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To describe CT characteristics of primary pancreatic lymphoma (PPL), a rare disease with features in common with adenocarcinoma.

The vitamin D system is deregulated during development and progression of several cancer types. Data on the expression of the vitamin D system in the diseased pancreas are missing. The aim of this study was to investigate the expression of the vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1), and the calcium-sensing receptor (CaSR), a vitamin D target gene, in the different regions of the pancreas in patients with chronic pancreatitis (n=6) and pancreatic ductal adenocarcinomas (PDAC) (n=17). We analyzed the expression of these genes at mRNA and protein level with quantitative real-time RT-PCR and immunostaining. mRNA expression of CYP24A1 and VDR was significantly increased in tumors compared with the adjacent non-tumorous tissue (p<0.01), while CaSR mRNA expression decreased. Both the VDR and the CaSR protein were highly expressed in the endocrine compared with the exocrine pancreas. In CP the CYP24A1 expression was highest in the endocrine pancreas, while in PDACs in the transformed ducts. In the PDAC patients CYP24A1 expression in the islets was significantly lower than in CP patients. Our data suggest that during ductal adenocarcinoma development the vitamin D system in the pancreas becomes deregulated on two levels: in the islets CYP24A1 expression decreases weakening the negative feedback regulation of the vitamin D-dependent insulin synthesis/secretion. In the transformed ducts CYP24A1 expression increases, impairing the antiproliferative effect of vitamin D in these cells.

The most common pancreatic diseases in cats are pancreatitis and exocrine pancreatic insufficiency (EPI). Non-invasive methods, such as serological quantification of feline pancreatic lipase immunoreactivity (fPLI), are often used in the diagnosis of pancreatitis. Previous studies have compared fPLI concentrations with histopathology, considered to be the gold standard for diagnosis of feline pancreatitis. However, fPLI concentrations in cats suffering from pancreatic tumours were rarely described. The aim of the present study was to determine the sensitivity and specificity of an in-house enzyme-linked immunosorbent assay (ELISA) for the quantification of fPLI in serum samples based on histopathological findings in cats diagnosed with various pancreatic diseases. Pancreatic biopsy samples from 80 cats were included. Five groups were defined on the basis of pancreatic histopathology: group 1, normal pancreas; group 2, nodular hyperplasia; group 3, mild pancreatitis; group 4, marked (moderate/severe) pancreatitis; and group 5, pancreatic neoplasia. Serum samples from all cats were tested by fPLI ELISA (<3.6 μg/l normal, 3.6-5.3 μg/l questionable, >5.3 μg/l pancreatitis). In group 1 (n = 19), serum fPLI values were within the reference interval in 74% of cases and in group 2 (n = 9) in 78%. Cats with mild pancreatitis (n = 23), marked pancreatitis (n = 11) and pancreatic neoplasms (n = 18) had significantly increased fPLI concentrations compared with group 1 (P = 0.004/0.001/≤0.0001). Cats with nodular hyperplasia had significantly lower fPLI values than cats with marked pancreatitis (P = 0.048) or tumours (P = 0.002). Serum fPLI concentrations in group 3 were <3.6 μg/l (n = 6), 3.6-5.3 μg/l (n = 4) and >5.3 μg/l (n = 13). Calculated test sensitivity for mild pancreatitis was fPLI >3.5 μg/l: 73.9% and fPLI >5.3 μg/l: 56.5%. In group 4 (n = 11), seven of nine cats (77.8%) with marked purulent pancreatitis had elevated fPLI. In group 4, a sensitivity of 81.8% was detected for fPLI >3.5 μg/l and 63.6% for fPLI >5.3 μg/l. Two cats with marked non-purulent pancreatitis had elevated fPLI, while two cats with marked purulent pancreatitis had normal fPLI values (<3.6 μg/l). In group 5, one cat with pancreatic adenoma and one with pancreatic acinar carcinoma had normal fPLI concentrations. The other cats with pancreatic adenoma (solid, n = 1; cystic, n = 4) or carcinoma (solid, n = 9; cystic, n = 2) had elevated or high fPLI values (4.1 to >40 μg/l, median 21.2 μg/l), probably caused by additional inflammation. The results of the present study confirm the importance of detailed histopathological characterization for the interpretation of clinical signs and fPLI values in feline pancreatitis. Primary pancreatic neoplasms may also lead to elevated fPLI concentrations as there is concurrent pancreatitis in most cases. However, severe pancreatic diseases, such as chronic non-purulent pancreatitis or tumours without inflammation, may result in normal fPLI values.

Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.

An increasing number of studies have demonstrated that disease states of the endocrine or exocrine pancreas aggravate one another, which implies bidirectional blood flow between islets and exocrine cells. However, this is inconsistent with the current model of unidirectional blood flow, which is strictly from islets to exocrine tissues. This conventional model was first proposed in 1932, and it has never to our knowledge been revisited to date. Here, large-scale image capture was used to examine the spatial relationship between islets and blood vessels in the following species: human, monkey, pig, rabbit, ferret, and mouse. While some arterioles passed by or traveled through islets, the majority of islets had no association with them. Islets with direct contact with the arteriole were significantly larger in size and fewer in number than those without contact. Unique to the pancreas, capillaries directly branched out from the arterioles and have been labeled as "small arterioles" in past studies. Overall, the arterioles emerged to feed the pancreas regionally, not specifically targeting individual islets. Vascularizing the pancreas in this way may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to changes in the blood levels of glucose, hormones, and other circulating factors.

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing. Results: Bray-Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each other. A total of 73 unique Amplicon Sequence Variants (ASVs) were shared between oral and pancreatic or intestinal samples. Only four ASVs showed significant concordance, and two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) showed consistent presence or absence patterns between oral and intestinal or pancreatic samples, after adjusting for within-subject correlation and disease status. Lastly, microbial co-abundance analyses showed distinct strain-level cluster patterns among microbiome members in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Conclusions: Our findings indicate that oral, intestinal, and pancreatic bacterial microbiomes overlap but exhibit distinct co-abundance patterns in patients with pancreatic cancer and other gastrointestinal diseases.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that is clinically asymptomatic in its early stages of development. Non-invasive testing for pancreatic cancer biomarkers would significantly improve early detection and patient care. Extracellular vesicles (EVs) are circulating tumor fragments present in the blood and may express cancer specific biomarkers that would enable early detection of pancreatic cancer. We tested the utility of a blood test enumerating EVs positive for the pancreas-specific marker Glycoprotein 2 (GP2) and the putative pancreatic cancer marker Glypican-1 (GPC1) in patients with PDAC. Various levels of GPC1-positive and GP2/GPC1-positive EVs were detected in PDAC patients but were not significantly higher than benign pancreatic disease (BPD) patients. The sensitivity and specificity of the GPC1 EV test was 26.67% and 87.50% respectively, whereas the sensitivity and specificity for the GPC1+GP2 EV test was 23.33% and 90.00% respectively. Immunohistochemistry of GPC1 expression in a tissue microarray of PDAC and various controls also did not demonstrate specificity of GPC1 to PDAC. Hence, enumeration of GPC1-positive EVs, solely or in conjunction with GP2, was unable to effectively distinguish between BPD and pancreatic cancer.

As ultrasound (US) is simple and less invasive than other imaging modalities, this technique is widely used for mass screening. However, visualizing the entire pancreas due to complicated anatomy, obesity and overlying gas can be difficult. US plays a key role in the diagnosis of pancreatic carcinoma (PC), of which tumors smaller than 10 mm (TS1a) and pancreatic carcinoma in situ are expected to have good prognosis. To detect these forms of PC, main pancreatic duct (MPD) dilatation (3 mm or more) and pancreatic cysts (5 mm or larger) are US findings of high-risk individuals (HRIs), and these subjects should be observed periodically. Scanning maneuvers are also important for both screening for PC and follow-up of HRIs. As lesions in the groove area and ventral pancreas do not affect the MPD or extrahepatic bile duct, we should pay attention to these areas. Visualization of the tail is also challenging due to gas and stool in the alimentary tract. As the position of the pancreas changes depending on the body posture, and several different body positions should be employed, such as the right lateral decubitus, sitting, and upright positions, rather than only applying strong compression with the transducer. In cases with poor visualization, the liquid-filled stomach method is highly recommended.

Pancreatic cancer (PC) has been the fourth cancer-related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T-cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high-throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. We found that there were significant differences related to TCR repertoire between PC and other pancreatic diseases, and PC is a relatively immunosuppressive tumour. Changes of peripheral TCR repertoire may be used to predict the progression of PC and the response to immunotherapy. And there may exist novel-specific antigens in PC patients which could be used to design targeting immunotherapy in the nearly future.

Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn's disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used.

The "Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases" Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

The Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report provides a summary of the proceedings from the workshop. The goals of the workshop were to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into six major theme areas, including 1) pancreas anatomy and physiology, 2) diabetes in the setting of exocrine disease, 3) metabolic influences on the exocrine pancreas, 4) genetic drivers of pancreatic diseases, 5) tools for integrated pancreatic analysis, and 6) implications of exocrine-endocrine cross talk. For each theme, multiple presentations were followed by panel discussions on specific topics relevant to each area of research; these are summarized here. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

Serum concentrations of the CA 19-9 and CA 50 antigens were determined in 129 patients with malignant and benign biliary and pancreatic diseases. Values for the two markers were highly correlated (P less than 0.001). The concentrations of CA 19-9 and CA 50 were positive in 84.6% and 80.7% of patients with pancreatic cancer, respectively. The overall specificity of CA 19-9 (92.4%) was slightly higher than that of CA 50 (88.5%). The sensitivity of CA 50 (91.3%) was greater than that of CA 19-9 (73.9%) in patients with diseases of the biliary tract. Elevated concentrations of CA 19-9 (12.9%) and CA 50 (35.2%) were also found in a number of cases with benign disease, especially in patients with obstructive jaundice. These data suggest that both CA 19-9 and CA 50 can be useful markers of pancreatic cancer in nonjaundiced patients. The joint use of the two markers does not yield a better diagnostic resolution than the use of either one alone.

Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States.

Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States.

Non-invasive criteria are needed for Crohn's disease (CD) diagnosis, with several biomarkers being tested. Results of individual diagnostic test accuracy studies assessing the diagnostic value of pancreatic autoantibodies-to-glycoprotein-2 (anti-GP2) tests for the diagnosis of CD appear promising.

Congenital anomalies of the pancreas are relatively uncommon. Most of these are asymptomatic and are detected incidentally, but can present with a variety of clinical manifestations like pancreatitis, duodenal obstruction, biliary obstruction, and rarely malignancy. Here in our study, we describe various congenital anomalies of the pancreas associated with various clinical manifestations, its management strategies, and outcomes. The aim was to study the various clinical manifestations of and management strategies for pancreatic diseases associated with congenital anomalies of the pancreas and their outcomes.

Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson's and Alzheimer's disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of α-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and Aβ deposits in the pancreatic tissue of Alzheimer's disease patients, we studied the immunoreactivity of amylin, tau and α-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic β-cells of these subjects present cooccurrence of misfolded proteins. Furthermore, we also assessed the pancreatic expression of prion protein (PrP) in these subjects and its interaction, both in the pancreas and brain, with α-synuclein, tau, Aβ and amylin. Our study shows, for the first time, that along with amylin, pancreatic α-synuclein, Aβ, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer's and Parkinson's disease. Furthermore, we show that the same mixed pathologies that are observed in the brains of patients with neurodegenerative diseases are also present outside the nervous system. Finally, we provide the first histological evidence of an interaction between PrP and Aβ, α-synuclein, amylin or tau in the pancreas and locus coeruleus. These findings will shed more light on the common pathological pathways shared by neurodegenerative diseases and type two diabetes, benefiting the exploration of common therapeutic strategies to prevent or treat these devastating amyloid diseases.

New applications of confocal laser endomicroscopy (CLE) have been developed, such as needle-based CLE (nCLE) for pancreatic masses, pancreatic cystic tumors, and lymph nodes. nCLE is feasible during endoscopic ultrasound (EUS) examination, and preliminary results are very encouraging and suggest this technology may be used in future as a useful adjunct in cases of inconclusive EUS-guided fine-needle aspiration. The aim of this paper is to give an update in this new technology and to define its place in the diagnosis of pancreatic masses and mediastinal diseases.