Results. Statistical Analysis. Gallstone Disease and Alcohol Abuse in Patients With Acute Pancreatitis

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2004;2: Trends in Incidence of Acute Pancreatitis in a Swedish Population: Is There Really an Increase? BJÖRN LINDKVIST,* STEFAN APPELROS,* JONAS MANJER,*, and ANDERS BORGSTRÖM* Departments of *Surgery and Community Medicine, Malmö University Hospital, Lund University, Malmö, Sweden Background & Aims: Recent 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. Methods: Clinical, 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 causeof-death registries. Results: A 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], ). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, ), 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). Conclusions: There 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. The annual incidence of acute pancreatitis reported in the literature ranges from 5 to 50 per 100,000, 1 15 and several reports suggest an increased incidence of acute pancreatitis over the past decades. 3,5 10,15 18 Suggested explanations are changes in established risk factors (i.e., increased gallstone prevalence or changed drinking habits). 3,5,6,8,9,15,19,20 Improved diagnostic procedures also may have contributed. 3,16 Many studies on the incidence of acute pancreatitis are retrospective caserecord studies from referral centers that do not serve a defined population, which implies a risk for selection bias. In Malmö, Sweden, with a population of about 250,000 inhabitants, there is only one hospital for somatic care, and there are no referrals of patients with acute pancreatitis to or from other hospitals. Exact population statistics are available. This allows complete retrieval of representative cases, and calculation of age- and sex-standardized incidence rates. A previous cross-sectional study has identified 547 first attacks of acute pancreatitis and assessed plausible cause. 1 That material covered too short a period to allow analysis of changes in incidence rates. The present study is a population-based longitudinal study on 929 consecutive first attacks of acute pancreatitis from 1985 to The aim of this study was to investigate trends in incidence of acute pancreatitis, and risk factors related to the disease. Patients and Methods Malmö is the third largest city in Sweden, with a population of approximately 250,000 inhabitants. Exact data on the size of the population, and its age and sex constitution for each year, was retrieved from the unit of planning and statistics at the city council. 21 Diagnostic Criteria of Acute Pancreatitis In the period from 1985 to 1999, cases of acute pancreatitis were identified from clinical, autopsy, and forensic diagnosis records by a computer search for diagnostic codes. Clinical notes, forensic protocols, and autopsy reports were validated according to a standard protocol. The diagnosis was accepted in cases with a clinical history of acute abdominal pain, confirmed at physical examination, in combination with an increase in serum amylase level. Evidence from laparoscopy, laparotomy, or autopsy also was accepted for diagnosis. Patients with a previous history of chronic pancreatitis were excluded. Attacks were classified as first attacks if there was no evidence of earlier attacks in clinical notes or diagnostic Abbreviation used in this paper: CI, confidence interval by the American Gastroenterological Association /04/$30.00 PII: /S (04)

2 832 LINDKVIST ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 9 records. Severe cases were defined according to the Atlanta classification. 22 Gallstone Disease and Alcohol Abuse in Patients With Acute Pancreatitis Gallstone disease. Gallstone disease was diagnosed using clinical and conventional imaging procedures (i.e., ultrasonography, endoscopic retrograde cholangiopancreatography, or computed tomography). The attack of acute pancreatitis was considered as related to gallstone disease only when there was radiologic evidence for gallstones and no signs of other risk factors, such as alcohol abuse, were present. Alcohol abuse. The attack of acute pancreatitis was considered as related to alcohol abuse when the patient reported a high regular intake of alcohol, or an alcoholic bout, directly before the onset of the disease, and no signs of other risk factors, such as gallstones, were present. Other risk factors. Uncommon factors related to the attack of pancreatitis were endoscopic retrograde cholangiopancreatography, pancreatic cancer, and postoperative pancreatitis. In the statistical analysis this group was analyzed together with attacks of unknown cause. Unknown cause. The cause was considered unknown when no risk factors could be found, or when alcohol abuse and gallstone disease were present at the same time and both factors were judged as equally plausible causes of the attack of acute pancreatitis. Gallstone Disease, Alcohol Abuse, and Lung Cancer in the Population at Risk Choledocolithiasis, cholecystolithiasis, and cholecystitis were used as markers for gallstone disease. The incidence of delirium tremens and mortality from cirrhosis were used as markers for alcohol abuse. The incidence of lung cancer was considered as a marker for smoking. Cases of gallstone-related conditions and delirium tremens were identified from hospital diagnosis records by a computer search for relevant diagnostic codes. Only the main diagnosis was accepted, and only the first occasion during the period was considered. Cases of lung cancer were identified from the regional Cancer Registry, a part of the Swedish Cancer Registry. Information on patients who died from cirrhosis was retrieved from the regional Causeof-Death Registry. Statistical Analysis Mean age at diagnosis of the first attack of acute pancreatitis was calculated for different subgroups of patients. Annual age- and sex-standardized incidence was calculated by using direct standardization. The total population in Malmö in 1985 was used as standard. All analyses also were stratified for sex, yielding age-standardized rates. Time trends with regard to incidence of pancreatitis, and related conditions, were examined regarding the incidence rate as a dependent variable (y-axis) and the year as an independent variable (x-axis). All tests were 2 tailed and a P value of less than 0.05 was regarded as statistically significant. First, Pearson s correlation coefficients (r), with corresponding P values, were used to reveal whether or not there was a trend in incidence over the period (i.e., how well incidence rates were arranged on a straight line). Second, linear regression analysis revealed the strength of the association (i.e., the slope of the line). This was expressed as the average annual change in percent with a 95% confidence interval (CI). 23 To investigate the homogeneity of different causative subgroups of patients, trends in mean age were investigated using Pearson s correlation coefficient and linear regression, as described earlier. The incidence of pancreatitis associated with gallstones was compared with the incidence of gallstone disease and lung cancer in the background population. Correspondingly, the incidence of pancreatitis associated with alcohol abuse was compared with the incidence of delirium tremens and lung cancer and the mortality rate from cirrhosis. The incidence of unspecified cases of pancreatitis was compared with all 4 conditions. In these comparisons, the logarithmic incidence of pancreatitis was entered as a dependent variable (y-axis), and the logarithmic incidence of related conditions was entered as an independent variables (x-axis). Pearson s correlation coefficient was used as described earlier. The strength of the association was expressed as -coefficients (95% CI) (i.e., the slope of the line). Results Incidence of Acute Pancreatitis The diagnosis of acute pancreatitis was found 1444 times during the investigated period, 1400 times Table 1. Number of Cases and Age at Occurrence All Men Women n Age (SD), yr n Age (SD), yr n Age (SD), yr All pancreatitis (17.9) (15.8) (19.8) Alcohol-associated pancreatitis (10.8) (10.8) (10.8) Gallstone-associated pancreatitis (18.1) (13.3) (20.3) Unknown/other pancreatitis (17.7) (16.5) (19.1) Delirium tremens (11.3) (10.9) (14.5) Mortality from cirrhosis (12.9) (12.1) (13.6) Lung cancer (10.7) (10.1) (11.9)

3 September 2004 INCREASING INCIDENCE OF ACUTE PANCREATITIS 833 Figure 1. Age- and sex-standardized incidence of first attacks of acute pancreatitis. Figure 2. Age-standardized incidence of gallstone-associated pancreatitis., Men; Œ, women. in clinical records, 28 times in autopsy records, and 16 times in forensic records. From this material, 929 correctly diagnosed first attacks of acute pancreatitis were identified, 493 (53.1%) in men and 436 (46.9%) in women (Table 1). Annual age- and sex-standardized incidence increased by 3.9% (95% CI, ) per year (Figure 1, Table 2). The increase was statistically significant in women, but not in men. Trends in Mean Age Mean age at diagnosis is reported in Table 1. In all patients with a first attack of acute pancreatitis, there was a statistically significant increase in the annual mean age of 0.4 years per year (95% CI, ). There was no statistically significant change in annual mean age of patients with gallstone-related pancreatitis, 0.0 years per year (95% CI, 0.3 to 0.4), or in the group of unknown and miscellaneous risk factors, 0.1 years per year (95% CI, 0.5 to 0.3). The mean age of patients with an alcohol-related first attack of acute pancreatitis increased over time, statistically significantly, with 0.4 years per year (95% CI, ). Risk Factors in Patients With Acute Pancreatitis and in the Population at Risk Gallstone disease. Gallstone disease was the most common risk factor, present in 42.2% (392 of 929) of all cases with a first attack of acute pancreatitis. The incidence of gallstone-related pancreatitis increased by 7.6% (95% CI, ) per year (Table 2). The increase was statistically significant among women, as well as among men (Figure 2, Table 2). In the general population there was a statistically significant increase in gallstone-related disease (Table 2). The incidence of gallstone-related pancreatitis was statistically significantly Table 2. Annual Incidence Change in Percent All Men Women r (P) Annual change in % (95% CI) r (P) Annual change in % (95% CI) r (P) Annual change in % (95% CI) All pancreatitis 0.81 ( 0.001) 3.9 ( ) 0.36 (0.19) 1.8 ( 0.8 to 4.5) 0.73 (0.002) 6.5 ( ) Alcohol-associated 0.77 (0.001) 5.1 ( 7.4 to 2.8) 0.68 (0.006) 5.5 ( 8.7 to 2.2) 0.34 (0.22) 2.1 ( 8.1 to 4.3) pancreatitis Gallstone-associated 0.78 (0.001) 7.6 ( ) 0.73 (0.002) 7.4 ( ) 0.68 (0.005) 8.0 ( ) pancreatitis Other or unknown 0.85 ( 0.001) 5.8 ( ) 0.54 (0.039) 3.8 ( ) 0.68 (0.005) 7.5 ( ) pancreatitis Gallstone disease 0.59 (0.021) 1.8 ( ) 0.57 (0.027) 1.8 ( ) 0.55 (0.034) 1.9 ( ) Delirium tremens 0.88 ( 0.001) 13.0 ( 16.7 to 9.1) 0.87 ( 0.001) 13 ( 17.0 to 9.3) 0.50 (0.058) 5.4 ( 14 to 4.4) Mortality from cirrhosis 0.74 (0.002) 4.4 ( 6.8 to 2.1) 0.73 (0.002) 4.3 ( 6.7 to 1.9) 0.55 (0.033) 5.7 ( 11 to 0.60) Lung cancer 0.78 (0.01) 1.6 ( 2.4 to 0.8) 0.87 ( 0.001) 4.0 ( 5.4 to 2.7) 0.76 (0.01) 2.6 ( )

4 834 LINDKVIST ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 9 Table 3. Correlation Between the Logarithmic Incidence of Different Subgroups of Pancreatitis and the Logarithmic Incidence of Gallstone Disease, Delirium Tremens, and Lung Cancer and Logarithmic Mortality From Cirrhosis in the General Population Pancreatitis associated with: Gallstone disease Mortality from cirrhosis Delirium tremens Lung cancer r (P) (95% CI) r (P) (95% CI) r (P) (95% CI) r (P) (95% CI) All Gallstones 0.65 (0.008) 0.14 ( ) 0.67 (0.007) 0.46 ( 0.78 to 0.15) Alcohol 0.79 ( 0.001) 0.58 ( ) 0.66 (0.007) 0.37 ( ) 0.56 (0.03) 0.15 ( ) Unknown/ 0.67 (0.007) ( ) 0.76 (0.01) 0.85 ( 1.3 to 0.41) 0.53 (0.041) 0.46 ( 0.89 to 0.023) 0.72 (0.03) 0.30 ( 0.46 to 0.13) other Women Gallstones 0.57 (0.026) 0.12 ( ) 0.59 (0.02) 0.61 ( ) Alcohol 0.09 (0.75) ( 0.30 to 0.40) 0.32 (0.25) 0.33 ( 0.26 to 0.91) 0.26 (0.34) ( 0.17 to 0.063) Unknown/ 0.23 (0.42) ( to 0.11) 0.24 (0.39) 0.46 ( 1.6 to 0.66) 0.13 (0.65) 0.44 ( 2.46 to 1.59) 0.61 (0.02) 0.41 ( ) other Men Gallstones 0.66 (0.007) 0.16 ( ) 0.49 (0.07) ( 0.16 to 0.006) Alcohol 0.59 (0.02) 0.53 ( ) 0.62 (0.014) 0.36 ( ) 0.67 (0.006) ( ) Unknown/ other 0.56 (0.03) 0.11 ( ) 0.31 (0.27) 0.26 ( 0.75 to 0.23) 0.41 (0.13) 0.22 ( 0.52 to 0.078) 0.36 (0.19) ( 0.12 to 0.025) NOTE. The slope of the line is expressed as -coefficients with a 95% CI. correlated to the incidence of gallstone-related disease in both men and women (Table 3, Figure 3). Alcohol abuse. Alcohol abuse was the second most common risk factor, found in 24.5% (228 of 929) of all cases. The incidence of alcohol-related pancreatitis decreased by 5.1% (95% CI, ) per year. This decrease consisted of a slight, and not statistically significant, decrease among women and a statistically significant decrease among men (Table 2, Figure 4). The decrease in alcohol-related pancreatitis among men was statistically significantly correlated to a decrease in delirium tremens, and a decrease in the mortality from cirrhosis in the male general population. There was no correlation between alcohol-related pancreatitis and delirium tremens or mortality from cirrhosis among women (Table 3). Lung cancer. The incidence of lung cancer decreased among men, and increased among women in the population at risk (Table 2). The incidence of alcoholrelated pancreatitis was statistically significantly correlated with the incidence of lung cancer in men but not in women (Table 3). Other or unknown risk factors. The remaining 33.3% (309 of 929) of all first attacks of acute pancreatitis consisted of attacks related to other or unknown risk factors (Table 2). This group consisted of 94 attacks of miscellaneous causes and 215 attacks of unknown cause. In 4.7% (10 of 215) of the attacks of acute pancreatitis that were classified as unknown, both gallstone disease and alcohol abuse were present and retrospective assessment of one major causative factor was not possible. The incidence of attacks of acute pancreatitis related to other or unknown risk factors increased statistically significantly during the investigated period, but its proportion of the total number of first attacks of acute pancreatitis remained similar (data not shown). Proportion of Severe Cases and Case- Fatality Rate The proportions of severe cases according to the Atlanta classification, 22 and case-fatality rate, were similar throughout the investigated period. The percentage of severe cases was 13.6% (126 of 929) during the whole period, from 1985 to 1994 it was 12.7% (70 of 550), and from 1995 to 1999 it was 14.8% (56 of 379). The case-fatality rate was 5.7% (53 of 929) during the whole period, from 1985 to 1994 it was 5.6% (31 of 550), and from 1995 to 1999 it was 5.7% (22 of 379). Discussion This is, to our knowledge, the largest study to date on trends in incidence of first attacks of acute pancreatitis with individual verification of all cases in a defined population. Both clinical and forensic data are included. A statistically significant increase in the incidence of first attacks of acute pancreatitis was found. Gallstone-related pancreatitis increased markedly, and this correlated with an increase in the incidence of gallstone-related disease in the population at risk. Alcohol-related pancreatitis decreased, and this correlated with a decrease in the incidence of delirium tremens and lung cancer, and mortality from cirrhosis in the population at risk. There is only one hospital in Malmö, and there are no referrals of patients to or from this hospital. Therefore, we consider the risk for selection bias as low, allowing reliable estimates of incidence. Large studies have been performed on the incidence of acute pancreatitis using diagnosis registers without in-

5 September 2004 INCREASING INCIDENCE OF ACUTE PANCREATITIS 835 Figure 3. Correlation between incidence of gallstone-associated pancreatitis and incidence of gallstone disease other than pancreatitis., Men; Œ, women. dividual validation of cases. 6,7,9,15 A report from the Netherlands 9 showed that in a national register only 83% were diagnosed correctly. This may lead to underor overestimation of true incidence rates. Such a misclassification bias is probably less likely in the present study because clinical notes and autopsy records were reviewed for all cases. Another problem with studies without individual case validation is that recurrences may have been mistaken for first attacks. This can lead to an overestimation of first attack incidence rates. This probably was less of a problem in the present study because previous medical history was reviewed in all cases of pancreatitis. Improved diagnostic procedures have been suggested as the explanation for an increased incidence of acute pancreatitis when reported by other investigators. 3,16 If improved diagnostic procedures could explain the increase in the incidence of acute pancreatitis, a proportional increase in cases related to alcohol abuse and cases related to gallstone disease would be expected. On the contrary, according to our data, alcohol-related pancreatitis decreased whereas gallstone-related pancreatitis increased. If improved diagnostic procedures were the reason for the increased incidence, an increased proportion of mild cases also would be expected. Because this was not the case in our study, we consider the risk for a detection bias to be low, and not likely to explain the observed increase in incidence of acute pancreatitis. Another type of misclassification is related to probable cause. In this study all cases were reviewed by only 2 different investigators, working in close contact, to obtain a uniform classification of probable cause. A problem in a retrospective setting is that clinical diagnostic tools might have changed during the investigated period. More sensitive and accessible ultrasonography in the end of the investigated period could be a risk for a false increase of gallstone-related pancreatitis on behalf of other causes. The mean age for patients with gallstonerelated pancreatitis, or pancreatitis related to other or unknown risk factors, remained unchanged during the investigated period, suggesting that these 2 groups are constituted by the same type of patients throughout the investigated period. Mean age of patients with alcohol-related acute pancreatitis increased whereas the incidence of conditions related to alcohol abuse decreased. Alcoholism is often a chronic disease. It is reasonable to assume that a decreased incidence of alcoholism, and thereby a decreased recruitment of younger cases, will result in an increased mean age of the prevalent cases. The increased mean age of patients with alcohol-related acute pancreatitis therefore might indicate that the observed decrease in the incidence of alcohol-related pancreatitis is not an artefact. Gallstone disease and alcohol abuse appeared as equally plausible causes in a subgroup of attacks of acute pancreatitis. Unfortunately, these initially were classified as unknown. However, after re-evaluation of the group with unknown cause, there were only 10 patients identified with both alcohol abuse and gallstone disease. We do not believe that these patients being analyzed together with patients with unknown cause has had any impact on the trends in alcohol- or gallstone-related pancreatitis reported in this study. Trends in the incidence of other conditions related to gallstone disease and alcohol abuse were investigated in Figure 4. Age-standardized incidence of alcohol-associated pancreatitis., Men; Œ, women.

6 836 LINDKVIST ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 9 the background population. The validity of these incidence rates probably is lower than incidence rates on acute pancreatitis because no perusal of clinical notes or autopsy records was performed. However, the purpose of these calculations was not to provide exact incidence rate on these conditions, but to confirm the observed trends in different subgroups of acute pancreatitis. An overestimation of the incidence rates is most likely to have occurred in the beginning of the period studied because patients with a prevalent disease may have been registered for the first time then. Because gallstone-related disease increased throughout the period, such a bias is likely only to have attenuated a true positive trend. Contrary to this, the decrease in delirium tremens may be explained to some extent by accumulated detection of prevalent disease in the beginning of the study period. Other investigators have reported results suggesting an increased incidence of acute pancreatitis. 3,5 10,15 18 Three different retrospective studies, based on national diagnosis registers, have shown an increased incidence of acute pancreatitis during the 1990s; the incidence rate increased in Great Britain from 14.5 to 20.7 per 100,000, between 1989 and ; in the Netherlands from 12.4 to 15.9, between 1985 and ; and in Scotland from 25.8 to 41.9, between 1984 and The incidence found in this material is consistent with most other reports from the Nordic countries 10,11,13 and Germany. 14 A higher incidence has been reported from Finland, but that report included recurrences. 6 The percentage of alcohol-related pancreatitis and gallstone-related pancreatitis found in this study is similar to what has been reported recently from Germany, 14 southern England, 24 and Iceland. 13 A prospective study from Norway showed a high percentage (51%) of gallstone-related pancreatitis in Many reports suggest a more pronounced increase in alcohol-related pancreatitis. 3,5,6,8,10,19,20 However, some evidence recently has been found for increased incidence of gallstonerelated pancreatitis; in the Netherlands the increased incidence of acute pancreatitis from 1985 to 1995 was correlated with an increased incidence of gallstone-related disease, whereas the national consumption of alcohol decreased. 9 In this study, the decrease in the incidence of alcoholrelated acute pancreatitis in men was correlated to a decrease in the incidence of delirium tremens and mortality from cirrhosis, 2 other conditions related to heavy alcohol consumption. The total alcohol consumption in the population can be regarded as the sum of legally sold alcohol, imported or smuggled alcohol, and homemade spirits, wine, and beer. There are no absolutely reliable statistics on the total alcohol consumption, estimates are made from the amount of legally sold alcohol, on which reliable statistics are available. From 1980 to 1996, the amount of legally sold alcohol in Malmö decreased about 36%. Interestingly, this decrease was owing to a marked reduction in the sales of hard liquor from 3.8 to 1.2 L of pure alcohol per inhabitant per year, whereas the sales of wine and beer were stable. 25 A specific correlation of acute pancreatitis with hard liquor, but not wine and beer, has been reported earlier by other investigators. 26 There was a statistically significant correlation between the incidence of lung cancer and the incidence of alcohol-related acute pancreatitis. Smoking is known to be correlated to alcohol consumption and a correlation between lung cancer and alcohol-related acute pancreatitis can be a manifestation of confounding. However, there is well-established evidence for an increased risk of chronic pancreatitis in smokers, 27,28 and there is some evidence for a correlation between smoking and acute pancreatitis Disturbed pancreatic secretion after nicotine exposure or smoking has been proven in both animal models and in humans. 32,33 There was a negative correlation between the incidence of lung cancer and gallstone-related acute pancreatitis and the incidence of lung cancer and pancreatitis related to other or unknown risk factors. We have found no evidence in the literature for a protective role of smoking in acute pancreatitis, and therefore it seems unlikely that smoking has influenced the incidence of these conditions. It is possible that decreased smoking habits have accentuated the decrease in alcohol-related pancreatitis, although no conclusions on causality can be drawn from these epidemiologic data. Gallstone-related pancreatitis increased markedly and this correlated with an increase in other gallstonerelated conditions in both men and women. From repeated investigations by postal questionnaires in Malmö, it is known that obesity and overweight are increasing. The prevalence of overweight, defined as body mass index of kg/m 2, increased from 26% in 1986, to 39% in 1994, and obesity (defined as body mass index 30 kg/m 2 ) increased from 5% in 1986 to 9% in This might be of importance for the increased incidence of gallstone-related disease and gallstone-related pancreatitis because obesity is related to these conditions. The incidence of cholecystectomies in Malmö remained stable throughout the period with an annual incidence of surgeries per 100,000, comparable with what has been seen in other Scandinavian countries. 34 Because the increased incidence of gallstonerelated disease has not been followed by an increase in the

7 September 2004 INCREASING INCIDENCE OF ACUTE PANCREATITIS 837 incidence of cholecystectomies, one might speculate that this may have contributed to the increase in gallstonerelated pancreatitis. In conclusion, there has been a considerable increase in the incidence of acute pancreatitis in this urban population from 1985 to This was caused by a pronounced increase in the incidence of gallstone-related acute pancreatitis. References 1. Appelros S, Borgström A. Incidence, aetiology and mortality rate of acute pancreatitis over 10 years in a defined urban population in Sweden. Br J Surg 1999;86: Bourke JB. Variation in annual incidence of primary acute pancreatitis in Nottingham, Lancet 1975;2: Trapnell JE, Duncan EH. Patterns of incidence in acute pancreatitis. BMJ 1975;2: Thomson HJ. Acute pancreatitis in north and north-east Scotland. J R Coll Surg Edinb 1985;30: Corfield AP, Cooper MJ, Williamson RC. Acute pancreatitis: a lethal disease of increasing incidence. 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Bjorn.Lindkvist@kir.mas.lu.se; fax: (46) Supported by grants from the Swedish Medical Research Council projects no 17-X A, the Foundations for Research at the University Hospital in Malmö, and the Einar and Inga Nilsson Foundation for surgical research at the Department of Surgery in Malmö.