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Background: A point-of-care diagnostic test for acute pancreatitis could help in early triage and management of this condition. Materials & methods: Urine trypsinogen dipstick test (UTDT) was performed in consecutive cases suspected to have acute pancreatitis and diagnostic accuracy calculated. Results: Of 187 patients, 90 were have acute pancreatitis and UTDT was positive in 61 (67.7%). In the 97 non pancreatitis cases, UTDT was positive in nine (9.3%). The sensitivity and specificity of UTDT for acute pancreatitis was 67.8% and 90.7%, respectively. In patients presenting within 3 days of abdominal pain, sensitivity and specificity were 72.7% and 91.8%, respectively. Discussion: While offering the possibility of a point of care diagnosis, the low sensitivity of UTDT could be a concern with its routine use.

Acute kidney injury (AKI) is a serious complication of acute pancreatitis (AP), which occurs in up to 70% of patients with severe AP and significantly increases the risk of mortality. At present, AKI is diagnosed based on dynamic increase in serum creatinine and decreased urine output; however, there is a need for earlier and more accurate biomarkers. The aim of the study was to review current evidence on the laboratory tests that were studied as the potential biomarkers of AKI in AP. We also briefly summarized the knowledge coming from the studies including sepsis or ICU patients since severe acute pancreatitis is associated with systemic inflammation and organ failure. Serum cystatin C and serum or urine NGAL have been shown to predict or diagnose AKI in AP; however, this evidence come from the single center studies of low number of patients. Other markers, such as urinary kidney injury molecule-1, cell cycle arrest biomarkers (tissue inhibitor metalloproteinase-2 and urine insulin-like growth factor-binding protein 7), interleukin-18, liver-type fatty acid-binding protein, or calprotectin have been studied in other populations suffering from systemic inflammatory states. In AP, the potential markers of AKI may be significantly influenced by either dehydration or inflammation, and the impact of these factors may be difficult to distinguish from kidney injury. The subject of AKI complicating AP is understudied. More studies are needed, for both exploratory (to choose the best markers) and clinical (to evaluate the diagnostic accuracy of the chosen markers in real clinical settings).

Recognizing patients at early phases of chronic kidney disease (CKD) is difficult, and it is even more challenging to predict acute kidney injury (AKI) and its transition to CKD. The gold standard to timely identify renal fibrosis is the kidney biopsy, an invasive procedure not usually performed for this purpose in clinical practice. SerpinA3 was identified by high-resolution-mass-spectrometry in urines from animals with CKD. An early and progressive elevation of urinary SerpinA3 (uSerpinA3) was observed during the AKI to CKD transition together with SerpinA3 relocation from the cytoplasm to the apical tubular membrane in the rat kidney. uSerpinA3/alpha-1-antichymotrypsin was significantly increased in patients with CKD secondary to focal and segmental glomerulosclerosis (FSGS), ANCA associated vasculitis (AAV) and proliferative class III and IV lupus nephritis (LN). uSerpinA3 levels were independently and positively associated with renal fibrosis. In patients with class V LN, uSerpinA3 levels were not different from healthy volunteers. uSerpinA3 was not found in patients with systemic inflammatory diseases without renal dysfunction. Our observations suggest that uSerpinA3 can detect renal fibrosis and inflammation, with a particular potential for the early detection of AKI to CKD transition and for the differentiation among lupus nephritis classes III/IV and V.

Background: Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis., Aim: To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan., Methods: Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria., Results: A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade., Conclusion: We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis., Competing Interests: Conflict-of-interest statement: The qualitative and quantitative analyses of urinary trypsinogen-2 were performed free of charge by Unitika Ltd. (Osaka, Japan). Mayumi T received research funding. The other authors declare no conflict of interest.

Systemic inflammatory response syndrome (SIRS) prevention is key to severe acute pancreatitis (SAP) treatment and the assessment of high-volume hemofiltration (HVHF) for treating SAP accompanying multiple organ dysfunction syndromes.In this prospective controlled study, 40 SAP patients were divided into 2 groups: control (n = 22, treated with fasting, decompression, and intravenous somatostatin) and HVHF (n = 18, HVHF administration in addition to the treatment in the control group) groups; and were assessed for serum and urine amylase, WBC, C-reactive protein (CRP), and hepatic and renal functions. Vital signs and abdominal symptoms were recorded, and complications and mortality were analyzed.APACHE II scores in the HVHF group were significantly lower than in the control group at 3 and 7 days (6.3 ± 1.7 vs 9.2 ± 2.1 and 3.3 ± 0.8 vs 6.2 ± 1.7, respectively). Compared with controls, serum, and urine amylase, WBC, CRP, and organ functions significantly improved after HVHF treatment. Meanwhile, mortality (16.7% vs 31.8%) and complication (11.1% vs 40.9%) rates were significantly reduced.The other clinical parameters were significantly ameliorated by HVHF. HVHF rapidly reduces abdominal symptoms and improves prognosis, reducing mortality in SAP patients; and is likely through systemic inflammatory response syndrome attenuation in the early disease stage., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A new nano optical sensor binuclear Pd-(2-aminothiazole) (urea), Pd(atz,ur) complex was prepared and characterized for the assessment of the activity of alpha amylase enzyme in urine and serum samples for early diagnosis of Pancreatitis disease. The assessment of alpha amylase activity is carried out by the quenching of the luminescence intensity of the nano optical sensor binuclear Pd(atz,ur) complex at 457nm by the 2-chloro-4-nitrophenol (2-CNP) which produced from the reaction of the enzyme with 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNPG3) substrate. The remarkable quenching of the luminescence intensity at 457nm of nano Pd(atz,ur) doped in sol-gel matrix by various concentrations of the 2-CNP was successfully used as an optical sensor for the assessment of α-amylase activity. The calibration plot was achieved over the concentration range 8.5×10(-6) to 1.9×10(-9)molL(-1) 2-CNP with a correlation coefficient of (0.999) and a detection limit of (7.4×10(-10)molL(-1)). The method was used satisfactorily for the assessment of the α-amylase activity over activity range (3-321U/L) in different urine and serum samples of pancreatitis patients. The assessment of the alpha amylase biomarker by the proposed method increases its sensitivity (96.88%) and specificity (94.41%) for early diagnosis of pancreatitis diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Acute Kidney Injury (AKI) is a serious early complications in patients with acute pancreatitis (AP) that signifcantly increases mortality rates compared to patients without AKI. The early diagnosis of AKI during its treatable phases and implementation of appropriate treatment protocols can improve outcomes for this group of patients. A promising biomarker for AKI is neutrophil gelatinase-associated lipocalin (NGAL)., Aim: This study evaluated the diagnostic value of NGAL concentrations in serum and in urine for patients developing AKI as an early complication of AP compared to AP patients without AKI., Material and Methods: The study group composed of 65 patients (34 men and 31 women) with a mean age of 62.2 ± 16 years with AP and hospitalized in the Surgery Department of the Direct Hospital in Sucha Beskidzka, Poland between January and December 2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer., Results: In the early phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1 and one with stage 2. AKI was associated with more severe AP, higher BISAP scores, the need for more intensive treatment, longer hospital stays and higher mortality. Both serum and urine NGAL concentrations were signifcantly higher in patients with AKI throughout the study and signifcantly predicted AKI in simple and multiple logistic regression adjusted for age, sex and comorbidities. Serum and urine NGAL concentrations were signifcantly correlated with levels of serum urea, creatinine, urine albumin, and the maximum change in serum creatinine. Serum and urine NGAL levels also correlated positively with direct neutrophil counts and CRP concentrations throughout the study., Conclusions: The measurement of NGAL levels, particularly in urine, is simple, easy to interpret, routinely available, and clinically useful in the assessment of dynamic changes in kidney function for patients with AP.

Background: The serum level of amylase (sAm) is commonly used as a biochemical marker for diagnosis and management of pancreatic disorders. However, the use of the urine level of amylase (uAm) is limited in practice, because the diagnostic ability of uAm is inferior to that of sAm. In the present study, the possible concordance of uAm-rerated parameters with sAm was investigated, and evaluate the usefulness of uAm for management of hyperamylasemia., Methods: From June 1995 to October 2009, 804 samples of both urine and blood were collected from 128 patients in order to measure the serum level of amylase (sAm) and the urine level of amylase (uAm) and creatinine (uCr). Concordance of parameters using uAm compared to sAm was assessed. Parameters used were uAm, amylase creatinine clearance ratio (ACCR), and the ratio of uAm to uCr (uAm/uCr)., Results: uAm/uCr had the best correlation with sAm (r = 0.779, p < 0.001) compared to uAm (r = 0.620, p < 0.001) and to ACCR (r = 0.374, p < 0.001), when sAm was over the standard level. The area under the receiver operating characteristic curve of uAm/uCr (0.884) was significantly higher than that of uAm (0.766) and of ACCR (0.666) (p < 0.001 for each). The cutoff value of uAm/uCr was 569.8, with a sensitivity of 81.0% and a specificity of 83.1%., Conclusions: The uAm/uCr ratio correlated with sAm, and may be an alternative to sAm for prediction of hyperamylasemia. Use of urine samples results in a decreased need for blood sampling, which is especially beneficial in pediatric patients.

Background: Currently, serum amylase and lipase are the most popular laboratory markers for early diagnosis of acute pancreatitis with reasonable sensitivity and specificity. Urinary trypsinogen-2 (UT-2) has been increasingly used but its clinical value for the diagnosis of acute pancreatitis and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has not yet been systematically assessed., Data Sources: A comprehensive search was carried out using PubMed (MEDLINE), Embase, and Web of Science for clinical trials, which studied the usefulness of UT-2 as a diagnostic marker for acute pancreatitis. Sensitivity, specificity and the diagnostic odds ratios (DORs) with 95% confidence interval (CI) were calculated for each study and were compared with serum amylase and lipase. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated., Results: A total of 18 studies were included. The pooled sensitivity and specificity of UT-2 for the diagnosis of acute pancreatitis were 80% and 92%, respectively (AUC=0.96, DOR=65.63, 95% CI: 31.65-139.09). The diagnostic value of UT-2 was comparable to serum amylase but was weaker than serum lipase. The pooled sensitivity and specificity for the diagnosis of post-ERCP pancreatitis were 86% and 94%, respectively (AUC=0.92, DOR=77.68, 95% CI: 24.99-241.48)., Conclusions: UT-2 as a rapid test could be potentially used for the diagnosis of post-ERCP pancreatitis and to an extent, acute pancreatitis. Further studies are warranted to confirm these results.

Aim: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission., Methods: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated., Results: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively., Conclusion: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.

Background: To study the role of urinary trypsinogen-2 in diagnosing and early prognosis of patients with acute pancreatitis (AP) and the relationship to length of hospital stay and mortality., Methods: Forty-two patients were included in the study. In all cases, blood cell count, serum chemistry, urine amylase and urine trypsinogen-2 were measured. A cut-off of 50 microg/L was established and, when positive, a second dilution was made (2000 microg/L). Other variables included were etiology, mean length of hospital stay, transfer to an ICU and death., Results: Out of the 42 patients, 29 (69%) were men and 13 (31%) women. Average age was 61 years. The most frequent cause was biliary, followed by alcohol. Mean hospital stay was 8.38 days. Transferred to an ICU: 4 (9.5%) patients. Two of them and a third, who had not been transferred, died (7.14%). High serum amylase was found in 33 (78.57%) patients and high lipase in 36 (85.71%). Urinary trypsinogen-2 was positive in 34 patients (80.95%). Statistical association between urinary trypsinogen-2 and age (p=0.016; r=0.893), glucose (p=0.005; r=0.901), serum amylase (p=0.029; r=0.852), lipase (p=0.022; r=0.809) and hypoxemia (p=0.001; r=0.962) was found. Regarding hospital stay, there was statistical association with age (p=0.046; r=0.784) and metabolic acidosis (p=0.016; r=0.839). With respect to mortality there was statistical association with hypocalcemia (p=0.008; r=0.899) and metabolic acidosis (p=0.032; r=0.814)., Conclusion: Testing urinary trypsinogen-2 in patients with AP is rapid and useful. Patients over the age of 65 with hypoxia, metabolic acidosis and hypocalcemia tend to present a prolonged average hospital stay and higher mortality.

Patients in the early phase of acute pancreatitis (AP) have reduced serum levels of arginine and citrulline. This may be of patho-biological importance, since arginine is the substrate for nitric oxide, which in turn is involved in normal pancreatic physiology and in the inflammatory process. Serum amino acid spectrum was measured daily for five days and after recovery six weeks later in 19 patients admitted to the hospital for acute pancreatitis. These patients had abnormal levels of most amino acids including arginine, citrulline, glutamine and glutamate. Phenylalanine and glutamate were increased, while arginine, citrulline, ornithine and glutamine were decreased compared to levels after recovery. NO(2)/NO(3) concentration in the urine, but not serum arginase activity, was significantly increased day 1 compared to day 5 after admission. Acute pancreatitis causes a disturbance of the serum amino acid spectrum, with possible implications for the inflammatory process and organ function both in the pancreas and the gut. Supplementation of selected amino acids could possibly be of value in this severe condition.

Aim: To evaluate the use of the trypsinogen-2 dipstick (Actim Pancreatitis) test for early diagnosis and prediction of severity in acute pancreatitis (AP)., Methods: Ninety-two patients with AP were included in this study. The control group was 25 patients who had acute abdominal pain from non-pancreatic causes. Urine trypsinogen-2 dipstick test (UTDT) and conventional diagnostic tests were performed in all patients. Patients were divided by the Atlanta classification into two groups as having mild or severe pancreatitis., Results: UTDT was positive in 87 (94.6%) of the AP patients and in two (8%) controls (P < 0.05). Positive UTDT was found in 61 (92.4%) of 66 (71.7%) patients with mild pancreatitis and in all (100%) of the 26 (28.3%) with severe pancreatitis (P > 0.05). UTDT positivity lasted longer in severe pancreatitis compared with that in mild pancreatitis (6.2 +/- 2.5 d vs 2.0 +/- 1.43 d, P < 0.05). The sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of UTDT were 91%, 72%, 96.6%, 70.4%, 3.4 and 0.1, respectively., Conclusion: UTDT is a simple, rapid and reliable method for use on admission. It has high specificity and low NLR for early diagnosis and prediction of severity in AP. However, its relatively low NPV does not allow trypsinogen-2 dipstick test to be a stand-alone tool for diagnosis of acute pancreatitis; the use of other conventional diagnostic tools remains a requirement.

The purpose of this study was to compare the clinical utility of the serum concentration of feline trypsin-like immunoreactivity (fTLI), the plasma and urine concentrations of trypsinogen-activation peptide (TAP), and the ratio of the urine TAP and creatinine concentrations (TAP:Cr) in the diagnosis of feline acute pancreatitis. We used 13 healthy cats and 10 cats with a diagnosis of acute pancreatitis. The mean serum fTLI and plasma TAP concentrations were significantly higher in the cats with acute pancreatitis than in the healthy cats (P < 0.05); the mean urine TAP concentrations and the median urine TAP:Cr ratios were not significantly different. Among the cats examined in this study, there was no benefit of plasma TAP over serum fTLI in the evaluation of suspected acute pancreatitis.

Aim: Acute pancreatitis (AP) is the most common and often severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine (ACC) can reduce the severity of disease in experimental model of AP., Methods: One hundred and six patients were randomly allocated to two groups. Fifty-five patients were given N-acetylcysteine (two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv, twice a day for two days after the ERCP). The control group consisted of 51 patients who were given iv. isotonic saline twice a day for two days after the ERCP. Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure. The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity., Results: There were no significant differences in the rate of post-ERCP pancreatitis between two groups (10 patients overall, 4 in the ACC group and 6 in the control group). There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group., Conclusion: N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis, as well as on serum and urine amylase activity.

Context: All work on human trypsinogen activation peptide (TAP) in acute pancreatitis has been carried out with the same assay. Despite the extensive use of this original TAP assay, there is no characterization of the TAP-like immunoreactivity measured., Objective: The aims of this study were to develop an additional TAP assay and to attempt to characterize the TAP-like immunoreactivity found in the urine of patients with acute pancreatitis., Methods: Antibodies against the human TAP were prepared using the whole octapeptide APFD4K, conjugated at its N-terminal end. Characterization of the immunoreactivity measured with these assays was performed using gel filtration of human pancreatic juice before and after activation of trypsinogen with enterokinase., Results: After activation of the pancreatic juice, there was a large initial increase in immunoreactive TAP and a decrease 6-24 hours later. Using our antiserum, we found low levels of immunoreactive TAP in urine from patients with acute pancreatitis, although many of these samples contained high levels of immunoreactive TAP when tested with the commercially available TAP kit (Biotrin). The pentapeptide D4K, used as a standard in the Biotrin kit, showed much lower immunoreactivity than the synthetic octapeptide APFD4K in our assay. The octapeptide, however, reacted similarly to D4K in the Biotrin kit assay., Conclusion: n Our antibody prepared against the synthetic octapeptide APFD4K is directed against the N-terminal part of the octapeptide and does not recognize the pentapeptide D4K. Immunoreactive TAP in urine in acute pancreatitis is mainly composed of the C-terminal pentapeptide, D4K.

Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in "idiopathic" acute recurrent pancreatitis.

Aim: To assess the usefulness of urinary trypsinogen-2 test strip, urinary trypsinogen activation peptide (TAP), and serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) in the diagnosis of acute pancreatitis., Methods: Patients with acute abdominal pain and hospitalized within 24 h after the onset of symptoms were prospectively studied. Urinary trypsinogen-2 was considered positive when a clear blue line was observed (detection limit 50 microg/L). Urinary TAP was measured using a quantitative solid-phase ELISA, and serum and urinary CAPAP by a radioimmunoassay method., Results: Acute abdominal pain was due to acute pancreatitis in 50 patients and turned out to be extrapancreatic in origin in 22 patients. Patients with acute pancreatitis showed significantly higher median levels of serum and urinary CAPAP levels, as well as amylase and lipase than extrapancreatic controls. Median TAP levels were similar in both groups. The urinary trypsinogen-2 test strip was positive in 68% of patients with acute pancreatitis and 13.6% in extrapancreatic controls (P<0.01). Urinary CAPAP was the most reliable test for the diagnosis of acute pancreatitis (sensitivity 66.7%, specificity 95.5%, positive and negative predictive values 96.6% and 56.7%, respectively), with a 14.6 positive likelihood ratio for a cut-off value of 2.32 nmol/L., Conclusion: In patients with acute abdominal pain, hospitalized within 24 h of symptom onset, CAPAP in serum and urine was a reliable diagnostic marker of acute pancreatitis. Urinary trypsinogen-2 test strip showed a clinical value similar to amylase and lipase. Urinary TAP was not a useful screening test for the diagnosis of acute pancreatitis.

Background: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass., Methods: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured., Results: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively., Conclusion: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.

Objective: To investigate the value of urinary trypsinogen activation peptide (TAP) in the early prediction of severe acute pancreatitis and to compare it with acute physiology and chronic health evaluation II (APACHE II)., Methods: We assessed the predictive value of urinary TAP concentrations measured by a competitive enzyme-linked immunosorbent assay. Urine samples were collected for detecting TAP concentrations at admission, and 24, 48, and 72 h from 41 patients with acute pancreatitis (12 with severe disease, 29 with mild disease) who presented within 48 h the onset of symptoms and from 11 control patients, while APACHE II scores were recorded at 48 h after admission., Results: The peak median urinary TAP concentration was seen at admission. The median urinary TAP concentration at admission for severe pancreatitis (95 nmol/L) was significantly higher than the median for patients with mild pancreatitis (20 nmol/L, P<0.005) and controls (15 nmol/L, P<0.005). TAP concentrations were significantly higher in patients with severe acute pancreatitis than the median in patients with mild pancreatitis (P<0.05) and controls (P<0.05) on days 2 to 3. The median APACHE II scores of severe patients were significantly different from those of mild patients (10.5 vs 6.0, P<0.01). The sensitivity, specificity, positive predictive, and negative predictive values of an admission urinary TAP>/=35 nmol/L for severe pancreatitis were 91.7%, 89.7%, 78.6% and 96.3%, whereas 48 h after admission the values for APACHE II scores (>/=9) were 75.0%, 72.7%, 52.9% and 87.5%. In prediction of disease severity, the urine TAP concentration was much better than APACHE II at 48 h., Conclusions: Urinary TAP obtained at the first 48 h of the onset of symptoms can predict severe acute pancreatitis. In prediction of disease severity, the urinary TAP is much better than APACHE II score.

Background: Early identification of patients at risk of developing a severe attack of acute pancreatitis (AP) is of great importance because rapid therapeutic interventions improve outcome. At a cutoff of 50 microg/L, trypsinogen-2 measured by a rapid urinary dipstick is a sensitive and specific diagnostic test in AP. The trypsinogen-2 concentration correlates with the severity of the disease, and a test with a higher cutoff might therefore be useful for prediction of disease severity., Methods: We increased the detection limit of the urinary trypsinogen-2 test strip (Actim Pancreatitis) from 50 microg/L to 2000 microg/L and evaluated the prognostic value of this test. The results were compared with those obtained with serum C-reactive protein and the acute physiology and chronic health evaluation II (APACHE II) score. The study population consisted of 150 consecutive patients with AP (42 with severe disease)., Results: The sensitivity of the rapid urinary test strip (detection limit, 2000 microg/L) for prediction of severe AP, both on admission and at 24 h, was 62%; specificities were 87% and 85%, respectively, positive predictive values were 65% and 62%, and negative predictive values were 85% and 85%. C-Reactive protein had a sensitivity of only 38% on admission, but at 24 h, it was 83%; specificities were 90% and 70%, respectively, whereas positive predictive values were 59% and 52%, and NPVs were 79% and 91%, respectively. On admission the positive-likelihood ratio for the urinary trypsinogen-2 test strip was 4.8, and at 24 h it was 4.2; for C-reactive protein, the values were 3.7 and 2.7, respectively., Conclusions: The urinary trypsinogen-2 dipstick is a simple and rapid method for prediction of severe acute pancreatitis.

Disturbances of the intestinal integrity, reflected by an increased intestinal permeability, are reported in cystic fibrosis (CF). Controversy exists whether the increased intestinal permeability is due to CF itself or a consequence of the concomitant exocrine pancreatic insufficiency (PI). We measured intestinal permeability by the sugar absorption test in 32 PI patients: 20 CF-PI, 12 nonCF-PI with chronic pancreatitis, and 50 controls. In the sugar absorption test, the lactulose/mannitol ratio is measured in 5-h urine samples after oral ingestion of a solution of lactulose and mannitol, hyperosmolar by the addition of sucrose. The lactulose/mannitol ratio was increased in both CF-PI and nonCF-PI versus controls (p < 0.0001). In CF, the L/M ratio and permeability for lactulose and mannitol did not change by increasing pancreatic enzyme supplementation by 30-50% for 2 wk (p = 0.74, p = 0.97, p = 0.74, respectively) nor by decreasing the osmolarity of the test solution by 75% (p = 0.24, p = 0.10, p = 0.39, respectively). We conclude that an increased intestinal permeability in CF is probably a consequence of PI and is not related to the dose of pancreatic enzyme supplementation nor the osmolarity of the test solution. The increase is due to an increased permeability for lactulose which might point toward a defect in the tight junctions of the villi and/or crypts. The cause of the increased intestinal permeability in the presence of PI is still unclear. An increased intestinal permeability points toward an impaired functional integrity of the small bowel, which may contribute to gastrointestinal dysfunction in CF.

We examined the clinical utility of urine trypsinogen-2 as a marker of acute pancreatitis (AP). Fifty-nine patients with AP, 42 with acute abdominal diseases of extrapancreatic origin, and 63 without evidence of acute abdominal disease were studied. Urine trypsinogen-2 was determined by a time-resolved immunofluorometric assay. As reference methods we used serum trypsinogen-2, urine amylase, and serum amylase. The diagnostic accuracy of the markers was evaluated by receiver-operating characteristic (ROC) analysis. At admission, urine trypsinogen-2 differentiated patients with AP from controls with high accuracy. The area under the ROC curve (AUC) was 0.978, which was equal to that of serum trypsinogen-2 (0.998) and serum amylase (0.969) and significantly larger than that of urine amylase. For differentiation between severe and mild AP, urine trypsinogen-2 (0.730) was equal to serum trypsinogen-2 (0.721), and clearly better than amylase in serum and urine. These results suggest that determination of urine trypsinogen-2 is a useful test to detect AP and to evaluate disease severity.

Human choriogonadotropin (hCG), its free beta subunit (beta hCG), and the core beta hCG fragment (c beta hCG) were measured by highly sensitive time-resolved immunofluorometric assays in the serum and urine of 29 patients with pancreatic cancer, 7 patients with biliary cancer, and 45 patients with benign pancreatic or biliary diseases. The results were compared with those of an age- and sex-matched reference population of nonpregnant women and men. Of the various forms of hCG assayed in serum, beta hCG showed the best diagnostic accuracy, and c beta hCG was the best marker in urine. Elevated serum concentrations of beta hCG were observed in 72% of the patients with pancreatic cancer, in 6 of 7 patients with biliary cancer, and in 9% of those with benign disorders. The serum concentrations of c beta hCG were elevated in 45%, 57%, and 2%, respectively, and those in urine in 55%, 71%, and 11%, respectively. The molar concentrations of c beta hCG in serum were mostly lower than those of beta hCG. Thus beta hCG secreted into serum appears to be the main source of c beta hCG in urine. Provided that they are measured by sufficiently sensitive and specific assays, beta hCG in serum and c beta hCG in urine appear to be useful markers for pancreatic and biliary cancer.

Amylase isoenzymes, separated by polyacrylamide gel electrophoresis, were measures in 25 normal persons (mean amylase to creatinine clearance ratio 3.0%), 15 patients with acute pancreatitis (mean clearance ratio 9.5%, P less than 0.0001), and 6 patients with hyperamylasemia due to common duct stones (mean clearance ratio 4.1%). Two isoamylases (P1, P2) resembling pancreatic isoenzymes and three isoamylases (S1, S2, S3) resembling salivary isoenzymes appeared regularly in normal serum and urine. Salivary amylases predominated in serum, but pancreatic amylases predominated in urine. This finding is consistent with renal clearance of pancreatic amylases exceeding that of salivary amylases under normal conditions. In patients with pancreatitis or common duct stones, essentially all of the increased amylase activity in serum and urine was due to pancreatic isoamylases (P1 and P2) in their normal proportions. No new or altered amylase isoenzymes were detected. The fraction of pancreatic amylases in the serum or urine was identical for the two diseases. Whereas the difference in amylase to creatinine clearance ratios observed between the two groups of patients is not a function of different amylase isoenzymes presented to the kidney, we conclude that the increased amylase clearance in acute pancreatitis is caused by an alteration of renal transfer of amylase, either at the glomerulus or tubule.

The Rapignost-Amylase urinary test strip (Behringwerke Laboratories) provides an estimation of urine amylase which takes a few minutes and is easy to perform. During a period of 9 months, 84 patients had their urine tested with this strip by casualty officers in the Accident and Emergency Department of St George's Hospital, London. In addition, urine amylase, and plasma amylase and creatinine were measured in the chemical pathology laboratory. In all but one instance, the result of the strip test agreed with the laboratory result. The Rapignost strip should prove useful in screening for acute pancreatitis in situations where there is likely to be a delay in obtaining a laboratory amylase result.

In patients with chronic pancreatitis, the development of exocrine pancreatic failure is generally thought to be an irreversible process. We found evidence to the contrary in a prospective study of 70 patients who were evaluated by endoscopic retrograde cholangiopancreatography and sequential measurements of stool fat, percent urinary PABA excretion, and serum trypsin during a follow-up time period of 1-4 yr. Initial p-aminobenzoic acid (PABA) testing showed exocrine failure in 51 patients, 35 of whom had low serum trypsin levels while 14 (27%) disclosed unexpectedly high trypsin concentrations. Ductal morphology was similar in patients with low and high trypsin values. In 8 of the latter cases, steatorrhea improved and pancreatic function tests became normal after pancreaticojejunostomy in 4 patients, alcohol abstinence in 3 patients, and spontaneous resolution of a pseudocyst in 1 patient. Pancreatic cancer was present in a further 3 patients. Of the 37 patients with low PABA and low trypsin at the outset, there was no improvement of exocrine function in 17 of 18 who were surgically treated. Conservative treatment had a similar effect in another 6 patients who were available for follow-up in this group. The mean duration of symptomatic disease was shorter (p less than 0.001) in patients with low PABA and high trypsin levels (1.4 +/- 1.2 yr) than in those with low PABA and low trypsin levels (4.5 +/- 1.3 yr). The results show that up to 20% of patients with chronic pancreatitis have exocrine pancreatic failure, which is apparently due to early ductal obstruction of a gland with preserved function; this situation can be suspected when low urinary PABA excretion and high serum trypsin levels are simultaneously found; and (c) exocrine failure may be reversible in these patients by using a pancreatic drainage procedure or alcohol abstinence. Such a peculiar pattern of pancreatic function tests may also suggest pancreatic cancer.

The serum and urine concentrations of a tumour-associated trypsin inhibitor, TATI, were determined by radioimmunoassay in patients with pancreatic cancer and with benign pancreatic and biliary diseases. Elevated serum levels (greater than 20 micrograms l-1) were found in 85% of the patients with pancreatic cancer, and elevated urine levels (greater than 50 micrograms g-1 creatinine) in 96% of the patients. Thus low TATI level, especially in urine, makes the possibility of pancreatic cancer less likely. Serial assay of TATI in serum from three patients with surgically removed pancreatic cancer showed elevation of the TATI level at the time of detection of recurrence. However, high serum and urine levels were also seen in pancreatitis and in benign extrahepatic cholestasis. Thus TATI is a sensitive, although not specific, indicator of pancreatic and biliary disease, but the use of TATI as a tumour marker in the primary diagnosis of pancreatic cancer is limited. Immunohistochemical staining of pancreatic lesions showed that half of the pancreatic tumours expressed TATI, but the pancreatic tissue adjacent to a carcinoma always stained stronger than the carcinoma. It therefore seems that the main source of TATI in serum and urine of patients with pancreatic cancer are the normal acini and not the tumour tissue. In pancreatitis the staining was intense and clearly stronger than in normal pancreas.

Isoamylase determinations and measurements of the ratio of the renal clearance of amylase relative to creatinine (CAm/CCr) were employed in an attempt to improve the diagnostic accuracy of the standard amylase measurement. An elevated CAm/CCr reflects defective proximal tubular reabsorption of amylase which occurs in virtually all patients with clear-cut acute pancreatitis. However, other conditions that apparently are associated with acute defective tubular function, such as burns and diabetic acidosis, may cause an elevated ratio. Thus, elevations of CAm/CCr cannot be considered to be specific for acute pancreatitis. Pancreatic isoamylase represents, on the average, about 33% of the normal serum amylase activity, whereas about 66% is salivary-type isoamylase. Isoamylase measurements are useful in determining whether an elevated value for serum amylase activity is of pancreatic origin. However, this measurement is not useful for determining whether patients with normal serum amylase activity have pancreatitis.

To verify whether renal tubular dysfunction may account for the CAm/CCr enhancement in acute pancreatitis (AP), we have measured the renal excretion of amylase, lysozyme, and gamma-glutamyl-transpeptidase (GGTP) in 22 patients with AP and in 8 with acute tubular necrosis. While the CAm/CCr ratio was elevated in most patients with AP, the CLys/CCr ratio fell within the normal range in 60% of these patients. The subdivision of patients with AP in subgroups with elevated and normal CLys/CCr ratios revealed a mean CAm/CCr not statistically different. Moreover, no correlation was present in AP between amylase vs. both lysozyme and GGTP clearances. These data suggest that tubular dysfunction does occur in some but not in all the patients with AP and seems not to play a major role in the pathogenesis of the increased CAm/CCr ratio in this condition.

An elevated CAm/CCr ratio has been used as evidence for the frequent occurrence of acute pancreatitis in the postoperative period. We measured CAm/CCr pre and postoperatively in 28 patients undergoing extraperitoneal surgical procedures. None of the patients had clinical evidence of pancreatitis, although 2 of the 28 patients had elevated CAm/CCr ratios preoperatively. Mean CAm/CCr rose from a preoperative level of 2.3 +/- 0.3% (1 SE) to 3.2 +/- 0.3% on the first postoperative day (P less than 0.001). Of the 26 patients with normal preoperative CAm/CCr, 12% (3 of 26) developed a clearly abnormal ratio and 12% (3 of 26) developed borderline elevated values. An elevated CAm/CCr appears to be a nonspecific postoperative finding and cannot be used as evidence of acute pancreatitis during this period.

Until now use of the PABA test together with [14C] PABA to calculate the PABA excretion index has probably been the best adaptation suggested to enhance the specificity of this non-invasive pancreatic function test. Drawbacks of the method are the application of radioactivity, the fact that children, pregnant women, and patients with renal insufficiency have to be excluded from the test, and the possible interference of drugs and isotopes. We propose simultaneous administration of p-aminosalicylic acid (PAS) in the PABA test and quantification of the urinary PABA and PAS excretion with liquid chromatography. Urinary PABA and PAS excretion in six hours are comparable (69.5 +/- 8.4% and 65.6 +/- 18.4% respectively in five healthy volunteers). Application of the PABA/PAS ratio was compared with the urinary PABA excretion in 21 normal controls, 38 patients with pancreatic disease, and 42 patients without pancreatic pathology. The PABA/PAS ratio and the per cent PABA excretion correlated very well in pancreatic patients: (PABA/PAS ratio) = 0.0149 (% PABA) + 0.052 (r = 0.902). Use of the PABA/PAS ratio enhanced the specificity of the test from 76 to 89%.

Urinary recovery and plasma time curve of PABA were determined in 15 control subjects and 65 patients during a six hour period after ingestion of a meal containing 1 g BT-PABA (2.333 mmol PABA). In controls, the plasma PABA time curve registered a peak at two hours followed by a rapid decrease to reach its lowest value at six hours. In patients with chronic pancreatitis (n=32), the peak was lower and was followed by a slow decrease; furthermore, it was delayed in those with severe pancreatic insufficiency. The best discrimination between controls and patients with chronic pancreatitis was obtained by using the maximal value of plasma PABA (MPPABA) at two or three hours. In 56 subjects a hyperbolic relationship between MPPABA and duodenal lipase output stimulated by a meal was mathematically demonstrated and it was calculated that the lower limit of normal MPPABA (mean -2 SD) corresponded to a lipase output equal to 20.6% of the mean value of normal subjects (lower limit of normal lipase output = 40%). By comparison, steatorrhoea occurred when lipase output was less than 10%. Consequently, MPPABA was low not only in all patients with steatorrhoea but also in some who had pancreatic deficiency but normal daily faecal fat. With lipase output as the reference, 12 subjects who had normal MPPABA were proved to have falsely abnormal urinary results. Urinary PABA excretion after oral administration of 2.333 mmol free PABA was also determined in 27 subjects. The PABA excretion index (PEI) was calculated: PEI = PABA urinary excretion after BT-PABA/PABA urinary excretion after free PABA. Seven patients with normal MPPABA but low urinary excretion after BT-PABA had a normal PABA excretion index. It was also observed that, in five patients with intestinal disease, free PABA absorption was not impaired. In conclusion, BTPABA test with MPPABA determination used as an index of exocrine function is (1) less sensitive than Lundh's test, but more sensitive than steatorrhoea; (2) more specific than the test with urinary recovery determination alone, and as specific as PABA excretion index, which requires a double test.

Serial six hourly urine collections were made for seven days on 20 patients with acute pancreatitis. Quantitative immunoassay of urinary albumin and IgG on the first urine sample after admission showed increased excretion rates in 14 and 13 patients, respectively. Urinary protein excretion rates remained normal or approached normal by seven days in 17 patients who made uneventful recoveries. The maximum urinary excretion rates of both albumin and IgG within the first 36 hours correlated with the serum C-reactive protein concentration 72 hours after admission. The highest IgG excretion rates were found in three patients who later developed severe complications. These preliminary data suggest that low proteinuria is a very early response in acute pancreatitis, and that it may reflect the severity of inflammation.

As a quantitative test of iron storage the six-hour urinary excretion of iron was measured after the intravenous infusion of the iron-chelating agent diethylenetriamine penta-acetic acid (D.T.P.A.). The value of this test in determining the presence and magnitude of the total body iron stores was assessed in patients with diseases of iron storage. In patients with idiopathic haemochromatosis and in their first-degree relatives with increased iron stores as measured by hepatic biopsy, the result of the D.T.P.A. test fell progressively as iron stores were reduced by venesection therapy. There was a significant correlation between the result of the D.T.P.A. test and the excess iron storage as measured retrospectively by the effects of venesection therapy, and also between the D.T.P.A. test and the unsaturated iron-binding capacity (U.I.B.C.) in these patients. In patients with excess iron stores due to diseases other than idiopathic haemochromatosis (e.g., alcoholic cirrhosis, haemochromatosis associated with refractory anaemia) the D.T.P.A. test demonstrated the presence of excess iron stores, but the results were very variable and did not correlate closely with the U.I.B.C. or the degree of hepatic haemosiderin deposits. Unexpectedly high results for the D.T.P.A. test were found in some patients with iron-deficiency anaemia.