Georgios I. Papachristou

Peroral Endoscopic Drainage/Debridement of Walled-off Pancreatic Necrosis

Background:Experience with minimal access, transoral/transmural endoscopic drainage/debridement of walled-off pancreatic necrosis (WOPN) after necrotizing pancreatitis is limited. We sought to determine outcome using this technique. Methods:Retrospective analysis. Results:From 1998 to 2006, 53 patients underwent transoral/transmural endoscopic drainage/debridement of sterile (27, 51%) and infected (26, 49%) WOPN. Intervention was performed a median of 49 days (range, 20–300 days) after onset of acute necrotizing pancreatitis. A median of 3 endoscopic procedures/patient (range, 1–12) were performed. Twenty-one patients (40%) required concurrent radiologic-guided catheter drainage of associated or subsequent areas of peripancreatic fluid and/or WOPN. Twelve patients (23%) required open operative intervention a median of 47 days (range, 5–540) after initial endoscopic drainage/debridement, due to persistence of WOPN (n = 3), recurrence of a fluid collection (n = 2), cutaneous fistula formation (n = 2), or technical failure, persistence of pancreatic pain, colonic obstruction, perforation, and flank abscess (n = 1 each). Final outcome after initial endoscopic intervention (median, 178 days) revealed successful endoscopic therapy in 43 (81%) and persistence of WOPN in 10 (19%). Preexistent diabetes mellitus, size of WOPN, and extension of WOPN into paracolic gutter were significant predictive factors for need of subsequent open operative therapy. Conclusions:Successful resolution of symptomatic, sterile, and infected WOPN can be achieved using a minimal access endoscopic approach. Adjuvant percutaneous drainage is necessary in up to 40% of patients, especially when WOPN extends to paracolic gutters or pelvis. Operative intervention for failed endoscopic treatment is required in about 20% of patients.

Comparison of BISAP, Ranson's, APACHE-II, and CTSI Scores in Predicting Organ Failure, Complications, and Mortality in Acute Pancreatitis

OBJECTIVES:Identification of patients at risk for severe disease early in the course of acute pancreatitis (AP) is an important step to guiding management and improving outcomes. A new prognostic scoring system, the bedside index for severity in AP (BISAP), has been proposed as an accurate method for early identification of patients at risk for in-hospital mortality. The aim of this study was to compare BISAP (blood urea nitrogen >25 mg/dl, impaired mental status, systemic inflammatory response syndrome (SIRS), age>60 years, and pleural effusions) with the “traditional” multifactorial scoring systems: Ransons, Acute Physiology and Chronic Health Examination (APACHE)-II, and computed tomography severity index (CTSI) in predicting severity, pancreatic necrosis (PNec), and mortality in a prospective cohort of patients with AP.METHODS:Extensive demographic, radiographic, and laboratory data from consecutive patients with AP admitted or transferred to our institution was collected between June 2003 and September 2007. The BISAP and APACHE-II scores were calculated using data from the first 24 h from admission. Predictive accuracy of the scoring systems was measured by the area under the receiver-operating curve (AUC).RESULTS:There were 185 patients with AP (mean age 51.7, 51% males), of which 73% underwent contrast-enhanced CT scan. Forty patients developed organ failure and were classified as severe AP (SAP; 22%). Thirty-six developed PNec (19%), and 7 died (mortality 3.8%). The number of patients with a BISAP score of ≥3 was 26; Ransons ≥3 was 47, APACHE-II ≥8 was 66, and CTSI ≥3 was 59. Of the seven patients that died, one had a BISAP score of 1, two had a score of 2, and four had a score of 3. AUCs for BISAP, Ransons, APACHE-II, and CTSI in predicting SAP are 0.81 (confidence interval (CI) 0.74–0.87), 0.94 (CI 0.89–0.97), 0.78 (CI 0.71–0.84), and 0.84 (CI 0.76–0.89), respectively.CONCLUSIONS:We confirmed that the BISAP score is an accurate means for risk stratification in patients with AP. Its components are clinically relevant and easy to obtain. The prognostic accuracy of BISAP is similar to those of the other scoring systems. We conclude that simple scoring systems may have reached their maximal utility and novel models are needed to further improve predictive accuracy.

Direct endoscopic necrosectomy for the treatment of walled-off pancreatic necrosis: results from a multicenter U.S. series

BACKGROUND Direct endoscopic necrosectomy (DEN) for treatment of walled-off pancreatic necrosis (WOPN) has been performed as an alternative to operative or percutaneous therapy. OBJECTIVE To report the largest combined experience of DEN performed for WOPN. DESIGN Retrospective chart review. SETTING Six U.S. tertiary medical centers. PATIENTS A total of 104 patients with a history of acute pancreatitis and symptomatic WOPN since 2003. INTERVENTIONS DEN for WOPN. MAIN OUTCOME MEASUREMENTS Resolution or near-resolution of WOPN without the need for surgical or percutaneous intervention and procedural complications. RESULTS Successful resolution was achieved in 95 of 104 patients (91%). Of the patients in whom it failed, 5 died during follow-up before resolution, 2 underwent operative drainage for persistent WOPN, 1 required surgery for massive bleeding on fistula tract dilation, and 1 died periprocedurally. The mean time to resolution from the initial DEN was 4.1 months. The first débridement was performed a mean of 63 days after the initial onset of acute pancreatitis. In 73%, the entry was transgastric with median tract dilation diameter of 18 mm. The median number of procedures was 3 with 2 débridements. Complications occurred in approximately 14% and included 5 retrogastric perforations/pneumoperitoneum, which were managed nonoperatively. Univariate analysis identified a body mass index >32 as a risk factor for failed DEN. LIMITATIONS Retrospective, highly specialized centers. CONCLUSIONS This large, multicenter series demonstrates that transmural, minimally invasive endoscopic débridement of WOPN performed in the United States is an efficacious and reproducible technique with an acceptable safety profile.

Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response.

Background: Obese patients appear to be at risk for complications of acute pancreatitis (AP). APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP. Aims: To determine if APACHE-O adds any predictive value to APACHE-II score and to test the hypothesis that obese patients are at increased risk of severe AP (SAP) because of a more intense inflammatory response to pancreatic injury. Methods: 102 AP patients were prospectively studied. Using a body mass index (BMI) >30, 28% of the subjects were obese. Nineteen patients developed organ dysfunction and were classified as SAP. Receiver-operating curves for prediction of SAP were calculated using admission APACHE-II and APACHE-O scores. Binary logistic regression was performed to assess if obesity is a risk for SAP and to determine the clinical factors associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as Ranson’s scores were compared between obese and non-obese patients. Results: Admission APACHE-O (area under the curve AUC 0.895) and APACHE-II (AUC 0.893) showed similar accuracy in predicting severe outcome. BMI was identified as a significant risk for SAP (OR 2.8, p = 0.048) and mortality (OR 11.2, p = 0.022). CRP levels were significantly higher in obese AP patients (p = 0.0001) as well as Ranson’s score (p = 0.021). IL-6 and MCP-1 levels were higher in obese patients but did not reach statistical significance. Conclusions: Obesity is an independent risk for SAP. Admission APACHE-O score is not more accurate than APACHE-II. Our study results suggest that obesity increases the severity of AP by amplifying the immune response to injury.

A comparison of direct endoscopic necrosectomy with transmural endoscopic drainage for the treatment of walled-off pancreatic necrosis

BACKGROUND Endoscopic therapy of walled-off pancreatic necrosis (WOPN) via direct intracavitary debridement is described. OBJECTIVE To compare direct endoscopic necrosectomy with conventional transmural endoscopic drainage for the treatment of WOPN. DESIGN Retrospective, comparative study. SETTING Academic tertiary-care center. PATIENTS Patients referred to Mayo Clinic, Rochester, Minnesota, since April 1998 for endoscopic drainage of WOPN. INTERVENTIONS Each patient underwent standard endoscopic drainage that consisted of transmural cavity puncture, dilation of the fistula tract, and placement of a large-bore stent(s). Patients were classified into the direct endoscopic necrosectomy group if, during any of their procedures, adjunctive direct endoscopic necrosectomy was performed; all others were in the standard drainage group. MAIN OUTCOME MEASUREMENTS Success was defined as resolution of the necrotic cavity without the need for operative or percutaneous intervention. RESULTS Forty-five patients were identified who met study criteria: 25 underwent direct endoscopic necrosectomy, and 20 underwent standard endoscopic drainage. There were no differences in baseline patient or cavity characteristics. Successful resolution was accomplished in 88% who underwent direct endoscopic necrosectomy versus 45% who received standard drainage (P < .01), without a change in the total number of procedures. The maximum size of tract dilation was larger in the direct endoscopic necrosectomy group (17 mm vs 14 mm, P < .02). Complications were limited to mild periprocedural bleeding with equivalent rates between groups. LIMITATIONS Retrospective, referral bias, single center. CONCLUSIONS Direct endoscopic necrosectomy achieves higher rates of resolution, without a concomitant change in the number of endoscopic procedures, complication rate, or time to resolution compared with standard endoscopic drainage for WOPN. The need for fewer postprocedural inpatient hospital days and a decrease in the rate of cavity recurrence are also likely benefits of this technique.

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.

Natural History Following the First Attack of Acute Pancreatitis

OBJECTIVES:Data on natural history following a sentinel attack of acute pancreatitis (AP) are limited. The objective of this study was to determine the risk of recurrent AP (RAP) and subsequent chronic pancreatitis (CP) diagnosis after the first attack of AP.METHODS:Using the Pennsylvania Health Care Cost Containment Council (PHC4) data set, we identified all unique White and Black Allegheny County residents who received a first-time primary inpatient discharge diagnosis of AP from 1996 through 2005. AP etiology was determined using associated diagnoses codes. We also checked whether any of these patients were readmitted for AP and/or received inpatient CP diagnosis until third quarter of 2007.RESULTS:In all, 7,456 unique residents (mean age 58±20 years, 45% male, 80% White) with incident AP admission were identified. Common etiologies included biliary (28%), alcohol (19%), and idiopathic (36%). Compared with other causes, alcoholic AP patients were significantly younger and more likely to be male and Black. Among survivors (98.1%) and those without pancreatic cancer, follow-up (median 40 months, interquartile range 18, 69) was available for 84% of patients. Readmission for primary or any AP was recorded for 22 and 29%; subsequent primary or any CP diagnosis was assigned to 6 and 12.8%, respectively. Significant independent predictors for RAP were alcohol etiology and tobacco abuse and for CP were RAP and tobacco abuse. RAP risk in biliary AP increased with the duration between AP and cholecystectomy.CONCLUSIONS:Readmissions following a sentinel attack of AP are common. Progression to CP is infrequent and usually occurs in the setting of RAP, alcohol, and smoking. Cholectstectomy should be considered as soon as feasible after an attack of biliary AP. Natural history of CP may be altered through early behavioral intervention.

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

Unsaturated fatty acids cause lipotoxicity and mediate acute adverse outcomes in obese individuals with pancreatitis. The Burden of Adiposity As if diabetes and heart disease were not burden enough, obese people who suffer trauma, burns, or other critical conditions have an increased likelihood of death. During these exacerbated illnesses, multiple organs can fail, a situation that is particularly hard to reverse. How the presence of excess adipose tissue contributes to the severity of these diseases is not clear, but understanding the mechanisms could provide clues for possible treatments. Pancreatitis is a relatively well-defined disease that tends to be worse in the obese and, in its most severe form, is accompanied by multi-organ failure. By using a combination of patient investigation, in vitro cell studies, and an animal model, Navina et al. have assembled evidence that pinpoints the culprits in the obesity-related complications of this disease: unsaturated fatty acids liberated by lipolysis from adipose tissue. The authors carefully examine the pancreases of 24 patients who had died of pancreatitis. The staining patterns indicated that nonesterified fatty acids, derived by lipolysis of excess intrapancreatic fat, contributed to the pancreatic necrosis in these patients. To test this idea, the authors used a cell culture system and showed that it is unsaturated fatty acids that do the damage, impairing acinar cell activities, inhibiting mitochondrial function, releasing calcium, and causing cell death. But what about the failure of other organs? To answer this question, the authors used obese mice with pancreatitis and, by inhibiting lipolysis with the drug orlistat, were able to prevent the pancreatic-associated rise in serum unsaturated fatty acids and, of most importance, to reduce damage to the lung and kidney, as well as mortality. It is not yet clear which lipase is the critical one for multiorgan failure or where it is located. But once revealed, this potential therapeutic target may specify a treatment that enhances the survival of critically ill obese patients. Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.

Elevated Serum Creatinine as a Marker of Pancreatic Necrosis in Acute Pancreatitis

OBJECTIVES:Pancreatic necrosis is a serious complication of acute pancreatitis. The identification of simple laboratory tests to detect subjects at risk of pancreatic necrosis may direct management and improve outcome. This study focuses on the association between routine laboratory tests and the development of pancreatic necrosis in patients with acute pancreatitis.METHODS:In a cohort of 185 patients with acute pancreatitis prospectively enrolled in the Severity of Acute Pancreatitis Study, patients with contrast-enhanced computerized tomography performed were selected (n=129). Serum hematocrit, creatinine, and urea nitrogen on admission and peak values within 48 h of admission were analyzed. The volume of intravenous fluid resuscitation was calculated for each patient.RESULTS:Of 129 patients, 35 (27%) had evidence of pancreatic necrosis. Receiver operating characteristic curves for pancreatic necrosis revealed an area under the curve of 0.79 for admission hematocrit, 0.77 for peak creatinine, and 0.72 for peak urea nitrogen. Binary logistic regression yielded that all three tests were significantly associated with pancreatic necrosis (P<0.0001), with the highest odds ratio, 34.5, for peak creatinine. The volume of intravenous fluid resuscitation was similar in patients with and without necrosis. Low admission hematocrit (≤44.8%) yielded a negative predictive value of 89%; elevated peak creatinine (>1.8 mg/dl) within 48 h yielded a positive predictive value of 93%.CONCLUSIONS:We confirm that a low admission hematocrit indicates a low risk of pancreatic necrosis (PNec) in patients with acute pancreatitis. In contrast, an increase in creatinine within the first 48 h is strongly associated with the development of PNec. This finding may have important clinical implications and warrants further investigation.

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.