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Tu1494 Early Prediction of Severity in Acute Paediatric Pancreatitis
Tu1494 Early Prediction of Severity in Acute Paediatric Pancreatitis Michael J. Coffey, Scott Nightingale, Chee Y. Ooi
AGA Abstracts
Background & Aims: Paediatric pancreatitis is poorly understood and recognised. Current predictive systems for severe acute pancreatitis (AP) are either based on adults or complex to utilise. We aimed to identify laboratory predictors of severe acute and recurrent acute pancreatitis in children. Methods: A retrospective review (Jan 2000-July 2011) was performed at two tertiary paediatric hospitals serving as derivation and validation cohorts respectively. AP was defined as abdominal pain (not attributable to other causes) associated with ≥2 times the upper limit of normal (x ULN) for serum lipase or amylase and/or imaging evidence of AP. Severe AP was defined by association with: pseudocyst, necrosis, haemorrhage, abscess, death, pancreatic surgery, ICU admission, or organ dysfunction (PaO2<60, O2 requirement or SBP <90mmHg). Descriptive univariate analysis was performed on laboratory parameters within the first 24 hours of presentation to predict severe AP and cut-offs for continuous variables were determined using ROC analyses. Univariate logistic regression was used to determine the significance of defined cut-offs. Multivariate logistic regression was then modelled to derive a clinical prediction rule for severe AP. Results: A total of 149 pancreatitis episodes were reviewed. Of the 79 episodes in the derivation cohort (63% male, median age: 11.6 (IQR: 7.7-13.9) years), 52 (66%) were classified as mild and 27 (34%) as severe. Of the 70 patients in the validation cohort (40% male, median age: 15.1 (IQR: 11.2-17.2) years), 53 (76%) were mild and 17 (24%) severe. In the derivation cohort; variables found to differ significantly (P<0.05) between mild and severe AP included: lipase, amylase, phosphate, white cell count (WCC), neutrophils and haemoglobin. These parameters all remained statistically significant (P<0.05) on univariate logistic regression analysis. Multivariate logistic regression analysis incorporating lipase ≥5x ULN, WCC ≥15x109/L and haemoglobin ≥145g/L showed lipase to be the only significant predictor of severe AP (odds ratio: 8.8 (95% CI: 1.7-45.0), P=0.009). In the validation cohort, lipase ≥5x ULN remained a significant predictor for severe AP (odds ratio: 8.9 (95% CI: 1.6-47.9), P=0.011). Predictive calculations of serum lipase ≥5x ULN within 24 hours of presentation were calculated based on univariate binary logistic regression analysis (Table). Lipase ≥5x ULN remained significant on multivariate analysis of the derivation cohort if a diagnostic cut-off for AP of ≥3x instead of ≥2x ULN was used; odds ratio: 6.9 (95% CI: 1.3-35.9), P=0.022. Conclusion: We derived and validated the ability of serum lipase to predict severity of AP (within 24 hours of presentation) in children. Therefore, serum lipase can be used not only to diagnose AP but aid in prognosticating and managing paediatric patients with AP.
Tu1492 Demographic, Clinical and Prognostic Characteristics of Acute Hypertriglyceridemic Pancreatitis Genaro Vazquez-Elizondo, Celina Rodríguez Leal, Jose A Gonzalez, Francisco J. Bosques, Hector J. Maldonado Background and aim. A serum triglycerides level of 800-1000 mg/dL (TGL) in a compatible clinical scenario is required for the diagnosis of acute hypertriglyceridemic pancreatitis (AHP). Since its low frequency, its true incidence is not well known. The aim of our study was to describe the demographic, clinical and prognostic characteristics of patients with AHP. Methods. From a prospective collected data base (2008 and 2010) we studied all consecutive patients admitted with AHP who had less than 72 hours since the onset of symptoms. The diagnosis was made based in clinical and laboratory criteria. Demographic, clinical, laboratory and prognostic variables were evaluated. Descriptive statistics were used. Results. A total of 221 patients with acute pancreatitis were admitted, 14.5% (n = 32) were classified as AHP. The mean age was 35.9 ± 8.2 years, and 84.4% (n = 27) were males. Most patients had their first episode of AHP (65.6%, n = 21). Mean body mass index was 31.2 ± 5.5 kg/m2. Patients with BMI ≥ 30 kg/m2 represent the 59.4% (n = 19). Metabolic syndrome criteria were fulfilled in 87.5% (n = 30) patients (ATPIII). Mean TGL level was 2636.3 ± 2953.1 mg/dL. At admission 21/32 patients had systemic inflammatory response syndrome (SIRS) of these patients 16 had persistent SIRS (48hrs). Of the 11 patients without SIRS at admission 4 patients developed SIRS (48hrs). The overall persistent SIRS was found in 20/32 patients (62.5%). In the persistent SIRS group (20/32); ten patients developed complications according to the Atlanta criteria. Only one death occurred (3.1%), and the mean hospital stay was 11.3 ± 13 days. Conclusions. AHP was found in 15% of the patients. Most of them were male, had obesity and metabolic syndrome. Patients with AHP developed persistent SIRS more frequently than other etiologies, but mortality seems to be similar. Tu1493 Diagnostic Potential of Pancreatic Cancer by Using Metabolomic Analysis Junko Umeda, Takao Itoi, Atsushi Sofuni, Fumihide Itokawa, Takayoshi Tsuchiya, Toshio Kurihara, Kentaro Ishii, Shujiro Tsuji, Nobuhito Ikeuchi, Reina Tanaka, Fuminori Moriyasu, Tomoyoshi Soga, Masahiro Sugimoto, Makoto Sunamura
Table: Predictive calculations for severe acute pancreatitis based on a serum lipase of ≥5x ULN within 24 hours of presentation to hospital. *P=0.002; **P=0.025; ***P<0.001.
Objective : Pancreatic enzymes and tumor markers such as CA19-9, DUPAN-2 and SPAN1 are commonly used for early diagnosis of pancreatic cancer as blood test. However, about 80% of the patients are graded as stage IVa or IVb at diagnosis; thus, development of new technology for early detection of pancreatic cancer is vital. Metabolomics, the newest omics, provides a comprehensive profiling of small molecules (metabolites) that enables us to analyse cellular functions and to diagnosis a wide range of diseases. The metabolomic pathways, downstream of the central dogma, transfers regulatory information from other omics data, such as transcriptomics and proteomics; thus, the metabolomic profile can be expected to directly reflect cellular phenotypes. The purpose of this study is to use this approach for pancreatic cancer diagnosis. Methods : Blood samples were obtained from 29 pancreatic cancer patients, 5 cystic pancreatic tumor patients, 10 biliary tract cancer, 54 patients with other inflammatory diseases of the pancreaticobiliary system, and 20 healthy adult volunteers. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) was employed for comprehensive analysis of charged metabolites mostly observed in the primary metabolic pathways. Blood tumor markers (CA19-9, SPAN-1, DUPAN-2, and CEA)were also analyzed from the identical patients. Result : CE-TOFMS-based analysis detected approximately 450 metabolites in the blood and successfully identified 150 metabolites. Statistically significant differences between the patients with pancreatic cancer and healthy adult volunteers were observed in 27 metabolites and, of these, 5 metabolites were increased in pancreatic cancer. Principle component analysis clearly separated pancreatic cancer patients from the healthy volunteers. Multivariate analyses revealed that combination tumor markers (Span-1 and CA19-9) and metabolomic profiles dramatically reduced false positive cases than the use of tumor markers alone, for pancreatic cancer diagnosis. Conclusion : We identified pancreatic cancer-specific metabolite profiles using CE-TOFMS and multivariate analysis demonstrated their diagnostic potential of pancreatic cancer. Furthermore, pancreatic cancer and chronic pancreatitis could be distinguished based on a combination with tumor markers and metabolite profiles. One of beneficial features to use CETOFMS is small sample volumes (10μL) required. We think metabolome analysis may also be applied in the sensitivity evaluation of anticancer drugs.
Tu1495
AGA Abstracts
Connective Tissue Growth Factor Production by Pancreatic Acinar Cells is Associated With Regulation of Immune Function in a Mouse Model of Alcoholic Chronic Pancreatitis Alyssa Charrier, David Brigstock Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is associated with production and action of connective tissue growth factor (CTGF) by pancreatic stellate cells (PSC). These studies were designed to investigate the role of acinar cell-derived CTGF, which we found to be produced in ACP before that of PSC and to precede onset of fibrosis. Pancreata from C57/Bl6 mice on Day 16 of ACP were examined by IHC for acinar CTGF and its relationship to inflammatory responses. CTGF or interleukin-1β (IL-1β) mRNA were evaluated by qRT-PCR in ethanolstimulated rat AR42J acinar cells In Vitro. Gene expression was interrogated in CTGFtransfected AR42J cells using an Inflammatory Cytokines and Receptors PCR Array, and the data were confirmed by qRT-PCR. The relationship between CTGF, IL-1β, and selected chemokines or chemokine receptors was investigated by siRNA-mediated knockdown of CTGF- or IL-1β. A fluorometric chemotaxis assay was used to test the response of concavalinA activated rat T-cells to conditioned medium from CTGF-transfected AR42J cells. In the In Vivo ACP model, there was strong CTGF immunofluorescence in acinar cells by Day 16 whereas α-SMA-positive cells were negative. Control mice receiving water instead of alcohol did not demonstrate acinar CTGF staining. As assessed by IHC and H&E staining, CTGF acinar staining in ACP mice was correlated with substantially increased F4/80-positive macrophage, neutrophil and T-cell infiltration and an enhanced production of acinar IL1β. In Vitro studies showed that comparable patterns of CTGF or IL-1β mRNA expression were stimulated in AR42J cells exposed to 6.25-100mM ethanol for up to 48 hours. Transfection of AR42J cells with CTGF cDNA resulted in significantly enhanced expression of IL-1β, chemokine (C-C motif) ligand-5 or -20 (CCL5, CCL20), C-C chemokine receptor type 6 (CCR6), or C-X-C motif chemokine 10 (CXCL10), and this effect was reversed by co-transfection of the cells with IL-1β siRNA. Treatment of wild-type AR42J cells with CTGF siRNA caused a 50% decrease in either CTGF or Il-1β mRNA expression. Conditioned medium from
S-848
AGA Abstracts
Background & Aims: Paediatric pancreatitis is poorly understood and recognised. Current predictive systems for severe acute pancreatitis (AP) are either based on adults or complex to utilise. We aimed to identify laboratory predictors of severe acute and recurrent acute pancreatitis in children. Methods: A retrospective review (Jan 2000-July 2011) was performed at two tertiary paediatric hospitals serving as derivation and validation cohorts respectively. AP was defined as abdominal pain (not attributable to other causes) associated with ≥2 times the upper limit of normal (x ULN) for serum lipase or amylase and/or imaging evidence of AP. Severe AP was defined by association with: pseudocyst, necrosis, haemorrhage, abscess, death, pancreatic surgery, ICU admission, or organ dysfunction (PaO2<60, O2 requirement or SBP <90mmHg). Descriptive univariate analysis was performed on laboratory parameters within the first 24 hours of presentation to predict severe AP and cut-offs for continuous variables were determined using ROC analyses. Univariate logistic regression was used to determine the significance of defined cut-offs. Multivariate logistic regression was then modelled to derive a clinical prediction rule for severe AP. Results: A total of 149 pancreatitis episodes were reviewed. Of the 79 episodes in the derivation cohort (63% male, median age: 11.6 (IQR: 7.7-13.9) years), 52 (66%) were classified as mild and 27 (34%) as severe. Of the 70 patients in the validation cohort (40% male, median age: 15.1 (IQR: 11.2-17.2) years), 53 (76%) were mild and 17 (24%) severe. In the derivation cohort; variables found to differ significantly (P<0.05) between mild and severe AP included: lipase, amylase, phosphate, white cell count (WCC), neutrophils and haemoglobin. These parameters all remained statistically significant (P<0.05) on univariate logistic regression analysis. Multivariate logistic regression analysis incorporating lipase ≥5x ULN, WCC ≥15x109/L and haemoglobin ≥145g/L showed lipase to be the only significant predictor of severe AP (odds ratio: 8.8 (95% CI: 1.7-45.0), P=0.009). In the validation cohort, lipase ≥5x ULN remained a significant predictor for severe AP (odds ratio: 8.9 (95% CI: 1.6-47.9), P=0.011). Predictive calculations of serum lipase ≥5x ULN within 24 hours of presentation were calculated based on univariate binary logistic regression analysis (Table). Lipase ≥5x ULN remained significant on multivariate analysis of the derivation cohort if a diagnostic cut-off for AP of ≥3x instead of ≥2x ULN was used; odds ratio: 6.9 (95% CI: 1.3-35.9), P=0.022. Conclusion: We derived and validated the ability of serum lipase to predict severity of AP (within 24 hours of presentation) in children. Therefore, serum lipase can be used not only to diagnose AP but aid in prognosticating and managing paediatric patients with AP.
Tu1492 Demographic, Clinical and Prognostic Characteristics of Acute Hypertriglyceridemic Pancreatitis Genaro Vazquez-Elizondo, Celina Rodríguez Leal, Jose A Gonzalez, Francisco J. Bosques, Hector J. Maldonado Background and aim. A serum triglycerides level of 800-1000 mg/dL (TGL) in a compatible clinical scenario is required for the diagnosis of acute hypertriglyceridemic pancreatitis (AHP). Since its low frequency, its true incidence is not well known. The aim of our study was to describe the demographic, clinical and prognostic characteristics of patients with AHP. Methods. From a prospective collected data base (2008 and 2010) we studied all consecutive patients admitted with AHP who had less than 72 hours since the onset of symptoms. The diagnosis was made based in clinical and laboratory criteria. Demographic, clinical, laboratory and prognostic variables were evaluated. Descriptive statistics were used. Results. A total of 221 patients with acute pancreatitis were admitted, 14.5% (n = 32) were classified as AHP. The mean age was 35.9 ± 8.2 years, and 84.4% (n = 27) were males. Most patients had their first episode of AHP (65.6%, n = 21). Mean body mass index was 31.2 ± 5.5 kg/m2. Patients with BMI ≥ 30 kg/m2 represent the 59.4% (n = 19). Metabolic syndrome criteria were fulfilled in 87.5% (n = 30) patients (ATPIII). Mean TGL level was 2636.3 ± 2953.1 mg/dL. At admission 21/32 patients had systemic inflammatory response syndrome (SIRS) of these patients 16 had persistent SIRS (48hrs). Of the 11 patients without SIRS at admission 4 patients developed SIRS (48hrs). The overall persistent SIRS was found in 20/32 patients (62.5%). In the persistent SIRS group (20/32); ten patients developed complications according to the Atlanta criteria. Only one death occurred (3.1%), and the mean hospital stay was 11.3 ± 13 days. Conclusions. AHP was found in 15% of the patients. Most of them were male, had obesity and metabolic syndrome. Patients with AHP developed persistent SIRS more frequently than other etiologies, but mortality seems to be similar. Tu1493 Diagnostic Potential of Pancreatic Cancer by Using Metabolomic Analysis Junko Umeda, Takao Itoi, Atsushi Sofuni, Fumihide Itokawa, Takayoshi Tsuchiya, Toshio Kurihara, Kentaro Ishii, Shujiro Tsuji, Nobuhito Ikeuchi, Reina Tanaka, Fuminori Moriyasu, Tomoyoshi Soga, Masahiro Sugimoto, Makoto Sunamura
Table: Predictive calculations for severe acute pancreatitis based on a serum lipase of ≥5x ULN within 24 hours of presentation to hospital. *P=0.002; **P=0.025; ***P<0.001.
Objective : Pancreatic enzymes and tumor markers such as CA19-9, DUPAN-2 and SPAN1 are commonly used for early diagnosis of pancreatic cancer as blood test. However, about 80% of the patients are graded as stage IVa or IVb at diagnosis; thus, development of new technology for early detection of pancreatic cancer is vital. Metabolomics, the newest omics, provides a comprehensive profiling of small molecules (metabolites) that enables us to analyse cellular functions and to diagnosis a wide range of diseases. The metabolomic pathways, downstream of the central dogma, transfers regulatory information from other omics data, such as transcriptomics and proteomics; thus, the metabolomic profile can be expected to directly reflect cellular phenotypes. The purpose of this study is to use this approach for pancreatic cancer diagnosis. Methods : Blood samples were obtained from 29 pancreatic cancer patients, 5 cystic pancreatic tumor patients, 10 biliary tract cancer, 54 patients with other inflammatory diseases of the pancreaticobiliary system, and 20 healthy adult volunteers. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) was employed for comprehensive analysis of charged metabolites mostly observed in the primary metabolic pathways. Blood tumor markers (CA19-9, SPAN-1, DUPAN-2, and CEA)were also analyzed from the identical patients. Result : CE-TOFMS-based analysis detected approximately 450 metabolites in the blood and successfully identified 150 metabolites. Statistically significant differences between the patients with pancreatic cancer and healthy adult volunteers were observed in 27 metabolites and, of these, 5 metabolites were increased in pancreatic cancer. Principle component analysis clearly separated pancreatic cancer patients from the healthy volunteers. Multivariate analyses revealed that combination tumor markers (Span-1 and CA19-9) and metabolomic profiles dramatically reduced false positive cases than the use of tumor markers alone, for pancreatic cancer diagnosis. Conclusion : We identified pancreatic cancer-specific metabolite profiles using CE-TOFMS and multivariate analysis demonstrated their diagnostic potential of pancreatic cancer. Furthermore, pancreatic cancer and chronic pancreatitis could be distinguished based on a combination with tumor markers and metabolite profiles. One of beneficial features to use CETOFMS is small sample volumes (10μL) required. We think metabolome analysis may also be applied in the sensitivity evaluation of anticancer drugs.
Tu1495
AGA Abstracts
Connective Tissue Growth Factor Production by Pancreatic Acinar Cells is Associated With Regulation of Immune Function in a Mouse Model of Alcoholic Chronic Pancreatitis Alyssa Charrier, David Brigstock Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is associated with production and action of connective tissue growth factor (CTGF) by pancreatic stellate cells (PSC). These studies were designed to investigate the role of acinar cell-derived CTGF, which we found to be produced in ACP before that of PSC and to precede onset of fibrosis. Pancreata from C57/Bl6 mice on Day 16 of ACP were examined by IHC for acinar CTGF and its relationship to inflammatory responses. CTGF or interleukin-1β (IL-1β) mRNA were evaluated by qRT-PCR in ethanolstimulated rat AR42J acinar cells In Vitro. Gene expression was interrogated in CTGFtransfected AR42J cells using an Inflammatory Cytokines and Receptors PCR Array, and the data were confirmed by qRT-PCR. The relationship between CTGF, IL-1β, and selected chemokines or chemokine receptors was investigated by siRNA-mediated knockdown of CTGF- or IL-1β. A fluorometric chemotaxis assay was used to test the response of concavalinA activated rat T-cells to conditioned medium from CTGF-transfected AR42J cells. In the In Vivo ACP model, there was strong CTGF immunofluorescence in acinar cells by Day 16 whereas α-SMA-positive cells were negative. Control mice receiving water instead of alcohol did not demonstrate acinar CTGF staining. As assessed by IHC and H&E staining, CTGF acinar staining in ACP mice was correlated with substantially increased F4/80-positive macrophage, neutrophil and T-cell infiltration and an enhanced production of acinar IL1β. In Vitro studies showed that comparable patterns of CTGF or IL-1β mRNA expression were stimulated in AR42J cells exposed to 6.25-100mM ethanol for up to 48 hours. Transfection of AR42J cells with CTGF cDNA resulted in significantly enhanced expression of IL-1β, chemokine (C-C motif) ligand-5 or -20 (CCL5, CCL20), C-C chemokine receptor type 6 (CCR6), or C-X-C motif chemokine 10 (CXCL10), and this effect was reversed by co-transfection of the cells with IL-1β siRNA. Treatment of wild-type AR42J cells with CTGF siRNA caused a 50% decrease in either CTGF or Il-1β mRNA expression. Conditioned medium from
S-848