Is the SPINK1 variant p.N34S overrepresented in patients with acute pancreatitis?

OBJECTIVES: Serine Protease Inhibitor Kazal type 1 (SPINK1) protects against premature intracellular activation of trypsinogen and development of acute pancreatitis. Our aim was to determine the prevalence of SPINK1 mutations (a) in unselected patients with first-time acute pancreatitis and (b) in the Danish background population (c) in a meta-analysis to combine the results with findings in similar investigations worldwide and (d) to evaluate whether patients with SPINK1 mutations had a more severe clinical course. METHODS: A total of 75 consecutive patients admitted to a surgical department with first-time acute pancreatitis were prospectively included. In addition, 188 healthy controls were tested for the SPINK1 variants: p.N34S, p.P55S, p.R65Q, p.R67C, and IVS3+2 T>C, in order to calculate the prevalence of SPINK1 mutations in the Danish background population. A meta-analysis was conducted on previous studies on acute pancreatitis and SPINK1 mutations. RESULTS: Two patients (2.7%) and two controls (1.1%) were heterozygous for the p.N34S variant. The meta-analysis confirmed that the p.N34S variant is overrepresented in patients with acute pancreatitis compared with the background population (OR=3.16, P<0.001). But this analysis did not clarify whether this was only true for patients with first-time acute pancreatitis or recurrent pancreatitis as the present studies do not provide this information, and those who do not have enough patients to reach levels of statistic significance, even if data are pooled. CONCLUSION: The SPINK1 variant p.N34S is overrepresented in patients with acute pancreatitis, but more studies distinguishing between first-time and recurrent acute pancreatitis have to be done to determine whether this is only true for patients with recurrent acute pancreatitis.

Cytokines and organ failure in acute pancreatitis: inflammatory response in acute pancreatitis.

OBJECTIVES: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). METHODS: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor α were measured on admission and at days 1, 2, and 14 in 60 patients admitted with first attack of AP. The prediction of single-organ and multiorgan failure from the cytokine profiles was evaluated by receiver operating characteristic analyses. RESULTS: Interleukin 6 and IL-8 levels were significantly higher in patients who developed renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor α was significantly elevated in all types of organ failures, except for intestinal failure. CONCLUSIONS: Synchronous measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early surrogate markers with regard to organ failures in AP. The fact that all of the cytokines were particularly elevated in patients with organ failures calls for evaluation of agents modifying the severe inflammatory response in patients with AP.

Variations in serum 25-hydroxyvitamin D during acute pancreatitis: an exploratory longitudinal study.

OBJECTIVES: We tested the hypothesis that 25-hydroxyvitamin D3 (25OHD) changes during acute inflammation in humans. METHODS: Patients with first episode of acute pancreatitis were included. Blood samples were acquired on admission and on days 1, 2, and 14. RESULTS: In total, 73 patients (35 males, median age 59) entered the study. On admission, the distribution of 25-OHD levels was as follows: severely deficient (<13 nmol/L) 23%; deficient (13-25 nmol/L) 20%; insufficient (26-50 nmol/L) 40%; and normal (<50 nmol/L) 17%. There was a significant fall and linear trend in 25OHD, albumin, and hemoglobin from day 0 to day 2. From day 0 to day 2 the drop in 25OHD was 3.1 nmol/L (95% CI 0.59-5.63). The changes from day 0 to day 2 in 25OHD were associated with changes in C-reactive protein (p = 0.02) but not with leukocyte or monocyte count. CONCLUSIONS: The 25OHD levels dropped during the first 2 days of acute pancreatitis beyond what was expected based on 25OHD half-life. This study supports our hypothesis that an acute inflammatory condition utilizes 25OHD, but other mechanisms could interfere.

Urinary trypsinogen-2 dipstick in acute pancreatitis.

OBJECTIVES: In acute pancreatitis (AP), rapid diagnosis and early treatment are of importance for clinical outcome. Urinary trypsinogen-2 has been suggested as a promising diagnostic marker; however, studies using the urinary trypsinogen-2 dipstick test (UTDT) have provided varying results. METHODS: The study was set to evaluate the use of the UTDT (Actim Pancreatitis; Medix Biochemica, Kauniainen, Finland, Medinor, Roskilde, Denmark) in apparent first attack of AP in daily clinics. Acute pancreatitis was defined as more than a 3-fold increase in plasma amylase levels. We included 75 patients admitted with AP. Thirty-four patients with acute abdominal pain of causes other than AP served as a control group. RESULTS: In 58 of 75 patients, the UTDT result was positive, giving a sensitivity of 77% (95% confidence interval [CI]: 66%-86%). In severe cases, the sensitivity improved to 87% (95% CI: 69%-96%). In 33 of 34 controls, the test result was negative, giving a specificity of 97% (95% CI: 84%-99.9%). CONCLUSION: The UTDT had a low sensitivity but high specificity. These results do not support the UTDT to replace standard plasma amylase for the diagnosis of apparent first attack of AP. However, the test demonstrated an adequate sensitivity to be used for rapid early screening of AP in daily clinics.

Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis. A prospective study.

OBJECTIVES: If differences of inflammatory pathways in acute pancreatitis exist for various etiologies, selective and specific antiinflammatory and other modulatory treatment regimens might be indicated. Circulating levels of prominent proinflammatory cytokines IL-6, 8, 18, and TNF-alpha were measured in patients having their first attack of either alcohol- or gallstone-induced acute pancreatitis. METHODS: Seventy-five consecutive patients were prospectively included over a 15-month period, sixty of them being either alcohol- or gallstone-induced. All patients were treated according to a standardized algorithm. Blood samples were obtained immediately on admission and, again, at days 1, 2, and 14. RESULTS: A significant effect of the etiology on the levels of IL-8 in the alcohol group as compared to the gallstone group (P=0.003) was found. No etiologic differences were observed for IL-6, IL-18, TNF-alpha, or CRP. Furthermore, no significant differences, either regarding the need for treatment at the intensive care unit or of 30-day mortality, were found. CONCLUSION: The present study confirms previous findings and supports the hypothesis that, except for IL-8, the biochemical profile and clinical outcome is independent of the underlying etiology. Revealing the complex spatial and temporal profile of proinflammatory cytokine expression in acute pancreatitis is necessary and important for the development of a more targeted rational therapy.

[Mortality and morbidity in patients with alcohol and biliary-induced acute pancreatitis]. / Mortalitet og morbiditet ved alkohol- og galdestensudløst akut pankreatitis.

INTRODUCTION: Acute Pancreatitis (AP) is a serious disease with a high mortality. The main aetiological factors involved in development of AP are alcohol and gallstones. Whether aetiology influences mortality and morbidity in AP is not clarified. MATERIALS AND METHODS: The aim of the present study was to determine if there was a significant difference in mortality in alcohol or biliary-induced AP. We retrospectively analysed data comprising all patients admitted to our department with a first attack of AP registered in a 5-year period (2000-2004). RESULTS: A total of 290 patients were included. The 30-day and 1-year mortality risks were 5% and 11% and independent of aetiology. ASA-score and severity of AP had a significant effect on the 30-day mortality risk (OR = 9.2 for ASA-score > 2 and OR = 4.2 for severe AP), while daily use of prescribed medicine and ASA-score had a significant effect on the 1-year mortality risk (OR = 10.4 for medicine and OR = 4.5 for ASA-score > 2). Severe AP was a significant predictor for treatment at the Intensive Care Unit (OR = 26.2), as was daily use of prescribed medicine (OR = 7.3). CONCLUSION: Our data shows that AP is associated with considerable mortality and that there is no significant difference in mortality in relation to alcohol or biliary aetiology.