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In this study, we developed a sensitive method for monitoring α-amylase using a fluorogenic approach based on the host-guest complexation between an amphiphilic pyrenyl derivative (1) and γ-cyclodextrins (γ-CDs). The compound 1 self-assembles into nanofibrils in aqueous solutions. Upon the introduction of γ-CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2 : 2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α-amylase, γ-CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α-amylase in human urine, offering a practical approach for early screening of pancreatic-related diseases., (© 2024 Wiley-VCH GmbH.)

Benign pancreatic hyperenzymemia, also known as Gullo's syndrome, is a little-known syndrome first described in 1996 in patients studied for an elevation of pancreatic enzymes while otherwise being asymptomatic. We describe the case of a 2-year-old patient who was found to have significant elevation of amylase and lipase levels while he was asymptomatic. Blood tests and imaging tests were performed to determine the etiology, but they gave normal results. The enzyme elevation can even be 10 times the normal value of the enzyme, and only 1 enzyme may elevate, although most often all pancreatic enzymes are elevated. The etiology is not known, although several hypotheses have been suggested. This enzyme elevation is described both in adults and children and also sporadically or with a familial pattern. Knowledge of it can limit the performance of the multiple complementary test, some of which are very invasive in patients who have elevated pancreatic enzymes while they are asymptomatic. It knowledge allows us to confirm a benign prognosis about it and reassure the family about this disease and that in the end it will not require aggressive treatments such as surgery or chemotherapy., (© American Society for Clinical Pathology 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: The purpose of this study was to clarify whether fatty pancreas might lead to impaired pancreatic endocrine or exocrine function., Material and Methods: The study involved 109 participants who had undergone the glucagon stimulation test and N-benzoyl-L-tyros-p-amino benzoic acid (BT-PABA) test to assess pancreatic function as well as unenhanced abdominal computed tomography (CT). Pancreatic endocrine impairment was defined as ΔC peptide immunoreactivity less than 2 [mmol/L] in the glucagon stimulation test, and pancreatic exocrine impairment was defined as a urinary PABA excretion rate less than 70% on the BT-PABA test. We defined as the mean CT value of pancreas / CT value of spleen (P/S ratio) as a marker to assess fatty pancreas. We analyzed the association between fatty pancreas and pancreatic impairment using the logistic regression model. The odds ratio (OR) is shown per 0.1 unit., Results: Pancreatic endocrine function was impaired in 33.0% of the participants, and 56.9% of those were regarded as having pancreatic exocrine impairment. The P/S ratio was significantly correlated with pancreatic endocrine impairment in univariate analysis (OR = 0.61, 95% confidence interval (CI) = 0.43-0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95% CI = 0.22-0.61, P < .0001) for all participants. Similar significant relationships were observed in both univariate (OR = 0.70, 95% CI = 0.49-0.99, P = 0.04) and multivariate (OR = 0.39, 95% CI = 0.21-0.66, P = 0.0002) analyses for the participants without diabetes (n = 93). The amount of pancreatic fat was not associated with exocrine impairment in univariate analysis (OR = 0.80, 95% CI = 0.59-1.06, P = 0.12)., Conclusion: Fatty pancreas was associated with pancreatic endocrine impairment but did not have a clear relationship with pancreatic exocrine impairment., Competing Interests: The authors have declared that no competing interests exist.

Graft survival after pancreas transplantation alone (PTA) is significantly poorer than graft survival after simultaneous pancreas kidney (SPK) and is particularly affected by difficulty in monitoring rejection. Exocrine bladder drainage allows assessment of pancreas graft function as urinary amylase (UA). However, standards for UA collection and interpretation are not well defined. In this study, 21 bladder-drained PTA recipients were monitored with daily values for UA and urine creatinine (Creat) concentration from post-transplant 10-mL samples and 24-h collections. Clinical events were documented and correlated to UA measurements. UA values were found to increase post-transplant until day 15, and large interpatient variability was noted (median 12 676 IU/L, range 668-60 369 IU/L). A strong correlation was found total 24-h UA production and spot UA/Creat ratio (r = 0.80, p < 0.001). UA/Creat ratio showed less variation during episodes of impaired renal function; therefore, urinary amylase baseline was defined as the median UA/Creat ratio after day 15. A > 25% decrease of UA predicted 9/13 (69%) events. We conclude that individual baselines should be set once the values have stabilized after 15 d post-transplant and that spot UA/Creat measures are reliable, patient friendly and indicate potential events after PTA., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The proteome varies with physiologic and disease states. Few studies have been reported that differentiate the proteome of those with pancreatic cancer., Aim: To apply proteomic-based technologies to body fluids. To differentiate pancreatic neoplasia from nonneoplastic pancreatic disease., Methods: Samples from 50 patients (15 healthy (H), 24 cancer (Ca), 11 chronic pancreatitis (CP)) were prospectively collected and underwent analysis. A high-throughput method, using high-affinity solid lipophilic extraction resins, enriched low molecular weight proteins for extraction with a high-speed 200-Hz matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-MS; Bruker Ultraflex III). Samples underwent software processing with FlexAnalysis, Clinprot, MatLab, and Statistica (baseline, align, and normalize spectra). Nonparametric pairwise statistics, multidimensional scaling, hierarchical analysis, and leave-one-out cross validation completed the analysis. Sensitivity (sn) and specificity (sp) of group comparisons were determined. Two top-down-directed protein identification approaches were combined with MALDI-MS and tandem mass spectrometry to fully characterize the most significant protein biomarker., Results: Using eight serum features, we differentiated Ca from H (sn 88%, sp 93%), Ca from CP (sn 88%, sp 30%), and Ca from both H and CP combined (sn 88%, sp 66%). In addition, nine features obtained from urine differentiated Ca from both H and CP combined with high efficiency (sn 90%, sp 90%). Interestingly, the plasma samples (considered by the Human Proteome Organization to be the preferred biological fluid) did not show significant differences. Multidimensional scaling indicated that markers from both serum and urine led to a highly effective clinical indicator of each specific disease state., Conclusions: The proteomic analysis of noninvasively acquired biological fluids provided a high level of predictability for diagnosing pancreatic cancer. While the proteomic analysis of serum was capable of screening individuals for pancreatic disease (i.e., CP and Ca vs. H), specific urine biomarkers further distinguished malignancy (Ca) from chronic inflammation (CP).

The aim of this study was to estimate the benchmark dose (BMD) for pancreas dysfunction caused by cadmium (Cd) exposure in smelters. Smelter workers who had been exposed to Cd for more than 1 year and matching nonoccupationally exposed subjects were asked to participate in this study. Urinary cadmium (UCd) was used as a biomarker for exposure, serum insulin and amylase were used as biomarkers for pancreatic effects. In this study, serum insulin and amylase were lower in the smelter workers than in the nonoccupationally exposed subjects. A significant dose-response relationship with UCd was displayed. BMDs in terms of urinary Cd corrected for creatinine were calculated by use of BMDS (version 1.3.2). The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that the BMDL10 for serum insulin and serum amylase was 3.7 and 5.3 microg/g Cr, respectively. Compared to the BMDL for renal damage caused by Cd exposure, identified by the effect biomarkers urinary beta2-microglobulin, urinary N-acetyl-beta-glucosaminidase, and urinary albumin (UALB), it was shown that BMDL10 for serum insulin is the lowest among all values and UALB gave the highest value (5.8 microg/g Cr). This study indicates that Cd exposure can result in pancreatic dysfunction and the effect appears at lower urinary Cd level than renal dysfunction. The endocrine function of the pancreas was affected at lower urinary levels of Cd, compared to the exocrine function, which was seen at higher urinary levels of Cd than those giving rise to renal tubular dysfunction.

Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

The purpose of the study reported here was to assess 3 commonly used screening tests for hyperadrenocorticism (low-dose dexamethasone suppression test, ACTH stimulation test, and urinary cortisol:creatinine ratio) in dogs with various diseases other than those of the adrenal glands (nonadrenal diseases). A group of 100 dogs was studied: 59 dogs with nonadrenal disease, 21 clinically normal dogs, and 20 dogs with pituitary-dependent hyperadrenocorticism. Of 59 dogs with nonadrenal disease, 20 (34%) had high baseline cortisol concentration (greater than reference range limits), and 22 (38%) and 33 (56%) had inadequate serum cortisol suppression at 4 and 8 hours, respectively, after administration of a low dose of dexamethasone. Compared with clinically normal dogs, dogs with nonadrenal disease had significantly (P < 0.05) higher mean serum cortisol concentration at 4 and 8 hours after administration of a low dose of dexamethasone; however, significant differences were not detected between the mean cortisol concentration at 8 hours after administration for dogs with nonadrenal disease and for dogs with hyperadrenocorticism. After ACTH stimulation, only 8 of 59 (14%) dogs with nonadrenal disease had high serum cortisol concentrations. Significant differences did not exist after ACTH stimulation between mean cortisol concentration of clinically normal dogs and that of dogs with nonadrenal disease. Of 59 dogs with nonadrenal disease, 45 (76%) had a high urinary cortisol:creatinine ratio. When compared with clinically normal dogs, dogs with nonadrenal disease had a significantly higher mean urinary cortisol:creatinine ratio, but significant differences did not exist between the mean urinary cortisol:creatinine ratio of dogs with nonadrenal disease and that of dogs with hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)

Although patients with chronic renal failure have a high incidence of chronic pancreatic disease, the condition is frequently overlooked. We have modified the pancreolauryl test--an indirect pancreatic function test--for anuric patients. The test permitted good discrimination between patients with chronic pancreatic disease and those with a normal pancreas when serum levels of fluorescein were measured 10 h after administration with a standard meal. The sensitivity at this time interval was 80% and the specificity 83%. We conclude that the pancreolauryl test with serum measurements provides a simple, noninvasive, and reliable diagnostic test for chronic pancreatic disease in anuric patients with chronic renal failure.

We have employed an oral test of pancreatic digestive function using fluorescein dilaurate (a substrate for pancreatic cholesterol ester hydrolase), administered together with pancreatic enzyme supplements, in order to test the hypothesis that urinary excretion of fluorescein provides a simple method for determining the optimal dose of oral pancreatic enzymes. Commercially available pancreatic enzyme supplements had negligible cholesterol hydrolase activity in vitro, and did not increase the urinary excretion of fluorescein when administered together with fluorescein dilaurate in 16 patients with pancreatic exocrine insufficiency. Inhibition of gastric secretion by ranitidine resulted in a statistically significant increase in urinary fluorescein excretion during the fluorescein dilaurate test. The fluorescein dilaurate test is not, therefore, suitable for determining the effectiveness of oral pancreatic enzyme replacement therapy. Moreover, the manufacturer's advice to stop oral pancreatic enzyme therapy for 5 days before performing the fluorescein dilaurate test appears unnecessary, since oral pancreatic enzymes do not alter test results.

Urinary indican excretion was studied in 5 patients with steatorrhoea of pancreatic origin, 4 patients with steatorrhoea due to other causes, and 5 normal subjects. Treatment with pancreatic extract resulted in an immediate increase in indican excretion to above the normal range in patients with steatorrhoea due to pancreatic insufficiency. Administration of pancreatic extract did not result in a rise in the patients with steatorrhoea not due to pancreatic insufficiency, or in the normal subjects. In one patient with pancreatic insufficiency maintained on a low protein diet, the rise in indican excretion on replacement therapy was much slower and did not reach as high a level as in the patients on a normal protein diet. The possible mechanisms underlying these observations are discussed. It is suggested that the finding of a low indican excretion in the presence of steatorrhoea and its rise to above normal on pancreatic enzyme therapy is strongly suggestive of exocrine pancreatic insufficiency.

The multiple amylases of the urine were examined in healthy persons and in patients with acute and chronic pancreatitis as well as with parotitis using the polyacryl amide gel disk electrophoresis. A separation into about 7 amylase-containing fractions was achieved which could be coordinated to the pancreatic juice and to saliva. In acute pancreatitis the pancreas amylases increased, in chronic pancreatitis, on the other hand, they decreased. In parotitis the salivary amylases increased. For diagnostic purposes the formation of quotients from certain fractions was useful. The examination of the multiple amylases of the urine according to the method mentioned leads to an improved clinico-chemical diagnostics of diseases of the exocrine pancreas and gives the possibility of their course control.

We describe and evaluate two frequently used indirect methods for assessing exocrine pancreatic function: the N-benzoyl-L-tyrosyl-p-aminobenzoic acid test (NBT-PABA) and the pancreolauryl test. In both procedures, the patient is orally administered a substrate that is metabolized into two or more products by pancreatic enzymes. At least one of the reaction products is absorbed from the gut, conjugated, and excreted in urine, where it can be measured. Both tests can be used in the diagnosis and monitoring of cystic fibrosis, chronic pancreatitis, and pancreatic carcinoma, and in monitoring pancreatic enzyme replacement therapy to determine the appropriate dose. In comparison with the NBT-PABA procedure, the pancreolauryl test seems to have better specificity and sensitivity, undergoes almost no interference from other drugs or serum compounds, requires no complex hydrolytic conditions, and is independent of renal function.

Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterin levels were related to the clinical activity of the viral disease. In patients with nonviral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.

24-hour urinary outputs of oxalate, calcium, and magnesium have been determined in a total of 62 children aged 3 months to 17 years who fell into the following groups: (i) 16 normal controls, (ii) 3 with primary hyperoxaluria, (iii) 9 with small and/or large intestinal resections, (iv) 9 with untreated coeliac disease, (v) 5 with pancreatic dysfunction, and (vi) a miscellaneous group of 20 children with a variety of intestinal disorders. Taken as a whole, 58% of patients with intestinal disorders had hyperoxaluria, and of these 7% had urinary outputs of oxalate which fell within the range seen in primary hyperoxaluria. The proportion of children with hyperoxaluria in the different diagnostic groups was as follows: intestinal resections (78%), coeliac disease (67%), pancreatic dysfunction (80%), and miscellaneous (45%). 35% of the patients with hyperoxaluria had hypercalciuria, whereas magnesium excretion was normal in all subjects studied. In 2 patients treatment of the underlying condition was accompanied by a return of oxalate excretion to normal. These results indicate that hyperoxaluria and hypercalciuria are common in children with a variety of intestinal disorders, and that such children may be at risk of developing renal calculi without early diagnosis and treatment.

The semiquantitative determination of amylase in urine with a stick-method has produced controversial results as to its diagnostical significance. In our study we compared the result of the Rapignost-test with the simultaneously measures activity of enzymes (total amylase, pancreatic isoamylase in serum and urine and lipase) in 323 samples of serum and urine taken from 32 patients affected with acute pancreatitis. On the 1st day of hospitalization Rapignost was positive in only 17 out of 32 cases. Both sensitivity and specificity of the test depended of the values referred to. Near range limits and in cases with slight or average increase of the enzymes, the correspondence of Rapignost results were unsatisfactory. We found a good correspondence in cases with normal low and excessively high values of the enzymes. On the whole, Rapignost showed the best correspondence with the pancreas isoamylase in urine. The result of Rapignost was also positive in 5 out of 15 cases with extrapancreatic increased urinary amylase, which confirms its lack of organ specificity. From case to case, the -, and + + test results of Rapignost did not lead to any conclusions as to the absolute values of the enzymes in serum and urine. Our results show that Rapignost does not offer enough safety either to confirm or to exclude an acute pancreatitis, and especially it should not be used as a screening test in emergency diagnostics. The determination of the enzyme, in particular in serum, can not be eluded.

The laboratory determination of serum and urine amylase activity is commonly requested by the Emergency physician. While depressed levels are occasionally seen, they are almost always secondary to chronic pancreatitis and pancreatic destruction. The typical abnormality is an elevation that may represent a normal physiologic process, a benign inflammation, the concomitance of ongoing disease, or an emergent problem. The differential diagnosis of hyperamylasemia is difficult, but most high levels are caused by pancreatitis and biliary tract disease. Serial determinations of amylase levels, as well as simultaneous assessments of urine and serum amylase, may be useful in determining the source of the problem. The laboratory methods for measurement are many and varied, reflecting the lack of a perfect test. Because of the different procedures, confusion has ensued over the units of description and the normal or reference ranges. Any standard equipped medical laboratory should be able to determine amylase activity in both serum and urine in a timely fashion. The average cost per amylase determination is $17.75. The actual time to perform the test in the laboratory is approximately 7.5 minutes, though turnaround times usually exceed 1 hour. The fractionation of amylase into isoenzymes is a sophisticated procedure requiring equipment not routinely found in a typical hospital laboratory.

The ratio between urinary clearance of cathodic trypsin-like immunoreactivity and creatinine clearance (CTr/CCr ratio) was evaluated as a test for pancreatic cancer in patients with chronic pancreatic diseases and gastrointestinal diseases clinically mistakable for pancreatic cancer. The efficiency of the CTr/CCr ratio in the diagnosis of pancreatic cancer was no better than the urinary clearances of albumin and beta2-microglobulin to creatinine clearance (CA1b/CCr ratio and C beta 2m/CCr ratio). An overall positive association was found between the three ratios. Furthermore, there was a positive relationship between proteinuria and elevation of any of the ratios--as well as between proteinuria and the degree of cancer dissemination. The latter was positively associated with elevation of any of the three ratios. The results point to a changed renal handling of proteins due to cancer disease per se as the mechanism causing elevated CTr/CCr ratios in pancreatic cancer.

P-Amino-benzoic acid (PABA) is split specifically by pancreatic chymotrypsin from the synthetic tripeptide N-benzoyl-L-tyrosyl-PABA. The urinary excretion of absorbed PABA serves as an index for exocrine pancreatic function. The peptide (0.015 g/kg) was administered orally to 20 controls (aged between 5 months and 16 years), 6 patients with exocrine pancreatic insufficiency caused by cystic fibrosis (CF), and 9 newborn infants. In the controls the mean 6-hour PABA recovery was 58.5% (+/- 11.2 SD). Recovery in patients with CF was lower (P less than 0.001) with no overlap. In newborn infants the mean 6-hour PABA recovery was 23.4 (+/- 17.7 SD); overlapping in 3 instances with the results in CF patients. This simple, noninvasive test thus appears promising and merits further investigation in younger infants, especially newborns.

The assessment of exocrine pancreatic function by the oral administration of a chymotrypsin labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) has proved to be an easy and reliable test of exocrine pancreatic function. It has the additional advantage that it can be used to study exocrine pancreatic function in all operative cases, even after gastrointestinal reconstruction. The recovery of p-aminobenzoic acid (PABA) correlates significantly with parameters of the PZ/CCK secretin (PS) test. Following Billroth II gastrectomy, the recovery of PABA decreased to 39.8 +/- 3.2% two weeks after and to 45.4 +/- 4.5% one to two months after operation, significantly lower than the 80.6 +/- 3.4% in normal subjects. In cases of cancer of the head of the pancreas, the exocrine function was 44.0 +/- 3.7%, and decreased to 17.5 +/- 3.0% after total pancreatectomy. Thus, BT-PABA enables a pertinent evaluation of pancreatic function in postoperative patients with various types of gastrointestinal reconstruction and also in cases when the PS test cannot be feasibly used.

The synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid is specifically cleaved by chymotrypsin to Bz-Ty and PABA. The liberated PABA is absorbed and excreted in the urine. Accordingly, PABA recovery reflects intraluminal chymotrypsin activity and is an index of exocrine pancreatic function. This test was evaluated in 24 patients with cystic fibrosis to determine its role in the diagnosis of exocrine pancreatic insufficiency. Cumulative percent PABA recovery in six hours was significantly lower in CF patients compared with the control group. No overlap was noted between the two groups. There was good correlation between PABA recovery, fecal chymotrypsin activity, and coefficient of fat absorption. These findings indicate that PABA recovery is significantly reduced in patients with CF and steatorrhea and may prove a practical and reliable test of pancreatic insufficiency.

Urinary oxalate excretion was measured in healthy persons and patients with Crohn's disease, colitis ulcerosa, sprue and other diseases accompanied with malabsorption, and patients with insufficiency of the exocrine pancreas gland. Further measurements were made in patients after resection of parts of the small intestine or the colon. We found a clear increase of urinary oxalate excretion in patients with resected parts of the small intestine, sprue or other malabsorption syndromes. In 4 patients with resected parts of small intestine or pancreas we even found urolithiasis. Urinary oxalate excretion correlated significantly with steatorrhoea and increased if larger parts of small intestine were resected. Increased resorption of oxalate from food causes increased urinary excretion. Details about the patho-mechanism of this increased excretion are not known yet; an important factor seems to be the reduced absorption of fat in the small intestine.

The large number of pancreas tests recommended today shows that no single method is satisfactory. In general, the rule holds that invasive methods are relatively conclusive and non-invasive are unreliable. In this report it is shown that by a rational combination of simple tests, a reliable procedure for pancreatic diagnosis in about 75% of cases is possible for the general practitioner. The methods described in recent years, such as scintigraphy, ultrasonography, angiography and retrograde pancreaticography are complicated and require great experience. In combination, they raise the accuracy to about 95%. Individual investigators can specialize in only one or a few of these methods. Diagnosis of pancreatic conditions which exceed the facilities of the doctor in practice is only possible in large centers or through co-operation of several specialists.

Using an immunoenzymatic method, we studied lipase in the serum and urine of 23 controls, 22 chronic pancreatitis patients in symptomatic remission, and in 9 patients with proven pancreatic cancer. Serum and urine lipase and its fractional urinary clearance were compared with those of amylase and immunoreactive trypsin. Lipase immunoreactivity was detectable in the urine of 81.5% of the studied subjects (controls: 82%, chronic pancreatitis: 86%, pancreatic cancer: 66%); its output was higher than the upper limit of controls in 31.8% of chronic pancreatitis and in only 1 of pancreatic cancer, and it was significantly correlated with the urinary output of trypsin (r = 0.487, P less than 0.001), but not with that of amylase. A significant correlation was found between urinary output and serum levels for lipase, but not for trypsin or amylase. Fractional clearance of lipase was of the same magnitude as that of trypsin but only 0.1% that of amylase. 19% of chronic pancreatitis and pancreatic cancer showed a fractional clearance of lipase above the upper limit of controls, compared with 45% for trypsin and 3.2% for amylase. No difference in urinary clearance of the three enzymes was found between chronic pancreatitis and pancreatic cancer. In conclusion, although of no diagnostic relevance in pain-free patients with chronic pancreatic disease, this measurement can provide information on the mechanisms of renal excretion of pancreatic enzymes.