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The development of proteomic methods, especially mass spectrometry, has brought new possibilities to tumor marker research. Pancreatic secretory trypsin inhibitor (PSTI), a common known biomarker for various malignancies, occurs on genetic variants that we are able to detect at the protein level with proteomic techniques using immunoaffinity capture prior to liquid chromatography-mass spectrometry (LC-MS). We also show that PSTI can be detected in urine from cancer patients using a two-step peptide enrichment technique and LC-MS. These results show that tumor-associated peptides can be detected in urine by proteomic techniques.

Background: Acute pancreatitis (AP) results in elevated concentrations of trypsinogen (T) isoenzymes in serum. Immunoreactive anionic trypsinogen in urin (irAT/u) is elevated in AP, and has recently been proposed as a rapid diagnostic instrument and severity predictor. These results have not been confirmed by other groups, and irAT/u has not been further characterized. The concentration of immunoreactive cationic trypsinogen in urine (irCT/u) and the serum irAT/irCT ratio in AP have not been extensively examined., Methods: Levels of irAT and irCT were studied in urine and serum from 50 AP patients and in urine from 41 non-AP patients. Severity was assessed according to the Atlanta classification. irAT/u was characterized by gel filtration., Results: Gel filtration revealed only AT in the urine. Highly significant differences in irAT/u were seen between AP/non-AP (p < 0.0001) and mild/severe disease (p = 0.0012). The irAT/irCT ratio in serum changed from normal 0.8 to 1.3 in AP., Conclusions: IrAT and only traces of irCT were found in the urine in AP. IrAT/u was higher in AP than in other acute abdominal disorders (non-AP) and also higher in severe than in mild AP. IrAT in serum (irAT/s) increased proportionally more than irCT/s in AP, but did not discriminate mild from severe forms. High levels of irAT/u in some non-AP cases and a wide range in AP cases make the clinical value of the test questionable.

Conclusions: Urinary TAP obtained within the first 48 h of the onset of symptoms can distinguish patients with severe acute pancreatitis., Background: Urinary trypsinogen activation peptide (TAP) has recently been described as an early marker of severity in acute pancreatitis., Methods: In a multicenter study, urine samples were collected for TAP concentration at 6-12, 24, and 48 h after admission from 139 patients with acute pancreatitis (99 with mild disease, 40 with severe disease) and from 50 control patients. Severity of acute pancreatitis was defined by the presence of organ failure and/ or pancreatic necrosis on dynamic contrast-enhanced computed tomography., Results: Median urinary TAP in the 139 patients with acute pancreatitis compared to the 50 control patients was significantly higher at admission, 4.6 vs 0.8 ng/mL (p < 0.001), and 6-12 h, 1.9 vs 0.55 ng/mL (p = 0.04). Among patients who presented within 48 h of the onset of symptoms, the median urinary TAP for severe pancreatitis (9 patients) compared to mild pancreatitis (40 patients) was significantly higher at admission, 29.6 vs. 3.6 ng/mL (p = 0.001). Also, when obtained within 48 h of the onset of symptoms, all patients with severe pancreatitis had an admission urinary TAP level > 10 ng/mL. The sensitivity and specificity of an admission urinary TAP > or = 10 for severe pancreatitis was 100 and 85%, respectively. Given a cutoff of 10 ng/mL for an admission urinary TAP obtained within 48 h of the onset of symptoms, the negative predictive value was 100% for mild pancreatitis.

Hyperamylasemia is a common finding in chronic renal failure (CRF) patients. It has been suggested that the diagnosis of acute pancreatitis in these patients is confirmed when serum amylase activities are greater than three times the upper normal limits. In order to evaluate the frequency, the type, and the hyperamylasemia levels in patients with various degree of chronic renal failure, the total serum amylase (Ta), the pancreatic (Pa) and salivary (Sa) types of serum isoamylases, as well as the urine isoamylases (Tu, Pu, Su, respectively) have been determined by the Phadebas method. Moreover, the levels of serum electrolytes and triglycerides were determined in order to study any relationship between serum electrolytes as well as triglycerides and alpha-amylase activities. We studied 102 patients of whom 33 (group A) had CRF with serum creatinine levels 8.5 +/- 3.1 mg/dL (mean +/- SD), 59 (group B) were receiving chronic hemodialysis, and 10 (group C) were on continuous ambulatory peritoneal dialysis as well as 47 normal individuals. None of the subjects studied had any clinical manifestation of acute pancreatitis. Our results showed that the Ta, Pa and Sa levels of groups A, B, and C were significantly elevated compared to normal subjects. Eighteen patients had Pa activities greater than three times the upper normal limits. In the present study, no relationship between serum electrolytes as well as triglycerides and alpha-amylases was found. In conclusion, hyperamylasemia was a much more common finding in CRF patients than previously reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Single random samples of urine were collected from 50 control subjects; 27 patients with chronic pancreatitis; 19 with acute pancreatitis; 6 with acute on chronic pancreatitis; five in the recovery phase of acute attack; four patients with pseudocysts. Salivary (S) and pancreatic (P) amylase values were measured by cellulose acetate electrophoresis. The P amylase values always exceeded those of S amylase in the control specimens. In acute pancreatitis, both the lower and upper levels of total and P amylase were considerably higher than in the controls, and these high values tended to return to normal during the recovery phase of acute pancreatitis. The S amylase values were often very low or undetectable during the acute phase. Values for P amylase exceeded control values in patients with pseudocysts even in the presence of chronic pancreatitis. In chronic calcific pancreatitis, S amylase was higher than P amylase. We conclude that P amylase is always greater than S amylase in normal urine specimens, and a change in this pattern may be helpful in diagnosing various forms of pancreatitis.

This study was performed to investigate the behavior of phospholipase A2 (PLA2) in serum and urine of patients with chronic pancreatic diseases and to ascertain whether any factors influenced the results. In 30 controls, 45 patients with pancreatic cancer, 54 with chronic pancreatitis, and 64 with extrapancreatic diseases, serum and urinary PLA2, pancreatic isoamylase and RNase, and urinary N-acetylglucosaminidase (NAG) were measured. Serum PLA2 levels were higher in patients with chronic pancreatitis than in all the other groups. In our patients, only occasionally was urinary PLA2 elevated, the increase occurring almost exclusively in the presence of an acute inflammatory disease, e.g., relapsed chronic pancreatitis or active inflammatory bowel disease. A correlation was found between serum PLA2 and serum RNase, an indicator of tissue damage, but not between serum PLA2 and pancreatic isoamylase. Urinary PLA2 output was correlated with its renal input and with RNase output. No correlation was found between PLA2 output and pancreatic isoamylase or NAG urinary excretion. In conclusion, (1) the determination of serum PLA2 activity may be an aspecific test of pancreatic disease; (2) PLA2 urinary excretion occasionally increases, especially in the presence of severe phlogosis, which occurs in chronic pancreatitis, in particular during relapse; and (3) irrespective of the tissue origin of urinary PLA2, its increased excretion may be accounted for in part by its increased circulating levels. It is, however, more likely the consequence of a renal tubular dysfunction, which is sometimes found in patients with pancreatic diseases.

The oligosaccharide Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc (Glc4), formed by amylolytic degradation of starch and glycogen, is excreted at extremely high levels in the urine of patients with acute pancreatitis. To determine if Glc4 is a useful indicator for this disease, we studied 55 patients admitted to the hospital because of acute abdominal pain (possibly acute pancreatitis). The highest values of Glc4 excretion in urine was found in a group of 11 patients with acute pancreatitis. The Glc4 values, but not serum and urine amylase values obtained at admission, correlated significantly with the severity of the disease. In two patients, followed through convalescence, the Glc4 excretion remained elevated for 7 and 2 wk in contrast to serum and urine amylase that returned to normal levels within a few days. It seems probable that glycogen, released from the liver and subsequently degraded by amylase originating from the pancreas, can be measured as Glc4 in the urine. This might be valuable for diagnosing acute pancreatitis and gives indications of the prognosis.

This study was undertaken in order to ascertain the behaviour of amylase and trypsin fractional clearances in chronic pancreatic disease and to speculate on the factors involved. Renal tubular function was also assessed in these patients. An increase of both clearances was found in a number of patients with pancreatic cancer and chronic pancreatitis. Amylase urinary output seems to be mainly related to the circulating enzyme levels; urinary IRT is principally accounted for by a functional tubular impairment. Tubular damage was observed in a number of patients with chronic pancreatic disease. This was related to pancreatic inflammation in chronic pancreatitis and to several factors, among which jaundice and pancreatic damage, in pancreatic cancer.