Role In Pancreatic Disease Research Articles

Pancreatic steatosis and metabolic pancreatic disease: a new entity?

Overweight and obesity are some of the most important health challenges. Many diseases are related to these metabolic disorders, and, among them, the pancreatic fat accumulation, also called "pancreatic steatosis" or "nonalcoholic fatty pancreas", seems to have an emerging role in different conditions. There are different method to evaluate the fat content in the pancreas, such as histology, different imaging techniques and endoscopic ultrasound, but there is no gold standard for the correct diagnosis and for the identification of "inter/intralobular" and "intra-acinar" pancreatic fat. However, the fat storage in the pancreas is linked to chronic inflammation and to several conditions, such as acute and chronic pancreatitis, type 2 diabetes mellitus and pancreatic cancer. In addition, pancreatic fat accumulation has also been demonstrated to play a role in surgical outcome after pancreatectomy, in particular for the development of postoperative pancreatic fistula. Different possible therapeutic approaches have been proposed, but there is still a lack of evidence. The aim of this review is to report the current evidence about the relationship between the obesity, the pancreatic fat accumulation and its potential role in pancreatic diseases.

Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention.

The pancreas is an abdominal organ with both endocrine and exocrine functions, and patients with pancreatic diseases suffer tremendously. The regulated cell death of various cells in the pancreas is thought to play a key role in disease development. As one of the newly discovered regulated cell death modalities, ferroptosis has the potential for therapeutic applications in the study of multiple diseases. Ferroptosis has been observed in several pancreatic diseases, but its role in pancreatic diseases has not been systematically elucidated or reviewed. Understanding the occurrence of ferroptosis in various pancreatic diseases after damage to the different cell types is crucial in determining disease progression, evaluating targeted therapies, and predicting disease prognosis. Herein, we summarize the research progress associated with ferroptosis in four common pancreatic diseases, namely acute pancreatitis, chronic pancreatitis, pancreatic ductal adenocarcinoma, and diabetes mellitus. Furthermore, the elucidation of ferroptosis in rare pancreatic diseases may provide sociological benefits in the future.

Single-base insertions in the VNTR of the carboxyl ester lipase gene Ц A role in pancreatic disease?

Single-base insertions in the VNTR of the carboxyl ester lipase gene Ц A role in pancreatic disease?

Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease

ObjectiveThe aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours,...

Exosomes and pancreatic diseases: status, challenges, and hopes.

Pancreatic disease, including pathologies such as acute pancreatitis (AP), chronic pancreatitis (CP), and pancreatic cancer (PC), is a complicated and dangerous clinical condition involving the disruption of exocrine or endocrine function. PC has one of the highest mortality rates among cancers due to insufficient diagnosis in early stages. Furthermore, efficient treatment options for the disease etiologies of AP and CP are lacking. Thus, the identification of new therapeutic targets and reliable biomarkers is required. As essential couriers in intercellular communication, exosomes have recently been confirmed to play an important role in pancreatic disease, but the specific underlying mechanisms are unknown. Herein, we summarize the current knowledge of exosomes in pancreatic disease with respect to diagnosis, molecular mechanisms, and treatment, proposing new ideas for the study of pancreatic disease.

Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer

ABSTRACTIncreasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation—all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases.However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

Single nucleotide polymorphisms and risk factors predictive of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote an early diagnosis and efficient follow-up, therefore avoiding its development. Single nucleotide polymorphisms, or SNPs, constitute the most abundant form of genetic variation in the human genome. SNPs are markers of diverse populations or individuals, yet also can be associated with differences in susceptibility or severity of certain diseases and/or individual responses to drugs. Many SNPs have previously been identified in studies of healthy subjects and patients with different alleles of a given gene. To date, around forty SNPs from the human genome have been correlated with predisposition to PDAC by pan-genomic studies or genome wide association studies (GWAS). However, parts of the human genome located within the GC-rich repeated domain of chromosomes are unsuitable for GWAS. Unfortunately, of those forty SNPs none are currently used in routine clinical protocols as potential biomarkers for PDAC. Exon 11 of the bile salt-dependent lipase gene ( BSDL ) plays a key role in pancreatic disease and encodes variable number of tandem repeat (VNTR) sequences, therefore Martinez et al . [Oncotarget. 2015; 6: 39855-39864.] hypothesized that a genetic link exists between mutations in VNTR loci and predisposition to pancreatic cancer (PC). Authors reported that the c.1719C>T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC group versus 27.30% in the control group). Notably, the odds ratio (OR) of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that the T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. Furthermore, a robust method using probes for droplet digital (dd)-PCR was designed to specifically discriminate the C/C major from C/T or T/T minor genotypes. Altogether, Martinez et al . propose that detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of these patients, particularly if associated with other potential risk factors of PC.

Copy number variants of carboxyl ester lipase – A role in pancreatic disease?

Copy number variants of carboxyl ester lipase – A role in pancreatic disease?

OC.09.1 CLINICAL, MORPHOLOGICAL AND FUNCTIONAL ASPECTS OF PATIENTS SUFFERING FROM PANCREATITIS ASSOCIATED WITH MUTATIONS OF CFTR AND SPINK1 GENES

OC.09.1 CLINICAL, MORPHOLOGICAL AND FUNCTIONAL ASPECTS OF PATIENTS SUFFERING FROM PANCREATITIS ASSOCIATED WITH MUTATIONS OF CFTR AND SPINK1 GENES

GSTP1 Ile105Val Polymorphism in Serbian Patients with Pancreatic Diseases

GSTP1 Ile105Val Polymorphism in Serbian Patients with Pancreatic DiseasesThe aim of the current preliminary case-control study was to identify glutathione S-transferase P1 (GSTP1) Ile105Val allele and genotype frequency and to evaluate its impact on susceptibility to pancreatic diseases in a Serbian population. This study has encompassed 157 patients with three major types of chronic pancreatic pathology: 47 with pancreatic cancer, 50 with chronic pancreatitis and 60 with type 2 diabetes mellitus, as well as 107 healthy individuals. The presence of GSTP1 Ile105Val polymorphism was analyzed using a PCR-RFLP method. Allele 105Val was less frequent in patients with pancreatic cancer (24.5%) and chronic pancreatitis (24.0%) and slightly more frequent in patients with type 2 diabetes mellitus (31.7%) in comparison to healthy individuals (29.9%), but the differences were not statistically significant. Distribution of Ile105Val polymorphism genotypes differed between the analyzed groups, but differences were also not statistically significant. There are only a few studies regarding the role of GSTP1 Ile105Val polymorphism in pancreatic diseases and their results are inconsistent. The significance of GSTP1 Ile105Val polymorphism for pancreatic pathology remains unclear and further studies are needed in order to elucidate its role in pancreatic diseases.

Tumor necrosis factor α and interferon γ genes polymorphisms and serum levels in pancreatic adenocarcinoma

Several biochemical pathways can lead to cancer cachexia, one of which involves the elevation of the cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). It was suggested that TNF-alpha and INF-gamma genes polymorphisms may influence these cytokines serum levels, but published data are still controversial. The aim of our study was to assess the clinical significance of -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms as well as TNF-alpha and INF-gamma serum levels in pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) as regards to healthy volunteers. We studied 41 patients with pancreatic adenocarcinoma, 56 with chronic pancreatitis and 50 healthy volunteers. Peripheral venous blood samples were obtained from all patients for TNF-alpha and INF-gamma serum concentrations measurement. After DNA isolation TNF-alpha and INF-gamma genes polymorphisms have been studied using restriction fragment length polymorphism (RFLP) analysis. Plasma levels of TNF-alpha were significantly higher in PA patients (32.7 pg/ml) compared with CP patients (3.2 pg/ ml) and control group (<1.6 pg/ml; p<0.01). Similarly, plasma levels of INF-gamma in PA patients (12.7 pg/ml) were higher from those in CP and control group (<7.1 pg/ml; p<0.01). In contrast, there were no differences between CP patients and healthy volunteers in INF-gamma levels. We observed a trend toward a correlation between weight loss in PA patients and TNF-alpha serum level (p=0.02). The TNF-alpha and INF-gamma genotype distribution were similar in patients with PA, CP and control group. We have not observed any association between TNF-alpha and INF-gamma serum levels and their genes polymorphisms. Our results suggest that elevated TNF-alpha serum level may have clinical significance in the development of cachexia in PA patients. -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms probably do not play important role in pancreatic diseases. Key words: pancreatic adenocarcinoma, tumor necrosis factor alpha, interferon gamma, cytokines, polymorphism.

Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis

Ten years ago, the groundwork for the discovery of the genetic basis of chronic pancreatitis was laid by linkage analyses of large kindreds with autosomal dominant hereditary chronic pancreatitis. Subsequent candidate gene sequencing of the 7q35 chromosome region revealed a strong association of the c.365G > A (p.R122 H) mutation of the PRSS1 gene encoding cationic trypsinogen with hereditary pancreatitis. In the following years, further mutations of this gene were discovered in patients with hereditary or idiopathic chronic pancreatitis. In vitro the mutations increase autocatalytic conversion of trypsinogen to active trypsin and thus probably cause premature, intrapancreatic trypsinogen activation in vivo. The clinical presentation is highly variable, but most affected mutation carriers have relatively mild disease. In this review, we summarize the current knowledge on trypsinogen mutations and their role in pancreatic diseases.

Therapeutic laparoscopy of the pancreas.

To communicate results of laparoscopic treatment of pancreatic pseudocyst (PP) and resection of benign lesions of the pancreas. Perioperative data, surgical outcomes, techniques and insights from 54 cases are presented. Although laparoscopic therapy for other solid organs has been widely adopted, reports of therapeutic laparoscopy of the pancreas have been few and of limited numbers, and its role in pancreatic disease is still unclear. Eighteen men and 11 women were selected for laparoscopic PP surgery. Four distinct laparoscopic approaches were used. An additional 9 men and 16 women underwent laparoscopic distal pancreatectomy (LDP) using a technique similar to the lesser sac approach. Laparoscopic PP surgery was completed successfully in 28 of 29 patients. The overall mean operative time was 2.8 hours and the mean postoperative length of stay was 4.4 days. Of the techniques described, the authors prefer cyst gastrostomy by the lesser sac approach or the minilaparoscopic cystic gastrostomy. LDP was attempted in 25 patients and completed successfully in 23. One underwent a successful hand-assisted enucleation of an insulinoma. In 12 cases the spleen was preserved. Mean operative time was 3.7 hours, and mean postoperative length of stay was 4.1 days. In the authors' experience, minimally invasive treatment of PP produces good results and avoids difficulties linked with percutaneous drainage or endoscopic internal procedures. However, combining upper endoscopy with intragastric laparoscopic surgery offers advantages of both. LDP compares well to open procedures and often allows preservation of the spleen.

Cholecystokinin Augmentation of 'Surgical' Pancreatitis

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.