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Conclusions: Pseudocyst contents are not indicative of pancreatic function. We presume that the nonresolving pseudocysts did not resolve because they were noncommunicating. The question of the kinetics of secretion into pancreatic pseudocysts is still unresolved., Background: Pseudocysts are one of the complications of chronic pancreatitis. We wanted to investigate whether it is of any value to measure enzyme activities (amylase and lipase) in pseudocyst contents, in order to answer the following questions: Is the enzymatic activity: 1. Reproducible in consecutive punctures of the same cyst; 2. Related to cyst age; 3. Indicative for the risk of relapse; and 4. Representative of exocrine pancreatic function., Methods: In a retrospective study we examined 28 patients with chronic pancreatitis complicated with pancreatic pseudocysts., Results: Reproducibility of enzyme activity in cyst juice in consecutive punctures of the same cyst was poor. We did not observe any correlation between enzyme activity and cyst age defined as the time between two cyst punctures. Enzyme activity in cyst juice was without indication for the risk of relapse. No correlation between enzyme activity and exocrine pancreatic function was found. The pseudocyst contents are not pancreatic juice in the common sense of the word

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

MK-329 (formerly L-364,718) is a new nonpeptide antagonist for the peripheral (type-A) cholecystokinin (CCK) receptor, which has proved effective in blocking the actions of both exogenous and endogenous CCK in several species. To evaluate the effect of MK-329 on CCK-stimulated pancreaticobiliary output in man, six normal subjects received 10 mg MK-329 or placebo orally in a randomized, crossover fashion, before a background intravenous infusion of secretin (5 pmol/kg/h) and two doses of CCK-8 (approximately 15 and 40 pmol/kg/h, each for 1 h). Gastric and duodenal juice were aspirated separately via two double-lumen tubes, with 51Cr-ethylene-diaminetetraacetic acid as a duodenal marker. After placebo treatment the background infusion of secretin produced maximum plasma concentrations of secretin similar to postprandial values, averaging about 5 pM. After placebo treatment the low dose CCK-8 infusion (15 pmol/kg/h) increased circulating CCK concentrations from basal levels of 1.8 +/- 0.2 pM to levels similar to those observed postprandially, averaging 9.2 +/- 1.3 pM, and the high dose of CCK-8 (40 pmol/kg/h) induced supraphysiologic levels of CCK, averaging 23.4 +/- 3.2 pM. Plasma concentrations of secretin and CCK were not significantly different during MK-329 treatment. As expected, infusion of CCK-8 at both doses stimulated pancreatic exocrine secretion and gallbladder contraction in placebo controls, as indicated by increases in the output of trypsin, amylase, bicarbonate, and bilirubin. Whereas MK-329 did not significantly reduce basal pancreatic secretion, the integrated incremental output of trypsin, amylase, and bicarbonate in response to stimulation with the low (physiologic) CCK dose was inhibited by 74% (p less than 0.01), 89% (NS), and 75% (p less than 0.05), respectively. Basal bilirubin output was virtually abolished after treatment with MK-329, and the response to the low dose of CCK was reduced by 98% (p less than 0.01), indicating almost complete inhibition of gallbladder contraction at physiologic circulating concentrations of CCK. It is concluded that MK-329 is an orally active antagonist of CCK-stimulated pancreaticobiliary output in man and could thus be utilized to explore the physiologic regulation of the exocrine pancreas and gallbladder by CCK.

Pancreatic secretion of zinc and copper in duodenal juice were measured in 7 healthy persons and in 9 patients with chronic pancreatitis. Stimulation with cholecystokinin and secretin increased secretion of zinc in healthy persons but not in patients. Copper secretion was not influenced. In patients with chronic pancreatitis, the correlations between zinc secretion, and amylase and trypsin secretion were significant while in healthy subjects they were not. Possibly pancreatic zinc secretion in the duodenal juice might be used as a measure of exogenic pancreatic function, and determination of zinc in duodenal juice may replace enzyme determinations in the diagnosis of chronic pancreatitis.

The exocrine pancreatic function was investigated in 16 patients with progressive systemic sclerosis by means of a meal test (Lundh test) and in 9 of the patients by the secretin-cholecystokinin test as well. Gastrointestinal involvement with progressive systemic sclerosis was evaluated by esophageal manometry and by routine roentgenographic series of the small bowel. Fecal fat excretion measurement, the D-xylose absorption test, and a small-intestinal biopsy procedure were carried out. Duodenal juice was cultured and bacterial counts were estimated. One-third of the patients had reduced exocrine pancreatic function, but only four patients had unequivocally a reduction that could be of clinical importance. The results obtained with the meal test were in accordance with the secretin-cholecystokinin test, indicating a preserved capacity for endogenous stimulation.

Concentrations of human pancreatic polypeptide (HPP) in serum were measured in the fasting state and after a meal in 19 control subjects and 24 patients with chronic pancreatitis (CP). The severity of CP was characterized on the basis of the duodenal lipase concentration after a test meal (Lundh test). Basal and postprandial HPP concentrations were significantly (p less than 0.01) decreased in severe and moderate chronic pancreatitis and in diabetes secondary to pancreatitis. There was only a weak correlation (r = 0.44; p less than 0.05) between exocrine secretion and delta HPP in CP. Fifty-eight percent of patients with CP had serum concentrations of HPP within the normal range, limiting the value of serum HPP measurement in the diagnosis of CP.

The exocrine pancreatic function was studied in 460 patients suffering from dyspepsia (defined as abdominal pain, chronic diarrhoea, and/or weight loss) by measuring the duodenal concentrations of amylase and lipase after a test meal (Lundh test). In 159 of the patients (35 per cent) a reduced pancreatic function was found. In 143 out of these a diagnosis of possible or verified chronic pancreatitis was made. In about half of these 143 patients, the diagnosis chronic pancreatitis was clinically unexpected. Consequently, chronic pancreatitis is to be suspected as a cause of dyspepsia when more usual causes have been excluded.

Glucose tolerance and B cell function were assessed in 30 consecutive chronic alcoholic patients without overt diabetes mellitus. Plasma glucose, insulin, and C peptide concentrations were measured during an oral glucose tolerance test. All patients underwent a liver biopsy and an exocrine pancreatic function test (Lundh test). Compared with the controls, the three groups of alcoholic patients (those with histologically normal livers, n = 12; those with steatosis, n = 10; and those with cirrhosis, n = 8) all had a two-fold increase in plasma concentrations of insulin as well as C peptide in the fasting state, despite normal fasting levels of glucose. After oral glucose all groups of patients had elevated plasma levels of glucose, insulin, and C peptide compared with the controls. The C peptide/insulin ratio was similar to that in the controls in all groups of alcoholics. Patients with decreased exocrine pancreatic function (n = 7) had a significantly lower insulin and C peptide response to glucose than the patients with normal exocrine pancreatic function. It is concluded that (1) chronic alcoholics even with histologically normal livers have endogenous insulin resistance, and (2) associated damage to the exocrine pancreas is more common than previously recognized and decompensation of B cell function could be demonstrated in patients with decreased exocrine pancreatic secretion.

To study the effects of trypsin on the pancreaticobiliary secretion and the release of secretin and cholecystokinin (CCK) to plasma, seven normal subjects were stimulated twice with duodenal perfusates containing 20 mM oleic acid (pH 6.0) with and without 1 g of bovine trypsin added per liter. In addition, six patients with advanced pancreatic insufficiency who received only the oleic acid were compared with eight normal subjects. The concentrations of secretin and CCK in plasma and the pancreatic enzyme and volume secretions were unaffected by the addition of trypsin, but the initial bile acid output and the bicarbonate secretion in the period after gallbladder emptying were reduced during perfusion with trypsin. The severely reduced enzyme secretion in chronic pancreatitis did not influence the basal or oleic acid-stimulated concentrations of the hormones in plasma. The study does not support the hypothesis of a trypsin-mediated negative feedback control of human pancreatic enzyme secretion. Furthermore, the reduced duodenal output of bicarbonate found in response to trypsin is not explained by changes in the release of secretin or CCK.

A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min periods. An inert, water-soluble marker (58Co-vitamin B12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine pancreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspirate did not vary significantly between consecutive 10-min periods during the last 20 min of the secretin stimulation period or during the last 50 min of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker is a closer estimate of the true volume than that obtained by the usual aspiration technique without a volume indicator.

The pancreatic response to physiological concentrations of secretin obtained after minute boluses of exogenous secretin was studied in 16 normal volunteers. Output of bicarbonate into the duodenum was measured by duodenal aspiration in 5 subjects and by endoscopic cannulation of the pancreatic duct in 11 subjects. Pure natural porcine secretin was injected intravenously in doses of 125, 250, and 500 fmol x kg-1 body weight (0.0013, 0.0027, and 0.0054 clinical units x kg-1). All three doses of secretin increased plasma secretin concentration, duodenal bicarbonate concentration, and duodenal bicarbonate output significantly. The bicarbonate output measured by the two techniques did not differ significantly. The increments in median plasma secretin concentration were 1.6, 3.0, and 6.4 pmol x 1(-1) after secretin, 125, 250 and 500 fmol x kg-1, and the corresponding 15-min bicarbonate output 283, 442, and 1435 micromol, respectively. The concentrations of secretin in plasma found after these doses of secretin are of the same order of magnitude as the secretin concentrations found during physiological conditions in man. It is concluded that the physiological concentrations or secretin influence pancreatic bicarbonate secretion.

The material comprises 25 patients with gluten-induced enteropathy and 16 patients with various intestinal disorders. The intestinal contents were aspirated in four subsequent periods of 20 minutes each after ingestion of a standard meal. The volume, pH, and the concentration of alpha-amylase, trypsin, chymotrypsin, and lipase were determined in the collections. Only minor deviations from normal pH-levels were observed. In both groups of patients, the secretion of lipase, and to a minor degree that of amylase, were more markedly reduced than the secretion of the proteolytic enzymes. With the exception of the values of trypsin, concentrations of enzymes were seen to be below the lowest normal value in approximately one-third of the patients throughout the period of digestion. It is concluded that the pancreatic function was genuinely reduced in several patients with enterogenous malabsorption. It may be explained as an unspecific effect of the malabsorption.

The material comprises 34 patients with anicteric biliary diseases, 20 with obstructive jaundice, 8 with hepatic cirrhosis, and 3 with haemochromatosis. The intestinal contents were aspirated in four subsequent periods of 20 minutes each after ingestion of a standard meal. The volume, pH, and the concentration of alpha-amylase, trypsin, chymotrypsin and lipase were determined in the collections. The concentration of lipase was more markedly reduced than concentrations of amylase and of trypsin in patients with anicteric biliary diseases and in patients with hepatic cirrhosis. Concentrations of enzymes below the lowest normal value throughout the period of digestion represented an uncommon finding. The exocrine pancreatic function is rarely found to be reduced in patients with biliary or with hepatic disorders.

1. In accordance with the admixture theory of the exocrine pancreatic secretion a linear relation between concentrations of bicarbonate and protein in the pancreatic juice is to be expected.2. Pancreatic juice was obtained through a Thomas cannula in three unanaesthetized dogs during digestion of a meal.3. The actual concentration of bicarbonate and protein showed a good approximation to a straight-line relation.4. The calculated concentration of bicarbonate in the distal secretion was nearly identical with the highest concentration of bicarbonate obtained in the pancreatic juice after stimulation with secretin.

This study comprises 39 patients with duodenal ulcer, 113 patients with partial gastrectomy, 9 with total gastrectomy and 6 patients with gastroenterostomy. After ingestion of a standard meal the intestinal contents were collected during 4 subsequent periods of 20 minutes each. The volume, pH, and the concentrations of alpha-amylase, trypsin, chymotrypsin, and lipase in the collections were determined. The pH was not below normal in patients with duodenal ulcer. The results indicated an admixture of salivary to pancreatic amylase in the intestine of patients with gastrojejunostomy, especially by concomitant hypochlorhydria. In all groups of patients, secretions of trypsin and chymotrypsin were closely related. In patients with partial or total gastrectomy, the secretion of lipase was more markedly reduced than the secretion of the other enzymes. The mean concentration of lipase in the efferent loop in Billroth II patients was found to be closely related to the fat absorption. Depending on the enzyme concerned, 10-20 per cent of the patients with duodenal ulcer, and 21-50 per cent of the patients subjected to Billroth II gastrectomy had abnormally low concentrations of enzymes in all collections. In these groups of patients, the mean concentration of the four enzymes was significantly reduced in all collections. In patients exposed to Billroth I gastrectomy, gastroenterostomy, or total gastrectomy, mean concentrations of the enzymes were below normal levels in collection I only.