Serum cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis or pancreatic steatorrhea

We compared serum concentrations of cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis (and of pancreatic steatorrhea in the 41 patients with steatorrhea) in 105 patients (57 men, 48 women) consecutively investigated because of clinical suspicion of chronic pancreatitis. Chronic pancreatitis (36 patients), pancreatic steatorrhea (24 patients), and other diseases were diagnosed without knowledge of the serum levels of the three enzymes. When evaluated by means of receiver operating characteristic curves, no differences were found in diagnostic performance of the enzymes with regard to chronic pancreatitis or pancreatic steatorrhea. The sensitivity and specificity for recognition of chronic pancreatitis ranged from 0.306 to 0.444 and from 0.942 to 0.986 when the discrimination values were chosen to give highest efficiencies. The similar ranges for pancreatic steatorrhea were 0.500-0.708 and 0.882-0.941. In conclusion, none of the three enzymes had any advantage over the others as diagnostic tests of chronic pancreatitis or of pancreatic steatorrhea. Only positive test results have clinical importance because of the low sensitivities of the three enzymes.     

Pancreatic hormone secretion in chronic pancreatitis without residual beta-cell function

Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.     

Functional reserve capacity of the exocrine pancreas

The functional reserve capacity of the pancreas, as reflected by the absence of steatorrhea, was correlated with the results of a secretin-pancreozymin test (SPT) in 47 patients with exocrine pancreatic insufficiency due to chronic pancreatitis. The results indicate that a severe reduction in enzyme output (but not in bicarbonate concentration and output) is usually associated with steatorrhea. However, there were a number of patients with steatorrhea despite only moderate enzyme output impairment, while others had normal fat excretion but severely reduced enzyme secretion. Thus, the degree of impaired pancreatic function, as measured by the SPT, cannot be predicted by the presence of steatorrhea; vice versa, a moderately abnormal SPT does not exclude the presence of pancreatic steatorrhea. Therefore, for a sophisticated evaluation of the functional reserve capacity of the exocrine pancreas, both the SPT and fecal fat analysis are considered necessary. The correlation between impaired glucose tolerance and exocrine pancreatic function was poor.     

Follow-up of patients with pseudotumoral chronic pancreatitis: Outcome and surveillance

AIM: To follow up patients with pseudotumoral chronic pancreatitis (PCP) to assess their outcome and identify an optimal surveillance interval.METHODS: Data obtained prospectively were analyzed in a retrospective manner. Patients with clinical evidence of chronic pancreatitis (abdominal pain in the epigastrium, steatorrhea, and diabetes mellitus), endoscopic ultrasound (EUS) criteria > 4, and EUS-fine needle aspiration (FNA) were included. A pseudotumor was defined as a non-neoplastic space-occupying lesion, a cause of chronic pancreatitis that may mimic changes typical of pancreatic cancer on CT or endoscopic ultrasound but without histological evidence. A real tumor was defined as a neoplastic space-occupying lesion because of pancreatic cancer confirmed by histology.RESULTS: Thirty-five patients with chronic pancreatitis were included, 26 (74.2%) of whom were men. Nine (25.7%) patients were diagnosed with pseudotumoral chronic pancreatitis and two (2/35; 5.7%) patients with pseudotumoral chronic pancreatitis were diagnosed with pancreatic cancer on follow-up. The time between the diagnosis of pseudotumoral chronic pancreatitis and pancreatic adenocarcinoma was 35 and 30 d in the two patients. Definitive diagnosis of pancreatic adenocarcinoma was made by surgery. In the remaining six patients with pseudotumoral chronic pancreatitis, the median of follow-up was 11 mo (range 1-22 mo) and they showed no evidence of malignancy on surveillance. In the follow-up of patients without pseudotumoral chronic pancreatitis but with chronic pancreatitis, none were diagnosed with pancreatic cancer. According to our data, older patients with chronic pancreatitis are at risk of pseudotumoral chronic pancreatitis.CONCLUSION: According to characteristics of patient, detection of PCP should lead a surveillance program for pancreatic cancer with EUS-FNA in < 1 mo or directly to surgical resection.     

Diabetes mellitus in Tropical Chronic Pancreatitis Is Not Just a Secondary Type of Diabetes.

AIMS: In chronic calcific pancreatitis of the tropics, etiology and relationship to developing diabetes mellitus are unknown. Some consider these cases a straightforward secondary type of diabetes, while others suggest selective beta-cell impairment. Testing pancreatic function, we investigated whether selective beta-cell impairment triggers diabetes associated with tropical pancreatitis. METHODS: At a Bangladeshi research institute, 8 chronic tropical pancreatitis and no diabetes mellitus subjects, 14 fibrocalculous pancreatic diabetics and 27 matched healthy controls underwent arginine (endocrine pancreatic function) and secretin (exocrine pancreatic function assessment) stimulation tests. RESULTS: All patients with clinically-diagnosed, chronic pancreatitis demonstrated pronounced exocrine pancreatic dysfunction with beta-cell functioning differing significantly between the two groups. Compared to controls, patients having tropical pancreatitis and no diabetes showed normal plasma C-peptide values at baseline and after arginine stimulation, while fibrocalculous pancreatic diabetics demonstrated a typical diabetic pattern for plasma C-peptide levels. In contrast, pancreatic alpha-cell functioning (glucagon response to arginine) was preserved in both pancreatitis groups. CONCLUSION: A preserved pancreatic alpha-cell function in diabetics with advanced chronic pancreatitis of the tropics supports the concept of two different pathogenic mechanisms, one eliciting chronic pancreatitis and the other selective pancreatic beta-cell impairment and subsequent diabetes mellitus.     

Clinical assessment of pancreatic diabetes caused by chronic pancreatitis

Despite the high prevalence of diabetes mellitus in patients with chronic pancreatitis, few studies of pancreatic diabetes have been reported. We investigated 154 patients with chronic pancreatitis, of whom 50% were diabetics, with special reference to the features and clinical course of pancreatic diabetes. We arrived to clarify the features of pancreatic diabetes by comparing pancreatic exocrine function in 112 patients with primary diabetes with findings in a separate group of 80 patients with chronic pancreatitis. Pancreatic diabetes is proposed as a type of diabetes in which exocrine pancreatic function is markedly decreased. Progressive and fatal angiopathies were found in patients with pancreatic diabetes after a long duration of diabetes. The present investigation suggests that treatment of malnutrition is necessary in patients with pancreatic diabetes and that control of blood glucose is often difficult in these patients because of the high incidence of insulin-induced hypoglycemic episodes. (Received Feb. 6, 1997; accepted July 25, 1997)     

Normal pancreatic secretion in children with progressive familial intrahepatic cholestasis type 1

OBJECTIVE: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a rare, autosomal, recessive, inherited disease resulting from mutations in the ATP8B1 gene which is expressed at high levels in the small intestine and pancreas and at lower levels in the liver. Given this expression pattern, patients might be expected to have a pancreatic phenotype. Although pancreatitis and steatorrhea have been reported in patients with PFIC1, the available data on pancreatic function are not fully convincing. Therefore, the objective of this study was to assess exocrine pancreatic function in patients with PFIC1. MATERIAL AND METHODS: Three subjects with a diagnosis of PFIC1 were included in the study. The diagnosis was confirmed by molecular analysis of ATP8B1. Prior to surgical treatment (biliary diversion), two patients had steatorrhea and in the third patient, a borderline value for fecal fat excretion was documented. In one patient, liver transplantation also was subsequently performed. Exocrine pancreatic secretion was assessed by the use of fecal elastase-1 and chymotrypsin tests. Fecal lipase concentrations were determined in order to exclude isolated lipase deficiency. Other typical diagnostic procedures were performed annually. RESULTS: The results of the fecal tests were within the normal range. None of the three patients experienced any episodes that could be related to acute or chronic pancreatitis. Laboratory tests including serum amylase and lipase tests were always normal. Abdominal ultrasonography findings did not show any pancreatic pathology. CONCLUSIONS: Pancreatic secretion in the study patients with progressive familial intrahepatic cholestasis type 1 was normal. The observed steatorrhea was not related to pancreatic insufficiency.     

Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis.

GOALS: To evaluate the quality of life (QoL) of patients with chronic pancreatitis before and after pancreatic enzyme replacement therapy in a prospective, multicentre, follow-up study. STUDY: Two groups of patients were evaluated. Group 1 consisted of 31 patients with newly diagnosed chronic pancreatitis who had never been treated with pancreatic enzyme preparations. Group 2 consisted of 39 patients whose disease was diagnosed on average 3.4 years before the start of the study. The latter group of patients had undergone pancreatic enzyme replacement therapy, but during follow-up this treatment proved to be insufficient. The dose of pancreatic enzyme replacement therapy was tailored in accordance with the degree of pancreatic exocrine insufficiency measured by means of exocrine pancreatic function tests. A modified European Organizaton for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was used to assess QoL. RESULTS: The social functioning and financial strain were significantly better, while the levels of hope and confidence were significantly reduced in group 1 compared with group 2. A significant gain in body weight and a significantly reduced defecation rate were found in both groups one month after the beginning of the pancreatic enzyme replacement therapy when compared with the pretreatment values. The prevalence of general and disease-specific symptoms and the intensity of pain were reduced in both groups after one month of enzyme substitution therapy. The working ability, the financial strain and the overall QoL scores were improved significantly in both groups, while the cognitive functioning score was found to be significantly improved during the follow-up only in group 1. The overall increase in the QoL score correlated significantly with the increase in body weight and the decrease in defecation number in both groups. CONCLUSIONS: Pancreatic enzyme replacement therapy in patients with chronic pancreatitis not only reduced the extent of steatorrhea and pain, but also significantly improved a variety of other symptoms and the patient's QoL. Individually tailored enzyme replacement therapy improved the QoL not only in the untreated chronic pancreatitis patients, but also in the inadequately treated group. This study demonstrated that the EORTC QLQ-C30 questionnaire, with the addition of two further questions about steatorrhea, is a useful tool for the evaluation of QoL in patients with chronic pancreatitis.     

Plasma cholecystokinin levels in patients with chronic pancreatitis

Using a sensitive and specific radioimmunoassay for cholecystokinin (CCK) we have measured plasma CCK levels in patients with and without chronic pancreatitis. All patients suffered from steatorrhea. The basal plasma values in patients with chronic pancreatitis (n = 10) were significantly higher compared with a control group of 40 normal subjects. After ingestion of a test meal peak plasma levels of CCK were significantly higher than in controls, but the integrated CCK release did not differ from the normal subjects. The findings indicate a close relationship between plasma CCK concentration and exocrine pancreatic function.     

Fat malabsorption screening in chronic pancreatitis

OBJECTIVES: As the major metabolic complications of chronic pancreatitis are exocrine and endocrine dysfunction, leading to malabsorption and diabetes, the aims of this study were to screen patients with chronic pancreatitis for exocrine dysfunction, to correlate the prevalence of such dysfunction with the etiology and severity of pancreatitis, and to evaluate the effect of dysfunction on weight loss. METHODS: Sixty patients were studied. In 44 patients, pancreatitis was alcoholic, and in 16, idiopathic. Patients' age, sex, alcohol consumption and smoking habits, duration of the disease, body mass index, and the presence of steatorrhea were recorded. The severity of pancreatitis was assessed by imaging procedures, including secretin-enhanced magnetic resonance cholangiopancreatography, and patients were classified according to the Cambridge system. Exocrine function was evaluated by the triolein breath test and acid steatocrit. RESULTS: A significant positive correlation was found between breath test and steatocrit values. As a screening test for exocrine pancreatic dysfunction, the sensitivity of clinical steatorrhea was insufficient (38%). Of the 60 patients, 38 (63%) developed exocrine dysfunction within 5 yr of the onset of the pancreatitis and 56 (94%) after 10 yr. Moreover, undetected or untreated malabsorption had a harmful effect on weight, even in the absence of overt clinical steatorrhea. CONCLUSIONS: To avoid nutritional deterioration, early screening for fat malabsorption should be recommended in chronic pancreatitis, whatever its etiology, using the acid steatocrit, a reliable, easy, and inexpensive test.     

Fecal Fat Concentration in the Differential Diagnosis of Steatorrhea

Many approaches have been proposed to differentiate between steatorrhea due to pancreatic insufficiency and intestinal disease. Bo-Linn and Fordtran recently suggested that fecal fat concentration (FFC) is a useful screening test for this distinction. Our aim was to validate their result in a large group of patients. Fecal fat concentrations were calculated for 613 fecal fat tests in 538 patients. Included were 88 patients with pancreatic steatorrhea (13 pancreatic carcinoma, 6 cystic fibrosis, and 69 chronic pancreatitis) and 525 with nonpancreatic steatorrhea. The mean FFC of patients with pancreatic disease (15.0 +/- 1.9 g%, mean +/- SEM) was significantly higher than that of patients with other diseases causing malabsorption (8.9 +/- 0.3 g%, p less than 0.001). Forty-two percent of patients with pancreatic steatorrhea had an FFC below 10 g%. The overlapping of the FFC of steatorrhea due to pancreatic disease and that produced by celiac disease, gastric resection, and other conditions suggests that this approach does not differentiate between pancreatic and intestinal steatorrhea.     

Circulating trypsin-like immunoreactivity in chronic pancreatitis

The present study has been designed to work out the factors regulating the fasting serum levels of trypsin-like immunoreactivity in chronic pancreatitis. One hundred patients with chronic pancreatitis have been included and studied during a painless phase of the disease. No relationships have been observed between serum trypsin-like immunoreactivity and the presence of pancreatic calcifications. Serum immunoreactive trypsin levels showed a gradual decline parallel to the progressive impairment of bicarbonate and enzyme (trypsin and chymotrypsin) outputs in duodenal aspirates during pancreatic secretory studies. Therefore, serum trypsin-like immunoreactivity levels are thought to reflect the functional capacity of the exocrine pancreas. Reduced levels of trypsin-like immunoreactivity were detected in almost all patients with diabetes and steatorrhea. However, the finding of low levels also in a minority of chronic pancreatitis patients with normal endoscopic retrograde cholangiopancreatography or pancreatic secretory tests points to other factors which, in addition to the atrophy of the pancreatic parenchyma, may influence the circulating levels of trypsin-like immunoreactivity in chronic pancreatitis.     

Does the pancreas really produce much more lipase than required for fat digestion?

Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1) the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2) in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3) human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4) in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion. This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.     

Pancreatic exocrine and endocrine responses in chronic pancreatitis

To test the discriminatory potential of certain indices of pancreatic function we performed duodenal perfusion studies and measured trypsin, bicarbonate, and lactoferrin outputs, and plasma concentrations of pancreatic polypeptide and motilin in the basal state and during continuous intravenous stimulation with 100 ng kg-1h-1 Ceruletide and 1 CU kg-1h-1 secretin. The following groups were studied: 12 normal volunteers (NV), seven patients with chronic pancreatitis with steatorrhea (CPS), and seven without steatorrhea (CP). Stimulated trypsin outputs, after 45 min of stimulation, were the best discriminant among the groups (NV versus CPS, p less than 0.0005; NV versus CP, p less than 0.005; CP versus CPS, p less than 0.05). Basal trypsin outputs showed similar patterns but failed to discriminate between NV and CP. Bicarbonate outputs were less discriminatory than trypsin outputs. Lactoferrin outputs failed to discriminate, but transient high peak outputs occurred in the initial stimulation period in all four patients with calcific chronic pancreatitis, suggesting a washout phenomenon. Basal motilin levels were elevated in both groups of pancreatitis (p less than 0.05). Stimulated pancreatic polypeptide levels were lower in CPS (NV versus CPS, p less than 0.05) but higher in CP (NV versus CP, p less than 0.005). These differences were also apparent in the basal state. We conclude that the best discrimination among the three groups was achieved by measurement of trypsin outputs, after 45 min of stimulation. In addition, the pancreatic polypeptide response may be used as a marker of residual pancreatic function in chronic pancreatitis.     

Exocrine pancreatic function in juvenile-onset diabetes mellitus.

Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.     

Clinical significance of main pancreatic duct dilation on computed tomography： Single and double duct dilation

AIM: To study the patients with main pancreatic duct dilation on computed tomography (CT) and thereby to provide the predictive criteria to identify patients at high risk of significant diseases, such as pancreatic cancer, and to avoid unnecessary work up for patients at low risk of such diseases. METHODS: Patients with dilation of the main pancreatic duct on CT at Emory University Hospital in 2002 were identified by computer search. Clinical course and ultimate diagnosis were obtained in all the identified patients by abstraction of their computer database records. RESULTS: Seventy-seven patients were identified in this study. Chronic pancreatitis and pancreatic cancer were the most common causes of the main pancreatic duct dilation on CT. Although the majority of patients with isolated dilation of the main pancreatic duct (single duct dilation) had chronic pancreatitis, one-third of patients with single duct dilation but without chronic pancreatitis had pancreatic malignancies, whereas most of patients with concomitant biliary duct dilation (double duct dilation) had pancreatic cancer. CONCLUSION: Patients with pancreatic double duct dilation need extensive work up and careful followup since a majority of these patients are ultimately diagnosed with pancreatic cancer. Patients with single duct dilation, especially such patients without any evidence of chronic pancreatitis, also need careful follow-up since the possibility of pancreatic malignancy, including adenocarcinoma and intraductal papillary mucinous tumors, is still high.     

Fecal elastase1 and acid steatocrit estimation in chronic pancreatitis

Background  

Measurement of pancreatic exocrine function and steatorrhea in chronic pancreatitis in the clinical setting has not received much attention.     

Evaluation of exocrine pancreatic function by the haptocorrin degradation test of the duodenal fluid collected by endoscopy

Two groups of biological methods are commonly used to evaluate the exocrine pancreatic function: tests which require tubes for the collection of duodenal juice and the tubeless tests which are indirect tests of pancreatic function. In this study we have attempted to improve a new test: the test of haptocorrin degradation (THD). This test measures the transfer of labelled cobalamin from haptocorrin to the intrinsic factor which is provoked by the degradation of the haptocorrin by proteases in the duodenal juice. We present the results of this test in 90 patients with chronic pancreatitis. THD was first assayed with basal duodenal juice collected by naso duodenal tubing during secretin cerulein stimulation. In this study the sensitivity and specificity of THD was 0.86 and 0.93, respectively. In the second part of this study we demonstrated that the means of collecting duodenal juice had no effect on the results of THD. Duodenal juice was collected during a secretin cerulein test or during a routine upper gastrointestinal endoscopy after pancreatic stimulation with secretin. The sensitivity and specificity of THD was 0.90 and 0.94, respectively, when duodenal juice was collected during endoscopy. THD was significantly correlated with the NBT-PABA test, steatorrhea, and with the activity of trypsin and chymotrypsin in the duodenal juice. In this study, NBT-PABA was less sensitive than THD for the diagnosis of chronic pancreatitis (sensitivity was 0.70 and 0.89, respectively). The specificity of THD was estimated at 0.94. THD seemed to be a valuable adjunct to test pancreatic function. As upper gastrointestinal endoscopy is usually performed in patients with proved or suspected chronic pancreatitis, THD seems to have a place of choice among the other tests of pancreatic exocrine function. Further evaluation of this test by a multicentric prospective trial is now needed.     

Update on diagnosis and management of chronic pancreatitis

Chronic pancreatitis should be considered in all patients with unexplained abdominal pain. The importance of small duct disease without obvious radiographic abnormalities is an important new concept. It is meaningful for the clinician to define whether the patient with chronic pancreatitis has small duct or large duct disease. Diagnostic evaluations should begin with a simple, noninvasive, inexpensive test such as serum trypsinogen, to be followed by more complicated testing such as the secretin stimulation test, particularly in those patients with small duct disease. Non-enteric-coated pancreatic enzyme preparations are preferred for the treatment of pain whereas enteric-coated pancreatic enzyme preparations are the drugs of choice for treating steatorrhea. Octreotide may become an important therapy for treating abdominal pain unresponsive to pancreatic enzyme therapy. Endoscopic treatment of the pain of chronic pancreatitis should be used only in highly selected patients and may cause damage to the pancreas. Surgical ductal decompression is appropriate in selected patients.     

Fecal immunoreactive lipase: a new tubeless pancreatic function test.

Immunoreactive lipase (IRL) was measured in 368 stool samples from 231 individuals by means of a new enzyme-linked immunoabsorbent assay technic, to test its validity as an indicator of exocrine pancreatic insufficiency. Ninety-seven stool samples from 64 healthy volunteers showed a logarithmically normal distribution of IRL values and a median IRL concentration of 17 micrograms/g (range, 2.75-117.3 micrograms/g) with a statistically calculated lower normal limit of 4 micrograms/g. In 100 stool samples from patients with chronic pancreatitis and proven steatorrhea the median IRL concentration of 6 micrograms/g (range, 0.002-107 micrograms/g) was significantly lower than that of normal controls and of 52 stool samples from patients with chronic pancreatitis without steatorrhea (IRL, 40 micrograms/g; range, 0.55-302 micrograms/g), 45 stool samples from 23 patients with celiac disease (IRL, 96 micrograms/g; range, 6.05-563 micrograms/g), and 30 stool samples from 26 patients with chronic diarrhea (IRL, 57 micrograms/g; range, 4.2-573 micrograms/g). It is concluded that fecal IRL is a promising new enzyme test with low diagnostic sensitivity (34%) but excellent diagnostic specificity (98%) in chronic pancreatitis and for diagnostic study of chronic diarrheal disorders. In contrast to fecal chymotrypsin, the test results are unaffected by pancreatic enzyme replacement therapy.