Bechien U. Wu

The Early Prediction of Mortality in Acute Pancreatitis: A Large Population-based Study

Background: Identification of patients at risk for mortality early in the course of acute pancreatitis (AP) is an important step in improving outcome. Methods: Using Classification and Regression Tree (CART) analysis, a clinical scoring system was developed for prediction of in-hospital mortality in AP. The scoring system was derived on data collected from 17 992 cases of AP from 212 hospitals in 2000–2001. The new scoring system was validated on data collected from 18 256 AP cases from 177 hospitals in 2004–2005. The accuracy of the scoring system for prediction of mortality was measured by the area under the receiver operating characteristic curve (AUC). The performance of the new scoring system was further validated by comparing its predictive accuracy with that of Acute Physiology and Chronic Health Examination (APACHE) II. Results: CART analysis identified five variables for prediction of in-hospital mortality. One point is assigned for the presence of each of the following during the first 24 h: blood urea nitrogen (BUN) >25 mg/dl; impaired mental status; systemic inflammatory response syndrome (SIRS); age >60 years; or the presence of a pleural effusion (BISAP). Mortality ranged from >20% in the highest risk group to <1% in the lowest risk group. In the validation cohort, the BISAP AUC was 0.82 (95% CI 0.79 to 0.84) versus APACHE II AUC of 0.83 (95% CI 0.80 to 0.85). Conclusions: A new mortality-based prognostic scoring system for use in AP has been derived and validated. The BISAP is a simple and accurate method for the early identification of patients at increased risk for in-hospital mortality.

Lactated Ringer's Solution Reduces Systemic Inflammation Compared With Saline in Patients With Acute Pancreatitis

BACKGROUND & AIMS Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis. We performed a randomized controlled trial to evaluate the impact of a goal-directed fluid resuscitation protocol on systemic inflammation in patients with acute pancreatitis. We then determined the impact of resuscitation with lactated Ringers solution, compared with normal saline. METHODS We performed a randomized controlled trial of 40 patients with acute pancreatitis at 3 New England hospitals from May 2009-February 2010. Patients received goal-directed fluid resuscitation with lactated Ringers solution, goal-directed fluid resuscitation with normal saline, standard fluid resuscitation with lactated Ringers solution, or standard fluid resuscitation with normal saline. Systemic inflammation was measured on the basis of levels of systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) level after 24 hours. RESULTS The volumes of fluid administered during a 24-hour period were similar among patients given goal-directed or standard fluid resuscitation (mean, 4300 vs 4600 mL, respectively; P = .87). Goal-directed resuscitation did not significantly reduce incidence of SIRS, compared with standard resuscitation (11.8% vs 13.0%, respectively; P = .85) or levels of CRP after 24 hours (87.1 vs 69.2 mg/dL, respectively; P = .75). By contrast, there was a significant reduction in SIRS after 24 hours among subjects resuscitated with lactated Ringers solution, compared with normal saline (84% reduction vs 0%, respectively; P = .035); administration of lactated Ringers solution also reduced levels of CRP, compared with normal saline (51.5 vs 104 mg/dL, respectively; P = .02). CONCLUSIONS Patients with acute pancreatitis who were resuscitated with lactated Ringers solution had reduced systemic inflammation compared with those who received saline.

A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis.

OBJECTIVES:Our aim was to prospectively evaluate the ability of the bedside index for severity in acute pancreatitis (BISAP) score to predict mortality as well as intermediate markers of severity in a tertiary center.METHODS:The BISAP score was evaluated among 397 consecutive cases of acute pancreatitis admitted to our institution between June 2005 and December 2007. BISAP scores were calculated on all cases using data within 24 h of presentation. The ability of the BISAP score to predict mortality was evaluated using trend and discrimination analysis. The optimal cutoff score for mortality from the receiver operating curve was used to evaluate the development of organ failure, persistent organ failure, and pancreatic necrosis.RESULTS:Among 397 cases, there were 14 (3.5%) deaths. There was a statistically significant trend for increasing mortality (P < 0.0001) with increasing BISAP score. The area under the receiver operating curve for mortality by BISAP score in the prospective cohort was 0.82 (95% confidence interval: 0.70, 0.95), which was similar to that of the previously published validation cohort. A BISAP score ≥3 was associated with an increased risk of developing organ failure (odds ratio=7.4, 95% confidence interval: 2.8, 19.5), persistent organ failure (odds ratio=12.7, 95% confidence interval: 4.7, 33.9), and pancreatic necrosis (odds ratio=3.8, 95% confidence interval: 1.8, 8.5).CONCLUSIONS:The BISAP score represents a simple way to identify patients at risk of increased mortality and the development of intermediate markers of severity within 24 h of presentation. This risk stratification capability can be utilized to improve clinical care and facilitate enrollment in clinical trials.

Comparison of Existing Clinical Scoring Systems to Predict Persistent Organ Failure in Patients With Acute Pancreatitis

BACKGROUND & AIMS It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches.

Early systemic inflammatory response syndrome is associated with severe acute pancreatitis.

BACKGROUND & AIMS There have been few clinical studies of systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis. The aim of this study was to evaluate the role of SIRS in assessing severity of acute pancreatitis. METHODS We prospectively enrolled 252 consecutive patients with acute pancreatitis who were admitted directly to our institution between 2005-2007. The incidence and duration of SIRS (transient <or=48 hours vs persistent >48 hours) during the first 7 days of hospitalization, and the number of SIRS criteria (0-4) on the first day of hospitalization (day 1) were evaluated with individual markers of severity, including persistent organ failure, pancreatic necrosis, need for intensive care unit, and mortality. RESULTS SIRS occurred in 155/252 patients (62%) on day 1. SIRS on day 1 predicted severe disease with high sensitivity (85%-100%). The absence of SIRS on day 1 was associated with a high negative predictive value (98%-100%). Patients with a higher number of systemic inflammatory response (SIR) criteria on day 1 and persistent SIRS had an increased risk for severe disease (P < .01). CONCLUSIONS The majority of patients hospitalized with acute pancreatitis have SIRS on day 1. The severity of acute pancreatitis is greater among patients with SIRS on day 1 and, in particular, among those with 3 or 4 SIRS criteria, compared with those without SIRS on day 1.

Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Meta-Analysis

BACKGROUND & AIMS International guidelines for the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate the risk of malignancy associated with each of these features of IPMNs. METHODS We performed a comprehensive search of MEDLINE from January 1, 1996, to November 11, 2011, for studies that included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Data were analyzed from 41 studies for the following features: cyst size greater than 3 cm, the presence of mural nodules, dilated main pancreatic duct, symptoms, and main duct vs branch duct IPMNs. Malignant IPMNs were defined as those with carcinoma in situ or more advanced histology. A separate meta-analysis was performed for each risk factor to calculate pooled odds ratios (ORs). A random-effects model was used, based on the assumption of variation among study populations. RESULTS The risks of malignancy associated with individual cyst features were as follows: cyst size greater than 3 cm (OR, 62.4; 95% confidence interval [CI], 30.8-126.3), presence of a mural nodule (OR, 9.3; 95% CI, 5.3-16.1), dilatation of the main pancreatic duct (OR, 7.27; 95% CI, 3.0-17.4), and main vs branch duct IPMN (OR, 4.7; 95% CI, 3.3-6.9). There was a moderate level of heterogeneity among studies (I(2) range, 34-67). CONCLUSIONS Based on a meta-analysis, cyst features proposed by the international guidelines for resection of IPMN were highly associated with malignancy. However, based on our findings, not all cyst features should be weighted equally when considering risk of malignancy; cyst size greater than 3 cm was associated most strongly with malignant IPMN.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

Abstract The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Early Changes in Blood Urea Nitrogen Predict Mortality in Acute Pancreatitis

BACKGROUND & AIMS Routine laboratory tests that reflect intravascular volume status can play an important role in the early assessment of acute pancreatitis (AP). The objective of this study was to evaluate accuracy of serial blood urea nitrogen (BUN) versus serial hemoglobin (Hgb) measurement for prediction of in-hospital mortality in AP. METHODS We performed an observational cohort study on data from 69 US hospitals from January 2003 to December 2006. Repeated measures analysis was used to examine the relationship between early trends in BUN and Hgb with respect to mortality. Multivariate logistic regression was used to evaluate the impact of admission BUN, change in BUN, admission Hgb, and change in Hgb on mortality. Time-specific receiver operating characteristic curves and multivariable logistic regression compared accuracy of BUN, Hgb, and additional routine laboratory tests. RESULTS BUN levels were persistently higher among nonsurvivors than survivors during the first 48 hours of hospitalization (F-test; P < .0001). No such relationship existed for Hgb (F-test; P = .33). For every 5-mg/dl increase in BUN during the first 24 hours, the age- and gender-adjusted odds ratio for mortality increased by 2.2 (95% confidence limits, 1.8, 2.7). Of the 6 routine laboratory tests examined, BUN yielded the highest area under the concentration-time curve (AUC) for predicting mortality at admission (AUC = 0.79), 24 hours (AUC = 0.89), and 48 hours (AUC = 0.90). Combining admission BUN and change in BUN at 24 hours produced an AUC of 0.91 for mortality. CONCLUSION In a large, hospital-based cohort study, we identified serial BUN measurement as the most valuable single routine laboratory test for predicting mortality in AP.

Blood urea nitrogen in the early assessment of acute pancreatitis: an international validation study.

BACKGROUND Objective assessment of acute pancreatitis (AP) is critical to help guide resuscitation efforts. Herein we (1) validate serial blood urea nitrogen (BUN) measurement for early prediction of mortality and (2) develop an objective BUN-based approach to early assessment in AP. METHODS We performed a secondary analysis of 3 prospective AP cohort studies: Brigham and Womens Hospital (BWH), June 2005 through May 2009; the Dutch Pancreatitis Study Group (DPSG), March 2004 through March 2007; and the University of Pittsburgh Medical Center (UPMC), June 2003 through September 2007. Meta-analysis and stratified multivariate logistic regression adjusted for age, sex, and creatinine levels were calculated to determine risk of mortality associated with elevated BUN level at admission and rise in BUN level at 24 hours. The accuracy of the BUN measurements was determined by area under the receiver operating characteristic curve (AUC) analysis compared with serum creatinine measurement and APACHE II score. A BUN-based assessment algorithm was derived on BWH data and validated on the DPSG and UPMC cohorts. RESULTS A total of 1043 AP cases were included in analysis. In pooled analysis, a BUN level of 20 mg/dL or higher was associated with an odds ratio (OR) of 4.6 (95% confidence interval [CI], 2.5-8.3) for mortality. Any rise in BUN level at 24 hours was associated with an OR of 4.3 (95% CI, 2.3-7.9) for death. Accuracy of serial BUN measurement (AUC, 0.82-0.91) was comparable to that of the APACHE II score (AUC, 0.72-0.92) in each of the cohorts. A BUN-based assessment algorithm identified patients at increased risk for mortality during the initial 24 hours of hospitalization. CONCLUSIONS We have confirmed the accuracy of BUN measurement for early prediction of mortality in AP and developed an algorithm that may assist physicians in their early resuscitation efforts.

Clinical Management of Patients With Acute Pancreatitis

Acute pancreatitis is the leading cause of hospitalization for gastrointestinal disorders in the United States. As rates of hospitalization for acute pancreatitis continue to increase, so does demand for effective management. We review approaches to best manage patients with acute pancreatitis, covering diagnosis, risk and prognostic factors, treatment, and complications, considering recommendations from current practice guidelines.