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Proteomic Identification of Novel Biomarkers of Ethanol Acute Pancreatitis
little is known about the postoperative pancreatic fistula rates of these procedures, and its impact on morbidity in comparison to that of PDs performed for malignancies. Methods: Perioperative data for patients who underwent PD, Berne, and Frey procedures for headpredominant CP, and PDs for periampullary malignancies from 2005 to 2015 were assessed. The International Study Group on Pancreatic Fistula definition was utilized to identify and grade postoperative pancreatic fistulas (POPF). The Clavien-Dindo classification was utilized to grade surgical complications. Results: The most common etiologies of CP were alcohol (n=46, 43.4%), idiopathic (n=35, 33.0%), and pancreatic divisum (n=14, 13.2%). The majority of patients underwent resective procedures, consisting of PD (n=44, 41.5%), and Berne (n=18, 17.0%). The Frey drainage procedure was utilized in 44 patients (41.5%). The PD, Berne and Frey patient cohorts were well matched with regards to age, gender, body-mass index, duration of disease, and pre-narcotic requirements (all P>0.05). The overall POPF rate was 5.7% (n=6), and consisted of 33.3% (n=2) grade A, 50% (n=3) grade B, and 16.7% (n=1) grade C fistulas. Despite worse perioperative metrics with regards to operative time, estimated blood loss, and length of stay (all P<0.01) in the PD cohort, there were no differences in the POPF rates (PD vs. Berne vs. Frey; 4.5% vs. 5.6% vs. 6.8%; P=0.74). Overall, POPFs were neither associated with increased length of stay (P=0.91) nor greater complication grades (P=0.20). Among 216 patients who underwent PD for periampullary malignancies, the POPF rate (n=28, 13%) was significantly higher than that of the CP cohort (P=0.04). Although the distribution of grade A (n=6, 21.4%), B (n=16, 57.2%) and C (n= 6, 21.4%) fistulas were similar to that of the CP cohort (P=0.84), POPFs in the periampullary malignancy cohort were associated with increased length of stay (15.8 vs. 11.7 days, P<0.01) and higher complication grades (P<0.01). Conclusions: Postoperative pancreatic fistulas occur less frequently and with less morbidity in patients with head-predominant chronic pancreatitis compared to patients with periampullary malignancies. Although pancreaticoduodenectomy is associated with worse perioperative metrics compared to the Berne and Frey procedures for patients with chronic pancreatitis, there is no difference in the postoperative rate of pancreatic fistulas.
Tu1396 PROTEOMIC IDENTIFICATION OF NOVEL BIOMARKERS OF ETHANOL ACUTE PANCREATITIS Aiste Gulla, Richard Waldron, Aurelia Lugea, Stephen J. Pandol Introduction: Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with no effective therapeutic remedies. The severity of the disease varies widely and only limited biomarkers and severity scores are available to assess its severity. Therefore, an urgent need is to develop additional biomarkers that can improve clinical course and minimize mortality in AP. Methods: Patient serum was obtained from 12 male AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 controls. Severity in AP patients was as a correlate of tissue damage was estimated by blood lactate dehydrogenase, with an average value of 1127 mg/dl. Median APACHEII score was 5.5, and IMRIE score was 3.5, indicating moderate to severe AP (please see the accompanying table for details). For proteomic analysis, less abundant proteins in plasma samples were enriched using Top 12 abundant protein depletion columns. Further processing was performed by a modified filter-associated sample preparation combined with tandem mass tag labeling for quantitation. Samples were analyzed by Orbitrap Elite instrument for state-of-the-art high resolution liquid chromatography-tandem mass spectrometry. Results: Our analysis revealed that 44 proteins exhibited 1.5-fold or higher increase in the AP compared to control patients. Gene ontology analysis indicated a strong correlation with exosomal origin in the elevated proteins, with 35/44 (80%) associated with this extracellularly-secreted compartment. Elevated proteins included established and proposed biomarkers of AP including C-reactive protein, LPS-binding protein, intercellular adhesion molecule-1, and von Willebrand factor, as well as several novel potential biomarkers. Conclusions: These results suggest that we are discovering novel biomarkers which can be used for measuring the severity of pancreatitis at any point in time during the course of disease. Table for Serum Biomarker Proteonomic Study_AGA 2017
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SSAT Abstracts
REOPERATION INCREASES THE INPATIENT MORTALITY IN PANCREATIC CANCER PATIENTS Chiranjeevi Gadiparthi, Rosann Cholankeril, Eddie L. Copelin, Eric R. Yoo, Muhammad Ali Khan, Menghan Hu, Aijaz Ahmed, Colin W. Howden, George Cholankeril, Ponnandai Somasundar Background and Aims Over the last two decades, long-term survival rates after surgical resection for pancreatic cancer have markedly improved. However, postoperative inpatient mortality among patients with resected pancreatic cancer is yet to be assessed. We aim to evaluate temporal trends and predictive risk factors associated with inpatient mortality in patients with resected pancreatic cancer. Methods Using the Healthcare Utilization ProjectNational Inpatient Sample (HCUP-NIS), we evaluated temporal trends and independent risk factors associated with postoperative inpatient morality in resected pancreatic cancer patients from 2004 to 2013. Inclusion criteria were patients with a primary diagnosis of pancreatic cancer who underwent pancreatic resection. Additionally, we performed a multivariate logistic regression analysis assessing risk factors including demographics (age, gender, ethnicity, insurance type), postoperative complications and clinical comorbidities associated with postoperative inpatient mortality in patients who underwent surgical resection for pancreatic cancer. Results Overall from 2004 to 2013, 13,758 patients underwent resection for pancreatic cancer during their hospitalization. Overall the postoperative inpatient mortality rate was 3.90 (per 100 resected pancreatic cancer hospitalizations). However, during this study period there was 41% overall reduction in mortality from 4.57 in 2004 to 2.68 in 2013 (Figure). After adjusting for demographics and severity of disease, our multivariate analysis demonstrated that reoperation, acute peptic ulcer disease, age above 75, cirrhosis and acute myocardial infarction were the most significant predictors of postoperative inpatient mortality (Table). Conclusion Inpatient mortality associated with surgical resection of pancreatic cancer has declined over the past decade. However, risk factors such as reoperation, peptic ulcer disease and older age demonstrate to adversely impact short-term survival in these patients. Future efforts to reduce preventable risk factors may aid in improving postoperative survival. Table. Significant predictors of postoperative inpatient mortality in resected pancreatic cancer patients
SSAT Abstracts
Tu1397 MODIFIED FRAILTY INDEX PREDICTS DISPOSITION AFTER MAJOR RESECTION FOR GASTROINTESTINAL CANCER Rebecca M. Dodson, Sarah Vermillion, Michael Kuncewitch, Perry Shen, Clancy J. Clark Introduction Gastrointestinal (GI) cancers disproportionally affect older adults who may present with limited physiologic reserve resulting in prolonged recovery. We hypothesized that a frailty index can predict postoperative disposition after major abdominal surgery. Methods All patients diagnosed with a GI malignancy (esophageal, gastric, pancreatic, liver, biliary, and colorectal) who underwent curative resection were identified in the 2011 and 2012 NSQIP Participant Use Files. Patients undergoing emergency procedures, not admitted from home, ASA 5, or diagnosed with preoperative sepsis were excluded. A modified Frailty Index (mFI) was defined by 11 variables within NSQIP previously used for the Canadian Study of Health and Aging-Frailty Index. mFI score of 0.27 or more was defined as high mFI. Univariate and multiple variable analyses were performed to evaluate postoperative disposition. Results 11,301 patients (age 64+/- 13, 46% female) underwent curative surgery for GI cancer with 4.3% (n= 482) having a high mFI (>=0.27). 61.8% (n = 6969) of patients were ASA 3/4 and 98.5% were independent prior to surgery. Postoperatively, 16.5% developed a major complication and 30-day mortality was 2.2%. 7.9% were discharged to a facility and 12.1% required readmission. High mFI was associated with increased risk of discharge to facility (OR 3.4, 95% CI 2.7-4.2, p<0.001) and readmission (OR 1.4, 95% CI 1.1-1.8, p = 0.013). After adjusting for age, race, albumin, length of operation, ASA, and cancer site, high mFI predicted discharge to facility (OR 1.8, 95% CI 1.4-2.4, p<0.001) and readmission (OR 1.5, 95% CI 1.1-2.0). Conclusions High modified Frailty Index is associated with increased risk of discharge to a facility and readmission after major surgery for gastrointestinal malignancy. Early identification of these high-risk patients can help focus resources for optimal disposition.
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Tu1396 PROTEOMIC IDENTIFICATION OF NOVEL BIOMARKERS OF ETHANOL ACUTE PANCREATITIS Aiste Gulla, Richard Waldron, Aurelia Lugea, Stephen J. Pandol Introduction: Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with no effective therapeutic remedies. The severity of the disease varies widely and only limited biomarkers and severity scores are available to assess its severity. Therefore, an urgent need is to develop additional biomarkers that can improve clinical course and minimize mortality in AP. Methods: Patient serum was obtained from 12 male AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 controls. Severity in AP patients was as a correlate of tissue damage was estimated by blood lactate dehydrogenase, with an average value of 1127 mg/dl. Median APACHEII score was 5.5, and IMRIE score was 3.5, indicating moderate to severe AP (please see the accompanying table for details). For proteomic analysis, less abundant proteins in plasma samples were enriched using Top 12 abundant protein depletion columns. Further processing was performed by a modified filter-associated sample preparation combined with tandem mass tag labeling for quantitation. Samples were analyzed by Orbitrap Elite instrument for state-of-the-art high resolution liquid chromatography-tandem mass spectrometry. Results: Our analysis revealed that 44 proteins exhibited 1.5-fold or higher increase in the AP compared to control patients. Gene ontology analysis indicated a strong correlation with exosomal origin in the elevated proteins, with 35/44 (80%) associated with this extracellularly-secreted compartment. Elevated proteins included established and proposed biomarkers of AP including C-reactive protein, LPS-binding protein, intercellular adhesion molecule-1, and von Willebrand factor, as well as several novel potential biomarkers. Conclusions: These results suggest that we are discovering novel biomarkers which can be used for measuring the severity of pancreatitis at any point in time during the course of disease. Table for Serum Biomarker Proteonomic Study_AGA 2017
Tu1394
SSAT Abstracts
REOPERATION INCREASES THE INPATIENT MORTALITY IN PANCREATIC CANCER PATIENTS Chiranjeevi Gadiparthi, Rosann Cholankeril, Eddie L. Copelin, Eric R. Yoo, Muhammad Ali Khan, Menghan Hu, Aijaz Ahmed, Colin W. Howden, George Cholankeril, Ponnandai Somasundar Background and Aims Over the last two decades, long-term survival rates after surgical resection for pancreatic cancer have markedly improved. However, postoperative inpatient mortality among patients with resected pancreatic cancer is yet to be assessed. We aim to evaluate temporal trends and predictive risk factors associated with inpatient mortality in patients with resected pancreatic cancer. Methods Using the Healthcare Utilization ProjectNational Inpatient Sample (HCUP-NIS), we evaluated temporal trends and independent risk factors associated with postoperative inpatient morality in resected pancreatic cancer patients from 2004 to 2013. Inclusion criteria were patients with a primary diagnosis of pancreatic cancer who underwent pancreatic resection. Additionally, we performed a multivariate logistic regression analysis assessing risk factors including demographics (age, gender, ethnicity, insurance type), postoperative complications and clinical comorbidities associated with postoperative inpatient mortality in patients who underwent surgical resection for pancreatic cancer. Results Overall from 2004 to 2013, 13,758 patients underwent resection for pancreatic cancer during their hospitalization. Overall the postoperative inpatient mortality rate was 3.90 (per 100 resected pancreatic cancer hospitalizations). However, during this study period there was 41% overall reduction in mortality from 4.57 in 2004 to 2.68 in 2013 (Figure). After adjusting for demographics and severity of disease, our multivariate analysis demonstrated that reoperation, acute peptic ulcer disease, age above 75, cirrhosis and acute myocardial infarction were the most significant predictors of postoperative inpatient mortality (Table). Conclusion Inpatient mortality associated with surgical resection of pancreatic cancer has declined over the past decade. However, risk factors such as reoperation, peptic ulcer disease and older age demonstrate to adversely impact short-term survival in these patients. Future efforts to reduce preventable risk factors may aid in improving postoperative survival. Table. Significant predictors of postoperative inpatient mortality in resected pancreatic cancer patients
SSAT Abstracts
Tu1397 MODIFIED FRAILTY INDEX PREDICTS DISPOSITION AFTER MAJOR RESECTION FOR GASTROINTESTINAL CANCER Rebecca M. Dodson, Sarah Vermillion, Michael Kuncewitch, Perry Shen, Clancy J. Clark Introduction Gastrointestinal (GI) cancers disproportionally affect older adults who may present with limited physiologic reserve resulting in prolonged recovery. We hypothesized that a frailty index can predict postoperative disposition after major abdominal surgery. Methods All patients diagnosed with a GI malignancy (esophageal, gastric, pancreatic, liver, biliary, and colorectal) who underwent curative resection were identified in the 2011 and 2012 NSQIP Participant Use Files. Patients undergoing emergency procedures, not admitted from home, ASA 5, or diagnosed with preoperative sepsis were excluded. A modified Frailty Index (mFI) was defined by 11 variables within NSQIP previously used for the Canadian Study of Health and Aging-Frailty Index. mFI score of 0.27 or more was defined as high mFI. Univariate and multiple variable analyses were performed to evaluate postoperative disposition. Results 11,301 patients (age 64+/- 13, 46% female) underwent curative surgery for GI cancer with 4.3% (n= 482) having a high mFI (>=0.27). 61.8% (n = 6969) of patients were ASA 3/4 and 98.5% were independent prior to surgery. Postoperatively, 16.5% developed a major complication and 30-day mortality was 2.2%. 7.9% were discharged to a facility and 12.1% required readmission. High mFI was associated with increased risk of discharge to facility (OR 3.4, 95% CI 2.7-4.2, p<0.001) and readmission (OR 1.4, 95% CI 1.1-1.8, p = 0.013). After adjusting for age, race, albumin, length of operation, ASA, and cancer site, high mFI predicted discharge to facility (OR 1.8, 95% CI 1.4-2.4, p<0.001) and readmission (OR 1.5, 95% CI 1.1-2.0). Conclusions High modified Frailty Index is associated with increased risk of discharge to a facility and readmission after major surgery for gastrointestinal malignancy. Early identification of these high-risk patients can help focus resources for optimal disposition.
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