography (SWE) performed during endoscopic ultrasound (EUS) is a promising tool for quantifying pancreatic stiffness, but its intra-session reproducibility remains incompletely defined. Meth ods: In this prospective single-center study, 86 consecutive patients (median age 66 years; 59.3% women) referred for diagnostic EUS underwent EUS-guided point SWE. Ten measurements were acquired from a 10 × 15 mm region of interest in the pancreatic body or tail when the breath was held by a single expert operator. Reproducibility was assessed by comparing the first and last five acquisitions; intra-individual variability was expressed as the coefficient of variation (CV). Results: Mean stiffness was 18.5 ± 8.9 kPa (2.31 ± 0.58 m/s). Agreement between early and late measurements was excellent in kPa (ICC = 0.99; r = 0.997; mean bias −0.06 kPa) and moderate in m/s (ICC = 0.61; r = 0.61). The mean CVs were 0.640 for kPa and 0.328 for m/s. Sex, age, and BMI had no significant influence on stiffness or reproducibility. The technical success rate was 97%, with no adverse events. Conclusions: EUS-guided point SWE provides highly reproducible pancreatic stiffness measurements within a single session, particularly when expressed in kPa. Demographic factors do not affect stability, supporting its integration into routine EUS practice. Further multicenter studies are needed to establish pathology-specific cut-offs and confirm clinical relevance.

Background: Direct-acting antiviral (DAA) therapy has transformed chronic hepatitis C virus (HCV) infection into a curable disease. Beyond viral eradication, increasing attention has been directed toward metabolic changes following sustained virological response (SVR), particularly alterations in lipid metabolism. This study aimed to assess the long-term evolution of lipid parameters after HCV cure in a real-world clinical cohort. Methods: We conducted a prospective, single-center observational study including 85 patients with chronic HCV infection who achieved SVR after DAA therapy. Lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, were assessed at baseline and during post-SVR follow-up at 24, 48, and 96 weeks. Body mass index (BMI) and non-invasive fibrosis indices were also evaluated. Longitudinal changes were analyzed using mixed-effects models. Results: Total cholesterol increased from 157.7 ± 35.6 mg/dL at baseline to 179.6 ± 42.9 mg/dL at SVR 24 and further to 189.0 ± 40.3 mg/dL at SVR 48, stabilizing at 177.7 ± 38.3 mg/dL at SVR 96. LDL-C showed a similar trajectory from 94.6 ± 30.8 mg/dL at baseline to 107.5 ± 33.3 mg/dL at SVR 24, further raising to 115.7 ± 36.2 mg/dL at SVR48, and 111.8 ± 39.5 mg/dL at SVR 96. HDL-C showed minimal change, while triglycerides demonstrated greater interindividual variability without a consistent population-level trend. BMI remained stable over follow-up (26.6 ± 4.7 to 27.6 kg/m²). Linear mixed-effects models confirmed a significant effect of time after SVR on total cholesterol and LDL-C (p < 0.05). Conclusions: In this real-world cohort, HCV cure with DAA therapy was associated with sustained long-term changes in lipid metabolism, characterized by increases in total cholesterol and LDL-C independent of major weight changes. These findings support the importance of continued metabolic monitoring after SVR, particularly in patients with additional cardiometabolic risk factors.