Minimal Change Patients Versus Obvious Chronic Pancreatitis: A Comparison of Classical Secretin Stimulation Testing Results.

OBJECTIVES: The objective was to assess if the peak bicarbonate level during secretin stimulation testing (SST) differs between patients with minimal change (or small duct) chronic pancreatitis (CP) versus those with obvious CP (or large duct) versus those without CP. METHODS: Two hundred nineteen patient records at the University of Florida who had been referred for SST were analyzed for peak bicarbonate, total volume of juice collected, age, sex, and clinical presentation. RESULTS: Fifty-one patients with minimal change CP were identified. Thirty-three patients were felt to have advanced CP, and 135 patients did not have CP by clinical criteria. The peak bicarbonate and total volume of pancreatic juice collected was significantly different (P < 0.001) between all 3 groups by multiple comparison testing. The peak bicarbonate of advanced CP and minimal change groups was less than controls (P < 0.001). There was a significant difference (P < 0.05) on direct testing between peak bicarbonate in advanced CP and minimal change CP. CONCLUSIONS: The peak bicarbonate and volume measured during SST differs among patients with minimal change CP, advanced CP and in disease controls. These results could be useful in diagnosing minimal change/early CP.

Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function.

The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography. Kidney function was measured with [18F]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared with placebo (secretin vs. placebo, means ± SD, 15.5 ± 7.4 vs. 9.7 ± 4.9 µmol/100 g/min, 95% confidence interval (CI) [2.2, 9.4], P = 0.004). Secretin also increased [18F]FDG renal clearance (44.5 ± 5.4 vs. 39.5 ± 8.5 mL/min, 95%CI [1.9, 8.1], P = 0.004), and eGFR was significantly increased from baseline after secretin, compared with placebo (17.8 ± 9.8 vs. 6.0 ± 5.2 ΔmL/min/1.73 m2, 95%CI [6.0, 17.6], P = 0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure.NEW & NOTEWORTHY Secretin increases myocardial glucose uptake compared with placebo, supporting a previously proposed inotropic effect. Secretin also increased renal filtration rate.

Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.

INTRODUCTION: Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma-induced hypergastrinemia causing excessive gastric acid secretion. Secretin stimulation tests (SSTs) are required for diagnosis in the majority of patients. Two case reports suggest that proton pump inhibitors (PPIs) cause false SST results. Consequently, PPIs are discontinued to allow hyperchlorhydria to recur; however, uncontrolled acidity can cause life-threatening complications in those with underlying undiagnosed ZES. The aim of this study was to determine whether PPIs influence the validity of SSTs for the diagnosis of ZES. METHODS: A retrospective chart review was performed. Charts of patients who underwent SSTs were reviewed to determine whether they were performed on or off PPI and the test's accuracy by comparing the results with gold standard tests (diagnostic laboratory testing performed off PPI or surgical pathology consistent with gastrinoma). Sensitivity, specificity, and positive predictive value (PPV) of SST on PPI were calculated and results compared with SST off PPI using noninferiority analyses. RESULTS: Twenty-eight patients corresponding to 29 SSTs were performed on PPI, and 70 patients corresponding to 107 SSTs were performed off PPI. Most of them were female and white and had multiple endocrine neoplasia type 1. We found no false-positive or false-negative SSTs on PPI. Sensitivity, specificity, and PPV of SSTs on PPI were determined to be noninferior to SSTs off PPI (P ≤ 0.05 for all). DISCUSSION: In our cohort, SSTs on PPI compared with SSTs off PPI were noninferior for sensitivity, specificity, and PPV. These results suggest that PPI withdrawal before SSTs may not be necessary.

Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial.

BACKGROUND: Objectives: We performed a randomized, double-blind, placebo-controlled trial to determine if using Secretin intra-operatively to identify leaks and subsequently target operative intervention would decrease the frequency of clinically significant post-operative pancreatic fistula formation. METHODS: Patients undergoing pancreaticoduodenectomy or distal pancreatectomy were randomized to receive intra-operative Secretin or placebo intra-operatively following the completed pancreaticojejunostomy or closure of the cut remnant stump. If a potential leak was identified, targeted therapy with directed suture placement was performed. RESULTS: 170 patients were randomized; 83 receiving placebo and 87 receiving Secretin. The rate of clinically significant fistula formation was 3% (3/87) in the Secretin group and 6% (5/83) in the placebo group (p = 0.489). The rate of biochemical leak was 29% (25/87) in the Secretin group and 19% (16/83) in the placebo group (p = 0.157). There were no Grade C post-operative fistula in either group. Of the 9% of patients in the Secretin group who had a targeted intra-operative intervention, none developed a clinically significant fistula. Adverse events were similar between groups. CONCLUSIONS: Compared to placebo, intra-operative Secretin administration was not associated with an overall reduction in clinically significant pancreatic fistula formation. However, patients with an intra-operative leak identified by Secretin may benefit from intervention (clinicaltrials.gov: NCT02160808).

Delayed Processing of Secretin-Induced Pancreas Fluid Influences the Quality and Integrity of Proteins and Nucleic Acids.

OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influence the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection; after 1, 2, and 4 hours on ice; or after storage overnight at 4°C with or without RNase or protease inhibitors (PIs). Electrophoresis and mass spectrometry analysis determined protein abundance and quality, whereas nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding PIs delayed degradation. RNA was significantly degraded under all conditions compared with the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding PIs immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.

Various Modalities Accurate in Diagnosing a Disrupted or Disconnected Pancreatic Duct in Acute Pancreatitis: A Systematic Review.

BACKGROUND: Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines. We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. METHODS: A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis. All data regarding diagnostic accuracy were extracted. RESULTS: We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis. Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies. A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography. The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83%. A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography. A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP. CONCLUSIONS: This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Amylase measurement in drain fluid should be standardized. Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality. Further prospective studies, however, are needed.

Secretin-Enhanced MRCP: How and Why-AJR Expert Panel Narrative Review.

Secretin-enhanced MRCP (S-MRCP) has advantages over standard MRCP for imaging of the pancreaticobiliary tree. Through the use of secretin to induce fluid production from the pancreas and leveraging of fluid-sensitive MRCP sequences, S-MRCP facilitates visualization of ductal anatomy, and the findings provide insight into pancreatic function, allowing radiologists to provide additional insight into a range of pancreatic conditions. This narrative review provides detailed information on the practical implementation of S-MRCP, including patient preparation, logistics of secretin administration, and dynamic secretin-enhanced MRCP acquisition. Also discussed are radiologists' interpretation and reporting of S-MRCP examinations, including assessments of dynamic compliance of the main pancreatic duct and of duodenal fluid volume. Established indications for S-MRCP include pancreas divisum, anomalous pancreaticobiliary junction, Santorinicele, Wirsungocele, chronic pancreatitis, main pancreatic duct stenosis, and assessment of complex postoperative anatomy. Equivocal or controversial indications are also described along with an approach to such indications. These indications include acute and recurrent acute pancreatitis, pancreatic exocrine function, sphincter of Oddi dysfunction, and pancreatic neoplasms.

Endoscopic ultrasound-based multimodal evaluation of the pancreas in patients with suspected early chronic pancreatitis.

BACKGROUND: Diagnosis of early chronic pancreatitis is a clinical challenge and hindered by the lack of a gold standard. Endoscopic ultrasound (EUS) and the endoscopic pancreatic function test (ePFT) are the most sensitive morphological and functional methods in this setting. EUS-elastography allows for the quantification (strain ratio) of pancreatic fibrosis, and the dynamic evaluation of the main pancreatic duct compliance provides additional information. We developed a multimodal EUS-based approach for the evaluation of the pancreas by integrating these four methods in a single procedure. OBJECTIVE: We aim to describe morphological and functional pancreatic abnormalities in patients with clinical suspicion of chronic pancreatitis and inconclusive EUS findings by using the multimodal EUS-based approach. METHODS: This was a prospective, cross-sectional, observational study of patients with clinically suspected chronic pancreatitis and indeterminate EUS criteria of the disease. EUS criteria of chronic pancreatitis, quantitative pancreatic elastography, ePFT and compliance of the main pancreatic duct were evaluated in a single procedure. RESULTS: In total, 53 patients with 3-4 EUS criteria of chronic pancreatitis were included (mean age 39.7 years, 29 male). Strain ratio was abnormally high in all patients. Peak bicarbonate concentration was decreased in 43 patients (81.1%) and the main pancreatic duct compliance was reduced in 41 patients (77.3%). Some 34 patients (64.1%) had abnormal results at EUS, elastography, ePFT and compliance of the main pancreatic duct. CONCLUSIONS: A multimodal EUS-based test for the morphological and functional evaluation of the pancreas is presented, which allows detecting mild pancreatic abnormalities in patients with suspected early chronic pancreatitis. The presence of abnormal morphological and functional evaluation of the pancreas could support the clinical suspicion of early chronic pancreatitis in the appropriate clinical setting.

Evaluation and Management of Suspected Early Chronic Pancreatitis (ECP).

PURPOSE OF REVIEW: Chronic pancreatitis in the advanced stages leads to significant health care utilization because of the associated complications. Early-stage diagnosis could prevent the development of these complications by appropriate management. In this article, we reviewed the recent evidence pertaining to the diagnosis and management of early chronic pancreatitis (ECP). RECENT FINDINGS: The working group for the International Consensus Guidelines for Chronic Pancreatitis has published consensus-based statements to streamline the diagnosis of ECP. There is no international consensus on the definition and diagnosis of ECP. The Revised Japanese Diagnostic Criteria for ECP based on clinical features and endoscopic ultrasound findings have been proposed. Large prospective cohort studies are needed to develop and validate internationally acceptable diagnostic criteria. ECP is recognized as a distinct stage in the development and progression of CP. Consensus-based definitions and diagnostic criteria need to be developed.

Secretin-Stimulated Magnetic Resonance Imaging Reveals Variable Diagnostic Accuracy According to Etiology in Pancreatic Disease.

OBJECTIVES: Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic exocrine secretion. In this prospective observational study, we compare the diagnostic accuracy of s-MRI for exocrine pancreatic failure due to different pancreatic diseases and healthy controls. METHODS: We performed s-MRI in 21 cystic fibrosis (CF) patients, 78 patients with chronic pancreatitis (CP) and 20 healthy controls. Exocrine failure was defined by fecal elastase-1 of less than 200 µg/g or bicarbonate concentration from endoscopic secretin test of less than 80 mmol/L. RESULTS: Eleven CF and 61 CP patients were exocrine insufficient. Insufficient CF patients had lower s-MRI volume output compared with all other groups (P < 0.05). Insufficient CP patients had reduced volume output compared with controls and sufficient CF (P < 0.05). Secretin-stimulated MRI yielded overall accuracy of 0.78 (95% confidence interval [CI], 0.70-0.86) for exocrine failure. When divided according to etiology, the test yielded accuracy of 0.95 (95% CI, 0.90-1) in CF and 0.73 (95% CI, 0.64-0.82) in CP. CONCLUSIONS: The accuracy of s-MRI volume output measures to diagnose exocrine failure was higher in CF than in CP. Differences in s-MRI volume output in patients with exocrine failure may be due to different etiological and pathogenic mechanisms in CF and CP.

Secretin Improves Visualization of Nondilated Pancreatic Ducts in Children Undergoing MRCP.

OBJECTIVE. The objective of our study was to assess whether secretin improves visualization of a nondilated pancreatic duct and whether it increases identification of variant duct anatomy on MRCP in pediatric patients. MATERIALS AND METHODS. This study is a delayed retrospective review of MRCP images that were prospectively obtained of 50 volunteers without a history of pancreatic disease who ranged in age from 6 to 15 years old. MRCP images (coronal 3D fast recovery fast spin-echo [FSE] and coronal single-shot FSE fat-saturated sequences) obtained before and after secretin administration were separated for review by three radiologists (reviewers 1-3). The reviewers were blinded to the purpose of the study and to secretin administration. Reviewers ranked subjective image quality (Likert scale, 1-5 points) and reported pancreaticobiliary duct anatomy and duct visibility (yes or no). Paired t tests were used for comparison of means, and the chi-square test or Fisher exact test was used for comparison of frequencies. Sensitivity and specificity of MRCP images obtained before secretin administration were judged against MRCP images obtained after secretin administration as the reference standard. RESULTS. The frequency of image quality scores of 4 or greater assigned to 3D MRCP images was statistically significantly greater after secretin administration for reviewer 2 (p < 0.0001) and reviewer 3 (p = 0.005) and approached statistical significance for reviewer 1 (p = 0.052). Mean number of visible pancreatic duct segments (head and uncinate, body, tail) was significantly greater on the MRCP images obtained after secretin administration than on those obtained before secretin administration for all reviewers (reviewer 1, 1.9 vs 1.3; reviewer 2, 1.9 vs 1.2; reviewer 3, 1.4 vs 0.8; all, p < 0.01). For all three reviewers, the sensitivity of MRCP images obtained before secretin administration was poor for variant pancreatic ductal anatomy (reviewer 1, 37.5%; reviewer 2, 50.0%; reviewer 3, 40.0%). CONCLUSION. Secretin administration improved subjective MRCP image quality, improved subjective visualization of the pancreatic duct, and provided greater sensitivity for anatomic variants such as pancreas divisum in a cohort of children with nondilated pancreatic ducts.

Prospective Assessment of Normal Pancreatic Secretory Function Measured by MRI in a Cohort of Healthy Children.

OBJECTIVES: Magnetic resonance imaging (MRI) with secretin stimulation promises to allow non-invasive testing for exocrine pancreatic insufficiency but normal data do not exist for children. The purpose of this study was to define, in healthy children, normal pancreatic secreted fluid volume and secretion rate, measured by MRI, in response to secretin. METHODS: In this Institutional Review Board-approved, prospective, cross-sectional study, 50 healthy children ages 6 to <16 years underwent MRI with secretin stimulation. Images were obtained before and at 1, 5, 10 and 15 min after secretin administration to calculate total secreted fluid volume and secretion rate based on image segmentation. Regression was used to define the relationship between secretory function and participant size measures, and linear quantile regression was used to define normal secretory values based on size measures. RESULTS: Median total secreted fluid volume post secretin was 79 mL (range: 32-162 mL; 5th and 95th percentiles: 43 and 123 mL) and median secretion rate was 5.1 mL/min (range: 2-9.4 mL/min; 5th and 95th percentiles: 2.3 and 7.7 mL/min). Secreted volume and secretion rate had the strongest correlation with body surface area (BSA) (r = 0.54 and 0.59, respectively) and multiple regression defined BSA as the only significant predictor of secretory function. Each 1 m2 increase in BSA was associated with a 38 mL increase in secreted fluid volume. CONCLUSIONS: In children, pancreatic secretory response to secretin, measured by MRI, depends on participant size, particularly BSA. Secreted volume <43 mL or a secretion rate <2.3 mL/min (5th percentile values) can be considered abnormal for children.

The clinical value of secretin-enhanced MRCP in the functional and morphological assessment of pancreatic diseases.

Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) provides a non-invasive way, with which, to evaluate pancreatic duct (PD) anatomy and exocrine pancreatic function. S-MRCP can be added to the routine pancreas MR examination in equivocal cases. Moreover, it can detect subtle PD involvement, allowing diagnosis of early, rather than end-stage, pancreatic diseases. Although S-MRCP is a valuable non-invasive diagnostic method, it is only performed in a few centres due to relative high cost. Furthermore, less familiarity with its indications, the examination technique, and image interpretation also contribute to its limited use. Thus, the purpose of this article is to explain secretin's mechanism of action, the examination technique, the clinically relevant indications, the advantages, and limitations. Finally, we will focus on image analysis and its role in achieving an early and accurate diagnosis of specific pancreatic and PD diseases.

The Impact of Risk Factors of Chronic Pancreatitis on Secretin Pancreatic Function Testing: Results of a 20-Year Study.

OBJECTIVES: The aim of this study was to determine the effect of established risk factors on the outcome of secretin pancreatic function testing (sPFT) in patients undergoing work-up for suspected chronic pancreatitis. METHODS: We completed a retrospective review of patients who underwent sPFT for suspected chronic pancreatitis over 20 years. We compared peak bicarbonate concentrations between groups and completed univariate and multivariate analyses to determine associations between risk factors and positive sPFT results (peak bicarbonate <80 mEq/L). RESULTS: Forty-three of 162 patients had positive sPFT results. There were significant differences in peak bicarbonate concentrations in patients with and without recurrent acute pancreatitis (RAP) and with local complications from acute pancreatitis (AP) (P ≤ 0.05). The bicarbonate concentration in patients with and without other risk factors such as tobacco use, alcohol use, and family history of pancreatitis was not significantly different. Female sex, a history of AP, and a history of RAP were associated with positive sPFT results on univariate analysis (P ≤ 0.05). On multivariate analysis, sex and RAP remained significant. CONCLUSIONS: Our study demonstrates that female sex, history of AP and RAP, and AP with local complications are associated with positive sPFT results or lower peak bicarbonate concentration. However, other risk factors do not impact the results of sPFT.

A study of the clinical utility of a 20-minute secretin-stimulated endoscopic pancreas function test and performance according to clinical variables.

BACKGROUND AND AIMS: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFTs), where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal, are now used more frequently. In this ePFT, aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration. The performance of ePFT in a cohort of patients with a presumptive diagnosis of CP referred to a pancreas clinic for consideration of an intervention including total pancreatectomy and islet autotransplantation was studied, compared with EUS, ERCP, histology, and consensus diagnosis. The effect of sedation, narcotic use, aspirate volume, body mass index, age, and proton pump inhibitors (PPIs) on test performance is reported. METHODS: After a test dose, synthetic human secretin was administered intravenously, and 30 minutes later sedation was achieved with midazolam and fentanyl or propofol. A gastroscope was advanced to the major papilla where 4 continuous aspiration samples were performed at 5-minute intervals in sealed bottles. PBC ≥80 mEq/L was normal. RESULTS: Eighty-one patients had ePFTs from August 2010 through October 2015. Twenty-seven patients (33%) were diagnosed with CP. Eighteen of the 27 patients with CP and 1 of the 54 patients without CP had an abnormal ePFT, producing a sensitivity of 66% (95% CI, 46.0-83.5), specificity 98% (95% CI, 90.1-99.9), positive predictive value 94.7% (95% CI, 74-99.9), and negative predictive value 85.5% (95% CI, 74.2-93.1). ERCP and PBC concordance was generally poor, but none of the patients without CP had major EUS changes, and only 3 patients with a PBC <80 mEq/L had a normal EUS. The PBC was affected by narcotics and PPI use. CONCLUSION: A 20-minute ePFT after secretin administration had a marginal sensitivity for diagnosis of CP. The diagnosis of CP should not rely on a single study and certainly not a PFT. The duodenal aspirate volume did not correlate with the PBC, which contrasts with current secretin-enhanced MRCP knowledge; therefore, further studies on this subject are warranted. Neither type of sedation, BMI, nor age affected test performance. Narcotics and PPIs may affect the PBC, so borderline results should be interpreted with caution in these groups.

Using an endoscopic distal cap to collect pancreatic fluid from the ampulla (with video).

BACKGROUND AND AIMS: Duodenal collections of pancreatic fluid can be used as a source of mutations and other markers of pancreatic ductal neoplasia, but admixing pancreatic juice with duodenal contents lowers the concentrations of mutations. Collecting pancreatic fluid directly from the ampulla could yield a purer sample of pancreatic fluid. METHODS: We used an endoscopic distal cap attachment to "cap" the ampulla and collect secretin-stimulated pancreatic fluid samples for 5 minutes from 81 patients undergoing pancreatic evaluation as part of the Cancer of the Pancreas Screening studies. We compared mutation concentrations (K-ras and GNAS) measured by droplet-digital PCR (ddPCR) in "cap-collected juice" samples to those found in juice samples obtained from 77 patients collected by aspiration from the duodenal lumen without capping the ampulla. RESULTS: Among all subjects, mutation concentrations were higher in pancreatic juice samples collected using the endoscopic cap method (median, .028%; IQR, 0-.077) compared with the noncap-collected (median, .019%; IQR, 0-.044; P = .055). Among pancreatic juice samples with detectable mutations, mutation concentrations were higher in the cap-collected juice samples than in those collected without the cap (.055%; IQR, .026-.092 vs .032%; IQR, .020-.066; P = .031). CONCLUSIONS: Collecting pancreatic juice directly from the ampulla using an endoscopic distal cap yields higher concentrations of pancreatic fluid mutations.

Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

BACKGROUND: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.

Pancreatic morpho-functional imaging as a diagnostic approach for chronic asymptomatic pancreatic hyperenzymemia.

BACKGROUND: Magnetic resonance cholangio-pancreatography (MRCP) findings in people with chronic asymptomatic pancreatic hyperenzymemia (CAPH) have shifted the hypothesis that CAPH is always non-pathological. However, there have been no studies including both secretin-MRCP (S-MRCP) and endoscopic ultrasonography (EUS) to examine the pancreatic morphology in these subjects. AIM: To prospectively assess the diagnostic approach for CAPH using both pancreatic EUS and S-MRCP. METHODS: In a case-control prospective study from January 2010 to December 2014, 68 consecutive subjects with CAPH were scheduled to undergo S-MRCP and EUS (CAPH group) in a tertiary care setting. In the same period, the EUS findings of this group were compared with 68 patients examined by EUS alone for submucosal lesions of the gastric fundus, matched for sex and age (control group). RESULTS: EUS detected pancreatic alterations in 60.3% of the CAPH group and 13.2% of controls (p<0.001). S-MRCP showed pancreatic alterations in 51.5% in the CAPH group. With the combined procedures, pancreatic abnormalities were detected in 63.3%. The diagnoses established by the two techniques were concordant in 51 (75%) of the 68 CAPH subjects; in the remaining 17 (25%) the two methods gave additional information. CONCLUSIONS: In people with CAPH S-MRCP and EUS are both recommended in order to detect pancreatic abnormalities before this biochemical alteration is confirmed as benign CAPH, or Gullo's syndrome.

Secretin-enhanced MR Imaging of the Pancreas.

Secretin is a hormone that stimulates the exocrine pancreatic secretion of bicarbonate-rich fluid from the acinar cells of the pancreas that accumulates within the pancreatic ductal lumen. The exogenous administration of secretin improves the visualization of pancreatic ducts at magnetic resonance (MR) cholangiopancreatography (MRCP), because of an enlargement of the pancreatic duct system and an increase of the fluid content within the lumen of the pancreatic ducts, responsible of an increase of MR signal. In this review, the technique of secretin-enhanced MRCP, which has the aim to depict the whole pancreatic duct system, the biliary tree, the major and minor papillae, and the duodenum, will be described. Because of the anatomic contiguity between the pancreas and the gastrointestinal tract, the presence of fluid within the stomach may overlap with the pancreatic duct system and therefore the pancreatic duct may be difficult to visualize, representing a potential source of diagnostic pitfalls. The technique to reduce the signal intensity of the static fluid present within the stomach and in the duodenal lumen is also described. The technique of secretin administration will be illustrated, with emphasis on the synchronization of secretin administration and MR image acquisition. Furthermore, the frequency and number of MRCP images necessary to achieve a temporal resolution adequate to visualize the physiologic changes in the pancreatic gland, induced by the administration of secretin, is described. The assessment of pancreatic, morphologic, and functional response to the administration of secretin, as depicted on MRCP images, will be illustrated. Finally, the indications for secretin-enhanced MRCP will be discussed to define which patients will benefit from secretin-enhanced MR imaging for their treatment planning. (©) RSNA, 2016.

Secretin-enhanced Magnetic Resonance Cholangio-pancreatography in Pancreatic Insufficient and Pancreatic Sufficient Cystic Fibrosis Patients.

BACKGROUND AND AIMS: Although indirect methods of assessment of the exocrine pancreatic function have become the standard of care in the monitoring of pancreatic status, it still remains a current clinical challenge. Our aim was to compare the width of the pancreatic duct in pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) patients using secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP). METHODS: Thirty-seven CF patients were enrolled for this cross-sectional study, including 21 PI and 16 PS, all of whom underwent SE-MRCP. Measurement of the diameter of the pancreatic duct was performed in the head, body, and the tail of the pancreas at the baseline and after 1, 2, 3, 5, and 10 minutes after secretin administration. RESULTS: The diameter of the pancreatic duct in the head of the pancreas after 5 and 10 minutes of secretin injection was greater in PI than in PS patients (median = 2.0 mm [interquartile range: 1.6-3.0] vs. 2.0 mm [1.0-2.0] and 2.0 mm [1.4-2.0] vs 1.0 mm [1.0-2.0], p=0.047 and p=0.040, respectively). Areas under ROC curves for discriminating between PI and PS patients were 0.693 (95% CI 0.521-0.866) and 0.698 (95% CI 0.528-0.868), respectively. No other differences in the width of the duct were identified at the baseline or during SE-MRCP. CONCLUSIONS: The measurement of the diameter of the pancreatic duct during secretin stimulation does not allow for differentiating between PS and PI status in CF patients.