Many tumors may secondarily involve the pancreas; however, only retrospective autopic and surgical series are available. We retrospectively collected data from all consecutive patients with histologically confirmed secondary tumors of the pancreas referred to five Italian centers between 2010 and 2021. We described clinical and pathological features, therapeutic approach and treatment outcomes. EUS characteristics of the lesions and the tissue acquisition procedures (needle, passages, histology) were recorded. A total of 116 patients (males/females 69/47; mean age 66.7) with 236 histologically confirmed pancreatic metastases were included; kidney was the most common primary site. EUS was performed to confirm the diagnosis in 205 lesions which presented as predominantly solitary (59), hypoechoic (95) and hypervascular (60), with a heterogeneous (n = 54) pattern and well-defined borders (n = 52). EUS-guided tissue acquisition was performed in 94 patients with an overall accuracy of 97.9%. Histological evaluation was possible in 88.3% of patients, obtaining final diagnosis in all cases. When cytology alone was performed, the final diagnosis was obtained in 83.3% of cases. A total of 67 patients underwent chemo/radiation therapy, and surgery was attempted in 45 (38.8%) patients. Pancreatic metastases are a possible event in the natural history of solid tumors, even long after the diagnosis of the primary site. EUS-guided fine needle biopsy may be suggested to implement the differential diagnosis.

Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett’s esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP^® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.

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.

Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration.

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.