Search

Pancreatic cancer (PC) is one of the deadliest malignant tumors worldwide, known as the 'king of cancers due to its insidious onset, high malignancy, and high mortality rate. PC is highly malignant and progresses rapidly, but its onset is insidious with atypical early symptoms, making it difficult to detect early lesions through conventional imaging studies. It is usually only discovered when symptoms like jaundice, abdominal and back pain occur. Surgical resection is currently the only curative option for PC. However, due to the difficulty in early diagnosis, the majority of patients are already in the middle to late stages at the time of diagnosis, missing the opportunity for surgery. Studies have confirmed that the progression of pancreatic cancer is relatively slow, with the initial tumor cells requiring at least 15 years to gain metastatic ability. Therefore, timely detection of pancreatic cancer through tumor markers could significantly improve the survival rate of patients. The most widely used and diagnostically valuable tumor marker in clinical practice is Carbohydrate antigen 199 (CA199). However, due to about 3% ~ 7% of pancreatic cancer patients being Lewis antigen-negative blood types and not expressing CA19-9, its sensitivity is only 79% ~ 81%, which does not provide good efficacy for the diagnosis of pancreatic cancer. Pancreatic juice, as a fluid near the tumor, has attracted much attention as a good source of tumor-related biomarkers. Many studies have confirmed the accuracy of using proteins, DNA, and exosomes in pancreatic juice for the diagnosis of pancreatic cancer, showing great prospects for pancreatic juice as a source of tumor markers for the diagnosis of pancreatic cancer. Therefore, this thesis reviews the efficacy of pancreatic juice as a specimen for the diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

This article explores the reflex phase of pancreatic secretion regulation in poultry after they consume feed. The pancreas is an important organ in the digestive process, and understanding how it adapts to different types of nutrition is crucial for improving poultry nutrition. The study reveals that pancreatic juice is continuously secreted throughout the day, with a notable increase after feed intake. The activity of pancreatic enzymes also varies throughout the day, with higher levels during the postprandial phase. The regulation of pancreatic secretion in broiler chickens involves complex reflexes and neurohormonal interactions, with the taste of the feed influencing pancreatic secretion. The article discusses the relationship between trypsin activity in the postprandial period and nitric oxide levels in the intestine and blood of poultry, suggesting that pancreatic enzymes play a role in regulating pancreatic secretory function. Additionally, it mentions the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in pancreatic secretion in mammals. The article concludes that the most effective adaptation of pancreatic enzymes to the composition of the diet occurs when partially digested food enters the duodenum. This information can be valuable for understanding pancreatic secretion regulation and enhancing chicken feed. [Extracted from the article]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, and developing an efficient and reliable approach for its early-stage diagnosis is urgently needed. Precancerous lesions of PDAC, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), arise through multiple steps of driver gene alterations in KRAS, TP53, CDKN2A, SMAD4, or GNAS. Hallmark mutations play a role in tumor initiation and progression, and their detection in bodily fluids is crucial for diagnosis. Recently, liquid biopsy has gained attention as an approach to complement pathological diagnosis, and in addition to mutation signatures in cell-free DNA, cell-free RNA, and extracellular vesicles have been investigated as potential diagnostic and prognostic markers. Integrating such molecular information to revise the diagnostic criteria for pancreatic cancer can enable a better understanding of the pathogenesis underlying inter-patient heterogeneity, such as sensitivity to chemotherapy and disease outcomes. This review discusses the current diagnostic approaches and clinical applications of genetic analysis in pancreatic cancer and diagnostic attempts by liquid biopsy and molecular analyses using pancreatic juice, duodenal fluid, and blood samples. Emerging knowledge in the rapidly advancing liquid biopsy field is promising for molecular profiling and diagnosing pancreatic diseases with significant diversity. [ABSTRACT FROM AUTHOR]

Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m2 (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection n = 5, biopsy n = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, p < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 KRAS, 15 TP53, 2 SMAD4, 3 CDKN2A 1 CTNNB1, and 1 PIK3CA), 19 in PJ (3 KRAS, 15 TP53, and 1 SMAD4), and 8 in tissue (2 KRAS, 2 CDKN2A, and 4 TP53). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection. [ABSTRACT FROM AUTHOR]

Background/Aims This study aimed to clarify the efficacy and safety of pancreatic duct lavage cytology combined with a cell-block method (PLC-CB) for possible pancreatic ductal adenocarcinomas (PDACs). Methods This study included 41 patients with suspected PDACs who underwent PLC-CB mainly because they were unfit for undergoing endoscopic ultrasonography-guided fine needle aspiration. A 6-Fr double lumen catheter was mainly used to perform PLC-CB. Final diagnoses were obtained from the findings of resected specimens or clinical outcomes during surveillance after PLC-CB. Results Histocytological evaluations using PLC-CB were performed in 87.8% (36/41) of the patients. For 31 of the 36 patients, final diagnoses (invasive PDAC, 12; pancreatic carcinoma in situ, 5; benignancy, 14) were made, and the remaining five patients were excluded due to lack of surveillance periods after PLC-CB. For 31 patients, the sensitivity, specificity, and accuracy of PLC-CB for detecting malignancy were 94.1%, 100%, and 96.8%, respectively. In addition, they were 87.5%, 100%, and 94.1%, respectively, in 17 patients without pancreatic masses detectable using endoscopic ultrasonography. Four patients developed postprocedural pancreatitis, which improved with conservative therapy. Conclusions PLC-CB has an excellent ability to detect malignancies in patients with possible PDACs, including pancreatic carcinoma in situ.

Abstract Background To study exocrine function of the remnant pancreas after pancreatoduodenectomy (PD), we propose the use of an exocrine index (PEI) that combines the volume of the remnant pancreas and the intraoperative amylase activity of the pancreatic juice. Here, we aimed to determine whether the PEI can predict non‐alcoholic fatty liver disease (NAFLD) following PD. Methods Fifty‐seven patients for whom pancreatic juice amylase activity was measured during PD were enrolled. NAFLD was defined as a liver‐to‐spleen attenuation ratio of 25 × 106. The prevalence of NAFLD in these groups was 53% (10/19), 11% (2/19), and 5% (1/19), respectively. In multivariable analyses, there was a significant association between NAFLD and the PEI (P value for trend = .042). Conclusion The PEI, calculated using the remnant pancreatic volume and the intraoperative pancreatic juice amylase activity, predicts NAFLD development following PD.

Abstract Background The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ‐CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results Median PJ‐CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ‐CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ‐CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8–70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non‐gastric type than in the gastric type (p < 0.001). The non‐gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion PJ‐CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ‐CEA predict the non‐gastric type, while low PJ‐CEA predict the gastric type.

Background: The progression of chronic pancreatitis (CP), an inflammatory disease of the pancreas, causes pancreatic stones to form within the pancreatic ductal lumen/parenchyma, which occurs via protein plug formation. Pain is the most common symptom that necessitates clinical attention, and pain relief is the therapeutic goal for these patients. Endoscopic therapy and surgery are complimentary forms of therapy for pain relief. This study was envisaged to clarify the mechanism by which protein plug/soft stones form in pancreatic ducts prior to undergoing calcification. Methods: Protein plugs were obtained from twenty CP patients undergoing therapeutic ERCP for stone removal. Pancreatic juice was obtained from five CP patients without stones. Proteins were isolated by TCA/acetone precipitation, SDS PAGE and 2-D gel electrophoresis to determine the protein profile. Protein spots from the 2-D gel were excised and subjected to matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) for identification. The effect of altered pH and elevated concentrations of trypsin on pancreatic juice protein was assessed by SDS‒PAGE to determine the protein profile. Differentially expressed protein bands were excised and subjected to MALDI-TOF. In silico analysis was performed by docking lithostathine with the calcite molecule using AutoDock Vina and PyMOL to clarify their interaction during stone formation. Results: Twenty-three and twenty-nine spots from 2D gels of protein plugs and pancreatic juice, respectively, revealed that lithostathine (Reg1A) was the only protein in the protein plugs, whereas digestive enzymes and lithostathine were identified in pancreatic juice. Altered pH levels and increased trypsin concentrations in the pancreatic juice caused a protein to degrade via an unknown mechanism, and this protein was identified as chymotrypsin C (CTRC) by MALDI-TOF. Docking studies showed that the binding affinity of calcite was higher with the cleaved lithostathine, explaining the deposition of calcium that was observed around the protein plugs after calcified stones were formed through precipitation. Conclusion: Our results suggest that chymotrypsin C (CTRC) is degraded in an acidic environment, leading to the precipitation of lithostathine in the ductal lumen. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Bacterial infection is involved in the progression of many gastrointestinal diseases, including those of pancreas; however, how and which bacteria colonize in pancreatic juice and tissue have yet to be elucidated. Recently, we reported that Enterococcus faecalis exists in the pancreatic juice and tissues of patients with chronic pancreatic disease. Here, we investigated the survival of E. faecalis in duodenal juice with different pH conditions. Methods Pancreatic juice samples from 62 patients with cancers of the duodeno‐pancreato‐biliary region were evaluated for the presence of E. faecalis. 16S ribosomal RNA polymerase chain reaction and 16S‐based metagenome analyses were performed to determine the bacterial composition. The survival of E. faecalis in various pancreatic juice conditions was evaluated. Results Of 62 samples, 27% (17/62) were positive for Enterococcus spp., among which 71% (12/17) contained E. faecalis. Enterococcus spp. showed the highest fitness for survival in alkaline pancreatic juice among various bacterial species. The microbiome of pancreatic juice from patients with pancreatic and bile duct cancer showed diversity, but Enterococcus spp. were enriched among duodenal tumors and intraductal papillary mucinous neoplasms. Conclusions Alkalinity is one of the important factors for the selective survival of E. faecalis among microbiota. E. faecalis can colonize the pancreatic duct when the pancreatic juice condition is altered.

The dismal prognosis of pancreaticobiliary malignancies is mainly attributed to the extremely difficult detection of early‐stage lesions, including intraepithelial neoplasia. To improve prognosis, several studies on the early detection of cancer have been conducted using bile and pancreatic juices for pathological or molecular analyses. One approach is liquid biopsy that includes information about the tumor, such as circulating tumor cells, circulating tumor DNA, microRNAs, and exosomes released by the tumor. Another approach is proteomics/metabolomics that reflects specific conditions in the tumor. These two approaches lead to artificial intelligence‐based multiomics analyses that comprises genomics, proteomics/metabolomics, and transcriptomics. Based on the findings of molecular analysis, pathological analysis using immunohistochemical staining/fluorescence in situ hybridization has also been developed. Moreover, there have been reports of new methods/ingenuities for obtaining appropriate samples for the diagnosis of early‐stage cancer. Here we review the knowledge on cutting‐edge pathological and molecular analyses of bile and pancreatic juices, introduce some ingenuities in sampling and sample processing to promote effective clinical practice, and provide a basis for future studies. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice. A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated. Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS , TP53 , CDKN2A , GNAS and SMAD4 mutations were evaluated most. Of these, TP5 3 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31–54%), specificity of 98% (95%-CI: 92%–100%) and diagnostic odds ratio of 36 (95% CI: 9–133). Of DNA methylation patterns, hypermethylation of CDKN2A , NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39–70% and specificity of 94–100% for distinguishing pancreatic cancer from controls. This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53 , SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel. [Display omitted] [ABSTRACT FROM AUTHOR]

Modern literature data indicate that the role of trypsin goes far beyond its digestive function. Once in the blood, trypsin is involved as part of the kallikreinkinin system in the regulation of blood pressure, regulates pancreatic function by activating PAR receptors, and influences inflammation and immunity in the cell. The interaction of trypsin in the intestine and serum in the living healthy organism has been insufficiently studied. On the basis of our own studies and literature data, we concluded that after overnight fasting the increase of trypsin activity in pancreatic juice and blood serum in the postprandial period occurs in parallel, which determines not only digestion of food protein but also the level of metabolism. Consequently, determining the optimal amount of crude protein in the diet during the morning meal is a paramount task for physiologists. [ABSTRACT FROM AUTHOR]

Backgrounds: Pancreatic juice (PJ) is directly associated with pancreatic lesions, including pancreatic ductal cancer and intraductal papillary mucinous neoplasm-derived cancer. Therefore, EVs secreted from these lesions into PJ can be promising biomarkers for early diagnosis. However, there are limited data from analysis of EVs in PJ samples. Aims and Methods: We aimed to determine the stability of EVs in PJ collected using endoscopic naso-pancreatic drainage (ENPD) tubes as well as catheter during endoscopic retrograde cholangiography (ERCP), with or without the impact of positive protease activity, and optimize the EV isolation method. Results: Size exclusion chromatography was found to be an optimal isolation method for EVs in PJ as it achieved higher recovery and purity of EVs compared with differential ultracentrifugation and polymer-based precipitation. Approximately 40% of the PJ samples collected during ERCP and more than 90% of those collected using ENPD tubes had positive protease activity. In vitro exposure to room temperature for less than 3 h was harmless to the structure of double-membrane EVs in PJ and the expression levels of TSG101, even with positive protease activity. Conclusions: We clarified the physiobiological status of EVs in PJ and optimized the EV isolation method using suitable PJ samples; these findings can be utilized to discover biomarkers for cancer diagnosis and elucidate their function. [ABSTRACT FROM AUTHOR]

Background: To study exocrine function of the remnant pancreas after pancreatoduodenectomy (PD), we propose the use of an exocrine index (PEI) that combines the volume of the remnant pancreas and the intraoperative amylase activity of the pancreatic juice. Here, we aimed to determine whether the PEI can predict non‐alcoholic fatty liver disease (NAFLD) following PD. Methods: Fifty‐seven patients for whom pancreatic juice amylase activity was measured during PD were enrolled. NAFLD was defined as a liver‐to‐spleen attenuation ratio of <0.9 on plain CT 1 year following surgery. We retrospectively evaluated clinical parameters, including the PEI, to identify predictors of NAFLD. Results: Fifty‐four patients (95%) were regularly administered 1200 mg of pancreatic lipase. NAFLD was diagnosed in 13 participants (23%) 1 year following surgery. NAFLD was associated with pancreatic ductal adenocarcinoma (P =.006), soft pancreas (P =.001), small main pancreatic duct (P = 0008), low remnant pancreatic volume (P <.001), low intraoperative amylase activity in the pancreatic juice (P =.001), high pancreatic fibrosis (P =.032), and large body weight loss (P =.015). The PEI was significantly lower in the participants with NAFLD than in those without (P <.001). The participants were then classified into tertiles of PEI: <5 × 106, 5‐25 × 106, and >25 × 106. The prevalence of NAFLD in these groups was 53% (10/19), 11% (2/19), and 5% (1/19), respectively. In multivariable analyses, there was a significant association between NAFLD and the PEI (P value for trend =.042). Conclusion: The PEI, calculated using the remnant pancreatic volume and the intraoperative pancreatic juice amylase activity, predicts NAFLD development following PD. [ABSTRACT FROM AUTHOR]

Modern literature data indicate that the role of trypsin goes far beyond its digestive function. Once in the blood, trypsin is involved as part of the kallikrein-kinin system in the regulation of blood pressure, regulates pancreatic function by activating PAR receptors, and influences inflammation and immunity in the cell. The interaction of trypsin in the intestine and serum in the living healthy organism has been insufficiently studied. On the basis of our own studies and literature data, we concluded that after overnight fasting the increase of trypsin activity in pancreatic juice and blood serum in the postprandial period occurs in parallel, which determines not only digestion of food protein but also the level of metabolism. Consequently, determining the optimal amount of crude protein in the diet during the morning meal is a paramount task for physiologists.

Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in an advanced stage, with minimal likelihood of long-term survival. Only a small subset of patients are diagnosed with early (T1) disease. Early detection is challenging due to the late onset of symptoms and limited visibility of sub-centimeter cancers on imaging. A novel approach is to support the clinical diagnosis with molecular markers. MicroRNA derived from extracellular vehicles (EVs) in blood has shown promise as a potential biomarker for pancreatic neoplasia, but microRNA derived from pancreatic juice (PJ) may be a more sensitive biomarker, given that is in close contact with ductal cells from which PDAC arises. This study aims to evaluate and compare the performance of PJ- and serum-derived EV-miRNA for the detection of PDAC. PJ was collected from the duodenum during EUS after secretin stimulation from 54 patients with PDAC and 118 non-malignant controls. Serum was available for a subset of these individuals. MiR-16, miR-21, miR-25, miR-155 and miR-210 derived from EVs isolated from PJ and serum were analyzed by qPCR, and serum CA19-9 levels were determined by electrochemiluminescence immunoassay. For statistical analysis, either a Mann-Whitney U test or a Wilcoxon Signed Rank test was performed. ROC curves and AUC were used to assess the sensitivity and specificity of miR expression for PDAC detection. Expression of EV-miR-21, EV-miR-25 and EV-miR-16 were increased in cases vs controls in PJ, while only EV-miR-210 was increased in serum. The potential to detect PC was good for a combination of PJ EV-miR-21, EV-miR-25, EV-miR-16 and serum miR-210, CA-19-9, with an area under the curve of 0.91, a specificity of 84.2% and a sensitivity of 81.5%. Detection of miRNA from EVs in PJ is feasible. A combined panel of PJ EV-miR-21, EV-miR-25, EV-miR-16, and serum EV-miR-210 and CA19-9 distinguishes cases with PDAC from controls undergoing surveillance with a specificity of 81.5% and sensitivity of 84.2%. [ABSTRACT FROM AUTHOR]

ObjectiveThe goals of this study were to characterize bacterial communities within fecal samples, pancreatic fluid, bile, and jejunal contents from patients undergoing pancreaticoduodenectomy (PD) and to identify associations between microbiome profiles and clinical variables.MethodsFluid was collected from the pancreas, common bile duct, and proximal jejunum from 50 PD patients. Postoperative fecal samples were also collected. The microbial burden within samples was quantified with droplet digital polymerase chain reaction. Bacterial 16S ribosomal RNA gene sequences were amplified, sequenced, and analyzed. Data from fecal samples were compared with publicly available data obtained from volunteers.ResultsDroplet digital polymerase chain reaction confirmed the presence of bacteria in all sample types, including pancreatic fluid. Relative to samples from the American Gut Project, fecal samples from PD patients were enriched with Klebsiella and Bacteroides and were depleted of anaerobic taxa (eg, Roseburia and Faecalibacterium). Similar patterns were observed within PD pancreas, bile, and jejunal samples. Postoperative fecal samples from patients with a pancreatic fistula contained increased abundance of Klebsiella and decreased abundance of commensal anaerobes, for example, Ruminococcus.ConclusionsThis study confirms the presence of altered bacterial populations within samples from PD patients. Future research must validate these findings and may evaluate targeted microbiome modifications to improve outcomes in PD patients.

(1) Background: The choice of appropriate surgical suture during operation is of great significance. Currently, there are no objective studies regarding the resistance of commonly used sutures in biliary tract surgery. (2) Methods: This fact leads one to conduct research concerning the resistance of the sutures (Polydioxanone, Poliglecaprone, Poliglactin 910, and their analogues coated with antibacterial triclosan) in the environment of sterile and contaminated bile and pancreatic juice. Tensile strength was tested at days 0, 7, 14, 21, and 28 of research. The study was performed in in vitro conditions for 28 days. (3) Results: Pancreatic juice and bile has a significant influence on the tensile strength of each suture. (4) Conclusions: The study indicated that sutures made of polydioxanone had the best qualities during the entire experiment. [ABSTRACT FROM AUTHOR]

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 < 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.

Background and Aim: Bacterial infection is involved in the progression of many gastrointestinal diseases, including those of pancreas; however, how and which bacteria colonize in pancreatic juice and tissue have yet to be elucidated. Recently, we reported that Enterococcus faecalis exists in the pancreatic juice and tissues of patients with chronic pancreatic disease. Here, we investigated the survival of E. faecalis in duodenal juice with different pH conditions. Methods: Pancreatic juice samples from 62 patients with cancers of the duodeno‐pancreato‐biliary region were evaluated for the presence of E. faecalis. 16S ribosomal RNA polymerase chain reaction and 16S‐based metagenome analyses were performed to determine the bacterial composition. The survival of E. faecalis in various pancreatic juice conditions was evaluated. Results: Of 62 samples, 27% (17/62) were positive for Enterococcus spp., among which 71% (12/17) contained E. faecalis. Enterococcus spp. showed the highest fitness for survival in alkaline pancreatic juice among various bacterial species. The microbiome of pancreatic juice from patients with pancreatic and bile duct cancer showed diversity, but Enterococcus spp. were enriched among duodenal tumors and intraductal papillary mucinous neoplasms. Conclusions: Alkalinity is one of the important factors for the selective survival of E. faecalis among microbiota. E. faecalis can colonize the pancreatic duct when the pancreatic juice condition is altered. [ABSTRACT FROM AUTHOR]

Background: The physiological flow patterns and the reciprocal relationship between pancreatic juice and bile excretion dynamics have not been clearly elucidated by imaging. Purpose: To assess the physiological flow patterns of bile and pancreatic juice simultaneously in order to clarify the pancreatobiliary flow dynamics using cine‐dynamic magnetic resonance cholangiopancreatography (MRCP) with a spatial selective inversion recovery (IR) pulse. Study Type: Retrospective. Population: A total of 85 patients with physiologically normal pancreatobiliary flow without ductal dilatation (normal group) and 19 patients with dilated pancreatic duct. Field Strength/Sequence: A 3 T, fast spin echo sequence with IR pulse to nullify the signal of static pancreatic juice and bile. Assessment: The frequency and secretion grade of the antegrade and reverse flow of the pancreatic juice and bile on cine‐dynamic MRCP were visually evaluated. Additionally, the reciprocal relationship between pancreatic juice and bile flow was evaluated based on its flow patterns. Statistical Tests: Spearman's rank correlation coefficient analysis and the Kruskal–Wallis and Mann–Whitney U tests were used. P values of <0.05 were considered to indicate statistical significance. Results: In the normal group, the antegrade pancreatic juice flow and no bile flow pattern was most frequently observed (29%), followed by the no pancreatic juice flow and no bile flow pattern (23%), the antegrade pancreatic juice flow and antegrade bile flow pattern (22%), and the no pancreatic juice flow and reverse bile flow pattern (9%). The flow of the pancreatic juice and bile were synchronized with each other in 47%, while they were not in 53%. In the dilated pancreatic duct group, the mean secretion grade of the antegrade bile and pancreatic juice flow was significantly lower than in the normal group. Data Conclusion: Cine‐dynamic MRCP with a spatially selective IR pulse can visualize the variations of the physiological flow patterns of bile and pancreatic juice including 53% of unsynchronized patterns. Level of Evidence: 4 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Abstract Background Perforation of a marginal peptic ulcer after pancreaticoduodenectomy (PD) can lead to severe conditions, although its clinical features have not been well reported. In this article, we present three cases of marginal peptic ulcer perforation after PD that we experienced in our institute and attempt to clarify its appropriate treatment and prevention. Case presentation Marginal ulcer perforation confirmed with computed tomography and/or surgical exploration occurred in 3 (1.8%) of 163 consecutive patients who underwent PD (including 160 patients who underwent a total or subtotal stomach-preserving procedure) at our institution. The three patients (one man and two women) had a median age of 77 (65–79) years. Two of these patients had a medical history of duodenal peptic ulcer. All three patients had biliary neoplasms. Two of the patients underwent subtotal stomach-preserving PD with antro-jejunal anastomosis, and the other patient underwent pylorus-preserving PD with duodenal jejunostomy. The perforation occurred with a sudden and severe onset of abdominal pain 34, 94, and 1204 days, respectively, after the PDs. At the time of the perforation, all of the patients had been withdrawn from postoperative prophylactic antipeptic ulcer agents, with the cessation periods ranging from 12 to 1008 days. In addition, all the patients were in fasting conditions for 1 to 13 days just before the perforation. Surgical treatment with direct suturing of the perforated ulcer was performed for two patients, while conservative therapy was performed for one patient. Their primary treatment courses were satisfactory. Chronic antisecretory agent therapy was prescribed for 562, 271, and 2370 days, respectively, from marginal ulcer perforation, and no ulcer recurrence was noted in any of the patients. Conclusions Lack of antisecretory therapy and fasting were considered an essential cause of marginal peptic ulcer perforation after PD. In addition, unlike the native duodenum, the jejunal limb used for reconstruction to a preserved stomach may be at increased risk of ulceration. Chronic permanent administration of antisecretory agents and fasting avoidance are desirable for patients who have undergone stomach-preserving PD to prevent marginal ulcer perforation.

Abstract Intraductal papillary mucinous neoplasm (IPMN) of pancreas has a high risk to develop into invasive cancer or co‐occur with malignant lesion. Therefore, it is important to assess its malignant risk by less‐invasive approach. Pancreatic juice cell‐free DNA (PJD) would be an ideal material in this purpose, but genetic biomarkers for predicting malignant risk from PJD are not yet established. We here performed deep exome sequencing analysis of PJD from 39 IPMN patients with or without malignant lesion. Somatic alterations and copy number alterations (CNAs) detected in PJD were compared with the histologic grade of IPMN to evaluate their potential as a malignancy marker. Somatic mutations of KRAS, GNAS, TP53, and RNF43 were commonly detected in PJD of IPMNs, but no association with the histologic grades of IPMN was found. Instead, mutation burden was positively correlated with the histologic grade (r = 0.427, P = 0.015). We also observed frequent copy number deletions in 17p13 (TP53) and amplifications in 7q21 and 8q24 (MYC) in PJDs. The amplifications in 7q21 and 8q24 were positively correlated with the histologic grade and most prevalent in the cases of invasive carcinoma (P = 0.002 and 7/11; P = 0.011 and 6/11, respectively). We concluded that mutation burden and CNAs detected in PJD may have potential to assess the malignant progression risk of IPMNs.

Story of Pavlov’s studies on food digestion including his Nobel Prize in 1904 are presented. Some new ideas and concepts are also viewed based on 3th International Conference on Food Digestion held in Wageningen (the Netherlands) in 2014.

Abstract Background Reliable methods are needed to identify patients with early-stage cancer or high-grade precancerous lesions in the pancreas. Analysis of pancreatic juice to detect somatic mutations could represent one such approach. Here we investigated the concordance between mutations found in the primary tumor and pancreatic juice from the same patient. Methods Amplicon-based targeted deep sequencing was performed on samples from 21 patients with pancreatic ductal adenocarcinoma (PDAC) who had undergone Whipple’s operation. Mutation profiles were determined in formalin-fixed sections of the primary tumor and in pancreatic juice sampled from the main pancreatic duct during surgery. Results Using a cut-off of 3% for variant allele frequency, KRAS mutations were detected in 20/21 primary tumors (95%) and in 15/21 (71%) juice samples. When also considering low-frequency variants, KRAS mutations were found in 20/21 juice samples. Most juice samples exhibited multiple KRAS variants not seen in the primary tumor, and only in 11 cases (52%) did the most abundant variant of the juice correspond to the KRAS mutation detected in the tumor. TP53 mutations were found in 16 tumors (76%) and six juice samples (29%). Among the positive juice samples, only one exhibited more than a single TP53 mutation. Detection of both KRAS and TP53 mutations was fully concordant in the primary tumor and juice sample in 7/21 cases (33%). Conclusions Pancreatic juice from PDAC patients is rich in KRAS mutations often not seen in the primary tumor and possibly reflecting precancerous lesions in other regions of the pancreas. The inclusion of TP53 mutation detection and additional markers must therefore be considered for fully exploiting the clinical potential of pancreatic juice samples in early cancer detection.

(1) Background: The choice of appropriate surgical suture during operation is of great significance. Currently, there are no objective studies regarding the resistance of commonly used sutures in biliary tract surgery. (2) Methods: This fact leads one to conduct research concerning the resistance of the sutures (Polydioxanone, Poliglecaprone, Poliglactin 910, and their analogues coated with antibacterial triclosan) in the environment of sterile and contaminated bile and pancreatic juice. Tensile strength was tested at days 0, 7, 14, 21, and 28 of research. The study was performed in in vitro conditions for 28 days. (3) Results: Pancreatic juice and bile has a significant influence on the tensile strength of each suture. (4) Conclusions: The study indicated that sutures made of polydioxanone had the best qualities during the entire experiment.

A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. This study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 105 IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%) The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD. [ABSTRACT FROM AUTHOR]

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 < 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. [ABSTRACT FROM AUTHOR]

Competing Interests: S. Varadarajulu is a consultant for Boston Scientific, Medtronic, and Olympus America.

Background: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies., Methods: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP)., Results: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively., Conclusions: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Resection using a stapler is a popular approach to distal pancreatectomy. However, the resulting leakage of pancreatic juice represents a serious problem. We have developed a force‐fluorescence measurement as a first step towards the quantitative evaluation of pancreatic leakage due to tissue tearing under compression. Methods: The system comprises a testing machine with an indenter, similar in size to a stapler, which controls compression speed and measures reaction force, and a fluorescence measurement system to measure pancreatic juice leakage. Pancreatic juice leakage is measured as the maximum value of the increasing rate of fluorescence intensity (max value). Ten excised swine pancreases were compressed at a speed of 500, 100, and 10 mm/min until their thicknesses became 2 mm. Results: A strong positive correlation (0.804) was observed between the increase in max value before and after compression and the amount of reaction force drop due to tissue destruction. No pancreatic juice leakage was observed when compressed slowly (10 mm/min). Conclusions: We have successfully developed a novel force‐fluorescence measurement system that can detect and quantify pancreatic juice leakage caused by tissue tearing. This system can determine the optimal compression conditions for preventing pancreatic juice leakage. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a digestive system tumor with insidious onset,high malignancy,and difficult diagnosis,and early diagnosis is the key to improving the survival rate and prognosis of patients with pancreatic cancer. This article introduces the research advances in abnormal methylation of cell-free DNA in pancreatic juice and the early diagnosis of pancreatic cancer,and it is believed that the detection of cell-free DNA methylation in pancreatic juice may be an effective method for the early diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

The efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. Forty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. Thirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. Repeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology. [ABSTRACT FROM AUTHOR]

Background: Perforation of a marginal peptic ulcer after pancreaticoduodenectomy (PD) can lead to severe conditions, although its clinical features have not been well reported. In this article, we present three cases of marginal peptic ulcer perforation after PD that we experienced in our institute and attempt to clarify its appropriate treatment and prevention.Case Presentation: Marginal ulcer perforation confirmed with computed tomography and/or surgical exploration occurred in 3 (1.8%) of 163 consecutive patients who underwent PD (including 160 patients who underwent a total or subtotal stomach-preserving procedure) at our institution. The three patients (one man and two women) had a median age of 77 (65-79) years. Two of these patients had a medical history of duodenal peptic ulcer. All three patients had biliary neoplasms. Two of the patients underwent subtotal stomach-preserving PD with antro-jejunal anastomosis, and the other patient underwent pylorus-preserving PD with duodenal jejunostomy. The perforation occurred with a sudden and severe onset of abdominal pain 34, 94, and 1204 days, respectively, after the PDs. At the time of the perforation, all of the patients had been withdrawn from postoperative prophylactic antipeptic ulcer agents, with the cessation periods ranging from 12 to 1008 days. In addition, all the patients were in fasting conditions for 1 to 13 days just before the perforation. Surgical treatment with direct suturing of the perforated ulcer was performed for two patients, while conservative therapy was performed for one patient. Their primary treatment courses were satisfactory. Chronic antisecretory agent therapy was prescribed for 562, 271, and 2370 days, respectively, from marginal ulcer perforation, and no ulcer recurrence was noted in any of the patients.Conclusions: Lack of antisecretory therapy and fasting were considered an essential cause of marginal peptic ulcer perforation after PD. In addition, unlike the native duodenum, the jejunal limb used for reconstruction to a preserved stomach may be at increased risk of ulceration. Chronic permanent administration of antisecretory agents and fasting avoidance are desirable for patients who have undergone stomach-preserving PD to prevent marginal ulcer perforation. [ABSTRACT FROM AUTHOR]

Background: Which suture material is optimal for pancreaticojejunostomy (PJ) anastomosis is a matter of debate with contradictory results. The aim of the present in vitro study was to determine the effects of pancreatic juice, bile, and their mixture on different suture materials in terms of breaking strength and disintegration. Material and Methods: Four suture materials, silk, polyglactin 910, polydioxanone, and polypropylene, were tested in pancreatic juice, bile, and their mixture. Determination of breaking strength and disintegration under electron microscope for each suture material was done on days 0, 3, 6, and 10. Results: The breaking strength of polyglactin 910 and silk was significantly higher than polypropylene and polydioxanone (p < .05). Polyglactin 910 significantly lost its breaking strength with time in pancreatic juice, bile, and their mixture (p < .001). The breaking strength of each type of suture did not significantly alter in pancreatic juice, bile, and their mixture at the baseline measurement and at the end of the experiment (p > .05). No obvious disintegration has been observed under electron microscope in the architecture and appearance of suture materials after days of exposure to pancreatic juice, bile, and their mixture. Conclusions: None of the suture materials was disintegrated on exposure to pancreatic juice, bile, and their mixture. Polyglactin 910 has the highest breaking strength and significantly loses its strength throughout the experiment but still remains higher than other suture materials. Polypropylene, polydioxanone, and silk showed less variation across the incubation period.