Severe Pancreatic Insufficiency Research Articles

Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency.

Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency in childhood. The aim of the present study is to evaluate the correlation between genotype and exocrine pancreatic insufficiency in CF patients. The special emphasis was put on the analysis of mild CFTR mutations. The study comprised 394 CF patients and 105 healthy subjects (HS). Elastase-1 concentrations were measured in all subjects. Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DeltaF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717-1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DeltaI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 + 1G-A, E92GK, E217G, 2789 + 5G-A. 3849 + 1kbC-T/3849 + 1kbC-T) genotype resulted in high elastase-1-values. However, in case of patients with genotype DeltaF508/3849 + 10kbC-T, 1717-1GA/3849 + 10kbC-T as well as with DeltaF508/R334W, both high and low elastase-1 concentrations were found. Low E1 values were found in a patient with DeltaF508/R347P genotype. Patients who carry two 'severe' mutations develop pancreatic insufficiency, whereas those who carry at least one 'mild' usually remain pancreatic sufficient. However, the presence of one mild mutation does not exclude pancreatic insufficiency.

Pancreatic enzyme replacement therapy.

Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus.

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 patients with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenetic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.

Behaviour of serum pancreatic enzymes in chronic pancreatitis

Aim. To establish whether serum pancreatic enzyme determination is useful in the identification of patients with chronic pancreatitis and in revealing the presence of exocrine pancreatic insufficiency. Patients and methods. A total of 50 patients with chronic pancreatitis were included in the investigation: 19 were studied during a painful attack of the disease and 31 were observed during clinical remission of the disease and underwent a secretin-caerulein test; 21 of the 31 patients had severe pancreatic insufficiency. Thirty patients with non pancreatic digestive diseases were also studied. Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase-1 were determined in all patients. Results. Serum levels of the 5 enzymes studied were significantly higher in patients with pancreatic pain than in those studied during a clinical remission of the disease, and in those with non-pancreatic digestive diseases. In patients with chronic pancreatitis studied during clinical remission of the disease serum levels of pancreatic isoamylase and trypsinogen were significantly lower than in those patients with non-pancreatic digestive diseases. Considering only low serum concentrations of the five enzymes studied in diagnosing chronic pancreatitis, trypsinogen showed a sensitivity of 28%, specificity of 100%, a predictive value of a positive test of 100% and a predictive value of a negative test of 96.4%. In the 21 patients with severe pancreatic insufficiency, abnormally low serum concentrations of trypsinogen were found in 12 patients (57%), of lipase and elastase-1 in 6 (29%), of pancreatic isoamylase in 5 (24%), and of amylase in 3 (14%). Conclusions. Serum pancreatic enzymes can not be considered a useful tool to identify patients with pancreatic insufficiency. However, of the five enzymes studied, serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis.

Partial CFTR genotyping and characterisation of cystic fibrosis patients with myocardial fibrosis and necrosis.

Myocardial necrosis and fibrosis is a rare complication of cystic fibrosis (CF) causing sudden and unexpected death in infancy due to cardiac arrest. Characteristic morphological lesions are recognisable postmortem. The 18 CF patients with this complication had varied clinical features including mild pulmonary involvement, early onset severe pancreatic insufficiency, and profound electrocardiogram (ECG) changes. In this group of patients, 5 were deltaF508 homozygotes, 1 was deltaF508/ N1303K and 1 was a deltaF508/M compound heterozygote. A pair of affected siblings (deltaF508 homozygotes) were fully concordant for myocardial involvement and for the general course of the disease. The co-existence of a genetic predisposition to myocardial lesions resulting most probably from severe cystic fibrosis transmembrane (CFTR) genotypes (such as deltaF508/deltaF508, deltaF508/N1303K) and deficiency of certain trophic factors necessary for metabolism of the myocardium, are postulated to cause myocardial complications in CF leading to circulatory failure and early death.

Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease.

Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the detrimental effects of nutrient deficiency, profound alterations of upper gastrointestinal secretory and motor functions may be an additional and hitherto underestimated consequence of increased nutrient delivery to distal intestinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. Modern enteric-coated pancreatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. However, lipid digestion cannot be completely normalized in most patients by current standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior therapeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutrient digestion in health and chronic pancreatitis. Second, rationale, current standards, options, and future aspects of enzyme replacement therapy are discussed.

Serum lipase levels pre and post Lundh meal: evaluation of exocrine pancreatic status in cystic fibrosis.

Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C-->T); group C, 17 healthy individuals. Basal lipase levels were 2-16.5, 16.4-73, and 8.5-27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.

Altered postprandial motility in chronic pancreatitis: Role of malabsorption

BACKGROUND & AIMS: Intraileal nutrients modulate gastrointestinal motility, but effects of maldigestion on postprandial motility are unknown. The aim of this study was to compare motor responses with ileal nutrient exposure in health and pancreatic insufficiency after a meal or intraluminal perfusion. METHODS: After oroileal multilumen intubation for duodeno-jejuno-ileal sampling, marker perfusion, and motility recording, 14 normal subjects and 12 patients with severe pancreatic insufficiency received a labeled liquid meal twice, either with placebo or pancreatin. Effects of intraileal nutrient perfusion on fed motility induced by duodenal amino acid perfusion were also investigated. RESULTS: Compared with normals, untreated patients had greater cumulative ileal nutrient delivery (69 +/- 21 vs. 487 +/- 232 kJ), shorter fed pattern (196 +/- 22 vs. 131 +/- 14 minutes), greater 90% gastric emptying (163 +/- 12 vs. 128 +/- 10 minutes), and faster small intestinal transit (86 +/- 9 vs. 44 +/- 6 minutes). Pancreatin reversed these changes. Ileal nutrient perfusion converted fed into interdigestive-like motility in normals (7 of 8) and patients (4 of 5). CONCLUSIONS: In subjects with pancreatic insufficiency, a low-energy liquid meal induces shorter fed motor pattern associated with accelerated gastric emptying and intestinal transit compared with healthy subjects. Because changes responded to enzyme treatment and could be reproduced by ileal nutrient perfusion, ileal delivery of malabsorbed chyme may be involved as a mechanism. (Gastroenterology 1997 May;112(5):1624-34)

Plasma Concentrations of Cholecystokinin and Neurotensin in Patients with Cystic Fibrosis

Background: Regulation of pancreatic exocrine secretion is controlled by vagovagal reflexes and hormones. A negative feedback control mechanism exists between the intraduodenal protease concentration and pancreatic enzyme secretion. In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks postprandial secretion. Neurotensin is released postprandially by nerval reflexes and fat. It has been claimed that both hormones are increased in patients with pancreatic insufficiency. Methods: We investigated CCK and neurotensin levels in patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2–24 years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5–24 years old) with cystic fibrosis without pancreatic insufficiency pre-and post-prandial CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme therapy had been withdrawn. Nine patients (3–14 years old) who had no complaint of abdominal disease served as controls. Results: Basal and postprandial CCK plasma levels did not differ statistically in the three groups, whereas basal and postprandial neurotensin levels were significantly increased in the cystic fibrosis groups. The severity of the disease had no effect on the neurotensin levels. Conclusions: Cystic fibrosis patients with severe pancreatic insufficiency did not have increased CCK plasma levels, suggesting that a CCK-mediated feedback mechanism of pancreatic enzyme secretion does not operate in our patients. In contrast, basal and postprandial neurotensin plasma levels were significantly increased in patients with cystic fibrosis but were independent of the severity of the pancreatic insufficiency.

Ursodeoxycholic acid for liver disease associated with cystic fibrosis: A double-blind multicenter trial

Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status. (Hepatology 1996 Jun;23(6):1484-90)

47 SENSITIVITY AND SPECIFICITY OF FECAL ELASTASE 1 IN CHILDREN: COMPARISON WITH THE SEKRETIN-PANCREOZYMIN-TEST

The determination of fecal concentration of pancreatic elastase 1 (E1) has recently been described as a valuable parameter for estimation of exocrine pancreatic function (Scheefers-Borchel U et al. Lab med 1992;16:427). The aim of our study was the comparison of the E1 concentration in feces with the results of sekretin-pancreozymin-test in CF-patients. Material and Methods: Sensitivity of fecal E1 concentration was determined in 16 CF-patients (median of age 17.3 yr) on pancreatic enzyme replacement therapy. Specificity was assessed in 23 healthy children (median of age 5.7 yr). Fecal E1 was determined with an ELISA based on two monoclonal antibodies against human Elastase 1 (Schebo•Tech GmbH, Wettenberg, Germany). Aliquots of a homogenized 24h-stool-collection were tested. Pancreatic function was classified according to fecal E1 concentration as follows: Table Results and conclusion: According to secretin-pancreozymin-test 15 of the 16 investigated CF-patients had a severe pancreatic insufficiency and only 1 patient was moderately insufficient. The determination of fecal E1 concentration had a sensitivity to (severe) pancreatic insufficiency of 100% and a specificity of 96%. E1 determination in stool seems to be a more sensitive and specific test for pancreatic insufficiency than other indirect tube-less tests. Moreover, pancreatic function can be assessed without interruption of pancreatic enzyme therapy.

Exocrine pancreatic insufficiency after allogeneic bone marrow transplantation

Several reports suggest a relationship between bone marrow transplantation and pancreatic damage. The authors describe two patients with pancreatic insufficiency after bone marrow transplantation. The first patient had weight loss arising from steatorrhea secondary to severe pancreatic insufficiency (lipase output result <3% of normal) due to pancreatic atrophy. The second patient had steatorrhea secondary to intestinal bacterial overgrowth, but moderate pancreatic insufficiency was present (results of trypsin and lipase outputs were 50 and 30% of normal). Before the diagnosis of pancreatic insufficiency, both patients had acute graft vs host disease and the second patient had chronic graft vs host disease. We conclude that graft vs host disease after bone marrow transplantation may damage the pancreas. Patients with persistent malabsorption after bone marrow transplantation should be tested for exocrine pancreatic insufficiency.

Kwashiorkor as early clinical manifestation in a baby with cystic fibrosis

A case of cystic fibrosis in a baby presenting Kwashiorkor (edema, hypoalbuminemia and anemia ) is described. This is a very unusual presentation, easily attributed to unfavourable socio-economic conditions of the population, and classically considered a marker for severe pulmonary disease during the first year of life. Presence of severe pancreatic insufficiency is related to genotype delta F508 (homozygote) but colonization and early infection with Staphylococcus aureus and Pseudomonas aeruginosa in this baby requires further study. Cystic Fibrosis is the most frequent genetic disease among Caucasians, and early diagnosis has prognostic implications, agreed upon by all.

The problem of classification and staging of chronic pancreatitis. Proposals based on current knowledge of its natural history.

Even though the four international meetings held so far on classification of pancreatitis have helped considerably to further our understanding of the disease, all have serious drawbacks that limit their clinical utility. The main problem with the Marseille classifications is the need for histologic proof, and the Cambridge classification relies on imaging modalities that are not sensitive or specific enough. Chronic pancreatic inflammation (CP) has been observed in association with several systemic diseases (such as autoimmune diseases), and since the natural history of the pancreatic affliction in these conditions is clearly distinct from that seen in other forms of CP, these need to be classified separately. Furthermore, many clinical/aetiologic forms of chronic calcifying pancreatitis (CCP) exist which differ sufficiently in their clinical features and management to deserve individual recognition. A subclassification of CCP into alcoholic, tropical, hereditary, hypercalcaemic, hyperlipoproteinaemic, drug-induced, and idiopathic is proposed. The staging of chronic alcoholic pancreatitis has been a controversial issue, mainly because of the apparent unpredictability of the course of pain. However, several large follow-up studies in the past decade suggest that recurrent acute exacerbations dominate the clinical picture in the first few years after onset of symptoms, and progressive pancreatic insufficiency is the predominant feature in the late stages of the disease. On the basis of the results of these studies it is proposed that alcoholic chronic pancreatitis be divided into four stages: I) latent or subclinical, II) early, or stage of inflammatory complications, III) late, or stage of severe pancreatic insufficiency, and IV) advanced, or stage of secondary painless pancreatitis.

Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests

Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test.

The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration.

Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program

Abstract The use of the dried-blood immunoreactive-trypsin assay for the detection of cystic fibrosis in newborns has been questioned on the grounds that it may fail to identify patients with enough pancreatic function to have normal fat absorption. To investigate this possibility, we assessed pancreatic function in 78 patients identified in a neonatal screening program as having cystic fibrosis. The diagnosis of cystic fibrosis was confirmed by abnormal results on a sweat chloride test. The results of measurements of fecal fat excretion, pancreatic-stimulation tests, and estimations of the serum level of pancreatic isoamylase indicated that 29 of the 78 children (37 percent) had substantial preservation of pancreatic function. These children (median age, four years) had growth that was close to normal and comparable to growth in children with severe pancreatic insufficiency who received oral enzyme therapy. Pancreatic insufficiency subsequently developed in 6 of the 29 patients, at 3 to 36 months of age....

Volume and enzyme kinetics of human pancreatic secretion after endogenous stimulation with the lundh test meal

The present study was undertaken to investigate the volume and enzyme kinetics of human pancreatic secretion, after endogenous stimulation with a Lundh test meal, and evaluate the most reliable enzyme and collection period. The prestimulatory volume rates did not differentiate normal from pathologic pancreatic function. After ingestion of the test meal, the immediate increase in volume secretion was identical in healthy subjects and patients with pancreatic insufficiency. The latter showed a drastic reduction of prestimulatory and postprandial enzyme secretion. Cimetidine taken orally 12 and 2 h before the test meal study had no effect on volume and enzyme secretion and endogenous CCK release. Especially in severe pancreatic insufficiency, this modification simplified the performance of the Lundh test. The estimation of lipase and trypsin gave a significant correlation between Lundh test and secretin-cerulein test. The endogenous stimulation by Lundh test meal is a reliable test for routine diagnostic and scientific purposes.

Reversible gall bladder dysfunction in severe pancreatic insufficiency.

The present study was undertaken to examine the intestinal phase of cholecystokinin (CCK) secretion and gall bladder contraction in patients with severe pancreatic insufficiency. Plasma CCK concentrations, measured by radioimmunoassay, and gall bladder contraction by cholescintigraphy were studied in response to intraduodenal fat with and without addition of pancreatic enzymes. Fasting plasma CCK concentrations were in the same range in six patients with pancreatic insufficiency with (2.6 (0.2) pmol/l) and without (2.6 (0.3) pmol/l) addition of pancreatic enzymes and in six healthy subjects (2.0 (0.4) pmol/l). The integrated plasma CCK secretion in response to intraduodenal fat was significantly (p less than 0.005) reduced in the patients without addition of enzymes (46 (13) pmol/1.90 min) compared with healthy subjects (199 (22) pmol/1.90 min), but increased significantly (p less than 0.01) by the addition of pancreatic enzymes (174 (25) pmol/1.90 min) to values not significantly different from healthy subjects. Similarly, gall bladder emptying in response to intraduodenal fat was significantly (p less than 0.01) reduced in patients with pancreatic insufficiency without addition of enzymes (at 90 min: 35 (11)%) compared with healthy subjects (at 90 min: 66 (7)%) but significantly (p less than 0.01) increased by addition of pancreatic enzymes (at 90 min: 70 (8)%) to values not significantly different from healthy subjects. These results indicate that patients with severe pancreatic insufficiency have impaired gall bladder emptying after intraduodenal fat, which can be normalised by the addition of pancreatic enzymes. This impaired gall bladder emptying appears to be the result of a reduced plasma CCK response. Thus, intra-intestinal pancreatic enzymes play an important role in the intestinal phase of CCK secretion and gall bladder emptying.

Clinical Usefulness of Dual-Label Schilling Test for Pancreatic Exocrine Function

The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for [58Co]cobalamin bound to hog R protein and [57Co]cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for [58Co]/[57Co] in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for [58Co]/[57Co] correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor. It suggested that the pancreatic dual-label Schilling test is useful for detecting not only patients with severe pancreatic insufficiency but also the relatively early stage of chronic pancreatitis with bicarbonate secretory dysfunction of the pancreas.