Acute pancreatitis. With special reference to the activation peptide from carboxypeptidase B (CAPAP) as a predictor of severity

University dissertation from Department of Surgery, Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden

Abstract: There is a wide range in the reported annual incidence of acute pancreatitis (AP). A minority of these patients develop a severe disease characterised by a high mortality and morbidity. In order to improve the outcome for patients with an attack of severe AP it is important to identify these patients early in the course of disease. A prediction of severity is especially important for selection of patients for therapeutic trials. The present study was undertaken to establish the indicence and aetiology of AP in Malmö, between 1985-94. To assess the incidence of severe AP, the mortality, causes of death and long-term outcome after a severe attack. To develop a method for early prediction of severity, measurement of levels of the activation peptide from the pancreatic enzyme carboxypeptidase B (CAPAP) in serum and urine. A high incidence of AP was found. The annual incidence of first attacks was 23.4/100 000 (men 58.1% and women 41.9%) and including relapses the corresponding figure was 38.2/100 000. Gallstones were the predominant aetiology in first attacks and with relapses included alcohol was the main aetiological factor. In more than 50% (16/31) of the fatal cases the diagnosis was established first at autopsy, 10 of these were found in the forensic material. Twelve cases were associated with pancreatic carcinoma. Severe AP developed in 8.9% of the cases. At follow-up of these cases, a median 7 years after the attack 14 out of 35 patients had developed diabetes and another 4 had impaired glucose tolerance, 9 had signs of severe exocrine dysfunction. The activation peptide from carboxypeptidase B (CAPAP) was purified from human pancreatic juice. The molecular mass of the protein was established to 9398+_ 5 Da corresponding to an 81 aminoacid activation peptide also in man. A radioimmunoassay for CAPAP was developed. The assay showed a slight (10%) cross-reaction with the proenzyme. In urine the assay only measures CAPAP as the proenzyme is not excreted in the urine. A high accuracy of 89.5% at a specificity of 95.9% was obtained resulting in a 85% risk of developing a severe attack for a patient with a CAPAP value above 100 nmol/l whereas a CAPAP value below 100 nmol/l indicates a less than 3% risk.

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