Pancreatic Exocrine Function Tests

Abstract

Background and aims. Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. However, the influence of acid and/or bile acids on human esophageal epithelial barrier function and the tight junction (TJ) proteins has not been fully elucidated. The aim of the study is to investigate the esophageal barrier function and TJ expression in healthy subjects and patients with GERD. The functionality of esophageal mucosa exposed to bile salt deoxycholic acid (DCA) and trypsin has been studied in vitro. Material and methods. Endoscopic biopsies from healthy controls and patients with GERD-related symptom with endoscopic erosive signs, as well as esophageal mucosa taken from patients undergoing esophagectomy were evaluated in Ussing chambers and by western blot and immunohistochemistry. Results. The esophageal epithelium from GERD patients had lower electrical resistance and higher epithelial currents than controls. Claudin-1 and -4 were significantly decreased in GERD patients. The bile salt DCA in the low concentration of 1.5 mM and trypsin increased the resistance and claudin-1 expression, while the higher concentration of 2.5 mM DCA and trypsin decreased the resistance and the claudin-3, -4 and E-cadherin expressions. Conclusion. In addition to acidic reflux, duodenal reflux components, such as bile salts and trypsin, have the potential to disrupt the esophageal barrier function, partly by modulating the TJ proteins. However, the expression of TJ is dependent on both the refluxed material as well as the concentration of the bile salt.     

Relationship between Pancreatic Exocrine Function and Histological Changes in Chronic Pancreatitis

To confirm correlation between function and histology of the exocrine pancreas in chronic pancreatitis, we compared exocrine pancreatic function, as estimated by cholecystokinin secretin test (CST), with histological findings in 108 patients. Exocrine pancreatic insufficiency was graded from 0 to 4 according to the number of abnormal CST parameters. Histological findings also were graded from 0 to 4. Results of CST in 108 patients were normal (grade 0) in 52, equivocal (grade 1) in 23, and abnormal (grades 2-4) in 33. Normal histological findings (grade 0) were observed in 54 patients, equivocal (grade 1) in 15, and abnormal (grades 2-4) in 39. We confirmed that there was a significant correlation between histological grading and overall scoring (tau = 0.59, p less than 0.01) or individual parameters (tau = -0.36 for volume, -0.45 for amylase output, and -0.54 for maximal bicarbonate concentration (p less than 0.01) of CST. Sensitivity of CST was 67% in 39 patients with histologically confirmed chronic pancreatitis, specificity was 90% in 69 patients without chronic pancreatitis, based on histological evidence, and efficiency was 81%. In conclusion, we confirmed a highly significant correlation between direct function test (CST) and histology of the exocrine pancreas.     

Exocrine Pancreatic Function in Hepatic Cirrhosis

Exocrine pancreatic function was assessed by the standard test meal method of Lundh in a control group, and 13 patients with nonalcoholic, postnecrotic cirrhosis of the liver. In six of these patients, splenorenal shunts were performed and exocrine pancreatic function was assessed before and three months after operation. In three of the six, the secretin-pancreozymin stimulation test was also performed.
An increased volume but normal trypsin output was observed in the un-operated cirrhotic patients. An increase both in volume and in trypsin was found in the cirrhotic patients after shunting using the test meal stimulation. There was no appreciable difference, however, when tested with secretin and pancreozymin.
Hypersecretion in cirrhotics, with or without shunts, is probably due to a by-pass of the hepatic degradation of normal pancreatic secretogogues produced by the intestine.     

Serum Pancreatic Enzyme Concentrations in Chronic Viral Liver Diseases

Serum amylase and lipase concentrations weredetermined in 78 patients with chronic liver diseases[26 chronic active hepatitis (CAH) and 52 livercirrhosis] and in 15 healthy subjects. Pancreaticisoamylase concentrations and macroamylase complexes wereassayed in hyperamylasemic sera. Serum amylase levelswere abnormally elevated in 27 patients (35%; 22 livercirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 livercirrhosis, 1 CAH). In 9 of the 27 hyperamylasemicpatients, the hyperamylasemia was of pancreatic type.Macroamylasemic complexes were not detected inhyperamylasemic sera. Patients with liver cirrhosis had serumlevels of amylase and lipase significantly higher thanboth the healthy subjects and the patients with CAH,while no significant differences were found in serum levels of these enzymes in patients with CAH ascompared to the healthy subjects. A decreased livermetabolism of serum amylase and lipase in patients withchronic infective liver disease, especially in those having liver cirrhosis, may lead to anaccumulation of these enzymes in the blood.     

Exocrine Pancreatic Function among Diabetic Patients in Thailand

Pancreozymin-secretin-stimulated secretion was measured for volume, bicarbonate concentration and total amylase output in 16 noninsulin-dependent patients and 23 age-, sex-, and weight-matched similar control subjects. Another group of 17 insulin-dependent patients was studied using secretin stimulation and the secretory response compared to a similar group of 37 control subjects. Pancreozymin-secretin-stimulated pancreatic function was normal in noninsulin-dependent patients. Abnormal values for at least one parameter of secretion were found in 82% of insulin-dependent patients. Amylase output was low in 35% and bicarbonate concentration was low in 30%. Hypersecretion occurred in 35%. One patient had abnormal values for all three parameters and three patients had two abnormal values. Hypersecretory response to secretin stimulation is considered to be an early finding of pancreatic exocrine dysfunction among insulin-dependent patients. Progressive secretory failure occurs as the pathological process increases, and a decrease in total amylase output becomes the most significant abnormality.     

Exocrine Pancreatic Function Test by a Synthetic Peptide

A new synthetic substance, N-Benzoyl-L-tyrosyl-p-aminobenzoic acid, is specially cleaved by pancreatic chymotrypsin after oral administration and the released p-aminobenzoic acid (P.A.B.A.) is absorbed and excreted in the urine. The P.A.B.A. recovery in the urine was examined to evaluate its diagnostic value as an exocrine pancreatic function test. The data permit the following conclusions: 1. There is a significant correlation between this test and maximal bicarbonate concentration, amylase output and volume of P.Z./C.C.K. secretin test. 2. More than one-half to two-thirds proximal or one-third distal of the pancreas must be removed before one can expect an abnormal result in this test. 3. This is a simple and useful test to detect exocrine pancreatic insufficiency of more than moderate degree but normal results may be obtained in minimal to mild exocrine pancreatic insufficiency. Only six of 11 cases (54.5%) with one abnormal factor of P-S test showed decreased P.A.B.A. recpvery, whereas 22 of 23 cases (95.7%) with two or three abnormal factors of P-S test showed decreased or borderline P.A.B.A. recovery.     

Intraoperative Radiation Enhances Decline of Pancreatic Exocrine Function After Pancreatic Head Resection

Intraoperative radiation therapy has been introduced to improve survival rates after resection of biliopancreatic cancer. Early and late effects of intraoperative radiation on the exocrine and endocrine functions of the residual pancreas were examined in 54 patients with pancreatic head resection. Of the 54 patients, 20 underwent intraoperative radiation (A group) and the other 34 did not (B group). Fasting blood sugar level, a 120-min value of the 75-g oral glucose tolerance test, N-benzol-l-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value (a pancreatic exocrine function test), and amount of postoperative pancreatic juice drainage were compared between groups A and B at preoperative and early and late postoperative times. Fasting blood sugar level and a 120-min value of the 75-g oral glucose tolerance test (OGTT) showed no change at the early (<2 months) postoperative period of the two groups. At the late (>6 months) postoperative period, fasting blood sugar showed no alteration, while the 75-g OGTT 120-min value increased compared to the preoperative level in both groups. In the group A, the 75-g OGTT 120-min value at the late postoperative period was significantly higher than those at the preoperative and early postoperative periods (289.4 ± 104.9 vs 193.0 ± 58.2 mg/dl, P = 0.0198 and 289.4 ± 104.9 vs 184.4 ± 104.9 mg/dl, P = 0.0285). Preoperative BT-PABA excretion value was not different between the two groups. It decreased at the early postoperative period and returned to the preoperative level at the late postoperative period in both the groups. The decline of BT-PABA in group A was 23 ± 21%, which was significantly larger than 11 ± 24% in group B. The total amount of postoperative pancreatic juice drainage from postoperative days (POD) 4–13 in group A was about half as much as that in group B (720.8 ± 916.4 vs 1433.8 ± 962.1 ml, P = 0.0128). Univariate and multivariate regression analysis of factors concerning the decline of BT-PABA values at the early postoperative period showed that intraoperative radiation was a significant independent determinant. In conclusion, these results suggest that intraoperative radiation causes significant deterioration of pancreatic exocrine function at the early postoperative period. Intraoperative radiation for resectable periampullary carcinoma should be reappraised based on the decline of the pancreatic exocrine function as well as the improvement of the survival curve.     

Cryoglobulinemia in Chronic Liver Diseases

Cryoglobulins were detected in six patients with chronic liver diseases. Three of them had postnecrotic cirrhosis, two had chronic active hepatitis and one had primary biliary cirrhosis. In none of them HBsAG or its antibody were detected. The cryoglobulin appeared during the course of the disease in two patients, one with chronic active hepatitis and the other with primary biliary cirrhosis. There was no proof for cause and effect relationship between the liver disease with cryoglobulinemia and an eventual infection with hepatitis B virus.
The cryoglobulinemia might be due to the liver disease per se and it seems that it is not always related to an infection caused by the hepatitis B virus.     

Pathological Pancreatic Exocrine Function and Duct Morphology in Patients with Cholelithiasis

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.     

13C-呼气试验评估胰腺外分泌功能的临床应用

三酰甘油、蛋白质和淀粉均可作为13C-呼气试验的底物，用于检测胰腺外分泌功能。目前研究最多的是13C-三酰甘油呼气试验，其中以13C-混合三酰甘油呼气试验（MTG—BT）最具优势。N-苯甲酰-L-酪胺酰-【1-13C】丙氨酸（Bz—Tyr—Ala）呼气试验无需试餐，近年逐渐受到关注。13C-淀粉呼气试验影响因素较多，研究近况不甚理想。本文对各类，13C-呼气试验的底物特点及其评估胰腺外分泌功能的临床应用作一综述。     

Ethnic Variations in Chronic Liver Diseases

Chronic liver disease is a major source of morbidity and mortality in the United States today. There is little information on the interethnic variation in the clinical presentation, therapeutic responses and prognosis of individuals with liver disease. This review will discuss the ethnic variations and implications of the most common liver diseases.     

Bone Disorders in Chronic Liver Diseases

Bone disease is a major complication of chronic liver disease. Osteomalacia is quite uncommon despite low vitamin D levels in the majority of patients with cirrhosis. In contrast, osteoporosis is quite common, occurring in up to 50% of patients. Osteoporosis can result in spontaneous or low-impact fractures in patients with chronic liver diseases, adversely affecting morbidity, quality of life, and survival. The general biology of osteoporosis, including its pathogenesis, diagnostic tools, and rationale for treatment, have been determined largely empirically from studies of postmenopausal women with osteoporosis. Treatment regimens with modification of risk factors, use of vitamin D, and supplementation with calcium and bisphosphonates have been shown to be effective in select groups of patients with chronic liver diseases.     

Relation of Exocrine Pancreatic Function to the Diameter of the Pancreatic and Common Bile Ducts

One hundred and thirty-nine patients were examined for possible chronic pancreatitis by means of both pancreozymin-secretin test and endoscopic pancreatography of pancreatocholangiography. Pancreatic function as assessed by the pancreozymin-secretin test was impaired in 89 (64%) of the entire group. No significant relationship was demonstrated between pancreatic secretion of fluid, bicarbonate and amylase and the diameter of main pancreatic duct in both the entire group of the subgroup of patients with pancreatic dysfunction. On pancreatogram no gross morphological abnormalities were found in a high proportion of patients whose pancreatic function was impaired in minimal to moderate degree. There was a significant linear correlation between the diameters of the main pancreatic duct and common bile duct. These data question the value of endoscopic pancreatography in the diagnosis of low to moderate grade chronic pancreatitis.     

Irreversible Exocrine Pancreatic Insufficiency in Alcoholic Rats Without Chronic Pancreatitis After Alcohol Withdrawal

Background: Long‐term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism. Methods: Forty‐eight healthy male Wistar rats were divided randomly into 4 groups: 6‐month control, 6‐month ethanol, 9‐month control, and 9‐month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK‐A receptors was quantitatively analyzed by Western blot. Results: Alcohol‐induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK‐A receptors. Conclusions: Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long‐standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.     

Exocrine Pancreatic Hypersecretion in Brazilian Alcoholics

Thirty percent of alcoholic patients without clinical evidence of pancreatic or hepatic disease showed hypersecretion of pancreatic bicarbonate in all three test periods after stimulation with secretin and secretincholecystokinin, and an increased amount of protein in the duodenal aspirate of the first test period, probably due to ductal wash-out. This hypersecretion must be taken into account when the secretin or secretin-cholecystokinin tests of alcoholics are interpreted, and, indeed, may be useful in identifying possible early pancreatic dysfunction that precedes insufficiency and clinical symptoms.     

Erythrocytes: Anemias in Chronic Liver Diseases

Anemia is a frequently observed manifestation during the clinical course of chronic liver disease. In this study, we retrospectively reviewed the hospital files of 500 chronic liver disease patients and assessed the frequency, etiology and morphology of anemia in 50 patients who fulfilled the criteria to be included in the study. The mean age of the patients was 48+/-16 years and male/female ratio was 1.4/1. The mean hemoglobin value was 9.54+/-2.03 g/dl. The mean MCV was 82.9+/-10.52 fl. Iron deficiency anemia, defined as absent bone marrow iron stores, was the most common anemia present in 50% of patients. Classical laboratory criteria used in the diagnosis of iron deficiency anemia (MCV < 80 fl, ferritin < 10 ng/ml) could not be applicable to all of the patients with iron deficiency anemia and hepatic disorders. Hemolytic anemia due to hypersplenism was the second most common anemia (24%) followed by anemias, namely anemia due to gastrointestinal hemorrhage (22%), anemia of chronic disease (8%), beta-thalassemia major (8%), folate deficiency (6%), vitamin B12 deficiency (4%), macrocytic anemia (2%), aplastic anemia (2%) and immune hemolytic anemia (2%). Twenty-eight percent of the patients had more than a single cause of anemia. Morphologically, microcytic anemia was the most common seen in 46% of the patients followed by normocytic (42%) and macrocytic anemia (12%). As patients do not always present with classical laboratory findings and may have more than a cause of anemia, a complex diagnostic approach should be considered in anemic patients with hepatic disorders.