Intraoperative amylase level of pancreatic juice as a simple predictor of pancreatic fistula after pancreaticoduodenectomy.

INTRODUCTION: 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. METHOD: 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. RESULTS: 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%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.

Analysis of lipase activity in duodenal juice. Comparison of an automated spectrophotometric assay to a fluorometric microplate assay, and factors affecting sample stability.

BACKGROUND: Direct pancreas function testing (DPFT) has been regarded as gold standard for assessment of exocrine pancreas function. One of the outcomes from DPFT is pancreatic lipase activity in duodenal juice, but no standard assay for measuring pancreas lipase activity in duodenal juice exists. AIMS: To optimize and evaluate an autoanalyzer assay for measuring lipase activity in duodenal juice. METHODS: We used samples of duodenal juice from our biobank, collected through a short endoscopic secretin test in patients with suspected exocrine pancreas insufficiency. Samples were analyzed on a Cobas autoanalyzer (Roche Diagnostics), using a colorimetric, kinetic enzyme activity assay. We compared stability of samples diluted in saline to samples diluted in 3-(N-morpholino) propane sulfonic acid (MOPS) buffer added bovine serum albumin (BSA). Results from the Cobas assay were compared to Confluolip method, a fluorometric, kinetic enzyme assay, modified to fit into a microplate setting. RESULTS: We tested the stability of 54 samples from 21 patients. Diluting samples with MOPS buffer added BSA gave stable results, and was superior to diluting samples in saline. We compared the two assays in 50 samples from 20 patients and found a good correlation between the two assays (r = 0.91, p < .001). There was a significant proportional bias between the two assays, but no significant systematic bias. CONCLUSION: Pancreatic lipase activity in duodenal juice samples diluted in MOPS buffer added BSA is stable for one hour at room temperature. Quantification of lipase activity in duodenal juice using a standard automated activity assay has comparable accuracy to a manual fluorometric method.

Telomerase activity in pancreatic juice differentiates pancreatic cancer from chronic pancreatitis: A meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the usefulness of genetic markers in pancreatic juice (PJ), and the combination of these markers with telomerase activity in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis. METHODS: We conducted a meta-analysis for the diagnostic utility of the four major altered genes in PDAC (KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4), telomerase activity, and a combination assay using PJ samples. A literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. Data were pooled and presented as diagnostic sensitivity and specificity with 95% confidence intervals (CIs). RESULTS: Thirty-nine studies fulfilled the inclusion criteria. Pooled estimates of KRAS analysis were as follows: sensitivity was 0.67 (95% CI, 0.63-0.71) and specificity, 0.82 (95% CI, 0.79-0.85). For telomerase activity analysis, sensitivity was 0.82 (95% CI, 0.76-0.87) and specificity, 0.96 (95% CI, 0.90-0.99). The other three tumor suppressors demonstrated low sensitivity. The data did not suggest any publication bias. A combined analysis of KRAS and telomerase activity showed a higher diagnostic sensitivity (0.94; 95% CI, 0.83-0.99) than KRAS alone. A combined analysis of telomerase activity and cytology revealed more reliable diagnostic accuracy than telomerase activity alone, with high sensitivity (0.88; 95% CI, 0.74-0.96) and specificity (1.00; 95% CI, 0.91-1.00). CONCLUSIONS: The most reliable marker in PJ samples for diagnosis of PDAC was telomerase activity. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and can increase diagnostic accuracy when combined with KRAS mutations or cytological examination.

Intra-operative amylase in peri-pancreatic fluid independently predicts for pancreatic fistula post pancreaticoduodectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a common and potentially life-threatening complication following pancreaticoduodectomy. The aim of this study was to assess the predictive value of intra-operative amylase concentration (IOAC) in peri-pancreatic fluid after resection for the diagnosis of POPF. METHODS: Consecutive patients who underwent a pancreaticoduodectomy between September 2014 and October 2015 were included in the analysis. IOAC was measured intraoperatively followed by drain fluid analysis for amylase on post-operative days (POD) 1, 3 and 5. Receiver operator characteristic (ROC) analysis was performed to evaluate the discriminative capacity of IOAC as a predictor of POPF. RESULTS: IOAC was measured after pancreaticoduodectomy in 62 patients. The IOAC correlated significantly with i) POD 1 and 3 drain amylase (p < 0.01), ii) the development of POPF (p < 0.01), iii) the development of clinically relevant fistula (Type B, C) (p < 0.01), iv) delayed gastric emptying (p < 0.01), and v) grade of complication as per the Clavien-Dindo definition (p = 0.02). ROC curve analysis confirmed the predictive relationship of IOAC and POPF as a good test with an area under the curve of 0.93, 95% CI 0.87-0.99, p < 0.01. In patients with IOAC of 200 U/L or higher the POPF rate was 80% (OR = 50.1, p < 0.0001). DISCUSSION: Measurement of IOAC allows early and accurate categorization of patients at risk for POPF.

Relationships between leucine and the pancreatic exocrine function for improving starch digestibility in ruminants.

Four Holstein heifers (215 ± 7 kg; means ± SD), fitted with one pancreatic pouch, duodenal re-entrant cannulas, and duodenal infusion catheters, were used in this experiment. In phase 1, the 24-h profile of pancreatic fluid was determined. Pancreatic fluid flow peaked 1h after feeding, but peaks of similar magnitude also occurred before the morning feed, necessitating 24-h collection of pancreatic fluid to estimate daily excretion. In phase 2, the effects of duodenal infusions of 0, 10, 20, or 30 g of leucine on pancreatic fluid flow were determined in a 4 × 4 Latin square design. The leucine was infused for 12h in 2,500 mL of the infusate, and samples of pancreatic fluid and jugular blood were collected in 1-h intervals from the beginning of the infusion for 36 h. The results showed that the secretion rate of pancreatic fluid (mL/h) was significantly higher in 10-g leucine group than the other groups (mL/h). Protein concentration (mg/mL) in pancreatic fluid was elevated proportional to the amount of leucine infused. Leucine infusions increased both the concentration (U/mL) and secretion rate (U/h) of α-amylase. Infusion of 10 g of leucine also increased the secretion rates (U/h) of trypsin, chymotrypsin, and lipase, but did not change their concentrations. No significant effects of leucine infusions on plasma glucose and insulin concentrations were found. The results indicate that leucine could act as a nutrient signal to stimulate α-amylase production and pancreatic exocrine function in dairy heifers.

Quantitative assessment of the diagnostic role of human telomerase activity from pancreatic juice in pancreatic cancer.

Many studies have shown that human telomerase activity could play potential role as a diagnostic biomarker of pancreatic cancer (PaC). The aim of this meta-analysis is to summarize the clinical value of human telomerase activity in the diagnosis of PaC. Eligible studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Sci Verse, Science Direct, Scopus, BioMed Central, Biosis previews, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang databases were searched concerning the diagnostic value of human telomerase activity in PaC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratio (DOR) for human telomerase activity in the diagnosis of PaC were pooled. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2) test. Meta-Disc 1.4 and Stata 12.0 software were used to analyze the data. Nine studies with a total 186 PaC patients and 132 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score ≥10). The summary estimate was 0.83 (95 % confidence interval (CI), 95 % CI = 0.77-0.88) for sensitivity and 0.72 (95 % CI = 0.64-0.79) for specificity. The positive likelihood (PLR), negative likelihood (NLR), and diagnostic odds (DOR) ratios were 3 (95 % CI = 1.67-5.41), 0.25 (95 % CI = 0.13-0.46), and 3 (95 % CI = 4.91-43.23), respectively. The area under the summary ROC curve (AUC) and Q* index for the diagnosis of PaC were 0.88 and 0.81, respectively. Our study demonstrates that telomerase could be a useful tumor marker for PaC diagnosis. Although more studies are needed to highlight the theoretical strengths, these results will provide theoretical basis for bringing telomerase activity detection into PaC screening plan.

Is the enteral replacement of externally drained pancreatic juice valuable after pancreatoduodenectomy?

PURPOSES: External drainage of pancreatic juice using a pancreatic duct stent following pancreatoduodenectomy is widely performed. We hypothesized that the replacement of externally drained pancreatic juice would help to prevent postoperative complications, including pancreatic fistulas. METHODS: Sixty-four patients who underwent pancreatoduodenectomy between 2006 and 2008 were randomly assigned to either a pancreatic juice non-replacement (NR) or replacement (R) group. Eighteen patients were excluded from the analysis because they had unresectable tumors (n = 4), low pancreatic juice output (<100 ml) (n = 11) or for other reasons (n = 3). A total of 46 patients (NR = 24, R = 22) were included in the final analysis. The volume and amylase levels of externally drained pancreatic juice were analyzed on postoperative days 7 and 14. The incidence of postoperative complications, including pancreatic fistulas and delayed gastric emptying, was also assessed. RESULTS: The total amylase secretion from the pancreatic tube on postoperative day 7 was significantly higher in the NR group compared with the R group (P = 0.044). The incidence of pancreatic fistulas (>Grade B) was also significantly higher in the NR group (33.3 vs. 9.1 %, P = 0.046). CONCLUSIONS: In cases for whom external pancreatic juice drainage from a stent is applied following pancreaticojejunostomy, enteral replacement of externally drained pancreatic juice may reduce the incidence of postoperative pancreatic fistula formation.

In vitro effects of proteases in human pancreatic juice on stability of liquid and carrier-bound fibrin sealants.

BACKGROUND: Fibrin sealants are used in pancreatic surgery to prevent leakage of pancreatic fluid and reduce associated complications. The efficacy of this approach is unclear. METHODS: Fibrin clots were generated in vitro from two commercially available liquid fibrin sealants (Tissucol Duo® and Evicel®) and the carrier-bound fibrin sealant Tachosil®, and exposed to normal saline or human pancreatic fluid. Stability of the sealants was assessed by release of the fibrin and collagen degradation products, D-dimer and hydroxyproline. The effect of protease inhibitors on sealant breakdown was assessed. RESULTS: Clots generated from liquid fibrin sealants degraded rapidly in pancreatic fluid, but not in normal saline. D-dimer release from fibrin clots by pancreatic fluid was approximately 1700 µg/ml after 24 h and less than 20 µg/ml by saline. Pancreatic fluid, but not normal saline, degraded both the fibrin and collagen component of Tachosil®. After 6 h, mean(s.e.m.) D-dimer levels in pancreatic fluid exposed to Tachosil® were 850(183) ng/ml, compared with 60(6) ng/ml in normal saline. The mean(s.e.m.) hydroxyproline concentration in pancreatic fluid was 497(17) µg/ml after a 24-h exposure to Tachosil®, compared with 26(12) µg/ml in normal saline. Protease inhibitors significantly inhibited breakdown of liquid sealants (D-dimer levels less than 50 µg/ml after 24 h) and Tachosil® (D-dimer release 179(12) ng/ml at 6 h; hydroxyproline release 181(29) µg/ml at 24 h). CONCLUSION: Proteases in pancreatic juice effectively degrade both liquid and carrier-bound fibrin sealants in vitro. The use of these products in pancreatic surgery with the aim of preventing leakage of pancreatic fluid is not supported by this experimental study.

Pancreatic lipase-colipase binds strongly to the thylakoid membrane surface.

BACKGROUND: Isolated thylakoid membranes, i.e. the photosynthetic membranes of green leaves, inhibit the activity of pancreatic lipase and colipase during hydrolysis of fat in vitro. This inhibition has been demonstrated to cause reduced food intake and improved hormonal and lipid profile in vivo. One of the reasons suggested for the inhibiting effect is binding of lipase-colipase to the thylakoid membrane surface. This prompted a study of the binding of lipase and colipase to thylakoids. RESULTS: The results showed that lipase and colipase strongly bind to the thylakoid membrane surface. The dissociation constant was determined at 1.2 × 10⁻8 mol L⁻¹; binding decreased after treatment of thylakoids with pepsin/trypsin to 1.0 × 10⁻7 and to 0.6 × 10⁻7 mol L⁻¹ after treatment with pancreatic juice. Similarly, delipidation of thylakoids caused a decrease in binding, the dissociation constant being 2.0 × 10⁻7 mol L⁻¹. CONCLUSION: The binding of pancreatic lipase-colipase to the thylakoid membrane is strong and may explain the inhibition of lipase-colipase activity by thylakoids. After treatment with proteases to mimic intestinal digestion binding is decreased, but is still high enough to explain the observed metabolic effects of thylakoids in vivo.

[Influence of pancreatic segment graft autotransplantation on its exocrine function].

In experiments on dogs the exocrine secretion of pancreatic segment graft after its autotransplantation and of pancreatic stamps after proximal resection of the pancreas was investigated. More significant impairment of the exocrine secretion of the pancreas was revealed in animals after pancreatic graft autotransplantation in comparison with animals after the proximal resection of the pancreas. Maintenance of the adaptation of pancreatic exocrine secretion to the nutritional composition of the intestinal contents and "generalized inhibition" of pancreatic exocrine secretion caused by duodenal trypsin infusion was revealed in all groups.

Corticosteroids correct aberrant CFTR localization in the duct and regenerate acinar cells in autoimmune pancreatitis.

BACKGROUND & AIMS: Corticosteroids are now widely accepted as a treatment for autoimmune pancreatitis (AIP). However, the molecular mechanism by which steroid treatment improves AIP remains largely unknown. The aim of this study was to elucidate cellular mechanisms by which corticosteroids improve both pancreatic exocrine function and histopathology in AIP. METHODS: Pancreatic exocrine function was evaluated by the secretin-stimulated function test and pancreatic biopsy specimens were processed for histologic analysis at the time of diagnosis and 3 months after initiation of steroid treatment. Expression and localization of proteins was assayed by immunohistochemistry. Analysis of immunoglobulin (Ig)G4-positive plasma cells was used to verify inflammation in AIP. RESULTS: The number of IgG4-positive plasma cells in pancreatic sections was decreased by steroid treatment, indicating reduced inflammation. Fluid, bicarbonate (HCO(3)(-)), and digestive enzyme secretions all were impaired in most patients with AIP. Corticosteroids improved both HCO(3)(-) and digestive enzyme secretion. A large fraction of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a central role in pancreatic duct HCO(3)(-) secretion, was mislocalized to the cytoplasm of duct cells before treatment. Corticosteroids corrected the localization of CFTR to the apical membrane, accounting for the improved HCO(3)(-) secretion. Steroid treatment resulted in regeneration of acinar cells, accounting for restored digestive enzyme secretion. CONCLUSIONS: Corticosteroids reduce inflammation and restore both digestive enzyme and HCO(3)(-) secretion in patients with AIP by regenerating acinar cells and correcting CFTR localization in pancreatic duct cells. Mislocalization of CFTR may explain aberrant HCO(3)(-) secretion in other forms of pancreatitis.

Pancreatic enzyme deficiency depends on dietary protein origin in milk-fed calves.

In young mammals, milk proteins and their substitutes are used in milk formula. Protein substitution modifies diet digestibility and pancreatic secretions. The aim of this study was to test if milk protein substitution could generate pancreatic deficiency in milk-fed calves. The effect of pancreatic juice on the digestibility of proteins was studied. Measurement of apparent fecal nutrient digestibility was used to estimate digestion. Ten calves (60 to 130 d old) were chronically fitted with pancreatic accessory duct cannulas and 2 duodenal cannulas to provide precise measurement, sampling, and reintroduction of pancreatic juice as well as additional infusions. Animals were fed milk formula based on skim milk powder or soybean concentrate. Level of deficiency depended on dietary protein origin. Twice as much protein or trypsin was required with a soybean concentrate diet than with a skim milk powder diet to obtain maximal nutrient digestibility. Pancreatic protein concentration in the juice can be used to differentiate between normal and deficient animals. Among these proteins, trypsin measurement is a good pancreatic deficiency marker. These results confirmed the major role of exocrine pancreatic secretions in producing optimal digestion in young calves. Furthermore, practical applications of these results can be applied for the young in other animal species and in humans.

Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44/14 by digestive lipases.

Gelucire 44/14 is a semi-solid self-emulsifying excipient used for the oral delivery of poorly water-soluble drugs. It is composed of C8-C18 acylglycerols and PEG-32 esters, all of which are potential substrates for digestive lipases. Here we studied the lipolysis of Gelucire 44/14 by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases. Human pancreatic lipase (HPL), the main lipase involved in the digestion of triacylglycerols, did not show any significant activity on Gelucire 44/14 or on either of its individual compounds, C8-C18 acylglycerols and PEG-32 esters. Other pancreatic lipases such as human pancreatic lipase-related protein 2 (HPLRP2) showed low activity on Gelucire 44/14 although the highest activity of HPLRP2 was that observed on the C8-C18 acylglycerol fraction, which accounts for 20% (w/w) of Gelucire 44/14. In addition, HPLRP2 showed low activities on the PEG-32 esters, whether these were tested individually or mixed together. Carboxyl ester hydrolase (CEH) showed high activity on Gelucire 44/14, and the highest activities of CEH were those recorded on the total PEG-32 ester fraction and on each individual PEG-32 ester, except for PEG-32 monostearate. The highest activity of all the enzymes tested was that of dog gastric lipase (DGL) on Gelucire 44/14, although DGL showed low activity on the PEG-32 ester fraction and on each individual PEG-32 ester. We compared the lipolysis of Gelucire 44/14 with that of Labrasol, another self-emulsifying excipient, which is liquid at room temperature. Human pancreatic juice showed similar rates of activity on both Gelucire 44/14 and Labrasol. This finding means that these excipients are hydrolyzed in vivo during pancreatic digestion, mainly by CEH in the case of Gelucire 44/14 and by both HPLRP2 and CEH in that of Labrasol, whereas HPL showed very low activities on each of these two excipients. This is the first time the effects of PEG and acyl chain length on the lipolytic activity of digestive lipases on PEG esters have been investigated.

[Regulation of pancreatic exosecretion].

The review contains the materials on scientific literature, research results of the author and his colleagues about organization of pancreatic exosecretion activity. Peptidegric regulatory mechanisms and pancreatic exosecretion of the hydrolytic enzymes, their participation in adaptation of the pancreatic enzymatic discharge to the nutrient composition of duodenal chyme are underlined.

[Application of somatulin in the treatment of complications after operations on the pancreatic gland].

The results of treatment of 32 patients with complications, occurring after operations on pancreatic gland, ended by the external pancreatic fistula formation, in the complex of their treatment Somatulin, somatostatin analogue of prolonged action, were studied. Application of the treatment tactics proposed have permitted to achieve the fistula closure in all the patients without the operative intervention. The terms of the pancreatic fistula closure after Somatulin injection had constituted 5-20 days, (11.1 +/- 0.7) days at average.

Pancreozymin bioassay in man based on pancreatic enzyme secretion: potency of specific amino acids and other digestive products.

The ability of products of digestion to stimulate pancreozymin secretion in man was investigated using a bioassay procedure, based on duodenal perfusion, which quantified the total outputs of pancreatic enzymes evoked by intraduodenal stimuli under steady-state conditions. Patterns of response resulting from physiologic intraduodenal concentrations of test material were basal output (with isotonic saline), washout of enzymes (with dextrose, micellar fatty acid, and amino acids), and sustained output of enzymes (with amino acids and micellar fatty acid). The sustained secretion of pancreatic enzymes found during the 2nd hr of perfusion and subsequently was characteristic of pancreozymin-induced secretion. The enzyme output in response to a mixture of essential and nonessential amino acids was significantly higher than that evoked by micellar fatty acid and was comparable with that resulting from the maximally tolerated dose of pancreozymin given by vein. Perfusion with essential amino acids caused enzyme outputs comparable to those induced by perfusion with the original amino acid mixture, whereas perfusion with nonessential amino acids had no effect. When the essential amino acids were tested individually, only phenylalanine, methionine, and valine caused significant increases in pancreatic enzyme output; the effect of tryptophan was indeterminate. However, the pancreatic enzyme output was less in response to these three essential amino acids than to mixtures containing all of them.

Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer.

Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63-0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not sufficient to determine treatment strategy in patients with a periampullary mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may be clinically useful.

Intra-Operative Amylase Concentration in Peri-Pancreatic Fluid Predicts Pancreatic Fistula After Distal Pancreatectomy.

Post-operative pancreatic fistula (POPF) is a potentially severe complication following distal pancreatectomy. The aim of this study was to assess the predictive value of intra-operative amylase concentration (IOAC) in peri-pancreatic fluid after distal pancreatectomy for the diagnosis of POPF. Consecutive patients who underwent a distal pancreatectomy between November 2014 and September 2016 were included in the analysis. IOAC was measured, followed by drain fluid analysis for amylase on post-operative days (PODs) 1, 3, and 5. Receiver operator characteristic (ROC) analysis was performed to evaluate the discriminative capacity of IOAC as a predictor of POPF. IOAC was measured after distal pancreatectomy in 26 patients. The IOAC correlated significantly with (i) PODs 1, 3, and 5 drain amylase (p < 0.01); (ii) the development of POPF (p < 0.01); and (iii) the Clavien-Dindo grade of surgical complications (p = 0.02). Eighty-three percent of patients with an IOAC > 1000 experienced a post-operative complication (OR 18.3, 95% CI 2.51-103, p < 0.01). ROC curve analysis confirmed the predictive relationship of IOAC and POPF as an excellent test with an area under the curve of 0.92 (95% CI 0.81-0.99, p < 0.01). Measurement of IOAC allows early and accurate categorization of patients at risk for POPF in distal pancreatectomy.

Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer.

Measurement of telomerase activity is a promising diagnostic tool for pancreatic cancer. Detection of mRNA for human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is also a diagnostic candidate. In the present study, we developed a telomeric repeat amplification protocol assay with real-time PCR and a protocol for quantification of hTERT mRNA with real-time PCR. To evaluate the feasibility of these methods for diagnosis of pancreatic cancer, we measured telomerase activity and hTERT expression in pancreatic cancer cell lines, pancreatic tissues, and pancreatic juice samples from patients with different pancreatic diseases. There were significant correlations between telomerase activity and hTERT expression in cell lines, tissues, and juice samples. The levels of telomerase activity and hTERT expression were significantly higher in tumoral tissues than in nontumoral tissues. In pancreatic juice specimens, some carcinoma samples showed remarkably high expression of hTERT. However, there were no significant differences in hTERT expression between patients with carcinoma and those with benign diseases, although significant differences in telomerase activity were observed. Our present results suggest that the combined assessment of hTERT and telomerase activities in pancreatic juice provides a potent diagnostic method for pancreatic cancer.

Pancreatic secretion differs according to the genotype of growing pigs.

The objective of this study was to investigate the secretion of pancreatic enzymes and antibacterial activity in weaned pigs of three pure breeds, Pietrain, Duroc and Polish synthetic line 990, to look for eventual differences related to the genotype. Six male pigs of each breed, about 24 kg mean body weight, were equipped with chronic pancreatic duct catheters and duodenal cannulas to assess pure pancreatic juice, and jugular vein catheters for blood withdrawal. Pancreatic juice was collected before and after the morning feeding. Protein output and enzyme activities revealed two distinct profiles: strong manifestation of the prandial phase in Pietrain and line 990 pigs, and weak manifestation in Duroc. The antibacterial activity did not follow the enzyme kinetics, and it was the strongest in pancreatic juice from Pietrain pigs. Postprandial insulinaemia was reduced in the order of: line 990>Pietrain>Duroc. A slight (not significant) tendency towards a reduction of leptin after feeding in synthetic line 990 corresponded with elevated secretion of pancreatic enzymes and plasma insulin. The presented results suggest that the prandial secretion of pancreatic juice differs according to genotype, and the differences may be in part related to release of insulin.