R. Haapiainen

Early antibiotic treatment in acute necrotising pancreatitis

Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.

The Risk of Gastric Carcinoma and Carcinoid Tumours in Patients with Pernicious Anaemia: A Prospective Follow-Up Study

BACKGROUNDnThis endoscopic follow-up study was undertaken to evaluate the risk of gastric cancer (GC) and carcinoids in patients with pernicious anaemia (PA) and to analyse whether early detection of GC could be provided by regular endoscopic follow-up.nnnMETHODSnScreening gastroscopy was performed in 71 patients with pernicious anaemia, and thereafter they were followed up with gastroscopies at 3-year intervals for a mean time of 5.8 years. Standardized incidence ratios (SIR) were calculated, the expected number being based on incidence rates in the whole Finnish population.nnnRESULTSnTwo GCs were found during the follow-up period; one of these patients was asymptomatic and the other had abdominal symptoms. The SIR was 5.0 (95% confidence interval, 0.6-18). Eight carcinoids were detected, and all but one were removed endoscopically, and no metastases were found. The patients who had carcinoid tumours were younger at the diagnosis of PA than those who did not develop carcinoids (mean, 40 versus 55 years). Additionally, the patients with carcinoids had longer duration of PA (mean, 11 versus 5 years).nnnCONCLUSIONSnDuring the follow-up period the risk of GC was increased. The risk of gastric carcinoids seems to be very high in patients with pernicious anaemia when compared with a normal population, but they are mostly relatively benign tumours. Regular routine gastroscopic follow-up is not indicated in patients with pernicious anaemia.

Early prediction of organ failure by combined markers in patients with acute pancreatitis.

Several biological markers and clinical scoring systems have been used to predict the course of acute pancreatitis. Because organ failure is the most severe complication of the disease, prognostic markers and their combinations that would predict organ failure on hospital admission were sought.

Diagnosis of Helicobacter pylori Infection in Patients with Atrophic Gastritis: Comparison of Histology, 13C-Urea Breath Test, and Serology

BACKGROUNDnAtrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used.nnnMETHODSnWe compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis.nnnRESULTSnH. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically).nnnCONCLUSIONSnH. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.Background: Atrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used. Methods: We compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis. Results: H. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically). Conclusions: H. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.

Plasma anti‐inflammatory cytokines and monocyte human leucocyte antigen‐DR expression in patients with acute pancreatitis

Background: Immune suppression plays a role in the pathogenesis of acute pancreatitis. The purpose was to describe plasma anti‐inflammatory cytokines and blood monocyte human leucocyte antigen (HLA)‐DR expression, a cellular marker of immune suppression, in relation to clinical outcome in acute pancreatitis. Methods: We studied 74 patients with acute pancreatitis admitted within 72u2005h after symptom onset; 27 had mild disease and 47 severe disease, of whom 20 developed organ failure. Plasma cytokine concentrations and monocyte HLA‐DR density were determined at admission and 1, 2, 3, 7, 14 and 21 days later. Results: The levels of interleukin‐1 receptor antagonist, interleukin‐6 and interleukin‐10 correlated inversely to monocyte HLA‐DR expression; each marker correlated with disease severity. Interleukin‐4, ‐11 and ‐13 levels were low. Organ failure occurred at median 36u2005h (range 8 to 158) after admission and was predicted at admission by the combination of interleukin‐6 and interleukin‐10 with sensitivity of 95%, specificity of 88% and positive likelihood ratio of 7.6 (95% confidence interval 3.3 to 17). Patients with secondary infections had a lower proportion of HLA‐DR positive monocytes than did controls at day 14 (median: 32% versus 65%; nu2005=u20057) and at day 21 (median: 49% versus 83%; nu2005=u20056), Pu2005<u20050.05 each. In the organ failure group, HLA‐DR expression did not differ between survivors and non‐survivors. Conclusions: Determining the severity of anti‐inflammatory reaction at admission and monitoring the course of immune suppression provide a means for predicting clinical outcome in acute pancreatitis.

Cellular markers of systemic inflammation and immune suppression in patients with organ failure due to severe acute pancreatitis.

BACKGROUNDnFew data are available on cellular markers of systemic inflammation and immune suppression in early acute pancreatitis. The aim of this study was to describe the cellular immune inflammatory status of patients with acute pancreatitis in relation to development of organ failure.nnnMETHODSnProspective study including 89 patients who presented within 72 h of onset of pain. Fifty-eight of them had mild disease (Grade I group), 19 had severe disease with no organ dysfunction (Grade II group) and 12 had severe disease with organ dysfunction (Grade III group). Serial blood samples were collected on admission and following 2 days. Phagocyte surface markers were analysed using flow cytometry.nnnRESULTSnThe proportion of HLA-DR-positive monocytes, a marker of immune suppression, and CD11b expression level on neutrophils and monocytes, a marker of systemic inflammation, were related to Grades I-III (P for trend <0.001). In Grade III patients, the proportion of HLA-DR-positive monocytes was low on presentation, or decreased rapidly during follow-up, whereas CD11b expression levels were persistently high. L-selectin and monocyte CD14 expression levels were not related to disease severity.nnnCONCLUSIONSnImmune suppression develops early, rapidly and unexpectedly in patients with acute pancreatitis. Monitoring immune inflammatory status may provide the means by which to identify patients who benefit from biological response modifier therapy.Background: Few data are available on cellular markers of systemic inflammation and immune suppression in early acute pancreatitis. The aim of this study was to describe the cellular immune inflammatory status of patients with acute pancreatitis in relation to development of organ failure. Methods: Prospective study including 89 patients who presented within 72 h of onset of pain. Fifty-eight of them had mild disease (Grade I group), 19 had severe disease with no organ dysfunction (Grade II group) and 12 had severe disease with organ dysfunction (Grade III group). Serial blood samples were collected on admission and following 2 days. Phagocyte surface markers were analysed using flow cytometry. Results: The proportion of HLA-DR-positive monocytes, a marker of immune suppression, and CD11b expression level on neutrophils and monocytes, a marker of systemic inflammation, were related to Grades I-III (P for trend <0.001). In Grade III patients, the proportion of HLA-DR-positive monocytes was low on presentation, or decreased rapidly during follow-up, whereas CD11b expression levels were persistently high. L-selectin and monocyte CD14 expression levels were not related to disease severity. Conclusions: Immune suppression develops early, rapidly and unexpectedly in patients with acute pancreatitis. Monitoring immune inflammatory status may provide the means by which to identify patients who benefit from biological response modifier therapy.

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.

Time Course Profile of Serum Trypsinogen-2 and Trypsin-2-a1-Antitrypsin in Patients with Acute Pancreatitis

Background: Trypsinogen-2 and the trypsin-2a1 antitrypsin complex are recently introduced new laboratory markers for acute pancreatitis. They show high sensitivity and specificity for acute pancreatitis on admission, but little is known on their time course profiles. Methods: The serum concentrations of trypsinogen-2 and trypsin-2a1-antitrypsin were monitored in 92 patients with verified acute pancreatitis. The follow-up period was 42 days in patients with severe acute pancreatitis ( N = 73) and 9 days in mild disease ( N = 19).Results:On admission the mean serum concentration of trypsinogen-2 was 2880 mg/l in severe and 920 mg/l in mild acute pancreatitis. These values were 32and 10-fold the upper reference limit, respectively. Trypsin-2a1-antitrypsin concentrations were 1250 mg/l (100-fold the upper reference limit) and 635mg/l (52-fold), respectively. The differences were statistically significant ( P = 0.026–0.001). The concentrations of trypsinogen-2 and trypsin-2a1-antitrypsin decreased gradually during the follow-up period, but they remained elevated for the entire study period in patients with severe and mild disease. Conclusions: The time course profile of trypsinogen-2 and trypsin-2a1-antitrypsin is favorable for diagnosing acute pancreatitis. The elevation starts within hours after the onset of the disease and it is very steep. Both markers remain elevated longer than amylase and the magnitude of the elevation correlates with the severity of the disease. This is further evidence to support the use of trypsinogen-2 and trypsin-2a1-antitrypsin for the evaluation of patients suspected of having acute pancreatitis.BACKGROUNDnTrypsinogen-2 and the trypsin-2-alpha1-antitrypsin complex are recently introduced new laboratory markers for acute pancreatitis. They show high sensitivity and specificity for acute pancreatitis on admission, but little is known on their time course profiles.nnnMETHODSnThe serum concentrations of trypsinogen-2 and trypsin-2-alpha1-antitrypsin were monitored in 92 patients with verified acute pancreatitis. The follow-up period was 42 days in patients with severe acute pancreatitis (N = 73) and 9 days in mild disease (N = 19).nnnRESULTSnOn admission the mean serum concentration of trypsinogen-2 was 2880 microg/l in severe and 920 microg/l in mild acute pancreatitis. These values were 32- and 10-fold the upper reference limit, respectively. Trypsin-2-alpha1-antitrypsin concentrations were 1250 microg/l (100-fold the upper reference limit) and 635 microg/l (52-fold), respectively. The differences were statistically significant (P = 0.026-0.001). The concentrations of trypsinogen-2 and trypsin-2-alpha1-antitrypsin decreased gradually during the follow-up period, but they remained elevated for the entire study period in patients with severe and mild disease.nnnCONCLUSIONSnThe time course profile of trypsinogen-2 and trypsin-2-alpha1-antitrypsin is favorable for diagnosing acute pancreatitis. The elevation starts within hours after the onset of the disease and it is very steep. Both markers remain elevated longer than amylase and the magnitude of the elevation correlates with the severity of the disease. This is further evidence to support the use of trypsinogen-2 and trypsin-2-alpha1-antitrypsin for the evaluation of patients suspected of having acute pancreatitis.

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 A 2 (PLA 2 ). 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) PLA 2 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 PLA 2 were measured by specific immunoassays. The mean concentration of BPI increased from 14 to 26 μg/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 PLA 2 before ERCP were consistently higher in the control patients than in the patients with pancreatitis, 65.8 and 14.2 μg/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 μg/L and increased in the pancreatitis group up to 27.5 μg/L. The difference was statistically significant (p = 0.007). Increased group II PLA 2 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 PLA 2 values in patients with mild or severe AP. The serum concentration of group I PLA 2 increased in the patients with post-ERCP pancreatitis from 5.4 to 37.5 μg/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 PLA 2 concentrations also were seen in patients with mild AP. The kinetics of group I PLA 2 resembles that of other pancreatic enzymes.

Elevated levels of the complement regulator protein CD59 in severe acute pancreatitis

Objective. Complement activation occurs in patients with acute pancreatitis (AP) and may contribute to the development of organ failure. Because a number of enzymes are released during AP that could influence the complement inhibitor CD59, the purpose of this study was to examine serum levels of CD59 in relation to severity of AP. Material and methods. Twelve patients with severe AP had organ failure (referred to as the grade 2 group). For each of them, we found 2–3 age-matched AP patients who served as controls (n=27). Of these, a total of 13 had mild AP (grade 0 group) and 14 severe AP without organ failure (grade 1 group). Blood samples were collected at admission and on days 1 and 3–7 post-admission. Grade 2 patients were compared with grade 0 and grade 1 patients. CD59 levels were measured by a sandwich enzyme immunoassay. Results. At admission, median CD59 levels were significantly higher (p=0.002) in grade 2 patients (median 104.2 ng/ml, range 26.1–186.3) than in grade 0 patients (37.3, range 30.3–75.9) and grade 1 patients (38.6, range 19.9–96.1). CD59 levels remained higher in grade 2 patients than in grade 0 and 1 patients on day 1 (p=0.001) and days 3–7 (p=0.002). The CD59 levels correlated significantly (p<0.05) with C-reactive protein (CRP) levels (R=0.40) and APACHE II scores (R=0.32) on admission. Conclusions. Organ failure and severity of AP are associated with elevated serum levels of CD59.