Theodoros V, Fotios F, Konstantinos M
… +29 more, Euaggelos C, Konstantinos A, George M, Konsantinos T, Paraskevi F, Spyridon M, Nikoletta M, Olga G, Evangelina V, George G, Ioannis D, Pantelis K, Maria T, Eirini Z, George T, Despoina A, Panagiota I, Margarita P, Christos L, Aggeliki C, Evanthia Z, Nikolaos K, Dimitrios N, Giorgos B, Jiannis V, Andreas K, Nikos V, Dimitrios C, George P
BACKGROUND: Studies from northern Europe indicate that patients with primary sclerosing cholangitis (PSC) are predominantly males and often have ulcerative colitis (UC) and increased risk of colorectal cancer (CRC). AIM:...BACKGROUND: Studies from northern Europe indicate that patients with primary sclerosing cholangitis (PSC) are predominantly males and often have ulcerative colitis (UC) and increased risk of colorectal cancer (CRC). AIM: To evaluate the epidemiological and clinical features and natural history of PSC in Greece, a southern European country. METHODS: In the HERACLIS-PSC study, consecutive patients with PSC-IBD followed at Greek inflammatory bowel disease (IBD) centers were included and compared to data from consecutive patients with PSC-only followed at a Greek liver center. RESULTS: Among PSC-IBD patients (n=112, males:56%), 62.5% had UC (pancolitis:76%), 35.7% Crohn's disease and 1.8% indeterminate colitis. PSC was diagnosed at a younger age in PSC-IBD than PSC-only patients (n=39; males:54%) (32±15 vs 40±15 years; p=0.007), while the two groups did not differ significantly in gender, extrahepatic bile duct involvement, or development of cirrhosis, cholangiocarcinoma or CRC, although CRC occurred only in PSC-IBD (n=8). Transplant-free survival was higher in PSC-IBD than PSC-only (5-/10-year:95%/87% vs 85%/77%; p=0.021), while older age at PSC diagnosis and cirrhosis development were independently associated with lower transplant-free survival. CONCLUSION: In Greece, PSC-IBD patients are usually males with UC, in whom PSC is diagnosed at a younger age demonstrating better transplant-free survival, compared to PSC-only.
BACKGROUND: Prospective evidence on Endoscopic Ultrasound-guided drainage (EUS-FCD) for Post-surgical Fluid Collections (PS-FCs) is lacking, and differences from Post-pancreatitis collections (PP-FCs) remain undefined. M...BACKGROUND: Prospective evidence on Endoscopic Ultrasound-guided drainage (EUS-FCD) for Post-surgical Fluid Collections (PS-FCs) is lacking, and differences from Post-pancreatitis collections (PP-FCs) remain undefined. METHODS: All consecutive patients undergoing EUS-FCD with Lumen Apposing Metal Stents (LAMSs) or Double-Pigtail Plastic Stents (DPPSs) between 2020-2024 were included in a prospective registry (PROTECT, ClinicalTrials.gov NCT04813055), with scheduled follow-up exploring efficacy and safety outcomes. RESULTS: At baseline, PS-FCs (N=41) versus PP-FCs (N=45) occupied fewer abdominal quadrants (p=0.04), showed reduced necrotic content (none/≤30% in 68% vs 42%, p<0.05), thus less frequently belonging to the high-risk Quadrant-Necrosis-Infection classifier (24% vs 49%, p=0.02). PS-FCs more frequently presented infection as the drainage indication (68% vs 29%, p=0.0003) and were drained earlier than PP-FCs (35 [17-69] vs 70 [40-200] days, p=0.0004), more frequently adopting DPPSs rather than LAMSs. Step-up (including necrosectomy) was significantly less frequent (20% vs 51%, p=0.002). Technical (100%) and Clinical success (95% vs 93%, p=0.9) were similar, whilst Adverse Events were lower in the PS-FCs (17% vs 40%, p=0.02), and no recurrence was registered (versus 7.5% in the PP group). CONCLUSIONS: PS-FCs occur earlier, are more often infected, but display simpler morphology, are more suitable for DPPS drainage, and carry a lower risk of step-up, adverse events, and recurrence.
BACKGROUND AND AIMS: Gastric outlet obstruction (GOO) is a late complication of several malignancies, markedly impairing quality of life. Surgical gastroenterostomy (S-GE) has long been the palliative standard, but outco...BACKGROUND AND AIMS: Gastric outlet obstruction (GOO) is a late complication of several malignancies, markedly impairing quality of life. Surgical gastroenterostomy (S-GE) has long been the palliative standard, but outcomes are variable and morbidity remains considerable. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We conducted a systematic review and meta-analysis comparing EUS-GE and S-GE, with a specific focus on malignant GOO. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Library were searched through September 2025. Eligible studies directly compared EUS-GE and S-GE and reported clinical success (CS), adverse events (AEs), severe AEs, and recurrence/reintervention. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: Thirteen studies (2 RCTs, 11 retrospective; 1,611 patients) were analyzed. Overall, EUS-GE achieved higher CS (OR 2.69; p=0.007), fewer AEs (OR 0.21; p<0.001) and severe AEs (OR 0.54; p=0.05) versus S-GE, with no significant difference in recurrence/reintervention rate (OR 0.54; p=0.22). In malignant GOO, CS (OR 1.90; p=0.12) and recurrence/reintervention rate (OR 0.68; p=0.50) were comparable, while overall AEs remained lower with EUS-GE (OR 0.26; p<0.01). CONCLUSIONS: In malignant GOO, EUS-GE provides comparable clinical efficacy to S-GE with fewer overall AEs. These data support EUS-GE as a preferred minimally invasive option in selected patients.
BACKGROUND: Stemness-related marker expression in hepatocellular carcinomas (HCC) has been associated with aggressive behavior. The association between miRNA expression and HCC stemness remains unclear. AIMS: To identify...BACKGROUND: Stemness-related marker expression in hepatocellular carcinomas (HCC) has been associated with aggressive behavior. The association between miRNA expression and HCC stemness remains unclear. AIMS: To identify miRNAs associated with stemness marker expression in HCC and their clinical significance. METHODS: MicroRNA microarray analysis was performed to identify microRNAs that were differentially expressed between EpCAM-positive and EpCAM-negative HCCs. The subcellular localization and expression level of miR-3920 was evaluated by locked nucleic acid-in situ hybridization analysis on surgically resected HCCs and paired non-tumor liver (NT). RESULTS: There was significant upregulation of miR-3920 in EpCAM-positive HCCs compared to EpCAM-negative cases (p = 0.025). Nuclear miR-3920 expression (p < 0.001) and the nuclear-to-total miR-3920 signal ratio (p < 0.001) were significantly higher in HCCs compared with NT. High nuclear-to-total miR-3920 signal ratio was positively correlated with stemness marker expression (EpCAM, p = 0.002; K19, p < 0.001), the presence of microvascular invasion (p = 0.004), major vessel invasion (p = 0.001) and mitosis (p < 0.001). Higher nuclear-to-total miR-3920 signal ratio was associated with significantly decreased overall survival (p = 0.010) and disease-free survival (p = 0.016). CONCLUSION: Increased expression of miR-3920 in the nuclei of HCC tumor cells was associated with stemness-related marker expression and aggressive clinicopathological features of HCC, suggesting a possible role for miR-3920 in HCC stemness and progression.
The PRODIGE 85-FFCD 1804-KANALRAD trial has been designed as a multicenter, randomized, open-label, phase III trial to compare the efficacy of induction chemotherapy (4 cycles of modified DCF: Docetaxel, Cisplatin, and 5...The PRODIGE 85-FFCD 1804-KANALRAD trial has been designed as a multicenter, randomized, open-label, phase III trial to compare the efficacy of induction chemotherapy (4 cycles of modified DCF: Docetaxel, Cisplatin, and 5-Fluorouracil) prior to standard chemoradiotherapy (CRT) versus standard CRT alone for histologically proven locally advanced squamous cell carcinomas of the anal canal (SCCA), either T3-4 or with lymph node involvement and no metastases. The primary endpoint is event-free survival at 2 years. Secondary endpoints include disease-free survival, complete response rate, patient quality of life, and monitoring of treatment-associated toxicities. A safety analysis is planned after enrollment of the 20 first patients in the experimental arm to ensure the feasibility of CRT after induction chemotherapy. In addition, genetic and epigenetic studies from tissue and circulating DNA will be conducted to assess their prognostic or predictive value. Overall, 310 patients will be recruited in France and will be followed for 3 years after randomization.
Aronico N, Santacroce G, Lucioni M
… +15 more, Lenti MV, Bianchi PI, Bagordo D, Vanoli A, Neri G, Ciacci C, Zingone F, Volta U, Elli L, Massironi S, Rossi RE, Corazza GR, Arcaini L, Paulli M, Di Sabatino A
BACKGROUND: Primary intestinal B-cell (IBCL) and T-cell (ITCL) lymphomas are rare and poorly characterized entities. AIM: To compare clinical features and survival outcomes of IBCL and ITCL. METHODS: We conducted a multi...BACKGROUND: Primary intestinal B-cell (IBCL) and T-cell (ITCL) lymphomas are rare and poorly characterized entities. AIM: To compare clinical features and survival outcomes of IBCL and ITCL. METHODS: We conducted a multicentre, retrospective study including patients diagnosed with primary intestinal lymphoma between 2001 and 2024. Clinical and laboratory variables were analysed using univariate and multivariate logistic regression. Discriminatory accuracy was assessed through ROC analysis. Overall survival was estimated with Kaplan-Meier curves. RESULTS: Ninety-four patients (41 IBCL and 53 ITCL) were included. IBCL were more frequently diagnosed at Lugano stage I (90% vs 5.7%; p<0.01) and showed markedly lower lactate dehydrogenase and β2-microglobulin levels compared with ITCL (p<0.01). Coeliac disease (CD) was strongly associated with ITCL (p<0.01). In multivariable analysis, CD and biomarker levels independently differentiated IBCL from ITCL, with excellent model discrimination (AUROC 0.95). Median follow-up was 56 months for IBCL and 12 months for ITCL. IBCL demonstrated significantly greater survival (HR 0.21; log-rank p=0.01). CONCLUSIONS: IBCL and ITCL exhibit distinct clinical and prognostic profiles, with IBCL showing more favourable clinical profile and better survival. Tailored diagnostic and therapeutic approaches that reflect the divergent behaviour of these lymphomas are urgently needed.
BACKGROUND: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of liver conditions, primarily driven by metabolic factors and characterized by steatosis. Extracellular vesicles and pa...BACKGROUND: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of liver conditions, primarily driven by metabolic factors and characterized by steatosis. Extracellular vesicles and particles (EVPs) are emerging as biomarkers for liver diseases as they reflect the state of their cells of origin and carry molecular cargo that can influence disease progression. We aimed to explore the role of EVPs with MASLD progression, smoking impact and EVPs effect on macrophages. METHODS: We analyzed EVPs using nanoparticle tracking analysis, transmission electron microscopy and flow cytometry. Cytokine expressions were quantified in EVPs-exposed macrophages. RESULTS: We showed that EVP number is higher in patients with steatohepatitis and they were correlated with the severity of liver inflammation and steatosis, as well as with biological markers. In particular CD63-ASGR1-EVPs were notably more prevalent in blood of patients with steatohepatitis. Active smoking further increased EVP numbers and CD63-ASGR1-EVPs in MASLD patients. Functionally, exposure of macrophages to CD63-EVPs from MASLD patients induced TGF-β and TIMP-1 secretion. CONCLUSION: This study highlights the potential of EVs as biomarkers for MASLD progression and their role in mediating disease mechanisms via intercellular communication, notably by their potential to contribute to fibrogenic signaling. Although exploratory, the study also highlights the potential impact of the exposome, particularly smoking, on MASLD pathogenesis.
BACKGROUND AND AIMS: Living donor liver transplantation (LDLT) helps address organ shortages but remains complex, particularly in Western countries where deceased donor liver transplantation (DDLT) is preferred. This stu...BACKGROUND AND AIMS: Living donor liver transplantation (LDLT) helps address organ shortages but remains complex, particularly in Western countries where deceased donor liver transplantation (DDLT) is preferred. This study evaluates improvements in LDLT outcomes over time for both donors and recipients. STUDY DESIGN: A single-center retrospective analysis from 2001-2023 including two periods: P-ONE (2001-2003, 36 cases) and P-TWO (2020-2023, 27 cases). Donor surgery after October 2022 marked the shift to a full robotic approach. Recipient procedures preserved the retro-hepatic vena cava, with standard vascular and biliary reconstruction. Comparisons include demographics, complications, and survival. RESULTS: P-ONE donors were younger (median age 32 vs. 46, P=0.003), while P-TWO recipients were older (63 vs. 56 years, P=0.005) with more comorbidities. P-TWO had more cases of hepatocellular carcinoma and low-MELD cirrhosis. Donor safety improved in P-TWO, with similar major complication rates (14% vs. 11%). Recipients in P-TWO had fewer severe complications (7% vs. 81%, P<0.001) and better 3-year graft survival. CONCLUSIONS: Advances in patient selection, minimally invasive surgery, and perioperative care have significantly improved LDLT outcomes. Despite persistent biliary challenges, LDLT remains a promising solution for end-stage liver disease and liver cancer.