Giulia Peserico

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a dismal prognosis; this is in part due to its late diagnosis at advanced stages. For many patients, medical treatment is the only practicable therapy. In recent years, the development of new technologies that investigate genomic biomarkers has improved the concept of precision medicine to treat patients with PDAC. Through endoscopic ultrasound–tissue acquisition (EUS-TA), tissue from pancreatic cancers can be collected; thus, it has the potential to advance personalized treatment by allowing the assessment of genomic alterations. In this review, we explore the role of EUS in genomic profiling and its strengths and pitfalls in obtaining samples for next-generation sequencing (NGS).

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited survival. Curative opportunities are only available for patients with resectable cancer. Palliative chemotherapy is the current standard of care for unresectable tumors. Numerous efforts have been made to investigate new therapeutic strategies for PDAC. Immunotherapy has been found to be effective in treating tumors with high microsatellite instability (MSI-H), including PDAC. The ability of the Endoscopic Ultrasound Fine Needle Biopsy (EUS-FNB) to reliably collect tissue could enhance new personalized treatment by permitting genomic alterations analysis. The aim of this study was to investigate the feasibility of obtaining adequate DNA for molecular analysis from EUS-FNB formalin-fixed-paraffin-embedded (FFPE) specimens. For this purpose, FFPE-DNA obtained from 43 PDAC archival samples was evaluated to verify adequacy in terms of quantity and quality and was tested to evaluate MSI-H status by droplet digital PCR (ddPCR). All samples were suitable for ddPCR analysis. Unlike the 1–2% MSI-H frequency found with traditional techniques, ddPCR detected this phenotype in 16.28% of cases. This study suggests the ddPCR ability to identify MSI-H phenotype, with the possibility of improving the selection of patients who may benefit from immunotherapy and who would be excluded by performing traditional diagnostic methods.

Ampullary lesions, neoplasms originating in the papilla of Vater, represent a rare yet clinically significant group of tumors with diverse etiologies and management challenges. This comprehensive review aims to elucidate the pivotal role of endoscopic ultrasound (EUS) in the diagnosis, staging, and management of ampullary lesions. This review begins by providing an overview of ampullary lesions, their epidemiology, and associated risk factors. We delve into their clinical presentation, emphasizing the importance of early and accurate diagnosis. Furthermore, we explore the limitations of traditional diagnostic modalities and highlight the growing relevance of EUS in ampullary lesion evaluation. We discuss the superior spatial resolution of EUS in comparison with other imaging methods, and we present an in-depth analysis of EUS-guided sampling and its pivotal role in obtaining histological samples for accurate diagnosis. In addition to diagnosis, we examine the indispensable role of EUS in ampullary lesion staging and its clinical implications. Furthermore, we discuss the potential of EUS in the surveillance and follow-up of ampullary lesions, ensuring timely detection of recurrence and monitoring treatment response in sporadic cases and in the context of familial syndromes, such as familial adenomatous polyposis (FAP). In conclusion, this review underscores the indispensable role of endoscopic ultrasound in the multifaceted approach to ampullary lesion evaluation. EUS not only enhances diagnostic accuracy but also informs treatment decisions and minimally invasive therapeutic interventions. As our understanding of ampullary lesions continues to evolve, EUS remains an invaluable tool for the improvement of patient outcomes and quality of life.

Background and Aims: Focal liver lesions (FLLs) are defined as abnormal solid or liquid masses differentiated from normal liver, frequently being clinically asymptomatic. The aim of this systematic review is to provide a comprehensive overview of current artificial intelligence (AI) applications, deep learning systems and convolutional neural networks, capable of performing a completely automated diagnosis of FLLs. Methods: We searched PubMed, Cochrane Library, EMBASE, and WILEY databases using predefined keywords. Articles were screened for relevant publications about AI applications capable of automated diagnosis of FLLs. The search terms included: (focal liver lesions OR FLLs OR hepatic focal lesions OR liver focal lesions OR liver tumor OR hepatic tumor) AND (artificial intelligence OR machine learning OR neural networks OR deep learning OR automated diagnosis OR ultrasound OR US OR computer scan OR CT OR magnetic resonance imaging OR MRI OR computer-aided diagnosis OR automated computer tomography OR automated magnetic imaging). Results: Our search identified a total of 32 articles analyzing complete automated imagistic diagnosis of FLLs, out of which 14 studies analyzing liver ultrasound images, 8 studies analyzing computer tomography images and 10 studies analyzing images obtained from magnetic resonance imaging. Conclusions: We found significant evidence demonstrating that implementing a complete automated system for FLLs diagnosis using AI-based applications is currently feasible. Various automated AI-based applications have been analyzed. However, there is no clear evidence about the superiority of any of the systems.

Background: Incidence of pancreatic cancer (PC) is increasing worldwide and is set to become the second leading cause of cancer-related death in 2040 with a poor 5-year overall survival (OS). The aim of this study was to analyze the impact of microscopic diagnosis of PC (MiDPC) on diagnostic–therapeutic management and outcome. Methods: The Veneto region (north-eastern Italy) has been covered by a cancer registry (CR) since 1987. Clinical and oncological data about all cases of PC in the Veneto region from 1987 were extracted from the Veneto CR database. Results: In 2018, 1340 incident cases of PC in the Veneto population were registered (4.1% of all malignant tumors), with an increasing trend in females and stable incidence in males. Five-year OS in patients with PC was 8%. The percentage of MiDPC increased from 44% in 2010 to 60% in 2018 (p = 0.001). MiDPC was higher among patients aged < 75 years old (84.4%) compared to those aged ≥75 years old (38.9%), p = 0.001. Between 2010 and 2018, a significant increase in biopsy on the primary neoplasm (24.9% vs. 13%, p < 0.001) was reported. Patients with MiDPC had higher 5-year survival than patients with no MiDPC (12.9% vs. 1.2%, p < 0.001). Conclusions: The implementation of MiDPC was essential to improve diagnostic–therapeutic pathways and consequently the survival of PC patients.

Background & Aims According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumors. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). Methods From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2‐5 cm; SEM‐HCC), 163 patients with larger tumors (>5 cm; LEM‐HCC) and 1,048 intermediate stage patients (BCLC B). Results LEM‐HCC patients had a worse overall survival (OS) than SEM‐HCC (31.0 vs. 49.0 months; p<0.0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29–2.05; p<0.0001). The small difference in OS between LEM‐HCC and BCLC B patients (31.0 vs. 27.0 months; p=0.03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77–1.25; p=0.89). In all monofocal tumors, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from “curative” to “palliative” therapies. The survival of resected patients with LEM‐HCC was significantly shorter than that of SEM‐HCC (44.0 vs. 78.0 months; p=0.002), but liver resection provided the highest survival benefit in both groups compared to other treatments. Conclusions Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.

Abnormal liver function tests (LFTs) are reported frequently in hospitalized coronavirus disease 2019 (COVID‐19) patients. A review of the literature shows that 46% of admitted COVID‐19 patients had elevated plasma aspartate aminotransferase (AST) and 35% had elevated alanine aminotransferase (ALT) levels on admission. Elevations of both AST and ALT are mostly below 5 times the upper reference limit and are associated with severe disease and increased inflammatory markers. AST and ALT elevations are more frequent in US patients compared to Chinese patients. Mild elevations in gamma‐glutamyltransferase (GGT), alkaline phosphatase (ALP) and total bilirubin are also reported, although less frequently. Significant impairment of liver function or overt liver failure as the cause of death in COVID‐19 rarely occur. There is no direct evidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) hepatic infection, although a subset of hepatocytes and cholangiocytes express the host receptor utilized for cellular entry by SARS‐CoV‐2. The presence of pre‐existing liver disease in patients with elevated LFTs on admission has not been comprehensively assessed in most studies but is unlikely to account for all abnormalities in LFTs. Although abnormal LFTs are already frequently present upon admission before the start of treatment, drug‐induced liver injury should be taken into consideration, especially after the use of acetaminophen, lopinavir/ritonavir and remdesivir, which are potentially hepatotoxic. In conclusion, these initial observations suggest that the prevalence of abnormal LFTs is high in COVID‐19 patients, but that the clinical relevance is limited and that treatment is not required. The mechanisms underlying abnormal LFTs in COVID‐19 are likely multifactorial and related to a hyper‐inflammatory status and thrombotic microangiopathy that are observed in severe COVID‐19 disease.