Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is usually diagnosed at advanced stages. The diagnosis of PDAC is established through pancreatic cytology/tissue biopsy, most commonly...Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is usually diagnosed at advanced stages. The diagnosis of PDAC is established through pancreatic cytology/tissue biopsy, most commonly obtained under endoscopic ultrasound-guidance. Although this approach is generally safe and accurate for the histological diagnosis, maintaining/obtaining material for additional molecular analysis may be challenging. Thus, there is growing interest in minimally invasive approaches capable of providing molecular information without necessarily requiring tissue sampling. Liquid biopsy (LB) represents a significant advancement in this regard, being a minimally invasive tool for biomarker analysis and with the potential to improve patient management at various levels. The most relevant biomarkers that LB can detect are circulating tumor cells, cell-free DNA, circulating miRNA, and extracellular vesicles. Integrating LB into the clinical workflow may improve the diagnosis, prognosis, and monitoring of the disease, even for patients affected by PDAC and with potential implications on early detection approaches. Despite significant progress, no LB assay is yet validated for routine PDAC management; however, growing evidence suggests that multimodal LB integration may soon reshape diagnostic and surveillance strategies. Here we provide a comprehensive overview on liquid biopsy in pancreatic cancer, presenting its current progress, limitations, and future perspectives.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly emerged as the leading cause of chronic liver disease worldwide, gradually replacing viral hepatitis in clinical and epidemiological relevance....Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly emerged as the leading cause of chronic liver disease worldwide, gradually replacing viral hepatitis in clinical and epidemiological relevance. Italian data mirror global trends, with prevalence escalating in general and high-risk populations, particularly among individuals with type 2 diabetes (T2D), obesity, and metabolic syndrome (MetS). Disease progression from steatosis to steatohepatitis (MASH) and advanced fibrosis markedly increases the risk of cirrhosis, hepatocellular carcinoma (HCC), and cardiovascular mortality. Recent regulatory frameworks from FDA and EMA have accelerated therapeutic development, with Resmetirom and Semaglutide representing the first agents to achieve histological efficacy in Phase 3 trials for patients with MASH and F2-F3 fibrosis. Building upon these advances, the AISF STEPS-MASH framework provides a structured approach for the identification, selection, and monitoring of patients eligible for therapy. This position paper outlines evidence-based recommendations for the integration of emerging pharmacological strategies into clinical practice in Italy, emphasizing both high-risk and broader metabolic populations.
Hepatocellular carcinoma (HCC) is a major global health burden, and imaging is crucial for its detection, characterization, and post-treatment assessment. The Liver Imaging Reporting and Data System (LI-RADS) was develop...Hepatocellular carcinoma (HCC) is a major global health burden, and imaging is crucial for its detection, characterization, and post-treatment assessment. The Liver Imaging Reporting and Data System (LI-RADS) was developed to standardize terminology, interpretation, and reporting in at-risk patients, reducing variability and improving communication in clinical practice. This review outlines the spectrum of focal liver lesions in cirrhosis and provides a comprehensive overview of LI-RADS across surveillance, diagnostic, and treatment response algorithms, with particular focus on the most recent updates, including the 2024 versions. Evidence from recent literature and current guidelines integration is summarized, and future perspectives are discussed, highlighting ongoing needs for wide adoption, simplification, and incorporation of novel imaging strategies.
Facciorusso A, Giannini EG, Tacelli M
… +12 more, Zanetto A, Spada C, Boskoski I, Furnari M, Pennisi G, Capurso G, Vitello A, Marasco G, Sarnelli G, Frulloni L, Maida M, Italian Society of Gastroenterology (SIGE)
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut...Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut-pancreas-liver axis have raised both therapeutic interest and safety concerns, particularly regarding hepatic outcomes, gastrointestinal cancers, peri-endoscopic management, and gastrointestinal adverse events. This position paper, endorsed by the Italian Society of Gastroenterology (SIGE), was developed according to the GRADE framework and provides evidence-based recommendations for the safe and effective management of GLP-1RAs in gastroenterology, highlighting their favorable benefit-risk profile while identifying key knowledge gaps requiring future prospective studies. GLP-1RAs may be safely used in patients with diabetes or obesity and metabolic dysfunction-associated steatotic liver disease. In cirrhotic patients with diabetes or obesity, GLP-1RAs appear safe and are associated with reduced hepatic decompensation. Available evidence does not support an increased risk of esophageal, gastric, colorectal, or pancreatic cancer, while a potential reduction in hepatocellular carcinoma incidence is suggested. Routine discontinuation of GLP-1RAs before upper gastrointestinal endoscopy is not recommended. GLP-1RAs increase the risk of mild, transient gastrointestinal adverse events and cholelithiasis but are not associated with severe gastrointestinal complications or acute pancreatitis.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with chemotherapy remaining the backbone of systemic treatment across disease stages. Although multi-agent regimens such as modified FOLFIRI...Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with chemotherapy remaining the backbone of systemic treatment across disease stages. Although multi-agent regimens such as modified FOLFIRINOX and gemcitabine plus nab-paclitaxel-based combinations, with or without cisplatin and capecitabine (AG or PAXG), have improved outcomes in selected patients, therapeutic benefit remains highly heterogeneous and frequently limited by toxicity. This review summarizes evidence supporting shift from empirical chemotherapy selection toward a more personalized approach integrating tumour biology, molecular biomarkers, and patient-related factors, including pharmacogenetics, comorbidities, and toxicity profiles. We discuss established standards of care and highlight the strengths and limitations of available randomized data. The molecular landscape of PDAC, including homologous recombination repair deficiency, mismatch repair deficiency, and rare actionable oncogenic fusions, currently enables precision strategies in a minority of patients. The rapid development of KRAS-targeted therapies may extend molecularly guided treatment to a broader population. Beyond genomics, emerging biomarkers such as transcriptomic signatures, liquid biopsies, proteomic and metabolomic markers, and tumour microenvironment features may refine treatment selection and guide de-escalation or intensification strategies. Finally, we review biomarker-driven clinical trials and outline future directions for adaptive, biology-informed chemotherapy. Integrating molecular and clinical data into routine care may enable a more rational use of chemotherapy and improve outcomes in PDAC.
Over the past decade, the field of liver transplantation (LT) has evolved remarkably, driven by advances in medical therapy, donor procurement, and candidate selection. The changing epidemiology of liver disease has resh...Over the past decade, the field of liver transplantation (LT) has evolved remarkably, driven by advances in medical therapy, donor procurement, and candidate selection. The changing epidemiology of liver disease has reshaped the LT candidate profile, with increasing numbers of sicker, older, frailer, and more comorbid patients requiring multidisciplinary evaluation and tailored perioperative management. Robust assessment of post-LT outcomes has supported the expansion of transplant eligibility criteria to include patients with alcohol-related liver disease with abstinence of <6 months, severe alcohol-related hepatitis not responding to medical therapy, and hepatocellular carcinoma with higher tumour burden than conventional criteria. Moreover, selected patients with hepatic malignancies previously considered contraindications-such as colorectal cancer metastases and intrahepatic cholangiocarcinoma-appear to gain a survival benefit from LT and may soon represent accepted indications to be applied in many transplant programs worldwide. Simultaneously, surgical innovations, organ harvesting and preservation techniques and harmonized allocation systems have enhanced organ utilization and reduced waiting list mortality. Contemporary LT practice thus reflects a delicate balance between innovation and ethical responsibility. Remaining challenges include promoting equitable access, refining prognostic and psychosocial assessment tools, and adapting allocation frameworks to evolving patient populations. The future evolution of LT will depend on integrating technological progress, personalized care, and evidence-based selection to maximize survival benefit and societal value.
Carconi C, Capurso G, Abati M
… +16 more, Vincenzi MM, Burini A, Cardellini S, Pavarini M, Ubeira-Gabellini MG, Palumbo D, Pecorelli N, Macchini M, Liscia N, Campisi A, Guarneri G, Vanella G, Fiorino C, Falconi M, Reni M, Orsi G
BACKGROUND & AIMS: Nutritional status alterations are common in pancreatic ductal adenocarcinoma (PDAC), but their prognostic role in patients undergoing chemotherapy remains unclear. We assessed the impact of clinical-n...BACKGROUND & AIMS: Nutritional status alterations are common in pancreatic ductal adenocarcinoma (PDAC), but their prognostic role in patients undergoing chemotherapy remains unclear. We assessed the impact of clinical-nutritional variables on treatment outcomes in advanced PDAC patients. METHODS: Clinical, anthropometric, and radiological data of locally advanced/metastatic PDAC patients treated with polychemotherapy (2019-2021), prospectively collected within the observational PAC-MAIN study (NCT04112836) were analyzed. Key predictors of progression-free (PFS) and overall survival (OS) were identified through a multistep feature selection process, developing the Pancreatic Adenocarcinoma Nutritional-Clinical Index (PANCIN). Associations with CA19.9, radiological response, chemotherapy dose intensity and toxicity were explored. RESULTS: Among 74 patients, Vitamin B12 levels, Mid-Upper Arm Circumference, and Visceral Fat-to-Muscle area Ratio were included in the PANCIN, emerging as strongest PFS/OS predictors. According to PANCIN stratification, median PFS was 6.2 (95% CI 3.5-9.7) vs 14.1 (8.8-20.3) months, and median OS was 10.4 (7.5-15.1) vs 19.8 (11.3-31.1) months, for high- vs low-risk patients, respectively (p < 0.001). PANCIN significantly correlated with CA19.9 and radiological response, infections and grade ≥3 hematologic toxicities. CONCLUSIONS: PANCIN is a novel prognostic tool combining clinical-nutritional and radiological features, potentially aiding risk stratification and early nutritional support in advanced PDAC patients.
BACKGROUND: Pediatric Pi*ZZ alpha-1 antitrypsin deficiency (A1ATD) can cause hepatocyte A1AT polymer retention and progressive liver injury, but estimates of childhood liver morbidity vary across studies and remain poorl...BACKGROUND: Pediatric Pi*ZZ alpha-1 antitrypsin deficiency (A1ATD) can cause hepatocyte A1AT polymer retention and progressive liver injury, but estimates of childhood liver morbidity vary across studies and remain poorly defined. AIM: To quantify liver-specific outcomes in pediatric Pi*ZZ A1ATD. METHODS: We systematically reviewed studies reporting liver-specific outcomes in children with confirmed Pi*ZZ/ZZ A1ATD (PROSPERO CRD42022335666). We extracted prevalence of fibrosis and cirrhosis, elevated liver enzymes, and liver transplantation. Random-effects meta-analysis pooled logit-transformed proportions (with sensitivity analyses assessing robustness to model assumptions). RESULTS: Thirteen studies including 398 children met inclusion criteria. Pooled prevalence was 41.3% (95% CI 29.6-54.0) for fibrosis and 17.3% (7.2-35.9) for cirrhosis, with substantial heterogeneity for cirrhosis (I 78.6%). Liver transplantation prevalence was 10.7% (6.3-13.0). Elevated liver enzymes occurred in 43.0% (19.2-70.5) with high heterogeneity (I 89.4%). Across cohorts, the proportion with elevated liver enzymes declined with increasing mean age, despite ongoing liver disease in reported histology-based outcomes. CONCLUSIONS: Clinically important liver disease occurs in a substantial subset of children with Pi*ZZ A1ATD. Declining rates of elevated liver enzymes with age should not be interpreted as disease resolution. Standardized registries are needed for longitudinal surveillance, to identify disease modifiers, and to guide early intervention in this high-risk population.
BACKGROUND: The Mediterranean Diet (MD) is considered a balanced dietary model, whereas high consumption of highly processed foods (HPF) may worsen metabolic health. We aimed to compare adherence to the MD and HPF consum...BACKGROUND: The Mediterranean Diet (MD) is considered a balanced dietary model, whereas high consumption of highly processed foods (HPF) may worsen metabolic health. We aimed to compare adherence to the MD and HPF consumption between patients with Crohn's Disease (CD) and Ulcerative Colitis (UC), and to assess their relationship with disease activity. A secondary objective was to explore the association between dietary patterns and metabolic parameters. METHODS: Adherence to the MD was assessed using the Pyramid Mediterranean Diet Score (PyrMDS), while HPF intake was evaluated with the short questionnaire on highly processed foods (sQ-HPF). RESULTS: 193 consecutive IBD patients were included. CD patients showed significantly lower adherence to the MD compared with UC patients (median PyrMDS 9.3 vs 9.8, p = 0.02), while HPF consumption was similar in both groups (median sQ-HPF 3). In CD patients, a trend toward an inverse correlation was observed between MD adherence and disease activity (p = 0.07). Higher HPF consumption was positively associated with metabolic syndrome (median sQ-HPF 4 vs 3, p = 0.01). CONCLUSIONS: CD patients exhibit lower adherence to the MD, particularly during periods of higher disease activity, while greater HPF intake is linked to adverse metabolic profiles. Tailored nutritional counseling is important for supporting healthier dietary patterns in individuals with IBD.
Metabolic liver diseases represent a growing global health concern with significant diagnostic and prognostic implications. Imaging offers non-invasive alternatives to biopsy for diagnosis, staging, and follow-up. This r...Metabolic liver diseases represent a growing global health concern with significant diagnostic and prognostic implications. Imaging offers non-invasive alternatives to biopsy for diagnosis, staging, and follow-up. This review summarizes current imaging techniques used in metabolic liver disease, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and advanced modalities such as MRI elastography and PET/MRI. Particular focus is given to quantitative biomarkers such as elastography, proton density fat fraction (PDFF) and R2* mapping, their clinical utility, and future directions in artificial intelligence and radiomics. A practical framework for imaging-based assessment is proposed to aid clinicians and radiologists in optimizing patient management.
Crippa S, de Nucci G, Belfiori G
… +28 more, Pollini T, Bonamini D, Di Salvo F, Manfredi G, Alicante S, Sperti C, Moletta L, Pozza G, Manes G, Muscia R, Carrara S, Di Leo M, Zerbi A, Antonini F, Frulloni L, De Marchi G, De Petris N, Blanco GDV, Galli A, Pezzullo A, Fantin A, Stillittano D, Monica F, Germanà B, Bellini M, Cannizzaro R, Buscarini E, Falconi M
BACKGROUND: Studies on surveillance of Intraductal Papillary Mucinous Neoplasms (IPMNs) are mainly retrospective with inherited bias. AIM: To identify factors associated with the development of relevant changes in low ri...BACKGROUND: Studies on surveillance of Intraductal Papillary Mucinous Neoplasms (IPMNs) are mainly retrospective with inherited bias. AIM: To identify factors associated with the development of relevant changes in low risk IPMN under surveillance. METHODS: This study analysed IPMN patients enrolled between 2015-2017 in the prospective observational multicentric registry PANcreatic CYsts (PANCY), focusing on brunch duct (BD). Extension of surveillance until December 31st, 2021 was proposed to the recruited patients. Relevant changes were defined as: worrisome features/high risk stigmata/pancreatic cancer, pancreatectomy, death due to IPMN/pancreatic cancer. RESULTS: At diagnosis, from 647 IPMNs, 547 (60%) were BD, 87 (9%) mixed type, and 13 (1%) main duct. 57 (8.8%) underwent immediate surgery and 590 (91.2%) active surveillance. Of them 34 (5.7%) underwent surgery with 2/3 malignancy. Malignancy rates for BD- and mixed-IPMNs under surveillance were 2.7% and 12.5%. Smoking (OR 2.2) and cyst size >15 mm at diagnosis (OR 7.1) were independent risk factors for relevant changes at multivariate analysis. The combination of cyst size ≤15 mm & age >65 was a protective factor at univariate analysis (OR 0.1), mainly in no smokers (OR 0.2, p < 0.01). CONCLUSIONS: BD-IPMN progression risk is low for lesions <15 mm in non-smokers, >65 years patients. Surgery and follow-up criteria are still imperfect, leading to inappropriate utilization of resources.
BACKGROUND AND AIMS: Lipocalin-2 (LCN-2), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/LCN-2 complex are emerging biomarkers for ulcerative colitis (UC). While extensively studied in adults, data in children are lim...BACKGROUND AND AIMS: Lipocalin-2 (LCN-2), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/LCN-2 complex are emerging biomarkers for ulcerative colitis (UC). While extensively studied in adults, data in children are limited. This study aimed to evaluate their serum levels in children with newly diagnosed UC, compare them with healthy controls, and assess correlations with disease severity and extent. METHODS: In this prospective case-control study, 32 children with UC (6-18 years) and 38 healthy controls were enrolled. Baseline clinical (Pediatric Ulcerative Colitis Activity Index/ PUCAI), laboratory (albumin, hemoglobin, Erythrocyte Sedimentation Rate, C-reactive protein/CRP, fecal calprotectin), and endoscopic (extent, Ulcerative Colitis Endoscopic Index of Severity/UCEIS) data were collected. Serum LCN-2, MMP-9, and MMP-9/LCN-2 complex levels were measured by ELISA. RESULTS: Serum LCN-2, MMP-9, and MMP-9/LCN-2 levels were significantly higher in UC patients than controls. ROC analysis indicated LCN-2 had the best diagnostic performance. Higher LCN-2 and MMP-9 levels were observed in children with more severe endoscopic disease (UCEIS > 4) or pancolitis. LCN-2 levels inversely correlated with albumin, whereas MMP-9 positively correlated with CRP and UCEIS. CONCLUSIONS: LCN-2 and MMP-9 are promising biomarkers in pediatric UC, reflecting disease severity and extent. Their measurement may have clinical utility in monitoring disease progression and guiding management in children.
Martin A, Bekdache O, Meyer A
… +12 more, Bassil C, Bou-Farah R, Bellanger C, Vibert E, Vaysse T, Laurent V, Steuer N, Houist GC, Carbonnel F, Amiot A, Meyrignac O, Boytchev I
INTRODUCTION: Accurate descriptions of the extent of disease in intrahepatic bile ducts are essential for managing patients with perihilar cholangiocarcinoma (pCCA). This study describes and assesses a new, automated Com...INTRODUCTION: Accurate descriptions of the extent of disease in intrahepatic bile ducts are essential for managing patients with perihilar cholangiocarcinoma (pCCA). This study describes and assesses a new, automated Computed Tomography (CT)-scan-based 3D reconstruction process (3DR) of biliary tree in these patients compared with magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied consecutive patients with histologically proven hilar cholangiocarcinoma, who were referred for biliary drainage by ERCP in our center between 2015 and 2023. Automated reconstruction of bile ducts from CT images was performed using an artificial intelligence software (Synapse 3D 6.7, Fujifilm, Tokyo, Japan). We compared the Bismuth-Corlette classification assessed by ERCP (gold-standard), MRCP, CT-scan, and 3DR by computing exact percentage and weighted Kappa agreements. RESULTS: We included 62 patients. As compared with ERCP, CT-scan without 3DR had an exact agreement of 48% and had a moderate weighted Kappa agreement (weighted Kappa 0.47; 95%CI: 0.27-0.67). The MRCP had an exact agreement of 52% and a moderate weighted Kappa agreement (weighted Kappa 0.57; 95%CI: 0.39-0.76). The 3DR had an exact agreement of 60%, and a strong weighted Kappa agreement (weighted Kappa 0.72; 95%CI: 0.60-0.85). CONCLUSION: 3DR is highly concordant with ERCP in assessing the extent of pCCA.
Colucci A, Creoli M, Umano GR
… +10 more, Rondinelli G, Giudice EMD, Milano M, Mennitti C, Vela V, Casertano M, Sessa AD, Cenni S, Scudiero O, Strisciuglio C
BACKGROUND: Several studies demonstrated a link between obesity and Disorders of Gut-Brain Interaction (DGBIs). In patients with obesity, it has been shown an alteration of inflammation markers. AIMS: The study aims to a...BACKGROUND: Several studies demonstrated a link between obesity and Disorders of Gut-Brain Interaction (DGBIs). In patients with obesity, it has been shown an alteration of inflammation markers. AIMS: The study aims to assess the prevalence of DGBIs in pediatric population with obesity and to examine any potential differences in inflammation markers between children with and without DGBIs. METHODS: We conducted a cross-sectional, observational study in children with obesity, analyzing age, sex, puberal stage, anthropometry, clinical history, laboratory tests, abdominal ultrasound, bile acid levels (BA) and evaluation of DGBIs assessed via Rome IV criteria RESULTS: A total of 200 children with BMI z-score > +2 SD were enrolled. Results showed that 36.5% of the children had at least one DGBI, with functional constipation (FC) (70.4%) being the most prevalent. A significant association was found between DGBIs and altered serum BA levels, with a higher prevalence in prepubertal children. Additionally, 41.1% of DGBI patients exhibited non-alcoholic fatty liver disease (NAFLD). CONCLUSION: Our results confirm that DGBIs are very common in the pediatric population with obesity and the most prevalent is FC. Moreover, the strong association between altered serum BA levels, NAFLD, and DGBI suggests a shared metabolic pathway that could be utilized for diagnosis and treatment.