Pancreatic Juice Research Articles

Antipathogenic and probiotic potential of Lactobacillus brevis strains newly isolated from Algerian artisanal cheeses.

From 98 Lactobacillus strains, isolated from Algerian homemade cheeses, 14 (B1-B14) were selected based on their anti-Escherichia coli and anti-Staphylococcus aureus activities. These strains were also tested towards Listeria monocytogenes 161 and Salmonella Typhimurium LT2 and further investigated for their resistance to simulated gastrointestinal digestion, cell surface properties, ability to adhere to HT-29 cells, cholesterol lowering, antioxidant activity, and technological traits. Five isolates (B9, B13, B18, B19, and B38) were active against L. monocytogenes and Salmonella. From them, three isolates, identified as Lactobacillus brevis (B9, B13, and B38) by MALDI-TOF spectrometry and 16S rDNA sequencing, exhibited high tolerance to pancreatic juice, bile salts and acidic juices, high percentages of hydrophobicity (87, 92, and 81%, respectively), auto-aggregation (61, 68, and 72%, respectively), and adherence to HT-29 cells (79, 84, and 74%, respectively), which testify on their potential of colonization of the human intestine. On the other way, the strains B9 and B13 manifested the most relevant antioxidant activity and cholesterol-lowering ability, respectively. L. brevis strains showed low acidifying and good proteolytic activities with noticeable heat tolerance. The results gathered in this study highlighted the richness of Algerian artisanal cheeses on new lactobacilli strains with an excellent probiotic potential and demonstrated that L. brevis, largely used as nonstarter in cheese manufacture, could be exploited also as a probiotic for human use.

Integrated analysis of metabolome in a EUS-FNA sample with transcriptome in the TCGA cohort of pancreatic head and body/tail adenocarcinoma

Metabolome profiles are largely unknown for pancreatic head cancers, in which the predominant anatomical feature is the exosure of bile, pancreatic juice, and duodenal juice. In this research, 30 head and 30 body/tail cytological samples acquired by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic adenocarcinoma were delivered for liquid chromatography coupled with mass spectrometry (LC-MS). Transcriptome analysis was performed using the sequencing data from The Cancer Genome Atlas (TCGA) cohort. LC-MS obtained 4,857 features in EUS-FNA cytological samples, and 586 metabolites were certified. Among them, 30 differential metabolites were identified. In the TCGA cohort, 247 differential metabolism genes were selected from 1,583 differential genes. The integrated analysis identified the top three enriched metabolic pathways as follows: branched chain amino acid (BCAA) biosynthesis; glycerophospholipid metabolism; and phenylalanine metabolism. In cell line, BCAA promoted pancreatic cancer proliferation and inhibited Oxaliplatin-induced apoptosis. In conclusion, metabolomic analysis with the EUS-FNA sample is feasible for pancreatic cancer. The integrated analysis can identify key metabolites and enzyme-coded genes between pancreatic head and body/tail adenocarcinoma. Anti-BCAA metabolism therapy may exert promising effect, especially for the body/tail cancer.

Association between the confluent form of pancreatic and bile duct and histopathological findings in pancreaticobiliary maljunction: A case series study

IntroductionPancreaticobiliary maljunction (PBM) is a congenital anomaly wherein the persistent reflux of the pancreatic juice into the biliary tract induces biliary tract cancer. The prediction criteria for gallbladder carcinogenesis have been reported previously through results obtained from examining carcinogenic and non-carcinogenic cases with the parameters that classified each confluent form in PBM. This study aimed to validate these previous study results and provide new recommendations for gallbladder carcinogenesis prevention. MethodsTwenty-four patients with PBM underwent hepaticojejunostomy. The prediction criteria for gallbladder carcinogenesis consist of three elements. The confluent forms that satisfied none or one of the three criteria were defined as a low score group, and those that satisfied two or three were defined as the high score group. Immunohistology and pathological search were performed on the gallbladders' sections in both groups to evaluate chronic inflammation. ResultsThe cases with dysplasia, positive Ki67 labeling index, and gallbladder cancer were more common in the high score group and tended to have more lymphocyte infiltration. These findings indicate that the degree of inflammation and cell proliferation might be more severe in the high score group than in the low score group. ConclusionsThere is a close relationship between the confluent form and the histopathological findings of the gallbladder in patients with PBM. The confluent forms observed in the high score group might have an additional correlation with increased proliferation activity and subsequent malignant transformation of the gallbladder epithelium.

Molecular Approaches Using Body Fluid for the Early Detection of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant form of gastrointestinal tumor and is the fourth leading cause of deaths due to cancer in Japan. This cancer shows a poor outcome due to the difficulty of its early diagnosis and its rapid growth. Once this disease becomes clinically evident, it is frequently accompanied by distant metastasis at the time of diagnosis. A recent multicenter study in Japan revealed that patients with the early stage of this disease (stage 0 and I) showed favorable prognosis after surgical resection, indicating the importance of early detection for improvement of PDAC prognosis. PDAC develops through a stepwise progression from the precursor lesion, and over the last few decades molecular analyses have shown the detailed genetic alterations that occur in this process. Since advances in molecular technologies have enabled the detection of genetic changes from a very small quantity of samples, a large number of non-invasive molecular approaches have been utilized in an attempt to find precursor or non-invasive carcinoma lesions. In this review, the current efforts in terms of the molecular approaches applied for the early detection of PDAC—especially using body fluids such as pancreatic juice, blood, and saliva—are summarized.

Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

Safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study

A delayed perforation can often occur after endoscopic treatment for duodenal neoplasms and may be fatal due to leakage of pancreatic and bile juices. We aimed to evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for duodenal neoplasms (D-LECS) in a multicenter, retrospective study. The clinical characteristics and surgical outcomes of 206 patients with duodenal neoplasms in whom D-LECS had initially been attempted at one of 14 institutions were reviewed retrospectively. Of the 206 patients, 63 (30.6 %), 128 (62.1 %), and 15 patients (7.3 %) had lesions at the bulb, second portion, and third portion of the duodenum, respectively. The rates of en bloc and R0 resections during D-LECS were 96.1 % and 95.1 %, respectively. Intraoperative and delayed perforations occurred in 10 (4.9 %) and 5 patients (2.4 %), respectively. No cases of recurrence were observed. Surgical duration of ≥ 180 minutes was an independent risk factor for postoperative complications. The results revealed that D-LECS was performed with oncological safety and technical feasibility.

空腸漿膜パッチおよび十二指腸憩室化にて救命しえた広範な外傷性十二指腸損傷の1例(A case of extensive traumatic duodenal injuries treated by jejunal patch and duodenal diverticulization)

要旨症例は38歳の男性。腹部鈍的外傷にて当院に搬送された。精査の結果，十二指腸損傷と診断し，受傷後2時間半ほど経過した時点で緊急手術を行った。十二指腸下行部が2/3周かつ長径10cm以上にわたり広範に損傷していた。まず局所修復法として空腸漿膜パッチにて壁損傷部位を閉鎖し，さらに修復した十二指腸下行部の狭窄がみられたため幽門側胃切除および胃空腸吻合術（Roux–en–Y法での再建）による十二指腸憩室化を同時に施行した。術後20日で独歩退院となった。外傷性十二指腸損傷の手術治療は術後合併症，特に縫合不全発生の危険性が高く予後不良とされ，損傷部位が大きく複雑になるに従い困難を極める。空腸漿膜パッチは腸管壁損傷が広範な場合においても閉鎖修復が可能でありかつ安全性も高い。さらに同時に十二指腸憩室化を組み合わせたことで修復腸管径の狭小化に伴う縫合不全や腸管内圧上昇，通過障害を回避し，極めて良好な経過を得られたと考えられた。

Frédéric Alphonse Musculus

Frédéric Alphonse Musculus (1828-1888) was a French military pharmacist who worked mainly on starch, its reactions, and derivatives, and urease. His found that dextrin was not the product of a hydration alone but the result of the decomposition of the starchy matter. Dextrin and glucose appeared always in the same 2:1 ratio. The same results were obtained using diluted sulfuric acid or diastase as the reaction agent. He showed that the results of Payen on the subject were wrong because he had used an impure dextrin. Together with David Gruber, a major brewer producer, synthesized many starch derivatives, among them, erythrodextrin, achroodextrin a, b, g , and soluble starch, and concluded that starch was a polysaccharide of formula n (C 12 H 20 O 10 ), where n was larger than 5 or 6. With Méring he studied the action of saliva and pancreatic juice upon glucose and glycogen. Musculus separated from putrefying urine a ferment, which eventually Miquel would name urease.

External drainage of bile and pancreatic juice after endoscopic submucosal dissection for duodenal neoplasm:Feasibility study (with video).

Endoscopic submucosal dissection (ESD) for superficial duodenal epithelial tumors (SDETs) is technically difficult and has a high risk of adverse events. Endoscopic nasobiliary and nasopancreatic duct drainage (ENBPD) may reduce the risk of delayed adverse events by preventing exposure of the post-ESD mucosal defect to bile and pancreatic juice. This study was performed to evaluate the safety and feasibility of ENBPD after duodenal ESD. Patients who underwent ESD for SDETs from July 2010 to March 2020 were included. We collected data on the success rate of ENBPD, adverse events due to insertion of a side-viewing endoscope, and pancreatitis after ENBPD. We also collected the clinical outcomes of duodenal ESD, including the incidence rate of delayed adverse events (defined as bleeding or perforation found after the endoscopic procedure). Among 70 patients without complete closure of the post-ESD mucosal defect, ENBPD was successfully performed in all 25 patients including 21 cases inserted immediately after ESD and four cases inserted later. There were no adverse events associated with ENBPD procedure intraoperatively, while pancreatitis after ENBPD occurred in four patients (16.0%). No patients who underwent immediate ENBPD required intervention for an intra-abdominal abscess or delayed perforation, whereas 3 of 49 patients (6.1%) who did not undergo immediate ENBPD required surgery or drainage of an abscess. Endoscopic nasobiliary and nasopancreatic duct drainage is technically feasible and might provide effective prophylaxis for delayed adverse events, even if a large mucosal defect is present after ESD.

Förster resonance energy transfer (FRET) nanoprobe could diagnose pancreatic juice activation due to postoperative pancreatic fistula

Introduction: Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy often causes activation of pancreatic juice, resulting in critical complications. In POPF, it is important to diagnose the activity of pancreatic juices in real time, so contributes to the development of postoperative management after pancreatoduodenectomy. This study suggests prosperious results of the clinical application of the FRET nanoprobe that is developed to distinguish between the active and inactive types of pancreatic juice. Methods: The FRET nanoprobe was a 12nm diameter nanoprotein capsule. It exuded a red color when the capsule structure was maintained. Activation of protease in the pancreatic juice on it, the capsules are reduced quantitatively, and FRET is abolished, changing in color from red to green. Pancreatic juice activation can be measured by the FRET signal. A total of 112 drainage fluid samples from 16 post-pancreatoduodenectomy patients were obtained and evaluated. Results: The pancreatic juice activation could be determined using the FRET signal with a boundary value of 1.6. Drainage fluid amylase (AMY) level was unrelated to pancreatic juice activation. This results suggested pancreatic juice was activated when drainage fluid was infected. Conclusion: The FRET nanoprobe enabled detection of the presence or absence of pancreatic fistula activation after pancreatodudenectomy. It was suggested that infection in drainage fluid was the major cause of pancreatic juice activation regardless of drainage fluid AMY levels.

Experimental results on pancreatic juice parenteral application in broiler growing

The paper presents the results of the use of pancreatic enzymes in the form of intramuscular injection of pure pancreatic juice obtained from fistulated chickens to broiler chickens. At 7 days of age during the formation of groups, the differences between the control and experimental chickens were 17.9% (p<0.05) in favor of the former. It was found that after the injection of the drug 1 time in 7 days, there was a stimulation of metabolism in the experimental group broilers. By 14 days of age, the differences between the groups were 17.4% (p<0.05), to 21 days of age - 9.1% (p<0.05), to 28 days of age - 5.3%, to 35 - day-old age - 4.9%. Consequently, as the chickens were raised by 28 days of age, the chickens of the experimental group caught up with the live weight of the control ones, and, considering the increase in live weight, even exceeded this indicator (50.1 g/day versus 42.7). The use of parenteral pancreatic juice of chickens at a dose of 0.1ml/kg of live weight of broiler chickens allows to conclude that the drug has a stimulating effect on poultry metabolism, manifested by an increase in live weight gain, an increase in the content of lymphocytes, as an indicator of immunity, activation of protein and mineral metabolism in the body when using an enzyme preparation.

Bile Metabolites and Risk of Carcinogenesis in Patients With Pancreaticobiliary Maljunction: A Pilot Study.

Pancreaticobiliary maljunction (PBM), a disease with reflux of pancreatic and bile juice in the pancreaticobiliary tract, is a high-risk factor for biliary tract cancer. The aim of this study was to investigate the mechanism of carcinogenesis in PBM using a metabolomics analysis of bile sampled during surgery. Three patients with PBM without biliary tract cancer, four patients with extrahepatic bile duct cancer (EHBC), and three controls with benign disease were enrolled. Metabolomics analysis of bile samples was performed using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to discriminate the amino acid and lipidomic profiles. The principal component analysis in the capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry revealed similar metabolites in patients with PBM and those with EHBC; furthermore, there was a clear difference between patients with PBM or EHBC compared to controls. The amino acid profiles revealed the following 20 potential carcinogenic candidates for PBM: isoleucine, phenylalanine, tyrosine, leucine, tryptophan, arginine, lysine, valine, asparagine, methionine, aspartic acid, serine, threonine, histidine, glutamine, alanine, proline, glutamic acid, and pyruvic acid. The lipidomic profiles revealed the following 11 carcinogenic candidates: lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidyl glycerol, lysophosphatidyl glycerol, triacylglycerol, diacylglycerol, ceramide, sphyngomyeline, fatty acid, hyperforin, and vitamin D. Among these characteristic metabolites, the branched-chain amino acids, methionine and lysophosphatidylcholine are known to be related to carcinogenesis. The bile metabolites were extremely similar in patients with PBM and those with EHBC. Furthermore, amino acid and lipid metabolism was markedly different in patients with PBM or EHBC compared to healthy controls.

Feasibility of Hyaluronate Carboxymethylcellulose-based Bioresorbable Membrane in Two-staged Pancreatojejunostomy

Background: Two-staged pancreatoduodenectomy with exteriorization of pancreatic juice is a safe procedure for high-risk patients. However, two-staged pancreatoduodenectomy requires complex re-laparotomy and adhesion removal. We analyzed whether using hyaluronate carboxymethylcellulose-based bioresorbable membrane (HCM) reduced the time required for the second operation and facilitated good fistula formation in two-staged pancreatoduodenectomy. Methods: Between April 2011 and December 2018, data were collected from 206 consecutive patients who underwent two-staged pancreatoduodenectomy. HCM has been used for all patients since 2015. Patients for whom HCM was used (HCM group; n=61) were compared to historical controls (before 2015) without HCM (Control group; n=145) in terms of feasibility of the second operation (operation time, adhesion grade, and complications) and optimal granulation around the external tube at second laparotomy. Results: The HCM group showed significantly shorter median operation time [105 min (30-228 min) vs. 151 min (30-331 min); p< 0.001] and smaller median blood loss [36 mL (8-118 mL) vs. 58 mL (12-355 mL); p< 0.001] for the second operation. Neither overall postoperative complication rate (p=0.811) nor severe-grade complication rate (p=0.857) differed significantly. Both groups showed good fistula formation, with no significant difference in rate of optimal fistula formation (HCM group, 95.1% vs. control, 95.9%; p=0.867). Conclusion: HCM placement significantly improved safety and duration for the second operation, while preserving good fistula formation.

Early Drain Removal Regardless of Drain Fluid Amylase Level Might Reduce Risk of Postoperative Pancreatic Fistula.

Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p<0.001, respectively). Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.

Preliminary Study on the Efficacy of Peritoneal Patch in Reducing the Incidence of Pancreatic Fistula after Pancreaticoduodenectomy

Introduction: Several studies have already evaluated the efficacy of different devices in decreasing the incidence of POPF by reinforcing the pancreatic anastomosis after pancreaticoduodenectomy. Unfortunately, until now none of them have shown any clear benefits. Purpose: To evaluate a new technique to perform a pancreaticojejunostomy in pancreas at high risk for fistula. Method: From June 2020, a total of 10 patients out of 33 who underwent a pancreaticoduodenectomy for cancer at our institution were selected for this study. All of the selected patients were at high risk for pancreatic fistula due to soft pancreatic parenchyma and/or non dilated pancreatic duct. A pancreaticojejunostomy with Blumgart’s technique was performed in every case. A peritoneal patch was used to cover the surface of the pancreatic stump before the anastomosis in order to give a sealing effect and strengthen the suture. A pancreatic stent was always placed through the pancreatic duct. We assessed the rate of POPF (ISGPF definition) within 30 postoperative days. Results: In those patients treated by the use of a peritoneal patch no fistula was observed. All patients underwent a pre-discharge CT-scan at day 7 showing no abdominal collections or vascular pseudo-aneurysms. The peritoneal patch might improve the anastomosis healing by lowering the outflow of pancreatic juice from the parenchyma during the immediate post-operative days. Conclusion: Preliminary data about the application of a peritoneal patch are encouraging and it might prove a useful tool in preventing POPF and PPH.

Деякі аспекти розвитку та корекції вторинної екзокринної недостатності підшлункової залози у дітей

Based on the analysis of literature sources, the main causes and mechanisms of the secondary exocrine pancreatic insufficiency in children are highlighted. The main mechanisms of regulation and peculiarities of functional activity of the pancreas in children are discussed. The importance of pancreatic enzymes for physiological digestion of food nutrients as well as for ensuring satisfactory nutritional status of a child is noted. It is shown that the main reason for the development of secondary exocrine insufficiency of the pancreas in children is a violation of the pancreatic enzymes activity in the duodenum. Factors that adversely affect the effectiveness of pancreatic enzymes by disrupting their activation or inactivation in the duodenum have been listed. They include: 1) motility disorders of the gastrointestinal tract; 2) bile acid deficiency; 3) violation of entero-pancreatic regulation of the pancreas; 4) hyperacidic conditions of the stomach and duodenum; 5) intestinal dysbacteriosis; 6) violation of the outflow of pancreatic juice into the duodenum. The mechanisms of negative influence of these factors on the activity of pancreatic enzymes are also revealed. It is noted that the increase in the prevalence of secondary exocrine pancreatic insufficiency is due to the peculiarities of diseases of the digestive system, namely, the combined nature of the lesions of different parts of the gastrointestinal tract. The effective properties of the mini-tablet enzyme preparation, as well as indications for its use are analyzed; the dosage of enzyme preparations for children in accordance with domestic and foreign recommendations was discussed. The list of pathological conditions in which it is advisable to use enzyme preparations, as well as the requirements that must be met when using enzyme preparations to achieve maximum effectiveness during enzyme replacement therapy. The author declares no conflict of interest. Key words: children, exocrine insufficiency of the pancreas, enzyme preparations.

Endoscopic Ultrasonography Diagnosis of Early Pancreatic Cancer.

Early diagnosis of pancreatic cancer (PC) can improve patients’ prognosis. We aimed to investigate the utility of endoscopic ultrasonography (EUS) for the early diagnosis of PC. This study included 64 patients with PC at an early stage treated at Onomichi General Hospital between January 2007 and January 2020. Diagnostic procedures included contrast computed tomography (CT), magnetic resonance cholangiopancreatography, EUS fine-needle aspiration, and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatic juice cytology. The mean age was 71.3 years. In all, 32 patients were stage 0, and 32 were stage I. As for image findings, the main pancreatic duct (MPD) stenosis was detected in several cases, although CT and MRCP seldom detected tumors. EUS had a high detection rate for stage 0 tumor lesions. The median observation period was 3.9 years. In cases with stage 0, the 1 year and 5 year survival rates were 100% and 78.9%, respectively. In cases with stage I, the 1 year and 5 year survival rates were 96.4% and 66.7%, respectively. EUS has the highest sensitivity among all imaging modalities for detecting small pancreatic tumors. Cases with MPD dilation or stenosis, especially with tumors that cannot be identified on CT and MRI, should have EUS performed. In some cases, EUS was not able to detect any tumor lesions, and ERCP-based pancreatic juice cytology should be useful for pathological diagnosis.

Early Detection of Pancreatic Cancer: Role of Biomarkers in Pancreatic Fluid Samples.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide. Most patients with PDAC present with symptomatic, surgically unresectable disease. Therefore, the establishment of strategies for the early detection is urgently needed. Molecular biomarkers might be useful in various phases of a strategy to identify high-risk individuals in the general population and to detect high-risk lesions during intense surveillance programs combined with imaging modalities. However, the low sensitivity and specificity of biomarkers currently available for PDAC, such as carbohydrate 19-9 (CA19-9), contribute to the late diagnosis of this deadly disease. Although almost all classes of biomarker assays have been studied, most of them are used in the context of symptomatic diseases. Compared to other body fluids, pancreatic juice and duodenal fluid are better sources of DNA, RNA, proteins, and exosomes derived from neoplastic cells and have the potential to increase the sensitivity/specificity of these biomarkers. The number of studies using duodenal fluid with or without secretin stimulation for DNA/protein marker tests have been increasing because of the less-invasiveness in comparison to pancreatic juice collection by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Genomic analyses have been very well-studied, and based on PDAC progression model, mutations detected in pancreatic juice/duodenal fluid seem to indicate the presence of microscopic precursors and high-grade dysplasia/invasive cancer. In addition to known proteins overexpressed both in precursors and PDACs, such as CEA and S100P, comprehensive proteomic analysis of pancreatic juice from patients with PDAC identified many proteins which were not previously described. A novel technique to isolate exosomes from pancreatic juice was recently invented and identification of exosomal microRNA’s 21 and 155 could be biomarkers for diagnosis of PDAC. Since many studies have explored biomarkers in fluid samples containing pancreatic juice and reported excellent diagnostic accuracy, we need to discuss how these biomarker assays can be validated and utilized in the strategy of early detection of PDAC.

Use of chromium nanoparticles as a protector of digestive enzymes and biochemical parameters for various sources of fat in the diet of calves

The gastrointestinal tract acts as a digestive conveyor and carries out a specific stage of food processing throughout its length. A non-traditional approach to feeding cattle unprotected vegetable fats/oils may involve minerals (Ca and/or Mg). In our study, we studied the biological effects associated with the use of chromium nanoparticles at a dose of 200 μg/kg feed, together with soy and sunflower oils, in the diet of 10-month-old Kazakh white-headed breed calves. The calves were surgically fitted with duodenal fistula and pancreatic duct. Results demonstrated that inclusion of chromium nanoparticles in the diet increased the digestibility of crude protein, NDF, ADF and crude fat (p ≤ 0.05). At the same time, inclusion of chromium nanoparticles in the diet led to changes in the blood serum: a 2-fold increase in aspartate aminotransferase (p &lt; 0.05), a 42.2% increase in lactate dehydrogenase and alanine levels similar to control values. We noted that the addition of lipids in the feed led to the mobilisation of triglycerides and cholesterol. At the same time, the inclusion of chromium nanoparticles contributed to a decrease in the level of total lipids in serum and inhibited peripheral metabolic pathways (a 2-fold increase in the de Ritis coefficient). These data may represent additional evidence of the activation of anabolic processes when chromium nanoparticles are introduced into the diet. The increase in the enzyme index was associated with an escalation of lipid peroxidation processes and a decrease in antioxidant defence activity. We showed that vegetable oils enhanced lipolytic and proteolytic activity of pancreatic juice enzymes in the gastrointestinal tract. Adding chromium nanoparticles to the diet reduced lipase activity, especially when used with soybean oil. These data indicate the inhibitory effect of chromium on the activity of pancreatic lipolytic enzymes.

Pancreatobiliary Diversion in the Mouse

The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates digestion and appetite, stimulates pancreatic growth, and participates in pancreatic carcinogenesis. The molecular mechanisms of CCK-induced effects are not fully understood. When the mechanisms are studied in animals, the surgical model of pancreatobiliary diversion (PBD) is frequently used. After animals have had PBD, their CCK secretion is no longer inhibited by pancreas-derived proteases, so circulating CCK is increased. PBD is established in rats and hamsters, but not in mice. In this study, we modified PBD procedures and established the model in the mouse. In an experiment, we performed PBD and sham operation (SO) in two groups of mice (20 mice per group). Twenty days after operation, 75% of the PBD mice and all SO mice survived. When plasma CCK was determined by radioimmunoassay, the PBD group had higher levels than the SO group (p < 0.001). To assess pancreatic growth, we determined pancreatic weight and pancreatic contents of protein and DNA. We also stained pancreatic sections by immunohistochemistry to show the proliferating cells that either expressed the proliferating cell nuclear antigen or were labeled with 5-bromo-2′-deoxyuridine. As a result, the pancreases of the PBD mice were heavier (p < 0.001) and had more protein (p < 0.001), DNA (p < 0.01), and proliferating cells (p < 0.01) than those of the SO counterparts. Thus, pancreatic growth was increased as a result of PBD-induced hypercholecystokininemia. The plasma and pancreatic data demonstrated that the PBD model was a success. This model may be used in CCK-related research. For instance, pancreatic cancer is frequently studied in transgenic mice. PBD may be combined with the cancer model to study the role of CCK in the molecular biology of pancreatic cancer.