Intravenous Administration Of Secretin Research Articles

Secretin-stimulated multi-detector CT versus mangafodipir trisodium-enhanced MR imaging plus MRCP in characterization of non-metastatic solid pancreatic lesions

Our study was aimed to compare multiphasic multi-detector computed tomography after secretin stimulation and mangafodipir trisodium-enhanced magnetic resonance imaging plus MR cholangiopancreatography in the characterization of solid pancreatic lesions. Forty patients with ultrasound diagnosis of solid pancreatic lesion prospectively underwent both multi-detector computed tomography and magnetic resonance imaging. Three minutes after intravenous administration of secretin, post-contrast computed tomography scans were performed 40, 80, and 180 s after contrast medium injection. MR protocol included axial/coronal, thin/thick-slab, single-shot T2 w sequences and axial/coronal T1 w breath-hold spoiled gradient-echo images before and 30-40 min after intravenous infusion of manganese dipyri-doxal diphosphate. Different observers blindly evaluated the ability of computed tomography and magnetic resonance imaging to characterize focal pancreatic lesions. Surgery, biopsy, and/or follow-up were considered as our diagnostic gold standard. Thirty-five focal pancreatic lesions (adenocarcinoma, n=18; focal chronic pancreatitis, n=4; endocrine tumor, n=6; metastasis, n=1; cystic tumor, n=3; indeterminate cystic lesions, n=3) were present in 34 patients since the remaining 6 subjects showed no pathological finding. Both multi-detector computed tomography and magnetic resonance imaging showed a statistically significant correlation with the gold standard and between themselves in the characterization of 29 solid lesions of the pancreas (p<0.05). Both imaging techniques well correlate to final diagnosis of non-metastatic solid pancreatic lesions and particularly of adenocarcinomas with a slight advantage for mangafodipir trisodium-enhanced magnetic resonance imaging plus MR cholangiopancreatography.

Pancreatic Function Testing Is Best Determined by the Extended Endoscopic Collection Technique

To evaluate whether the extended secretin-stimulated direct endoscopic pancreatic function test (ePFT) technique is superior to the rapid 15 minute secretin-stimulated ePFT in determining pancreatic exocrine function. We conducted a retrospective study of 53 patients with chronic abdominal pain and normal pancreatic imaging. These patients had ePFT testing with the following modified endoscopic collection system. Porcine synthetic or human secretin was intravenously administered 15 minutes before endoscopic duodenal aspiration. The first 10-minute collection was performed in the third portion of the duodenum. A Liguory drainage tube was placed in the third portion of the duodenum. Two additional 10-minute-period collections were obtained via the drainage tube at 30 and 45 minutes after intravenous administration of secretin. All fluid collections were analyzed for bicarbonate (HCO3) concentration. Peak HCO3 concentrations at 15 minutes occurred in 62%, at 30 to 40 minutes in 23%, and at 45 to 55 minutes in 15%. Normal concentrations of HCO3 (> or =80 mEq/L) were seen in 70%, abnormal concentration in 7%, and equivocal concentrations (60-79 mEq/L) in 23% even after 55 minutes of duodenal collections. Collections beyond 15 minutes are necessary to improve accuracy of the ePFT in determining pancreatic exocrine function.

Symptomatic Annular Pancreas in an Elderly Adult Diagnosed by EUS and Secretin MRCP

Purpose: Annular pancreas (AP) is a rare congenital abnormality in which the ventral portion of the pancreas fails to rotate with the duodenum during embryological development, thus causing the ventral portion to remain partially or fully enveloped around the duodenum. The incidence of AP is unknown, as many cases are asymptomatic and undiagnosed. Adults with AP may present with a variety of symptoms suggestive of gastric outlet obstruction, or may present with gastrointestinal bleeding, pancreatitis, or biliary obstruction. Although as many as 50% of patients present in adulthood, there have been no published reports of cases above the age of 76. Surgery continues to remain the diagnostic “gold standard” for AP, but imaging techniques such as computed tomography (CT), magnetic resonance imaging, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS) can now be used to make the diagnosis. We report the case of an 85 year old gentleman who presents with symptoms of partial gastric outlet obstruction who was diagnosed with AP by EUS and secretin magnetic resonance cholangiopancreatography (MRCP). Methods: N/A Results: An 85 year old gentleman with a past medical history of hypertension, diabetes, and cerebrovascular disease was admitted to the hospital for the evaluation of intermittent abdominal pain, nausea, vomiting, and weight loss. CT of the abdomen revealed a soft tissue mass surrounding the second portion of the duodenum causing duodenal compression. Esophagogastroduodenoscopy revealed a narrowed duodenal lumen as well as the presence of a duodenal diverticulum. EUS was performed revealing the soft tissue mass to be pancreatic tissue of normal echogenicity with the presence of an annular duct confirming the diagnosis of AP. ERCP was unable to be performed as the major papilla was within the duodenal diverticulum and could not be cannulated. Dynamic MRCP, with the intravenous administration of secretin, was performed to evaluate both the pancreatic and biliary ducts revealing no ductal dilatation but again confirming the diagnosis of AP. Conclusion: AP is a rare presentation in the elderly, yet a high index of suspicion needs to be maintained in elderly patients with a presentation of gastric and duodenal outlet obstruction. We highlight the role of EUS and secretin MRCP as highly sensitive and safe modalities compared to standard ERCP, with its associated risk of pancreatitis, to diagnose AP and its associated ductal abnormalities.

Pancreatic transplants: secretin-stimulated MR pancreatography

Our study was aimed to evaluate the functional status of pancreatic transplants using dynamic MR pancreatography after secretin stimulation. Thirteen asymptomatic patients previously submitted to isolated pancreas (n = 6) or combined kidney-pancreas (n = 7) transplantation, with enteric-portal pancreatic drainage, underwent MR examination at 1.5 T using a phased-array coil. After the acquisition of axial and coronal T1- and T2-weighted sequences, dynamic MR pancreatography was performed using a coronal breath-hold, thick-slab (40-60 mm), single-shot T2-weighted fast spin-echo sequence. After the intravenous administration of secretin (Secrelux, Sanochemia; 1 cU/kg body/weight), a single-slice image acquisition was repeated every 30 s up to 15 min. We estimated the calibre changes of the pancreatic ductal system and the filling of the donor's duodenum on the basis of pancreatic secretion after secretin stimulation, also evaluated by using a mean signal intensity/time histogram in a chosen region of interest including the transplanted pancreas and the connected small bowel. All patients well tolerated the examination, and no side effects were reported after secretin administration. In 12/13 cases, a significant increase (more than 1 mm) in the diameter of the mean pancreatic duct was observed after secretin stimulation; in all patients, a noticeable filling of the duodenal graft was demonstrated during dynamic MR pancreatography on both qualitative and quantitative analyses. Dynamic MR imaging after secretin administration allows non-invasive evaluation of exocrine function of the pancreatic transplants and could be used to differentiate patients with graft rejection from those with normal graft function.

Secretin and autism: a basic morphological study about the distribution of secretin in the nervous system

For the first time, the relationship between secretin and autism has been demonstrated by one of us. Intravenous administration of secretin in autistic children caused a fivefold higher pancreaticobiliary fluid secretion than in healthy ones and, at least in some of the patients, better mental functions were reported after the secretin test. Because the precise localization of secretin in the brain is still not completely known, the abovementioned observation led us to map secretin immunoreactivity in the nervous system of several mammalian species. In the present work, the distribution of secretin immunoreactivity in cat and human nervous systems was compared with that of rats using an immunohistochemical approach. Secretin immunoreactivity was observed in the following brain structures of both humans and in colchicine-treated rats: (1) Purkinje cells in the cerebellar cortex; (2) central cerebellar nuclei; (3) pyramidal cells in the motor cortex; and (4) primary sensory neurons. Additionally, secretin immnoreactive cells were observed in the human hippocampus and amygdala and in third-order sensory neurons of the rat auditory system. In cats, secretin was only observed in the spinal ganglia. Our findings support the view that secretin is not only a gastrointestinal peptide but that it is also a neuropeptide. Its presence or the lack of its presence may have a role in the development of behavioral disorders.

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.)

Effects of Intravenous Secretin on Language and Behavior of Children With Autism and Gastrointestinal Symptoms: A Single-Blinded, Open-Label Pilot Study

Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration. To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms. We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a standard set of developmentally appropriate toys. Participants then returned for follow-up evaluations, with readministrations of the PLS-3 at 1, 2, 3, and 5 weeks' postinfusion, and videotaping of each session for later blinded review by 2 independent observers using the Autism Observation Scale, uninformed about week of posttreatment. We also surveyed parents of our study children about their impressions of the effects of secretin using a 5-point Likert scale for parents to rate changes seen in their child. With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in the sample. Despite the objective lack of drug effect, 70% of parents in our study reported moderate to high change in their child's language and behavior. Furthermore, 85% of parents reported that they felt that their child would obtain at least some additional benefits from another infusion of secretin. The results of our pilot study indicate that intravenous secretin had no effects in a 5-week period on the language and behavior of 20 children with autism and gastrointestinal symptoms. The open-label, prospective design of our study with blinded reviews of patients both before and after secretin administration follows the scientific method by seeking to reproduce an observed phenomenon using validating and reliable outcome measures. Pilot studies remain a mandatory step for the design of future randomized, clinical trials investigating potential treatments for children with autism.

Functional assessment of pancreatic parenchyma after secretin administration using serial T2-weighted echo-planar magnetic resonance imaging.

Signal intensity (SI) changes of pancreatic parenchyma were evaluated after intravenous administration of secretin using T2-weighted single-shot spin-echo echo-planar imaging (EPI) to assess this method as a magnetic resonance (MR) test of pancreatic exocrine function. Nine volunteers were studied with serial single-shot EPI of the pancreas for 15 minutes after the injection of secretin or saline. The normal pattern of pancreatic SI change was demonstrated after intravenous injection of secretin, a single peak at 3-4 minutes in the head, body, and tail, followed by a gradual decrease in SI. Saline injection did not induce a significant SI change. There was no statistical difference in the peak contrast ratios (first mean, 1.21-1.25, vs. second mean, 1.18-1.22) and peak times (first mean, 3.2-3.7 minutes, vs. second mean, 3.1-3.6) in a repeat study. By evaluating the pattern of time-response curves obtained from serial T2-weighted EPI after secretin injection, pancreatic exocrine function may be directly assessed at the level of the head, body, and tail.

A secretin releasing peptide exists in dog pancreatic juice

Canine pancreatic juice has been shown to stimulate exocrine pancreatic secretion in the dog. In the present study we investigated whether there is a secretin-releasing peptide in canine pancreatic juice. Pancreatic juice was collected from the dogs with Thomas gastric and duodenal cannulas while pancreatic secretion was stimulated by intravenous administration of secretin at 0.5 μ/gk/gh and CCK-8 at 0.2 μg/kg/h, respectively. The pancreatic juice was separated into three different molecular weight (MW) fractions (Fr) by ultrafiltration (Fr 1; MW > 10,000, Fr 2; MW = 10,000 − 4,000 and Fr 3; MW < 4,000), respectively. All the fractions were bioassayed in anesthetized rats. Fraction 3 dose-dependently and significantly stimulated pancreatic juice flow volume from 78.0% to 99.4% (p < 0.05) and bicarbonate output from 128.9% to 202.1% (p < 0.01), respectively. Plasma secretin concentration also increased from 1.2 ± 0.5 pM to 5.0 ± 0.8 pM and 6.0 ± 1.0 pM (p < 0.05). None of these fractions increased pancreatic protein secretion or plasma CCK level. The stimulatory effect of Fraction 3 on pancreatic secretion and the release of secretin was completely abolished by treatment with trypsin (1 mg ml for 60 min at 37 ° C) but not by heating (100 ° C, 10 min). Intravenous injection of a rabbit anti-secretin serum, which rendered plasma secretin almost undetectable in rat plasma, also abolished Fr 3-stimulated pancreatic secretion of fluid and bicarbonate secretion. These observations suggest that a secretin-releasing peptide exists in the canine pancreatic juice. It is trypsin-sensitive and heat-resistant. This peptide may play a significant physiological role on the release of secretin and regulation of exocrine pancreatic secretion.

Canine pancreatic juice stimulates the release of secretin and pancreatic secretion in the dog.

A secretin-releasing factor (SRF) was found in canine pancreatic juice that increases plasma secretin and stimulates pancreatic secretion in rats, suggesting that a positive feedback mechanism may be involved in the regulation of pancreatic secretion. In the present study, we investigated to determine whether or not SRF releases endogenous secretin and stimulates exocrine pancreatic secretion in conscious dogs. Fresh pancreatic juice was collected from four dogs by intravenous administration of secretin at 0.5 microg. kg(-1). h(-1) and CCK at 0.2 microg. kg(-1). h. The juice was boiled for 10 min at 100 degrees C. Experiments were carried out in phase I of spontaneous cycle of interdigestive pancreatic secretion. The testing solutions were infused intraduodenally in separate experiments: NaHCO3 solution (0.1 M, 4.5 ml/min, 60 min), a corn oil (Lipomul, 2 ml/min, 10 min), boiled pancreatic juice (BPJ, 4.5 ml/min, 60 min), and mixture of BPJ and Lipomul. Pancreatic secretion of fluid and bicarbonate was significantly increased by either BPJ or a mixture of BPJ and Lipomul (34- and 31-fold or 41- and 38-fold, respectively). Plasma secretin level also significantly increased by 164.7 +/- 13.4% and 223.1 +/- 35.0%, respectively, from basal concentration of 1.7 +/- 0.5 pM. In contrast, neither bicarbonate solution nor Lipomul influenced the plasma secretin level or pancreatic secretion. In addition, when Lipomul was incubated with BPJ, no fatty acid was produced. Thus the increased pancreatic secretion in the dog infused with a combination of BPJ and Lipomul was caused by SRF in BPJ, which released endogenous secretin. Moreover, the increases by BPJ of both plasma secretin level and bicarbonate secretion were completely blocked by intravenous administration of an antisecretin antibody in these dogs. The observations suggest that SRF in pancreatic juice exerts a positive feedback effect on exocrine pancreatic secretion that is mediated by the release of secretin in the interdigestive state in dogs.

Potentiation of cholecystokinin and secretin-induced pancreatic exocrine secretion by endogenous insulin in humans.

To investigate the effects of endogenous insulin on pancreatic exocrine secretion in humans, we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 21 healthy subjects (14 men and seven women). Samples of pancreatic juices were collected after intravenous injection of either glucose (50%, 40 ml), secretin (0.25 CU/kg), and cholecystokinin-8 (CCK) (40 ng/kg), or a combination of glucose, secretin, and CCK in six 5-min periods. The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose were measured. After infusion of glucose, the plasma insulin and C-peptide levels were significantly increased and remained at high levels during 30-min experiments, intravenous administration of secretin and CCK resulted in significant increases of pancreatic secretion including volume, bicarbonate, and protein output. When glucose was simultaneously administered with secretin and CCK, pancreatic secretion was significantly increased, more than the effects achieved by the secretin and CCK. However, glucose alone did not increase basal pancreatic secretion. These observations suggest that endogenous insulin intensifies pancreatic secretion stimulated by secretin and CCK in humans.

Optimized serum pancreolauryl test for differentiating patients with and without chronic pancreatitis

The serum pancreolauryl test has limited sensitivity for detecting mild pancreatic insufficiency. The aim of this study was to optimize the serum pancreolauryl test so as to increase the probability of positive results in patients with chronic pancreatitis. The study had three parts. First, the sampling time was optimized by analyzing retrospectively the frequency of fluorescein peaks at different times from 0 to 240 min in 560 consecutive patients. Second, the calculation of serum fluorescein concentrations by means of a standard calibration factor was prospectively compared in 271 consecutive patients with a modification involving a specimen-specific calibration factor for each patient. Third, the clinical utility of the intravenous injection of secretin before ingestion of the test meal was prospectively evaluated in a further 32 patients. As a result, the optimized serum pancreolauryl test developed differs from the former version of the test in utilizing intravenous administration of secretin before the test meal, calculation of serum fluorescein based on specimen-specific calibration factors, and blood samples taken only at 0 (basal), 120, 150, 180, and 240 min. This optimized pancreolauryl test was abnormal more frequently in patients with chronic pancreatitis than was the formerly used test, especially for cases of mild and moderate disease.

Effect of secretin on lower esophageal sphincter pressure in patients with esophageal achalasia

The effect of a bolus intravenous administration of secretin (2.0 U/kg) on resting lower esophageal sphincter pressure (LESP) was investigated in seven patients with esophageal achalasia. Basal LESP before secretin injection in the patients was 60.1 +/- 3.4 mmHg (Mean +/- SEM), which was significantly higher than 26.9 +/- 2.5 mmHg in normal controls consisting of eight healthy volunteers. LESP significantly decreased within 1 min after the injection both in the patients and the controls. The maximum pressure change from each basal LESP was 31.2 +/- 5.2 mmHg in the patients, which was significantly greater than 12.1 +/- 1.8 mmHg in the controls. The effect of secretin disappeared within 5 min in the controls. The effect in the patients, however, lasted throughout the investigation time of 30 min. It is concluded that secretin has a long-acting effect on muscular relaxation of the lower esophageal sphincter in esophageal achalsia patients.

Effect of pancreatic proteases on plasma cholecystokinin, secretin, and pancreatic exocrine secretion in response to sodium oleate

The effect of pancreatic proteases or juice on the sodium oleate-stimulated pancreatic secretion and plasma concentrations of secretin and cholecystokinin in anesthetized rats was investigated. Each rat received sodium oleate in a dose of 0.12 mmol · h−1 via a duodenal tube. Sodium oleate infusion significantly increased pancreatic secretion (volume and protein output) compared with the saline given the control group. The increase in pancreatic secretion paralleled significant elevations of plasma concentrations of secretin and cholecystokinin. To determine a possible role of pancreatic proteases on the responses induced by sodium oleate, saline, chymotrypsin, and trypsin, a combination of chymotrypsin and trypsin or pancreatic juice was infused into the duodenum. The pancreatic secretioo was significantly reduced by pancreatic proteases or pancreatic juice, and the reduction paralleled the decreases in plasma concentrations of the two hormones. These agents suppressed both pancreatic secretion and plasma hormone levels in the following order of magnitude: (pancreatic juice or chymotrypsin + trypsin) > (trypsin) > (chymotrypsin). The reduction of pancreatic secretion by pancreatic proteases was reversed by intravenous administration of secretin and cholecystokinin in physiological doses. It is concluded that negative-feedback regulation of pancreatic secretion is operative in the intestinal phase in rats and that both secretin and cholecystokinin are involved in the regulation.

Effect of Pancreatic juice and Trypsin on Oleic Acid-Stimulated Pancreatic Secretion and Plasma Secretin in Dogs

We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.

Calcium carbonate saturation in human pancreatic juice: Possible role of ductal H+ secretion

Saturation with calcium carbonate was measured in human pancreatic juice anaerobically collected for diagnostic purposes in 15 patients who were ultimately found not to have pancreatic disease. Bicarbonate, Pco2, proteins, and total and ionized calcium were measured in samples collected every minute during a 20-min period after intravenous administration of secretin (1 U/kg) and, 10 min later, caerulein (75 ng/kg). All samples were supersaturated with calcium carbonate. The first sample (washing-out sample) contained the highest concentrations of ionized calcium (Ca2+) and proteins but was least supersaturated with calcium carbonate. Washing-out samples also differed significantly from samples under caerulein by having a lower pH (7.52 ± 0.30) and higher Pco2 (103.1 ± 32.20 mmHg) versus 8.22 ± 0.15 and 38.4 ± 4.5 mmHg, respectively. Values of Pco2 increased and bicarbonate concentration decreased linearly with protein concentration in washing-out samples but not under hormonal stimulation. This suggests that a concentration of pancreatic juice occurs in pancreatic ducts in association with luminal H+ secretion and CO2 formation, which results from bicarbonate neutralization. During stimulation, ionized calcium concentration increased with protein concentration without any change of Pco2, so that supersaturation was more pronounced under caerulein than under secretin stimulation. Disturbances of the ductal concentration of pancreatic juice during interdigestive periods could be important for pancreatic stone formation in humans.

Calcium Carbonate Saturation in Human Pancreatic juice: Possible Role of Ductal H+ Secretion

Saturation with calcium carbonate was measured in human pancreatic juice anaerobically collected for diagnostic purposes in 15 patients who were ultimately found not to have pancreatic disease. Bicarbonate, PCO2, proteins, and total and ionized calcium were measured in samples collected every minute during a 20-min period after intravenous administration of secretin (1 U/kg) and, 10 min later, caerulein (75 ng/kg). All samples were supersaturated with calcium carbonate. The first sample (washing-out sample) contained the highest concentrations of ionized calcium (Ca2+) and proteins but was least supersaturated with calcium carbonate. Washing-out samples also differed significantly from samples under caerulein by having a lower pH (7.52 +/- 0.30) and higher PCO2 (103.1 +/- 32.20 mmHg) versus 8.22 +/- 0.15 and 38.4 +/- 4.5 mmHg, respectively. Values of PCO2 increased and bicarbonate concentration decreased linearly with protein concentration in washing-out samples but not under hormonal stimulation. This suggests that a concentration of pancreatic juice occurs in pancreatic ducts in association with luminal H+ secretion and CO2 formation, which results from bicarbonate neutralization. During stimulation, ionized calcium concentration increased with protein concentration without any change of PCO2, so that supersaturation was more pronounced under caerulein than under secretin stimulation. Disturbances of the ductal concentration of pancreatic juice during interdigestive periods could be important for pancreatic stone formation in humans.

Values of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic material in the diagnosis of malignant pancreatic tumor

The diagnostic accuracy of the measurement of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic fluid in the diagnosis of pancreatic tumors was assessed in 32 patients with malignant pancreatic tumors and 19 patients with pancreatitis. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation with a duodenofiberscope after intravenous administration of secretin. Pancreatic material was obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance. Abnormally high CA 19-9 levels in the serum were significantly more frequent in patients with malignant pancreatic tumors than in those with pancreatitis: they were elevated in 71.9% of the patients with pancreatic tumors. High CA 19-9 levels were found primarily in patients with a tumor of the head of the pancreas, in those with a tumor greater than 3 cm in its greatest diameter, and in those with an unresectable cancer. Only 57.1% of seven patients with a tumor of less than 3 cm in its greatest diameter showed an increase in CA 19-9 level. The CA 19-9 levels in pure pancreatic juice were significantly higher in patients with pancreatic tumors than in patients with pancreatitis without pancreatic stone. However, it was not useful for differentiating pancreatic tumors from pancreatitis with pancreatolithiasis. The CA 19-9 level in pancreatic materials obtained by aspiration biopsy was significantly higher in patients with malignant pancreatic tumors than in those with pancreatitis. Eight patients (80%) with pancreatic tumors had values above 1000 U/ml, whereas all five patients with pancreatitis had values of less than 30 U/ml. Although CA 19-9 levels in pancreatic materials was useful only when cytologic examination did not provide any evidence of malignancy, the combination of the CA 19-9 assay and the cytologic study of specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

EFFECT OF SECRETAGOCUES ON PANCREATIC EXOCRINE SECRETION IN THE MONKEY AND THE DOG

The effects of secretin, cholecystokinin, dopamine, histamine and acetylcholine on the secretion of pancreatic juice were investigated in the monkey and the dog. In the resting state, bicarbonate concentration and the volume of pancreatic juice in the monkey were greater than those in the dog. However, the protein concentration of pancreatic juice in the monkey was less than that in the dog. Intravenous administration of secretin, cholecystokinin, histamine and acetylcholine caused a dose dependent increase in pancreatic secretion in both species. The responses in the monkey were greater than those in the dog. Dopamine caused pancreatic secretion only in the dog. The increase in bicarbonate concentrations of pancreatic juice induced by secretin and histamine in the monkey were greater than that in the dog. Increase in protein concentrations of the juice induced by cholecystokinin and acetylcholine in the monkey were less than that in the dog. However, pancreatic juice pH in both species was the same and was not affected by the secretagogues in the resting state or during the stimulation by secretogogues. From these results, it is concluded that there is a species difference in the secretory actions of the secretagogues in the monkey and the dog.