Synthetic Porcine Secretin Research Articles

788a: Intraduodenal Hydrochloride Acid Infusion for Facilitation of Cannulation of the Dorsal Pancreatic Duct At ERCP in Patients With Pancreas Divisum—A Preliminary Study

Minor papilla (dorsal pancreatic duct) cannulation at endoscopic retrograde cholangiopancreatography (ERCP) is an important step in diagnosis of pancreas divisum and in prevention of pancreatitis attacks for patients with recurrent acute pancreatitis secondary to pancreas divisum by performing sphincterotomy or stent placement in the dorsal duct. To achieve a successful cannulation of the minor papilla may be very difficult. Intravenous injection of biological porcine secretin or synthetic porcine secretin has significantly increased the minor papilla cannulation rate.

The role of endoscopy in the management of patients with diarrhea

The role of endoscopy in the management of patients with diarrhea

Endogenous secretin in the rat--evidence for a role as an enterogastrone but failure to influence serum calcium homeostasis.

The release of secretin into plasma by intraduodenal (id) infusion of HCl or iso-osmotic (290 mosm l-1) NaCl, and the associated changes of moderately stimulated gastric acid, serum gastrin, two calciotropic hormones, total and 45calcium (Ca), were examined in the rat. The possible role of endogenous secretin as an enterogastrone and as a mediator of the hypothesized endocrine gut-thyroid-parathyroid axis was further characterized with the aid of secretin immunoneutralization and exogenous secretion. The id-HCl-stimulated secretin, measured by a sensitive radioimmunoassay, was accompanied by a decrease in gastric acid secretion, whereas secretin blockage by anti-secretin immune serum resulted in a significant increase in acid secretion. The correlation between plasma secretin and acid output was only slight. Gastrin and Ca metabolism remained unchanged during secretin stimulation. Intravenous synthetic porcine secretin at a dose reported to be effective in other target preparations (2 CU (0.58 microgram) kg-1 h-1) had no effect on gastric acid secretion and Ca metabolism. In contrast, a pharmacological dose, 32 CU (9.3 micrograms) kg-1 h-1, inhibited acid secretion, decreased serum Ca and total protein, and increased serum parathyroid hormone, but left calcitonin and gastrin unchanged. Endogenous secretin appeared to act as an enterogastrone, but whether it was the only one is unclear. No role was detected for secretin in the gut-thyroid-parathyroid axis, since the Ca changes observed may have been unspecifically mediated.

Comparison of Endoscopic Ultrasound Chronic Pancreatitis Criteria to the Endoscopic Secretin-Stimulated Pancreatic Function Test

Endosonography (EUS) has emerged as a major diagnostic tool in pancreatic imaging. Direct tests of pancreatic function are considered the most sensitive and accurate method to establish a diagnosis of chronic pancreatitis (CP), particularly when imaging studies are inconclusive. The aim of this study was to compare current EUS CP criteria with our newly described, purely endoscopic, secretin-stimulated pancreatic function test (ePFT). Fifty-six patients (25 male, mean age = 44 years) who were referred for evaluation/treatment of chronic abdominal pain with or without CP underwent both EUS and ePFT. The EUS protocol included the following: (1) EUS images were obtained in a standardized fashion from both gastric and duodenal stations, and (2) EUS images were scored independently by one of three therapeutic endoscopists for 0--9 parenchymal/ductal criteria as follows: 0-3 = normal, 4-5 = equivocal, >/=6 = definite CP. Endoscopic pancreatic function test (ePFT) protocol included the following: (1) upper endoscopy, (2) intravenous synthetic porcine secretin (0.2 mcg/kg, ChiRhoClin, Inc.) after test dose, (3) duodenal fluid aspirated every 15 min for 1 h, and (4) autoanalyzed for [HCO3] cutpoint of 80 mEq/L. According to EUS, 33 were normal, 13 equivocal, and 10 definite for CP. The mean peak [HCO3 -] range (in mEq/L) for each group was normal CP (83.7, range = 58-118), equivocal CP (68, range = 30-88), and definite CP (56, range=19-84). Using a peak [HCO3 -] of </=80 mEq/L as diagnostic for CP, the referent values (sensitivity%/specificity%) for EUS in the diagnosis of CP were normal (60/72), equivocal (36/94), and definite (26/100), respectively. An EUS score or greater than 5 had the best specificity (100%) and negative predictive value (100%). We conclude that endoscopic pancreatic function testing with secretin confirms that as EUS score increases, the peak pancreatic fluid bicarbonate decreases. We also conclude that EUS has excellent statistical inferences for diagnosing CP when at least 6 or more criteria are present. EUS as a screening test in patients with chronic abdominal pain and equivocal imaging studies may be of limited value.

Comparison of the Secretin Stimulated Endoscopic Pancreatic Function Test to Retrograde Pancreatogram

Duodenal intubation techniques with hormonal stimulation are the most accurate at diagnosing early chronic pancreatitis. Pancreatography (ERCP), the radiologic gold standard, can accurately diagnose chronic pancreatitis, but is expensive, may expose the patient to radiation, and/or induce acute pancreatitis. We have developed an endoscopic pancreatic function test (ePFT) that can assess pancreatic secretory function during upper endoscopy. We sought to determine the accuracy of the endoscopic secretin pancreatic function test using retrograde pancreatogram as the gold standard. Patients referred to The Pancreas Clinic for the evaluation and management of chronic abdominal pain and suspected chronic pancreatitis who had both endoscopic function testing and pancreatic duct imaging (ERCP) were studied. Pancreatograms were scored for duct morphologic characteristics (Cambridge classification) and compared to peak bicarbonate concentration in secretin stimulated duodenal juice. The ePFT consisted of a test dose of intravenous synthetic porcine secretin (0.2 microg), full-dose intravenous secretin (0.2 microg/kg) over 1 min, (3) upper endoscopy with moderate sedation, (4) gastric fluid aspirated and discarded, (5) duodenal fluid aspirations at 0, 15, 45, and 60 min after secretin injection, and (6) fluid analysis with lab autoanalyzer for bicarbonate concentration (historical normal cutpoint >80 mEq/L). Thirty-six patients had both the endoscopic function test and ERCP. Seventeen had chronic abdominal pain with normal pancreatograms, and nineteen had chronic abdominal pain with abnormal pancreatograms, consistent with chronic pancreatitis. The sensitivity and specificity of the endoscopic function test were 94% and 79%, respectively. The positive and negative predictive values were 80% and 94%, respectively. Overall agreement with ERCP was 86%. The ePFT with synthetic porcine secretin has excellent correlation with abnormal pancreatogram (chronic pancreatitis). Furthermore, a normal bicarbonate (negative function test, HCO(3) >80 mEq/L) essentially rules out chronic pancreatitis as a diagnostic cause of abdominal pain. Endoscopic pancreatic function testing may decrease the need for ERCP in patients with chronic abdominal pain.

The Effect of Moderate Sedation on Exocrine Pancreas Function in Normal Healthy Subjects: A Prospective, Randomized, Cross-Over Trial Using the Synthetic Porcine Secretin Stimulated Endoscopic Pancreatic Function Test (ePFT)

We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4,323-6563) respectively (p= 0.0656). The mean peak bicarbonate concentrations for sedated (n = 8) versus non-sedated (n = 8) groups were 103 +/- 11 meq/L (range 78-125) and 106 +/- 11 meq/L (range 87-138), respectively (p= 0.1346). There was excellent correlation of peak bicarbonate concentrations when sedation and no sedation groups were compared (r= 0.744, p < 0.05; Spearman rank correlation). There were no episodes of pancreatitis. (a) Moderate sedation used for upper endoscopy does not effect the clinical diagnostic parameters (peak bicarbonate concentration or total bicarbonate output) utilized to diagnose pancreatic insufficiency. (b) Analysis of duodenal drainage fluid collected endoscopically after synthetic secretin stimulation produces an identical pancreatic secretory curve described with traditional gastroduodenal tube collection methods.

A PROSPECTIVE, RANDOMIZED, CROSSOVER TRIAL IN HEALTHY SUBJECTS (HS) COMPARING ENDOSCOPIC AND DREILING TUBE (DT) COLLECTION METHODS FOR PANCREATIC FUNCTION TESTING (PFT).

We have developed an endoscopic method that eases collection of duodenal aspirates (ePFT); however validation requires a rigorous comparison to the DT method. Aim: To compare [HCO3−] obtained by the ePFT and DT methods in HS. Methods: HS were randomized to secretin DT or ePFT, then crossed over to the remaining test after a minimum 1-wk washout. An age/weight-based sedation bolus was used for each test. DT protocol: Endoscopic placement of a DT confirmed by fluoroscopy. EPFT protocol: Endoscopy performed using a 6-mm endoscope. After IV synthetic porcine secretin (0.2mcg/kg, ChiRho-Clin, Inc.), duodenal fluid collected in 15-min increments for 1 hr and auto-analyzed for bicarbonate. Median differences in [HCO3−] were analyzed at each time point and at peak. Results: 11 HS enrolled (mean age 30yrs; 6F). [HCO3−] were not significantly different at times 30, 45, or 60; however, [HCO3−] at time 15 were significantly different [Table]. Although median peak [HCO3−] was lower for DT compared to ePFT, all HS achieved a peak [HCO3−] >80 mEq/L for both collection methods.TABLE: [HCO3 −] Values for DT and ePFTConclusions: 1. The diagnostic accuracy of ePFT is similar to DT since both collection methods demonstrate peak [HCO3−] >80 mEq/L in HS. 2. [HCO3−] is variable during the early phase of pancreatic secretion but reaches a steady state after 15 min of secretin stimulation. Clinical Implication: The secretin ePFT holds promise as an accurate and less cumbersome method of direct PFT.

PRELIMINARY OBSERVATIONS OF A PROSPECTIVE CROSS-OVER TRIAL COMPARING ENDOSCOPIC AND DREILING TUBE (DT) COLLECTION METHODS FOR PANCREATIC FUNCTION TESTING (PFT)

Purpose: Collection of hormone-stimulated duodenal fluid using a DT is considered the gold standard PFT; however this method is cumbersome and not widely available. We have developed an endoscopic test (ePFT) which eases collection of duodenal aspirates. Our aim is to compare peak duodenal fluid [HCO3−] obtained by DT and ePFT methods after secretin stimulation. Methods: Healthy subjects (HS) and CP pts were randomized to secretin DT or ePFT, then crossed over to the remaining test after a minimum 1-wk washout. An age/weight-based sedation bolus was used for each test. Dreiling tube method: endoscopic placement of a DT was confirmed using fluoroscopy. After IV synthetic porcine secretin (0.2 mcg/kg, ChiRho-Clin, Inc.), duodenal fluid was collected in 15-min increments for 1 hour. Endoscopic Pancreatic Function Test (ePFT) method: 1) Upper endoscopy was performed using a 6-mm endoscope, 2) IV secretin, 3) duodenal aspirates were obtained every 5 min for 1 h and 4) fluid was sent for [HCO3−] analysis on autoanalyzer. Results: 6 HS and 4 CP pts have been randomized to date. All patients tolerated both procedures without complication. Median peak [HCO3] for DT and ePFT for the HS was 103 and 109 mEq/L, respectively (p = 0.31). Median peak [HCO3] for for the CP pts was 70 mEq/L for both tests (p = 0.88). There was a significant correlation in peak [HCO3] obtained by each method (r = 0.7, p = 0.03, Pearson).[figure 1]Figure: Peak [HCO3 −] for EPFT and DPFTConclusions: 1. The peak [HCO3−] observed with each collection method are similar. 2. The peak [HCO3−] obtained by the E-PFT shows a good correlation with peak [HCO3−] obtained by a DT. 3. Patients are continuing to be enrolled into this prospective trial.

Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects

Traditional pancreatic function tests are sensitive for the diagnosis of pancreatic exocrine insufficiency but are cumbersome and difficult to perform. A sedationless endoscopic pancreatic function test that has the potential for wide clinical application was developed by us, but data on the results of this method in healthy subjects are lacking. This study analyzed endoscopically collected duodenal fluid from healthy subjects after synthetic porcine secretin stimulation. Healthy subjects underwent the sedationless endoscopic pancreatic function test. After secretin stimulation, duodenal aspirates were obtained every 5 minutes for 1 hour. The collected fluid was analyzed for electrolyte concentrations. Sixteen healthy subjects (8 women, 8 men; median age 34.5 years) underwent the endoscopic pancreatic function test. The concentrations of the sodium ([Na+]) and potassium ([K+]) cations remained constant, similar to normal concentrations in plasma (median [Na+], 155 mEq/L; median [K+], 4.3 mEq/L). The concentrations of the bicarbonate ([HCO 3 - ]) and chloride anions increased and decreased, respectively, in an inverse and reciprocal manner, similar to the previously characterized "secretory curve." The median peak [HCO 3 - ] was 108 mEq/L IQR: 99-110). By the 20-minute collection, the [HCO 3 - ] was greater than 80 mEq/L for 94% (15/16) of subjects, the historic cut point for [HCO 3 - ] in studies based on traditional methods of pancreatic function testing. Endoscopic collection of pancreatic fluid reproduces the anion-cation secretory curve described by prior studies of pancreatic secretory physiology based on traditional collection methods.

A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: A multicenter, randomized, double-blind comparative study

Background: Secretin, a 27 amino acid polypeptide released in response to duodenal luminal acidification, stimulates secretion of water and bicarbonate from pancreatic ductal cells. To date the only secretin available for clinical use has been a biologically derived compound extracted from porcine duodenums. Although used to facilitate pancreatic duct cannulation, secretin has not been approved for this indication. In this study, a new synthetic porcine secretin with an identical amino acid composition was compared with saline solution for the facilitation of minor papilla cannulation in patients with pancreas divisum. Methods: A multicenter, prospective, randomized, placebo-controlled, double-blind, comparative trial was conducted at 4 centers with expertise in pancreaticobiliary endoscopy. Patients with pancreas divisum in whom minor papilla cannulation initially was unsuccessful were enrolled. Either saline solution (placebo) or synthetic porcine secretin was administered. If the minor papilla orifice and/or pancreatic juice flow was noted, cannulation was attempted and success or failure was documented (phase 1), as well as the time taken for successful cannulation. If cannulation was unsuccessful, no juice flow was noted, or the orifice was not seen, the alternate agent was administered (phase 2). Results: Twenty-nine patients (7 men, 22 women; mean age 51 years, range 21-76 years) were enrolled. In phase 1, cannulation was achieved in 1 of 13 patients (7.7%) after the placebo was given and in 13 of 16 patients (81.3%) after synthetic porcine secretin was given (p < 0.0001). In phase 2, cannulation was achieved in 12 of 12 patients (100%) after synthetic porcine secretin was given and in 0 of 3 patients (0%) after the placebo was given (p = 0.0022). Overall, cannulation was successful in 25 of 28 patients (89.3%) who received synthetic porcine secretin and in 1 of 16 (6.3%) who received the placebo (p < 0.0001). Mean time to cannulation was significantly greater for the placebo than for the synthetic porcine secretin (4.75 min vs. 2.63 min; p = 0.0001). No adverse events directly attributable to synthetic porcine secretin administration were documented. Conclusions: This study confirmed the use and safety of synthetic porcine secretin in facilitating cannulation of the minor papilla in patients with pancreas divisum in whom cannulation was difficult. Use of this agent has the potential to further increase the cannulation success rate in this group of patients. (Gastrointest Endosc 2003;57:643-7.)

An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis

Background: Pancreatic function tests are the most reliable methods for the diagnosis or exclusion of chronic pancreatitis in patients without obvious radiologic changes, but they are cumbersome, time consuming, and unavailable in clinical practice. Synthetic porcine secretin, a 27 amino acid peptide identical to the biologic form, is available for exocrine function testing. This study examined the utility of a simple, newly developed, purely endoscopic pancreatic function test with synthetic porcine secretin. Methods: Three groups of patients were studied: patients with chronic abdominal pain with and without risk factors for chronic pancreatitis, and patients with advanced chronic pancreatitis. All patients with abdominal pain had “pancreatic type” pain for greater than 6 months and negative radiographic imaging studies. All patients with chronic pancreatitis had advanced disease based on retrograde pancreatography and/or CT findings. Participants underwent the following protocol: (1) standard endoscopy to the descending duodenum with the patient under conscious sedation; (2) intravenous administration of secretin (0.2 μg/kg); (3) endoscopic duodenal fluid collection at 0, 15, 30, 45, and 60 minutes after secretin injection; and (4) fluid analysis for bicarbonate concentration. Results: Eighteen patients were studied (5 abdominal pain without risk factors, 7 abdominal pain with risk factors, and 6 advanced chronic pancreatitis). Median peak (interquartile range) bicarbonate concentrations in meq/L for each group were, respectively, 87 (6, range 84-108), 72 (10, range 68-90), and 35 (27, range 18-88). Median peak bicarbonate concentration values for the 3 groups are significantly different (p = 0.010; Kruskal-Wallis test). Bicarbonate secretion in patients with chronic pancreatitis was markedly reduced compared with that in patients with abdominal pain without risk factors (p = 0.038; the Fisher exact test). The secretory function curve for patients with abdominal pain with risk factors was markedly abnormal, resembling the attenuated secretory curve seen in patients with chronic pancreatitis. The test was safe and well tolerated. Conclusions: A simple endoscopic pancreatic function test with synthetic porcine secretin appears to distinguish patients with known chronic pancreatitis from those with chronic abdominal pain without chronic pancreatitis. This simple, practical endoscopic test can be performed during upper endoscopy and may decrease the need for invasive procedures in patients with abdominal pain and normal radiographic imaging studies. (Gastrointest Endosc 2003;57:37-40.)

An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis

Background: Pancreatic function tests are the most reliable methods for the diagnosis or exclusion of chronic pancreatitis in patients without obvious radiologic changes, but they are cumbersome, time consuming, and unavailable in clinical practice. Synthetic porcine secretin, a 27 amino acid peptide identical to the biologic form, is available for exocrine function testing. This study examined the utility of a simple, newly developed, purely endoscopic pancreatic function test with synthetic porcine secretin. Methods: Three groups of patients were studied: patients with chronic abdominal pain with and without risk factors for chronic pancreatitis, and patients with advanced chronic pancreatitis. All patients with abdominal pain had “pancreatic type” pain for greater than 6 months and negative radiographic imaging studies. All patients with chronic pancreatitis had advanced disease based on retrograde pancreatography and/or CT findings. Participants underwent the following protocol: (1) standard endoscopy to the descending duodenum with the patient under conscious sedation; (2) intravenous administration of secretin (0.2 μg/kg); (3) endoscopic duodenal fluid collection at 0, 15, 30, 45, and 60 minutes after secretin injection; and (4) fluid analysis for bicarbonate concentration. Results: Eighteen patients were studied (5 abdominal pain without risk factors, 7 abdominal pain with risk factors, and 6 advanced chronic pancreatitis). Median peak (interquartile range) bicarbonate concentrations in meq/L for each group were, respectively, 87 (6, range 84-108), 72 (10, range 68-90), and 35 (27, range 18-88). Median peak bicarbonate concentration values for the 3 groups are significantly different ( p = 0.010; Kruskal-Wallis test). Bicarbonate secretion in patients with chronic pancreatitis was markedly reduced compared with that in patients with abdominal pain without risk factors ( p = 0.038; the Fisher exact test). The secretory function curve for patients with abdominal pain with risk factors was markedly abnormal, resembling the attenuated secretory curve seen in patients with chronic pancreatitis. The test was safe and well tolerated. Conclusions: A simple endoscopic pancreatic function test with synthetic porcine secretin appears to distinguish patients with known chronic pancreatitis from those with chronic abdominal pain without chronic pancreatitis. This simple, practical endoscopic test can be performed during upper endoscopy and may decrease the need for invasive procedures in patients with abdominal pain and normal radiographic imaging studies. (Gastrointest Endosc 2003;57:37-40.)

A Randomized, Double-Blind, Placebo-Controlled Trial of Porcine Versus Synthetic Secretin for Reducing Symptoms of Autism

To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms. Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy. Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups. No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately.

Facilitation of pancreatic duct cannulation using a new synthetic porcine secretin

OBJECTIVES: Cannulation of the pancreatic duct at ERCP can represent a technical challenge, even to experienced pancreaticobiliary endoscopists. Secretin is a polypeptide hormone that increases the volume and bicarbonate content of pancreatic secretions. We report our single center experience in the use of a new synthetic porcine secretin (sPS) for the facilitation of cannulation of either the major or minor pancreatic orifice during ERCP. METHODS: Patients presenting for a variety of indications were enrolled. If identification or cannulation of the desired pancreatic duct was difficult, 0.2 μg/kg of sPS was administered i.v. Cannulation success or failure was recorded. RESULTS: Between March, 1999, and May, 2000, a total of 25 patients (seven men and 18 women) were enrolled. The most frequent indication (15 of 25 cases) was facilitation of dorsal pancreatic duct cannulation in patients with pancreas divisum. The overall rate of successful cannulation secretin administration was 24 of 25 cases (96%). No adverse events directly attributable to secretin were observed. CONCLUSIONS: The results of this study show that sPS is safe and efficacious in faciliting cannulation of either the major or minor pancreatic orifice at ERCP in the subset of patients who represent cannulation difficulties. Once commercially available, sPS can be added to the armamentarium of techniques to facilitate ERP.

Facilitation of pancreatic duct cannulation using synthetic porcine secretin

Facilitation of pancreatic duct cannulation using synthetic porcine secretin

Facilitation of pancreatic duct cannulation using synthetic porcine secretin

Facilitation of pancreatic duct cannulation using synthetic porcine secretin

7238 Facilitation of pancreatic duct cannulation using synthetic porcine secretin.

INTRODUCTION: Secretin, for diagnostic use, is a gastrointestinal peptide hormone consisting of 27 amino acids. Its primary pharmacologic action is to increase the volume and bicarbonate content of secreted pancreatic juices. Its approved uses are for the diagnosis of chronic pancreatitis and gastrinoma and as an adjunct to obtain pancreatic cells for cytology. Previously, only secretin extracted from porcine duodenums had been available. Recently, a pure synthetic porcine secretin (ChiRhoClin) with an identical amino-acid sequence and structure has been developed. AIM: To assess the pharmacological and clinical efficacy and safety profile of this new synthetic porcine secretin in facilitating cannulation of either the major or minor pancreatic orifice at ERCP. METHODS: In this prospective study, patients were administered 0.2ug/kg IV (max. 16ug) of synthetic porcine secretin if protracted efforts to locate or cannulate the major or minor pancreatic orifice had failed. Exclusion criteria were acute pancreatitis, known sensitivity or adverse reaction to secretin and pregnant or nursing females. RESULTS: Between March and November, 1999, 29 patients were enrolled (M:F 8:21; Average age 52.8 years, range 23-81 years). The indications for secretin injection were: to aid in minor papilla cannulation in patients with pancreas divisum (18), to aid in finding main PD orifice (4), to find PD orifice post biliary sphincterotomy (3), to facilitate intact major papilla cannulation (2), to aid in finding minor papilla (1), and to facilitate minor papilla cannulation in normal PD anatomy (1). Successful cannulation was achieved in 26/29 (89.7%) patients. In one case, cannulation of the minor papilla was still not possible because of its location in a duodenal diverticulum. In the two remaining cases, deep cannulation of the pancreatic duct was not deemed essential and was not pursued. No adverse events were recorded. SUMMARY: A new, pure, synthetic secretin aided successful cannulation of the major or minor pancreatic orifices in 26/29 patients in whom protracted efforts to locate or cannulate the pancreatic duct had failed. These data suggest this new agent is both effective and safe for this clinical indication. CONCLUSIONS: Synthetic porcine secretin is a safe and useful agent, and its administration can be added to the armamentarium of techniques to facilitate pancreatic duct cannulation.

Effect of secretin on bile formation in rats with cirrhosis of the liver: Structure-function relationship

To investigate whether the hypercholeresis seen in cirrhotic humans and animals is due to ductular proliferation or altered inactivation of secretin, or both, we studied the response of bile flow and biliary erythritol clearance to synthetic porcine secretin in rats rendered cirrhotic by chronic exposure to phenobarbital/carbon tetrachloride (n = 11) and untreated control rats (n = 5). Bile duct mass was determined morphometrically. Furthermore, plasma disappearance of secretin was measured by radioimmunoassay. Basal bile flow did not differ between the two groups. Whereas secretin had no effect in the control group, it stimulated bile flow by 49% ± 33% in the cirrhotic group (p < 0.001). Erythritol bile-to-plasma ratio was lower and biliary bicarbonate concentration higher in the cirrhotic rats, suggesting some ductular contribution to bile flow even in the absence of secretin. Biliary bicarbonate concentration did not increase further during secretin administration, whereas bile salt concentration decreased from 27±6 to 18±4 mM. The elimination half-life of secretin was not affected by cirrhosis, averaging 5 ± 2 min in both groups. Bile duct volume was increased in cirrhotics (2.9% ± 1.4% vs. 0.2% ± 0.1%; p < 0.01) and showed an excellent correlation with the maximal secretin-induced increment of bile flow. Our results suggest that the proliferating ductules contribute to bile flow and that increased secretin responsiveness is not due to altered pharmacokinetics in cirrhotic rat liver.

Effect of chronically‐administered secretin on the nude mouse

Secretin plays an important role in the growth regulation of certain cancers in vitro. The nude mouse is a suitable model for evaluation of the effects of this hormone on tumor xenografts in vivo, but little is known about long-term actions of secretin in this species. We investigated the impact of chronically administered synthetic porcine secretin in the nude mouse. Six groups of mice (eight animals each) received twice-daily intraperitoneal injections of saline or secretin at 0.5, 5, 50, 500, or 5,000 micrograms/kg for 14 days. Body weight and general health were unaffected by exogenous secretin, and no apparent behavioral effects were observed. Seven abdominal organs were examined at necropsy and all were histologically normal. The only organ that showed a weight change was the pancreas (13% decrease at the highest secretin dose). This was accompanied by decreases in DNA and RNA content, indicating pancreatic hypoplasia. Secretin administration caused changes in DNA and/or RNA content (but not protein content or weight) in liver, small bowel, cecum, and large bowel. No effect of secretin on stomach or kidney was observed. Our work demonstrates the safety of frequent injections of pharmacologic doses of secretin in this frail animal and suggests that the nude mouse is an appropriate model for the in vivo study of tumor growth regulation by secretin.

Human secretin: Biologic effects and plasma kinetics in humans

The action of synthetic human secretin, which differs in two amino acid residues from porcine secretin, was compared with synthetic porcine secretin in 6 healthy volunteers. Pancreatic secretion was assessed by a marker perfusion technique and plasma secretin concentrations were assessed by a specific radioimmunoassay. Increasing doses of either human or porcine secretin produced increasing bicarbonate output (p < 0.01), whereas trypsin and lipase were not stimulated over basal. The highest doses of secretin induced a significant increase in pancreatic amylase secretion. The two secretin preparations were found to be equipotent with respect to pancreatic secretion and plasma kinetics. Significant increases of plasma secretin were observed after a steak meal in 15 volunteers (p < 0.001). When human secretin was infused at postprandial concentrations, significant increases in pancreatic bicarbonate output were observed (p < 0.05). We conclude (a) that the substitution of two amino acids in human secretin does not affect biologic activity and plasma metabolism of the compound; (b) secretin does not stimulate pancreatic enzyme secretion at physiologic concentrations; and (c) the stimulatory effects of secretin on pancreatic amylase remain to be elucidated. The study suggests that human secretin is a true hormone.