Circulating Markers of Necroptosis in Acute Pancreatitis.

OBJECTIVES: Necroptosis, a programmed inflammatory cell death, is involved in the pathogenesis of acute pancreatitis (AP). We compared levels of interleukin (IL)-33 (released upon necroptosis), sST2 (soluble IL-33 receptor), MLKL, RIPK1 and RIPK3 (necroptosis executioner proteins), and proinflammatory cytokines IL-6, TNF and IL-1ß at various severity categories and stages of AP. METHODS: Plasma from 20 patients with early mild AP (MAP) (symptom onset < 72 h), 7 with severe AP (SAP) without and 4 with persistent organ failure (OF) at sampling, 8 patients with late SAP and 20 healthy controls (HC) were studied by ELISAs. RESULTS: Early sST2 and IL-6 levels predicted the development of SAP and were higher in both MAP and early and late SAP than in HC. RIPK3 levels were higher than in HC in the patients who had or would later have SAP. MLKL levels were associated with the presence of OFs, particularly in the late phase, but were also higher in MAP than in HC. CONCLUSIONS: sST2, RIPK3 and IL-6 levels may have prognostic value in AP. Elevated MLKL levels are associated with OF in AP. Better understanding of necroptosis in AP pathophysiology is needed to evaluate whether inhibiting and targeting necroptosis is a potential therapeutic option in AP.

ACUTE PANCREATITIS in HELSINKI in 2016-2018: INCIDENCE, ETIOLOGY and RISK FACTORS - analysis of 1378 acute pancreatitis episodes in a Finnish normal population.

OBJECTIVES: Updated population-based studies on acute pancreatitis (AP) in Finland are lacking. Our aim was to evaluate the current data for AP in Helsinki. MATERIALS AND METHODS: We performed an electronic health care records (EHRs) search on AP patients treated at Helsinki University Hospital between the years 2016 - 2018. Incidence was calculated, etiological and potential risk factors, as well as severity of AP were documented and analyzed. RESULTS: Between 2016 and 2018 we found 1378 AP episodes on 1084 patients, 35% of the patients had several AP episodes, i.e., recurrent AP (RAP). The domicile-adjusted incidence was 42.2/100 000. 47% of the patients had alcohol etiology (59% men, 27% women) and 23% had biliary etiology, 21% were idiopathic and 2.9% were post-ERCP pancreatitis. 13.1% of the patients had passed at the end of September 2021. 45% of the patients were currently smoking, 11% were ex-smokers, and the highest percentage of smokers was in the group of alcohol-caused AP with 74% ever-smokers. Biliary AP had the highest amount of overweight patients. 24% of the patients used anticoagulation (AC) medication, and the percentage was significantly higher with idiopathic AP (48%). RAP, female sex and normal BMI associated with a mild form of AP. CONCLUSIONS: Incidence of AP and the percentage of alcohol etiology are lower than earlier reported for Finland although still higher than in other Nordic countries. Smoking and the use of AC medication associate with AP.

Development and external validation of DISPAIR fistula risk score for clinically relevant postoperative pancreatic fistula risk after distal pancreatectomy.

BACKGROUND: Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. RESULTS: Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. CONCLUSION: The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.