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BACKGROUND: We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease.METHODS: We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738).RESULTS: Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers.CONCLUSIONS: YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, wit

BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP).METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated the prevalences and incidences of death, cancers, and comorbidities among subjects with CP (cases) compared with age- and sex-matched individuals (controls). In total, 11,972 cases (71,814 person-years) and 119,720 controls (917,436 person-years) were included in the analysis. Hazard ratios (HR) were estimated by Cox proportional hazards regression.RESULTS: Forty-six percent of the cases died during the follow-up period, compared with 13.0% of controls (mean age, 63.7 vs 72.1 y; P < .0001), corresponding to a HR of 5.0 for CP (95% confidence interval [CI], 4.8-5.2). Cancer was a frequent cause of death among cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic pulmonary disease (HR, 1.9; 95% CI, 1.8-2.1), ulcer disease (HR, 3.6; 95% CI, 3.3-3.9), diabetes (HR, 5.2; 95% CI, 5.0-5.6), and chronic renal disease (HR, 1.7; 95% CI, 1.5-1.9) occurred more frequently among patients with CP, but myocardial infarction did not (HR, 0.9; 95% CI, 0.8-1.0).CONCLUSIONS: Based on a Danish nationwide cohort study, individuals with CP are at higher risk for death from cancer (particularly pancreatic cancer) and have a higher incidence of comorbidities than people without CP.

BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP).METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated the prevalences and incidences of death, cancers, and comorbidities among subjects with CP (cases) compared with age- and sex-matched individuals (controls). In total, 11,972 cases (71,814 person-years) and 119,720 controls (917,436 person-years) were included in the analysis. Hazard ratios (HR) were estimated by Cox proportional hazards regression.RESULTS: Forty-six percent of the cases died during the follow-up period, compared with 13.0% of controls (mean age, 63.7 vs 72.1 y; P < .0001), corresponding to a HR of 5.0 for CP (95% confidence interval [CI], 4.8-5.2). Cancer was a frequent cause of death among cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic pulmonary disease (HR, 1.9; 95% CI, 1.8-2.1), ulcer disease (HR, 3.6; 95% CI, 3.3-3.9), diabetes (HR, 5.2; 95% CI, 5.0-5.6), and chronic renal disease (HR, 1.7; 95% CI, 1.5-1.9) occurred more frequently among patients with CP, but myocardial infarction did not (HR, 0.9; 95% CI, 0.8-1.0).CONCLUSIONS: Based on a Danish nationwide cohort study, individuals with CP are at higher risk for death from cancer (particularly pancreatic cancer) and have a higher incidence of comorbidities than people without CP.

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.

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.

BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP).METHODS: Twelve male patients with severe CP and 11 matched controls ingested 40 g alcohol. Plasma cytokine concentrations were measured for 24 h and assessed by sandwich ELISA techniques.RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after alcohol intake (P < 0.04), and a significantly greater rise was found at 1 h compared to pre-stimulatory conditions and controls (P < 0.01). MCP-1 plasma levels in CP were significantly decreased at I h (P < 0.01) and 4 h (P < 0.001) compared to pre-stimulatory levels and controls, and a variance analysis showed significantly (P < 0.001) lower post-stimulatory levels at 1 h and 4 h both in CP and in controls. Alcohol consumption (40 g), however, did not influence plasma levels of TGF-1beta, IGF-I or IGFBP-3 in either of the two groups at the time frame applied.CONCLUSIONS: Acute alcohol intake induces a rise in the plasma levels of IL-6 in CP as compared to controls. The low circulating concentrations of MCP-1 1 and 4 h following alcohol consumption might possibly reflect that this mediator acts locally via autocrine mechanisms.

BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP).METHODS: Twelve male patients with severe CP and 11 matched controls ingested 40 g alcohol. Plasma cytokine concentrations were measured for 24 h and assessed by sandwich ELISA techniques.RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after alcohol intake (P < 0.04), and a significantly greater rise was found at 1 h compared to pre-stimulatory conditions and controls (P < 0.01). MCP-1 plasma levels in CP were significantly decreased at I h (P < 0.01) and 4 h (P < 0.001) compared to pre-stimulatory levels and controls, and a variance analysis showed significantly (P < 0.001) lower post-stimulatory levels at 1 h and 4 h both in CP and in controls. Alcohol consumption (40 g), however, did not influence plasma levels of TGF-1beta, IGF-I or IGFBP-3 in either of the two groups at the time frame applied.CONCLUSIONS: Acute alcohol intake induces a rise in the plasma levels of IL-6 in CP as compared to controls. The low circulating concentrations of MCP-1 1 and 4 h following alcohol consumption might possibly reflect that this mediator acts locally via autocrine mechanisms.

Pancreaticopleural fistula secondary to chronic pancreatitis is a rare cause of recurrent pleural effusion. The demonstration of the fistula with endoscopic retrograde pancreatography and CT is invasive or limited. We report in two patients the use of magnetic resonance pancreatography as a noninvasive alternative to endoscopic retrograde pancreatography for the diagnosis of pancreaticopleural fistula.

[No abstract available]