Activated matrix metalloproteinase 8 in serum predicts severity of acute pancreatitis.

OBJECTIVES: Severe acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP-8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP. METHODS: The study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis. RESULTS: Serum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542-738 ng/ml) compared to MSAP (358 ng/ml, 175-564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128-507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively). CONCLUSIONS: Serum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP.

Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in Relation to Disease Severity.

Intracellular signalling in blood leucocytes shows multiple aberrations in acute pancreatitis (AP) complicated by organ dysfunction (OD). We studied whether the aberrations associate with severity of AP and occur in sepsis complicated by OD. The study comprises 14 sepsis patients (11 with shock), 18 AP patients (nine mild; six moderately severe; three severe) and 28 healthy volunteers. Within 48 h after admission to hospital, phosphorylation of nuclear factor-ĸB (NF-ĸB), signal transducers and activators of transcription (STATs) 1,3, and extracellular signal-regulated kinases 1/2 were measured from stimulated or non-stimulated leucocytes using phosphospecific whole blood flow cytometry. In sepsis, as compared with healthy subjects, phosphorylated NF-ĸB levels of monocytes promoted by bacterial lipopolysaccharides, tumour necrosis factor or Escherichia coli cells were lower (P < 0.001 for all), pSTAT1 levels of monocytes promoted by IL-6 were lower (P < 0.05 for all), and STAT3 was constitutively phosphorylated in monocytes, neutrophils and lymphocytes (P < 0.001 for all). In AP, severity was associated with proportions of pSTAT1-positive monocytes and lymphocytes promoted by IL-6 (P < 0.01 for both), constitutive STAT3 phosphorylation in neutrophils (P < 0.05), but not with any of the pNF-ĸB levels. Monocyte pSTAT3 fluorescence intensity, promoted by IL-6, was lower in sepsis and AP patients with OD than in AP patients without OD (P < 0.001). Collectively, signalling aberrations in sepsis with OD mimic those described previously in AP with OD. Possibility that aberrations in STAT1 and STAT3 pathways provide novel markers predicting evolution of OD warrants studies including patients presenting without OD but developing it during follow-up.

Classification, Severity Assessment, and Prevention of Recurrences in Acute Pancreatitis.

BACKGROUND: Acute pancreatitis is a common disease, the incidence of which is 75-100/100,000/year in Finland. The worldwide incidence of acute pancreatitis is increasing. The identified mildcases usually show rapid recovery with conservative treatment allowing early discharge. Severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. The revised Atlanta classification of acute pancreatitis was introduced in 2012-2013. A recurrent acute pancreatitis is defined as two or more well-documented separate attacks of acute pancreatitis with complete resolution in between. Alcoholic pancreatitis is the most common recurrent acute pancreatitis type. METHODS: In this review current severity classifications and literature on the prevention of recurrent acute pancreatitis are analyzed. RESULTS: The severity of the disease is classified as mild, moderately severe, and severe acute pancreatitis. Novel entities include acute peripancreatic fluid collections in mild acute pancreatitis and acute necrotic collections in necrotizing acute pancreatitis lesser than 4 weeks after the onset and pancreatic pseudocyst in mild acute pancreatitis and walled-off necrosis in necrotizing acute pancreatitis more than 4 weeks after the onset of the disease. After the first attack of alcohol-induced acute pancreatitis, 46% of the patients develop at least one recurrence within 10- to 20-year follow-up. With repeated intervention against alcohol consumption, it is possible to reduce the recurrences. Removing the gall bladder after biliary pancreatitis is the key preventing recurrences. In mild cases, even during the index admission; in severe cases, it is recommended to wait until the inflammatory changes have resolved. Of total, 59% of the idiopathic pancreatitis had sludge of stones in the gall bladder. In other etiologies, addressing the etiological factor may prevent recurrent acute pancreatitis. CONCLUSIONS: This review describes current use of novel severity classifications and also different possibilities to prevent recurrent acute pancreatitis with different etiologies including idiopathic.

Early gastric cancer: clinical characteristics and results of surgery.

BACKGROUND: Early gastric cancer (EGC) is associated with better prognosis than advanced cancer of the stomach. Unfortunately, EGC accounts for a minority of operated gastric cancers in Europe. The aim of this study was to evaluate the clinical characteristics of EGC and the outcome after surgery. METHODS: The study group comprised 94 EGC patients having undergone surgery at Helsinki University Central Hospital between April 1983 and July 2007. RESULTS: The overall 5-year survival rate of EGC patients was 92.4%. Tumor location in the upper part of the stomach and mixed histological type impaired the prognosis (p = 0.043 and 0.008, respectively). The probability of lymph node metastasis was significantly higher when the tumor infiltrated gastric submucosa rather than mucosa (p = 0.012). Existence of lymph node or distant metastases decreased the survival rates (both p < 0.001). Total gastrectomy, pancreatic resection, and extended D2 lymph node dissection increased the complication rate, but did not have effect on survival. CONCLUSION: The overall prognosis of EGC is favorable. The survival rates of EGC decreased when the tumor was located in the upper part of the stomach or was of mixed histological type, or the patient had lymph node or distant metastasis.

A novel modification of a flow cytometric assay of phosphorylated STAT1 in whole blood monocytes for immunomonitoring of patients on IFN alpha regimen.

We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)alpha regimen. CD14+ monocytes responded strongly to IFNalpha/gamma being sensitive indicators for recent immune activation. At 45 min after s.c. IFNalpha 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long-term deficient phosphorylated STAT1 response to IFNalphain vitro that in patients on standard IFNalpha regimen lasted for 48 h. In patients on pegylated IFNalpha the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.

Clinical outcome after D1 vs D2-3 gastrectomy for treatment of gastric cancer.

BACKGROUND: Clinical benefit from extended lymphadenectomy for gastric cancer remains controversial as a considerable variation exists between results of different studies. METHODS: 562 patients were treated at HUCH between 1987-2003, whereof 223 underwent gastrectomy with curative intent. Of these, 114 patients underwent subtotal/total gastrectomy with D1 (standard) lymphadenectomy and 109 patients had D2-3 (extended) lymph node dissection. The clinical outcome of these patients was analysed retrospectively. RESULTS: The incidence of surgical complications was 33.0% in D2-3 and 16.8% in D1 lymphadenectomy groups (p = 0.008). Abscess was the most common complication (11.0%) among D2-3 operated patients and haemorrhage (4.4%) in D1 group. Hospital mortality was 3.7% in D2-3 and 1.8% in D1 group (p = 0.438). The only statistically significant factor influencing the rate of complications was D2-3 lymphadenectomy (OR 2.620, 95% C.I. 1.375 to 4.991). D2-3 was associated with a longer postoperative hospital stay and operation time, greater blood loss and increased need for blood transfusions compared to D1. The 5-year survival was not statistically different between lymphadenectomy groups. CONCLUSION: It is justified to perform a D2-3 gastrectomy in Europe with a acceptable postoperative mortality but with a significant morbidity. Further studies are needed to assess the value of extended lymphadenectomy in gastric cancer.

Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

BACKGROUND: Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. RESULTS: EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. CONCLUSIONS: ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Endoscopic treatment of pancreatic pseudocysts.

BACKGROUND: This study aimed to assess the effectiveness of therapeutic endoscopy in the treatment of pancreatic pseudocysts, and to define factors limiting endoscopic therapy. METHODS: The results of therapeutic endoscopy were evaluated for 170 patients with pancreatic pseudocysts treated at the Department of Surgery, Helsinki University Central Hospital, during the 6-year period from 1998 to 2003. RESULTS: The therapeutic endoscopy success rate was 86.1%, with 23 (13.9%) patients requiring operative treatment because therapeutic endoscopy was unsuccessful or technically impossible. There was little morbidity and no procedure-related mortality. The majority of the 38 complications, which arose from 380 procedures, could be treated conservatively. CONCLUSIONS: Endoscopic methods are safe and effective for the treatment of pancreatic pseudocysts. The indications for surgery include inaccessible pancreatic duct, location, or content of the pseudocyst rendering the problem not amenable to endoscopic therapy, as well as complications of the endoscopic treatment.

Intron 1 retaining cyclooxygenase 1 splice variant is induced by osmotic stress in human intestinal epithelial cells.

The biological roles of intron 1 retaining cyclooxygenase (Cox) 1 splice variants Cox-3 and PCox-1a (Cox-1ir) are not known. In humans, Cox-3 transcription has previously been shown to occur in the brain and in the aorta. However, conclusive evidence regarding the existence of a human Cox-3 protein is lacking. We studied the expression of intron 1 retaining cyclooxygenase 1 splice variants in the human colon cancer cell line Caco-2 and in human colonic tissue samples. In Caco-2 cells, their transcription was induced up to 47-fold by osmotic stress. The corresponding protein, however, could not be detected by Western blotting. In human colonic tissue samples derived from intact and inflamed areas, a low level of Cox-1ir mRNA (1500 +/- 1280 copies per 100 ng total RNA; mean+/-standard deviation; n = 20) was also found. In Caco-2 cells, induction of Cox-1ir under osmotic stress was reversed by addition of the organic osmolyte betaine. Under hypertonic but not under isotonic conditions, splice variant-specific degradation of Cox-1ir mRNA using RNA interference resulted in increased production of fully spliced Cox-1 and Cox-2 mRNA (P = 0.002). In summary, our results indicate that the intron 1 retaining Cox-1 splice variant RNA molecules are expressed by human intestinal epithelial cells in a controlled manner, are most likely not translated and play a regulatory role in the cyclooxygenase mediated epithelial osmoregulation.

Clinical value of severity markers in acute pancreatitis.

Acute pancreatitis is a common digestive disease of which the severity may vary from mild, edematous to severe, necrotizing disease. An improved outcome in the severe form of the disease is based on early identification of disease severity and subsequent focused management of these high-risk patients. However, the ability of clinicians to predict, upon presentation, which patient will have mild or severe acute pancreatitis is not accurate. Prospective systems using clinical criteria have been used to determine severity in patients with acute pancreatitis, such as the Ranson's prognostic signs, Glasgow score, and the acute physiology and chronic health evaluation II score (APACHE II). Their application in clinical practise has been limited by the time delay of at least 48 h to judge all parameters in the former two and by being cumbersome and time-consuming in the latter. Contrast-enhanced computed tomography is presently the most accurate non-invasive single method to evaluate the severity of acute pancreatitis. It cannot, however, be performed to all patients with acute pancreatitis. Therefore, considerable interest has grown in the development of reliable biochemical markers that reflect the severity of acute pancreatitis. In this article we critically appraise current and new severity markers of acute pancreatitis in their ability to distinguish between mild and severe disease and their clinical utility.

Differential expression of SPARC and thrombospondin 1 in wound repair: immunolocalization and in situ hybridization.

SPARC and thrombospondin 1 (TSP-1) are secreted glycoproteins expressed by similar types of cells in culture and in tissues. To compare these two proteins in vivo, we analyzed the differential expression of SPARC and TSP-1 during wound repair. Full-thickness incision wounds were made in rats and biopsied at 12 hr-14 days. Antibodies against SPARC revealed an increased proportion of immunoreactive fibroblastic cells at the wound edge at 3 days with maximal numbers at 7 days. In situ hybridization for SPARC produced results consistent with those of immunohistochemistry. With combined immunohistochemistry and in situ hybridization, some of the macrophages at the wound edge expressed SPARC mRNA. In contrast, immunoreactivity for TSP-1 was extracellular; expression at the wound edge was noted at 12 hr and was maximal at 1-2 days. TSP-1 mRNA was found in the thrombus, but not at the wound edge. In conclusion, SPARC and TSP-1 have contrasting roles during wound healing. SPARC expression from the middle through late stages of repair was consistent with its previously proposed functions in remodeling; in contrast, the transient expression of TSP-1 early in repair might facilitate the action of other proteins in recruitment and/or proliferation of cells in the healing wound.

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia.

BACKGROUND: There are few data on the natural course of Helicobacter pylori-related atrophic gastritis. AIM: To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus. METHODS: Twenty-two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow-up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy. RESULTS: During the 7.5-year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 microg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy. CONCLUSIONS: The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.

Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study.

AIMS: To assess the risk of gastric carcinoma in patients with histologically verified dysplasia and atrophic gastritis of the stomach. METHODS: One hundred and one patients with mild (n = 84), moderate (n = 14), or severe (n = 3) dysplasia among 359 elderly men who smoked underwent gastroscopy because of low serum pepsinogen. Patients with dysplasia were prospectively followed up for an average of four years with repeated gastroscopies and multiple biopsies. RESULTS: Four of the 84 (4.8%) cases of mild dysplasia had progressed to moderate dysplasia during the follow up. Most of the cases of mild dysplasia had resolved spontaneously. No surgical intervention was required. Three of the 14 (21%) cases of moderate dysplasia had progressed to severe dysplasia, but no carcinomas were observed during follow up. Five moderately dysplastic lesions were removed surgically or endoscopically. In two of these five cases, moderate or severe dysplasia recurred. Two of the three severe dysplasias progressed to carcinoma. CONCLUSIONS: In atrophic gastritis progression of mild and moderate dysplastic lesions seems to be a slow process and is rare in mild dysplasia. However, severe dysplasia is highly predictive of subsequent cancer. It is suggested that a five year follow up interval is sufficient in cases with mild dysplasia and two years in those with moderate dysplasia. Local removal of moderate dysplasia is indicated but does not guarantee that the lesion will not progress. Severe dysplasia requires immediate surgical intervention.

Presence of high-level DNA copy number gains in gastric carcinoma and severely dysplastic adenomas but not in moderately dysplastic adenomas.

Our aim was to investigate the presence of DNA copy number changes in gastric adenomas and to identify the changes that may play a role in gastric carcinogenesis. DNA copy number changes in 16 patients with gastric adenoma and in 22 tumors from patients with intestinal type gastric carcinomas were studied by using comparative genomic hybridization. DNA copy number changes were found in 44% of the adenoma cases and in 86% of the intestinal type gastric carcinomas. On average, gains were more common than losses (0.9 vs. 0.5 in adenomas and 4.1 vs. 1.8 in carcinomas). In adenomas, the most common gains involved chromosome 8 in 3 cases, and gain of chromosome 7 and 20q was detected in 2 cases. The most frequent losses were observed at 5q (three times). Only adenomas with severe dysplasia showed high-level amplifications that were detected at chromosome 13, 17cen-q22, and 20q12-ter. In gastric cancer, the most common gains were detected at 20q (55%), 17q12-q21 (41%), and 8q (41%), and the most common losses were detected at 18q (41%) and 4q (32%). High-level amplifications were observed at 20q (3 tumors), 17cen-q21 (3 tumors), 2p (1 tumor), and 18q (1 tumor). These findings suggest that the progression of dysplasia is associated with higher levels of DNA copy number increase (e.g., the gains at 17q and 20q), which were typically observed in the intestinal type gastric cancer. Furthermore, the results support the hypothesis that adenoma precedes cancer.

DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma.

We screened 18 specimens of Barrett adenocarcinoma for genetic alterations using comparative genomic hybridization (CGH) to analyze DNA copy number changes. The most common gains were at 20q (56%) and 17q (39%). High-level amplifications were observed in the same chromosomes. The most common losses were in chromosomes 4 (22%) and 5 (22%). Other recurrent changes were gains of chromosomes 8, 10q, and 13. We compared the copy number changes in Barrett adenocarcinoma and those previously reported in the intestinal type of stomach carcinoma. The similarities we found suggest a common molecular pathogenesis, whereas dissimilarities seen between Barrett adenocarcinoma and esophageal squamous cell carcinoma are in keeping with a well-known different etiology.

Comparative genomic hybridization reveals differences in DNA copy number changes between sporadic gastric carcinomas and gastric carcinomas from patients with hereditary nonpolyposis colorectal cancer.

Comparative genomic hybridization was used to search for DNA copy number changes in samples of gastric cancer from 12 hereditary nonpolyposis colon cancer (HNPCC) patients and in samples of sporadic gastric carcinoma from 13 patients. The gastric cancer samples from HNPCC patients showed gains affecting 19q, Xp, and whole chromosome 22, each in a single patient. Neither high-level amplifications nor losses of DNA copy number were detected. On the other hand, 10 of the 13 (77%) sporadic gastric carcinoma samples had multiple DNA copy number changes. The most frequent gains occurred with minimal common overlapping regions at 1q22-q31, 8q23-qter, 17p11.2-q22, and 20q, all at a frequency of 31%. High-level amplifications were also seen at 17q21 in three cases (23%). Losses were rare, and the most frequent loss was with a minimal common overlapping region at 4q32 (23%). This suggests that multiple DNA copy number changes are needed for the development of sporadic gastric carcinoma but not for gastric carcinoma in HNPCC patients.

Bactericidal/permeability-increasing protein and group I and II phospholipase A2 during the induction phase of human acute pancreatitis.

Activated endogenous mediators of inflammation have important roles in the pathogenesis and complications of acute pancreatitis (AP). These mediators include bactericidal/ permeability-increasing protein (BPI) and phospholipase A2 (PLA2). The time course of their activation during human AP is not known. The aim of this study was to evaluate the kinetics of BPI, group I (pancreatic) and group II (synovial type) PLA2 during human AP with temporally defined onset, as being induced by endoscopic retrograde cholangiopancreatography (ERCP). Serum samples of 273 consecutive patients undergoing ERCP were collected before and at 3, 6, and 24 h after ERCP. Twenty-four (8.7%) patients developed ERCP-induced pancreatitis. Seven of them were graded to have a severe disease. Forty randomly selected patients undergoing ERCP without evidence of pancreatitis served as controls. The serum concentrations of BPI and groups I and II PLA2 were measured by specific immunoassays. The mean concentration of BPI increased from 14 to 26 microg/L at 24 h after ERCP in patients with AP. In the control group, BPI values remained unchanged, and the difference was statistically significant (p<0.001). The increase of BPI was seen in 22 of 28 patients with AP at 3 h after the onset of the disease. BPI values were higher in severe post-ERCP pancreatitis than in mild disease (p = 0.07; NS). The serum concentrations of group II PLA2 before ERCP were consistently higher in the control patients than in the patients with pancreatitis, 65.8 and 14.2 microg/L, respectively. High baseline values in the control group were associated with preexisting infectious diseases. Thereafter, the mean concentration decreased in the control group to 44 microg/L and increased in the pancreatitis group up to 27.5 microg/L. The difference was statistically significant (p = 0.007). Increased group II PLA2 values were seen in 10 of 17 patients with mild AP and in five of seven patients with severe disease. There were no significant differences in group I or II PLA2 values in patients with mild or severe AP. The serum concentration of group I PLA2 increased in the patients with post-ERCP pancreatitis from 5.4 to 37.5 microg/L at 24 h. The difference was statistically significant, (p< 0.001) as compared with controls. In conclusion, in acute pancreatitis, the increase of BPI in serum starts at 3 h after the onset of the disease, and the concentration seems to correlate with the severity of the disease. Increased group II PLA2 concentrations also were seen in patients with mild AP. The kinetics of group I PLA2 resembles that of other pancreatic enzymes.

Extracellular phospholipases A2 in relation to systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis.

The pathophysiology of severe acute pancreatitis (AP) resembles other conditions with systemic inflammatory response syndrome (SIRS) such as sepsis predisposing to remote organ failure. Because extracellular phospholipases A2 (PLA2) have been implicated in AP, their serum concentrations were analyzed with respect to SIRS and systemic complications in patients with severe AP. The serum samples were collected daily for 12 days in 57 patients with severe AP. SIRS, early organ complications, local complications, and outcome of AP were recorded. Time-resolved fluoroimmunoassays were used for group I and group II PLA2 measurements. Thirty-nine (68.4%) patients fulfilled the criteria of SIRS within 12 days from admission. Pancreatic necrosis was detected in 43 (75.4%) patients. Infected necrosis was found preoperatively or at operation in five (8.8%) patients. Twenty-six (45.6%) and eight (14.0%) patients had respiratory or renal failure, respectively. Seven (12.3%) patients died of their disease. All patients with systemic complications fulfilled the criteria of SIRS. The increasing number of positive SIRS criteria was associated with increased frequency of systemic complications. Pancreatic necrosis was not significantly associated with SIRS. The serum concentration of group II PLA2 was significantly higher in patients with SIRS (p < 0.05) compared with patients without from day 7 onward. The concentration of group II PLA2 increased (p < 0.01) in patients with SIRS but decreased in patients without. The serum concentration of group II PLA2 did not differ significantly with respect to systemic complications. The concentration of group I PLA2 decreased (p < 0.05) similarly in patients with and without SIRS or systemic complications during follow-up, respectively. Early systemic complications of severe AP are associated with SIRS with increasing frequency as the number of positive SIRS criteria increases. Group II PLA2 but not group I PLA2 may have pathophysiologic importance in severe AP-associated SIRS. Increasing serum concentration of group II PLA2 seems to reflect the ongoing systemic inflammation in severe AP-associated SIRS.

Severe acute pancreatitis: prognostic factors in 270 consecutive patients.

Acute pancreatitis (AP) is a common abdominal disorder with severity varying from mild to fatal disease. Predicting a patient's outcome remains problematic. The aim of this study was to analyze a large consecutive series of patients with severe AP and to identify prognostic factors for hospital mortality. Between 1989 and 1997, a consecutive series of 270 patients with severe AP were included in the study. All patients fulfilled the criteria of Atlanta classification for severe AP. Retrospectively and prospectively collected data included age, gender, etiology, number of previous episodes of pancreatitis, medication history, type of admission, body-mass index (BMI), respiratory failure, renal failure, need for pressor support, and abdominal surgery performed during hospitalization. The overall mortality rate was 24.4%. In univariate survival analysis advanced age, history of continuous medication, patient transferred from other hospital, high BMI, respiratory or renal failure, need for pressor support, and need for abdominal surgery were significant prognostic factors for hospital mortality. In a multivariate stepwise logistic regression analysis, the need of pressor support, renal failure requiring dialysis, advanced age, history of continuous medication and need for abdominal surgery were identified as independent prognostic factors for mortality. A logistic regression analysis of variables available on admission (the first seven above mentioned variables) showed that transferral admission, advanced age, and history of continuous medication were independent prognostic factors for mortality. In patients with severe AP, advanced age, history of continuous medication, and need for dialysis, mechanical ventilator support, and pressor support predict fatal outcome and thus should be taken into account in clinical evaluation.

Comparison of urine trypsinogen-2 test strip with serum lipase in the diagnosis of acute pancreatitis.

BACKGROUND/AIMS: The accuracy of a new rapid urinary trypsinogen-2 test strip (actim Pancreatitis) was compared with that of serum lipase for detection of acute pancreatitis in patients with acute abdominal pain. METHODOLOGY: A prospective study was conducted which consisted of 237 consecutive patients with acute abdominal pain admitted to the emergency unit at Helsinki University Central Hospital. The patients were tested on admission with the actim Pancreatitis test strip. Serum amylase, serum lipase, and urine trypsinogen-2 concentrations were also determined quantitatively. RESULTS: The actim Pancreatitis test strip result was positive in 27 out of 29 patients with acute pancreatitis (sensitivity 93%) and in 16 of 208 patients with non-pancreatic abdominal pain (specificity 92%). This was superior to that of serum lipase (sensitivity 79% and specificity 88%). With a cut-off > 3x the upper reference limit, the sensitivity of serum lipase was only 55% while the specificity was 99%. The high sensitivity for the actim Pancreatitis test strip resulted in a very high negative predictive value of 99%. All six patients with severe acute pancreatitis were detected by the dipstick. With a higher cut-off value (> 3x upper reference limit) for lipase, two patients with severe acute pancreatitis remained undetected. Combining the actim Pancreatitis dipstick with serum lipase a positive predictive value of 94% was obtained. CONCLUSIONS: Acute pancreatitis can be excluded with a higher probability with the actim Pancreatitis strip than with serum lipase determination, and therefore appears to be more suitable for screening of acute pancreatitis. With its high specificity with a cut-off > 3x the upper reference limit, serum lipase is suitable as a confirmatory test for pancreatitis when a positive dipstick result is obtained.