Pure Pancreatic Juice Research Articles

PSEUDO-KYSTE DU PANCREAS CHEZ LA PERSONNE AGEE : A PROPOS D’UNE OBSERVATION A L’HOPITAL NATIONAL DONKA, CHU DE CONAKRY ET REVUE DE LA LITTERATURE

Introduction: Pancreatic pseudocysts (PKP) are fluid collections without their own epithelium, developed at the expense of or in contact with the pancreas, containing pure pancreatic juice or mixed with necrotic debris, following pancreatitis or trauma, or of undetermined cause. Treatment of PKP usually requires drainage. We discuss the diagnostic and therapeutic aspects of a case of pseudocyst of the pancreas drained by conventional surgery in an elderly patient with a good post-operative course. Observation: We admitted an 80-years-old patient with epigastric abdominal mass, pain, physical asthenia and anorexia evolving for 1 year. She had no previous medical history. Examination revealed a painful epigastric abdominal mass, more or less mobile in relation to the deep plane, with a smooth surface and irregular, matt edges. Pelvic touch was unremarkable. CT scan showed a large intra-abdominal cystic mass (pancreatic cyst? mesenteric cyst?). Biology revealed anemia and hyperleukocytosis. After laparotomy, we found a voluminous, firm cystic mass, about 10x5x8 cm in size, at the expense of the body of the pancreas. We proceeded to internal drainage of the cyst by retrogastric cystogastrostomy according to JEDLICKA. The patient was followed up for one year without any particularities. Conclusion: In our case, a symptomatic pancreatic pseudocyst was drained by surgical retrogastric cystogastrostomy with a favorable outcome. The management of pancreatic pseudocysts requires a multidisciplinary approach and an adequate technical platform. Key words: Pseudocyst, pancreas, diagnosis, treatment, elderly patient

ID: 3525194 ROLE OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY AND INTRADUCTAL SECRETIN TEST IN THE DIAGNOSIS OF EXOCRINE PANCREATIC INSUFFICIENCY

Chronic Pancreatitis (CP) may be difficult to diagnose in the early stages when imaging may be normal. Exocrine pancreatic insufficiency (EPI) may be considered as a surrogate marker of CP, although not all patients with CP have EPI. During performance of endoscopic retrograde cholangiopancreatography, addition of an Intraductal Secretin Test (IDST) may further aid the evaluation of EPI, based on determination of pure pancreatic juice (PPJ) volume and bicarbonate concentration (BC). The optimal collection time for IDST is unknown.

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.

Role of Endoscopic Retrograde CholangioPancreatography (ERCP) and Intraductal Secretin Test (IDST) in the Diagnosis of Chronic Pancreatitis (CP)

Background: 
 CP may be difficult to diagnose in the early stages when imaging may be normal. An IDST performed at ERCP may further evaluate for CP, with determination of pure pancreatic juice (PPJ) volume and bicarbonate concentration (BC). The optimal collection time for IDST is unknown. We report our experience with the IDST in 447 patients with suspected CP. 
 Experimental Design: 
 IDSTs performed from 2006-2018 were reviewed, with fluid collected at 5-min intervals for 20-60 minutes. Parameters evaluated were PPJ volume, Secretory Flow Rate (SFR), time of peak SFR, maximum BC and time to maximum BC. 
 Results: 
 Maximum BC was reached by 10-min in 59 patients (13.2%); 15-min: 207 patients (46.3%); 20 min: 340 patients (76.1%); 25-min: 384 patients (85.9%); 30-min: 421 patients (94.1%). Peak SFR was reached by 10-min in 92 patients (20.6%); 15-min: 177 patients (39.6%); 20-min: 240 patients (53.7%); 25-min: 284 patients (63.5%); 30-min: 323 patients (72.3%). Final diagnosis (normal vs. CP) for both SFR and BC was determined by 20-min (i.e. in CP pts, either the SFR or BC was low (SFR <3ml/min, BC <105mEq/L) and remained low throughout collection, or normal (>3ml/min and >105mEq/L) within the first 20-min. Further collection did not change the diagnosis. 
 Conclusion: 
 At IDST, a 20-minute collection period is necessary to categorize patients into normal or suspected CP groups. A study in control patients (no suspicion of CP) to validate these data is currently underway.

Next-Generation Sequencing Revealed TP53 Mutations to Be Malignant Marker for Intraductal Papillary Mucinous Neoplasms That Could Be Detected Using Pancreatic Juice.

The aims of this study were to identify the genetic mutations associated with malignant intraductal papillary mucinous neoplasms (IPMNs) and evaluate the possibility of detecting mutations in pure pancreatic juice by next-generation sequencing. Resected tissues were collected from 50 patients with IPMN, and pure pancreatic juice samples were collected from 19 patients who had a resection. The extracted DNA was amplified by multiplex polymerase chain reaction targeting 52 cancer-related genes, including KRAS, GNAS, RNF43, and TP53; the mutations were then detected by next-generation sequencing and then analyzed for correlations with the clinicopathological characteristics. In the resected tissues, the most frequently detected mutations were in KRAS, GNAS, TP53, and RNF43, in 88%, 76%, 36%, and 30% of cases, respectively. Univariate and multivariate analyses revealed that only TP53 mutations were associated with malignant IPMNs (P = 0.023). In the pure pancreatic juice, TP53 mutations were detected in 5 of 10 resected samples with malignant IPMN and in 4 of 5 pancreatic juice samples with mutation in resected samples. From 52 cancer-related gene analysis, only TP53 mutation was associated with malignant IPMNs. TP53 mutation could also be detected in pure pancreatic juice, potentially making it a useful tool to diagnose malignant IPMNs preoperatively.

Comparative Proteomic Analysis of Whole-Gut Lavage Fluid and Pancreatic Juice Reveals a Less Invasive Method of Sampling Pancreatic Secretions.

OBJECTIVES:There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system (“pancreatic juice”) has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery.METHODS:WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity.RESULTS:We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion.CONCLUSIONS:WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer.

No prophylactic drain placement for pancreatoduodenectomy by measuring intraoperative amylase level of the pure pancreatic juice from the main pancreatic duct

No prophylactic drain placement for pancreatoduodenectomy by measuring intraoperative amylase level of the pure pancreatic juice from the main pancreatic duct

Remarkable Clinical Improvement of Exocrine Pancreas Insufficiency and Gastritis Syndrome Induced by Citrates: Their Secretin-Releasing Capacity Disclosed in Human Pancreatic Fistula Test

Introduction: Following Polak’s personal communication, we decided to elucidate the efficacy of a pharmaceutical mixture of citric acid and citrates in gastritis, dyspeptic syndromes, and exocrine pancreas insufficiency (EPS). Its undisputed success led it to be well known by patients as “magic power.” Objective: To elucidate citrates’ intrinsic physiologic mechanism of action. Methods: Two women (40 and 53 years old, respectively) and 1 man (71 years old) were evaluated with secretin tests (Boots 1,0 U/kg), according to Dreiling’s technique, before and after being subjected to sphincterotomy of Vater’s papilla. Pure pancreatic juice draining from the Wirsung duct by means of an unwilling catheter was collected at 120 minutes. During the first test, following a 30-minute basal period, the 3 patients were given 100 mL of orange lumen juice (OLJ) without sugar. Pure pancreatic juice was collected during its ingestion and for subsequent 30-minute periods. The second test consisted of a regular meal (RM). When recovery from surgery permitted, the 3 patients were given a regular meal consisting of either steak, chicken or fish, green vegetables, mashed potatoes, and a bowl of soup with noodles. As dessert, they received a piece of cheese. As beverage they drank 1 or 2 glasses of mineral water. As they were eating, pure pancreatic juice was collected and this was continued for 120 minutes in 4 30-minute samples. Results: The first OLJ ingestion (100 mL) induced a marked and significant increase of pure pancreatic juice over those of the basal stage (Figure 1). The second RM ingestion showed delayed peak values.Figure 1Conclusion: The present study reveals that a small amount (100 mL) of OLJ exerts an excitatory effect in EPS. The rate of flow as well as bicarbonate and enzyme are of the same order or even greater than those induced by a regular meal. These observations ratify Polak’s finding that the ingestion of a solution of citric acid induces marked and sustained release of secretin. It is surprising and unexpected when the OLJ finding is compared with those of a regular secretin test in which both agents evoke a similar fluid and electrolyte secretin but the enzyme output is greater with the OLJ than with secretin.

Deep Sequencing of Cancer-Related Genes Revealed GNAS Mutations to Be Associated with Intraductal Papillary Mucinous Neoplasms and Its Main Pancreatic Duct Dilation

BackgroundTo clarify the genetic mutations associated with intraductal papillary mucinous neoplasms (IPMN) and IPMN-related pancreatic tumours, we conducted cancer-related gene profiling analyses using pure pancreatic juice and resected pancreatic tissues.MethodsPure pancreatic juice was collected from 152 patients [nine with a normal pancreas, 22 with chronic pancreatitis (CP), 39 with pancreatic ductal adenocarcinoma (PDAC), and 82 with IPMN], and resected tissues from the pancreas were collected from 48 patients (six IPMNs and 42 PDACs). The extracted DNA was amplified by multiplexed polymerase chain reaction (PCR) targeting 46 cancer-related genes containing 739 mutational hotspots. The mutations were analysed using a semiconductor-based DNA sequencer.ResultsAmong the 46 cancer-related genes, KRAS and GNAS mutations were most frequently detected in both PDAC and IPMN cases. In pure pancreatic juice, GNAS mutations were detected in 7.7% of PDAC cases and 41.5% of IPMN cases (p<0.001 vs. others). All PDAC cases with GNAS mutations (n = 3) were accompanied by IPMN. Multivariate analysis revealed that GNAS mutations in IPMN cases were associated with dilated main pancreatic ducts (MPD, p = 0.016), while no statistically independent associations with clinical variables were observed for KRAS mutations. In the resected pancreatic tissues, GNAS mutations were detected in 50% of PDAC cases concomitant with IPMN, 33.3% of PDAC cases derived from IPMN, and 66.7% of IPMN cases, while no GNAS mutations were detected in cases of PDAC without IPMN.ConclusionsThe GNAS mutation was specifically found in the cases with IPMN and it was speculated that some PDACs might be influenced by the concomitant but separately-located IPMN in their pathogenic mechanism. Furthermore, the GNAS mutation was significantly associated with MPD dilatation in IPMN cases, suggesting its role in mucus hypersecretion.

NPTX2 Hypermethylation in Pure Pancreatic Juice Predicts Pancreatic Neoplasms

The neuronal pentraxin II (NPTX2) gene is methylated in over 90% primary pancreatic cancer tissues but rarely in normal pancreatic ductal epithelia. Here, the authors investigated the utility of methylated NPTX2 as a diagnostic marker for pancreatic cancer in pure pancreatic juice samples of patients with benign and malignant pancreatic diseases, including pancreatic cancer, intraductal papillary mucinous neoplasm or chronic pancreatitis using methylation-specific polymerase chain reaction (MSP) and quantitative MSP. MSP assays revealed that the incidence of aberrant NPTX methylation in pure pancreatic juice samples was 64.5% (20 of 31) in patients with pancreatic cancer, 70.0% (7 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 33.3% (2 of 6) in patients with benign intraductal papillary mucinous neoplasm and 21.7% (5 of 23) in patients with chronic pancreatitis. NPTX2 hypermethylation in patients with chronic pancreatitis was significantly lower than that of pancreatic cancer (P<0.01) or patients with intraductal papillary mucinous neoplasm (P<0.05). At a cutoff value of 1.39 for quantitative MSP, the incidence of aberrant NPTX2 methylation was 61.3% (19 of 31) in patients with pancreatic cancer, 50.0% (5 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 0% in patients with benign intraductal papillary mucinous neoplasm and 8.7% (2 of 23) in patients with chronic pancreatitis. There was a significant difference in NPTX2 methylation between pancreatic cancer and chronic pancreatitis (P<0.01). Our findings indicate that detection of aberrant methylation of NPTX2 in pure pancreatic juice samples could be useful as a molecular marker to discriminate between patients with malignant and benign disease of the pancreas.

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice.To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer.Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications.Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc.Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the effectiveness of treatment and prognosis of patients with pancreatic cancer.

MUC1 Is a Useful Molecular Marker for Malignant Intraductal Papillary Mucinous Neoplasms in Pancreatic Juice Obtained From Endoscopic Retrograde Pancreatography

Some intraductal papillary mucinous neoplasms (IPMNs) have no proliferation to malignant IPMNs, and benign IPMNs can observe the natural course without a surgical intervention. Therefore, an accurate assessment is required to determine the appropriate decision on managing malignant IPMNs. Quantitative real-time reverse transcription-polymerase chain reaction was performed for pancreatic juice by a LightCycler instrument focused on carcinoembryonic antigen, MUC1, and human telomerase reverse transcriptase. MUC1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) ratio in intraductal papillary mucinous carcinoma (IPMC; median, 4710.7) was significantly higher in intraductal papillary mucinous adenoma (IPMA; median, 727; P = 0.0229). Furthermore, the MUC1/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in carcinoma in situ and minimum invasive IPMC (median, 26,490) was significantly higher than that in IPMA (P = 0.0152). The cutoff level of MUC1 ratio was determined as 1600 for the division of IPMC from IPMA by the receiver-operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MUC1 mRNA were 88.9%, 71.4%, 80.0%, 83.3%, and 81.3%, respectively. Quantitative reverse transcription-polymerase chain reaction using MUC1 is useful for the detection of malignant IPMN in pure pancreatic juice.

Single-Pattern Convergence of K-ras Mutation Correlates With Surgical Indication of Intraductal Papillary Mucinous Neoplasms

One or more patterns of 6 K-ras mutations are detected in cells from the pancreatic juice of patients with intraductal papillary mucinous neoplasms (IPMNs). We investigated whether these mutations are associated with malignant progression. Between January 2002 and December 2007, 53 patients with IPMN were subjected to collection of pure pancreatic juice to evaluate K-ras mutation. According to the histological and radiological findings, the IPMNs were classified into 4 groups: carcinoma group, adenoma group, high-risk group, and low-risk group. We retrospectively investigated the mutation with these groups. In patients with a positive K-ras mutation, a single pattern of K-ras mutation was observed in 80% (8/10) of the carcinoma group, in 71% (5/7) of the adenoma group, in 40% (2/5) of the high-risk group, and in 38% (8/21) of the low-risk group. The rate of a single pattern of K-ras mutation decreased in a stepwise order (P = 0.017). The incidence of a single pattern of K-ras mutation was significantly higher in the patients who received surgical therapy (75%, 12/16) than in those who did not (38%, 10/26; P = 0.033). The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of IPMNs.

Nonprevention of Post-Endoscopic Retrograde Cholangiopancreatographic Pancreatitis by Pancreatic Stent After Aspiration of Pure Pancreatic Juice in Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas

The objective of this study was to evaluate the efficacy of a pancreatic stent regarding the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis after aspiration of pure pancreatic juice in patients with intraductal papillary mucinous neoplasms. A retrospective study was made to assess the outcome in 121 consecutive patients with intraductal papillary mucinous neoplasms who underwent endoscopic aspiration of pure pancreatic juice for cytologic examination between July 2001 and October 2007. From July 2001 to March 2004, 58 patients did not undergo pancreatic stent insertion (the no-stent [nS] group). The remaining 63 patients did undergo stent insertion (stent [S] group). The overall incidences of post-ERCP pancreatitis was 11 (9.1%). The incidences of post-ERCP pancreatitis in the S and nS groups were 8 (12.7%) and 3 (5.2%; P = 0.21), respectively. In the male patients and the patients with a smaller diameter of the main pancreatic ducts, post-ERCP pancreatitis was seen more frequently in those in the S group (13% and 21%, respectively) than in those in the nS group (0% and 0%, respectively; P = 0.04, 0.03). The pancreatic stent did not seem to decrease the incidence of post-ERCP pancreatitis in patients with intraductal papillary mucinous neoplasms. Furthermore, the pancreatic stent seems to be potentially detrimental in male patients and in patients with small-diameter main pancreatic ducts.

Frequent and Significant K-ras Mutation in the Pancreas, the Bile Duct, and the Gallbladder in Autoimmune Pancreatitis

To assess the relationship between autoimmune pancreatitis (AIP) and pancreatic cancer, we analyzed K-ras mutation in the pancreatobiliary tissues of patients with AIP. An analysis of K-ras mutation and an immunohistochemical study were performed on the pancreas of 8 patients with AIP and 10 patients with chronic alcoholic pancreatitis and on the common bile duct and the gallbladder of 9 patients with AIP. K-ras mutation was analyzed in the pure pancreatic juice from 3 patients with AIP. High-frequency K-ras mutation (2+ or 3+) was detected in the pancreas of all the 8 patients and in the pancreatic juice of the other 2 patients. The mutation in codon 12 of the ras gene was GAT in all the 10 patients. High-frequency K-ras mutation was detected in the common bile duct of 5 patients with AIP and in the gallbladder epithelium of 4 patients with AIP. The K-ras mutation was detected in the fibroinflammatory pancreas, the bile duct, and the gallbladder, with abundant infiltrating IgG4-positive plasma and Foxp3-positive cells of patients with AIP with elevated serum IgG4 levels. Significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP. Autoimmune pancreatitis may be a risk factor of pancreatobiliary cancer.

Combined detection of p16 aberrant methylation and K-ras gene mutation in pancreatic juice for diagnosis of pancreatic cancer

Objective To investigate the diagnostic significance of detecting p16 aberrant meth-ylation and K-ras gene mutation in pancreatic juice for pancreatic cancer. Methods Aberrant p16 methylation was detected using the methylation-specific PCR (MSP) in pure pancreatic juice(PPJ) col-lected from the pancreatic duct through a nasopancreatic tube put under endoscopic retrograde cholan-giopancreatography (ERCP). K-ras gene 12 codon mutation was detected using the m PCR-RFLP in the pure PPJ. Results The DNA was obtained from PPJ through a nasopancreatic tube. Aberrant p16 methylation and K-ras gene mutation were detected in the same samples of PPJ. Sensitivity, specifici-ty,positive predictive values, negative predictive values and accuracy of HE staining for pancreatic cancer were 40%, 100%, 100%,45.4% and 60.0%, respectively. Of the 20 cases of pancreatic canc-er,K-ras gene mutation was detected in 14 (70%) and the p16 gene was shown to be methylated in 7(35%). Of the 8 cases of chronic pancreatitis,K-ras gene mutation was detected in 2 (25%). Of the 2cases of mucinous cystoadenoma of pancreas,K-ras gene mutation was detected in 1 (50%). Aberrant methylation of p16 was not detected in pancreatic juice samples from patients with chronic pancreatitis and mucinous cystoadenoma of pancreas. Sensitivity, specificity, positive predictive values, negative predictive values and accuracy of detection K-ras gene mutation for pancreatic cancer were 70%, 70%,82.4%,53.8% and 70.0%, respectively. The sensitivity, specificity, positive predictive values, nega-tive predictive values and accuracy of detection of K-ras gene mutation and p16 methylation for pancre-atic cancer were 70%, 100%, 100%,62.5% and 80%, respectively. Conclusion Pancreatic juice can be used for molecular analysis of pancreatic juice obtained using nasopanereatic drainage during ERCP.Detecting aberrant methylation of p16 and K-ras gene mutation from pancreatic juice may be a new tool to diagnose pancreatic cancer. Key words: Pancreatic cancer; ERCP; Pancreatic neoplasms; Methylation; K-ras gene

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs. Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct's largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations. Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2-8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2-5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323). The incidence of K-ras mutation may be associated with the hypersecretion of mucin.

Clinicopathological study on the intraductal spread of small pancreatic cancer

The aim of this study was to evaluate histopathologically the frequency, direction, and length of intraductal spread (IS) along the main pancreatic duct from the main tumor of small pancreatic cancer. Resected specimens from 20 cases of pTS1 (histologically 2 cm or less in diameter) pancreatic cancer (September 1983 to December 2005) were examined histopathologically. As controls, 40 resected specimens from cases of pTS2 (more than 2 cm and less than 4 cm in diameter) or larger sized pancreatic cancer (pTS2<or=) were examined in the same manner. The specimens were evaluated histopathologically as to (1) the prevalence of IS, (2) the direction and length of IS, and (3) the positive rates of transpapillary cytology of pure pancreatic juice (TPC) and biopsy of the main pancreatic duct (TPB), performed preoperatively. IS was observed in 45% of pTS1 and 13% of pTS2<or= cases. In 88% of cases of pTS1, IS was observed in the direction of the ampullary side. In 40% of cases of pTS2<or=, IS toward the ampullary side was seen. The mean length of IS in pTS1 and pTS2<or= cases was 11.8 mm and 7.2 mm, respectively. Positive rates of TPC and TPB in pTS1 cases were 70% and 75%, respectively, and in pTS2<or= cases, 50% and 44%, respectively. The frequency of IS was high in pTS1 cases, which suggests there is potential for improvement in establishing the histocytological diagnosis of small pancreatic cancer via the transpapillary approach with the development of adequate tools.

Intraductal Secretin Stimulation Test: What Is the Proper Collection Time?

Pancreatic function tests are helpful methods to establish or exclude a diagnosis of chronic pancreatitis (CP). Many studies confirm the clinical utility of the intraductal secretin test (IDST), and that the most discriminatory parameters used are secretory flow rate (SFR) and bicarbonate concentration (BC)∗. Forty-five minutes (min) IDST collection time was recommended by some investigators. A shorter collection time has been proposed to increase the practicality of the IDST, but the precise time has been not well defined. The aim of our study is to establish the IDST proper collection time. Method: The results of 68 IDSTs done in our center were evaluated. Pure pancreatic juice (PPJ) was collected after an IV injection of 16 μg of synthetic secretin (SecreFlo, ChiRhoClin, Inc, Burtonsville). The first 5-min collection was discarded and the PPJ was then collected at 5 minutes intervals up to 45 min. A triple lumen manometry catheter was used to collect the PPJ. The parameters evaluated were the peak SFR, time of peak SFR, max BC (measured by back titration), and time of max BC. Normal SFR was defined as ≥3 ml/min and normal BC was defined as ≥105 mEq/L∗. Results: Max BC was reached by the collection time of 6-10 min in 11 patients (pts) (16%), by 11-15 min in 43 pts (63%), by 16-20 min in 60 pts (88%), by 21-25 min in 65 pts (95%) and by 26-30 min in all pts (100%). Peak SFR was reached by the collection time 6-10 min in 24 pts (36%), by 11-15 min in 37 pts (55%), by 16-20 min in 52 pts (77%), by 21-25 min in 57 pts (84%) and by 26-30 min in all pts (100%). However, all pts reached their final diagnostic classification (normal versus CP) for both the SFR and BC by 20 min collection period [i.e. either the SFR was low (<3 ml/min) from the beginning and remained low throughout the collection time, or normal (≥3 ml/min) within the first 20 min collection time; the same was seen for BC]. Further collection time did not change their final diagnosis. Based on BC criteria, 15 pts had CP (22%). Based on SFR criteria, 31 pts had CP (45%), by either criteria 45% had CP. Summary: The final clinical diagnosis of CP was established or excluded by the first 20 min collection period (for both SFR and BC) in all pts. Conclusions: The first 20-minute collection period during IDST was sufficient time for diagnosing or excluding CP in all pts in this series. This data confirms prior studies showing adequacy of 15-20 min IDST collection time.∗∗Sivak M. Gastroenterologic Endoscopy. 2nd W.B. Saunders Company, 2000:1116-1118.

Ileal exposure to pig pancreatic juice and bile inhibit exocrine pancreatic secretion in pigs

The mechanisms involved in the down regulation of the exocrine pancreas are still not fully elucidated. The purpose of the present study was to examine the effect of duodenal and ileal exposure to pancreatic enzymes and bile on pancreatic secretion. Experiments were performed with pigs fitted with pancreatic duct, ileal and jugular vein catheters, and duodenal T-shaped cannula. A negative feedback regulation of pancreatic secretion was found for both duodenal and ileal delivery of pancreatic juice. Pancreatic secretion was unaffected by duodenal delivery of bile and bile salts, while ileal delivery of bile and bile salts lowered it. On the other hand, pancreatic secretion was increased by duodenal loading of commercial non- or activated pancreatic enzyme preparations, thus probably recognised as dietary protein. Plasma cholecystokinin (CCK) level was lowered only by duodenal delivery of pancreatic juice. In conclusion, the results prove the existence of negative feedback mechanism regulating pancreatic secretion dependent on the presence of pure pancreatic juice or bile at the ileal level. The mechanism at the duodenal level is exclusively sensitive to pure pancreatic juice. (c) 2007 Elsevier B.V All rights reserved. (Less)