Anders Borgström

Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase?

BACKGROUND AND AIMSnRecent reports have suggested an increasing incidence of acute pancreatitis, and changing patterns of risk factors, over the past decades. The aim of this study was to investigate trends in the incidence of acute pancreatitis, and risk factors related to the disease, in a general population over a 15-year period.nnnMETHODSnClinical, autopsy, and forensic records for all patients with a first attack of acute pancreatitis in Malmö, Sweden, from 1985 to 1999, were validated retrospectively. Evidence for diagnosis was reconsidered and plausible cause was assessed. The incidence of gallstone disease, lung cancer, and alcohol-related conditions in the background population were retrieved from hospital diagnosis records and cancer and cause-of-death registries.nnnRESULTSnA total of 929 first attacks of acute pancreatitis were identified. The total incidence of acute pancreatitis increased by 3.9% per year (95% confidence interval [CI], 2.1-5.8). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, 4.0-11.4), and this correlated with an increase in the incidence of other gallstone-related conditions ( r = 0.68; P = 0.005). Alcohol-related pancreatitis decreased by -5.1% per year (95% CI, -7.4 to -2.8), and this correlated with a decrease in the incidence of delirium tremens ( r = 0.75; P = 0.001), mortality from cirrhosis ( r = 0.81; P < 0.001), and incidence of lung cancer ( r = 0.57; P = 0.026).nnnCONCLUSIONSnThere was a statistically significant increase in the incidence of acute pancreatitis. Gallstone-related pancreatitis increased, and alcohol-related pancreatitis decreased. Both of these trends were statistically significant and correlated with trends in the incidence of other conditions associated with either gallstone disease or alcohol abuse.

A Prospective Cohort Study of Smoking in Acute Pancreatitis

Background/Aims: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. Methods: From 1974 to 1992, selected birth-year cohorts of residents in Malmö, Sweden (born 1921–1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox’s analysis revealed RR. Results: Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48–3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20–30 cigarettes/day) (RR 3.19, 95% CI 2.03–5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98–13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59–4.08) and for γ-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32–3.49). There was also a weak correlation between BMI and acute pancreatitis. Conclusions: Smoking is associated with the incidence of acute pancreatitis in a dose-response manner.

Expression and characterization of trypsinogen produced in the human male genital tract.

Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.

A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer

BackgroundThe relationship between Helicobacter pylori infection and pancreatic cancer has been investigated in three previous studies with contradictory results. The aim of the present study was to investigate the association between H. pylori seropositivity and the risk for pancreatic cancer in a nested case-control study within a population based cohort.MethodsSelected birth-year cohorts (born 1921–1949) of residents in Malmö, Sweden, were invited to a health screening investigation. A total of 33 346 subjects participated. Cases with pancreatic cancer (n = 87) were matched to controls (n = 263) using age, sex and time for baseline investigation as matching variables. H. pylori serology was analysed in stored serum samples using an enzyme-linked immunosorbent assay. Odds ratios (OR) for pancreatic cancer were calculated with 95% confidence intervals (CI) using logistic regression.ResultsH. pylori seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75–2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06–13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97–4.69) adjusted for smoking).ConclusionWe conclude that no association between H. pylori infection and the risk for pancreatic cancer was found in the total cohort. However, in never smokers and in subjects with low risk alcohol consumption, a positive H. pylori serology was associated with an increased risk for pancreatic cancer. These findings should be interpreted cautiously due to the limited number of cases in these subgroups.

Protease Activation, Pancreatic Leakage, and Inflammation in Acute Pancreatitis: Differences between Mild and Severe Cases and Changes over the First Three Days

Background/Aims: The pathophysiology of acute pancreatitis (AP) may be studied using markers of protease activation (active carboxypeptidase B (aCAP), the activation peptide of carboxypeptidase B (CAPAP)), leakage of pancreatic enzymes (trypsinogen-2, procarboxypeptidase B (proCAP), amylase), and inflammation (monocyte chemoattractant protein-1 (MCP-1), CRP). Methods: This prospective study included 140 cases of AP. Mild (n = 124) and severe (n = 16) cases were compared with respect to serum levels of trypsinogen-2, proCAP, amylase, aCAP, CAPAP (serum/urine), MCP-1 (serum/urine) and CRP on days 1, 2 and 3 from onset of symptoms. All patients with information on all 3 days were included in a time-course analysis (n = 44–55, except amylase: n = 27). Results: High levels in severe versus mild cases were seen for trypsinogen-2, CAPAP in serum and urine, and MCP-1 in serum on days 1–3. No differences were seen for proCAP, amylase and aCAP. MCP-1 in urine was significantly elevated on day 1–2, and CRP on day 2–3. CAPAP and MCP-1 levels peaked early and stayed elevated for 48 h in serum. Conclusion: Protease activation and inflammation are early events in AP, with high levels of these markers within 24 h. Protease activation declines after 48 h, whereas inflammation is present for a longer time.

Different Markers of Alcohol Consumption, Smoking and Body Mass Index in Relation to Risk of Pancreatic Cancer

Background/Aim: The association between alcohol consumption and pancreatic cancer is not clear. This study investigates different prediagnostic measurements of alcohol consumption, a laboratory marker (γ-glutamyltransferase; γ-GT), and a score measuring alcohol addiction (Mm-MAST), in relation to the risk of pancreatic cancer. Furthermore, the study investigated whether smoking and alcohol consumption interact with each other, or if the risk of pancreatic cancer associated with these factors is modified by obesity or weight gain. Methods: A cohort of 33,346 subjects provided prediagnostic information on the above factors. During a mean follow-up of 22.1 years, 183 cases of pancreatic cancer occurred. Cox’s analysis yielded relative risks (RR) with 95% confidence intervals (CI). Results: The highest γ-GT quartile was associated with a high risk of pancreatic cancer (RR = 2.15, 95% CI = 1.34–3.44), and this association was even stronger in subjects that reported a previous weight gain (RR = 3.61, 95% CI = 1.29–10.09). A high Mm-MAST score was also associated with pancreatic cancer (p = 0.02). Current smoking was associated with pancreatic cancer (RR = 2.34, 95% CI = 1.60–3.43), and obese smokers had an even higher risk (RR = 7.45, 95% CI = 1.65–33.64). Conclusion: High alcohol intake is associated with subsequent risk of pancreatic cancer and this risk may be higher following weight gain. The risk associated with smoking may be even higher in obese subjects.

Monocyte Chemoattractant Protein 1, Active Carboxypeptidase B and CAPAP at Hospital Admission Are Predictive Markers for Severe Acute Pancreatitis

Background: CAPAP, the activation peptide of procarboxypeptidase B, is a predictor of severe acute pancreatitis (AP). Active carboxypeptidase (aCAP) may be a better predictor, as its turnover is slower. Monocyte chemotactic protein-1 (MCP-1) is an early inflammatory marker and increases before complications in severe AP. We conducted a cohort study to evaluate these markers as predictors for severe AP. Method: 140 patients with AP were included, retrospectively grouped as severe or mild by the Atlanta classification. CAPAP, MCP-1 and aCAP were analyzed in admission samples. Receiver operating characteristic curves determined high vs. low levels. Results: The levels of all markers were significantly higher in patients with severe disease. High levels of serum MCP-1 was associated with a high risk of developing severe AP (OR 40.8; 95% CI 8.5–195). High ORs were also seen for urine MCP-1 (OR 7.3; 95% CI 2.2–24.3), serum CAPAP (OR 5.4; 95% CI 1.6–17.7), urine CAPAP (OR 4.8; 95% CI 1.6–14.2), and serum aCAP (OR 3.7; 95% CI 1.2–11.3). Conclusion: Serum MCP-1 at admission was strongly associated with development of severe AP. MCP-1 in urine, CAPAP in serum and urine and aCAP may also be useful for predicting severe AP.

Active Carboxypeptidase B Is Present in Free Form in Serum from Patients with Acute Pancreatitis.

Background: Active carboxypeptidase B (aCAP) is the main product of activation of procarboxypeptidase. The other product derived from procarboxypeptidase B (proCAP), the activation peptide carboxypeptidase B (CAPAP), has been shown to be a marker for severity in acute pancreatitis. There have been relatively few studies dealing with the role of this enzyme in acute pancreatitis. Methods: A double-antibody ELISA for immunoreactive aCAP (ir-aCAP) was developed, and ir-aCAP was determined in the serum of patients with acute pancreatitis and characterized using gel filtration. Results: Serum from healthy individuals contained minimal levels of ir-aCAP, while serum from 25 patients with acute pancreatitis contained between 0.6 and 158 nmol/l. Gel filtration of serum samples from patients with acute pancreatitis showed the presence of two peaks of ir-aCAP, one corresponding to the molecular size of the free active enzyme and one corresponding to cross-reactive proCAP. When pure aCAP was mixed with serum in vitro, all ir-aCAP was recovered as one peak of free enzyme. No immunoreactivity disappeared or changed in molecular size, as might be expected if the active enzyme was bound to an inhibitor. Conclusion: aCAP is present in free form in the circulation of patients with acute pancreatitis.

Peritoneal lavage with aprotinin in patients with severe acute pancreatitis : Effects on plasma and peritoneal levels of trypsin and leukocyte proteases and their major inhibitors

SummaryConclusionAlthough high-dose aprotinin given intraperitoneally to patients with severe acute pancreatitis seems to inhibit activated trypsin in the peritoneal cavity, the treatment has little effect on the balance between proteases and antiproteases. Plasma levels of leukocyte proteases were high in all the patients, indicating leukocyte activation to be an important feature of the pathophysiology of severe acute pancreatitis. A surprise finding was that the patients had higher peritoneal levels of pancreatic secretory trypsin inhibitor (PSTI) after the lavage procedure.BackgroundAlthough most studies have shown protease inhibitor therapy to have little or no effect on acute pancreatitis, in an earlier study we found that very high doses of the protease inhibitor aprotinin given intraperitoneally to patients with severe acute pancreatitis seemed to reduce the need of surgical treatment for pancreatic necrosis. In the present study we have further analyzed plasma and peritoneal samples from the same patients to ascertain whether the aprotinin treatment affects the balance between proteases and endogenous antiproteases.MethodsIn a prospective double-blind randomized multicenter trial, 48 patients with severe acute pancreatitis were treated with intraperitoneal lavage. One group (aprotinin group,n=22) was also treated with high doses (20 million KIU given over 30 h) of aprotinin intraperitoneally. The remaining 26 patients made up the control group. The protease-antiprotease balance was studied by measuring immunoreactive anionic trypsin (irAT), cationic trypsin (irCT), complexes between cationic trypsin and alpha 1-protease inhibitor (irCT-α1PI), leukocyte elastase and neutrophil proteinase 4 (NP4), as well as the endogenous protease inhibitors, pancreatic secretory trypsin inhibitor (PSTI), alpha 2-macroglobulin (α 2M), alpha 1-protease inhibitor (α 1PI), antichymotrypsin (ACHY), and secretory leukocyte protease inhibitor (SLPI). Intraperitoneal levels were studied before and after the lavage procedure, and plasma levels were followed for 21 d.ResultsThe control group had lower plasma levels of SLPI and analysis of peritoneal fluid showed the reduction of irCT-α 1PI to be more pronounced in the aprotinin group. None of the other variables measured differed significantly between the two groups. All patients had very high levels of leukocyte elastase and NP4 both in peritoneal exudate and in plasma. Peritoneal levels of PSTI were higher after the lavage procedure in contrast to the other measured variables that all showed lower peritoneal levels after the lavage.

Splenic Rupture following ESWL for a Pancreatic Duct Calculus

Extracorporeal shock wave lithotripsy (ESWL) is an established and extensively used treatment alternative for urinary calculi. It is also an established method of dealing with pancreatic duct calculi complementing endoscopic techniques in selected cases. Three reports of splenic injury following and probably caused by ESWL for urinary calculi have previously been published. We report a case of splenic rupture presenting with life-threatening hemorrhage 6 days after a single ESWL therapy session for pancreatic duct calculi.