Pancreatic cancer is one of the most aggressive tumors, with a dismal prognosis due to poor detection rates at early stages, rapid progression, post-surgical complications, and limited effectiveness ...of conventional oncologic therapies. There are no consistently reliable biomarkers or imaging modalities to accurately diagnose, classify, and predict the biological behavior of this tumor. Therefore, it is imperative to develop new and improved strategies to detect pancreatic lesions in the early stages of cancerization with greater sensitivity and specificity. Extracellular vesicles, including exosome and microvesicles, are membrane-coated cellular products that are released in the outer environment. All cells produce extracellular vesicles; however, this process is enhanced by inflammation and tumorigenesis. Based on accumulating evidence, extracellular vesicles play a crucial role in pancreatic cancer progression and chemoresistance. Moreover, they may represent potential biomarkers and promising therapy targets. The aim of the present review is to review the current evidence on the role of extracellular vesicles in pancreatic cancer.
Pancreatic cancer (PC) is an increasing cause of cancer-related death, with a dismal prognosis caused by its aggressive biology, the lack of clinical symptoms in the early phases of the disease, and ...the inefficacy of treatments. PC is characterized by a complex tumor microenvironment. The interaction of its cellular components plays a crucial role in tumor development and progression, contributing to the alteration of metabolism and cellular hyperproliferation, as well as to metastatic evolution and abnormal tumor-associated immunity. Furthermore, in response to intrinsic oncogenic alterations and the influence of the tumor microenvironment, cancer cells undergo a complex oncogene-directed metabolic reprogramming that includes changes in glucose utilization, lipid and amino acid metabolism, redox balance, and activation of recycling and scavenging pathways. The advent of omics sciences is revolutionizing the comprehension of the pathogenetic conundrum of pancreatic carcinogenesis. In particular, metabolomics and genomics has led to a more precise classification of PC into subtypes that show different biological behaviors and responses to treatments. The identification of molecular targets through the pharmacogenomic approach may help to personalize treatments. Novel specific biomarkers have been discovered using proteomics and metabolomics analyses. Radiomics allows for an earlier diagnosis through the computational analysis of imaging. However, the complexity, high expertise required, and costs of the omics approach are the main limitations for its use in clinical practice at present. In addition, the studies of extracellular vesicles (EVs), the use of organoids, the understanding of host–microbiota interactions, and more recently the advent of artificial intelligence are helping to make further steps towards precision and personalized medicine. This present review summarizes the main evidence for the application of omics sciences to the study of PC and the identification of future perspectives.
Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence ...highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient’s gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.
(1) Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. The lack of validated disease biomarkers makes timely diagnosis challenging in most cases. Cell ...membrane and surface proteins play a crucial role in several routes of oncogenesis. The aim of this study was to evaluate the expression of six membrane antigens on PDAC (CA 19-9, mucin 1 and 4 (MUC1, MUC4), mesothelin (MSLN), Annexin A10 (ANXA10), Glypican-1 (GPC-1)) and their correlation with oncologic outcomes. (2) Methods: Immunohistochemical staining for CA 19.9, MUC1, MUC4, MSLN, ANXA10, and GPC-1 of surgical samples of 50 consecutive patients with PDAC was performed. Antigen expression for tumor, ductal, and acinar tissues was classified according to the histo-score (H-score) by two pathologists. (3) Results: Recurrence rate was 47% and 18 patients (36%) deceased (median follow-up 21.5 months). Immunostaining for CA 19-9 and MUC1 showed a significantly higher expression in the neoplastic tissue compared to non-tumor ductal and acinar tissues (p < 0.001). MUC4, MSLN, ANXA10, and GPC-1 were selectively expressed in the neoplastic tissue (p < 0.001). A CA 19-9 H-score value >270 was independently associated with a worse overall survival (p = 0.05) and disease-free survival (p = 0.05). (4) Conclusions: CA 19-9 and MUC1 are highly expressed in PDAC cells. The histological expression of CA 19-9 may predict prognosis. MUC4, MSLN, ANXA10, and GPC-1 are selectively expressed by neoplastic tissue and may represent a potential histological biomarker of disease.
The development of new applications in ultrasound (US) imaging in recent years has strengthened the role of this imaging technique in the management of different pathologies, particularly in the ...setting of liver disease. Improved B-mode imaging (3D and 4D), contrast-enhanced US (CEUS) and especially US-based elastography techniques have created the concept of multiparametric ultrasound (MP-US), a term borrowed from radiological sectional imaging. Among the new elastography techniques, shear wave dispersion is a newly developed imaging technology which enables the assessment of the shear waves' dispersion slope. The analysis of the dispersion qualities of shear waves might be indirectly related to the tissue viscosity, thus providing biomechanical information concerning the pathologic state of the liver such as necroinflammation. Some of the most recent US devices have been embedded with software that evaluate the dispersion of shear waves/liver viscosity. In this review, the feasibility and the clinical applications of liver viscosity are reviewed based on the preliminary findings of both animal and human studies.
The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal ...functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.
The aim of this study was to investigate the feasibility, the correlation with previously validated 2D-SWE by supersonic imagine (SSI), and the accuracy in fibrosis-staging of a novel point ...shear-wave elastography device (X+pSWE) in patients with chronic liver disease.
This prospective study included 253 patients with chronic liver diseases, without comorbidities potentially affecting liver stiffness. All patients underwent X+pSWE and 2D-SWE with SSI. Among them 122 patients also underwent liver biopsy and were classified according to histologic fibrosis. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while receiver operator characteristic curve (ROC) analysis with Youden index was used to establish thresholds for fibrosis staging.
A very good correlation was found between X+pSWE and 2D-SWE with SSI (r2 = 0.94;
< 0.001), with X+pSWE average liver stiffness values 0.24 kPa lower than those obtained with SSI. AUROC of X+pSWE for the staging of significant fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4) using SSI as a reference standard was 0.96 (95% CI, 0.93-0.99), 0.98 (95% CI, 0.97-1) and 0.99 (95% CI, 0.98-1), respectively. The best cut-off values for diagnosing fibrosis ≥F2, ≥F3 and F4 were, respectively, 6.9, 8.5 and 12 for X+pSWE. According to histologic classification, X+pSWE correctly identified 93 out of 113 patients (82%) for F ≥ 2 and 101 out of 113 patients (89%) for F ≥ 3 using the aforementioned cut-off values.
X+pSWE is a useful novel non-invasive technique for staging liver fibrosis in patients with chronic liver disease.
Patients affected by inflammatory bowel diseases (IBD) can nowadays benefit from a growing number of pharmacological options. However, in moderate-to-severe cases, the therapeutic response is still ...far from optimal, and treatment changes and optimizations are often required. Thus, researchers in this field are strongly engaged in studies aiming to identify new potential therapeutic targets. Extracellular vesicles (EVs) are tiny subcellular bodies with a phospholipid bilayer envelope containing bioactive molecules, which are released from different cells and are involved in intercellular communication. Recent pre-clinical data show their emerging role in the pathogenesis and treatment of IBD. In our review, we summarize current evidence about the function of EVs as active therapeutic agents in ulcerative colitis and Crohn's disease, analyzing the properties of EVs derived from different cellular sources and the mechanisms through which they may improve intestinal inflammation.
: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic ...tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described.
To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards.
: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome.
Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days:
0.525; 90-days:
0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days:
0.002; 90-days:
< 0.001). Delta-PCT was associated with a lower 28-days (
0.007; OR = 0.12, 95%CI 0.02-0.46) and 90-days mortality (
0.001; OR = 0.17, 95%CI 0.06-0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days:
0.047; 90-days:
0.049). Severe vitamin D deficiency was associated with a higher 28-days (
0.058; OR = 3.95, 95%CI 1.04-19.43) and 90-days mortality (
0.054; OR = 2.94, 95%CI 1.00-9.23).
: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.
Ultrasound imaging is the first-line investigation for patients with abdominal symptoms, as it effectively depicts the gastrointestinal tract and enables the diagnosis of multiple pathological ...conditions. Among different recent ultrasound technological advancements, elastography enables the evaluation of various tissue characteristics, such as neoplastic transformation or fibroinflammatory status. In recent years, ultrasound elastography has been utilized extensively for the study of liver diseases and in numerous other clinical settings, including gastrointestinal diseases. Current guidelines suggest the use of transabdominal ultrasound elastography to characterize bowel wall lesions, to assess gastrointestinal contractility, to diagnose and grade chronic pancreatitis; however, no specific indications are provided. In the present paper, we summarize the evidence concerning the application of different ultrasound elastography modalities in gastrointestinal non-liver diseases.
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