Serum amylase determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.     

Hyperamylasemia after cardiac surgery in infants and children

OBJECTIVE: This study was conducted to clarify the incidence of hyperamylasemia after cardiac surgery in infants and children. DESIGN AND PATIENTS: 186 infants and children operated on at Children's Hospital. Helsinki, during an 11-month period were enrolled in the study. Serum samples were taken before and on 3 consecutive days after cardiac surgery at the intensive care unit and before discharge from the hospital. MEASUREMENTS: We measured serum total amylase and serum pancreatic amylase with two different assays (1) reduction of salivary amylase from total amylase activity and (2) measurement of mass concentration with monoclonal antibodies. RESULTS: Preoperative values for both total amylase and pancreatic isoenzymes were strongly age-related. At least one of the three tests showed postoperative hyperamylasemia (> +/- 2 SD above starting values of the age group and maximal value > 3 times the individual starting value) in 64/186 (34%) patients. 22/186 (12%) patients had abnormal results in all assays. A more than tenfold rise in pancreatic amylase, suggesting pancreatitis, was found in 14 patients (8%). Mortality was 21% in this subgroup, but 5% in the rest of the patients. Hyperamylasemia was more common after 1 year of age, and after open-heart surgery, especially homograft implantation or cardiac transplantation. CONCLUSIONS: Hyperamylasemia is a common finding after cardiac surgery in pediatric patients. Amylase isoenzyme measurements are needed for clinical decision making. Age-group-related reference values are mandatory for the right interpretation of amylase values.     

What is the best biochemical test to diagnose acute pancreatitis? A prospective clinical study

OBJECTIVE: To determine which biochemical test is best to distinguish acute pancreatitis from other pancreatic and nonpancreatic diseases associated with hyperamylasemia. DESIGN: We conducted a prospective clinical study of 836 consecutive patients who had a total serum amylase test requested by a physician during a 7-month period. MATERIAL AND METHODS: Radioimmunoassay and enzymatic activity methods were used to measure pancreas-specific proteins of varied size, charge, and stability. In addition, scoring systems were used for the diagnosis of pancreatitis, and statistical analyses were done to determine sensitivity and specificity. RESULTS: We found minor differences in sensitivity and specificity for diagnosis of acute pancreatitis among pancreatic isoamylase, phospholipase A2, colipase, lipase, and carboxylester lipase. Of these tests, the combination of isoamylase and phospholipase A2 had a small but statistically significant increased sensitivity (90%; 95% confidence interval [CI] = 74 to 98%) and specificity (93%; 95% CI = 91 to 95%) over isoamylase (90% and 92%, respectively; 95% CI = 90 to 94%) and phospholipase A2 (90% and 75%, respectively; 95% CI = 72 to 78%) alone for the diagnosis of acute pancreatitis. CONCLUSION: Pancreas-specific proteins are satisfactory for diagnosing acute pancreatitis if the test is validated by the laboratory. Clinically, the slight advantage of using both isoamylase and phospholipase A2 does not outweigh the expense of performing two assays; we recommend using isoamylase to diagnose acute pancreatitis.     

Thoracoscopic surgery using voice controlled robot for spontaneous pneumothorax

Although there is abundant literature on the association of L-asparaginase and acute pancreatitis in patients undergoing chemotherapy, few studies have investigated the usefulness of pancreatic enzyme measurement in the early diagnosis of L-asparaginase-induced acute pancreatitis. We measured levels of serum pancreatic enzymes before, during, and after L-asparaginase therapy in nine children with acute lymphocytic leukaemia or non-Hodgkin lymphoma. Serum levels of amylase, pancreatic isoamylase, and lipase did not change between the 1st and 30th day of L-asparaginase administration. However, the serum trypsin and elastase- levels, 10 and 20 days after beginning L-asparaginase therapy, were significantly higher than those prior to therapy. CONCLUSION: L-asparaginase may induce subclinical pancreatitis and the estimation of serum trypsin and elastase-1 may be useful in the early diagnosis of L-asparaginase-induced acute pancreatitis.     

Phenformin and hyperamylasemia in lactic acidosis

All cases of lactic acidosis occurring during a 23-month period in a metropolitan teaching hospital were reviewed to ascertain the frequency of hyperamylasemia. Serum amylase activity had been measured in 12 of 26 patients and was elevated in eight (67%). Hyperamylasemia was not significantly more frequent in patients with phenformin-associated lactic acidosis than in patients with lactic acidosis who had not received phenformin. Serum amylase activity did not correlate with the severity of acidosis (arterial pH) or with renal function (serum creatinine).     

Glutathione and ATP levels, subcellular distribution of enzymes, and permeability of duct system in rabbit pancreas following intravenous administration of alcohol and cerulein

In order to reproduce what might occur during the initial phase in some cases of acute alcohol-induced pancreatitis, rabbits were infused with diluted ethanol and low-dose cerulein. The duct permeability was assessed by recovery of fluoresceinated dextran (molecular weight 19,500) in central venous blood following orthograde duct perfusion with this substance in the anesthetized animal. Serum ethanol, lipase, and amylase were measured; pancreatic duct morphology was examined by light microscopy and electron microscopy. ATP and glutathione were measured, as were amylase, trypsinogen/trypsin, cathepsin B, and DNA levels in differential centrifugates. As expected, acinar amylase and trypsinogen showed a significant decrease in the experimental group; cathepsin B activity was similarly diminished. Compared with the control group, the activity of serum amylase and lipase in the experimental group demonstrated a significant increase. However, no differences between saline-infused control animals and the treated group regarding pancreatic duct permeability, continuity of lumen-lining epithelium, ATP and glutathione levels, and the relative subcellular distribution of pancreatic digestive and lysosomal enzymes were observed. Thus, our findings do not support the relevance of some of the most common hypotheses on the pathophysiology of acute pancreatitis in its early stage for at least a certain subgroup of patients with acute alcohol-induced pancreatitis.     

Clinical value of pancreatitis-associated protein in acute pancreatitis

OBJECTIVES: Pancreatitis-associated protein (PAP) is a secretory protein that is overexpressed by the pancreas during acute pancreatitis. This study was carried out to assess the clinical value of PAP in acute pancreatitis, particularly its ability to indicate the severity of the disease. METHODS: Twenty-one healthy subjects, 58 patients with acute pancreatitis, and 20 patients with nonpancreatic acute abdomen were studied. In addition to serum PAP concentration, serum concentrations of amylase, lipase, and C-reactive protein (CRP) were measured at admission and, in patients with acute pancreatitis, during the following 5 days. RESULTS: On admission, serum PAP concentrations were abnormally high in 46 of the 58 patients with acute pancreatitis (79%); serum amylase, in 57 patients (98%); serum lipase, in all patients (100%); and serum CRP, in 40 patients (69%). During the subsequent days of the study, PAP and CRP tended to increase, whereas amylase and lipase decreased. No significant differences in PAP or amylase and lipase concentrations were found between patients with mild pancreatitis and those with severe pancreatitis during the entire study period, whereas from the third day to the sixth day, CRP concentrations were significantly higher in patients with severe pancreatitis than in those with mild pancreatitis. Among the 20 patients with nonpancreatic acute abdomen, PAP concentrations were abnormally high in 10 (50%), whereas amylase concentrations were abnormally high in five (25%), and lipase concentrations were high in two (10%). CONCLUSIONS: Our results indicate that the clinical value of PAP in acute pancreatitis is quite limited and, in particular, that PAP is not a useful marker for determining the severity of the disease.     

Effects of glycosaminoglycans on the glomerular changes induced by Adriamycin

BACKGROUND: A model of moderate acute necrotizing pancreatitis is essential for the study of the pathophysiology of the disease and novel therapies. We tried to establish a model of bile salt-induced acute necrotizing pancreatitis in rats. METHODS: Acute pancreatitis was induced by retrograde infusion of bile salt into the cannulated pancreatobiliary duct. Twenty-six rats wee divided into 3 groups. Group I (n = 8) received 0.2 ml of glycodeoxycholic acid (GDOC) 10 mmol/l; group II (n = 10) 0.2 ml of 2.5% sodium taurodeoxycholate (NaTDC); group III (n = 8) the mixture of 0.2 ml GDOC 10 mmol/l and 10 U enterokinase. Serum levels of amylase and lipase, hematocrit, mean arterial pressure and heart rate were determined at baseline and 5 hours later. Then the pancreas was removed for histopathology and grading (0-3; absent-severe) with regard to leukocyte infiltration, edema, necrosis, hemorrhage and acinar cell vacuolization. RESULTS: Serum levels of amylase and lipase increased significantly in 5 hours in all the groups. Serum amylase levels were significantly lower in group III than in group II. No significant difference of serum lipase was found among the groups. Group II had the highest scores of necrosis and acinar cell vacuolization, whereas group III had the highest scores of leukocyte infiltration and edema. The degree of necrosis was significantly more severe in group II than in group I. The hematocrit increased significantly in 5 hours in groups I and II. The mean arterial pressure in 5 hours decreased significantly in group I. There was no significant difference of the changes of heart rate in 5 hours among 3 groups. CONCLUSIONS: Intraductal infusion of NaTDC was a good method to induce moderate acute necrotizing pancreatitis in rats. GDOC caused mild pancreatitis, and pancreatic injury was aggravated when enterokinase was added. The severity of pancreatic histopathology was not correlated with the changes of serum levels of pancreatic enzymes, hematocrit or mean arterial pressure at the early stage of pancreatitis.     

Effect of granulocyte colony-stimulating factor on the course of infection with gram-positive bacteria in mice during granulocytopenia induced by sublethal irradiation or cyclophosphamide

Ligation of the common bile-pancreatic duct induces hyperamylasemia and acute pancreatitis in rats. Pancreatic morphologic changes include edema, acinar cell damage, and mild inflammation. The pathogenesis of acute pancreatitis in this model is not understood, but may involve altered secretion and intrapancreatic activation of acinar proteases. We hypothesized that trypsinogen activation, measured by the production of plasma and pancreatic trypsinogen activation peptides (TAP), occurs early in this model. We performed the following experiments: rats were prepared with (1) bile-pancreatic ducts ligated and (2) ducts dissected but not ligated (sham). Rats were killed after 6, 24, and 48 hr. Serum amylase was measured and histologic sections were analyzed for morphologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal. anti-TAP antibody in an enzyme-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreatic duct ligation, hyperamylasemia and acute morphologic changes of acute pancreatitis were observed. Evidence of acinar cell destruction was not evident until 48 hr after ligation. Levels of serum and pancreatic tissue TAP were significantly elevated at both 24 and 48 hr after ligation compared to those of sham. We conclude that increased intrapancreatic trypsinogen activation occurs early in this form of experimental acute pancreatitis and that it occurs prior to evidence of acinar cell destruction. These data and observations support the possibility that intrapancreatic protease activation contributes to the pathogenesis of ligation-induced acute pancreatitis.     

A cause of hyperamylasemia associated with chronic liver disease

The cause of hyperamylasemia associated with chronic liver disease is unclear. In an attempt to identify the tissue of origin of hyperamylasemia in 3 patients with chornic active hepatitis their serum was isoelectrically focused. The isoamylase patterns obtained were compared to those of pancreatic and salivary amylase. The apparent salivary gland origin of the excessive blood amylase in the patients studied was substantiated by radiological demonstration of parotid sialoectasia in one patient and histological evidence of sialoadenitis in another. Further evidence was the coincident isoelectric points of the predominant isoamylase in the sera of the liver disease patients and of patients with parotid inflammatory disease. Hyperamylasemia associated with chronic liver disease may be of salivary gland origin and as such forms part of the spectrum of extrahepatic manifestations of chronic active hepatitis.     

Serum Amylase elevation following hepatic resection in patients with chronic liver disease

BACKGROUND: Factors liable to cause hyperamylasemia after hepatectomy were studied retrospectively in 140 patient with chronic liver disease. METHODS: The pringle maneuver was performed in 113 patients (Pringle group), the hemihepatic vascular occlusion technique in 21 (hemihepatic group), and no vascular occlusion in 6 (no-occlusion group). RESULTS: In the Pringle group, postoperative serum amylase levels were elevated significantly in comparison with the preoperative levels, but were not elevated in hemihepatic and no-occlusions groups. In the Pringle group, there were 4 patients whose postoperative serum amylase levels exceeded 3.5 times the upper limit of the normal range together with serum pancreatic isoamylase or lipase elevation or both. When compared with the other 109 patients, these 4 patients had a significantly longer vascular occlusion time (51 +/-3 minutes versus 94 +/- 8 minutes P<0.005). One of them developed pancreatitis and died from hepatic failure. CONCLUSION: Prolongation of portal congestion carries a potential risk of serum amylase elevation and pancreatitis after hepatectomy in patients with underlying liver disease.     

Is the association of serum lipase with beta2-microglobulin or C-reactive protein useful for establishing the diagnosis and prognosis of patients with acute pancreatitis?

In the Emergency Department it is mandatory to establish the diagnosis and the prognosis of acute pancreatitis as soon as possible. To evaluate whether the association of serum lipase either with serum beta2-microglobulin or with C-reactive protein allows simultaneously to establish the diagnosis and the prognosis of acute pancreatitis, 96 patients with acute abdomen were studied. Fifty-eight patients had non-pancreatic acute abdomen and the remaining 38 had acute pancreatitis: 23 mild acute pancreatitis, and 15 severe acute pancreatitis. Forty healthy subjects were studied as controls. Lipase, beta2-microglobulin and C-reactive protein were determined in the serum of all subjects, using commercial kits. One patient with acute pancreatitis was not correctly classified when lipase was used to discriminate between patients with non-pancreatic acute abdomen and those with acute pancreatitis. For the discrimination of patients with severe acute pancreatitis from those with the mild form of the disease in the remaining 37 acute pancreatitis patients, beta2-microglobulin had a sensitivity of 53.3 %, specificity of 81.8%, and prognostic accuracy of 70.3 % (27 of the 37 patients correctly classified); 87.5 % of the 96 cases were correctly classified. C-reactive protein showed a lower prognostic accuracy than beta2-microglobulin: sensitivity 86.7%, specificity 45.5%, accuracy 62.2 %; 84.4 % of the cases were correctly classified. Using the polychotomous logistic regression analysis we found the same accuracy in discriminating between patients with acute pancreatitis and those with non-pancreatic acute abdomen (99.0%) but a lower accuracy (54.1%) between patients with severe acute pancreatitis and those with the mild form of the disease. Our study shows that the association of serum lipase with beta2-microglobulin or with C-reactive protein is not useful in simultaneously establishing the diagnosis and prognosis of acute pancreatitis.     

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis. To evaluate the role of substance P, pancreatitis was induced in mice that genetically lack NK1R by administration of 12 hourly injections of a supramaximally stimulating dose of the secretagogue caerulein. During pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil sequestration in the pancreas, and pancreatic acinar cell necrosis were significantly reduced in NK1R-/- mice when compared with wild-type NK1R+/+ animals. Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R-/- animals. These effects of NK1R deletion indicate that substance P, acting via NK1R, plays an important proinflammatory role in regulating the severity of acute pancreatitis and pancreatitis-associated lung injury.     

Octreotide in the prevention of hyperamylasemia following ERCP (a controlled multicenter study)

The aim of the multicentric trial was to study the effect of octreotide (Sandostatin) on the rise of pancreatic amylase in the serum after ERCP based on a large number of patients. The study was carried out in a prospective random manner in 2102 patients in 11 endoscopic centers. Patients in the treated group received 0.1 mg octreotide acetate, and those of the nontreated (control) group received isotonic sodium-chloride subcutaneously before the ERCP and 45 minutes after. Serum amylase and blood sugar were checked before the endoscopic procedure, 6 and 24 hours later. Out of the total number of patients involved, data of 1199 patients (599 in the treated group, and 600 in the control group) were evaluated. Octreotide diminished the percentual increase of serum amylase levels following ERCP. However, the frequency of hyperamylasaemia was decreased only after in patients with chronic obstructive pancreatitis or in such patients after endoscopic sphincterotomy. The peak serum level of blood sugar was higher in the treated group compared to the controls. There was no difference in the clinical symptoms following ERCP between the two groups. Conclusion: the prophylactic use of long-acting somatostatin may diminish the frequency of hyperamylasemia after ERCP in patients with chronic obstructive pancreatitis or in those patients who subsequently underwent EST.     

Acute intermittent porphyria with relapsing acute pancreatitis and unconjugated hyperbilirubinemia without overt hemolysis

A 36-year-old woman was admitted to hospital with a first attack of acute intermittent porphyria. At the same time increased serum levels of amylase and lipase as well as an increased amylase clearance to creatinine clearance ratio were observed, permitting the diagnosis of acute pancreatitis. The etiology of the latter could not be determined. In addition, elevation of indirect bilirubin without evidence of hemolysis was observed Gilbert's syndrome was suspected. 40 weeks after the first episode, a second attack of identical abdominal pain was noted, with elevation of pancreatic enzymes in the serum. There is evidence that acute intermittent porphyria and acute relapsing pancreatitis may have some etiological connection in this patient.     

Idiopathic hyperamylasemia

A 25-year-old pregnant Japanese woman was diagnosed with idiopathic hyperamylasemia. The administration of a beta-stimulant caused a further increase in the serum levels of pancreas-type amylase and lipase.The patient's hyperamylasemia concomitant with elevated serum levels of lipase, elastase 1, and trypsin lasted over a 4 year-period, in which the patient remained asymptomatic. It is possible that the pancreas in some women with the idiopathic hyperamylasemia can respond to a beta-adrenoceptor stimulation with respect to pancreatic enzyme secretion.     

Amylase activity of parotid saliva in acute and chronic pancreatitis

The activity of the alpha-amylase was estimated in the parotid resting saliva of 17 subjects without evidence of pancreatic disease, 17 patients with chronic relapsing pancreatitis in the intervals between acute attacks, and also in 4 patients with acute pancreatitis and 3 patients with an acute attack of chronic relapsing pancreatitis. In the patients with chronic relapsing pancreatitis between attacks the concentration, output and specific activity of the salivary amylase were significantly lowered. The patients with acute pancreatitis exhibited salivary amylase concentrations in the uppper normal to grossly supranormal range, whereas those of the patients with acute attacks of chronic relapsing pancreatitis were distinctly reduced. Unlike the amylase output, the amylase concentration was independent of the rate of salivary flow. Simultaneous infusion of secretin and pancreozymin produced a significant increase in the parotid salivary amylase levels in both the patients without pancreatic disease and in those with chronic relapsing pancreatitis between acute attacks.     

Amylase thermolability in body fluids

The thermolability of amylase was measured in saliva, pancreatic juice, urine, adult and neonatal sera. The mean percentage thermolability from these fluids was 100%, 99%, 87%, 44% and 23% respectively. In patients with acute pancreatitis and mumps the amylase was 84% and 83% thermolabile during the acute phase. On resolution of the pancreatitis this dropped towards normal. Patients with a pancreatic pseudocyst showed a high mean percentage thermolability (82%). These results could suggest that a component of amylase in human serum is not of pancreatic or salivary origin. In addition, this simple technique may be helpful in the diagnosis of pancreatic pseudocyst.     

Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy--Italian Group

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP. METHODS: We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years)--208 in the gabexate group and 210 in the placebo group--were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain. RESULTS: After the procedures, 276 patients (66 percent) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups. Mean serum amylase values were higher in the placebo group than in the gabexate group through 24 hours of observation (P=0.03). Twelve patients in the gabexate group and 29 in the placebo group had abdominal pain (6 percent vs. 14 percent, P=0.009). Sixteen patients in the placebo group and five in the gabexate group had acute pancreatitis (8 percent vs. 2 percent, P=0.03). Two patients treated with gabexate and six given placebo had adverse events, all of which resolved. Two patients given placebo died of acute pancreatitis; one was excluded from the evaluation because pancreatitis was present before endoscopy. One patient in the gabexate group died, from a myocardial infarction. CONCLUSION: Prophylactic treatment with gabexate reduced pancreatic damage related to ERCP, as reflected by reductions in the extent but not the frequency of elevated enzyme levels and in the frequency of pancreatic pain and acute pancreatitis.     

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.